53
Public Health Action EDITORIAL Taking on the diabetes-tuberculosis epidemic in India: paving the way through operational research Srinath Satyanarayana, 1 Ajay M. V. Kumar, 1 Nevin Wilson, 1 Anil Kapur, 2 Anthony D. Harries, 3,4 Rony Zachariah 5 of the two diseases, treatment of persons with dual disease and prevention of TB in persons with DM. 5 For each of these challenges, the knowledge gaps are high- lighted along with the research questions that need to be answered if care and control of the dual burden of disease are to be achieved. The second review article looks at existing and new technologies for screening and diagnosing type 2 DM that may be more suitable for TB patients in low- and middle-income countries. 6 As pointed out, these new technologies should be low cost, rapid, easy to use, non-invasive, requiring mini- mal additional infrastructure and able to differentiate between transient and longer term hyperglycaemia. Several tools in development, such as point-of-care glycated haemoglobin and glycated albumin assays, non-invasive advanced glycation end (AGE) product readers and sudomotor function-based screening de- vices, are discussed. The eight operational research papers assess 1) bi- directional screening of the two diseases in one facil- ity, 7 2) screening of DM patients for TB in one facility, 8 and 3) screening of TB patients for DM in the other fa- cilities, 9–14 with one of these facilities also evaluating treatment outcomes. 13 A few key messages that are consistent across sites emerge. First, the yield of diabe- tes was high among TB patients, with higher yields seen among patients aged more than 35–40 years, pa- tients with smear-positive pulmonary TB, current ciga- rette smokers and those with recurrent TB. The pro- portion with newly diagnosed DM as a result of blood test screening was higher among TB patients man- aged in peripheral health facilities compared to ter- tiary care centres, highlighting the need to prioritise active screening efforts at the peripheral level. Second, the yield of TB among DM patients was relatively low, and further research is required to optimise the screen- ing criteria and diagnostic algorithms for diagnosing TB. One study showed that DM patients who were male, older, had a longer duration of DM, required combined oral hypoglycaemic drugs and insulin medi- cation and had poorly controlled DM were more likely to have TB. 7 Third, while the results reported are use- ful, the one study that assessed treatment outcomes was not adequately powered to answer the question about whether DM adversely affects outcomes. 12 There was a statistically non-significant trend towards failure of DM-TB patients to smear convert at 2 months, but this whole area requires adequately powered, prospec- tive cohort research. InternaƟonal Union Against Tuberculosis and Lung Disease Health soluƟons for the poor VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013 http://dx.doi.org/10.5588/pha.13.0039 I n September 2011, a national stakeholders meeting was held in Delhi, India, to discuss how to move for- ward with bi-directional screening of tuberculosis (TB) and diabetes mellitus (DM). Agreement was reached about how to 1) implement screening at hospitals and peripheral health institutions, 2) monitor and record the process and outcomes of screening for each indi- vidual patient and 3) report on aggregate data at quar- terly intervals. The meeting was followed by training of health care personnel involved in the work, imple- mentation of screening and a reconvening of im - plementing partners to share data and discuss chal- lenges. This body of work culminated in two published papers presenting the process and aggregate data on bi-directional screening of TB and DM in India. 1,2 These pilot projects, conducted within the routine health services, produced good quality evidence that has led to changes in policy and practice. A policy di- rective has been issued that all patients registered with TB in India should be screened for DM. Patient TB treatment cards and TB registers have been modified to accommodate these new parameters, recording whether screening has taken place for DM, whether the patient has received a diagnosis of DM and the results of blood glucose measurements during TB treatment. A Minis- try of Health Training Manual on screening TB pa- tients for DM has also been developed for health care workers in the field. 3 Importantly, a policy directive from the Directorate General of Health Services now links India’s Revised National TB Control Programme to the National Programme for Non-Communicable Diseases (NCD) at the sub-centre level so that data on TB patients screened for DM are reported to the NCD programme. The NCD programme is in a nascent phase in the country, but it is also evolving rapidly, and this model of convergence, adapting and incorporating the DOTS framework with its ‘cohort reviews’, is impor- tant for this evolution. This bi-directional approach will be the first of its kind to be implemented at na- tional level, with such initiatives recently being en- dorsed by the 66th World Health Assembly Resolution on 25 May 2013. 4 In this context, the current supplement on DM and TB is timely and important. It consists of two review articles and eight operational research papers. The first review article provides an up-to-date international per- spective on the epidemiology of and interaction be- tween DM and TB, and examines three important op- erational challenges for care—bidirectional screening AFFILIATIONS 1 International Union Against Tuberculosis and Lung Disease (The Union), South-East Asia Office, New Delhi, India 2 World Diabetes Founda- tion, Gentofte, Denmark 3 The Union, Paris, France 4 London School of Hygiene & Tropical Medicine, London, UK 5 Médecins Sans Frontières, Medical Department, Operational Research Unit, Brussels Operational Center, Luxembourg, Luxembourg CORRESPONDENCE e-mail: ssrinath@theunion. org; [email protected] PHA 2013; 3(S1): S1–S2 © 2013 The Union

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Public Health Action

EDITORIAL

Taking on the diabetes-tuberculosis epidemic in India: paving the way through operational research Srinath Satyanarayana,1 Ajay M. V. Kumar,1 Nevin Wilson,1 Anil Kapur,2 Anthony D. Harries,3,4

Rony Zachariah5

of the two diseases, treatment of persons with dual disease and prevention of TB in persons with DM.5 For each of these challenges, the knowledge gaps are high-lighted along with the research questions that need to be answered if care and control of the dual burden of disease are to be achieved. The second review article looks at existing and new technologies for screening and diagnosing type 2 DM that may be more suitable for TB patients in low- and middle-income countries.6 As pointed out, these new technologies should be low cost, rapid, easy to use, non-invasive, requiring mini-mal additional infrastructure and able to differentiate between transient and longer term hyperglycaemia. Several tools in development, such as point-of-care glycated haemoglobin and glycated albumin assays, non-invasive advanced glycation end (AGE) product readers and sudomotor function-based screening de-vices, are discussed.

The eight operational research papers assess 1) bi-directional screening of the two diseases in one facil-ity,7 2) screening of DM patients for TB in one facility,8 and 3) screening of TB patients for DM in the other fa-cilities,9–14 with one of these facilities also evaluating treatment outcomes.13 A few key messages that are consistent across sites emerge. First, the yield of diabe-tes was high among TB patients, with higher yields seen among patients aged more than 35–40 years, pa-tients with smear-positive pulmonary TB, current ciga-rette smokers and those with recurrent TB. The pro-portion with newly diagnosed DM as a result of blood test screening was higher among TB patients man-aged in peripheral health facilities compared to ter-tiary care centres, highlighting the need to prioritise active screening efforts at the peripheral level. Second, the yield of TB among DM patients was relatively low, and further research is required to optimise the screen-ing criteria and diagnostic algorithms for diagnosing TB. One study showed that DM patients who were male, older, had a longer duration of DM, required combined oral hypoglycaemic drugs and insulin medi-cation and had poorly controlled DM were more likely to have TB.7 Third, while the results reported are use-ful, the one study that assessed treatment outcomes was not adequately powered to answer the question about whether DM adversely affects outcomes.12 There was a statistically non-signifi cant trend towards failure of DM-TB patients to smear convert at 2 months, but this whole area requires adequately powered, prospec-tive cohort research.

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi.org/10.5588/pha.13.0039

In September 2011, a national stakeholders meeting was held in Delhi, India, to discuss how to move for-

ward with bi-directional screening of tuberculosis (TB) and diabetes mellitus (DM). Agreement was reached about how to 1) implement screening at hospitals and peripheral health institutions, 2) monitor and record the process and outcomes of screening for each indi-vidual patient and 3) report on aggregate data at quar-terly intervals. The meeting was followed by training of health care personnel involved in the work, imple-mentation of screening and a reconvening of im-

plementing partners to share data and discuss chal-lenges. This body of work culminated in two published papers presenting the process and aggregate data on bi-directional screening of TB and DM in India.1,2

These pilot projects, conducted within the routine health services, produced good quality evidence that has led to changes in policy and practice. A policy di-rective has been issued that all patients registered with TB in India should be screened for DM. Patient TB treatment cards and TB registers have been modifi ed to accommodate these new parameters, recording whether screening has taken place for DM, whether the patient has received a diagnosis of DM and the results of blood glucose measurements during TB treatment. A Minis-try of Health Training Manual on screening TB pa-tients for DM has also been developed for health care workers in the fi eld.3 Importantly, a policy directive from the Directorate General of Health Services now links India’s Revised National TB Control Programme to the National Programme for Non-Communicable Diseases (NCD) at the sub-centre level so that data on TB patients screened for DM are reported to the NCD programme. The NCD programme is in a nascent phase in the country, but it is also evolving rapidly, and this model of convergence, adapting and incorporating the DOTS framework with its ‘cohort reviews’, is impor-tant for this evolution. This bi-directional approach will be the fi rst of its kind to be implemented at na-tional level, with such initiatives recently being en-dorsed by the 66th World Health Assembly Resolution on 25 May 2013.4

In this context, the current supplement on DM and TB is timely and important. It consists of two review articles and eight operational research papers. The fi rst review article provides an up-to-date international per-spective on the epidemiology of and interaction be-tween DM and TB, and examines three important op-erational challenges for care—bidirectional screening

AFFILIATIONS1 International Union

Against Tuberculosis and Lung Disease (The Union), South-East Asia Office, New Delhi, India

2 World Diabetes Founda-tion, Gentofte, Denmark

3 The Union, Paris, France4 London School of Hygiene

& Tropical Medicine, London, UK

5 Médecins Sans Frontières, Medical Department, Operational Research Unit, Brussels Operational Center, Luxembourg, Luxembourg

CORRESPONDENCEe-mail: [email protected]; [email protected]

PHA 2013; 3(S1): S1–S2© 2013 The Union

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Public Health Action Editorial S2

The interaction between DM and TB is rapidly becoming a hot topic for research, with projects examining the biological and mo-lecular reasons for the linkages and addressing questions about how best to manage and integrate care. These operational research studies from various sites in India will begin to pave the way to-wards a better understanding of the two diseases, in addition to better care and, ultimately, better health outcomes.

References 1 India Tuberculosis-Diabetes Study Group. Screening of patients with tubercu-

losis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645. 2 India Diabetes Mellitus-Tuberculosis Study Group. Screening of patients with

diabetes mellitus for tuberculosis in India. Trop Med Int Health 2013; 18: 646–654.

3 Central Tuberculosis Division, Ministry of Health and Family Welfare, Gov-ernment of India. Screening of tuberculosis patients for diabetes mellitus—training module for the staff of the Revised National Tuberculosis Control Programme. New Delhi, India: Directorate General of Health Services, Minis-try of Health and Family Welfare, Government of India, 2013.

4 World Health Organization. Sixty-Sixth World Health Assembly, Agenda Item 13. Follow-up to the Political Declaration of the High-level Meeting of the General Assembly on the Prevention and Control of Non-Communicable Diseases. A66/A/CONF./1 Rev.1 (25 May 2013). Geneva, Switzerland: WHO, 2013. http://apps.who.int/gb/e/e_wha66.html Accessed August 2013.

5 Harries A D, Satyanarayana S, Kumar A M V, et al. Epidemiology and inter-action of diabetes mellitus and tuberculosis and the challenges for care: a re-view. Public Health Action 2013; 3 (Suppl): S3–S9.

6 Adepoyibi T, Weigl B, Greb H, Neogi T, McGuire H. New screening technolo-gies for type 2 diabetes mellitus appropriate for use in tuberculosis patients. Public Health Action 2013; 3 (Suppl): S10–S17.

7 Prakash B C, Ravish K S, Prabhakar B, et al. Tuberculosis-diabetes mellitus bi-directional screening at a tertiary care centre, South India. Public Health Ac-tion 2013; 3 (Suppl): S18–S22.

8 Kumpatla S, Sekar A, Achanta S, et al. Characteristics of patients with diabe-tes screened for tuberculosis in a tertiary care hospital in South India. Public Health Action 2013; 3 (Suppl): S23–S28.

9 Dave P, Shah A, Chauhan M, et al. Screening patients with tuberculosis for diabetes mellitus in Gujarat, India. Public Health Action 2013; 3 (Suppl): S29–S33.

10 Naik B, Kumar A M V, Satyanarayana S, et al. Is screening for diabetes among tuberculosis patients feasible at the fi eld level? Public Health Action 2013; 3 (Suppl): S34–S37.

11 Nair S, Kumari A K, Subramonianpillai J, et al. High prevalence of undiag-nosed diabetes among tuberculosis patients in peripheral health facilities in Kerala. Public Health Action 2013; 3 (Suppl): S38–S42.

12 Achanta S, Tekumalla R R, Jaju J, et al. Screening tuberculosis patients for di-abetes in a tribal area in South India. Public Health Action 2013; 3 (Suppl): S43–S47.

13 Khanna A, Lohya S, Sharath B N, Harries A D. Characteristics and treatment response in patients with tuberculosis and diabetes mellitus in Delhi, India. Public Health Action 2013; 3 (Suppl): S48–S50.

14 Jali M V, Mahishale V K, Hiremath M B, et al. Diabetes mellitus and smoking among tuberculosis patients in a tertiary care centre in Karnataka, India. Public Health Action 2013; 3 (Suppl): S51–S53.

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

Page 3: DM TB Review Nov 2013_entire publication.pdf

Public Health Action

REVIEW ARTICLE

Epidemiology and interaction of diabetes mellitus and tuberculosis and challenges for care: a reviewA. D. Harries,1,2 S. Satyanarayana,3 A. M. V. Kumar,3 S. B. Nagaraja,4,5 P. Isaakidis,6 S. Malhotra,7

S. Achanta,4 B. Naik,4 N. Wilson,3 R. Zachariah,8 K. Lönnroth,9 A. Kapur10

still exacts a huge toll, especially among the poorest people on the globe.3 Several key obstacles continue to thwart control efforts: many people are infected with Mycobacterium tuberculosis and are at risk of developing active TB during their lifetime; many vulnerable peo-ple with presumptive TB do not have access to afford-able, high-quality TB diagnostic and treatment services; multidrug-resistant TB (MDR-TB, defi ned as M. tuber-culosis resistant to at least isoniazid and rifampicin) is a serious threat in some settings; and in Africa, espe-cially in the southern part of the continent, HIV/AIDS fuels an already burgeoning epidemic. Other risk fac-tors have also emerged in recent years as important determinants of the TB epidemic, one of which is DM.

In this review, we discuss 1) the global epidemiol-ogy of and evidence for interaction of the two diseases, DM and TB; 2) the new collaborative framework for the care and control of TB and DM; and 3) challenges for care.

GLOBAL EPIDEMIOLOGYOF DIABETES MELLITUS AND TUBERCULOSIS

Diabetes mellitusDM is a chronic condition that occurs when the body cannot produce enough insulin or cannot use it effec-tively. As a result, a person with DM does not utilise glucose properly, and glucose circulates in the blood at high levels (hyperglycaemia), causing tissue damage over time. DM was fi rst recognised in 1500 BC by the ancient Egyptians, and the term diabetes mellitus was used by Greek physicians to describe persons with uri-nary frequency and in whom the urine also tasted sweet.4 According to the World Health Organization (WHO), three common forms of DM account for the majority of cases: type 1, type 2 and gestational dia-betes mellitus (GDM); their defi nitions are given in Ta-ble 1.5 People with high blood glucose levels that are below the thresholds required for a diagnosis of DM are said to have pre-diabetes. This may occur either as impaired fasting glucose or as impaired glucose toler-ance (IGT), and these people have an increased risk of type 2 DM.

People with DM may suffer from a number of seri-ous health problems, such as cardiovascular disease, renal disease (nephropathy), eye disease (retinopathy), nerve damage (neuropathy), diabetic foot and infec-tions that include TB. DM may be diagnosed on the

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi.org/10.5588/pha.13.0024

The global burden of diabetes mellitus (DM) is immense, with numbers expected to rise to over 550 million by 2030. Countries in Asia, such as India and China, will bear the brunt of this unfolding epidemic. Persons with DM have a significantly increased risk of developing active tu-berculosis (TB) that is two to three times higher than in persons without DM. This article reviews the epidemiol-ogy and interactions of these two diseases, discusses how the World Health Organization and International Union Against Tuberculosis and Lung Disease developed and launched the Collaborative Framework for the care and control of TB and DM, and examines three important challenges for care. These relate to 1) bi-directional screen-ing of the two diseases, 2) treatment of patients with dual disease, and 3) prevention of TB in persons with DM. For each area, the gaps in knowledge and the priority re-search areas are highlighted. Undiagnosed, inadequately treated and poorly controlled DM appears to be a much greater threat to TB prevention and control than previ-ously realised, and the problem needs to be addressed. Prevention of DM through attention to unhealthy diets, sedentary lifestyles and childhood and adult obesity must be included in broad non-communicable disease preven-tion strategies. This collaborative framework provides a template for action, and the recommendations now need to be implemented and evaluated in the field to lay down a firm foundation for the scaling up of interventions that work and are effective in tackling this dual burden of disease.

Chronic, non-communicable diseases such as car-diovascular disease, diabetes mellitus (DM), can-

cer and chronic obstructive pulmonary diseases have emerged as the next twenty-fi rst century global epi-demic, and have already become the leading causes of death and disability worldwide.1 Among these diseases, the global burden of DM is immense. In 2012, there were an estimated 371 million people living globally with DM, with numbers expected to rise to 552 mil-lion by 2030.2 Over half of these patients are undiag-nosed, and complications due to diabetes are a major cause of disability and reduced quality of life.

Tuberculosis (TB) is a major communicable disease which, along with the human immunodefi ciency vi-rus and acquired immune-defi ciency syndrome (HIV/AIDS) and malaria, is responsible for considerable mor-bidity and mortality worldwide. Although TB control has come a long way in the last 20 years, the disease

AFFILIATION 1 International Union

Against Tuberculosis and Lung Disease (The Union), Paris, France

2 London School of Hygiene & Tropical Medicine, London, UK

3 The Union South-East Asia Office, New Delhi, India

4 Office of the WHO Representative in India, World Health Organization, New Delhi, India

5 Department of Community Medicine, Employees State Insurance Corporation (ESIC) Medical College, Bangalore, India

6 Médecins Sans Frontières, Brussels Operational Centre, Mumbai, India

7 All India Institute of Medical Sciences, New Delhi, India

8 Medical Department, Operational Research Unit, Médecins Sans Frontières, Brussels Operational Centre, Luxembourg, Luxembourg

9 Stop TB Department, World Health Organization, Geneva, Switzerland

10 World Diabetes Foundation, Gentofte, Denmark

CORRESPONDENCEA D Harries Old Inn CottageVears LaneColden CommonWinchester SO21 1TQ, UK Tel: (+44) 1962 714 29 e-mail: [email protected]

KEY WORDSDM; TB; DM-TB interaction; epidemiology; challenges for care

PHA 2013; 3(S1): S3–S9© 2013 The Union

Received 3 May 2013Accepted 15 July 2013

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Public Health Action Interaction of DM and TB S4

basis of fasting plasma glucose, 2-hour plasma glucose following a 75 g oral glucose tolerance test (OGTT), random plasma glucose in a patient with classic hyperglycaemic symptoms or glycosylated haemoglo-bin (HbA1c). The different cut-off values used by the WHO, which are generally those used in most low- and middle-income countries (LMICs), are shown in Table 2.6 In recognition of the widespread use of capil-lary sampling in these countries, fasting values for venous and capillary plasma glucose are regarded as identical,6 although not all front-line clinicians are prepared to accept this stance.

Recent, up-to-date estimates of the worldwide DM burden are provided by the International Diabetes Federation in their Diabetes Atlas.2 Data for this are supplemented through epidemiological studies, health examination surveys, population-based prevalence studies and WHO STEPwise surveillance studies.7,8 In the 2012 update to the Atlas, it was estimated that 371 million people worldwide had DM. About 80% live in LMICs, and, if the trends of the past 10–15 years con-tinue, over 550 million people will have DM by 2030. This equates to one in ten globally, although there will be marked differences from country to country, de-pending on factors such as urbanisation and lifestyle. In 2012, a further 280 million people worldwide had IGT, with the number expected to rise to 398 million by 2030.

The majority of people with DM are in the age group 40–59 years, with little difference in terms of sex. The mean age at onset of type 2 DM in LMICs is at least a decade earlier than in industrialised countries. Given the association between DM and lifestyles such as unhealthy diet and physical inactivity, there are more people with DM in urban areas than in rural areas, with the divide in 2030 estimated at 314 million to 143 mil-lion, respectively. It is estimated that about 50% of peo-ple who have DM, mostly those with type 2 disease, are undiagnosed. In 2012, an estimated 4.8 million people aged 20–79 years died from DM, with little dif-ference between males and females. LMICs account for 88% of all premature mortality due to DM.2

Asia is the global region most affected by DM.2,9 The disease develops at a younger age than in white populations of European descent, and associated car-diovascular disease is common in young Asian people. China and India are the two countries with the highest prevalence of DM, with respectively 92.3 million and 63 million people aged 20–79 years estimated to have the disease in each country. In India, DM prevalence peaks at 60–69 years, while in China it peaks later, at 70–89 years. Other high-burden Asian countries include Indonesia, Japan, Pakistan, Bangladesh, Malaysia and the Philippines. Type 2 DM in Asia is often associated with a strong family history of diabetes, with most Asian patients having a fi rst-degree relative with the disease. It is unclear at present whether this strong family history is genetic and/or whether it is a result of shared risk behaviour and early life programming.

TuberculosisTB is an infectious disease of equally great antiquity as DM, with evidence of spinal involvement being found in Egyptian mummies dating back to several thousand years BC. Although common in various populations over the centuries, it acquired notoriety during the Industrial Revolution in Europe as ‘the captain of all these men of death’.10 The discovery of the tubercle bacillus in 1882 by Robert Koch, the documentation of the close link between TB and poverty, undernutri-tion and poor living conditions, the discovery and use of anti-tuberculosis drugs between the 1940s and 1970s and the introduction of combination chemotherapy to cure disease and prevent the development of drug resistance all led to modern-day control efforts.

ACKNOWLEDGEMENTSA workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Opera-tional Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Operational Research Unit, Médecins Sans Frontières, Luxembourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark. The views expressed in this article are the sole responsi-bility of the authors and do not necessarily reflect the positions and views of their affiliated institutions.Conflict of interest: none declared.

TABLE 1 Classification of diabetes mellitus*

Classification Definition

Type 1 DM Type 1 diabetes mellitus encompasses the majority of cases that are primarily due to pancreatic islet beta-cell destruction, attributable either to an autoimmune process or to an unknown cause (idiopathic). These patients are prone to ketoacidosis and require insulin injections for survival. It does not include cases with beta-cell destruction or failure to which specific causes can be assigned (e.g., cystic fibrosis, mitochondrial defects, etc.)

Type 2 DM Type 2 is the most common form of diabetes mellitus. It is characterised by disorders of insulin action and insulin secretion, either of which may be the predominant feature. Both are usually present at the time that this form of diabetes manifests clinically. By definition, the specific reasons for the development of these abnormalities are not yet known.

Gestational DM Gestational diabetes is carbohydrate intolerance resulting in hyperglycaemia of variable severity, with onset or first recognition during pregnancy. It does not exclude the possibility that the glucose intolerance may antedate pregnancy but had been previously unrecognised. The definition applies irrespective of whether or not insulin is used for treatment or whether the condition persists after pregnancy. Gestational DM usually resolves after pregnancy, but mothers and babies both have a higher risk of developing type 2 DM later in life.

* Adapted from World Health Organization.5DM = diabetes mellitus.

TABLE 2 World Health Organization diagnostic criteria for DM or pre-diabetes*

DM Pre-diabetes

Fasting plasma glucose ⩾7.0 mmol/l 6.1–6.9 mmol/l⩾126 mg/dl 110–125 mg/dl

2 h plasma glucose after OGTT

⩾11.1 mmol/l 7.8–11.0 mmol/l⩾200 mg/dl 140–199 mg/dl

Random plasma glucose ⩾11.1 mmol/l⩾200 mg/dl

Glycosylated haemoglobin ⩾6.5%

* Adapted from World Health Organization and International Diabetes Federation.6DM = diabetes mellitus; OGTT = oral glucose tolerance test.

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Public Health Action Interaction of DM and TB S5

In 1994, the WHO developed a standardised framework for TB control, branded as ‘DOTS’.11 The crucial components of DOTS are: 1) standardised case fi nding and registration, 2) standard-ised anti-tuberculosis treatment regimens for new and previously treated disease, and 3) monitoring, recording and reporting of cases and treatment outcomes using internationally agreed defi ni-tions.12 The Stop TB Partnership, which has been in existence for nearly a decade and has over 700 partners worldwide, endorsed two epidemiological targets in 2000, linked to the Millennium Development Goals. These targets are by 2015 to reduce TB preva-lence and death rates by 50% compared with 1990 levels, and by 2050 to eliminate TB as a public health problem (defi ned as an in-cidence of less than 1 TB case per million people per year). To achieve these targets, a Stop TB Strategy was agreed upon in 2006 (Table 3) and launched along with a Global Plan to Stop TB.13,14 The Stop TB Strategy is focused on the expansion of high quality DOTS, but at the same time addresses other important issues such as HIV-associated TB, drug-resistant TB, engagement of all public and private health care providers, health systems strength-ening, patient-centred approaches and programme-based opera-tional research.

From 1995, DOTS-based programmes were initiated worldwide, and by 2011, 204 countries and territories were using DOTS and reporting data to the WHO. During this time, the global case detec-tion rate of TB rose from 15% to 67%, and the treatment success rate in new smear-positive pulmonary TB rose from 77% to 87%.15 It is estimated that 51 million people have been successfully treated for TB in countries that have adopted the DOTS strategy, saving

20 million lives, and as a consequence of such efforts, the incidence of and mortality from TB have been falling for several years.

Despite the progress made, TB continues to be a major public health problem in many LMICs. In 2011, there were an estimated 8.7 million cases of TB (13% co-infected with HIV) and 1.4 mil-lion TB-related deaths.15 The burden of TB is highest in Asia and Africa, with India and China together accounting for almost 40% of the world’s TB cases; India has an estimated 2.2 million cases per annum and China about 1.0 million. Globally, 5.8 million TB cases were notifi ed and reported to the WHO in 2011, leaving 2.9 million patients unaccounted for. The emergence of MDR-TB has been of major global concern: of the 310 000 estimated new MDR-TB cases in 2011, only 19% were notifi ed and even fewer were treated according to international recommendations.15

About one third of the world’s population is infected with M. tu-berculosis, of whom about 5–10% will develop active TB at some time in their lives, the greatest risk being within the fi rst few years of infection. Infants and young children up to the age of 5 years are at relatively high risk, while those aged 5–15 years are rela-tively resistant; the risk then rises again through adolescence, re-mains stable during adulthood and increases once again in the el-derly. Other risk factors, including DM, are shown in Table 4. HIV/AIDS is the strongest risk factor, with the incidence of TB in-creasing as the CD4 lymphocyte count declines.16 Although at the individual level the risk of developing TB is considerably lower in people with DM compared with those who have HIV, the much larger and rapidly growing pool of people with DM makes the global and population-attributable fraction of TB due to DM simi-lar to that seen with HIV.3

INTERACTION BETWEEN DIABETES MELLITUS AND TUBERCULOSIS

Evidence of interactionThe association between DM and TB was suggested as far back as Roman times and, since then until recently, anecdotal reports and case studies have kept the link alive. As effective treatment for both DM and TB became available and successful public health measures were put in place to control TB, the association between the two diseases was perceived to be less relevant, especially as TB became relatively rare in high-income countries where DM was prevalent, while DM was believed to be a minor problem in poor countries where TB was endemic.

The situation has changed dramatically in the last decade, with recognition of the enormous and unfolding epidemic of DM in LMICs, a slower decline in global TB incidence rates than would be expected from epidemiological modelling, and a rekindling of interest in the association between DM and TB. The interaction between the two diseases was brought to global attention by three important publications in 2007 and 2008. Catherine Stevenson

TABLE 3 The 2006 Stop TB Strategy*

1 Pursue high quality DOTS expansion and enhancement• Secure political commitment with adequate and sustained funding• Ensure case detection through quality-assured bacteriology• Provide standardised treatment, with supervision and patient support• Ensure an effective drug supply and management system• Monitor and evaluate performance and impact

2 Address TB-HIV, MDR-TB and needs of poor, vulnerable populations• Implement and scale up collaborative TB-HIV activities• Scale up the prevention and control of MDR-TB• Address the needs of prisoners, refugees and other high-risk groups

and situations3 Contribute to health systems strengthening based on primary

health care• Actively participate in efforts to improve health policies, human

resources, financing, management, service delivery and information systems

• Strengthen infection control in health services and congregate settings

• Upgrade laboratory networks and implement the Practical Approach to Lung Health

• Adapt successful approaches and innovations from other fields4 Engage all care providers

• Involve public-public and public-private mix (PPM) approaches• Promote the use of International Standards for Tuberculosis Care

(ISTC) 5 Empower people with TB and communities through partnership

• Pursue advocacy, communication and social mobilisation• Foster community participation in TB care and prevention• Promote use of the Patient’s Charter for Tuberculosis Care

6 Enable and promote research• Conduct programme-based operational research• Advocate research to develop new diagnostics, drugs and vaccines

* Adapted from World Health Organization.13

TB = tuberculosis; HIV = human immunodeficiency virus; MDR-TB = multidrug-resistant tuberculosis (Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin).

TABLE 4 Risk factors for the development of active TB

• HIV/AIDS• Other causes of immune suppression (e.g., treatment with

corticosteroids)• Silicosis• Malnutrition • Indoor air pollution• Cigarette smoking• Harmful alcohol use and other drug abuse• Diabetes mellitus

TB = tuberculosis; HIV = human immunodeficiency virus; AIDS = acquired immune-deficiency syndrome.

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Public Health Action Interaction of DM and TB S6

and colleagues undertook a Medline literature search of studies published after 1995 that quantifi ed the association between DM and TB.17 They identifi ed nine studies that all showed signifi cant and clinically important associations, with the increase in the risk (odds) of TB varying from 1.5 to 7.8 for those with DM. Limita-tions were that most studies had not measured or controlled ade-quately for potential confounders. The same group further as-sessed through an epidemiological model the potential impact of DM as a risk factor for incident pulmonary TB in India.18 In 2000, it was estimated that DM accounted for 14.8% of pulmonary TB cases (uncertainty range 7.1–23.8%) and 20.2% of smear-positive pulmonary TB cases (uncertainty range 8.3–41.9%). A systematic review and meta-analysis by Jeon and Murray used various data-bases to identify observational studies dating back to 1965 that had reported an age-adjusted quantitative estimate of the associa-tion between DM and active TB.19 Thirteen observational studies met the selection criteria, with 1 786 212 participants and 17 698 TB cases. Across the three cohort studies, the relative risk of TB in DM patients was 3.1 (95% confi dence interval [CI] 2.3– 4.3), and in the case control studies the odds ratios (ORs) ranged from 1.16 to 7.83. Further reviews have confi rmed these fi ndings and have suggested that overall the risk of TB in persons with DM is two to three times higher.20,21

Is the interaction between diabetes mellitus and tuberculosis biologically plausible? The answer is ‘yes’. DM increases the general risk of infection, but the precise mechanisms by which DM predisposes to TB are still not clear and require further research. Unlike the situation with HIV infection, in which cell-mediated immunity is gradually compromised by progressive depletion and dysfunction of CD4 T-lymphocytes, DM impairs cell-mediated immunity by impairing the function and activation of macrophages, monocytes and lym-phocytes, with additional potential roles played by pulmonary microangiopathy, renal dysfunction and vitamin defi ciencies.17 In addition, patients with uncontrolled hyperglycaemia appear to be at higher risk for TB than those with controlled blood glucose lev-els, suggesting that uncontrolled hyperglycaemia is an important determinant in this interaction.22,23

Collaborative Framework for Care and Control of Diabetes and TuberculosisIn December 2009, an expert meeting was held in Paris to review the evidence of the association between DM and TB,24 to defi ne the research agenda needed to reduce the dual burden of disease,25

and to assess whether the evidence was strong enough to formu-late international guidelines for the care and control of dual dis-ease. After much refl ection, it was decided that the currently avail-able evidence to support specifi c recommendations, although incomplete, was suffi cient to develop a provisional framework for action, and that this should be used to stimulate further research to strengthen the evidence base for appropriate interventions. This framework was launched in August 2011, and it now serves as a guide to help policy makers and implementers move forward to combat the looming epidemic of DM and TB.26 The framework includes provisional recommendations (pending better evidence) packaged under three main themes: 1) the establishment of mech-anisms for collaboration, 2) the detection and management of TB in patients with DM, and 3) the detection and management of DM in patients with TB (Table 5).26 Operational and other research is encouraged to build the evidence base, which will be reviewed in 2015 to determine whether recommendations at that time can be made more defi nitive.

CHALLENGES FOR CARE FOR DUAL DISEASE

Within the Framework for Care and Control of DM and TB,26 there are three main challenges, which are discussed below.

Bi-directional screening of diabetes and tuberculosis in routine settingsThe framework provisionally recommends screening for DM in all people diagnosed with TB, and screening for TB in people with DM in countries with a high prevalence of TB (>100 per 100 000 population). The latter recommendation has recently been re-peated in the WHO’s 2013 guidelines on systematic screening for active TB in risk groups.27

A systematic review of bi-directional screening for DM and TB in 2009 using strict inclusion criteria identifi ed 12 studies on screening people with DM for TB and 18 studies on screening TB patients for DM.28 In persons with DM, screening for TB showed high rates of TB, ranging from 1.7% to 36%, with the screening yield being highly dependent on the underlying TB prevalence and on the severity of DM. Because DM is much more common than TB, in patients with TB the screening for DM yielded a high prevalence of DM, ranging from 1.9% to 35%.

Studies in the last 2–3 years have shown a high frequency of TB and DM co-morbidity in many areas of the world. Unpub-lished reports show a very high prevalence of DM in people with TB in the South Pacifi c of between 40% and 45%. In South India, one study in the state of Karnataka showed a DM prevalence of 32% in TB patients;29 in the state of Kerala, 44% of TB patients had DM,30 and in the state of Tamil Nadu, 25% of TB patients had DM and a further 25% had IGT.31 On the Texas-Mexico border, the prevalence of DM among TB patients was 39% in Texas and 36% in Mexico.32 In a recent study from Tanzania, the prevalence of DM in TB patients was 16.7% compared with 9.4% amongst controls, with a stronger association among non-HIV-infected compared with HIV-infected patients.33 A similar case-control study in Pakistan reported a DM prevalence of 16.0% and an IGT prevalence of 34% among TB patients, compared with 7% and 28%, respectively, in the general community.34

There is little published information on whether DM has any effect on TB case notifi cations or estimated case numbers at coun-try level. An ecological association between changes in DM and TB prevalence across 46 countries has been observed,35 and an

TABLE 5 Collaborative activities to reduce the dual burden of diabetes and TB*

1 Establish mechanisms for collaboration• Set up means of coordinating diabetes and TB activities• Conduct surveillance of TB disease prevalence among people with

diabetes in medium and high TB burden settings • Conduct surveillance of diabetes prevalence in TB patients in

all countries• Conduct monitoring and evaluation of collaborative diabetes and TB

activities2 Detect and manage TB in patients with diabetes

• Intensify detection of TB among people with diabetes • Ensure TB infection control in health care settings where diabetes is

managed• Ensure high-quality TB treatment and management in people

with diabetes 3 Detect and manage diabetes in patients with TB

• Screen TB patients for diabetes• Ensure high-quality diabetes management among TB patients

* Adapted from World Health Organization and International Union Against Tubercu-losis and Lung Disease.26

TB = tuberculosis.

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analysis in India has suggested that increased DM prevalence be-tween 1998 and 2008 contributed to an increase in the total num-ber of TB cases which exceeded the rate of population growth during the same time period.36 It will be important to monitor these associations more closely in the future, especially in coun-tries in Asia with escalating DM epidemics.

At the health facility level, there are various challenges with bi-directional screening. In TB patients, DM cannot be recognised clinically and some form of blood glucose measurement is there-fore required to determine its presence or absence. How this is best done in a routine situation still needs to be clarifi ed. In India and China, two large operational studies showed that TB patients could be screened for DM at the time of registration by asking fi rst about the presence or absence of known DM, and, in those denying any known disease, using random blood glucose mea-surements to identify those at risk, followed by fasting blood glu-cose measurements in those needing further screening.37,38 In both countries, the large majority of patients were willing to be screened, and a total of 12–13% of TB patients screened had DM, with previously unrecognised new disease being diagnosed in 3% of patients in China and 5% of patients in India based on fasting blood glucose values. The majority of these patients were referred for diabetes care. Screening of TB patients is thus useful in help-ing to identify the large proportion of persons with DM who have undiagnosed disease in the community and who would benefi t from earlier diagnosis and treatment.

Many questions, however, need to be answered. For example, previous studies have shown that it may be more reliable to screen for DM later in the course of anti-tuberculosis treatment rather than at the start, because as a chronic infectious disease TB may elevate blood glucose levels, resulting in false-positive diagno-ses.39–42 On the other hand, in a large DM prevalence study in China,7 it was found that screening with fasting blood glucose missed nearly half of the DM patients diagnosed with a 2 h 75 g OGTT. The latter test is suitable for research surveys but inappro-priate for screening individuals within routine general health ser-vices. These issues highlight the need at the screening level for better, simpler and non-expensive point-of-care glucose measure-ment tests.

In India and China, pilot studies assessed the screening of DM patients for TB with a traditional symptom-screen approach every time the patient came to the clinic, and referral of those with a positive screen for TB investigations.43,44 This approach was feasi-ble and resulted in high detection rates of TB that varied from 300 to 800 per 100 000 people screened per quarter in China to 600–950/100 000 in India. However, several operational chal-lenges were identifi ed that need to be overcome if such screening is to be rolled out on a larger scale. These include 1) the reluc-tance of busy DM doctors to take on the additional work needed to screen for and monitor this infectious disease, 2) the low sensi-tivity of current TB diagnostic approaches that rely on sputum smear examination and chest radiography, and 3) the absence of structured recording or reporting systems in most DM clinics, making it diffi cult to have reliable denominators for calculating TB case detection rates. In particular, symptom screening has low sensitivity, especially for the detection of TB early in the course of the disease. Screening by chest radiography would give a higher yield,45 but the cost and logistical challenges would also be greater. More research is needed to determine the most appropriate screening and diagnostic algorithm and the cost-effectiveness of different approaches.

With both bi-directional screening systems, more information is also needed about what phenotypes are especially at risk of dual

disease (age, sex, body mass index), the effects of co-morbid dis-ease and associated exposures such as alcohol and smoking, and how dual care can best be integrated within the same health facil-ity or clinic while at the same time paying attention to good TB infection control.

Treatment of patients with dual diseaseA systematic review of studies from 1980 to 2010 focused on the treatment of patients with dual disease and assessed the results of sputum culture conversion at 2–3 months of anti-tuberculosis treatment, death during treatment, and relapse of TB after success-ful completion of treatment.46 There were nine studies assessing the infl uence of DM on prolonging culture positivity at 2–3 months of treatment, with six studies reporting relative risks (RRs) of >2, and three reporting RRs of <1. The risk of death during TB treat-ment was assessed in 23 studies, with a pooled and signifi cantly higher RR of 1.89 (95%CI 1.52–2.36) in patients with DM. Four of these studies adjusted for age and other potential confounders and found a pooled OR of 4.95 (95%CI 2.69–9.10), suggesting that patients who die during anti-tuberculosis treatment have other strong risk factors for death, such as HIV and co-morbidities, which reduce the impact of DM in the unadjusted analyses. Five studies assessed the risk of TB relapse, with a pooled and increased signifi cant RR of 3.89 (95%CI 2.43–6.23) in patients with DM. Whether these patients experienced a recurrence of the former in-fection (true relapse) or re-infection with a new strain of M. tuber-culosis is not known. No consistent associations were found be-tween DM and drug-resistant TB, although this area requires more detailed and prospective research.

Current international guidelines disseminated by the WHO recommend that treatment for new cases of TB be standardised for 6 months with rifampicin-based TB treatment regimens, re-gardless of other co-morbidities such as HIV infection or DM.12

Whether longer or different treatment in TB patients with DM has a benefi cial effect on treatment outcomes and whether it re-duces the risk of recurrent disease is not known, and needs pro-spective research. Similarly, whether more aggressive management and control of DM might improve the treatment response to TB remains unclear. There are many other unanswered questions that include the infl uence of poor DM control on death and recurrent TB, the best oral hypoglycaemic drugs to use with anti-tuberculosis drugs, drug-drug interactions and overlapping toxicities, the tim-ing and aetiology of death in DM patients, the reasons for recur-rent disease, and interventions that may reduce the frequency of these adverse events. Moreover, as second-line anti-tuberculosis treatment is increasingly being offered to patients in settings with a high MDR-TB burden, we need to study the challenges of co-a dministration of second-line anti-tuberculosis agents with oral hypoglycaemic drugs. These questions are best answered through prospective studies, such as a recently published study from south-ern Mexico, which found that patients with DM and TB had higher rates of delayed sputum conversion, treatment failure and recurrent TB after treatment, with one fi fth of the recurrence due to new infection.47 While there is no direct evidence that early diagnosis and optimal treatment of DM in people with TB im-proves TB treatment outcomes, such an effect is plausible. More-over, considering the high prevalence of undiagnosed DM in peo-ple with TB, screening and proper management of DM in TB patients should be pursued to improve general health outcomes.

Preventing tuberculosis in people with diabetesTwo studies conducted before the 1970s showed that active TB in people with DM could be prevented with TB chemoprophylaxis.48,49

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However, both studies were methodologically fl awed, and the true benefi t of chemoprophylaxis remains unknown. The question can only be properly answered through a randomised controlled trial. As poor glucose control is associated with a higher risk of devel-oping TB, it is plausible that improved DM management in itself is a means of preventing TB disease in a person with latent tu-berculous infection. However, no trial has been conducted to evaluate such an effect. Finally, it will be important to ascertain whether DM clinics are areas where TB transmission occurs, and, if so, to determine the measures that need to be put in place to prevent this spread of TB.

CONCLUSION

In LMICs, and especially in Asia, the DM epidemic is growing rap-idly. There is now strong evidence that there is an important asso-ciation between DM and TB and that this association results in poor TB treatment outcomes. Undiagnosed, inadequately treated and poorly controlled DM appears to be a much greater threat to TB care and prevention than previously realised,50,51 and this needs to be tackled. Upstream prevention of DM through attention to healthier diets, more physical activity and reduction of childhood and adult obesity must be included in broad non-communicable disease prevention strategies. Simple point-of-care diagnostic tests are needed for DM, and simple, standardised and affordable inter-ventions to treat and monitor established DM and IGT that are easy to access must be scaled up in all countries. Adapting DOTS principles may help to bring a more structured approach to DM care delivery, something that is currently lacking in most high DM burden countries.52,53 Heightened clinical suspicion for TB is needed for people with DM, especially among those who live in TB-endemic areas, and systematic screening should be considered. However, more research is needed to establish appropriate TB screening eligibility criteria and algorithms in people with DM. A framework has now been established for reducing the dual bur-den of disease, and pilot studies have started to show how to im-plement some of the screening and monitoring initiatives. A col-lection of evidence is needed to bring about the scaling up of interventions that work and that clearly make a difference.

References 1 Lozano R M, Naghavi M, Foreman K, et al. Global and regional mortality from

235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study. Lancet 2012; 380: 2095–2128.

2 International Diabetes Federation. IDF diabetes atlas. 5th ed, 2012 update. Unwin N, Whiting D, Guariguata L, et al., eds. Brussels, Belgium: Interna-tional Diabetes Federation, 2012. http://www.idf.org/diabetesatlas/5e/Update 2012 Accessed August 2013.

3 Lönnroth K, Castro K G, Chakaya J M, et al. Tuberculosis control and elimi-nation 2010–2050: cure, care, and social development. Lancet 2010; 375: 1814–1829.

4 Polonsky K S. The past 200 years in diabetes. N Engl J Med 2012; 367: 1332– 1340.

5 World Health Organization, Department of Non-communicable Disease Sur-veillance. Defi nition, diagnosis and classifi cation of diabetes mellitus and its complications. Report of a WHO Consultation. WHO/NCD/NCS/99.2. Ge-neva, Switzerland: WHO, 1999.

6 World Health Organization/International Diabetes Federation. Defi nition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Sum-mary of technical report and recommendations. Report of a WHO/IDF con-sultation. Geneva, Switzerland: WHO, 2006.

7 Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China. N Engl J Med 2010; 362: 1090–1101.

8 Danaei G, Finucane M M, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analy-sis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 2011; 378: 31– 40.

9 Ramachandran A, Ma R C W, Snehalatha C. Diabetes in Asia. Lancet 2010; 375: 408– 418.

10 Harries A D, Dye C. Tuberculosis. Ann Trop Med Parasitol 2006; 100: 415– 431. 11 World Health Organization. Global tuberculosis programme. Framework for

effective tuberculosis control. WHO/TB/94.179. Geneva, Switzerland: WHO, 1994.

12 World Health Organization. Treatment of tuberculosis: guidelines for na-tional programmes. 4th ed. WHO/HTM/TB/2009.420. Geneva, Switzerland: WHO, 2010.

13 World Health Organization. The Stop TB Strategy. Building on and enhancing DOTS to meet the TB-related Millennium Development Goals. WHO/HTM/TB/2006.368. Geneva, Switzerland: WHO, 2006.

14 Stop TB Partnership/World Health Organization. Global plan to stop TB 2006–2015. WHO/HTM/STB/2006.35. Geneva, Switzerland: WHO, 2006.

15 World Health Organization. Global tuberculosis report 2012. WHO/HTM/TB/2012.6. Geneva, Switzerland: WHO, 2012.

16 Lawn S D, Harries A D, Williams B G, et al. Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it? Int J Tuberc Lung Dis 2011; 15: 571–581.

17 Stevenson C R, Critchley J A, Forouhi N G, et al. Diabetes and the risk of tu-berculosis: a neglected threat to public health. Chronic Illn 2007; 3: 228–245.

18 Stevenson C R, Forouhi N G, Roglic G, et al. Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence. BMC Public Health 2007; 7: 234.

19 Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tubercu-losis: a systematic review of 13 observational studies. PLOS Med 2008; 5: e152.

20 Dooley K E, Chaisson R E. Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis 2009; 9: 737–746.

21 Ruslami R, Aarnoutse R E, Alisjahbana B, van der Ven A J, van Crevel R. Im-plications of the global increase of diabetes for tuberculosis control and pa-tient care. Trop Med Int Health 2010; 15: 1289–1299.

22 Leung C C, Lam T H, Chan W M, et al. Diabetic control and risk of tubercu-losis: a cohort study. Am J Epidemiol 2008; 167: 1486–1494.

23 Harries A D, Lin Y, Satyanarayana S, et al. The looming epidemic of diabetes-associated tuberculosis: learning lessons from HIV-associated tuberculosis. Int J Tuberc Lung Dis 2011; 15: 1436–1444.

24 Ottmani S-E, Murray M B, Jeon C Y, et al. Consultation meeting on tubercu-losis and diabetes mellitus: meeting summary and recommendations. Int J Tuberc Lung Dis 2010; 14: 1513–1517.

25 Harries A D, Murray M B, Jeon C Y, et al. Defi ning the research agenda to re-duce the joint burden of disease from diabetes mellitus and tuberculosis. Trop Med Int Health 2010; 15: 659–663.

26 World Health Organization/International Union Against Tuberculosis and Lung Disease. Provisional collaborative framework for care and control of tuberculosis and diabetes. WHO/HTM/TB/2011.15. Geneva, Switzerland: WHO, 2011.

27 World Health Organization. Systematic screening for active tuberculosis: principles and recommendations. WHO/HTM/TB/2013.04. Geneva, Switzer-land: WHO, 2013.

28 Jeon C Y, Harries A D, Baker M A, et al. Bi-directional screening for tubercu-losis and diabetes: a systematic review. Trop Med Int Health 2010; 15: 1300–1314.

29 Gupta S, Shenoy V P, Bairy I, Srinivasa H, Mukhopadhyay C. Diabetes melli-tus and HIV as co-morbidities in tuberculosis patients of rural South India. J Infect Public Health 2011; 4: 140–144.

30 Balakrishnan S, Vijayan S, Nair S, et al. High diabetes prevalence among tu-berculosis cases in Kerala, India. PLOS ONE 2012; 7: e46502.

31 Viswanathan V, Kumpatla S, Aravindalochanan V, et al. Prevalence of diabetes and pre-diabetes and associated risk factors among tuberculosis patients in In-dia. PLOS ONE 2012; 7: e41367.

32 Restrepo B I, Camerlin A J, Rahbar M H, et al. Cross-sectional assessment re-veals high diabetes prevalence among newly-diagnosed tuberculosis cases. Bull World Health Organ 2011; 89: 352–359.

33 Faurholt-Jepsen D, Range N, Praygod G, et al. Diabetes is a risk factor for pulmonary tuberculosis: a case-control study from Mwanza, Tanzania. PLOS ONE 2011; 6: e24215.

34 Codlin A, Nadeem A, Lotia I, et al. Diabetes, pre-diabetes and tuberculosis in an Asian mega-city: Karachi, Pakistan. Int J Tuberc Lung Dis 2012; 16 (Suppl 1): S338–S339. [Abstract]

35 Goldhaber-Fiebert J D, Jeon C Y, Cohen T, Murray M B. Diabetes mellitus and tuberculosis in countries with high tuberculosis burdens: individual risks and social determinants. Int J Epidemiol 2011; 40: 417– 428.

36 Dye C, Trunz B B, Lönnroth K, Roglic G, Williams B G. Nutrition, diabetes and tuberculosis in the epidemiological transition. PLOS ONE 2011; 6: e21161.

37 Li L, Lin Y, Mi F, et al. Screening of patients with tuberculosis for diabetes mellitus. Trop Med Int Health 2012; 17: 1294–1301.

38 India Tuberculosis-Diabetes Study Group. Screening of patients with tuber-culosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

39 Kishore B, Nagrath S P, Mathur K S, Hazra D K, Agarwal B D. Manifest, chem-ical and latent chemical diabetes in pulmonary tuberculosis. J Assoc Physi-cians India 1973; 21: 875–881.

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Public Health Action Interaction of DM and TB S9

47 Jimenez-Corona M E, Cruz-Hervert L P, Garcia-Garcia L, et al. Association of diabetes and tuberculosis: impact on treatment and post-treatment out-comes. Thorax 2013; 68: 214–220.

48 Pfaffenberg R, Jahler H. [Isoniazid and recurrence of tuberculosis in diabet-ics]. Z Tuberk 1958; 111: 167–173. [German]

49 Lesnichii A V, Karpina L Z. [Experience with the chemoprophylaxis of pul-monary tuberculosis in diabetes mellitus patients]. Probl Tuberk 1969; 47: 1–3. [Russian]

50 Sullivan T, Amor Y B. The co-management of tuberculosis and diabetes: chal-lenges and opportunities in the developing world. PLOS Med 2012; 9: e1001269.

51 Kapur A, Harries A D. The double burden of diabetes and tuberculosis—pub-lic health implications. Diabetes Res Clin Pract 2013; Jan 7: pii: S0168-8227(12)00497-4.

52 Harries A D, Jahn A, Zachariah R, Enarson D. Adapting the DOTS framework for tuberculosis control to the management of non-communicable diseases in sub-Saharan Africa. PLOS Med 2008; 5: e124.

53 Khader A, Farajallah L, Shahin Y, et al. Cohort monitoring of persons with diabetes mellitus in a primary health care clinic for Palestine refugees in Jor-dan. Trop Med Int Health 2012; 17: 1569–1576.

40 Goyal B N, Nigam P, Dubey A L, Joshi L D, Saxena H N. Study of the diabetic status in pulmonary tuberculosis. J Diabetic Association India 1978; 18: 191–197.

41 Singh M M, Biswas S K, Shah A. Impaired glucose tolerance in active pulmo-nary tuberculosis. Indian J Tuberc 1984; 31: 118–121.

42 Oluboyo P O, Erasmus R T. The signifi cance of glucose intolerance in pulmo-nary tuberculosis. Tubercle 1990; 71: 135–138.

43 Lin Y, Li L, Mi F, et al. Screening patients with diabetes mellitus for tubercu-losis in China. Trop Med Int Health 2012; 17: 1302–1308.

44 India Diabetes Mellitus-Tuberculosis Study Group. Screening of patients with diabetes mellitus for tuberculosis in India. Trop Med Int Health 2013; 18: 646–654.

45 van’t Hoog A H, Langendam M W, Mitchell E, et al. A systematic review of the sensitivity and specifi city of symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative persons and persons with unknown HIV status. Report–Version March 2013. World Health Organiza-tion, Geneva, Switzerland: WHO, 2013. http://who.int/tb/Review2Accuracy ofscreeningtests.pdf Accessed 7 August 2013.

46 Baker M A, Harries A D, Jeon C Y, et al. The impact of diabetes on tuberculosis treatment outcomes: a systematic review. BMC Med 2011; 9: 81.

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

Le fardeau mondial du diabète sucré (DM) est immense et l’on s’attend à ce que le nombre de cas augmente d’ici 2030 jusqu’à plus de 550 millions. Les pays d’Asie, comme l’Inde et la Chine, devront supporter le poids principal de cette épidémie en expansion. Le risque de développer une tuberculose (TB) active est significativement accru chez les patients atteints de DM : il est de deux à trois fois supé -rieur à celui des personnes sans DM. Cet article fait la revue de l’épidémiologie et des interactions de ces deux maladies, discute la façon dont l’Organisation Mondiale de la Santé et l’Union Internatio-nale Contre la Tuberculose et les Maladies Respiratoires ont élaboré et lancé le réseau de collaboration pour les soins et la lutte contre la TB et le DM et examine trois défis importants pour les soins de ces affec-tions. Ceux-ci sont en relation avec 1) un dépistage bidirectionnel des deux maladies, 2) le traitement des patients atteints des deux mala-dies, et 3) la prévention de la TB chez les sujets atteints de DM. Pour

chaque secteur, les déficiences en matière de connaissances et les zones prioritaires de recherche sont soulignées. Un diabète sucré non diagnostiqué, traité de manière inadéquate et médiocrement con-trôlé semble une menace beaucoup plus importante pour la préven-tion et la lutte contre la TB qu’on ne l’avait pensé précédemment, et ce problème doit être abordé. La prévention du diabète grâce à une attention portée aux régimes inadéquats, au style de vie sédentaire et à l’obésité de l’enfant et de l’adulte doit être incluse dans de larges stratégies de prévention des maladies non transmissibles. Le réseau de collaboration fournit un modèle d’action et les recommandations doivent à présent être mises en œuvre et évaluées sur le terrain afin de donner un fondement solide à l’extension d’interventions qui fonctionnent et sont efficientes pour lutter contre le double fardeau de ces maladies.

La carga mundial de morbilidad por diabetes sacarina (DM) es con-siderable y se prevé que se sobrepasen los 550 millones de personas en el 2030. Países de Asia como la India y la China soportarán la mayor parte de la carga de esta epidemia en expansión. Las personas que padecen DM presentan un riesgo considerable de contraer tu-berculosis (TB) activa, el cual es de dos a tres veces mayor que el riesgo de las personas que no sufren DM. En el presente artículo se consideran las características epidemiológicas de ambas enferme-dades, se analizan la elaboración y la puesta en marcha del marco conjunto de atención y de lucha contra la TB y la DM de la Orga-nización Mundial de la Salud y la Unión Internacional contra la Tuber-culosis y las Enfermedades Respiratorias y se examinan además tres dificultades importantes que plantea la atención. Estos problemas hacen referencia a: 1) el cribado bidireccional de ambas enfermedades, 2) el tratamiento de pacientes aquejados de ambas enfermedades, y

3) la prevención de la TB en las personas diabéticas. Se destacaron las deficiencias en los conocimientos y los dominios prioritarios de investi-gación en cada aspecto. La DM no diagnosticada, tratada inadecua-damente o mal equilibrada constituye una amenaza a la prevención y la lucha contra la TB, que es más determinante de lo que se conside-raba y es preciso atenderla. La prevención de la DM mediante la cor-rección de los regímenes poco saludables, los estilos de vida sedenta-rios y la obesidad infantil se debe incorporar a las estrategias globales de prevención de las enfermedades no transmisibles. El marco con-junto de atención ofrece un modelo para la acción y es preciso poner en práctica sus recomendaciones y evaluarlas en el terreno, a fin de sentar unas bases firmes a la ampliación de escala de las intervenciones que dan resultados y abordan eficazmente esta carga de morbilidad doble.

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Public Health Action

REVIEW ARTICLE

New screening technologies for type 2 diabetes mellitus appropriate for use in tuberculosis patientsT. Adepoyibi,1 B. Weigl,1 H. Greb,1 T. Neogi,1,2 H. McGuire1

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi.org/10.5588/pha.13.0036

Type 2 diabetes mellitus (DM), which is epidemic in low- and middle-income countries (LMICs), may threaten gains made in tuberculosis (TB) control, as DM is both a major risk factor for developing active TB and it can lead to adverse TB treatment outcomes. Despite World Health Organization guidance that all TB patients should be screened for DM, most facilities in LMICs that manage TB patients do not currently perform screening for DM, due in part to the cost and complexity involved. DM screen-ing is further complicated by the presentation of transient hyperglycemia in many TB patients, as well as differences in diabetes risk factors (e.g., body mass index) between TB patients and the general public. In this article, we re-view existing and new technologies for DM screening that may be more suitable for TB patients in LMICs. Such methods should be rapid, they should not require fasting, and they should allow the provider to differentiate between transient and longer-term hyperglycemia, using inexpen-sive tools that require little training and no specialized in-frastructure. Several methods that are currently under de-velopment, such as point-of-care glycated hemoglobin and glycated albumin assays, non-invasive advanced gly-cation end-product readers, and sudomotor function-based screening devices, offer interesting performance charac-teristics and warrant evaluation in populations with TB.

Type 2 diabetes mellitus (DM) triples the risk of de-veloping tuberculosis (TB), and rates of TB are

higher in people with DM than in the general popula-tion.1,2 DM is also associated with adverse TB treat-ment outcomes.2 With the epidemiological transition underway in many countries around the world, cur-rent predictions indicate that the prevalence of DM will reach 552 million by 2030.3 Approximately 80% of these cases will be in low- and middle-income coun-tries (LMICs), where TB prevalence is high.4 Although the links between diabetes and TB have been known for decades,5,6 the unprecedented global rise in DM led the World Health Organization (WHO) and the Inter-national Union Against Tuberculosis and Lung Disease to issue a global recommendation in 2011 that all TB patients should be screened for DM and vice versa,4 and countries including China and India have com-menced TB-DM screening programs.7–9 Despite this, global response to the crisis has been hampered by a lack of knowledge regarding the most appropriate screening methods and technologies to use in TB set-tings.4 The need to develop and evaluate more accu-

AFFILIATIONS1 PATH, Washington, DC,

USA2 University of Washington

School of Medicine, Department of Family Medicine, Seattle, Washington, USA

CORRESPONDENCETemitope AdepoyibiPATH455 Massachusetts AveWashington, DC 20001, USA Fax: (+1) 202 457 1466e-mail: [email protected]

ACKNOWLEDGEMENTSThe authors acknowledge the work of J K Drake, PATH.Conflict of interest: none declared.

KEY WORDSDM; TB; technology; screening

PHA 2013; 3(S1): S10–S17© 2013 The Union

Received 31 May 2013Accepted 3 August 2013

rate, rapid, non-invasive and cost-effective point-of-care (POC) diagnostic and monitoring tests—including measurements of blood glucose and blood glycated hemoglobin (A1c)—was acknowledged in 2011 at a con-sultation meeting of global experts on TB and DM.10

Technologies for the detection of diabetes face spe-cial challenges in their use among TB patients.9 As with other infectious diseases, TB may temporarily ele-vate blood glucose levels, resulting in false-positive DM diagnoses.9,11 Current DM detection tools are not optimized for LMICs, where the majority of TB pa-tients are found,4 and are often inaccurate, expensive, invasive and inconvenient.12 Multiple tests are often required to establish a diagnosis, as is referral to a spe-cialist center for confi rmatory diagnosis.13 These cir-cumstances present special challenges for TB patients who are already burdened with the fi nancial costs as-sociated with 6–24 months of TB treatment, depend-ing on whether drug resistance is present or not. A sys-tematic review found that the costs (both direct and indirect) associated with TB treatment in sub-Saharan Africa can be as much as 10 times the average annual income for TB patients in the poorest 20% of the pop-ulation, and for many households such costs are con-sidered catastrophic.14

Nonetheless, screening and treatment for hypergly-cemia and DM is essential, due to the potential impact on TB treatment outcomes and the effectiveness of TB medications.15,16 Individuals with elevated blood glu-cose may have delayed or impaired recovery, face worse treatment outcomes, or may even require al-tered doses or schedules of TB medications.15,16

This article builds on the recent publication from Weigl and Drake in Point of Care,12 and will outline a proposed target product profi le for a POC DM test for use in TB patients. Optimal test characteristics, includ-ing accuracy, suitability for use in current TB program structures, patient acceptability, suitability for use given TB patient infection status, convenience and cost will be considered. The current pipeline for POC DM screen-ing technologies appropriate for LMICs will then be examined to identify the candidate technologies that best meet the optimal test characteristics as described, and which may require further evaluation within TB populations.

Existing technologies and approaches for diabetes screening in tuberculosis patientsAccording to the WHO, DM is diagnosed by the pres-ence of one of the following:17 a fasting plasma glucose

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Public Health Action DM screening for TB patients S11

level ⩾ 7.0 mmol/l (126 mg/dl); plasma glucose ⩾ 11.1 mmol/l (200 mg/dl) 2 h after a 75 g oral glucose load in a glucose toler-ance test; symptoms of hyperglycemia and casual plasma glu-cose ⩾ 11.1 mmol/l (200 mg/dl); glycated hemoglobin (HbA1c) ⩾ 6.5%.18 A clinical DM diagnosis also requires retesting on an-other day by any of the above methods, unless the patient is symptomatic and the plasma glucose is unequivocally elevated.18 It is important to note the overlap between DM screening and diagnosis, as various screening and diagnosis algorithms may be employed.19 The WHO recommends screening TB patients for DM using existing DM country guidelines.4 Table 1 shows DM screen-ing and diagnosis guidelines from a selection of the 22 countries with the highest TB burdens in the world from which informa-tion regarding national DM guidelines was available. 20–27

Screening approaches for DM in TB patients—as in the general population—may include questionnaire-based risk assessments (used to create risk scores) as well as blood, urine, and non-invasive tests that determine the levels of biochemical markers or physio-logical responses correlated with diabetes risk.19,28

Diabetes risk assessmentsDM risk assessment questionnaires commonly include the follow-ing components: age; sex; family history; biometric measurements such as body mass index (BMI), waist circumference, and waist-to-hip ratio; and history of hypertension.19,28 Risk of DM is gener-ated through a scoring system related to each of these attributes, and a biochemical test may be included automatically, or a high

score may lead to a biochemical test.19, 28 The benefi ts of using DM risk scores to evaluate DM risk in TB patients in the context of TB programs include the fact that they are relatively easy to adminis-ter (TB program staff could potentially be trained relatively easily to administer a DM risk score), promote recommended guidelines relating to targeted biochemical screening, and are low cost in themselves.28 One disadvantage associated with using DM risk scores in the context of TB programs is the fact that, of the seven risk scores recommended for adaptation in routine clinical prac-tice,29 all were developed in North America or Europe, and none of the 22 countries that account for 90% of the global TB burden is in Europe or North America.30 This raises questions regarding the applicability of the risk scores in these countries. In addition, not enough is known about how active TB disease infl uences the phenotypic characteristics associated with DM as measured by standard risk scores; for example, TB-DM co-morbid patients may have, on average, a lower BMI or lower hip-to-waist ratio than their TB-negative DM patient counterparts. This article proposes that more research is required to develop a risk score optimized for use in TB populations.

Biochemical testsThe most commonly used biochemical diabetes screening and di-agnostic tests are blood or plasma glucose tests, variants of which include random plasma glucose (RPG), random blood glucose, fasting plasma glucose (FPG), fasting blood glucose (FBG) and the oral glucose tolerance (OGTT) and challenge tests.17 Glucose

TABLE 1 DM screening and diagnosis guidelines from selected high TB burden countries20–27

Country DM screening DM diagnostic criteria

Bangladesh20 Venous RPG At least two of:More than one characteristic and sign of DMVenous FPG >7.0 mmol/l

Urine glucose Venous RPG taken at least 2 h after eating or after taking 75 g glucose ⩾11.1 mmol/l

Presence of diabetic retinopathy, orRandom sample on more than one occasion >11.1 mmol/l

Brazil21 Risk scoreCapillary glucose test

FBG >126 mg/dl, and 2 h after ingestion of 75 g anhydrous glucose, ⩾200 mg/dl + symptoms

FBG ⩾126 mg/dl on more than one occasionFBG >126 mg/dl + symptoms

China22 RBG FBG ⩾7.0 mmol/l on at least two occasionsEthiopia23 Capillary glucose test At least two of the following on subsequent days:

FBG ⩾126 mg/dlRBG ⩾200 mg/dl2 h oral glucose test ⩾200 mg/dl, as confirmed on a

subsequent day by any one of the three methodsIndia24 Capillary glucose test,

random Risk score

2 h post-glucose load ⩾200 mg/dl

FBG ⩾ 126 mg/dlKenya25 Capillary glucose test Venous FPG >7.8 mmol/l on more than one occasion

Plasma glucose >11.1 mmol/l in symptomatic patientsSouth Africa26 Risk score In patients without symptoms, at least two of the

following:FPG FPG ⩾7.0 mmol/l

2 h plasma glucose ⩾11.1 mmol/lRPG RPG ⩾11.1 mmol/l A1c A1c >6.5%

One of the above + symptomsUganda27 Risk score

Urine glucoseBlood glucose A1c

Blood glucose

A1c

DM = diabetes mellitus; TB = tuberculosis; RPG = random plasma glucose; FBG = fasting blood glucose; RBG = random blood glucose; FPG = fasting plasma glucose; A1c = blood glycated hemoglobin.

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testing may be conducted via venous blood usually drawn for lab-oratory instrument-based testing, or via capillary blood—or fi nger-prick—for glucometer testing using portable POC devices. FPG and RPG are single-point glucose measurements taken in blood after fasting or at random times, respectively, whereas the OGTT measures the response to a glucose challenge by measuring blood glucose levels before and after receiving it (the fi rst glucose mea-surement being an FPG).28 The OGTT is considered the gold stan-dard diagnostic test for DM,17 although its inconvenience (pa-tients must wait for 2 h) and cost makes FPG preferable in clinical practice settings.12,28 Other common tests include urine glucose and A1c measurements.19 Although the WHO has advised that A1c can also be considered a diagnostic test for DM, in addition to its use as a glycemic control monitoring test for diagnosed DM patients,31 of the countries listed in Table 1, only South Africa and Uganda use it for either purpose. The usefulness of urinary glu-cose as a screening test for undiagnosed DM is limited because of its low sensitivity, which some studies show to range from 21% to 64%, although specifi city is high, at >98%.19

There are notable disadvantages with each of these currently used and recommended tests in relation to the TB care context. FPG and OGTT both require patient preparation in the form of fasting, and in the case of OGTT, extended clinic waiting times and multiple blood draws are required.12,32 These approaches therefore reduce the ability to test TB patients opportunistically as they come into contact with the health system, thus delaying di-agnosis and resulting in increased risk of serious consequences, as TB patients with DM are more likely to experience delays in spu-tum culture conversion, increased case fatality rates during treat-ment, and increased relapse rates of TB after successful comple-tion of treatment.2,33 In many of the countries listed in Table 1, DM screening is performed via FPG or RPG, using a POC glucom-eter device on a capillary specimen. The WHO has recognized the widespread use of capillary sampling in LMICs, although venous plasma glucose is considered the standard measurement and re-porting method.18 Although venous and capillary measurements give the same fasting result, unfortunately the most cost-effective and commonly used glucometer devices exhibit universally low accuracy, often due to incorrect and/or infrequent calibration.34 Moreover, although it has a specifi city of >90%, the sensitivity of FPG is only 40–65%.32 RPG does not require fasting and is there-fore more conducive to opportunistic screening of TB patients, but as with FPG, POC glucometer devices are commonly used. In

the case of RPG, capillary glucose samples give values that are higher than venous sample values, and therefore value conver-sion must be performed.18 This complication is in addition to the poor and variable sensitivity and specifi city of RPG of respectively 40–79% and 66–96%.32

A1c has advantages over both FPG and RPG in that the test does not require fasting and is generally more sensitive than FPG, at 78–81% sensitivity, although its specifi city is 79–84%.32 A1c is especially sensitive in the detection of early type 2 DM in at-risk subjects.35 The main drawbacks in the use of A1c for TB patients are the lack of standardization and the cost; the consumables re-quired for POC-compatible A1c instruments, and the instruments themselves, are cost-prohibitive in many LMICs.12 In addition, race, ethnicity and hemoglobin variants may all impact on A1c readings, as is the case with conditions such as anemia (including that caused by malaria) and vitamin B12 defi ciency.36,37 Taking these factors into consideration, there is a paucity of data regard-ing A1c performance from the high TB burden countries featured in Table 1. Despite the low sensitivity of urinary glucose testing, it may be useful in LMICs where no other procedure is possible.19 Because of the importance of high sensitivity in a DM screening test for TB patients, however, urinary glucose testing is considered to have serious limitations.

The transitory hyperglycemia that many TB patients exhibit due to the nature of the disease often resolves upon commence-ment of TB treatment.4 To this end, to accurately represent true DM presence or risk, a DM screening test for TB patients should represent a deviation of actual blood glucose from normal values averaged over a time period long enough to distinguish between temporary elevation in blood glucose brought on by active TB. The biochemical tests commonly used in the high TB burden countries shown in Table 1 face disadvantages in this regard. FPG and RPG are single-point glucose measurements and are therefore unable to identify chronically elevated blood glucose, and OGTT measures the response to a glucose challenge.12 Of the commonly available tests, A1c is the most appropriate for identifying chronic hyperglycemia, as it represents blood glucose levels averaged over 3 months,36 although as discussed, the test is cost-prohibitive for many LMICs.12

Table 2 reviews key attributes and performance of these vari-ous tests for DM screening and diagnosis.17,35,38 The selection of a screening tool can be limited by cost, complexity of use and a lack of trained personnel, and, in some cases, a lack of availability.

TABLE 2 Common DM screening and diagnostic tests17,35,38

Test FPG, FBG OGTT RPG, RBG Urine A1c

Measures Glucose post 8 h fast Glucose after fasting + 2 h post-glucose load

Glucose regardless of when person last ate

Presence of glucose in urine

% of Hb that is glycated

Specimen Capillary venous blood Capillary venous blood Capillary venous blood Voided mid-stream urine

Capillary venous blood

Test Glucometer laboratory measurement

Glucometer laboratory measurement

Glucometer laboratory measurement

Dipstick Glucometer laboratory measurement

Performance 40–65% sensitivity, >90% specificity17

96.8% max sensitivity, 90.8% max specificity38

40–79% sensitivity, 66–96% specificity17

21–64% sensitivity; specificity >98%17

78–81% sensitivity, 79–84% specificity35

Normal range FPG ⩽99 mg/dl (7.0 mmol/l)

2 h PGL ⩽139 mg/dl (7.0 mmol/l)

RPG <200 mg/dl (11/1 mmol/l)

0–15 mg/dl A1c <5.7%

Pre-diabetes FPG = 100–125 mg/dl (5.6–6.9 mmol/l); IFG

140–199 mg/dl(7.8–11.0 mmol/l); IFG

Cannot be used to diagnose pre-diabetes

>15 mg/dl A1c = 5.7–6.4%.

Distinguishes transient hyper-glycaemia

No No No No Yes

DM = diabetes mellitus; FPG = fasting plasma glucose; FBG = fasting blood glucose; OGTT = oral glucose tolerance test; RPG = random plasma glucose; RBG = random blood glucose; A1c = blood glycated hemoglobin; PGL = post-glucose load; IFG = impaired fasting glucose.

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Typically the urine glucose test strips are the least expensive, while the hemoglobin A1c tests are the most expensive screen-ing option.39

Tuberculosis program requirementsTB patients in the public sector are usually diagnosed and man-aged via two mechanisms: 1) through a vertical TB program struc-ture, via TB clinics and microscopy centers/laboratories staffed by specialized personnel, as is the case in India,40 a country that a ccounted for 26% of global TB cases in 2011,30 or 2) in an inte-grated manner, where TB is one of numerous conditions managed as part of a package of primary health care interventions overseen by multidisciplinary staff within one facility, as in Mexico.41 Often a combination of the two systems is present, in that the TB clinic and microscopy center/laboratory are physically co-located within the primary health care structure, and staff are shared between the two, as in Tanzania.42 To reduce the burden of referral on TB patients (even within the same structure), an optimal screening test is one that can be used safely and with acceptance by the cadres of clinical and laboratory staff who currently manage TB pa-tients, integrated within their current systems and using existing infrastructure, such as ambient temperature storage and adequate waste disposal for portable glucometer test strips. A recent study highlighted that a waste management system in TB microscopy centers existed in only 50% of the 22 high-burden TB countries.43 The indoor temperature always remained below 35ºC in only 23% of the countries, but 82% had gloves in stock.43

The DM burden in the 22 high-burden TB countries continues to grow,3 and it is estimated that globally between 30% and 90% of those with DM are undiagnosed.28 In examining the various disadvantages associated with current DM screening tests relating to their use in TB patients, it is clear that to address the WHO’s recommendation for the universal screening of TB patients for DM, two distinct screening needs emerge: 1) a POC DM assay that requires no patient preparation, is acceptably accurate, sensitive and specifi c, is low cost, requires minimal infrastructure and is easy to use; and 2) an assay that differentiates transient hypergly-cemia from pre-diabetes and DM.

TARGET PRODUCT PROFILE FOR A DIABETES POINT-OF-CARE SCREENING TEST FOR TUBERCULOSIS PATIENTS

A target product profi le (TPP) is simply a statement of the essen-tial attributes of a clinically and commercially successful product; many TPPs, however, are not widely publicized,44 despite the fact that they can be very valuable in terms of evaluating the appro-priateness of existing technologies, and in guiding discovery and development activities.45 A TPP can stimulate innovation and de-velopment by reducing the risks for companies that are considering developing products for underserved markets such as those found in many high-burden TB countries, by providing a consensus doc-ument containing optimal target product specifi cations developed by experts and informed by clinical needs assessments.44,45

In identifying a TPP for a DM POC screening test for TB pa-tients, there is signifi cant overlap with potential TPPs for general populations in LMIC settings. Indeed, the TPP proposed here builds upon the TPP for a DM POC screening test for low-resource set-tings described by Weigl and Drake.12 Although there are overlaps, there is utility in identifying the attributes of a DM screening test that can be easily deployed within TB program structures, poses minimal burden upon TB patients, and is appropriate given the physiological attributes of this population. Appropriate tests should

be able to be deployed within optimized algorithms that may in-clude non-device-based screening approaches, and algorithm re-search and development should be prioritized in this regard. This article proposes the following ideal attributes for a DM POC screen-ing test for use in TB patients:

• Ability to distinguish between short-, medium- and longer-term glycemic control with a single measurement at a single point in time. To avoid false-positive results, determining multiple pa-rameters correlated to chronic hyperglycemia is especially im-portant in TB patients, as active TB can result in transient hy-perglycemia.7 Such a test would be useful not only for screening but also for glycemic control monitoring in patients already identifi ed as having prediabetes or DM.

• Low cost. A benchmark cost for comparison would be US$1, which is comparable to that of the glucose test strips used for RPG, FPG, or OGTT tests.12 Cost will be a critical consideration in the operationalization of the WHO’s recommendation to screen all TB patients for DM, and resource-poor TB programs and nascent, underfunded non-communicable disease programs will have to work together to identify additional budgetary allo-cations for screening and ongoing care and management of TB-DM patients.

• Ability to be administered without fasting. Ideally, there should be no preparation required for the patient, to avoid the need for repeat visits. Fasting may present an additional burden for TB patients in particular, who already face signifi cant loss of income and inconvenience due to the repeated interactions with the health system required by 6–24 months of treatment.

• Minimal waiting time for results. The presence of DM increases the risk of poor treatment outcomes in TB patients.2 It is there-fore imperative that DM in TB patients be identifi ed and man-aged without delay.

• High sensitivity. Although a screening test/device should ide-ally have as high a sensitivity and specifi city as possible, trade-offs always have to be made with respect to test function and sensitivity and specifi city. A screening tool should primarily serve a ‘rule-out’ function, and have as high a sensitivity as possible to ensure that patients are not mistakenly declared negative,46 and, in the case of a TB patient, falsely determined to be DM-negative, risking adverse treatment outcomes.

• Simplicity of use. The reality of many settings is that the man-agement of TB patients is left to lower cadres of health workers. To reduce the burden of referral on TB patients, an optimal DM screening device should be simple enough for use by the health care and laboratory staff currently providing care to TB patients.

• Non-invasive/minimally invasive. The priority for any screening device should be to minimize patient inconvenience and dis-comfort by requiring only non-invasive or minimally invasive sample collection.

• Minimal requirement for associated infrastructure. Given the in-frastructure constraints experienced by TB microscopy centers in the 22 high-burden TB countries,43 an ideal test/device would require no maintenance or calibration, and would have no temperature or storage control requirements. There should not be any need for reagents that are not included with the disposable or kit.

• Indigenous manufacture and distribution. Distribution and mar-keting costs for glucose tests can comprise more than 50% of the total end-user costs.12 Any optimal test/device should be able to be manufactured in high TB burden countries and dis-tributed using existing supply chains, to keep costs to a mini-mum. The cost savings associated with producing a DM test close to or within a target country can have a huge impact.

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DIABETES SCREENING TECHNOLOGY PIPELINE—ARE THERE CANDIDATES SUITABLE FOR TUBERCULOSIS PATIENTS?

The pipeline for DM detection technologies is relatively robust, although product development priorities have been shaped by the traditional markets in high-income settings.12 This has meant that many promising candidate technologies are not fully opti-mized for use in LMIC settings such as those in Table 1. An exten-sive review of the literature has shown no previous studies that have examined the attributes of technologies currently in the pipeline for applicability in TB programs, given the particular characteristics required. Among the promising novel DM screen-ing technologies currently under investigation and development, some are in routine use, but none has been widely evaluated for use in TB patient populations. Table 3 provides a summary of novel DM screening technologies identifi ed, and indicates whether they meet the proposed TPP requirements described earlier.35,47–49 A summary of each category of test is also provided below.

Point-of-care compatible A1c readersand low-cost test disposablesA1c readers are one of a class of DM screening devices that deter-mine glucose in protein-bound form. Glucose not only exists in free forms, it also persists in protein-bound forms in blood and other tissues (e.g., glycated hemoglobin and glycated albumin in blood, and advanced glycation end products in skin). After the initial formation of a Schiff base by glucose and protein mole-cules, an irreversible reaction forms a stable ketoamine. As the re-action is irreversible, in vivo protein half-life determines the aver-aging time of glycemic control. Although A1c readers are now POC-compatible, accurate and provide blood glucose levels aver-aged over a 3-month period, their suitability for use in TB programs is limited by the fact that they are invasive (requiring a fi nger-prick sample) and require expensive disposables that require re-frigeration. Low-cost A1c test disposables are required.12

Autofluorescence-based readersThis category of device measures skin fl uorescence due to the accumulation of DM-related advanced glycation end products (AGEs) in the dermal collagen, and biomarkers of metabolism and oxidative stress to determine a subject’s risk of having undiag-nosed pre-diabetes and DM.50 AGEs are thought to play a central role in the pathogenesis of DM complications, and are the result

of a chain of chemical reactions after an initial glycation reac-tion.50,51 Specifi c and accurate measurement of AGEs requires gra-dient high-pressure liquid chromatography analysis or gas or liquid chromatography-mass spectrometry, which is not available in most clinical settings.51 For this reason, non-invasive tools using skin autofl uoresence quantifi cation that correlate with levels of tissue AGEs have been developed that take advantage of the characteris-tic fl uorescence of AGEs in the skin.49 Due to the fact that the gly-cated products (the major contribution in fl uorescence comes from fl uorescent AGEs linked mostly to collagen, but also to other pro-teins and lipids) remain present in the dermal layer for a long pe-riod of time, measurements from AGE readers represent averages of hyperglycemia over a long period of time (average 12 months);51 they therefore present an opportunity for use in TB patients, given the need to distinguish medium- and long-term glycemic control from short-term, infection-induced hyperglycemia.

Two non-invasive AGE devices are currently at an advanced stage of development, by the companies DiagnOptics Technologies BV (AGE Reader™; Groningen, The Netherlands) and Veralight (SCOUT DS®; Miraculins Inc., Winnipeg, MB, Canada).12 While the capital cost of their devices is currently quite high, they are simple to use, and there are no consumables and little to no main-tenance, although electricity is required. They do not require pa-tient fasting or preparation and are non-invasive, and both pro-vide results in a few short minutes after the patient places the underside of the forearm on the device.12 Although more studies are required, one study demonstrated the SCOUT DS® to have 74.7% sensitivity, and the same study calculated the sensitivity differential to mean that the device would detect 28.8% more in-dividuals in the OGTT-defi ned positive screening class than FPG testing and 17.1% more than A1c testing.49 Despite these promis-ing results, more information is needed regarding the performance of AGE readers in the 22 high TB burden countries, given poten-tial variations in performance due to genetic and socio-cultural variations, skin color, skin dryness, or the use of topical creams and substances. Overall, in addition to their non-invasiveness and operational advantages, AGE readers offer the potential for very low-cost screening. They do not require disposables, are easy to operate by minimally trained users, and have relatively low oper-ating costs. The initial instrument costs could be amortized very quickly in settings with high-patient throughput, and with suffi -ciently high volumes per test, costs might ultimately be much lower than A1c per-test costs.

TABLE 3 Novel DM screening methods with potential utility in TB populations35,47–49

1,5-anhydroglucitolGlycated albuminand fructosamine

Sudomotorfunction readers POC A1c readers AGE readers

Distinguishes transient hyperglycemia

1–3 months GA = 1 monthF = mixed

Yes 3 months 12 months

Low cost No Yes Low per test cost, high device cost

Low device cost, high per test cost

Low per test cost, high device cost

No fasting Yes Yes Yes Yes Yes<5 min results No Yes Yes Yes YesHigh sensitivity Yes 64.1%47 75%48 78–81%35 74.7%49

Simple use No No Yes Yes YesNon-invasive No No Yes No YesNo calibration No No Yes No YesNo minimum operating

temperatureYes No No No No

POC No Yes Yes Yes YesOther Early in development

pipelineEarly in development

pipelineEarly in development

pipelineEarly in development

pipeline

DM = diabetes mellitus; TB = tuberculosis; POC = point-of-care; A1c = blood glycated hemoglobin; AGE = advanced glycation end product; GA = glycated albumin; F = fructosamine.

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Sudomotor function devicesThe EZSCAN Sudomotor reader (Impeto Medical, Paris, France) is an alternative DM screening device based on electrochemical po-tential measurements across hand and foot skin surfaces to deter-mine emergent neuropathy.52 Small fi ber neuropathies are com-mon in people with insulin resistance and prediabetes.48 EZSCAN is a dynamic test equivalent to a stress test, which measures the capacity of the sweat glands to release chloride ions in response to electrochemical activation.48 A low voltage of variable ampli-tude is applied to electrodes on the skin in regions with a high density of sweat glands (palms, feet), and the electrical potential difference caused by the electrochemical reaction on these elec-trodes is measured.48 The information is then used to determine the patient’s cardiometabolic risk.53 The test does not require pa-tient preparation, such as fasting, and does not require blood drawing. Results are available within 2 min, and clinical studies have shown their sensitivity and specifi city to be as high as 75% and 100%, respectively.48,53 More studies are required to assess the utility of the test for TB patients.

Other promising biomarkersThe ability to distinguish between short-, medium- and longer-term glycemic control with a single measurement at a single point in time is a key priority for any DM screening device intended for use in TB populations. To this end, a possible solution may be the development of a multivalent platform that contains a set of ana-lytical targets from glycated products selected to demonstrate a range of half-lives, allowing the differentiation between short-, medium- and long-term glycemic control. Promising biomarkers are currently being evaluated, for example, that identify physio-logical changes due to elevated glucose levels early in pregnancy, which result in transitory hyperglycemia.12 The main biomarker being investigated in this regard is glycated albumin (GA), which remains in circulation approximately one third as long as A1c; a GA reading will thus represent the effects of elevated glucose over an average of 1 month. 54

GA is currently being investigated by PATH in relation to a ges-tational DM project, in addition to fructosamine and 1,5-anhydro-glucitol (1,5-AG).12 Fructosamine measures a mixture of glycated proteins that exhibit both longer and shorter half-lives than GA, and 1.5-AG has a very short half-life, averaging glycemic control for a 1–3 month period.55 Other markers that have thus far mainly been investigated in relation to gestational DM, but may have utility for DM screening in TB patients, include cytokines, chemo-kines, hormones and transcription factors stimulated by the AGE/receptor for advanced glycation end-product signaling pathway.56

The benefi ts of a multivalent diagnostic platform are many, and additional parameters of relevance to TB patients, such as the human immunodefi ciency virus, could be tested on such a screen-ing platform.

CONCLUSION

With an estimated 8.7 million new cases of TB in 2011, and the majority of these in LMICs,30 the ability to implement the WHO’s recommendation that all TB patients be screened for DM will re-quire the identifi cation of technologies that are appropriate for TB patients and current TB program structures. Research and ad-vocacy are necessary to ensure that evidence is generated regarding the potential for the DM technologies currently in the pipeline to be used in TB populations, given current program structures. This article provides a fi rst step towards understanding the current

landscape of DM screening technologies and an analysis of the opportunities and challenges associated with each. It is important to note, however, that while better screening tools can improve and increase the diagnosis of DM among TB patients, TB patients must also have access to treatment, monitoring and ongoing care for DM and support to successfully complete their TB treatment.

References 1 Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tubercu-

losis: a systematic review of 13 observational studies. PLOS Med 2008; 5: e152.

2 Baker M A, Harries A D, Jeon C Y, et al. Systematic review: the impact of dia-betes on tuberculosis treatment outcomes. BMC Med 2011; 9: 81.

3 International Diabetes Federation. The global burden. IDF diabetes atlas. 5th ed. Unwin N, Whiting D, Guariguata L, et al., eds. Bussels, Belgium: Inter-national Diabetes Federation, 2012. http://www.idf.org/diabetesatlas/5e/the-global-burden Accessed August 2013.

4 World Health Organization/International Union Against Tuberculosis and Lung Disease. Provisional collaborative framework for care and control of tuberculosis and diabetes. WHO/HTM/TB/2011.15. Geneva, Switzerland: WHO, 2011. http://whqlibdoc.who.int/publications/2011/9789241502252_eng.pdf Accessed August 2013.

5 Dooley K E, Chaisson R E. Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis 2009; 9: 737–746.

6 Restrepo B I. Convergence of the tuberculosis and diabetes epidemics: re-newal of old acquaintances. Clin Infect Dis 2007; 45: 436– 438.

7 Li L, Lin Y, Mi F, et al. Screening of patients with tuberculosis for diabetes mellitus in China. Trop Med Int Health 2012 July 25. Epub ahead of print.

8 India Tuberculosis–Diabetes Study Group. Screening of patients with tubercu-losis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

9 Balakrishnan S, Vijayan S, Nair S et al. High diabetes prevalence among tu-berculosis cases in Kerala, India. PLOS ONE 2012; 7: e46502.

10 Ottmani S-E, Murray M B, Jeon C Y, et al. Consultation meeting on tubercu-losis and diabetes mellitus: meeting summary and recommendations. Int J Tuberc Lung Dis 2010; 14: 1513–1517.

11 Basoglu O K, Bacakoglu F, Cok G, Sayiner A, Ates M. The oral glucose toler-ance test in patients with respiratory infections. Monaldi Arch Chest Dis 1999; 54: 307–310.

12 Weigl B, Drake J K. Developing an adaptable set of point-of-care diabetes screening technologies for low-resource settings. Point Care 2012; 12: 33– 40.

13 Whiting D R, Hayes L, Unwin N C. Diabetes in Africa. Challenges to health care for diabetes in Africa. J Cardiovasc Risk 2003; 10: 103–110.

14 Barter D M, Agboola S, Murray M B, Barnighausen T. Tuberculosis and pov-erty: the contribution of patient costs in sub-Saharan Africa—a systematic review. BMC Public Health 2012; 12: 980.

15 Kapur A, Harries A D. The double burden of diabetes and tuberculosis—public health implications. Diabetes Res Clin Pract 2013, Jan 7. E-pub ahead of print.

16 Jeon C Y, Murray M B, Baker M A. Managing tuberculosis in patients with diabetes mellitus: why we care and what we know. Expert Rev Anti Infect Ther 2012; 10: 863–868.

17 World Health Organization. Defi nition, diagnosis and classifi cation of dia-betes mellitus and its complications. Report of a WHO consultation. Part 1: diagnosis and classifi cation of diabetes mellitus. WHO/NCD/NCS/99.2. Ge-neva, Switzerland: WHO, 1999. http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf Accessed August 2013.

18 World Health Organization. Defi nition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. Ge-neva, Switzerland: WHO, 2006. http://www.idf.org/webdata/docs/WHO_IDF_defi nition_diagnosis_of_diabetes.pdf Accessed August 2013.

19 World Health Organization. Screening for type 2 diabetes: report of a World Health Organization and International Diabetes Federation meeting. WHO/NMC/MNH/03.1. Geneva, Switzerland: WHO, 2003. http://www.who.int/ diabetes/publications/en/screening_mnc03.pdf Accessed August 2013.

20 World Health Organization/Bangladesh Institute of Research and Rehabilita-tion in Diabetes, Endocrine and Metabolic Disorders. Guidelines for care of type 2 diabetes mellitus in Bangladesh. Dhaka, Bangladesh: BIRDEM, 2003. http://www.slideshare.net/roger961/guidelines-for-care-of-type-2-diabetes-mellitus-in-bangladesh Accessed August 2013.

21 Ministry of Health, Brazil. [Plan for reorganization of care for hypertension and diabetes mellitus]. Brasilia, Brazil: MOH, 2001. http://bvsms.saude.gov.br/bvs/publicacoes/miolo2002.pdf Accessed August 2013. [Portuguese]

22 Chinese Diabetes Society. [Clinical practice recommendations for the Chi-nese]. Beijing, China: CDS, 2010. http://cdschina.org/news_show.jsp?id=402.html Accessed August 2013. [Chinese]

23 Food, Medicines and Healthcare Administration and Control Authority. Minimum standards for health centres. Addis Ababa, Ethiopia: Ethiopian Federal Ministry of Health, 2010.

24 National Programme for Prevention and Control of Cancer, Diabetes,

Page 16: DM TB Review Nov 2013_entire publication.pdf

Public Health Action DM screening for TB patients S16

Cardiovascular Diseases and Stroke, Directorate General of Health Services, Ministry of Health and Family Welfare. Operational guidelines. New Delhi, India: Government of India, 2008–2009. http://health.bih.nic.in/Docs/Guide lines-NPCDCS.pdf Accessed August 2013.

25 Ministry of Health, Kenya. Clinical guidelines for diagnosis and treatment of common conditions in Kenya. Nairobi, Kenya: MoH, 2002. http://apps.who.int/medicinedocs/documents/s16427e/s16427e.pdf Accessed August 2013.

26 Society for Endocrinology, Metabolism and Diabetes of South Africa. The 2012 SEMDSA guideline for the management of type 2 diabetes mellitus: summary. Sandton, South Africa: SEMDSA, 2012. http://www.semdsa.org.za/images/guideline_2013_new.pdf Accessed August 2013.

27 Ministry of Health, Republic of Uganda. Uganda clinical guidelines: na-tional guidelines on management of common conditions. Kampala, Re-public of Uganda: Government of Uganda, 2010. http://health.go.ug/docs/ucg_2010.pdf Accessed August 2013.

28 International Diabetes Federation. Clinical guidelines taskforce: global guidelines for type 2 diabetes. Brussels, Belgium: International Diabetes Fed-eration, 2005. http://www.idf.org/webdata/docs/IDF%20GGT2D.pdf Accessed August 2013.

29 Noble D, Mathur R, Dent T, Meads C, Greenhalgh T. Risk models and scores for type 2 diabetes: systematic review. BMJ 2011; 343: d7163.

30 World Health Organization. Global tuberculosis report, 2012. WHO/HTM/TB/2012.6. Geneva, Switzerland; WHO, 2012. http://www.who.int/tb/publications/global_report/en/ Accessed August 2013.

31 World Health Organization. Use of glycated haemoglobin (HbA1c) in the di-agnosis of diabetes mellitus. Abbreviated report of a WHO consultation. WHO/NMH/CHP/CPM/11.1. Geneva, Switzerland: WHO, 2011. http://www.who.int/diabetes/publications/diagnosis_diabetes2011/en/ Accessed August 2013.

32 American Diabetes Association. Diagnosis and classifi cation of diabetes mel-litus. Diabet Care 2011; 33 (Suppl): S62–S69.

33 Guler M, Unsal E, Dursun B, Aydln O, Capan N. Factors infl uencing sputum smear and culture conversion time among patients with new case pulmo-nary tuberculosis. Int J Clin Pract 2007; 61: 231–235.

34 D’Orazio P, Burnett R W, Fogh-Andersen N, et al. Approved IFCC recommen-dation on reporting results for blood glucose (abbreviated). Clin Chem 2005; 51: 1573–1576.

35 Perry C R, Shankar R R, Fineberg N, McGill J, Baron A D. HbA1c measure-ment improves the detection of type 2 diabetes in high-risk individuals with nondiagnostic levels of fasting plasma glucose. Diabet Care 2001; 24: 465–471.

36 Gallagher E J, Bloomgarden Z T, Le Roith D. Review of hemoglobin A1c in the management of diabetes. J Diabet 2009; 1: 9–17.

37 Roberts W L, De B K, Brown D, et al. Effects of hemoglobin C and S traits on eight glycohemoglobin methods. Clin Chem 2002; 48: 383–385.

38 Hansarikit J, Manotaya S. Sensitivity and specifi city of modifi ed 100-g oral

glucose tolerance tests for diagnosis of gestational mellitus. J Med Assoc Thai 2011; 94: 540Y544.

39 Bennett C M, Guo M, Dharmage S C. HbA(1c) as a screening tool for detec-tion of type 2 diabetes: a systematic review. Diabet Med 2007; 24: 333–343.

40 Chauhan L S, Agarwal S P. Tuberculosis control in India. Chapter 3. Revised National Tuberculosis Control Program. Directorate General of Health Ser-vices, Ministry of Health and Family Welfare. New Delhi, India: Government of India, 2005. http://tbcindia.nic.in/pdfs/Tuberculosis%20Control%20in %20India-Final.pdf Accessed August 2013.

41 Frenk J. Bridging the divide: global lessons from evidence-based health pol-icy in Mexico. Lancet 2006; 368: 954–961.

42 Kwesigabo G, Mwangu M A, Kakoko D C, et al. Tanzania’s health system and workforce crisis. J Pub Health Pol 2012; 33: S35–S44.

43 Denkinger C, Nicolau I, Ramsay A, Chedore P, Pai M. Are peripheral micros-copy centres ready for next generation molecular TB diagnostics? Eur Respir J 2013; 42: 544–547.

44 Weigl B, Gaydos C A, Kost G, et al. The value of clinical needs assessments for point-of-care diagnostics. Point Care 2012; 11: 108–113.

45 Pai N P, Vadnais C, Denkinger C, Engel N, Pai M. Point-of-care testing for in-fectious diseases: diversity, complexity, and barriers in low- and middle-income countries. PLOS Med 2012; 9: e1001306.

46 Lee W-C. Selecting diagnostic tests for ruling out or ruling in disease: the use of the Kullback-Leibler distance. Int J Epidemiol 1999; 28: 521–525.

47 Dominiczak M H, Macrury S M, Orrell J M, et al. Long-term performance of the fructosamine assay. Ann Clin Biochem 1988; 25: 627–633.

48 Tavee J, Zhou L. Small fi ber neuropathy: a burning problem. Clev Clin J Med 2009; 76: 297–305.

49 Maynard J D, Rohrscheib M, Way J F, Nuyen C M, Ediger M N. Noninvasive type 2 diabetes screening: superior sensitivity to fasting plasma glucose and A1c. Diabet Care 2007; 30: 1120–1124.

50 Bucala R, Cerami A. Advanced glycosylation: chemistry, biology, and impli-cations for diabetes and aging. Adv Pharmacol 1992; 23: 1–34.

51 Ahmed N, Thornalley P J. Quantitative screening of protein biomarkers of early glycation, advanced glycation, oxidation and nitrosation intracellular and extracellular proteins by tandem mass spectrometry multiple reaction monitoring. Biochem Soc Trans 2003; 31: 1417–1422.

52 Schwarz P E H, Brunswick P, Calvet J H. EZSCAN, a new technology to detect diabetes risk. Br J Diabetes Vasc Dis 2011; 11: 204–209.

53 Mayaudon H, Miloche P O, Bauduceau B. A new method for assessing sudo-motor function: relevance in type 2 diabetes. Diabetes Metab 2010; 36: 450–454.

54 Koga M, Kasayama S. Clinical impact of glycated albumin as another glyce-mic control marker. Endocr J 2010; 57: 751–762.

55 Behan K J, Merschen J. HbA1c does not always estimate average glucose. Clin Lab Sci 2011; 24: 71–77.

56 Bierhaus A, Humpert P M, Morcos M, et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl) 2005; 83: 876–886.

L’épidémie de diabète sucré (DM) de type 2 dans les pays à revenus faibles et moyens (LMIC) peut constituer une menace pour les progrès de la lutte contre la tuberculose (TB), car le DM est à la fois un facteur majeur de risque et de développement d’une TB active et peut aussi entrainer des résultats défavorables du traitement de la TB. En dépit de la directive de l’Organisation mondiale de la Santé selon laquelle tous les patients TB devraient faire l’objet d’un dépistage pour le DM, la plupart des services des LMIC qui traitent les patients TB ne ré-alisent pas actuellement le dépistage du DM, en partie en raison du coût et de la complexité qu’il implique. Le dépistage du DM est par ailleurs compliqué par l’existence d’une hyperglycémie transitoire chez beaucoup de patients TB ainsi que par les différences de facteurs de risque de DM (par exemple l’indice de masse corporelle) entre les patients TB et la population générale. Dans cet article, nous révi-

sons les technologies existantes et nouvelles pour le dépistage du DM qui pourraient être les plus applicables aux patients TB dans les LMIC. De telles méthodes devraient être rapides, elles devraient ne pas exiger le jeûne et elles devraient permettre aux pourvoyeurs de soins de di-stinguer entre des hyperglycémies transitoires et de plus longue durée au moyen d’outils peu coûteux, n’exigeant que peu de formation et aucune infrastructure spécialisée. Différentes méthodes sont actuelle-ment en cours de développement, tels que les tests sur l’hémoglobine glycosylée aux lieux de soins et sur l’albumine glycosylée, les lecteurs des produits finaux d’une glycation avancée non-invasive et les outils de dépistage basés sur la fonction sudomotrice ; elles offrent des car-actéristiques intéressantes de performance et méritent une évaluation dans les populations TB.

La diabetes (DM) de tipo 2 presenta características epidémicas en los países con ingresos bajos e intermedios (LMIC) y puede poner en peligro los avances alcanzados en materia de control de la tuberculo-sis (TB); la DM constituye un factor de riesgo importante de padecer la enfermedad TB activa y también puede tener consecuencias desfa-vorables en el desenlace del tratamiento antituberculoso. Pese a la re-comendación de la Organización Mundial de la Salud de realizar la detección sistemática de la DM en todos los pacientes TB, la mayoría

de los establecimientos que atienden a estos pacientes en los LMIC no cumplen con esta práctica, en parte debido a los costos y a la complejidad de la misma. La detección de la DM se complica además por la hiperglucemia transitoria que suele observarse en muchos paci-entes TB y por las diferencias en los factores de riesgo de DM, pre-sentes en los pacientes con TB y la población general, por ejemplo el índice de masa corporal. En el presente artículo se analizan las técni-cas existentes y los nuevos métodos de detección sistemática de la

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DM que pueden ser más adaptados a los pacientes con TB de los LMIC. Estos métodos deben ser rápidos, no deben precisar el estado de ayuno y deben permitir al profesional de salud diferenciar entre la hiperglucemia transitoria y la hiperglucemia de largo plazo, medi-ante la utilización instrumentos de bajo costo, que exijan poco en-trenamiento y no necesiten infraestructuras especializadas. En la actuali-dad, se encuentran en curso de desarrollo varios métodos como las

pruebas de hemoglobina glucosilada y albúmina glucosilada realizadas en el punto de atención, los lectores no invasivos de productos finales de la glucosilación avanzada y los dispositivos de detección basados en la función sudomotora; estos métodos ofrecen características de rendimiento interesantes y merecen una evaluación en las poblaciones de pacientes con diagnóstico de TB.

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

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Public Health Action

Tuberculosis-diabetes mellitus bidirectional screening at a tertiary care centre, South IndiaB. C. Prakash,1,2 K. S. Ravish,2 B. Prabhakar,1,2 T. S. Ranganath,2 B. Naik,3 S. Satyanarayana,4 P. Isaakidis,5 A. M. V. Kumar4

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi.org/10.5588/pha.13.0032

Setting: Tuberculosis (TB) and diabetes mellitus (DM) clinics at Bowring and Lady Curzon Hospital, a tertiary care centre in Bangalore, India.Obejctive: To assess the feasibility and results of TB-DM bidirectional screening.Methods: A descriptive study conducted from 1 March to 30 September 2012, in which all TB patients were as-sessed for DM and vice versa. Fasting blood glucose val-ues of ⩾126 mg/dl and 110–125 mg/dl were considered as DM and pre-diabetes, respectively. Results: Of 510 TB patients, 32 (6.3%) had been previ-ously diagnosed with DM. Screening among the remain-ing 478 patients yielded 15 (2.9%) with pre-diabetes and 15 (2.9%) newly diagnosed cases of DM. A higher preva-lence of DM was found among patients aged ⩾40 years, patients with pulmonary TB and smokers. Of the 47 TB-DM patients, 45 were enrolled in DM care. Of 1670 DM patients followed up in DM clinics, 45 already had TB. Among the remaining 1625 patients screened, 152 (9%) had symptoms suggestive of TB; two of these were found to have the disease. Conclusion: Bidirectional screening for DM and TB is fea-sible and produces a high yield for DM among TB patients. The yield of TB among DM patients was low and needs future research using new, improved TB diagnostic tools.

With an annual tuberculosis (TB) incidence of 2.2 million cases (range 2.0–2.5 million) and an

estimated 63 million people living with diabetes melli-tus (DM), India has the highest TB burden and second highest DM burden in the world.1–3 Nearly half of DM patients do not know their status, and a further 77 mil-lion people are estimated to have impaired glucose tol-erance and are at higher risk of becoming diabetic.2–4

DM is known to increase the risk of active TB ap-proximately three fold, and contributes to adverse TB treatment outcomes such as death, treatment failure and relapse.5–6 The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (The Union) have launched a new ‘Col-laborative framework for the care and control of dia-betes and tuberculosis’, with one of the main activities being the routine implementation of bidirectional screening of the two diseases.7 Bidirectional screening aims at early detection of TB among DM patients and vice versa, and assists with an integrated approach to the management of the co-morbidity.

Available data from various sites in India show that the prevalence of DM among TB patients ranges from

AFFILIATIONS1 Bowring and Lady Curzon

Hospital, Bangalore, India 2 Bangalore Medical College

& Research Institute, Bangalore, India

3 World Health Organization Country Office in India, New Delhi, India

4 International Union Against Tuberculosis and Lung Disease, South-East Asia Office, New Delhi, India

5 Médecins Sans Frontières, Operational Research Unit, Luxembourg

CORRESPONDENCEK S RavishAssistant ProfessorDepartment of Community MedicineBangalore Medical College & Research InstituteFort, K R Road Bangalore 560002, IndiaTel: (+91) 98450 47773Fax: (+91) 80267 04342e-mail: [email protected]

KEY WORDSTB; DM; bidirectional screening; India; feasibility

PHA 2013; 3(S1): S18–S22© 2013 The Union

Received 22 May 2013Accepted 3 July 2013

25% to as high as 44%.8–10 A pilot project was initiated in India in 2012 to assess the feasibility of bidirec-tional screening. Bowring and Lady Curzon Hospital, Bangalore, the teaching hospital of Bangalore Medical College and Research Institute in the South Indian State of Karnataka, was one of eight tertiary health fa-cilities that participated in this pilot project. We report on the feasibility and results of bidirectional screening of TB and DM at this centre.

METHODS

Design This is a descriptive study.

SettingBowring and Lady Curzon hospital is a 570-bed multi-speciality teaching hospital in Bangalore. The out-patient department caters for an average of 900 patients per day. The hospital has a separate TB clinic and a DM clinic. TB patients diagnosed at different clinics and hospital departments are referred to the TB clinic for treatment per the Revised National TB Control Pro-gramme (RNTCP) guidelines.11 An average of 1000 TB patients are treated in the TB clinic each year. The DM clinic is open 1 day a week and is visited by an average of ∼100 DM patients per week.

Study populationAll consecutively diagnosed TB patients aged ⩾15 years who attended the hospital’s TB clinic from 1 March to 30 September 2012 were screened for DM. At the DM clinic, all DM patients aged ⩾15 years were screened for TB over the same period.

Screening procedures The screening procedures and the recording and re-porting tools used were as per the protocols developed for the pilot project. The details of these procedures have been described in detail elsewhere.12–13 Briefl y, all of the patients at the TB clinic were asked about their history of DM. Patients not aware of their status were offered random blood glucose (RBG) testing. Venous blood samples were collected from the patients and blood glucose was tested by the hexokinase method. If RBG was ⩾110 mg/dl, the patients were offered fasting blood glucose (FBG) testing. The cut-offs used in the study were as follows: FBG < 110 mg/dl was consid-ered normal; FBG 110–125 mg/dl was diagnosed as pre-diabetes; and FBG ⩾ 126 mg/dl was diagnosed as DM.14 Patients with known DM and newly diagnosed DM were

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referred to the diabetes clinic for further management. Testing for human immunodefi ciency virus (HIV) in-fection was offered routinely to TB patients; informa-tion on HIV status was extracted from the TB registers.

At the DM clinic, patients were asked whether they were under TB treatment. Those who were not were asked about specifi c symptoms and signs indicative of TB (cough for ⩾2 weeks, prolonged fever, weight loss, loss of appetite, enlarged glands). Patients who gave an affi rmative answer for any of these symptoms were referred to the TB clinic for further evaluation. At the TB clinic, these patients underwent investigations in-cluding sputum smear microscopy, chest radiography and other investigations per RNTCP guidelines. Type of TB was classifi ed per the national guidelines, which are in line with WHO recommendations.11

Data collection and validationAt the TB clinic, an additional TB-DM register was used to record data on the following variables: age, sex, cur-rent smoker (defi ned as a person who had smoked to-bacco at least once during the last 3 months), residence (urban or rural), HIV status, RBG and FBG levels, dates of TB diagnosis, RBG and FBG tests and referral and enrolment into DM care. At the DM clinic, a separate treatment card for each patient was used to record data about the patient’s DM history and current DM status, screening for TB symptoms, the result of screen-ing and the result of the investigations. The existing staff of the TB and DM clinics in the routine health care setting were trained and involved in the study; no additional manpower or infrastructure was used. Su-pervision and site visits were undertaken by staff from The Union and the RNTCP during the study, and all the records were checked for completeness, consis-tency and accuracy.

Data analysis and statisticsThe individual patient data were double-entered into EpiData software, version 3.1 (EpiData Association, Odense, Denmark), validated and analysed. The data were summarised using frequencies and proportions. Differences between groups were compared using the χ² test. A P value of <0.05 was considered statistically signifi cant. The number needed to test (NNT, defi ned as reciprocal proportion of the sum of new DM and pre-diabetes cases) was calculated, disaggregated by demo-graphic and clinical characteristics.

Ethics approvalWe obtained administrative approval from the head of the Bangalore Medical College and Research Institute, Bangalore. The entire protocol was reviewed and ap-proved by the Ethics Advisory Group of The Union.

RESULTS

Screening tuberculosis patients for diabetes mellitusThe results of DM screening among TB patients are sum-marised in Table 1. The median (interquartile range) age of the TB patients was 35 (25–45) years. Of 510 TB pa-tients, 32 (6.3%) had been previously diagnosed with

DM. Screening among the remaining 478 patients yielded 15 (2.9%) and 15 (2.9%) pre-diabetes and new DM cases, respectively. Of the 47 known/newly diag-nosed patients, 45 (96%) were registered at the DM clinic for further management. Almost all patients un-derwent RBG testing within one day of the date of TB diagnosis; >95% of the patients eligible for FBG un-derwent the test within 2 days of the RBG test.

The demographic and clinical characteristics of TB patients associated with DM prevalence are shown in Table 2. DM prevalence was signifi cantly higher among

ACKNOWLEDGEMENTSThe authors acknowledge their Dean/Director, Banga-lore Medical College and Research Institute, and the Medical Superintendent, Bowring and Lady Curzon hospital for their support.A workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Opera-tional Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Opera-tional Research Unit, Médecins Sans Frontières, Luxembourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark.Conflict of interest: none declared.

TABLE 1 Screening TB patients for DM at Bowring and Lady Curzon Hospital, Bangalore, India, March–September 2012

Indicator n (%)

Patients with TB registered over the study period 510Patients with a known diagnosis of DM 32 (6.3)Patients needing to be screened with RBG 478Patients screened with RBG 478 (100)Patients with RBG ⩾110 mg/dl 110Patients screened with FBG 109 (99.1)

Patients with FBG <110 79Patients with FBG 110–125 15 (2.9)Patients with FBG ⩾126 mg/dl

(newly diagnosed with DM) 15 (2.9)Patients with known or newly diagnosed DM 47 (9.2)Patients with known and newly diagnosed DM

referred to DM care 47 (100)Patients with known or newly diagnosed DM

reaching DM care 45 (95.7)

TB = tuberculosis; DM = diabetes mellitus; RBG = random blood glucose; FBG = fasting blood glucose.

TABLE 2 Characteristics of TB patients screened for DM at Bowring and Lady Curzon Hospital, Bangalore, India, March–September 2012

Characteristic

TotalTB patients

n

Patientswith DM

n (%) P value

Total 510 47 (9.2)Age, years

<40 319 12 (3.8) <0.001⩾40 191 35 (18.3)

Sex Male 316 32 (10.1) 0.36Female 194 15 (7.7)

Residence Urban 393 38 (9.7) 0.52Rural 117 9 (7.7)

Smoking status* Smoker 137 23 (16.8) <0.001Non-smoker 372 23 (6.2)

HIV statusPositive 83 8 (9.6) 0.54Negative 423 38 (9.0)Unknown 4 1 (25.0)

Type of TBPulmonary 205 30 (14.6) <0.001Extra-pulmonary 305 17 (5.6)

* Not recorded for one TB patient.TB = tuberculosis; DM = diabetes mellitus; HIV = human immuno-deficiency virus.

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TB patients aged ⩾40 years, among smokers, and in patients with pulmonary TB (PTB).

The NNT to fi nd a new case of DM and/or pre-diabetes is sum-marised in Table 3. The overall NNT in this cohort of TB patients was 16. However, the NNT was lower among TB patients aged ⩾40 years, smokers, and individuals with PTB.

Screening diabetes mellitus patients for tuberculosisThe results of TB screening among DM patients are shown in Ta-ble 4. Overall, 1670 DM patients were seen at least once during this period. Of these, 45 were already known TB patients: 17 new smear-positive PTB, 9 new smear-negative PTB, 16 new extra-pulmonary TB, 1 new-others and 2 treatment after default. Of the remaining 1625 patients screened for TB, 152 (9.3%) were found to have symptoms suggestive of TB, and they were referred to the

TB clinic for further evaluation. All those referred reached the TB clinic and underwent evaluation. Among the 152 symptomatic patients, two new smear-positive TB patients were diagnosed and initiated on TB treatment. The NNT to detect one person with symptoms suggestive of TB was ∼10, and for detection of one TB case it was ∼812.

DISCUSSION

The fi ndings of this study provide important insights into the programme management of TB-DM co-morbidity, and have sev-eral health policy implications.

First, we implemented bidirectional screening for TB and DM using existing resources and staff, thus indicating that this is fea-sible. Almost all TB patients underwent screening for DM and vice versa. One of the primary reasons for the low loss to follow-up was the close proximity of the TB and DM clinics. The process of screening yielded additional new cases of DM and TB, although the NNT to detect one new TB case among DM patients was high compared with the NNT to detect DM among TB patients.

Second, about 10% of TB patients attending the TB clinics had DM. This is lower than the prevalence reported from other sites in South India, where it ranged from 25% to 44%.8–10 It should be noted that the median age of our study population was lower than that in the other studies, and it is well known that the prev-alence of diabetes increases with age. The tests and criteria used for the diagnosis of DM in our study (RBG followed by FBG) dif-fered from those used in other studies.8–9 The sensitivity of FBG is lower than that of the 75 g oral glucose tolerance test, and this may have resulted in underestimation of the true proportion of DM in our population. Furthermore, the screening yielded 15 pa-tients with pre-diabetes who are at higher risk of developing type 2 DM in the future. These patients could be targeted for counsel-ling and other preventive services. Another reason is probably the higher proportion of extra-pulmonary TB patients observed in our study, who are known to have a lower prevalence of DM.15

Third, nearly two thirds of all identifi ed DM patients knew their status prior to screening. This could be because of the nature of the study setting, i.e., a tertiary care hospital where patients have the opportunity to periodically undergo various investigations, including those for DM. Given the ease and speed of performing DM tests, the results are usually available earlier than those for TB tests. This might also have contributed to the higher proportion of previously known DM. Nevertheless, the early identifi cation of patients with co-morbidity, especially among the newly diagnosed cases, helped us to link these patients to appropriate DM care, which could lead to improved TB treatment outcomes.

Fourth, nearly 10% of the DM patients screened (at least once during the study period) in the DM clinics had symptoms sugges-tive of TB. This is higher than in the general health facility set-ting, where it is estimated that ∼2–3% of patients have TB symp-toms.16–17 However, we found very few TB cases among them. While the exact reasons for the low yield are not clear, it could be due to the fact that DM patients were managed by individual phy-sicians at diagnosis, and only after glycaemic control was achieved were they referred to DM clinic for periodic visits and collection of free drugs. Patients attending DM clinics were therefore more likely to have adequate glycaemic control and could thus have had a lower risk of having TB.15 The other reason for the low yield could be the lack of availability of state-of-the-art diagnostic tools, such as nucleic acid amplifi cation tests or culture. Future studies should focus on the use of these tools to evaluate whether this could increase the yield of TB among screened DM patients.

TABLE 3 Number needed to screen to find a new case of DM and pre-diabetes among TB patients at Bowring and Lady Curzon Hospital, Bangalore, India, March–September 2012

Characteristic

APatients with

unknownDM status

n

BNew

DM casesdiagnosed

n

CPre-diabetes

cases diagnosed

nNNT

(A/B+C)

Total TB patients 478 15 15 16Age, years

<40 312 5 5 31⩾40 166 10 10 8

SexMale 294 10 11 14Female 184 5 4 20

ResidenceUrban 367 12 12 15Rural 111 3 3 18

Smoking status*Smoker 122 8 5 9Non-smoker 355 6 10 22

HIV statusPositive 77 2 1 25Negative 397 12 14 15Unknown 4 1 0 40

Type of TBPulmonary 184 9 8 11Extra-pulmonary 294 6 7 23

* Not recorded for one TB patient.DM = diabetes mellitus; TB = tuberculosis; NNT = number needed to test; HIV = h uman immunodeficiency virus.

TABLE 4 Screening of DM patients for TB at Bowring and Lady Curzon Hospital, Bangalore, India, March–September 2012

Indicator n (%)

Patients seen in the DM clinic during this period 1670Patients already diagnosed with TB elsewhere 45Patients screened at least once for TB symptoms in

this period 1625Of those screened, patients with a positive TB

symptom screen 152 (9.3)Patients with a positive TB symptom screen referred for

TB investigations 152Patients diagnosed with TB after referral for investigations 2 (0.1)Patients identified with TB (known and new) 47 (2.8)Patients with TB receiving treatment 47

DM = diabetes mellitus; TB = tuberculosis.

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Public Health Action Bidirectional TB-DM screening S21

One limitation of our study was that we were not able to ascer-tain whether a high FBG in patients with TB was indicative of true DM or of infection-induced hyperglycaemia. This requires periodic blood glucose testing over the course of TB treatment, which was beyond the scope of the current study. Further research is needed to ascertain this and the optimum timing of DM screening among TB patients. The other related limitation was that we could not use a glycosylated haemoglobin test for the diagnosis of DM, and this might have led to an under-diagnosis of pre-diabetes and DM. However, as the glycosylated haemoglobin test is expensive, its use in programme conditions needs further evaluation.

In conclusion, our study showed that bidirectional screening for DM and TB was feasible, with a high yield of DM among TB patients. Screening TB patients for DM could be an effi cient tool for the programme management of TB-DM co-morbidity. The yield of TB among DM patients was low and needs future research using new, improved TB diagnostic tools.

References 1 World Health Organization. Global tuberculosis report 2012. WHO/HTM/

TB/2012.6. Geneva, Switzerland: WHO, 2012. www.who.int/tb/publications/global_report/gtbr12_main.pdf Accessed August 2013.

2 International Diabetes Federation. IDF diabetes atlas. 5th ed. Unwin N, Whiting D, Guariguata L, et al., eds. Brussels, Belgium: International Diabe-tes Federation, 2012. http://www.eatlas.idf.org Accessed August 2013.

3 Ramachandran A, Ma R C W, Snehalatha C. Diabetes in Asia. Lancet 2010; 375: 408– 418.

4 Danaei G, Finucane M M, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 2011; 378: 31– 40.

5 Stevenson C R, Critchley J A, Forouhi N G, et al. Diabetes and the risk of tu-berculosis: a neglected threat to public health. Chronic Illn 2007; 3: 228–245.

6 Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tuberculo-sis: a systematic review of 13 observational studies. PLOS Med 2008; 5: e152.

7 World Health Organization/International Union Against Tuberculosis and Lung Disease. Provisional collaborative framework for care and control of tuberculosis and diabetes. WHO/HTM/TB/2011.15. Geneva, Switzerland: WHO, 2011.

8 Vishwanathan V, Kumpatla S, Aravndalochanan V, et al. Prevalence of diabe-tes and prediabetes and associated risk factors among tuberculosis patients in India. PLOS ONE 2012; 7: e41367.

9 Balakrishnan S, Vijayan S, Nair S, et al. High diabetes prevalence among tuberculosis cases in Kerala, India. PLOS ONE 2012; 7: e46502.

10 Gupta S, Shenoy V P, Bairy I, Srinivasa H, Mukhopadhyay C. Diabetes melli-tus and HIV as co-morbidities in tuberculosis patients of rural South India. J Infect Public Health 2011; 4: 140–144.

11 Central Tuberculosis Division, Directorate General of Health Services, Min-istry of Health & Family Welfare. Technical and operational guidelines for tuberculosis control, Revised National Tuberculosis Control Programme. New Delhi, India: Government of India, 2005. http://www.tbcindia.nic.in/pdfs/Technical%20&%20Operational%20guidelines%20for%20TB%20Control.pdf Accessed August 2013.

12 India Tuberculosis-Diabetes Study Group. Screening of patients with tuber-culosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

13 India Diabetes-Tuberculosis Study Group. Screening of patients with diabe-tes mellitus for tuberculosis in India. Trop Med Int Health 2013; 18: 646–654.

14 Directorate General of Health Services, Ministry of Health & Family Welfare. Operational guidelines. National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease and Stroke (NPCDCS). New Delhi, India: Government of India, 2008–2009. http://health.bih.nic.in/Docs/Guide lines/ Guidelines-NPCDCS.pdf Accessed August 2013.

15 Leung C C, Lam T H, Chan W M, et al. Diabetic control and risk of tubercu-losis: a cohort study. Am J Epidemiol 2008; 167: 1486–1494.

16 Directorate General of Health Services, Ministry of Health & Family Welfare. Training module for medical practitioners. Revised National TB Control Pro-gramme. New Delhi, India: Government of India, 2010. http://www.tbcindia. nic.in/pdfs/Training%20Module%20for%20Medical%20Practitioner.pdf Ac-cessed August 2013.

17 Santha T, Garg R, Subramani R, et al. Comparison of cough of 2 and 3 weeks to improve detection of smear-positive tuberculosis among out-patients in India. Int J Tuberc Lung Dis 2005; 9: 61–68.

Contexte : Dispensaires de tuberculose (TB) et de diabète (DM) à l’Hôpital Bowring et Lady Curzon, un centre de soins tertiaires à Bangalore, Inde.Objectif : Evaluer la faisabilité et les résultats d’un dépistage bidirec-tionnel TB-DM.Méthodes : Il s’agit d’une étude descriptive menée entre le 1er mars et le 30 septembre 2012 pendant laquelle les patients TB ont fait l’objet d’une évaluation pour DM et vice versa. Un glucose sanguin à jeun ⩾126 mg/dl et a été considéré comme DM et un glucose sanguin à jeun de 110–125 mg/dl comme prédiabète.Résultats : Sur 510 patients TB, 32 (6,3%) avaient été diagnostiqués antérieurement comme diabétiques. Le dépistage parmi les 478 pa-tients TB restants a eu un rendement de 15 sujets prédiabétiques

(2,9%) et de 15 nouveaux cas de diabète (2,9%). On a trouvé une prévalence plus élevée de DM chez les patients de ⩾40 ans, chez les patients atteints de TB pulmonaire et chez les fumeurs. Sur 47 patients TB-DM, 45 ont été pris en charge pour leur DM. Sur 1670 patients DM suivis dans les dispensaires du DM, 45 avaient déjà une TB. Parmi les 1625 restants et dépistés, 152 (9%) souffraient de symptômes suggestifs de TB, parmi lesquels deux patients souffraient de TB.Conclusion : Le dépistage bidirectionnel pour DM et TB est réalisable et donne un rendement élevé pour le DM chez les patients TB. Le rendement de TB parmi les patients DM est faible et nécessite des recherches ultérieures utilisant des outils améliorés pour le diagnostic de la TB.

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Public Health Action Bidirectional TB-DM screening S22

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

Marco de referencia: Los consultorios de tuberculosis (TB) y diabetes (DM) en el Hospital Bowring y Lady Curzon, un centro de atención terciaria de Bangalore en la India.Objetivo: Se buscó evaluar la factibilidad del cribado bidireccional de la TB y la DM y los resultados de esta intervención. Métodos: Fue este un estudio descriptivo realizado entre el 1° de marzo y el 30 de septiembre del 2012, en el cual se investigó en to-dos los pacientes TB el diagnóstico de DM y vice versa. Una glucemia en ayunas igual o superior a 126 mg/dl determinó el diagnóstico de DM y entre 110 y 125 mg/dl definió el diagnóstico de prediabetes. Resultados: De los 510 pacientes con TB, 32 contaban con un di-agnóstico previo de DM (6,3%). Con el cribado de los 478 pacientes restantes se estableció el diagnóstico de 15 casos de prediabetes

(2,9%) y de 15 casos nuevos de DM (2,9%). Se observó una prevalen-cia de DM más alta en los pacientes ⩾40 años de edad, los pacientes con TB pulmonar y los fumadores. Cuarenta y cinco de los 47 pacientes con TB y DM se inscribieron en el programa de atención de la DM. De los 1670 pacientes atendidos en las consultas de DM, en 45 se había establecido ya el diagnóstico de TB. De los 1625 pacientes re-stantes que participaron en el cribado, 152 presentaban signos indic-ativos de TB (9 %) y en dos de ellos se confirmó el diagnóstico. Conclusión: La detección sistemática bidireccional de la DM y la TB es factible y ofrece un alto rendimiento diagnóstico de casos de DM en los pacientes que sufren TB. El rendimiento diagnóstico del cribado de la TB en los pacientes DM fue bajo y se precisan nuevas investigaciones que utilicen instrumentos diagnósticos de la TB nuevos y mejorados.

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Public Health Action

Characteristics of patients with diabetes screened for tuberculosis in a tertiary care hospital in South IndiaS. Kumpatla,1 A. Sekar,1 S. Achanta,2 B. N. Sharath,2,3 A. M. V. Kumar,4 A. D. Harries,5,6 V. Viswanathan1

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://doi.dx.org/10.5588/pha.13.0035

Setting: Tertiary care hospital for diabetes mellitus (DM) in Tamil Nadu, South India.Objective: To compare the socio-demographic, clinical and biochemical characteristics in DM patients with and without tuberculosis (TB).Design: A descriptive study involving a review of rou-tinely maintained records to capture the results of screen-ing of DM patients for TB between March and December 2012. DM patients were first asked whether they already had TB, and if not they were screened for TB symptoms, followed by investigations for and possible diagnosis of TB. Results: Of 7083 DM patients, 38 already had TB. Of the remainder, 125 (1.8%) had TB symptoms; 71 were inves-tigated and 12 were newly diagnosed with TB. Of the 50 TB patients, 64% had smear-positive pulmonary TB (PTB). DM-TB patients were older, and had lower education level and economic status, a higher frequency of alcohol use, lower body mass index, a longer duration of DM, a greater likelihood of receiving insulin and poorer glycae-mic control.Conclusion: Screening of DM patients for TB was feasible in a tertiary care hospital. The yield of new TB cases was low and merits further investigation. Socio-demographic and clinical characteristics were different in patients with DM and TB compared to those with DM only.

AFFILIATIONS1 MV Hospital for Diabetes

and Prof M Viswanathan Diabetes Research Centre, Chennai, India (World Health Organization Collaborating Centre for Research, Education and Training in Diabetes)

2 World Health Organization Country Office in India, New Delhi, India

3 Department of Commu-nity Medicine, Employees State Insurance Corpora-tion (ESIC) Medical College, Bangalore, India

4 International Union Against Tuberculosis and Lung Disease ( The Union), South-East Asia Office, New Delhi, India

5 The Union, Paris, France6 London School of Hygiene

& Tropical Medicine, London, UK

CORRESPONDENCEVijay ViswanathanMV Hospital for Diabetes & Prof M Viswanathan Diabetes Research Centre No. 4Main Road, Royapuram, Chennai–600013, India Tel: (+91) 44259 54913Fax (+91) 44259 54919e-mail: [email protected]

KEY WORDSDM; TB; India; screening

PHA 2013; 3(S1): S23–S28© 2013 The Union

Received 24 May 2013Accepted 17 July 2013

screening of the two diseases.11 However, screening methods, recording and reporting for the two diseases in routine health care settings have not been well de-termined, and operational research is needed to pro-vide better information in this area.12 Based on these recommendations, a standardised procedure for bi-directional screening, a monitoring tool and a quarterly system of recording and reporting were recently devel-oped and implemented in eight tertiary centres and more than 60 peripheral health facilities across India. Our hospital was one of the eight tertiary health care facilities that participated in the pilot screening of DM patients for TB. Evaluation of this pilot in 2012 by the India Diabetes Mellitus–Tuberculosis Study Group showed that it is feasible to screen DM patients for TB within the routine setting, resulting in high rates of detection of TB.13

Despite these good results, there is a paucity of in-formation on the association of socio-demographic characteristics and clinical features in DM patients with TB. In the present study, we therefore aimed to describe the screening of DM patients for TB and the socio-demographic characteristics, clinical features and biochemical variables of DM patients in relation to the diagnosis of TB in a tertiary care hospital for DM in South India.

METHODS

Study designThis was a descriptive study involving a review of rec-ords maintained during the pilot screening of DM pa-tients for TB.

SettingThe study was conducted at the MV Hospital for Dia-betes, a 100-bed tertiary care hospital for DM in the state of Tamil Nadu, South India. More than 200 000 DM patients have been registered in care at the hospi-tal since its opening, and 100–200 patients visit the hospital every day on an out-patient basis. Patients at-tending the hospital and suspected of having DM are screened using the 2 h 75 g oral glucose tolerance test. The diagnosis of DM is based on previous DM history or on the WHO’s criteria for the classifi cation of glu-cose intolerance.14 Fasting and postprandial samples are collected from known cases of DM.

For the TB screening, all DM patients presenting to the out-patient department were asked whether they had already been diagnosed with TB and were on TB treatment. If the answer was yes, this was recorded and the patient was not asked again about TB until

Diabetes mellitus (DM) has become a global epi-demic, especially in low- and middle-income

countries, where 80% of DM-related mortality is esti-mated to occur.1 Currently, there are more than 61 mil-lion people living with DM in India.2 In a similar vein to DM, about one third of the world’s population is currently infected with Mycobacterium tuberculosis, and approximately 8.8 million new cases of active TB are identifi ed globally each year.3 India also has a huge TB burden, with an estimated 2.3 million new cases every year.4

There is good evidence that the risk of TB among people with DM is three times higher than in those without DM,5 and patients with both DM and TB have poorer TB treatment outcomes.6–8 India, which has a high dual burden of DM and TB,9,10 could benefi t if patients were screened early for either disease. The World Health Organization (WHO) and the Interna-tional Union Against Tuberculosis and Lung Disease (The Union) launched the ‘Collaborative framework for the Care and Control of Diabetes and Tuberculo-sis’, with one of several important recommendations being the routine implementation of bidirectional

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Public Health Action Screening DM patients for TB S24

completion of TB treatment. If the answer was no, the patient was screened for symptoms by trained staff, based on the Revised National TB Control Programme (RNTCP) guidelines.13,15 Briefl y, patients with cough for ⩾2 weeks or any suspicion of active pulmonary TB (PTB) or extra-pulmonary TB were categorised as hav-ing presumptive TB and were further investigated to confi rm the disease. Two same-day sputum specimens from presumptive TB patients were collected in the DM clinic and transported to the government-run microscopy centre (1.5 km away) for sputum smear microscopy by Ziehl-Neelsen staining.15 Patients with negative sputum smears or extra-pulmonary TB sus-pects underwent appropriate investigations such as chest radiography to confi rm TB. Those subsequently diagnosed with TB were referred to the RNTCP for TB treatment. All patient data were recorded on treatment cards and captured in an electronic database.

The TB screening process started in March 2012 and was performed when the patient visited the clinic. Screening was done on every patient visit. For the pur-pose of this study, however, we only describe the re-sults of screening on the fi rst visit.

Study populationAll DM patients aged ⩾15 years attending the MV hospital for their routine DM care and screened for TB between March and December 2012 were included in the study.

Data variables and sources of dataData variables included: 1) socio-demographic charac-teristics: DM registration number, age, sex, residence, education, occupation and socio-economic status, smoking (current smoker was defi ned as a history of

smoking in the last 3 months) and alcohol consump-tion (60 ml of alcohol daily). Occupation status was classifi ed as skilled (carpenter, painter, electrician, fi t-ter, etc.), unskilled (farmer, labourer), business, and ‘others’ for categories such as retired people, home-makers and the unemployed. Economic status was classifi ed as low (family income <US$200 per month), middle (family income US$200–400 per month) and high (family income >US$400 per month); 2) clinical features: family history of DM, weight and height (for body mass index [BMI]), duration of DM and current medication for DM; and 3) blood glucose measure-ments performed at the time of TB screening, including fasting and postprandial glucose in mg/dl and glyco-sylated haemoglobin (HbA1c) in %. Plasma glucose was estimated using the glucose oxidase peroxidase method. HbA1c was estimated using the high-performance liquid chromatography method with Bio-Rad Variant Turbo equipment (Bio-Rad Laboratories, Hercules, CA, USA; Appendix Table A). Data were also collected on the TB screening process, diagnosis of TB, type of TB and referral for TB care.

Analysis and statisticsData were extracted from the electronic database and analysed using SPSS (Statistical Package and Service Solutions, version 16.0, SPSS Inc, Chicago, IL). The fl ow of patients from screening to diagnosis of TB was described, and the socio-demographic characteristics, clinical features and biochemical variables of DM pa-tients without TB symptoms (DM only) and with TB (previously known and newly diagnosed DM-TB) were evaluated. Patients with symptoms of TB who were ei-ther not investigated or not diagnosed with TB and patients with missing data were not included in this

ACKNOWLEDGEMENTSThe authors acknowledge the help rendered by R Priya-darshini, Krishna, M Rajalak-shmi, V Arulmozhi and C Deepika for data collec-tion. They also acknowledge Selvan and A Vigneswari for conducting data analysis. The authors thank all their patients for cooperating with them throughout the study. A workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Opera-tional Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Opera-tional Research Unit, Médecins Sans Frontières, Luxembourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark.Conflict of interest: none declared.

FIGURE Flow chart showing the results of screening DM patients for TB in a tertiary care hospital in South India, March–December 2012. DM = diabetes mellitus; TB = tuber-culosis; M = male; F = female.

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Public Health Action Screening DM patients for TB S25

comparative analysis. Mean and standard deviations (SD) were calculated. Continuous variables such as age, BMI and duration of DM were converted to categorical variables and compared u sing the χ² test where appropriate. Levels of signifi cance were set at 5%.

Ethics approvalEthics approval for the study was obtained from the Institutional Ethics Committee of MV Diabetes Research Centre and The Union Ethics Advisory Group.

TABLE 1 Types and categories of TB in DM patients screened for TB in a tertiary care hospital between March and December 2012

Category and type of TBPatients

n

New 45Smear-positive PTB 27Smear-negative PTB 12Extra-pulmonary TB 4Not recorded 2

Retreatment 5Relapse smear-positive PTB 1Failure smear-positive PTB 1Return after default smear-positive PTB 3

TB = tuberculosis; DM = diabetes mellitus; PTB = pulmonary tuberculosis.

TABLE 2 Socio-demographic characteristics of DM patients with and without TB* in a tertiary care hospital in South India, March–December 2012

Characteristic

DMpatientswith TBn (%)

DMpatients

with no TB*n (%) P value

Total 47 (100) 6113 (100)Sex

Male 39 (83) 3544 (58) <0.001Female 8 (17) 2569 (42)

Age, years, mean ± SD 57.4 ± 12.7 53.8 ± 11.2 0.03Age, years

15– 44 5 (10.6) 1135 (18.6) 0.2345–64 32 (68.1) 3956 (64.7) 0.74⩾65 10 (21.3) 1022 (16.7) 0.52

ResidenceUrban 27 (57.4) 3383 (55.3) 0.77Rural 20 (42.6) 2730 (44.7)

Educational statusNo school 8 (17) 1182 (19.3) 0.83Primary/high school 31 (66) 2555 (41.8) <0.001Technical/diploma 2 (4.3) 964 (15.8) 0.05University degree 6 (12.8) 1412 (23.1) 0.13

OccupationSkilled 5 (10.6) 741 (12.1) 0.93Unskilled 16 (34) 517 (8.5) <0.001Business 3 (6.4) 974 (15.9) 0.11Other 23 (48.9) 3881 (63.5) 0.05

Economic statusLow 13 (27.7) 1783 (29.2) 0.95Middle 33 (70.2) 3433 (56.2) 0.07High 1 (2.1) 897 (14.7) 0.03

Current smoking 7 (14.9) 589 (9.6) 0.22Alcohol consumption 13 (27.7) 627 (10.3) <0.001

* Those with no symptoms suggestive of TB.DM = diabetes mellitus; TB = tuberculosis; SD = standard deviation.

TABLE 3 Clinical features in DM patients with and without TB* in a tertiary care hospital in South India, March–December 2012

Characteristic

DMpatientswith TBn (%)

DMpatients

with no TB*n (%) P value

Total 47 (100) 6113 (100)Family history of DM 22 (46.8) 4740 (77.5) <0.001BMI, kg/m2, mean ± SD 22.8 ± 5.03 27.3 ± 4.45 <0.001

<18 8 (17.0) 49 (0.8) 0.00118–23 19 (40.4) 865 (14.2) <0.001>23 20 (42.6) 5199 (85) <0.001

Duration of DM, years, mean ± SD 10.9 ± 8.7 5.93 ± 5.99 <0.001

<5 17 (36.2) 3793 (62.0) <0.0015–10 6 (12.8) 1135 (18.6) 0.41>10 24 (51.1) 1185 (19.4) <0.001

Current DM treatmentDiet only 0 184 (3.0) NAOral medication only 8 (17.0) 3465 (56.7) <0.001Insulin only 4 (8.5) 98 (1.6) <0.01Oral plus insulin 35 (74.5) 2366 (38.7) <0.001

* Those with no symptoms suggestive of TB.DM = diabetes mellitus; TB = tuberculosis; BMI = body mass index.

RESULTS

The TB screening process is shown in the Figure. Of 7083 DM patients screened for TB, (mean age 54 [SD 11.3] years, 4255 [60%] male), 38 had a known history of TB and were on treatment (26 smear-positive PTB, 8 smear-negative PTB, 2 extra-pulmonary TB and 2 with no information on TB type; 33 new and 5 retreat-ment patients). There were 6920 patients with no symptoms of TB and 125 (1.8%) who screened positive for TB symptoms. Of these 125 patients, 71 (57%) submitted two sputum specimens for smear examination and were investigated for TB, and 12 were diagnosed with TB (6 new smear-positive PTB, 4 new smear-negative PTB and 2 extra-pulmonary TB). The clinical and socio-demographic characteristics of the 71 patients examined for TB did not differ substantially from those of the 54 patients not in-vestigated (Table A). In all, there were 50 patients (0.7%) with TB among the DM patients; the categories and types of TB are shown in Table 1. Notably, 32 patients (64%) had smear-positive PTB.

The socio-demographic characteristics of DM-TB and DM-only patients are shown in Table 2. A signifi cantly higher proportion of DM-TB patients were male, older and had a lower education level and socio-economic status than the DM-only patients. More patients in the DM-TB group consumed alcohol compared to the DM-only group. The percentage of subjects defi ned as current cigarette smokers was also higher in the DM-TB group than that in the DM-only group, but the difference was not statistically signifi cant.

The clinical features of the DM-TB and DM-only patients are shown in Table 3. There were signifi cant differences between the DM-TB and DM-only groups: there was a stronger family history of DM in the DM-only group; the mean BMI was lower in the DM-TB group; and the DM-TB group had a higher proportion of patients with a duration of DM >10 years, and who were on com-bined oral medication and insulin.

Biochemical variables in DM-TB patients and DM-only patients are shown in Table 4. Although there were no differences in fasting and postprandial plasma glucose between the two groups, more in-dividuals had HbA1c ⩾9% in the DM-TB than the DM-only group.

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Public Health Action Screening DM patients for TB S26

DISCUSSION

This study shows that the fi rst-time screening of DM patients for TB is feasible in a routine health care setting of a tertiary care hos-pital for DM in South India. Over a period of 9 months, during which DM patients attending the clinic were screened, we de-tected 50 patients with TB, giving a case rate of 706 per 100 000 screened patients. Moreover, 64% of the patients diagnosed had smear-positive disease and were therefore highly infectious. Most of the patients had been diagnosed outside the DM clinic and were already on treatment at the time of screening. This is proba-bly due to the very good geographical coverage of the RNTCP and good access to community TB case fi nding services in India.16 The relatively low yield in detecting new TB cases merits further inves-tigation. However, if we exclude those already diagnosed with TB, the case rate for newly diagnosed cases would be 169 per 100 000 patients, which is still higher than the total TB case notifi cation rate in India.

DM patients with TB tended to be male, older, have low BMI and were more likely to consume tobacco and alcohol than pa-tients without TB. These fi ndings might be expected given the ep-idemiology of TB. Rieder has reported that age and sex are strong determinants of TB, with the highest risks being found in elderly people,17 and this was evident in the current study.. Systematic re-views have shown that undernutrition, smoking, diabetes and al-cohol misuse are individual risk factors that can double or triple the risk of developing active TB.18 A mathematical modelling analysis of the effects of smoking on TB infection and mortality projected that smoking would produce an excess of 18 million TB cases and 40 million deaths from TB between 2010 and 2050.19 It was also reported that smoking could delay the attainment of the Stop TB Partnership target of reducing TB mortality by 50% from 1990 to 2015.19 A large part of the TB burden in India can be attributed to smoking (40%)20 and DM (15%).21 Alcohol misuse and DM are predicted to increase in low- and middle-income countries, and might be crucial factors in the coming decades.22,23 More patients with both DM and TB came from the unskilled workforce sector with lower socio-economic status, more had had their metabolic disease for >10 years, were on combination ther-apy with oral and insulin medication and their glycosylated hae-moglobin levels were signifi cantly higher, indicating poorer gly-caemic control. These data all indicate that DM patients with TB were poorer and had long-standing, severe and uncontrolled dis-

ease, an association that has previously been reported as a risk factor for TB.24

The strengths of this study were that a large number of DM pa-tients were screened, the registration of patients was consecutive and robust, allowing a denominator for the study, and the record-ing and reporting system using the established electronic database worked well. There were a number of limitations and challenges. First, over 40% of patients with symptoms suggestive of TB were reluctant to give sputum specimens for reasons that are currently unclear and may be related to stigma or disbelief that they might have TB, and this requires further prospective research using qual-itative methods. Second, we are reporting only on the results of the fi rst screening, and it is possible that patients returning to the clinic and being screened again may be found to have TB on sub-sequent occasions. This is also the subject of further research, as we will be prospectively following up this cohort of 7000 patients over several years to determine the yield of TB screening at each subsequent clinic visit. Third, we relied on symptom screening and sputum smear examination, both of which lack sensitivity for diagnosing TB. Screening by chest radiography might give a higher yield, but the cost and logistical challenges would also be greater. More research is needed to determine the most appropri-ate screening and diagnostic algorithm for DM patients attending clinics, and also whether it is cost-effective to use newer technol-ogy such as Xpert® MTB/RIF (Cepheid, Inc, Sunnyvale, CA, USA) for diagnosing TB.25 Advocacy and the political will to deploy more effective and affordable point-of-care diagnostics at DM clinics might assist in the diagnosis and management of both of these diseases. This is urgently required if we are to move forward in making TB screening routine in DM clinics. Fourth, the lower mean BMI in the DM-TB group compared to the DM-only group should be interpreted with caution, given the cross-sectional na-ture of the study, and it is not clear whether TB led to low BMI or whether TB occurred as a result of a low BMI. Fifth, a multiple re-gression model would have strengthened the conclusions of the study, but due to the small number of TB-DM cases, we felt it pru-dent to limit our analysis to bivariate associations.

In terms of policy, the screening of TB patients for DM is rela-tively straightforward, and in pilot studies in different states in India this has resulted in a high rate of detection of DM in TB pa-tients (10–15%).26 A decision was thus made by the Ministry of Health to scale up screening of DM in TB patients countrywide, with a national training manual and revised registers and treat-ment cards to support this activity. However, screening of DM pa-tients for TB is less easy, with pilot studies in India documenting challenges such as poor registration of DM patients, a reluctance by DM doctors to undertake this additional work and systemati-cally record every screening event, and resistance of patients to submit sputum specimens.13 Our current study also confi rms these fi ndings. Importantly, an electronic recording system can be used to reliably collect and report on the necessary data. Paper-based systems could probably not work long-term in this type of setting with patients in chronic care, and there is a need for elec-tronic health systems, as shown elsewhere in DM clinics in Africa and the Middle East.27,28 Further research is needed to better un-derstand some of these challenges, and in particular the value of repeated screening and use of point-of-care TB diagnostics at each subsequent clinic visit. This study shows the importance of good collaboration between communicable and non-communicable disease programmes.

In conclusion, the study highlights that screening of DM pa-tients for TB is feasible in the routine health care setting of a terti-ary care hospital. DM-TB patients were older, had lower education

TABLE 4 Biochemical variables in DM patients with and without TB* in a tertiary care hospital of South India, March–December 2012

Characteristic

DMpatientswith TB

(N = 47)mean ± SD

or n (%)

DMpatients

with no TB*(N = 6920)mean ± SD

or n (%) P value

Fasting plasma glucose,mg/dl 189.4 ± 75.1 170.4 ± 69.7 0.17

Postprandial plasma glucose, mg/dl 302.9 ± 124 265 ± 111 0.05

Glycosylated haemoglobin† 9.2 ± 2.1 8.5 ± 2.1 0.03<7 7 (15.9) 1234 (24.4) 0.267–8.9 13 (29.5) 1988 (39.3) 0.24⩾9 24 (54.5) 1834 (36.3) 0.02

* Those with no symptoms suggestive of TB.† Data available for 44 DM patients with TB and 5056 DM patients without TB.TB = tuberculosis; DM = diabetes mellitus.

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Public Health Action Screening DM patients for TB S27

levels and socio-economic status, a higher frequency of smoking and alcohol use, a longer duration of DM, a greater likelihood of being on oral medication and insulin and lower BMI and poorer glycaemic control.

APPENDIX

tional Diabetes Federation, 2012. http://www.eatlas.idf.org/diabetesatlas/5e/update2012 Accessed August 2013.

3 World Health Organization. Global tuberculosis control, 2011. WHO/HTM/TB/2011.16. Geneva, Switzerland: WHO, 2011.

4 World Health Organization. Global tuberculosis report, 2012. WHO/HTM/TB/2012.6. Geneva, Switzerland: WHO, 2012. http://www.who.int/tb/data Accessed August 2013.

5 Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tubercu-losis: a systematic review of 13 observational studies. PLOS Med 2008; 5: e152.

6 Alisjahbana B, Sahiratmadja E, Nelwan E J, et al. The effect of type 2 diabetes mellitus on the presentation and treatment response of pulmonary tuberculosis. Clin Infect Dis 2007; 45: 428– 435.

7 Restrepo B I, Fisher-Hoch S P, Smith B, et al. Mycobacterial clearance from sputum is delayed during the fi rst phase of treatment in patients with diabetes. Am J Trop Med Hyg 2008; 79: 541–544.

8 Wang C S, Yang C J, Chen H C, et al. Impact of type 2 diabetes on manifesta-tions and treatment outcome of pulmonary tuberculosis. Epidemiol Infect 2009; 137: 203–210.

9 Viswanathan V, Kumpatla S, Aravindalochanan A, et al. Prevalence of dia-betes and pre-diabetes and associated risk factors among tuberculosis pa-tients in India. PLOS ONE 2012; 7: e41367.

10 Balakrishnan S, Vijayan S, Nair S, et al. High diabetes prevalence among tu-berculosis cases in Kerala, India. PLOS ONE 2012; 7: e46502.

11 World Health Organization/International Union Against Tuberculosis and Lung Disease. Provisional collaborative framework for care and control of tuberculosis and diabetes. WHO/HTM/TB/2011.15. Geneva, Switzerland: WHO, 2011.

12 Harries A D, Murray M B, Jeon C Y, et al. Defi ning the research agenda to re-duce the joint burden of disease from diabetes mellitus and tuberculosis. Trop Med Int Health 2010; 15: 659–663.

13 India Diabetes Mellitus–Tuberculosis Study Group. Screening of patients with diabetes mellitus for tuberculosis in India. Trop Med Int Health 2013; 18: 646–654.

14 World Health Organization. Defi nition, diagnosis and classifi cation of diabe-tes mellitus and its complications. Report of WHO consultation. Part 1: Diagnosis and classifi cation of diabetes mellitus. WHO/NCD/NCS/99.2. Ge-neva, Switzerland: WHO, 1999. http://whqlibdoc.who.int/hq/1999/who_ncd_ ncs_99.2.pdf Accessed August 2013.

15 Central Tuberculosis Division, Revised National Tuberculosis Control Pro-gramme, Directorate General of Health Services, Ministry of Health and Family Welfare. Technical and operational guidelines for tuberculosis con-trol. New Delhi, India: Government of India, 2005.

16 Sachdeva K S, Kumar A, Dewan P, Kumar A M V, Satyanarayana S. New vision for Revised National Tuberculosis Control Programme (RNTCP): universal access—‘Reaching the un-reached’. Ind J Med Res 2012; 135: 690–694.

17 Rieder H. Epidemiologic basis of tuberculosis control. Paris, France: Interna-tional Union Against Tuberculosis and Lung Disease, 1999.

18 Lönnroth K, Castro K G, Chakaya J M, et al. Tuberculosis control and elimi-nation 2010–50: cure, care and social development. Lancet 2010; 375: 1814–1829.

19 Basu S, Stuckler D, Bitton A, Glantz S A. Projected effects of tobacco smoking on worldwide tuberculosis control: mathematical modelling analysis. BMJ 2011; 343: d5506.

20 Hassmiller K. The impact of smoking on population level tuberculosis out-comes. TSRU progress report, 2007. The Hague, The Netherlands: KNCV, 2007.

21 Stevenson C R, Forouhi N G, Roglic G, et al. Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence. BMC Public Health 2007; 7: 234.

22 Dooley K E, Chaisson R E. Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis 2009; 9: 737–746.

23 World Health Organization, Department of Mental Health and Substance Abuse. Global status report on alcohol 2004: country profi les Uganda. Ge-neva, Switzerland: WHO, 2004.

24 Restrepo B I, Fisher-Hoch S P, Pino P A, et al. Tuberculosis in poorly con-trolled type 2 diabetes: altered cytokine expression in peripheral white blood cells. Clin Infect Dis 2008; 47: 634–641.

25 Boehme C C, Nabeta P, Hillemann D, et al. Rapid molecular detection of tu-berculosis and rifampin resistance. N Engl J Med 2010; 363: 1005–1015.

26 India Tuberculosis–Diabetes Study Group. Screening of patients with tuber-culosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

27 Allain T J, van Oosterhout J J, Douglas G P, et al. Applying lessons learnt from the ‘DOTS’ tuberculosis model to monitoring and evaluating persons with diabetes mellitus in Blantyre, Malawi. Trop Med Int Health 2001; 16: 1077–1084.

28 Khader A, Farajallah L, Shahin Y, et al. Cohort monitoring of persons with diabetes mellitus in a primary healthcare clinic for Palestine refugees in Jor-dan. Trop Med Int Health 2012; 17: 1569–1576.

TABLE A Data variables

N = 125 (M:F 79:46)

P value

DM patientswith symptomssuggestive ofTB who wereinvestigated

n = 71 (46:25)n (%)

DM patientswith symptomssuggestive ofTB who were

not investigatedn = 54 (32:22)

n (%)

Socio-demographic characteristics Age, years, mean ± SD 57.1 ± 11.3 56 ± 11.1 0.58 Residence

Rural 24 (33.8) 17 (31.5) 0.85 Urban 47 (66.2) 37 (68.5)

Educational status No schooling 5 (7) 4 (7.4) 0.75 Primary/high school 51 (71.8) 41 (75.9) 0.76 Technical/diploma 6 (8.5) 5 (9.3) 0.87 University degree 9 (12.7) 4 (7.4) 0.51

Occupation Skilled 6 (8.5) 2 (3.7) 0.48 Unskilled 14 (19.7) 7 (13) 0.45 Business 11 (15.5) 12 (22.2) 0.47 Other 40 (56.3) 33 (61.1) 0.72

Socio-economic status (USD) Low (<200) 5 (7) — Middle (200–400) 60 (84.5) 47 (87) 0.89 High (>400) 6 (8.5) 7 (13) 0.60

Current smoking 7 (9.9) 4 (7.4) 0.76 Alcohol consumption 9 (12.7) 4 (7.4) 0.39Clinical features Positive family history of DM 52 (73.2) 36 (66.7) 0.44 BMI, kg/m2, mean ± SD 24.6 ± 4.8 27.3 ± 4.9 0.002 Duration of DM

<5 years 29 (40.8) 21 (38.9) 0.97 5–10 years 16 (22.5) 18 (33.3) 0.25 >10 years 26 (36.6) 15 (27.8) 0.39

Current DM treatment Diet only 1 (1.4) — Oral medication only 28 (39.4) 24 (44.4) 0.7 Insulin only 2 (2.8) 2 (3.7) 0.82 Oral plus insulin 40 (56.3) 28 (51.9) 0.75

Biochemical variablesFasting plasma glucose,

mg/dl 165.8 ± 67.6 172 ± 82 0.687Postprandial plasma

glucose, mg/dl 238.9 ± 90.1 265.6 ± 92.5 0.12Glycosylated haemoglobin

% 9.1 ± 2.3 8.6 ± 1.9 0.19

M = male; F = female; DM = diabetes mellitus; TB = tuberculosis; SD = standard deviation.

References 1 World Health Organization. Diabetes. Fact sheet no. 312. Updated March

2013. WHO Media Centre: WHO, 2013. http://www.who.int/mediacentre/factsheets/fs312/en/index.html Accessed August 2013.

2 International Diabetes Federation. IDF diabetes atlas. 5th ed, 2012 update. Unwin N, Whiting D, Guariguata L, et al., eds. Brussels, Belgium: Interna-

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Public Health Action Screening DM patients for TB S28

Contexte : Hôpital de soins tertiaires pour le diabète sucré (DM) à Tamil Nadu, Inde du Sud.Objectif : Comparer les caractéristiques socio-démographiques, cli-niques et biochimiques chez les patients DM atteints ou non de tu-berculose (TB).Schéma : Etude descriptive impliquant une révision des dossiers en-tretenus en routine entre mars et décembre 2012 pour y prélever les résultats du dépistage chez les patients DM à la recherche d’une TB. On a d’abord demandé aux patients DM s’ils avaient déjà été diag-nostiqués avec une TB et dans la négative, on les a dépistés à la recherche de symptômes de TB, puis investigués et diagnostiqués en matière de TB.Résultats : Sur 7083 patients DM, 38 souffraient déjà de TB. Parmi les restants, 125 (1,8%) étaient atteints de symptômes de TB, 71 ont été

investigués et 12 nouveaux cas de TB ont été diagnostiqués. Une TB pulmonaire à frottis positif existait chez 64% de l’ensemble des 50 pa-tients TB. Les patients DM-TB étaient plus âgés, bénéficiaient d’une éducation et d’un statut socio-économique moins favorables, con-naissaient une fréquence plus élevée d’utilisation d’alcool, avaient un indice de masse corporelle plus bas et une durée plus longue du DM ainsi qu’une susceptibilité plus grande de recevoir de l’insuline et un contrôle moins bon de la glycémie.Conclusion : Le dépistage de la TB chez les patients DM est réalisable dans un hôpital de soins tertiaires. Le rendement en nouveaux cas de TB est bas et mérite d’être investigué davantage. Les caractéristiques socio-démographiques et cliniques sont différentes chez les patients atteints de DM-TB par comparaison avec ceux atteints seulement de DM.

Marco de referencia: Un hospital de atención terciaria de la diabetes (DM) en Tamil Nadu, en el sur de la India.Objetivo: Comparar las características sociodemográficas, clínicas y bioquímicas entre los pacientes con diagnóstico de DM que padecen tuberculosis (TB) y los pacientes que sufren exclusivamente de DM. Métodos: Fue este un estudio descriptivo, que consistió en examinar los expedientes clínicos corrientes, a fin de investigar los resultados del cribado de la TB en los pacientes con diagnóstico de DM entre marzo y diciembre del 2012. Inicialmente se preguntó a los pacientes DM sobre el antecedente personal de TB y en los casos negativos, se buscaron los síntomas indicativos de la enfermedad y se practicó la investigación y el diagnóstico de la TB. Resultados: De los 7083 pacientes con diagnóstico de DM, 38 tenían un antecedente de TB y del resto de pacientes, 125 presentaban sínto-mas indicativos de la enfermedad (1,8%), se investigaron 71 pacientes

y se detectaron 12 casos nuevos de TB. De los 50 pacientes que padecían TB, el 64% correspondió a una TB pulmonar con bacilosco-pia positiva. Los pacientes con ambas enfermedades eran mayores, poseían un menor grado de instrucción, presentaban una situación económica menos favorable, mayor frecuencia de consumo de alcohol, un índice de masa corporal más bajo, una evolución más prolongada de la DM, mayor probabilidad de estar recibiendo insulina y exhibían un equilibrio menos eficaz de la glucemia.Conclusión: Es posible practicar la detección de la TB en los pacientes DM en un hospital de atención terciaria. Se obtuvo un bajo rendi-miento diagnóstico de casos nuevos de TB, lo cual justifica nuevas investigaciones. Al comparar los pacientes que padecen DM única-mente con los pacientes que padecen ambas enfermedades se observa-ron diferencias en las características sociodemográficas y clínicas.

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

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Public Health Action

Screening patients with tuberculosis for diabetes mellitus in Gujarat, India

P. Dave,1 A. Shah,2 M. Chauhan,1 A. M. V. Kumar,3 A. D. Harries,4,5 S. Malhotra,6 K. Pujara,1 P. Patel,1M. Mane,1 A. Thakkar,1 S. Bharaswadkar,2 B. N. Sharath,7 S. Achanta2

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi.org/10.5588/pha.13.0027

Setting: Anklav Tuberculosis Unit, Anand, Gujarat, India. Objective: To determine in a cohort of TB patients 1) the prevalence of diabetes (DM) and impaired fasting glucose (IFG), 2) the time taken for diagnosis, 3) demographic and clinical factors associated with DM and IFG, and 4) the number needed to screen (NNS) for diagnosing new cases of DM and IFG.Design: Descriptive study. TB patients registered be-tween January and September 2012 were asked whether they had a history of DM. Those with unknown DM were tested for random and fasting blood glucose (FBG). FBG of ⩾126 mg/dl and 110–125 mg/dl were considered in-dicative of DM and IFG, respectively.Results: Of 556 TB patients, 553 (99%) were assessed: 36 (6.5%) had diabetes (14 had been previously diag-nosed DM and 22 were newly diagnosed), and 39 (7%) had IFG. The median (interquartile range) time to DM diagnosis was 5 (1–17) days. Age ⩾35 years was associ-ated with DM. The NNS was 25 and 14 for one new case of DM and IFG, respectively, with a lower NNS in males, those aged ⩾35 years, those with smear-positive pulmo-nary TB, retreatment patients and smokers.Conclusion: This pilot project shows that it is feasible and valuable to screen patients with TB for DM in a rou-tine setting, resulting in earlier identification of DM and opportunities for better management of comorbidity.

Tuberculosis (TB) continues to be a major health problem in India, with an estimated 3.1 million

prevalent cases and an average annual mortality of 0.32 million.1 This high national burden of TB is made potentially worse by other diseases, such as human immunodefi ciency virus/acquired immune-defi ciency syndrome (HIV/AIDS), in some districts that can lead to higher rates of disease, increased transmission of in-fection and poor treatment outcomes.

With India in transition in terms of socio-economic development and lifestyle changes, there is also a ris-ing epidemic of diabetes mellitus (DM). It is estimated that there are over 60 million people currently with DM in the country, and almost half are undiagnosed, with the number expected to increase to 80 million by 2030.2,3 This increase in the prevalence of DM has been noted in both urban and rural areas. A recent re-view reported that the prevalence of DM ranged from 3% to 12% across different rural areas of the country,

AFFILIATIONS1 Department of Health,

Government of Gujarat, Gandhinagar, India

2 World Health Organization Country Office for India, New Delhi, India

3 International Union Against Tuberculosis and Lung Disease (The Union), South-East Asia Office, New Delhi, India

4 The Union, Paris, France5 Department of Infectious

and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK

6 All India Institute of Medical Sciences, New Delhi, India

7 Employees State Insurance Corporation (ESIC) Medical College, Bangalore, India

CORRESPONDENCEAmar ShahWorld Health Organization Country Office for India5 Jivraj Mehta BhavanSector-10Gandhinagar, Gujarat, India Tel: (+91) 94281 00915e-mail: [email protected]

KEY WORDSTB; DM; pre-diabetes; screening; Gujarat

PHA 2013; 3(S1): S29–S33© 2013 The Union

Received 14 May 2013Accepted 27 June 2013

with an expected rate of increase of 2.0 per 1000 pop-ulation per year.4

DM has been shown to be an independent risk factor for TB,5 and there is evidence showing high DM preva-lence in TB patients in community-based studies mainly from the southern part of India.6–8 DM is said to account for about 10% of the population-attributable fraction of TB cases globally,9 although this will vary from coun-try to country depending on the degree of overlap be-tween DM and TB in the population. It has been sug-gested by modelling analysis that DM may account for 15% of all TB and 21% of smear-positive TB cases.10

This strong association raises the question as to whether TB patients should be routinely screened for DM. In this regard, a systematic review of screening conducted in multiple settings showed that the yield of DM from screening patients with TB varied from 1.7% to 36%, with this proportion being infl uenced by the underlying burden of TB and the severity of DM.11 The presence of concomitant DM amongst TB patients is also associated with a higher risk of poor treatment out-comes in terms of treatment failure, relapse and death.12 Screening for DM in TB patients could thus potentially identify DM cases early; this might lead to early link-age to DM care,13 which in turn might improve treat-ment outcomes.14

There has been an international call for investment in collaborative care directed towards TB and DM.15 Appreciating the need to implement this joint frame-work in India, a consensus was reached among multi-ple stakeholders, including the national authorities, to initiate screening for DM among TB patients in pilot settings across India. The results of this countrywide screening have been reported in terms of aggregate data,13 and this has encouraged the belief that DM screening and care should be integrated into India’s Revised National TB Control Programme (RNTCP). We report the implementation fi ndings and lessons learnt in Gujarat, one of the network of pilot sites where the feasibility of and yield from introducing DM screening for TB patients under routine programme settings were assessed. The specifi c objectives of this study were to determine 1) the prevalence of DM and impaired fasting glucose (IFG) in a cohort of TB pa-tients, 2) the time intervals for the diagnosis of DM and IFG, 3) demographic and disease-related factors associated with DM and IFG, and 4) the number needed to screen (NNS) for diagnosing patients with newly di-agnosed DM and IFG.

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Public Health Action Screening of TB patients for DM S30

METHODS

Study setting and populationAnand, a district in Gujarat State in western India, has a population of 2.1 million. It has 11 community health centres, 43 primary health centres and two ter-tiary care centres, in the form of one private medical college and one civil hospital. For its TB control activi-ties, the district is covered by the RNTCP, which has been operating since 2004 along the same basic princi-ples as the World Health Organization’s (WHO’s) DOTS strategy. Under the RNTCP, the district has four Tuber-culosis Units (TUs), geographical areas defi ned as sub-district level programme management units, each covering a population of 250 000–500 000, with TB di-agnostic and treatment services being delivered through a network of primary, secondary and tertiary health care facilities. The district also has 23 designated mi-croscopy centres—1 per 0.1 million population—for performing quality assured sputum microscopy, and 33 sputum collection and transportation centres situ-ated in the remotest parts of the district where no other health care facility or easy transport system is available.

In the last 5 years, the district has consistently achieved the twin RNTCP objectives, i.e., treatment success rates of ⩾85% among new smear-positive cases and detection rates of ⩾70% of estimated cases. In 2012, 14 963 patients with presumptive TB were in-vestigated, and 2999 TB patients were placed on stan-dardised treatment.

The implementation site for the current descriptive study was the Anklav TU in the Anand district. This TU covers a population of 0.57 million, 85% of whom live in rural areas. The TU has 16 government health facilities in the form of peripheral health institutions (PHIs), where this project was implemented.

Screening procedures for diabetes mellitusAll health facilities were provided with DM testing kits containing glucometers and test strips. Laboratory technicians were instructed to perform DM screening as soon as a patient was confi rmed as having TB. The RNTCP diagnostic algorithm was used for the diagno-sis of TB.16 In some patients where the diagnosis was made through sputum collection centres, screening was performed during outreach sessions (‘Mamata Day’) organised in the village locally by a laboratory techni-cian. These sessions were held for other primary care activities into which the DM screening activity was in-tegrated to enhance TB screening coverage within the district.

At all sites, patients were fi rst asked whether they had previously been diagnosed with DM. Patients with a previous diagnosis were referred back for DM care so that their blood glucose levels could be controlled. Those with no known diagnosis of DM underwent a random blood glucose (RBG) test based on a capillary blood sample with a glucometer, followed by an FBG test at the next visit if the RBG was ⩾110 mg/dl. The diagnosis of DM followed national guidelines, with FBG cut-off thresholds as recommended by the WHO.17 Briefl y, FBG ⩾126 mg/dl (⩾7 mmol/l) indicates DM;

FBG 110–125 mg/dl (6.1–6.9 mmol/l) indicates IFG; and FBG <110 mg/dl (<6.1 mmol/l) is normal.

Provision of care for diabetes mellitus TB patients with FBG of ⩾126 mg/dl were diagnosed with presumptive DM and referred to the diabetes ser-vices in public hospitals with DM facilities for a defi ni-tive diagnosis and enrolment in care. Three DM health care facilities are distributed equally within the TU, one of which is at the private medical college.

The state level offi cer and district TB offi cer were trained at national level in January 2012, after which district and sub-district level staff were trained using a training module.18 The DM testing kits were supplied at the end of February 2012.

Study participantsAll TB patients (adults and children) registered from January to September 2012 were enrolled into the screening programme. DM screening was initiated in the facilities from 1 March 2012.

Data collection and data variablesAn additional TB-DM register was developed and used to capture the screening results. All sites were visited by the study investigators at monthly intervals to check for completeness, consistency and accuracy of data, and any issues relating to recording and report-ing were resolved. Variables related to the study objec-tives were sourced from the TB-DM register and TB register.

Data entry analysis and statisticsAll data from the TB-DM register were double entered into an electronic database created using EpiData en-try software version 3.1 (EpiData Association, Odense, Denmark), validated for discrepancies and corrected. Additional variables such as age, sex, type of TB and HIV status, were captured in MS Excel® (Microsoft, Palisade Corp, Newfi eld, NY, USA) and merged into the EpiData database before analysis. The data was an-alysed using EpiData analysis software (version V2.2.2.180). Statistical differences between patient characteristics among prevalent DM cases and patients with no DM were evaluated using the χ² test or Fisher’s exact test, as appropriate. Confi dence intervals of 95% were used; the level of signifi cance was set at ⩽0.05.

Ethics Ethics approval was obtained from the Ethics Advisory Group of the International Union Against Tuberculosis and Lung Disease, Paris, France. Programmatic approval was granted for the study at state and national level.

RESULTS

Of the 556 TB patients (median age 35 years, inter-quartile range [IQR] 25–50 years) registered, the major-ity were screened for DM (Table 1). Of these patients, 36 (6.5%) were found to have DM: 14 (2.5%) had a previous diagnosis of DM and 22 (4%) were newly diagnosed. The median FBG in newly diagnosed DM patients was 248 mg/dl (IQR 153–337 mg/dl); 39 (7.0%)

ACKNOWLEDGEMENTSA workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Opera-tional Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Opera-tional Research Unit, Médecins Sans Frontières, Luxembourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark. Conflict of interest: none declared.

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had IFG. Most DM patients were referred to and enrolled into DM care; no action was taken for patients with IFG. Of the 74 pa-tients with extra-pulmonary TB, 54 had lymphadenopathy, 18 pleural effusion, 1 abdominal TB, 1 bone TB; of these, 3 had DM.

The time intervals between the start of TB treatment and the RBG and FBG measurements are shown in Table 2. The glucometer and test strips were not available in the health care facility, as the National Programme for Prevention and Control of Cancer, Diabe-tes and Stroke (NPCDCS) had not been implemented in the dis-

trict; these had to be procured through external sources, and they arrived towards the end of the fi rst quarter. For the two quarters combined, the median (IQR) time interval from TB treatment to DM diagnosis was 5 days (1–17)—with a median of 2 days between TB treatment initiation and RBG, and a further 2 days between RBG and FBG.

The number of TB patients with DM and the NNS for diagnos-ing DM and IFG are shown in Table 3. The only characteristic as-sociated with increased DM prevalence was age ⩾35 years (P = 0.001). There were no characteristics associated with IFG. Among those screened, 18 (3.2%) were children. None of these was diag-nosed with DM. The NNS for all TB patients was 25 for one new DM case, and 14 for one new case of IFG. The NNS for identifying a new case of DM was lower in males, those aged ⩾35 years, those with smear-positive pulmonary TB, those on a re-treatment regi-men, smokers and those who were HIV-negative. The median age of the HIV-infected subjects was 30 years (IQR 20.5–38.0).

TABLE 1 Screening of patients with TB for DM in Anklav Tuberculosis Unit, Gujarat, January–September 2012

Indicator n %

Patients with TB registered over the 3 quarters 556Patients with a known diagnosis of DM 14 2.5Patients needing to be screened with RBG 542Patients screened with RBG 539 99.4Patients with RBG >110 mg/dl, needing to be screened

with FBG 229Patients screened with FBG 227 99.1Patients with FBG ⩾126 mg/dl (newly diagnosed

with DM) 22 4.1Patients with FBG ⩾110 to <126 mg/dl (impaired

fasting glucose) 39 7.0Patients with known and newly diagnosed DM 36 6.5Patients with known and newly diagnosed DM referred

for DM care 34 94.4Patients with known or newly diagnosed DM who

reached DM care 32 94.1

TB = tuberculosis; DM = diabetes mellitus; RBG = random blood glucose; FBG = fasting blood glucose.

TABLE 2 Interval between start of TB treatment and diagnosis of DM in TB patients in Anklav Tuberculosis Unit, Gujarat, January–September 2012

Quarter 2duation, daysmedian [IQR]

Quarter 3duration, daysmedian [IQR]

TB treatment start date to RBG 2 [0–24] 2 [0–7]RBG to FBG 2 [1–12] 3 [2–5]

TB = tuberculosis; DM = diabetes mellitus; IQR = interquartile range; RBG = ran-dom blood glucose; FBG = fasting blood glucose.

TABLE 3 TB patients NNS to identify new case of DM, one new case with IFG, and both DM and IFG, in Anklav Tuberculosis Unit, Gujarat, January–September 2012

Characteristic

TBpatients

registeredn

TBpatients with DM

n

New DMn

IFGn

NNS for new DM

n

NNS for new IFG

n

NNS for both

DM and IFGn

Total 556 36 22 39 25 14 9Age, years

<35 236 4 2 12 118 20 17⩾35 320 32 20 27 16 12 7

SexMale 371 27 18 25 21 15 9Female 185 9 4 14 46 13 10

Initial sputum smear result*Smear-positive 364 26 17 28 21 13 8Smear-negative 120 8 4 6 30 20 12

Type of TB†

New case 429 24 15 34 29 13 9Retreatment 126 12 7 5 18 25 11

Current smoking status‡

Current smoker 89 9 9 11 10 8 4Non-smoker 462 25 13 28 36 17 11

Disease classificationPulmonary 482 34 21 36 23 13 8Extra-pulmonary 74 2 1 3 74 25 19

HIV statusNegative 532 35 22 38 24 14 9Positive 24 1 0 1 — 24 24

* Initial sputum results were not recorded for 65 extra-pulmonary TB patients and 7 pulmonary TB patients.† One transfer-in patient not included. ‡ Defined as having smoked tobacco at least once in the last month; data not available for 5 patients.TB = tuberculosis; NNS = number needed to screen; DM = diabetes mellitus; IFG = impaired fasting glucose; HIV = human immunodeficiency virus.

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Public Health Action Screening of TB patients for DM S32

DISCUSSION

In the setting of a TU in India with a predominantly rural popula-tion, screening of TB patients for DM and IFG was feasible, with nearly 100% of patients agreeing to be tested, and over 13% being diagnosed with either DM or IFG. The time from the start of TB treatment to diagnosis was <1 week, which was short, consider-ing that this was a two-step process requiring RBG to identify those at risk and FBG to establish the diagnosis. The baseline characteristic signifi cantly associated with DM was age, with pa-tients aged ⩾35 years having an increased prevalence of disease. No case of DM or IFG was found among children suffering from TB. This suggests that child TB patients do not need to be screened for DM. The NNS to identify one new case of DM was 25, with fewer needed for certain categories of patient, including men, those aged ⩾35 years, those with smear-positive and recurrent disease and smokers.

At 6.5%, the prevalence of DM in TB patients in our TU was low compared with other pilot sites in India.13 This is probably explained by the fact that our patients came mainly from rural areas, with a relatively low median age. A study in the urban pop-ulation of Ahmedabad, Gujarat, found a 14% prevalence of type 2 DM and 6% IFG.19 Due to the young age of the HIV-infected indi-viduals, the incidence of pre-existing DM in this group was rela-tively low.

There are concerns that TB may induce infection-related hyperglycaemia,20–22 and that investigations for DM should be conducted later during the course of TB treatment to avoid false-positive diagnoses. In our study, the median FBG in newly diag-nosed DM patients was almost 250 mg/dl, which is twice as high as the cut-off threshold. This suggests that even if stress-induced hyperglycaemia is present, it is important to screen early during TB treatment so that appropriate measures can be taken to reduce the high blood glucose levels. A caveat is that we do not currently know whether good blood glucose control early on in the course of TB treatment affects treatment outcomes.

The strengths of this study are that we implemented screening within the routine system with existing staff. Furthermore, with just one day of training, clinical and nursing staff were able to fol-low the diagnostic algorithm and record appropriate data in the devised formats. There were, however, some challenges. First, as the NPCDCS had not been implemented in the district, the glucometer and test strips had to be procured through external sources. Sec-ond, for the same reason, there was no free supply of oral hypo-glycaemic drugs, and some patients had to pay for these as out-of-pocket expenses. Third, the fact that it was a rural area meant that only one specialised doctor was available to manage clinically com-plicated DM-TB patients, and patients needed special counselling to ensure that they visited the specialist for regular follow-up.

In conclusion, this study demonstrates the feasibility and value of screening TB patients for DM in a predominantly rural area. The information from this study is also useful for national scale-up. It shows that simple diagnostic technology should be in place at the start of screening activities, and that DM drugs should be available free of charge for patients to avoid out-of-pocket ex-penses; both of these issues highlight the importance of scaling up DM screening in parallel with the scale-up of the NPCDCS pro-gramme and/or the scale-up of state health systems resources. Our

study also indicates the importance of training peripheral health care workers in the simple management of DM so that patients do not have to make long journeys for specialist care and follow-up.

References 1 World Health Organization. Global tuberculosis report 2012. WHO/HTM/

TB/2012.6. Geneva, Switzerland: WHO, 2012. http://www.who.int/tb/publications/global_report/en/ Accessed 9 August 2013.

2 International Diabetes Federation. IDF diabetes atlas, 5th ed. Unwin N, Whiting D, Guariguata L, et al., eds. Brussels, Belgium: International Diabetes Federation, 2011. http://www.eatlas.idf.org/ Accessed 9 August 2013.

3 Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047–1053.

4 Misra P, Upadhyay R P, Misra A, Anand K. A review of the epidemiology of diabetes in rural India. Diabetes Res Clin Pract 2011; 92: 303–311.

5 Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tubercu-losis: a systematic review of 13 observational studies. PLOS Med 2008; 5: e152.

6 Gupta S, Shenoy V P, Bairy I, Srinivasa H, Mukhopadhyay C. Diabetes melli-tus and HIV as co-morbidities in tuberculosis patients or rural South India. J Infect Public Health 2011; 4: 140–144.

7 Balakrishnan S, Vijayan S, Nair S, et al. High diabetes prevalence among tuberculosis cases in Kerala, India. PLOS ONE 2012; 7: e46502.

8 Viswanathan V, Kumpatla S, Aravindalochanan V, et al. Prevalence of diabetes and pre-diabetes and associated risk factors among tuberculosis patients in India. PLOS ONE 2012; 7: e41367.

9 Lönnroth K, Castro K G, Chakaya J M, et al. Tuberculosis control and elimi-nation 2010–50: cure, care, and social development. Lancet 2010; 375: 1814–1829.

10 Stevenson C R, Forouhi N G, Roglic G, et al. Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence. BMC Public Health 2007; 7: 234.

11 Jeon C Y, Harries A D, Baker M A, et al. Bi-directional screening for tubercu-losis and diabetes: a systematic review. Trop Med Int Health 2010; 15: 1300–1314.

12 Zhang Q, Xiao H, Sugawara I. Tuberculosis complicated by diabetes mellitus at Shanghai Pulmonary Hospital in China. Jpn J Infect Dis 2009; 62: 390–391.

13 India Tuberculosis-Diabetes Study Group. Screening of patients with tuber-culosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

14 Ruslami R, Aarnoutse R E, Alisjahbana B, van der Ven A J, van Crevel R. Implications of the global increase of diabetes for tuberculosis control and patient care. Trop Med Int Health 2010; 15: 1289–1299.

15 World Health Organization/International Union Against Tuberculosis and Lung Disease. Provisional collaborative framework for care and control of tuberculosis and diabetes. WHO/HTM/TB/2011.15. Geneva, Switzerland: WHO, 2011.

16 Central TB Division, Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India. Managing tuberculosis in your area—a training course (module 1–4). New Delhi, India: Government of India, 2011. http://www.tbcindia.nic.in/pdfs/Module%201%20to%204.zip/ Accessed 9 August 2013.

17 World Health Organization. Defi nition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Summary of Technical Report and Rec-ommendations. Report of a WHO/IDF consultation. Geneva, Switzerland: WHO, 2006.

18 Central TB Division, Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India. Screening of tuberculosis patients for diabetes mellitus: pilot project. Training module for RNTCP staff. New Delhi, India: Government of India, 2012. http://www.tbcindia.nic.in/pdfs/TB-DM%20Training%20Module_Final.pdf/ Accessed 9 August 2013.

19 Nayak H K, Vyas S, Solanki A, Tiwari H. Prevalence of type 2 diabetes in ur-ban population of Ahmedabad, Gujarat. Indian J Medical Specialities 2011; 2: 101–105.

20 Goyal B N, Nigam P, Dubey A L, Joshi L D, Saxena H N. Study of the diabetic status in pulmonary tuberculosis. J Diabetes Assoc India 1978; 18: 191–197.

21 Kishore B, Nagrath S P, Mathur K S, Hazra D K, Agarwal B D. Manifest, chemical and latent chemical diabetes in pulmonary tuberculosis. J Assoc Physicians India 1973; 21: 875–881.

22 Oluboyo P O, Erasmus R T. The significance of glucose intolerance in pulmo-nary tuberculosis. Tubercle 1990; 71: 135–138.

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Public Health Action Screening of TB patients for DM S33

Contexte : Unité de Tuberculose (TB) d’Anklav, Anand, Gujarat, Inde.Objectif : Déterminer dans une cohorte de patients TB, 1) la préva-lence du diabète (DM) et les détériorations du glucose à jeun (IFG), 2) la durée avant le diagnostic, 3) les facteurs démographiques et cliniques associés à DM et IFG, et 4) le nombre de sujets à dépister (NNS) pour diagnostiquer un nouveau cas de DM et d’IFG.Schéma : Etude descriptive : on a interrogé les patients TB enregistrés entre janvier et septembre 2012 au sujet d’antécédents de DM. Chez ceux dont le DM n’était pas connu le glucose a été mesuré au hasard et à jeun (FBG). On a considéré respectivement comme DM et IFG un FBG de ⩾126 mg/dl et 110–125 mg/dl.Résultats : Sur 556 patients TB, 553 (99%) ont fait l’objet d’une

évaluation ; 36 (6,5%) souffraient de diabète (14 dont le DM était déjà connu et 22 nouvellement diagnostiqués) et 39 (7%) souffraient d’IFG. La durée médiane (IQR) avant le diagnostic a été de 5 jours (1–17). Un âge ⩾ 35 ans a été en association avec le DM. Le NNS était respectivement de 25 et de 14 pour un nouveau cas de DM et d’IFG, avec un NNS plus faible chez les hommes, dans le groupe d’âge ⩾ 35 ans, dans les TB pulmonaires à frottis positif, chez les patients en retraitement et chez ceux fumant actuellement.Conclusion : Ce projet pilote démontre qu’il est faisable et valable de dépister le DM chez les patients atteints de TB dans un contexte de routine, ce qui entraine une identification plus précoce du DM et des occasions d’une meilleure prise en charge de cette co-morbidité.

Marco de referencia: La Unidad de Tuberculosis (TB) de Anklav del distrito de Anand, en el estado de Gujarat, en la India.Objetivo: Determinar en una cohorte de pacientes TB los siguientes aspectos: 1) la prevalencia de diabetes (DM) y alteración de la glu-cemia en ayunas (IFG, prediabetes), 2) el lapso necesario hasta el diagnóstico, 3) los factores demográficos y clínicos que se asocian con la DM y la IFG, y 4) el número de personas que se deben examinar (NNS) con el fin de diagnosticar un caso nuevo de DM y IFG.Méthodos: Fue este un estudio descriptivo, en el cual se interrogó a los pacientes registrados por TB entre enero y septiembre del 2012 sobre sus antecedentes de DM. A los pacientes que desconocían su situación con respecto a la DM se practicaron pruebas de glucemia casual (RBG) y glucemia en ayunas (FBG). Se consideró como predia-betes una IFG de 110 a 125 mg/dl y se estableció el diagnóstico de DM con una FBG de ⩾126 mg/dl.

Resultados: Se examinaron 553 de los 556 pacientes con TB (99%); se diagnosticó DM en 36 pacientes (6,5%; 14 de ellos conocían el diagnóstico y 22 fueron casos nuevos) y 39 pacientes presentaron una IFG (7%). La mediana del lapso hasta el diagnóstico de DM fue 5 días (IQR a 17). La edad ⩾35 años se asoció con el diagnóstico de DM. El NNS a fin de detectar un caso de DM fue 25 y para un caso de IFG fue 14. Esta cifra fue inferior en los hombres, en las personas ⩾35 años de edad, en los casos de TB con baciloscopia positiva, en los pacientes en retratamiento de la TB y en los fumadores actuales.Conclusión: El presente proyecto piloto pone en evidencia que es posible y útil practicar una detección sistemática de la TB y la DM en la práctica corriente y que con esta intervención se logra una detección más temprana de la DM y se ofrecen ocasiones de mejorar el trata-miento de esta morbilidad asociada.

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

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Public Health Action

Is screening for diabetes among tuberculosis patients feasible at the fi eld level?B. Naik,1 A. M. V. Kumar,2 S. Satyanarayana,2 M. D. Suryakant,3 N. M. V. Swamy,4 S. Nair,1 P. Isaakidis,5 A. D. Harries6,7

and TB recommends bidirectional screening of the two diseases.6

A countrywide project was conducted in 2012 to better understand the optimal screening procedures, implementation, monitoring, results and challenges of screening patients with TB for DM within eight tertiary health care settings and more than 60 periph-eral health institutions (PHIs). The aggregate data of the project have been reported elsewhere.7,8 In this ar-ticle, we pre sent on a more individual basis the feasi-bility and results of screening TB patients for DM in 17 PHIs in a district of South India, and the challenges faced during implementation.

METHODS

Design This was a descriptive study involving the implemen-tation of DM screening procedures for TB patients in routine programmatic settings.

Setting Bangarpet (population 0.5 million) is one of the Tu-berculosis Units (TU) in the Kolar district in the south-ern part of India. TB diagnosis and treatment ser-vices are delivered in a decentralised manner at all the 17 PHIs of the TU. Under India’s Revised National TB Control Programme (RNTCP), a PHI is defi ned as any health facility with a sanctioned medical offi cer posi-tion. All presumptive TB cases are investigated for the disease at the designated microscopy centres. After being diagnosed with TB, patients receive intermit-tent treatment three times a week for a period of 6–9 months, delivered under direct observation in ac-cordance with national guidelines.9 TB patients are registered and followed up until completion of treat-ment as per national guidelines.

While facilities for DM screening are available at all PHIs, treatment services are provided only by the spe-cialists at the district level hospital and are continued in the PHI closest to the patient. The average distance from the PHIs to the district hospital is 35 km. Patients had to travel to the specialist hospital at their own ex-pense. The drugs for treating DM were available in the general pharmacy and dispensed by the hospital phar-macist on prescription by the treating doctor. All ser-vices for the diagnosis and treatment of DM were pro-vided free of charge.

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi.org/10.5588/pha.13.0022

Setting: Seventeen peripheral health institutions (PHI) in Kolar district (population: 0.5 million), South India. Objective: To assess the feasibility and results of screen-ing patients with tuberculosis (TB) for diabetes mellitus (DM) at peripheral level.Design: From January to September 2012, all TB patients were assessed for DM. Those with unknown DM status were screened for the disease (free of charge) by trained laboratory technicians at each PHI, using a glucometer sup-plied by the national programme on a capillary blood sam-ple. Those with fasting blood glucose (FBG) ⩾ 126 mg/dl (⩾7 mM) were diagnosed as DM-positive.Results: Of 362 TB patients, 358 (99%) were assessed for DM and 62 (17.1%) had the diseases—53 (14.6%) had a previous history of DM and 9 (2.9%) were newly diagnosed. All new DM patients were enrolled into DM care. Higher DM prevalence was found among TB patients aged ⩾40 years, smokers and those with smear-positive pulmonary TB. To detect a new case of DM, the number needed to screen (NNS) among TB patients was 40. Conclusion: Screening of TB patients for DM was feasi-ble and effective in a peripheral setting. The availability of trained laboratory technicians and free services at e very PHI made the intervention feasible. The study has contributed towards a national policy decision in this regard.

The world is facing a new epidemic of non-c ommunicable diseases due to various factors

such as urbanisation, a sedentary lifestyle, rising obe-sity and other lifestyle factors. In 2012, there were an estimated 371 million people living globally with dia-betes mellitus (DM), with numbers expected to rise to 552 million by 2030.1 India is badly affected by the DM epidemic, with over 60 million people estimated to have the disease.1

Previous studies have shown that people with DM have a higher risk of developing tuberculosis (TB) compared to those who do not have diabetes.2,3 Recent studies in India have also found a high prevalence of DM in TB patients.4,5 With a high DM burden in India, routine screening of TB patients for DM would appear to be worthwhile at all levels of care, including periph-eral health facilities. A recently launched World Health Organization–International Union Against Tuberculo-sis and Lung Disease (The Union) Framework for Col-laborative Activities to reduce the dual burden of DM

AFFILIATIONS1 World Health Organization

Country Office for India, New Delhi, India

2 International Union Against Tuberculosis and Lung Disease (The Union), South-East Asia Office, New Delhi, India

3 State Tuberculosis Centre, Ministry of Health and Family Welfare, Govern-ment of Karnataka, Banga-lore, India

4 District Tuberculosis Centre, Ministry of Health and Family Welfare, Government of Karnataka, Kolar, India

5 Médecins Sans Frontières, Mumbai, India

6 The Union, Paris, France 7 London School of Hygiene

& Tropical Medicine, London, UK

CORRESPONDENCEBalaji NaikOffice of the Joint Director (TB)Lady Willingdon State TB Centre4th Main RoadSampangiramanagaraBangalore 560 027, IndiaTel: (+91) 93410 60148e-mail: [email protected]

KEY WORDStuberculosis; diabetes m ellitus; screening; op erational research; India

PHA 2013; 3(S1): S34–S37© 2013 The Union

Received 3 May 2013Accepted 28 May 2013

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Public Health Action Field screening for diabetes in TB patients S35

Study populationAll TB patients registered from January to September 2012 in 17 PHIs in Bangarpet TU were included in the study.

Diabetes mellitus screening, variables and data collection The methods of screening, diagnosis and referral of TB patients with DM to diabetes care have been described in detail elsewhere.8 Briefl y, TB patients were asked if they had a history of DM. Among those with un-known DM status, a random blood glucose (RBG) test was offered, followed by a fasting blood glucose (FBG) test if the RBG was ⩾110 mg/dl (⩾6.1 mM). Blood glu-cose was assessed using a glucometer supplied by the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease and Stroke (NPCDCS) on a capillary blood sample. Those with an FBG ⩾126 mg/dl (⩾7 mM) were diagnosed with DM, and those with an FBG between 110 and 125 were di-agnosed with pre-diabetes (impaired fasting glucose), in accordance with national guidelines.10

Screening was performed by PHI laboratory tech-nicians trained by NPCDCS district nodal offi cers as part of the strategy adopted by the NPCDCS to screen all people aged >30 years at the point of primary con-tact with any health care facility. No additional staff were deployed for this project. Variables of interest to the study were sourced from the TB register and the TB-DM register.

Data analysis and statisticsData were entered in duplicate into an EpiData soft-ware package (EpiData entry version 3.1; EpiData As-sociation, Odense, Denmark, http://www.epidata.dk), the databases were compared and discrepancies re-solved by checking the original register. The propor-tion of DM cases that were ‘newly diagnosed’ was cal-culated. To find one additional DM case, the number needed to be screened (NNS) among TB patients was

determined. All variables were described as propor-tions, and differences between groups were compared for statistical significance using the χ2 test or Fisher’s exact test, as applicable. P values <0.05 were consid-ered statistically significant.

Ethics approvalThe protocol was reviewed and approved by The Union Ethics Advisory Group, Paris, France.

RESULTS

There were 362 patients registered in the TU, of whom 68% were male. The median age of the cohort was 40 years (interquartile range [IQR] 27–56), and the me-dian age of females was 30 years (IQR 21–45) com-pared to 45 years (IQR 32–60) among males. The re-sults of screening are presented in Table 1. Of the 362 TB patients, 358 (99%) were assessed for DM. More than 75% of the TB patients were found to have had their RBG tested within 3 days of starting TB treatment, and among those eligible for FBG, more than 75% had had their FBG tested within 6 days of the RBG. Among the 358 patients, 62 (17.1%) were found to have DM: 53 (14.6%) had a previous history of DM and 9 (2.9%) were newly diagnosed. In addition, 11 patients were di-agnosed with pre-diabetes. All newly diagnosed DM patients were referred and enrolled into DM care.

Further analysis showed that the prevalence of DM among TB patients aged ⩾40 years was signifi -cantly higher than among patients aged <40 years (Table 2). There was a higher prevalence of DM in new smear-positive pulmonary TB patients compared with new extra-pulmonary TB cases, and in smokers com-pared to non-smokers.

TABLE 1 Screening patients with TB for DM at 17 peripheral health institutions of the Bangarpet Tuberculosis Unit, Kolar, India, January–September 2012

Parameter n (%)

Patients registered with TB 362Patients with known diagnosis of DM 53 (14.6)Number needed to be screened with RBG 309Patients screened with RBG 305 (98.7)Patients with RBG ⩾110 mg/dl (⩾6.1 mM) and needing to be screened with FBG 101Patients screened with FBG 92FBG results FBG <110 mg/dl (<6.1 mM) FBG ⩾110 to 125 mg/dl (⩾6.1 mM to 6.9 mM) FBG ⩾126 mg/dl (⩾7 mM)

72 11 9

Newly diagnosed with DM* 9 (2.9)Patients with known or newly diagnosed DM 62 (17.1)Patients with newly diagnosed DM enrolled in DM care 9 (100)

* Percentage of screened patients with TB with a new diagnosis of DM.TB = tuberculosis; DM = diabetes mellitus; RBG = random blood glu-cose; FBG = fasting blood glucose; mM = millimoles.

ACKNOWLEDGEMENTSA workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Opera-tional Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Opera-tional Research Unit, Médecins Sans Frontières, Luxembourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark. Conflict of interest: none declared.

TABLE 2 Prevalence of DM among TB patients according to different variables, Kolar District, India, January–September 2012

Characteristic

TB patients

n

Patients with DM

n (%) P value

Total 362 62 (17.1)Age, years <40 173 10 (5.8) <0.01 ⩾40 189 52 (27.5)Sex Male 246 43 (17.5) 0.79 Female 116 19 (16.4)Type of TB New smear-positive pulmonary TB 162 36 (22.2) <0.01 New smear-negative pulmonary TB 45 7 (15.6) 0.20 New extra-pulmonary TB 95 8 (8.4) Reference Retreatment 60 11 (18.3) 0.07Current smoker* Yes 157 34 (21.7) 0.04 No 205 28 (13.7)HIV status Positive 22 1 (4.5) 0.15 Negative 340 61 (17.9)

* Current smoker = smoked in the last month.DM = diabetes mellitus; TB = tuberculosis; HIV = human immuno deficiency virus.

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Public Health Action Field screening for diabetes in TB patients S36

To detect a new case of DM, the NNS among TB patients was 40 (Table 3). Among the new smear-positive TB patients, the NNS was 23 compared to 30 among previously treated TB cases.

Some challenges were noted during the implementation of the screening process. There was a shortage of test kits (strips for the glucometer) for a brief period of 8 days, and the laboratory tech-nicians used the expired strips, re-calibrating the glucometers. This was later rectifi ed by the district programme manager of the NPCDCS, who obtained supplies of fresh batches of test strips.

DISCUSSION

This is part of the fi rst nationwide study from India reporting on the feasibility and outcomes of routine screening of patients with TB for DM. The results of this current study suggest that it is feasi-ble to implement routine screening of TB patients for DM at the peripheral level. Near-universal screening of TB patients shows that testing for DM is acceptable among TB patients. The availability of staff trained in using glucometers supplied by the NPCDCS and of free DM diagnostic and treatment services helped to make this intervention feasible, with no requirement for additional re-sources. While most of the TB patients underwent RBG testing within 3 days of starting TB treatment, nearly 8% of those with RBG levels >110 mg/dl (6.1 mM) who were eligible for FBG did not return. The exact reasons for this are not clear, although it could be due to implementation problems in the initial stages of the pilot project.

The overall prevalence of DM among TB patients was high, at 17%, although lower than in other parts of South India.4,5 The ac-tual prevalence could be much higher, as we used FBG to diag-nose DM and it is well known that FBG is not as sensitive as the 75 g oral glucose tolerance test (OGTT) and that it may miss cases of impaired glucose tolerance.11 A hospital-based study conducted in Karnataka State reported a DM prevalence of 30% among TB

patients. This higher prevalence may be attributed to selection bias due to hospital-based sampling.12 Previous studies from other South Indian states, such as Kerala and Tamil Nadu, reported a prevalence of 44% and 25% respectively.4,5 As has been reported in earlier studies, patients aged >40 years and those with smear-positive pulmonary TB had a higher prevalence of DM.4 Nearly 44% of the TB patients were smokers, and DM prevalence was higher among smokers than non-smokers. As smoking and DM are risk factors for unfavourable TB treatment outcomes and health outcomes in general, this group needs special attention and should be linked to smoking cessation services in addition to DM care. We are planning to prospectively follow the whole co-hort of this study population to examine the joint impact of DM and smoking on TB treatment outcomes.

Among the DM cases found in our study, the proportion of previously diagnosed DM was high, at 86%, compared to about 50% in other studies of South India.4,5 This could be attributed to the fact that Kolar is one of the 100 districts in the country where the NPCDCS has launched a programme for early diagnosis of chronic non-communicable diseases by screening all persons aged >30 years at the point of primary contact with any health care fa-cility.6 It is worth mentioning here that the RNTCP was quick to take advantage of the momentum of the screening programme launched by the NPCDCS and extend it to TB patients, with bene-fi ts for both national programmes. This universal screening strategy was one of the reasons for the relatively high NNS found in our study. Despite this fact, several new cases of DM and pre-diabetes were still found during our screening. Studies have shown that pa-tients with pre-diabetes have a higher risk of developing type 2 DM, and they also need to be targeted for preventive interventions.13

Several challenges were noted in the supply chain manage-ment of glucometer strips, and some instances of strip shortages and expiry were experienced during fi eld visits. The fact that labo-ratory staff were using the glucometer strips after expiry indicates a need for training. The NPCDCS is still in its infancy, and mecha-nisms need to be put in place to ensure uninterrupted supplies for smooth implementation of screening.

One of the limitations of our study is that the results obtained by the expired strips could not be excluded from the analysis, as we could not ascertain the exact number of tests performed with the expired strips or on whom they were performed in that pe-riod. Another limitation is the lack of confi rmatory repeat FBG testing before making a diagnosis of DM, as recommended by the American Diabetes Association.13 We did not do this in our study, as this recommendation is not included in the national guidelines in India. We are not aware whether this was done at the point of enrolment into DM care and therefore cannot comment on the implications.

This study contributed to a policy decision made by the RNTCP in India to routinely offer DM screening for all TB patients. A plan for recording, reporting and monitoring this important in-tervention has been prepared, and a training manual for health care providers has been drafted. There is now a need to monitor the roll-out of the intervention and lessons need to be learnt through fi eld-based operational research. It is time to convert pol-icy to practice and ensure implementation as per guidelines.

References 1 Unwin N, Whiting D, Guariguata L, et al., eds. IDF diabetes atlas. 5th ed. Brus-

sels, Belgium: International Diabetes Federation, 2011. http://www.eatlas. idf.org Accessed 6 August 2013.

2 Stevenson C R, Critchley J A, Forouhi N G, et al. Diabetes and the risk of tu-berculosis: a neglected threat to public health. Chronic Illn 2007; 3: 228–245.

TABLE 3 NNS to find an additional case of DM among TB patients, according to different variables, Kolar District, India, January–September 2012

Characteristic

a

Unknown DM status

n

bNew DM

among those screened

n

a/b

NNS N

Total 362 9 40Age, years <40 173 5 35 ⩾40 189 4 47Sex Male 246 8 31 Female 116 1 116Type of TB New smear-positive pulmonary TB 162 7 23 New smear-negative pulmonary TB 45 0 NA New extra-pulmonary TB 95 0 NA Retreatment 60 2 30Current smoker* Yes 157 6 27 No 205 3 68HIV status Negative 340 8 43 Positive 22 1 22

* Current smoker = smoked in the last month.NNS = number needed to screen; DM = diabetes mellitus; TB = tuberculosis; NA = not applicable; HIV = human immunodeficiency virus.

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Public Health Action Field screening for diabetes in TB patients S37

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

3 Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tubercu-losis: a systematic review of 13 observational studies. PLoS Med 2008; 5: e152.

4 Balakrishnan S, Vijayan S, Nair S, et al. High diabetes prevalence among tu-berculosis cases in Kerala, India. PLoS ONE 2012; 7: e46502.

5 Viswanathan V, Kumpatla S, Aravindalochanan V, et al. Prevalence of diabe-tes and pre-diabetes and associated risk factors among tuberculosis patients in India. PLoS ONE 2012; 7: e41367.

6 Stop TB Department, World Health Organization, International Union Against Tuberculosis and Lung Disease. Provisional collaborative framework for care and control of tuberculosis and diabetes. WHO/HTM/TB/2011.15. Geneva, Switzerland: WHO, The Union, 2011. http://whqlibdoc.who.int/publications/2011/9789241502252_eng.pdf Accessed 6 August 2013.

7 India Diabetes-Tuberculosis Study Group. Screening of patients with diabetes mellitus for tuberculosis in India. Trop Med Int Health 2013; 18: 646–654.

8 India Tuberculosis-Diabetes Study Group. Screening of patients with tuber-culosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

9 Central TB Division. Technical and operational guidelines for tuberculosis control. New Delhi, India: Directorate of Health Services, Ministry of Health and Family Welfare, 2005. http://tbcindia.nic.in/pdfs/Technical%20&%20Operational%20guidelines%20for%20TB%20Control.pdf Accessed 6 August 2013.

10 National Programme for Prevention and Control of Cancer, Diabetes, CVD and Stroke. Operational guidelines. New Delhi, India: Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. http://health.bih.nic.in/Docs/Guidelines/Guidelines-NPCDCS.pdf Ac-cessed 6 August 2013.

11 Mannucci E, Ognibene A, Sposato I, et al. Fasting plasma glucose and gly-cated haemoglobin in the screening of diabetes and impaired glucose toler-ance. Acta Diabetol 2003; 40: 181–186.

12 Gupta S, Shenoy V P, Bairy I, Srinivasa H, Mukhopadhyay C. Diabetes melli-tus and HIV as co-morbidities in tuberculosis patients of rural south India. J Infect Public Health 2011; 4: 140–144.

13 American Diabetes Association. Diagnosis and classifi cation of diabetes mel-litus. Diabetes Care 2006; 29 (Suppl 1): S43–S48.

Contexte : Dix-sept institutions de santé périphériques (PHI) du Dis-trict de Kolar (population: 0,5 million d’habitants), Inde du Sud. Objectif : Evaluer la faisabilité et les résultats du dépistage au niveau périphérique du diabète sucré (DM) chez les patients atteints de tu-berculose (TB).Schéma : Au cours de la période de janvier à décembre 2012, on a évalué tous les patients TB en matière de DM. Ceux dont le statut DM était inconnu ont été dépistés pour le DM (gratuitement) par un technicien entrainé de laboratoire dans chaque PHI sur un échantillon de sang capillaire, au moyen d’un glycomètre fourni par le pro-gramme national. Ceux dont le glucose sanguin à jeun (FBG) était ⩾126 mg/dl (⩾7 mM) ont été diagnostiqués comme DM. Résultats : Sur 362 patients TB, 358 (99%) ont été évalués pour DM

et 62 (17,1%) souffraient de DM ; chez 53 (14,6%) le DM était déjà connu antérieurement et chez 9 (2,9%) le diagnostic de DM était nouveau. Tous les nouveaux patients DM ont été enrôlés pour des soins du DM. Une prévalence plus élevée de DM a été observée parmi les patients TB âgés de ⩾40 ans, parmi les fumeurs et chez ceux at-teints d’une TB pulmonaire à frottis positif. Pour détecter un nouveau cas de DM, le nombre de personnes à dépister (NNS) chez les pa-tients TB est de 40.Conclusion : Le dépistage du DM chez les patients TB est réalisable et efficient dans un contexte périphérique. La disponibilité de tech-niciens entrainés de laboratoire et le service gratuit dans chaque PHI ont rendu l’intervention réalisable. Cette étude a contribué à une dé-cision politique nationale dans ce domaine.

Marco de referencia: Diecisiete establecimientos sanitarios periféri-cos en el Distrito de Kolar, que cuenta con una población de medio millón de habitantes en el sur de la India. Objetivo: Evaluar la factibilidad de introducir una detección si-stemática de la diabetes (DM) en los pacientes con tuberculosis (TB) y analizar los resultados que aportaría esta iniciativa en el nivel periférico. Métodos: Entre enero y septiembre del 2012 se investigó en todos los pacientes con TB el diagnóstico de DM. En las personas que desconocían su situación frente a la DM, un técnico de laboratorio capacitado practicó el examen diagnóstico en cada establecimiento (sin costo alguno), en una muestra de sangre capilar, con el uso de un glucómetro que suministraba el programa nacional. Se estableció el diagnostico de DM en todos los pacientes con una glucemia en ayunas ⩾126 mg/dl (⩾7 mM/dl).

Resultados: De los 362 pacientes con TB se investigó la DM en 358 (99%) y se estableció el diagnóstico en 62 casos (17,1%), de los c uales 53 (14,6%) conocían su diagnóstico y en nueve (2,9%) se trató de un diagnóstico nuevo. Todos los pacientes con diagnóstico reciente se inscribieron en el programa de atención de la DM. La mayor prevalencia de DM se observó en los pacientes TB a partir de los 40 años de edad, fumadores y que presentaban una TB pulmonar con baciloscopia positiva. Con el fin de detectar un nuevo caso de DM fue necesario practicar el cribado en 40 pacientes TB. Conclusión: Practicar la detección sistemática de la DM en los paci-entes con diagnóstico de TB constituye una estrategia factible y eficaz en un centro periférico de salud. La presencia de técnicos de labora-torio capacitados y de servicios sin costo alguno en cada estableci-miento periférico hizo posible la intervención. El estudio contribuyó a una decisión de política nacional en este sentido.

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Public Health Action

High prevalence of undiagnosed diabetes among tuberculosis patients in peripheral health facilities in KeralaS. Nair,1 A. K. Kumari,1 J. Subramonianpillai,2 D. S. Shabna,2 S. M. Kumar,2 S. Balakrishnan,3 B. Naik,3 A. M. V. Kumar,4 P. Isaakidis,5 S. Satyanarayana4

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi.org/10.5588/pha.13.0037

Setting: Two tertiary care hospitals and 12 peripheral health institutions (PHIs) in Trivandrum, Kerala, India.Objective: To determine factors associated with the prev-alence of diabetes mellitus (DM) among tuberculosis (TB) patients and examine differences in the proportion of new DM cases among TB patients diagnosed at tertiary care centres and PHIs.Design: A descriptive study: TB patients diagnosed dur-ing March–September 2012 were screened for known DM. Those with unknown DM status were tested for ran-dom blood glucose and fasting blood glucose (FBG); FBG ⩾ 126 mg/dl was diagnosed as new DM.Results: Of 920 TB patients, 689 (72%) were male and the mean (standard deviation) age was 47.6 (16.4) years. Of these, 298 (32.4%) were diabetic: 235 (26%) had pre-viously known DM and 63 (7%) were newly diagnosed. During the screening at PHIs and tertiary care hospitals, respectively 30/183 (16.4%) and 33/737 (4.5%) were newly diagnosed with DM (OR 3.71; 95%CI 2.17–6.32). Overall, age >50 years and pulmonary tuberculosis were independently associated with a higher prevalence of diabetes.Conclusion: As nearly one in three TB patients had DM, we recommend that TB patients should be routinely screened for DM in Kerala. As the proportion of new DM was higher among TB patients diagnosed at PHIs, we would recommend that specific attention and investment be directed to PHIs.

India, the country with the highest number of tuber-culosis (TB) cases in the world (an estimated 2.2 mil-

lion cases in 2011),1 also has a very high burden of di-abetes mellitus (DM), with an estimated 63 million cases in 2012.2 In India, 15% of pulmonary tuberculo-sis (PTB) cases have been estimated to be attributable to DM.3 DM also affects TB treatment outcomes and may delay sputum conversion, increase case fatality rates during treatment, lead to increased failure rates in non-drug-resistant cases and also increase relapse rates of TB after successful completion of treatment.4,5 Given this scenario, it has been felt that active screen-ing for DM in TB patients may allow identifi cation of previously undiagnosed DM and improve TB treat-ment outcomes through improved DM care.

Diabetes is common in Kerala, a state in South India with a population of 34.6 million, with an estimated community prevalence of 16–20%.6,7 The state treated 25 917 TB patients in 2012, including all types of TB.8 Kerala is known to have a high prevalence of DM in

AFFILIATIONS1 Department of Pulmonary

Medicine, Medical College, Trivandrum, Thiruvananthapuram, India

2 Directorate of Health Services, Thiruvanan-thapuram, Kerala, India

3 World Health Organization Country Office in India, New Delhi, India

4 International Union Against Tuberculosis and Lung Disease, South-East Asia Office, New Delhi, India

5 Médecins Sans Frontières, Operational Research Unit, Luxembourg

CORRESPONDENCESanjeev NairDepartment of Pulmonary MedicineMedical CollegeTrivandrum 695011, IndiaTel: (+91) 94463 27204 (+91) 47123 27204e-mail: [email protected]

KEY WORDSTB; DM; screening; RNTCP; Kerala

PHA 2013; 3(S1): S38–S42© 2013 The Union

Received 27 May 2013Accepted 8 July 2013

TB patients, with a recent study reporting a prevalence of 44%.9

As standardised procedures for DM screening among TB patients for use in hospitals and TB units (TUs)—a sub-district level tuberculosis programme management unit covering a population of 500 000, made up of varying numbers of peripheral health in-stitutions (PHIs)—were not available in India, a moni-toring tool linked to the TB registration and quarterly reporting system was developed and implemented, starting in multiple centres in India in 2012. The fi nd-ings of this pilot study10 showed that the screening procedures worked well, and the overall prevalence of DM in over 8000 screened TB patients was 13%. Trivandrum, in Kerala, was one of the sites that imple-mented screening at both hospital and fi eld level in the TU, allowing for comparison of the yield from the different levels of screening.

This study aimed to determine factors associated with the diagnosis of DM during screening of TB pa-tients under programme conditions. Specifi c objectives were to determine 1) the prevalence of DM, 2) the de-mographic and clinical factors associated with preva-lence of DM, and 3) whether the yield of newly diag-nosed DM was different in tertiary care facilities compared to that in PHIs.

METHODS

Study designThis descriptive study was part of a national level im-plementation project on bidirectional TB-DM screen-ing performed within the routine health services in India in 2012.10

Study settingThe study was conducted in Trivandrum City in Ker-ala, a state in the south of India. In 2012, 1750 smear-positive TB patients were diagnosed and 2676 TB patients (including pulmonary smear-positive, pulmo-nary smear-negative and extra-pulmonary TB) were registered for treatment in Trivandrum district.8 Accord-ing to national guidelines,11 TB patients are classifi ed as PTB based on sputum smear examination for acid-fast bacilli (AFB) or, in those who are sputum smear-negative, by chest radiograph within 2 weeks of the negative result being obtained. Extra-pulmonary TB cases are diagnosed by the treating doctor based on a combination of radiology, histopathology, demon-stration of AFB by smear or culture and/or clinical fea-tures. All TB patients are treated with a short-course,

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Public Health Action DM in TB patients in Kerala S39

fully intermittent (thrice weekly), standardised treat-ment regimen containing rifampicin throughout, de-livered under direct observation.

The three centres that took part in the study in Trivandrum included two tertiary care hospitals and a TU consisting of 12 PHIs. The two hospitals were the Government Medical College Hospital, Trivandrum, and the Chest Disease Hospital, Pulayanarkotta. The Government Medical College Hospital is a 1916-bed, multi-specialty teaching hospital, with a daily out-patient load of 1800 and approximately 850 cases of TB diagnosed annually. The Chest Disease Hospital, Pulayanarkotta, which caters for patients with respira-tory diseases, including TB, has 508 beds and a daily out-patient load of about 60; some 325 TB patients are diagnosed and treated there every year. As TB care in India is mainly domiciliary, TB patients are referred to peripheral centres to continue their treatment, and the hospitals provide in-patient care only for the man-agement of complications or co-morbidities. The fi eld-level programme management unit that participated in the study was the Trivandrum DTC (district TB cen-tre) TU (covering a population of 0.5 million), which consists of 12 health care facilities, providing diagnosis of TB and directly observed treatment for TB patients. This unit registered 413 TB patients in 2012.

Trivandrum is the southernmost district of Kerala, with both a rural and an urban population. Patients are referred to the tertiary care hospitals from the PHIs or from private hospitals. Smaller PHIs are used by a pre-dominantly rural population, whereas the tertiary care hospitals receive patients from both urban and rural areas. All of these hospitals provide free or subsidised care for patients. As a pulmonary care centre, the Chest Disease Hospital deals more with PTB, whereas the Gov-ernment Medical College Hospital has various special-ity departments providing care for extra-pulmonary TB patients.

Study participantsAll TB patients aged ⩾15 years diagnosed consecutively at the two hospitals, or those registered for treatment at the Trivandrum DTC TU, between March and Sep-tember 2012 made up the study population. The Chest Disease Hospital, Pulayanarkotta, started patient re-cruitment on 15 March 2012 and the Medical College Hospital, Trivandrum, on 19 March 2012. DTC Trivan-drum TU started recruiting cases from 1 April 2012.

Data collection and analysisThe methods of screening, recording and reporting have been described in detail elsewhere.10 Briefl y, all TB patients were asked whether they had DM, and those with unknown DM status underwent random blood glucose (RBG) testing. If RBG was ⩾110 mg/dl, the patient was screened for fasting blood glucose (FBG). If FBG was ⩾126 mg/dl, DM was diagnosed. Ve-nous blood samples were collected for blood sugar level measurement at the participating centre. Data on age, sex, smoking status (current smoker was defi ned as a person who smoked in the last month), RBG and FBG values were collected in the TB-DM register, the

study tool, by the fi eld-level worker of the Revised Na-tional TB Control Programme (RNTCP), and were cross-checked by the District TB Offi cer of Trivandrum, the Medical Offi cer of the Medical College RNTCP cell and the principal investigator. The main outcomes for analysis were the number and proportion (with 95% confi dence interval [CI]) of TB patients with a diag-nosis of DM (previously known and newly diagnosed), stratifi ed by age, sex, place of diagnosis and type of TB. Bivariate analysis was conducted to examine whether those factors were associated with the prevalence of DM. Odds ratios (OR) with 95%CI were used to mea-sure associations. Multivariate analysis using logistic regression was conducted to calculate the adjusted OR. Only those variables that were statistically signifi cant (P < 0.05) in bivariate analysis were considered for multivariate analysis. EpiData Version 3.5.3 (EpiData Association, Odense, Denmark) was used to analyse the data.

Ethics approvalThe study was approved by the Institutional Ethics Committee of Government Medical College, Trivan-drum. As this was a pilot project aiming to test the fea-sibility of DM screening among TB patients with a view to learning lessons for national scale-up approved by RNTCP authorities, the requirement for individual in-formed consent was waived by the Institutional Ethics Committee. All diagnosed DM patients were linked to DM care. Permission to use, report and publish the collected data in the pilot study was also obtained from the International Union Against Tuberculosis and Lung Disease Ethics Advisory Group, Paris, France.

ACKNOWLEDGEMENTSThe authors acknowledge the assistance and support provided by the staff of the State Tuberculosis Cell, District Tuberculosis Officers, the Medical College Revised National TB Control Programme Cell and their staff in the State of Kerala in the process of data collection.A workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Opera-tional Research, International Union Against Tuberculosis and Lung Disease ( The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Opera-tional Research Unit, Médecins Sans Frontières, Luxembourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark. Conflict of interest: none declared.

TABLE 1 Demographic and clinical profile of TB patients screened and prevalence of DM among these by site, Trivandrum, Kerala, India, March–September 2012

Category

All patients n (%)

CDH n (%)

MCH n (%)

DTC TU n (%) P value

Total 920 (100) 313 (100) 424 (100) 183 (100)Age, years

>50 407 (44) 173 (55) 143 (34) 91 (50) <0.01⩽50 513 (56) 140 (45) 281 (66) 92 (50)

SexMale 670 (73) 264 (84) 274 (65) 132 (72) <0.01Female 250 (27) 49 (16) 150 (35) 51 (28)

Current smokerYes 370 (41) 117 (38) 174 (42) 79 (41) 0.29No 531 (59) 194 (62) 236 (58) 101 (59)

Type of TBPulmonary 545 (59) 245 (78) 167 (39) 133 (73) <0.01Extra-pulmonary 375 (41) 68 (22) 261 (69) 50 (27)

DMYes 298 (32) 127 (43) 117 (28) 54 (30) <0.01No 622 (68) 186 (60) 307 (72) 129 (71)

New DM (among DM cases only)

New 63 (21) 27 (21) 6 (5) 30 (56) <0.01Previously

diagnosed 235 (80) 100 (79) 111 (95) 24 (44)

TB = tuberculosis; DM = diabetes mellitus; CDH = Chest Disease Hospital; MCH = Medical College Hospital; DTC TU = district TB centre TB unit (consisting of 21 pe-ripheral health institutions).

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Public Health Action DM in TB patients in Kerala S40

RESULTS

A total of 948 TB patients were screened in all three sites. Of these, 920 (97%) fi nished the entire screening process, completing all their required blood measurements. These 920 patients were in-cluded in the analysis. Of these, 670 (72%) were male and the mean (standard deviation) age was 47.8 (16.2) years. The median (interquartile range) age was 49 (37–59) years. The profi le of the patients screened and the overall prevalence of DM among TB pa-tients, desegregated by age, sex, smoking status and type of TB and for each site, are shown in Table 1. TB patients diagnosed at the Medical College Hospital had a higher proportion of extra-

pulmonary TB, females and those aged ⩽50 years. Of the 920 TB patients screened, 298 (32%) were diagnosed with DM. Of these, 63 (21%) were newly diagnosed DM cases, whereas 235 (79%) had previously known DM. The proportion of new DM was higher among TB patients diagnosed at PHIs compared to those at ter-tiary care hospitals.

Factors associated with a higher prevalence of DM among the TB patients are shown in Table 2. Age >50 years, male sex, PTB and current smoking were associated with higher prevalence of DM on bivariate analysis. In multivariate modelling, only age >50 years and PTB were found to be independently associated with DM.

Factors associated with the prevalence of new (previously un-diagnosed) DM among the TB patients are shown in Table 3. Di-agnosis in a PHI, age >50 years and PTB were found to be inde-pendently associated with new DM after multivariate modelling.

DISCUSSION

We found a high prevalence of DM among TB patients treated in Trivandrum; it was signifi cantly higher among those aged >50 years and in those with PTB. The prevalence of DM among the TB patients was higher in Trivandrum than in the other sites that took part in the pilot study (personal communication, SS): the overall prevalence of diabetes in TB patients in the nationwide pilot was 13%,10 whereas that in the Trivandrum centres was 32.4%.

More than three quarters of the TB patients with DM knew their DM status before the screening; however, this proportion was lower among TB patients screened at PHIs. Among the TB pa-tients screened at peripheral TU level, more than half the cases of DM diagnosed were new cases. This probably indicates that pa-tients reaching the major hospitals have multiple opportunities for screening before the diagnosis of TB, whereas patients diag-nosed with TB at peripheral level are likely to miss a diagnosis of DM if they do not undergo active screening after TB diagnosis.

The high prevalence of DM among TB patients in Trivandrum could be explained by the high prevalence of DM in the general population in Kerala, which, as reported by previous studies among the adult population, is 16–20%,6,7 and is much higher than in other states in India. TB patients in Kerala are also older than in other Indian states, which could be another reason for the high prevalence of DM in TB patients. The prevalence of TB is lower in Kerala than in the rest of the country.12,13 Kerala also has a lower prevalence of human immunodefi ciency virus (HIV) infec-tion in the general population compared to other states of South India: the prevalence of HIV in the general population of India is 0.31% compared to 0.19% in Kerala.14 DM could therefore be one of the main factors driving the TB epidemic in Kerala, unlike other high TB burden countries.15

A study looking at the prevalence of DM in TB patients in Ker-ala showed a high prevalence of DM, with 44% of TB patients having the disease.9 However, this prevalence was determined by glycated haemoglobin (HbA1c) testing, which is not feasible in fi eld conditions. The use of the HbA1c measurement could also be the reason for the higher diagnosis of DM in TB patients. This study also showed that almost half the DM patients diagnosed on screening were unaware of their DM status at the time of screen-ing, and they would have remained undiagnosed if the screening had not been undertaken. Factors associated with a diagnosis of DM in TB patients in that study were male sex and age >50 years.

The strengths of this study are that a large number of TB pa-tients were consecutively screened in the study sites in Trivan-drum and are thus representative. Trivandrum was the only one

TABLE 2 Factors associated with DM (previously and newly diagnosed) prevalence among TB patients, Trivandrum, Kerala, India, March–September 2012

Category

TB patients

n

Patients with DM

n (%) OR (95% CI)Adjusted

OR (95%CI)*

Age, years>50 418 182 (45) 2.8 (2.1–3.7)† 2.5 (1.9, 3.3)†

⩽50 530 116 (22)Sex

Male 689 233 (34) 1.5 (1.1–2.1)† 1.0 (0.7, 1.5)Female 259 65 (25)

Type of TBPulmonary 567 216 (38) 2.3 (1.7–3.1)† 1.9 (1.4, 2.7)†

Extra-pulmonary 383 82 (21)Current smoker

Yes 377 144 (38) 1.6 (1.2–2.1)† 1.3 (0.96, 1.9)No 546 152 (28)

Site of diagnosisPHI 183 54 (30) 0.9 (0.6–1.2)Tertiary care 737 244 (33)

* Adjusted for age, sex, type of TB and smoking status. † P < 0.05.DM = diabetes mellitus; TB = tuberculosis; OR = odds ratio; CI = confidence interval; PHI = peripheral health institution.

TABLE 3 Factors associated with proportion of new DM among TB patients screened, Trivandrum, Kerala, India, March–September 2012

Category

TB patients

n

Patientswith newly diagnosed

DMn (%) OR (95%CI)

Adjusted OR (95%CI)*

Age, years>50 407 41 (10.1) 2.5 (1.5– 4.3)† 2.2 (1.3, 3.8)†

⩽50 513 22 (4.3)Sex

Male 668 48 (7.2) 1.2 (0.7–2.2) 0.98 (0.5, 2.0)Female 252 15 (6)

Type of TBPulmonary 545 50 (9.2) 2.8 (1.5–5.3)† 2.1 (1.1, 4.1)†

Extra-pulmonary 375 13 (3.5)Current smoker

Yes 370 28 (7.6) 1.2 (0.7–1.9) 0.9 (0.5, 1.7)No 531 35 (6.6)

Site of diagnosisPHI 183 30 (16.4) 4.2 (2.5–7.1)† 3.7 (2.2, 6.4)†

Tertiary care 737 33 (4.5)

* Adjusted for age, sex, type of TB, smoking status and site of diagnosis.† P < 0.05.DM = diabetes mellitus; TB = tuberculosis; OR = odds ratio; CI = confidence interval; PHI = peripheral health institution.

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Public Health Action DM in TB patients in Kerala S41

of two cities where screening was performed at both tertiary care hospital and PHI level, allowing a comparison to be made be-tween the two different sites of screening of the yield and propor-tion of new DM diagnosed in the same population. Also, the use of a screening tool developed at national level allows for a com-parison of the proportion of DM diagnosed in Trivandrum to that in other states in India. Possible limitations of the study include the lack of information on other possible confounding factors, as the information collected was limited to that included in the screening tool. Only patients notifi ed to the RNCTP were included in the screening. There is a possibility that some patients, particu-larly those with extra-pulmonary TB being treated with individu-alised regimens outside the RNTCP, were not included in the study.

This study has major policy implications. First, it demonstrates the feasibility of screening for DM in TB patients using a standard screening tool. Second, it reiterates the high prevalence of DM in TB patients in Kerala, highlighting once again the importance of DM as a risk factor for TB in Kerala. Third, it demonstrates that screening for DM in TB patients at fi eld level results in a higher proportion of previously undiagnosed DM patients being detected, which shows the importance of early screening of TB patients at fi eld level. The RNTCP can also support India’s non-communicable disease programme by early diagnosis of DM in a group of pa-tients who would otherwise be undiagnosed, linking them to care and with a consequent reduction in morbidity and mortality. All of this requires close coordination between the RNTCP and the National Non-Communicable Disease Control Programme.

This study reinforces the view that DM screening in TB pa-tients should be part of the minimum standard of care offered to all TB patients in Kerala and that it needs to be a high priority area for implementation. The state of Kerala has since taken a pol-icy decision to screen all of its TB patients for DM. The govern-ment of India subsequently also made this a policy for the rest of the country. In addition, steps have been taken to link the RNTCP and the National Non-Communicable Disease Control Programme at PHI level in Kerala, allowing for DM screening and improved care of TB patients diagnosed with DM.

CONCLUSION

This study confi rms the high prevalence of DM in TB patients in Kerala and that a signifi cant proportion of DM patients may not

be aware of their status; screening for diabetes is thus an urgent requirement and a minimum standard of care for TB patients, par-ticularly at fi eld level.

References 1 World Health Organization. Global tuberculosis report, 2012. WHO/HTM/

TB/2012.6. Geneva, Switzerland: WHO, 2012. 2 International Diabetes Federation. IDF diabetes atlas. 5th ed. Unwin N,

Whiting D, Guariguata L, et al., eds. Brussels, Belgium: International Dia-betes Federation, 2012. http://www.idf.org/diabetesatlas Accessed August 2013.

3 Stevenson C R, Forouhi N G, Roglic G, et al. Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence. BMC Public Health 2007; 7: 234.

4 Baker M A, Harries A D, Jeon C Y, et al. The impact of diabetes on tuberculosis treatment outcomes: a systematic review. BMC Med 2011; 9: 81.

5 Balakrishnan S, Prema J, Sunilkumar M, et al. Diabetes mellitus increases risk of failing treatment in drug-susceptible TB patients. Int J Tuberc Lung Dis 2011; 15 (Suppl): S348.

6 Raman Kutty V, Joseph A, Soman C R. High prevalence of type 2 diabetes in an urban settlement in Kerala, India. Ethn Health 1999; 4: 231–239.

7 Menon V U, Kumar K V, Gilchrist A, et al. Prevalence of known and unde-tected diabetes and associated risk factors in central Kerala—ADEPS. Diabe-tes Res Clin Pract 2006; 74: 289–294.

8 Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare. TB India 2013. Revised National TB Control Pro-gramme annual status report. New Delhi, India: Government of India, 2013. http://www.tbcindia.nic.in/pdfs/TB%20India%202013.pdf Accessed Septem-ber 2013.

9 Balakrishnan S, Vijayan S, Nair S, et al. High diabetes prevalence among tuberculosis cases in Kerala, India. PLOS ONE 2012; 7: e46502.

10 India Tuberculosis-Diabetes Study Group. Screening of patients with tuber-culosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

11 Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare. Technical and operations guidelines for tubercu-losis control. New Delhi, India: Government of India, 2005. http://tbcindia. nic.in/pdfs/Technical%20&%20Operational%20guidelines%20for%20TB% 20Control.pdf Accessed August 2013.

12 Kumar S, Radhakrishna, Chadha V K, et al. Prevalence of tuberculous i nfection among school children in Kerala. Indian J Tuberc 2009; 56: 10–16.

13 Chadha V K, Agarwal S P, Kumar P, et al. Annual risk of tuberculous infec-tion in four defi ned zones of India: a comparative picture. Int J Tuberc Lung Dis 2005; 9: 569–575.

14 National AIDS Control Organization, Ministry of Health and Family W elfare. State fact sheets. March 2012. New Delhi, India: Government of India, 2012. http://www.nacoonline.org/NACO/Quick_Links/Publication/State_Fact_ Sheets/Fact_Sheets/State_Fact_Sheet_-_March_2012/ Accessed August 2013.

15 Lönnroth K, Castro K, Chakaya J M, et al. Tuberculosis control 2010–2050: cure, care and social change. Lancet 2010; 375: 1814–1829.

Contexte : Deux hôpitaux de soins tertiaires et 12 institutions péri-phériques de santé (PHI) à Trivandrum, Kerala, Inde.Objectif : Déterminer les facteurs en association avec la prévalence du diabète sucré (DM) chez les patients tuberculeux ( TB) et examiner la différence des proportions de nouveaux DM entre les patients TB diagnostiqués dans les centres de soins tertiaires et dans les PHI.Schéma : Etude descriptive. On a dépisté un diabète déjà connu chez les patients TB diagnostiqués pendant la période de mars à septembre 2012, et chez les patients dont le statut de DM était inconnu on a mesuré le glucose sanguin au hasard et le glucose sanguin à jeun (FBG) ; les sujets dont le FBG était ⩾ 126 mg/dl ont été diagnostiqués comme nouveaux cas de DM.Résultats : Sur 920 patients TB, il y a eu 689 hommes (72%). Leur âge moyen était de 47,6 années (16,4). D’entre eux 298 (32,4%)

étaient diabétiques ; 235 (26%) souffraient d’un DM déjà connu et 63 (7%) ont été nouvellement diagnostiqués. Dans les PHI, 30/183 (16,4%) ont été nouvellement diagnostiqués comme diabétiques au cours du dépistage et dans les hôpitaux de soins tertiaires 33/737 (4,5%) l’ont été également (OR 3,71 ; IC 95% 2,17–6,32). Au total, un âge >50 ans et la TB pulmonaire sont en association indépen-dante avec une prévalence plus élevée du DM.Conclusion : La DM existe chez près d’un patient TB sur trois. Dès lors, nous recommandons le dépistage en routine du DM chez les pa-tients TB de Kerala. La proportion de nouveaux cas de DM étant plus élevée chez les patients TB diagnostiqués dans les PHI, nous recom-mandons dès lors qu’une attention et un investissement spécifiques soient portés à ce problème dans les PHI.

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Public Health Action DM in TB patients in Kerala S42

Marco de referencia: Dos hospitales de atención terciaria y 12 cen-tros periféricos de atención de salud de Trivandrum, en el estado de Kerala en la India.Objetivo: Determinar los factores que se asocian con la prevalencia de diabetes (DM) en los pacientes aquejados de tuberculosis (TB) y examinar las diferencias en la proporción de casos nuevos de DM di-agnosticados en los establecimientos de atención terciaria y en los centros periféricos de salud. Métodos: Fue este un estudio descriptivo; se interrogó a los pacien-tes con diagnóstico de TB establecido entre marzo y septiembre del 2012 sobre el antecedente personal de DM y a los pacientes que desconocían su situación frente a la DM se practicaron pruebas de glucemia casual y glucemia en ayunas (FBG); el diagnóstico de un caso nuevo de diabetes se definió con una FBG ⩾ 126 mg/dl.Resultados: De los 920 pacientes con TB, 689 eran de sexo mascu-lino (72%) y la mediana de la edad fue 47,6 años (desviación estándar

16,4 años). De estos pacientes, 298 eran diabéticos (32,4%), de ellos 235 conocían su diagnóstico (26%) y se diagnosticaron 63 casos nuevos (7%). La proporción de casos nuevos diagnosticados en los centros periféricos fue de 30 en 183 pacientes (16,4%) y en los hos-pitales de atención terciaria fue de 33 en 737 (4,5%) (OR 3,71; IC95% de 2,17 a 6,32). En general, una edad >50 años y la presencia de TB pulmonar fueron factores asociados de manera independiente con una mayor prevalencia de DM. Conclusión: Cerca de uno de cada tres pacientes TB presentaba DM; por esta razón se recomienda la detección sistemática de la DM en los pacientes con diagnóstico de TB en Kerala. La proporción de casos nuevos de DM fue mayor en los pacientes TB diagnosticados en los centros periféricos de atención sanitaria, por lo cual se preconiza prestar una mayor atención a este aspecto y realizar inversiones espe-cíficas en estos centros.

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

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Public Health Action

Screening tuberculosis patients for diabetes in a tribal area in South IndiaS. Achanta,1 R. R. Tekumalla,2 J. Jaju,1 C. Purad,1 R. Chepuri,1 R. Samyukta,3 S. Malhotra,4 S. B. Nagaraja,1,5 A. M. V. Kumar,6 A. D. Harries7,8

http://dx.doi.org/10.5588/pha.13.0033

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

Setting: Ten peripheral health institutions of a tribal t uberculosis unit, Saluru, Vizianagaram District, South India. Objective: To assess among tuberculosis (TB) patients: 1) the feasibility of screening for diabetes mellitus (DM), 2) the prevalence of DM, 3) the demographic and clinical features associated with DM, and 4) the number needed to screen (NNS) to find one new case of DM.Design: Cross-sectional study: all TB patients registered from January to September 2012 were screened for DM using a screening questionnaire and random blood glu-cose, followed by fasting blood glucose (FBG) measure-ments using a glucometer. DM was diagnosed if FBG was ⩾126 mg/dl.Results: Of 381 patients, 374 (98%) were assessed for DM, suggesting feasibility of screening, and 19 (5%) were found to have DM (12 were newly diagnosed and 7 had a previous diagnosis of DM). The only characteristic asso-ciated with DM was age ⩾40 years. The NNS to detect a new case of DM among all TB patients was 31; among those aged ⩾40 years, the NNS was 20, and among cur-rent smokers it was 21.Conclusion: Screening of TB patients for DM was fea-sible and effective, and this should inform national scale-up. Other key considerations include the continued pro-vision of free TB-DM screening, with co-location and integration of services.

AFFILIATIONS1 World Health Organization

Country Office in India, New Delhi, India

2 District TB Centre, Ministry of Health and Family Welfare, Government of Andhra Pradesh, Visakhapatnam, India

3 State TB Cell, Directorate General of Health Services, Ministry of Health and Family Welfare, Govern-ment of Andhra Pradesh, Hyderabad, India

4 All India Institute of Medical Sciences, New Delhi, India

5 Department of Commu-nity Medicine, Employees State Insurance Corpora-tion (ESIC) Medical College, Bangalore, India

6 International Union Against Tuberculosis and Lung Disease ( The Union), South-East Asia Office, New Delhi, India

7 The Union, Paris, France8 London School of Hygiene

& Tropical Medicine, London, UK

CORRESPONDENCES AchantaDistrict TB CentreGovernment Hospital for Chest and Communicable DiseasesPedda WaltairVisakhapatnam Andhra Pradesh, India 530017e-mail: [email protected]; [email protected]

KEY WORDSTB; bidirectional screening; DM; India; NNS

PHA 2013; 3(S1): S43–S47© 2013 The Union

Received 22 May 2013Accepted 2 July 2013

showed that of 8109 TB patients who were assessed for DM, 1084 (13%) were found to have DM, based on fasting blood glucose (FBG) measurements. Based on these data, a policy decision was made by India’s Re-vised National TB Control Programme (RNTCP) to im-plement countrywide screening of TB patients for DM.11 One limitation of this study, however, was that it published only aggregate data from all sites, and may have missed site-specifi c variations, and other socio-demographic and clinical factors affecting the ef-fectiveness and feasibility of the screening programme. We therefore analysed individual patient data and de-scribed the effectiveness of screening all TB patients for DM in one tribal TU.

The tribal area is remote and diffi cult to access due to poor connectivity and lack of other basic infrastruc-ture. Indicators relating to literacy, economic status, social status and access to health care services are poor among tribes compared to the general population.12 The tribes are in transition from a forest-centred way of life to a rural, settled farming lifestyle. Given the different lifestyle, more access to unprocessed, fi bre-rich foods, including fruit and vegetables in their diet and greater daily physical activity, we hypothesized that the prevalence of DM would be considerably lower in tribal areas when compared with the rest of the country. The specifi c objectives of the study were to assess, among a cohort of TB patients: 1) the feasibility of screening for DM, 2) the prevalence of DM, 3) the demographic and clinical features associated with DM, and 4) the number needed to screen (NNS) to fi nd one new case of DM among TB patients.13,14

METHODS

Study designThis was a descriptive study of all TB patients attend-ing the study TU.

SettingThe study was conducted in Saluru TU (a geographical area defi ned under the RNTCP as a sub-district-level programme management unit, covering a population of 250 000), with TB diagnostic and treatment services being delivered through a network of primary, second-ary and tertiary health care facilities. Saluru TU is a sub-division of one of the initial 30 districts identifi ed in India for piloting the roll-out of non-communicable disease prevention and control activities through the National Programme for Prevention of Cancer, Diabetes, Cardiovascular Disease and Stroke, with community-based screening of all individuals aged >30 years for

India has the highest burden of tuberculosis (TB) in the world,1 and an estimated 63 million people liv-

ing with diabetes mellitus (DM).2 Evidence suggests that the DM population has a signifi cantly increased risk of developing active TB (two or three times higher than in those without DM).3–6 Three recently pub-lished epidemiologic studies in South India in about 1500 patients with TB found a high prevalence of DM: about 25% in Tamil Nadu,7 32% in Karnataka8 and 44% in Kerala.9

A landmark project conducted by the International Union Against Tuberculosis and Lung Disease (The Union), the World Health Organization (WHO) and the national authorities in India on bidirectional screen-ing of TB and DM, modelled on the Collaborative Framework for care and control of tuberculosis and di-abetes, was implemented in eight tertiary centres and more than 60 peripheral health facilities in eight tuber-culosis units (TUs), including Vizianagaram.10 The India Tuberculosis–Diabetes Study Group (ITDG) assessed the feasibility and results of screening TB patients for DM with pooled data from the project sites.11 The study

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Public Health Action TB-DM screening in a tribal TU, India S44

DM.15 The TU is termed tribal because >70% of the population belong to one of the Scheduled Tribes.

Screening and diagnosis of DM followed national guidelines, which stipulate that FBG should be used with cut-off thresholds in line with those recommended by the WHO.16 Briefl y, FBG ⩾ 126 mg/dl (⩾7 mM) indi-cates DM; FBG 110–125 mg/dl (6.1–6.9 mM) indicates impaired fasting glucose (IFG); and FBG < 110 mg/dl (<6.1 mM) is normal.

TB patients were categorised as ‘new’ and ‘previ-ously treated’ based on their past history of TB treat-ment. The diagnosis of new smear-positive or new smear-negative TB was based on quality assured smear microscopy and chest radiography, while that of extra-pulmonary TB was based on a combination of clini-cal, radiological and histopathological evidence per RNTCP guidelines.17

For the screening process in TB patients, all patients attending the TU were asked by laboratory technicians or attending nurses in the health facility whether they had already been diagnosed with DM. Those who con-fi rmed that they had DM were referred to the nearest public health facility offering DM care. Per protocol, TB patients with known DM status were not tested again. In those with no known diagnosis of DM, ran-dom blood glucose (RBG) tests were performed on cap-illary blood using glucometers, followed by FBG test-ing by the same method at the next visit if the RBG was ⩾110 mg/dl. If patients with TB were found to have an FBG of ⩾126 mg/dl, they were diagnosed as having presumptive DM and referred to DM services for defi n-itive diagnosis and enrolment in care. Those with RBG of between 110 mg/dl and 126 mg/dl were considered to have IFG, and no specifi c action was taken, apart from informing and counselling the patients. Screen-ing for DM and TB and all care for diagnosed cases were provided free of charge.

Study population and study periodThe study was conducted from January to September 2012. All TB patients registered in the TU at the 10 pe-ripheral health institutions (PHIs) formed the study population.

Data variables, collection and validationThe data variables relating to the study objectives were sourced from the TB register and an additional TB-DM register that was developed and used to record data from the screening questionnaire used for the purpose of the pilot study. These data were extracted to pre-tested, structured collection sheets, which were checked for completeness and consistency by TB laboratory su-pervisors of the programme once a week, and by the principal investigator once a fortnight. All staff in-volved in data collection, data validation and data entry were trained in performing the respective procedures using the study protocol and data collection sheets.

Data entry, analysis and reportingThe data were double-entered by two data entry opera-tors into a pre-designed data entry form using EpiData software, Version 3.1 (EpiData Association, Odense, Denmark), with inbuilt checks to minimise data entry

errors. Both databases were compared and discrepan-cies resolved by referring to the original data collec-tion sheets. All analyses were done using EpiData anal-ysis software, Version 2.2.2.180. A descriptive analysis was performed to determine DM prevalence. Compari-sons were then made between TB patients with and without DM using the χ² test. Levels of signifi cance were set at 5%. The NNS to diagnose an additional case of DM is the reciprocal of the proportion of newly detected DM cases. We adhered to STROBE guidelines for reporting observational studies in writing this manuscript.18

Ethics approvalLocal administrative approval was obtained from the District TB Centre, Vizianagaram, for conducting the study. Confi dentiality was assured, as data collection sheets were maintained securely by programme staff and electronic databases contained no personal identi-fi ers. Ethics approval was obtained from the Ethics Ad-visory Group of The Union.

RESULTS

The screening process for DM is shown in Table 1. Of 381 TB patients, 374 (98%) were assessed for DM and 19 (5.1%) were found to have the disease. Of these, 7 (1.9%) had a previously known diagnosis of DM and 12 (3.2%) were newly detected based on blood glucose measurements. IFG was diagnosed in 32 (8.5%) pa-tients. Of all the TB-DM cases, four known DM cases had already been enrolled in DM care; the remaining 15 TB-DM cases were referred for DM care (3 with known DM and 12 with new DM), of whom 12 were enrolled in care.

ACKNOWLEDGEMENTSThe authors acknowledge the assistance provided by the staff of the State Tuber-culosis (TB) Cell, the National Programme for Prevention of Cancer, Diabetes, Cardiovas-cular Disease and Stroke, Peripheral Health Institution Medical Officers and their staff, and the staff of the Revised National Tuberculosis Control Programme of Saluru, Vizianagaram District of the State of Andhra Pradesh, in the process of data collection. The authors also express their gratitude to all the TB patients of Saluru, whose participation in the study made this research possible.A workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Opera-tional Research, International Union Against Tuberculosis and Lung Disease ( The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Opera-tional Research Unit, Médecins Sans Frontières, Luxembourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the World Health Organization.Conflict of interest: none declared.

TABLE 1 DM screening among TB patients registered under the RNTCP in Saluru TU, Vizianagaram, South India, January–September 2012

Indicator n (%)

A Total patients registered with TB 381B Number and proportion of (A) assessed for

DM as per protocol 374 (98.2)C Number and proportion of (B) with a

known diagnosis of DM 7 (1.9)D Patients needing to be screened for RBG 367E Number and proportion of (D) screened

with RBG 367 (100)F Patients with RBG ⩾110 mg/dl and

needing to be screened for FBG 117G Number and proportion of (F) screened

with FBG 115 (98.3)H Patients with FBG ⩾126 mg/dl (newly

diagnosed for DM) 12I Patients with IFG (blood glucose levels

110–126 mg/dl) 32J Number and proportion of (B) with known

and newly diagnosed DM 19 (5.1)K Number and proportion of ( J) referred for

DM care 15 (78.9)L Number and proportion of ( J) who

reached DM care 12 (63.2)

DM = diabetes mellitus; TB = tuberculosis; RNTCP = Revised National Tuberculosis Control Programme; TU = tuberculosis unit; RBG = random blood glucose; FBG = fasting blood glucose; IFG = impaired fasting glucose.

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Public Health Action TB-DM screening in a tribal TU, India S45

Characteristics associated with DM are shown in Table 2. Age >40 years was the only factor signifi cantly associated with a higher prevalence of DM, and no differences were observed with respect to sex, smoking status, human immunodefi ciency virus (HIV) status or type of TB. Of the 19 TB-DM cases, 12 were new smear-positive TB cases, 4 new smear-negative cases, 2 new extra-pulmonary cases and one was a previously treated extra-pulmonary case (data not shown).

The NNS to detect a new case of DM is shown in Table 3. The NNS was 31 for all patients; among those aged ⩾40 years, it was 20, and among smokers it was 21.

DISCUSSIONA low prevalence of diabetes has been reported among tribal and rural populations in India.19 ‘Lifestyle’ diseases are increasing steadily, however, with the gradual domestication of tribal areas and the increased infl ux of tribes into the mainstream popula-tion. Sparse data are available on the prevalence of DM among TB patients, and little is known about the effectiveness of screening all TB patients among the tribal population. This is to our knowl-edge the fi rst study from India to examine the screening process for DM among TB patients in a peripheral TU in a tribal area.

This study confi rms that, given the setting of a tribal TU in India, screening of TB patients for DM can be effectively imple-mented within the existing framework of health care delivery. Questions about previous DM diagnosis and blood tests for those who have no known previous history of DM can be undertaken reliably, and the recording and monitoring system was shown to work well. The overall prevalence of DM in this tribal population, both known and newly detected, was approximately 5%. This was low compared to the overall prevalence of 9% DM among TB pa-tients in TUs found by the ITDG,11 indicating that DM prevalence is heterogeneous across geographical areas and various health set-tings in India. Nevertheless, the screening strategy in our study detected more new DM cases than previously diagnosed DM cases. This probably indicates a lack of awareness about DM, poor access to services for managing DM in these populations, and the poten-tial of the screening strategy for detecting new DM cases.

Similar to fi ndings by a study in China,20 nearly 10% of new cases were diagnosed as having IFG, an indicator for a future high risk of DM or stroke.21,22 Co-existing TB disease could be responsi-ble for stress-induced hyperglycaemia in some of these patients, but this is also probably an early indicator of a future risk of DM. Lifestyle modifi cation measures and health promotion strategies may help to prevent DM in most of these patients,22 and this is something to be considered for future management, as little ac-tion was taken in our study apart from informing and counselling the patients. All of the newly detected TB-DM patients were re-ferred to DM care services in the nearest public health facilities, and although specifi c data were not captured in this study, the majority of the known cases of DM were already enrolled in care.

Our study found that the prevalence of DM in TB patients was signifi cantly associated with age ⩾40 years, but did not vary by sex or type of TB. HIV positivity was associated with absence of DM, and no HIV patient was found to have DM in our study, sim-ilar to fi ndings elsewhere.23 A sub-analysis of the NNS to detect one new case of DM showed that it might be more cost-effective to screen patients aged ⩾40 years and possibly current smokers, but this requires more formal, prospective research.

The strengths of the study are that it was implemented with-out any additional resources within the existing health care system and with minimum training needs. The screening of patients was well accepted in the community, with almost 100% of registered TB patients undergoing the screening process that was offered. High acceptability in the community with minimum additional resources deployed for the screening process suggests that the study is feasible.

There are some limitations to the study. First, decisions on the diagnosis of DM were based on capillary blood glucose levels, as venous blood glucose measurements were not available in the PHIs. However, the WHO states that capillary and venous blood sam-ples should be regarded as almost identical.16 Second, the skill lev-els of health staff in correctly using this technology and the qual-ity control of the glucometers were not assessed during the study. Third, the measurements of RBG and FBG may be inaccurate in

TABLE 2 Demographic and clinical characteristics associated with DM in TB patients in Vizianagaram, South India, January–September 2012

Characteristic

TB patients without DM

n (%)

TB patientswith DM (known

and newly diagnosed)

n (%) Total P value

Total 355 19 374 Age, years

<40 185 (52.1) 4 (21.1) 189 <0.01⩾40 170 (47.8) 15 (78.9) 185

SexMale 221 (62.2) 15 (78.9) 236 0.14Female 134 (37.7) 4 (21.1) 138

Type of TBNew 308 (86.7) 18 (94.7) 326 0.48

Previously treated 47 (13.2) 1 (5.2) 48HIV test

Reactive 25 (7.04) 0 25 0.62Non-reactive 314 (88.4) 17 (89.5) 331Unknown 16 (4.5) 2 (10.5) 18

Smoking statusCurrent smoker 80 (22.5) 5 (26.3) 85 0.77Not current smoker 275 (77.4) 14 (73.6) 289

DM = diabetes mellitus; TB = tuberculosis; HIV = human immunodeficiency virus.

TABLE 3 Number needed to screen to detect a new case of DM among TB patients in Vizianagaram, South India, January–September 2012

Characteristic

Patientsassessedfor DM

n

Patients newlydiagnosed with DM(FBG ⩾126 mg/dl)

n (%) NNS*

Total 374 12 (3.2) 31Age, years

<40 189 3 (1.6) 63⩾40 185 9 (4.9) 20

SexMale 236 10 (4.2) 24Female 138 2 (1.4) 69

Type of TBNew 326 12 (3.7) 27Previously treated 48 0 NA

Smoking statusCurrent smoker 85 4 (4.7) 21Not current smoker 289 8 (2.8) 36

* Rounded to nearest integer.DM = diabetes mellitus; TB = tuberculosis; FBG = fasting blood glucose; NNS = number needed to screen; NA = not applicable.

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Public Health Action TB-DM screening in a tribal TU, India S46

diagnosing DM. Rapid swings in blood glucose levels can occur with RBG and FBG measurements.24–26 It has also been accepted that FBG alone may fail to diagnose approximately 30% of cases of previously undiagnosed DM, relative to those assessed by a 75 g oral glucose tolerance test,27,28 which may have to be performed when indicated in certain cases to avoid delayed diagnosis of true DM. Glycosylated haemoglobin (HbA1c) provides a more stable measure of blood glucose levels over 2 to 3 months,24–26 but this form of measurement was too expensive and was not used in the current study. Fourth, the timing of DM screening during TB treat-ment can also affect blood glucose readings, and studies have shown that the prevalence of hyperglycaemia decreases over time during TB treatment.29–32 However, as the effect of transient hyperglycaemias on TB treatment outcomes is not fully understood, we would argue that it is better to screen patients at the earliest opportunity so that we can try to diagnose and treat DM early in the course of TB treat-ment. Assessing the effect of better DM control on TB treatment out-comes and on the reported risk of recurrent TB33 was beyond the scope of this study but should be the subject of future research.

There are some key issues for policy makers to consider before implementing this strategy more widely. First, the high accept-ability of DM testing among TB patients in our study was facili-tated by the widespread free availability of DM testing services at all 10 PHIs. Availability of free DM testing services at all peripheral health facilities is probably a prerequisite for the successful imple-mentation of this screening strategy. Second, the total number of DM screening tests performed will increase substantially as a re-sult of the roll-out of this strategy, and both national programmes need to plan for enhanced procurement and supply chain man-agement. Third, it is acknowledged worldwide that timely referral of cases for proper care and management is vital in co-morbid conditions such as HIV-TB,34 and the co-location and integration of services is key to successful programme collaboration.35 Simi-larly, the integration of DM and TB management services must be considered as scale-up takes place, and this could mark the begin-ning of strong cooperation and collaboration between communi-cable and non-communicable disease programmes.

In conclusion, our study found that the screening of TB pa-tients for DM was feasible and effective, and in a tribal TU where prevalence rates of DM might be expected to be lower than in ur-ban populations, we still detected one in 20 cases of DM. Age was a factor signifi cantly associated with the prevalence of DM, and if resources are limited, it might be worth focusing the screening of TB patients on those aged ⩾40 years.

References 1 World Health Organization. Global tuberculosis report 2012. WHO/HTM/

TB/2012.6. Geneva, Switzerland: WHO, 2012. 2 International Diabetes Federation. IDF diabetes atlas. 5th ed, 2012 update.

Unwin N, Whiting D, Guariguata L, et al., eds. Brussels, Belgium: Interna-tional Diabetes Federation, 2012. http://www.idf.org/diabetesatlas/5e/Update 2012 Accessed August 2013.

3 Stevenson C R, Critchley J A, Forouhi N G, et al. Diabetes and the risk of tu-berculosis: a neglected threat to public health. Chronic Illn 2007; 3: 228–245.

4 Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tuberculo-sis: a systematic review of 13 observational studies. PLOS Med 2008; 5: e152.

5 Dooley K E, Chaisson R E. Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis 2009; 9: 737–746.

6 Ruslami R, Aarnoutse R E, Alisjahbana B, van der Ven A J A M, Van Crevel R. Implications of the global increase of diabetes for tuberculosis control and patient care. Trop Med Int Health 2010; 15: 1289–1299.

7 Viswanathan V, Kumpatla S, Aravindalochanan V, et al. Prevalence of dia-betes and pre-diabetes and associated risk factors among tuberculosis patients in India. PLOS ONE 2012; 7: e41367.

8 Gupta S, Shenoy V P, Bairly I, Srinivasa H, Mukhopadhyay C. Diabetes mel-litus and HIV as co-morbidities in tuberculosis patients of rural South India. J Infect Public Health 2011; 4: 140–144.

9 Balakrishnan S, Vijayan S, Nair S, et al. High diabetes prevalence among tu-berculosis cases in Kerala, India. PLOS ONE 2012; 7: e46502.

10 World Health Organization/International Union Against Tuberculosis and Lung Disease. Provisional collaborative framework for care and control of tuberculosis and diabetes. WHO/HTM/TB/2011.15. Geneva, Switzerland: WHO, 2011.

11 India Tuberculosis–Diabetes Study Group. Screening of patients with tuber-culosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

12 M Gopinath Reddy, K Anil Kumar. Political economy of tribal development: a case study of Andhra Pradesh. Working paper no. 25. Hyderabad, India: Centre for Economic and Social Studies, 2010. http://www.cess.ac.in/cess-home/ wp/WP_85.pdf Accessed August 2013.

13 Naik B, Kumar Mv A, Lal K, et al. HIV prevalence among persons suspected of tuberculosis: policy implications for India. J Acquir Immune Defi c Syndr 2012; 59: e72–76.

14 Achanta S, Kumar A M, Nagaraja S B, et al. Feasibility and effectiveness of provider initiated HIV testing and counseling of TB suspects in Vizianaga-ram District, South India. PLOS ONE 2012; 7: e41378.

15 Directorate General of Health Services, Ministry of Health and Family Welfare, National Programme for Prevention and Control of Cancer, Diabetes, Cardio-vascular Disease and Stroke. Operational guidelines. New Delhi, India: Gov-ernment of India, 2010. http://health.bih.nic.in/Docs/Guidelines-NPCDCS.pdf Accessed August 2013.

16 World Health Organization. Defi nition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Summary of Technical Report and Rec-ommendations. Geneva, Switzerland: WHO, 2006. http://whqlibdoc.who.int/publications/2006/9241594934_eng.pdf Accessed September 2013.

17 Central Tuberculosis Division, Revised National Tuberculosis Control Pro-gramme, Directorate General of Health Services, Ministry of Health and Family Welfare. Technical and operational guidelines for tuberculosis con-trol. New Delhi, India: Government of India, 2005.

18 Von Elm E, Altman D G, Egger M, Pocock S J, Gotzsche P C, Vandenbroucke J P. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting obser-vational studies. Bull World Health Organ 2007; 85: 867–872.

19 Gupta R, Misra A. Type 2 diabetes in India: regional disparities. Br J Diabetes Vasc Dis 2007; 7: 16–19.

20 Li L, Lin Y, Mi F, et al. Screening of patients with tuberculosis for diabetes mellitus in China. Trop Med Int Health 2012; 17: 1294–1301.

21 Lee M, Saver J L, Hong K S, Song S, Chang K H, Ovbiagele B. Effect of pre-diabetes on future risk of stroke: meta-analysis. BMJ 2012; 344: e3564.

22 Perreault L, Pan Q, Mather K J, Watson K E, Hamman R F, Kahn S E, for the Diabetes Prevention Program Research Group. Effect of regression from pre-diabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 2012; 379: 2243–2251.

23 Faurholt-Jepsen D, Range N, Praygod G, et al. Diabetes is a risk factor for pulmonary tuberculosis: a case-control study from Mwanza, Tanzania. PLOS ONE 2011; 6: e24215.

24 International Expert Committee. International expert committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 2009; 32: 1327–1334.

25 Kumar P R, Bhansali A, Ravikiran M, et al. Utility of glycated hemoglobin in diagnosing type 2 diabetes mellitus: a community-based study. J Clin Endocrinol Metab 2010; 95: 2832–2835.

26 World Health Organization. Use of glycated haemoglobin (HbA1c) in the di-agnosis of diabetes mellitus: abbreviated report of a WHO consultation. WHO/NMH/CHP/CPM/11.1. Geneva, Switzerland: WHO, 2011. http://www.who.int/cardiovascular_diseases/report-hba1c_2011_edited.pdf Accessed Au-gust 2013.

27 Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China. N Engl J Med 2010; 362: 1090–1101.

28 Ramachandran A, Snehalatha C, Latha E, Vijay V. Evaluation of the use of fasting plasma glucose as a new diagnostic criterion for diabetes in Asian In-dian population. Diabetes Care 1998; 21: 666–667.

29 Kishore B, Nagrath S P, Mathur K S, Hazra D K, Agarwal B D. Manifest, chem-ical and latent chemical diabetes in pulmonary tuberculosis. J Assoc Physicians India 1973; 21: 875–881.

30 Goyal B N, Nigam P, Dubey A L, Joshi L D, Saxena H N. Study of the diabetic status in pulmonary tuberculosis. J Diabetes Assn India 1978; 18: 191–197.

31 Singh M M, Biswas S K, Shah A. Impaired glucose tolerance in active pulmo-nary tuberculosis. Indian J Tuberc 1984; 31: 118–121.

32 Oluboyo P O, Erasmus R T. The signifi cance of glucose intolerance in pulmo-nary tuberculosis. Tubercle 1990; 71: 135–138.

33 Baker M A, Harries A D, Jeon C Y, et al. The impact of diabetes on tuberculo-sis treatment outcomes: a systematic review. BMC Med 2011; 9: 81.

34 Lawn S D, Wood R. Timing of antiretroviral therapy or HIV-1-associated tuberculosis. N Eng J Med 2012; 366: 474.

35 Howard A A, El-Sadr W M. Integration of tuberculosis and HIV services in sub-Saharan Africa: lessons learned. Clin Infect Dis 2010; 50 (Suppl): S238–S244.

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Public Health Action TB-DM screening in a tribal TU, India S47

Contexte : Dix institutions périphériques de santé d’une unité tribale de tuberculose (TB), Saluru, district de Vizianagaram, Inde du Sud. Objectif : Evaluer parmi les patients TB : 1) la faisabilité du dépistage de diabète (DM), 2) la prévalence du DM, 3) les caractéristiques dé-mographiques et cliniques associées au DM, et 4) le nombre de sujets à dépister (NNS) pour trouver un nouveau cas de DM.Schéma : Etude transversal : on a recherché le DM chez tous les pa-tients TB enregistrés entre juillet et septembre 2013 au moyen d’un questionnaire de dépistage et d’un prélèvement au hasard du glucose sanguin suivi par des mesures du glucose à jeun au moyen d’un glu-comètre. On a diagnostiqué le DM lorsque le glucose sanguin à jeun était ⩾126 mg/dl.

Resultants : Sur 381 patients, 374 (98%) ont fait l’objet d’une évalua-tion pour DM, ce qui suggère la faisabilité du dépistage, et chez 19 (5%) on a trouvé un DM (12 nouveaux diagnostics et 7 diagnostics antérieurs de DM). La seule caractéristique associée avec le DM est l’âge ⩾40 ans. Le NNS pour détecter un nouveau cas de DM pour l’ensemble des patients TB est de 31 ; parmi ceux âgés de ⩾40 ans, le NNS est de 20 et chez les fumeurs actuels il est de 21. Conclusion : Le dépistage du DM chez les patients TB est réalisable et efficient, et ceci devrait influencer une extension nationale. D’autres considérations-clé comportent la fourniture continue d’un dépistage gratuit TB-DM avec une co-localisation et une intégration des services.

Marco de referencia: Diez establecimientos periféricos de atención de salud de una unidad de tuberculosis (TB) tribal de Saluru en el dis-trito Vizianagaram del sur de la India.Objective: Evaluar los siguientes aspectos en los pacientes tratados por TB: 1) la factibilidad del cribado de la diabetes sacarina (DM), 2) la prevalencia de DM, 3) las características demográficas y clínicas que se asocian con la DM, y 4) el número de personas que se debe examinar (NNS) con el fin de detectar un caso nuevo de DM. Métodos: Se llevó a cabo un estudio transversal en el cual se prac-ticó una detección sistemática de la DM en todos los pacientes regi-strados con TB entre enero y septiembre del 2012, mediante un cues-tionario y una prueba de glucemia casual, seguida de una glucemia en ayunas, con el uso de un glucómetro. Se definió el diagnóstico de DM con un resultado de la glucemia en ayunas ⩾126 mg/dl.Resultados: De los 381 pacientes tratados por TB, se investigó la DM

en 374 (98%), lo cual indica la factibilidad del cribado y se estableció el diagnóstico DM en 19 pacientes (5%), de los cuales 12 fueron casos nuevos y 7 personas conocían su diagnóstico. La única característica asociada con el diagnóstico de DM fue la edad ⩾40 años. El NNS con el fin de detectar un caso de DM en todos los pacientes con TB fue 31; en los pacientes de ⩾40 años de edad, el NNS fue 20 y en los fu-madores actuales fue 21.Conclusión: La detección sistemática de la DM en los pacientes con TB constituye una medida factible y eficaz; estos resultados servirán para documentar las iniciativas nacionales de ampliación de escala de estas intervenciones. Otros aspectos que merecen atención especial son la provisión continua de detección de la TB y la DM sin costo al-guno en un mismo centro y la integración de los servicios de atención de ambas enfermedades.

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

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Public Health Action

Characteristics and treatment response in patients with tuberculosis and diabetes mellitus in New Delhi, IndiaA. Khanna,1 S. Lohya,1 B. N. Sharath, 2 A. D. Harries 3,4

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi/10.5588/pha.13.0025

Diabetes mellitus (DM) is known to increase the risk of tuberculosis (TB) and adversely affect TB treatment out-comes. A descriptive study was carried out in registered TB patients screened for DM at Lok Nayak Hospital, New Delhi, India. Of 458 TB patients, 66 (14%) had DM. In those with dual disease, age ⩾40 years, smear-positive pulmonary TB and recurrent TB were significantly more common. There was no effect of DM on TB treatment outcomes, although there was a trend towards smear non-conversion at 2 months. Screening for DM works well, and certain patient characteristics are more com-mon in those with dual disease.

AFFILIATIONS1 Lok Nayak Chest Clinic

(TB), Lok Nayak Hospital, New Delhi, India

2 ESIC Medical College, Bangalore, India

3 International Union Against Tuberculosis and Lung Disease, Paris, France

4 London School of Hygiene & Tropical Medicine, London, UK

CORRESPONDENCEAshwani KhannaLok Nayak Chest Clinic (TB)Lok Nayak Hospital, E-202 Greater Kailash -1New Delhi 110048, IndiaTel: (+91) 98 101 64127e-mail: [email protected]

ACKNOWLEDGEMENTSA workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Operational Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Operational Research Unit, Médecins Sans Frontières, Luxem-bourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark. Conflict of interest: none declared.

KEY WORDStuberculosis; diabetes mellitus; India; recurrent TB; TB treatment outcomes

PHA 2013; 3(S1): S48–S50© 2013 The Union

Received 9 May 2013Accepted 20 June 2013

15 February to 30 September 2012 were included in the study.

Patients were fi rst screened verbally for known DM. In those with unknown DM status, blood tests were carried out using glucometers and test strips as previ-ously described.6 Patients were diagnosed with DM if fasting blood glucose was ⩾ 126 mg/dl (7 mmol/dl), in line with World Health Organization guidelines.8 Re-gardless of DM status, all TB patients received stan-dardised TB treatment in accordance with national guidelines,9 and were followed until the end of treat-ment. Treatment outcomes were monitored through registers and treatment cards, and reported in standard fashion according to the guidelines.9 For the purpose of the study, treatment outcomes were categorised as successful (cured with negative sputum smear at the end of treatment, and treatment completed with no smears performed) and other (died, lost to follow-up, failed treatment, and transferred out with no outcome reported). All screening and treatment were provided free of charge.

The data were sourced from TB treatment cards, TB registers and TB-DM registers set up for the purpose of the pilot study. Data were extracted from the registers into paper-based forms and double entered into Epi-Data version 3.1 (EpiData Association, Odense, Den-mark, http://www.epidata.dk). Patients were grouped according to whether or not they had DM, and cate-gorical variables such as baseline characteristics and treatment outcomes were compared using the χ² test, with odds ratios and 95% confi dence intervals as ap-propriate, with levels of signifi cance set at 5%.

Ethics approval was obtained from the institutional ethics committee of Maulana Azad Medical College, New Delhi, and the International Union Against Tu-berculosis and Lung Disease Ethics Advisory Group, Paris, France.

RESULTS

Of the 458 registered TB patients, 226 (49%) were male. The mean age of the patients was 32 years (inter-quartile range 20– 42). Of 66 patients (14.5%) diagnosed with DM, 40 (60%) had a previous diagnosis. The base-line characteristics, sputum smear status during treat-ment and treatment outcomes for TB patients with and without DM are shown in the Table. In terms of baseline characteristics, age ⩾ 40 years, smear-positive pulmonary TB (PTB) and recurrent TB were signifi cantly more common in DM patients, while extra-pulmonary TB was signifi cantly less common. There were no other differences. An increased proportion of patients with

India, a middle-income country, has the highest tu-berculosis (TB) burden in the world, with an esti-

mated 2.3 million cases annually.1 The country is expe-riencing urbanisation, ageing and changes in lifestyle, and these are associated with an escalating epidemic of diabetes mellitus (DM); in 2012, there were an esti-mated 63 million prevalent cases.2 There is now good evidence that people with DM have 2–3 times the risk of developing active TB compared with those who do not have DM.3,4 Not only may this lead to an increase in the TB burden, but patients with dual disease ap-pear to have an increased frequency of adverse TB treat-ment outcomes, with delayed sputum culture conver-sion, an increased risk of death during anti-tuberculosis treatment and an increased risk of recurrent disease after successful completion of treatment. 5

In 2012, a series of pilot studies was conducted in In-dia on bi-directional screening for DM and TB in a rou-tine setting, with aggregate data showing that screen-ing in both directions was both feasible and effective.6,7 No information, however, was presented on whether DM affects patient outcomes in a routine setting. We therefore decided to assess whether sputum smear conversion and treatment outcomes were affected by DM status in a hospital setting in Delhi, India.

METHODS

A descriptive study was carried out using the records and reports of India’s Revised National TB Control Programme. The setting was a chest clinic at a tertiary care teaching hospital (Lok Nayak) in New Delhi, which has been implementing TB control activities for the last 10 years. The clinic has a catchment popula-tion of 0.5 million, and was one of the collaborating centres for the TB-DM bi-directional pilot project.6,7 All adult TB patients diagnosed and registered from

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Public Health Action Screening TB patients for diabetes S49

DM who had their sputum smears examined did not experience smear conversion at the end of the initial phase of treatment, but this did not reach statistical signifi cance when compared with pa-tients who did not have DM. Final treatment outcomes did not differ between the groups.

DISCUSSION

In this observational study, it was feasible to routinely screen all TB patients for DM. Among patients with DM, there was a higher prevalence of older individuals and patients with smear-positive

PTB and recurrent TB. Older age might be expected, because type 2 DM disease tends to occur in older subjects. The reasons for the higher prevalence of PTB are unclear, but may be related to pul-monary microangiopathy and defi cient activation of pulmonary macrophages, which are reported to occur in DM and may predis-pose patients to TB.3 An increased risk of recurrent TB disease among DM patients has previously been reported.5 In a recent prospective study in Mexico this association was confi rmed, and was also shown to be due to reactivation of the same strain of My-cobacterium tuberculosis in 80% of cases and reinfection with a dif-ferent strain in 20%.10 More work is needed in India to under-stand the reasons for recurrent TB in patients with DM.

We found no signifi cant effect of DM on sputum smear con-version or treatment outcomes, although an increased proportion of patients with DM remained sputum smear-positive at 2 months. Delays in sputum culture conversion have been reported in asso-ciation with DM, although not consistently, and this also requires further study.5

The strength of the study was that it was conducted in a pro-gramme setting with no additional resources apart from govern-ment funds. Its limitations relate to any record review where data may be inaccurate and, in this study, the small sample group of patients with dual disease.

In conclusion, screening of TB patients for DM worked well in this tertiary hospital setting. The study also identifi ed certain pa-tient characteristics that may be more prevalent in those with DM, thus allowing targeting of screening if resources are constrained.

References 1 World Health Organization. Global tuberculosis report 2012. WHO/HTM/

TB/2012.6. Geneva, Switzerland: WHO, 2012. 2 International Diabetes Federation. IDF diabetes atlas. 5th ed, 2012 update.

Unwin N, Whiting D, Guariguata L, et al., eds. Brussels, Belgium: Interna-tional Diabetes Federation, 2012. http://www.idf.org/diabetesatlas/5e/Update 2012 Accessed 7 August 2013.

3 Stevenson C R, Critchley J A, Forouhi N G, et al. Diabetes and the risk of tu-berculosis: a neglected threat to public health. Chronic Illn 2007; 3: 228–245.

4 Jeon C Y, Murray M B. Diabetes mellitus increases the risk of active tubercu-losis: a systematic review of 13 observational studies. PLOS Med 2008; 5: e152.

5 Baker M A, Harries A D, Jeon C Y, et al. The impact of diabetes on tuberculosis treatment outcomes: a systematic review. BMC Med 2011; 9: 81.

6 India Tuberculosis-Diabetes Study Group. Screening of patients with tuber-culosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

7 India Diabetes Mellitus-Tuberculosis Study Group. Screening of patients with diabetes mellitus for tuberculosis in India. Trop Med Int Health 2013; 18: 646–654.

8 World Health Organization. Defi nition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Summary of Technical Report and Rec-ommendations. Geneva, Switzerland: WHO, 2006.

9 Central Tuberculosis Division, Revised National Tuberculosis Control Pro-gramme. Directorate General of Health Services, Ministry of Health and Fam-ily Welfare. Technical and operational guidelines for tuberculosis control. New Delhi, India: Government of India, 2005.

10 Jimenez-Corona M E, Cruz-Hervert L P, Garcia-Garcia L, et al. Association of diabetes and tuberculosis: impact on treatment and post-treatment out-comes. Thorax 2013; 68: 214–220.

TABLE Baseline characteristics, smear conversion and treatment outcomes of TB patients with and without diabetes registered at Lok Nayak Hospital, Delhi, India, in 2012

Characteristic

TB patientswith DM(n = 66)

n (%)

TB patientswithout DM(n = 392)

n (%) OR (95%CI)*

SexMale 40 (61) 186 (47)Female 26 (39) 206 (53)

Age, years<40 12 (18) 315 (80) 18.4 (9.3–36)†

⩾40 54 (82) 77 (20)Disease classification

Pulmonary smear-positive 38 (57) 151 (39) 2.2 (1.3–3.7)‡

Pulmonary smear-negative 17 (26) 80 (20)Extra-pulmonary 11 (17) 161 (41) 0.3 (0.1–0.6)†

Type of TBNew 43 (66) 302 (77)Previously treated 23 (34) 90 (23) 1.8 (1.0–3.1)‡

HIV statusPositive 0 17 (4)Negative 66 (100) 370 (94)Unknown 0 10 (2)

Smoking statusSmoker 9 (14) 49 (13)Non-smoker 57 (86) 343 (87)

Sputum smear conversionEnd of intensive phase

Converted 28 (74) 122 (83)Not converted 9 (24) 18 (12)Unknown 1 (2) 7 (5)

End of treatmentConverted 32 (88) 127 (91)Not converted 2 (6) 3 (2)Unknown 2 (6) 9 (7)

Treatment outcomesTreatment success 58 (88) 362 (92)Other outcomes 8 (12) 30 (8)

* OR only shown for comparisons where there were significant differences.† P < 0.001.‡ P < 0.05.TB = tuberculosis; DM = diabetes mellitus; OR = odds ratio; CI = confidence interval; HIV = human immunodeficiency virus.

On sait que le diabète sucré (DM) augmente le risque de tuberculose (TB) et influe de façon défavorable les résultats du traitement de la TB. On a mené une étude descriptive chez les patients TB enregistrés et dé-pistés pour DM à l’Hôpital Lok Nayak de New Delhi, Inde. Sur 458 pa-tients TB, 66 (14%) souffraient de DM. Chez ceux atteints des deux maladies, un âge ⩾40 ans, une TB pulmonaire à frottis positif et une

rechute de TB sont significativement plus courants. Il n’y a pas d’effet du DM sur les résultats du traitement de la TB, quoiqu’il y ait une ten-dance vers la non-négativation du frottis à 2 mois. Le dépistage du DM fonctionne correctement et certaines caractéristiques du patient sont plus courantes chez ceux atteints des deux maladies.

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Public Health Action Screening TB patients for diabetes S50

Se conoce que la presencia de diabetes sacarina (DM) aumenta el riesgo de contraer la tuberculosis (TB) y ejerce un efecto desfavorable sobre el desenlace del tratamiento antituberculoso. Se llevó a cabo un estudio descriptivo de los pacientes tuberculosos registrados, en quienes se investigó el diagnóstico de DM en el Hospital Lok Nayak de Nueva Delhi en la India. De los 458 pacientes registrados con TB, 66 presentaban DM (14%). En los pacientes con ambas enferme-

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha

dades fue significativamente más frecuente que tuvieran una edad de ⩾40 años, que padecieran TB pulmonar con baciloscopia positiva y recaídas de la TB. No se presentó ningún efecto de la DM sobre el desenlace terapéutico, aunque se observó una tendencia a la falta de conversión de la baciloscopia a los 2 meses de tratamiento. El cribado de la DM es eficaz y algunas características son más frecuentes en los pacientes que padecen ambas enfermedades.

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Public Health Action

Diabetes mellitus and smoking among tuberculosis patients in a tertiary care centre in Karnataka, IndiaM. V. Jali,1 V. K. Mahishale,2 M. B. Hiremath,1 S. Satyanarayana,3 A. M. V. Kumar,3 S. B. Nagaraja,4 P. Isaakidis5

Interna onal Union Against Tuberculosis and Lung DiseaseHealth solu ons for the poor

VOL 3 SUPPLEMENT 1 PUBLISHED 4 NOVEMBER 2013

http://dx.doi.org/10.5588/pha.13.0031

Diabetes mellitus (DM) and smoking are risk factors for adverse outcomes in the treatment of tuberculosis (TB). In a tertiary care hospital at Belgaum in the South Indian State of Karnataka, all TB patients aged ⩾18 years con-secutively diagnosed from February to September 2012 were evaluated for DM and smoking. Of 307 TB patients, 35.5% were found to have DM, 9.8% were current smok-ers, and 3.6% had DM and were also smokers. Measures to assess and address both these factors need to be taken into account during TB treatment.

AFFILIATIONS1 KLES Diabetes Centre,

KLES Dr Prabhakar Kore Hospital & Medical Research Centre, Belgaum, Karnataka, India

2 Department of Pulmonary Medicine, KLES Dr Prabha-kar Kore Hospital & Medical Research Centre, Belgaum, Karnataka, India

3 International Union Against Tuberculosis and Lung Disease, South-East Asia Office, New Delhi, India

4 Employees State Insurance Corporation (ESIC) Post Graduate Institute of Medical Science and Research and Model Hospital, Rajaji Nagar, Bangalore, India

5 Médecins Sans Frontières, Mumbai, India

CORRESPONDENCEM V JaliKLES Dr Prabhakar Kore Hospital & Medical Research CenterBelgaum, Karnataka, India Tel: (+91) 831 2473777Fax: (+91) 831 2470732e-mail: [email protected];[email protected]

KEY WORDSDM; TB; smoking;prevalence; India

PHA 2013; 3(S1): S51–S53© 2013 The Union

Received 23 May 2013Accepted 13 June 2013

consecutively during the period February to Septem-ber 2012 who were referred to the DOTS centre for TB treatment were included in the study. All eligible pa-tients were asked about their history of DM. If there was no known history of DM, patients underwent ran-dom blood glucose (RBG) tests using a glucometer. Pa-tients with RBG levels ⩾ 110 mg/dl (>6.1 mM) were requested to undergo a fasting blood glucose (FBG) test. Patients with FBG levels ⩾ 126 mg/dl (⩾7 mM) and between 110 and 125 mg/dl (6.1–7.0 mM) were diagnosed with DM and IFG, respectively, and referred for diabetes care. Simultaneously, TB patients with a history of at least one episode of tobacco smoking in the last 3 months were identifi ed as ‘current smokers’. The procedure for screening, recording (in a separate register) and reporting (on a standard quarterly report-ing form) has been described in detail elsewhere.6

Data variables, data entry and analysisThe following data were extracted from the registers: age, sex, type of TB, RBG levels, FBG levels, and history of at least one episode of smoking in the last 3 months. The data were entered into a pre-structured data entry form created in EpiData Version 3.1 (EpiData Associa-tion, Odense, Denmark) and analysed. The data were summarised by frequencies and proportions.

Ethics approvalThis project protocol was reviewed and approved by the International Union Against Tuberculosis and Lung Disease Ethics Advisory Group.

RESULTS

Of 307 patients referred to the DOTS centre, 247 (80.5%) underwent all appropriate blood glucose tests and screening for current smoking status. About two thirds (64.2%) were male. Overall, 7.8% of patients had IFG, 35.5% had DM, 9.8% were current smokers and 3.6% both had DM and were current smokers (Table). The prevalence of DM and smoking was higher among the younger age groups.

DISCUSSION

Despite India’s good Revised National TB Control Pro-gramme, DM and tobacco consumption have the po-tential to hamper TB control efforts. Research studies published recently in South India have found a high prevalence of DM among TB patients of approximately 25% in the State of Tamil Nadu and 44% in the State of Kerala.6–8 These studies have shown that in addition

Diabetes mellitus (DM) and tobacco smoking are independent risk factors for adverse tuberculosis

(TB) treatment outcomes such as relapse, treatment failure and death.1,2 Individuals with DM who smoke ⩾1 pack of cigarettes daily are at particularly high risk of death from TB.3 It has been recommended that TB patients should be routinely screened for both of these risk factors and that, if present, they should be ad-dressed to improve TB treatment outcomes.3

India, with an annual incidence of 2.2 million TB cases, has the highest TB burden in the world.4 Nearly 63 million people (∼8% of the adult population aged ⩾20 years) are estimated to have DM, and 120 million are estimated to be tobacco smokers (∼14% of the adult population).5 Previous studies have estimated the prev-alence of diabetes and smoking among TB patients in-dependently of each other, but none of these studies has screened for both conditions in the same setting and reported on the co-existence of both of these risk factors among TB patients.5 These data will be useful to assess the extent of DM care and smoking cessation services required during the course of TB treatment. In this study we report the prevalence of impaired fasting glucose (IFG), DM and current smoking in a cohort of TB patients diagnosed at a medical college teaching hospital in the South Indian state of Karnataka.

METHODS

Study settingKLES Dr Prabhakar Kore Hospital is a 2400-bed hospital in the Belgaum district of Karnataka State in South India. TB patients diagnosed in the hospital are sent from var-ious departments to the DOTS centre for TB treatment.

Study design, study population, screening procedures, recording and reportingThis was a cross-sectional study involving record review. All TB patients aged ⩾18 years diagnosed

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to DM, tobacco smoking needs to be addressed during TB treatment.9 Of note, all of the current smokers in the study were male, highlighting the cultural tradition in this part of the country for women not to smoke.

Independent international guidelines exist for the management of co-morbid conditions, such as DM, tobacco smoking, human immunodefi ciency virus infection, etc., among tuberculosis patients.10–12 De-pending on the local situation, national TB pro-grammes in high TB burden countries need to adopt and incorporate these guidelines and integrate the im-plementation and monitoring of the management of co-morbidities. This must begin at least in the tertiary care centres, where the resources and expertise are available and, based on the experiences gained, imple-mentation can then be extended to the peripheral health facilities.

The strength of this study is that we implemented and documented the screening of both factors within the routine hospital system, with no special budget allocated to support these activities. With nearly 80% of the TB patients successfully undergoing screening for both conditions, it appears that screening is feasible. About 20% were not screened, and the exact reasons were not clear. As our facility is a tertiary care centre with many specialised services, we were able to link patients with these co-morbidities to appropriate care. The limitations of the study were that 1) it was im-plemented in a tertiary care centre and the fi ndings may not be generalisable, and 2) we defi ned a current smoker as anyone who had smoked at least one tobacco product within the last 3 months, and documented this status. In India, tobacco products are either chewed or smoked—both of which are equally danger-ous to personal health—and the consumption pattern of these two forms of tobacco varies widely across the country. As we mentioned the integration of services,

we feel with hindsight that we should also have docu-mented information on chewable forms of tobacco and used standardised defi nitions.

CONCLUSIONS AND RECOMMENDATIONS

It is feasible to screen for DM and tobacco smoking among TB patients in tertiary care settings. We recom-mend that TB and DM clinics and smoking cessation services develop links towards an integrated, compre-hensive package of services that could lead to im-proved care and better patient outcomes.

References 1 Jee S H, Golub J E, Jo J, et al. Smoking and risk of tuberculosis

incidence, mortality, and recurrence in South Korean men and women. Am J Epidemiol 2009; 170: 1478–1485.

2 Restrepo B I, Fisher-Hoch S P, Crespo J G, et al. Type 2 diabetes and tuberculosis in a dynamic bi-national border population. Epidemiol Infect 2007; 135: 483– 491.

3 Reed G W, Choi H, Lee S Y, et al. Impact of diabetes and smok-ing on mortality in tuberculosis. PLOS ONE 2013; (2): e58044.

4 Whiting D R, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabet Res Clin Pract 2011; 94: 311–321.

5 World Health Organization. Global tuberculosis report 2012. Geneva, Switzerland: WHO, 2012. http://www.who.int/tb/publications/global_report/en/ Accessed August 2013.

6 India Tuberculosis-Diabetes Study Group. Screening of patients with tuberculosis for diabetes mellitus in India. Trop Med Int Health 2013; 18: 636–645.

7 Vijay V, Satyavani K, Vigneswari A, et al. Prevalence of diabe-tes and pre-diabetes and associated risk factors among tuber-culosis patients in India. PLOS ONE 2012; 7: e41367.

8 Balakrishnan S, Vijayan S, Nair S, et al. High diabetes preva-lence among tuberculosis cases in Kerala, India. PLOS ONE 2012; 7: e46502.

9 Slama K, Chiang C-Y, Enarson D A, et al. Tobacco and tubercu-losis: a qualitative systematic review and meta-analysis. Int J Tuberc Lung Dis 2007; 11: 1049–1061.

10 World Health Organization/International Union Against Tuberculosis and Lung Disease. Provisional collaborative framework for care and control of tuberculosis and diabetes.

ACKNOWLEDGEMENTSA workshop was convened in Delhi, India, for the purpose of writing the papers that are published in this supple-ment. The workshop was run by the Centre for Opera-tional Research, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France; The Union South-East Asia Office, New Delhi, India; the Operational Research Unit, Médecins Sans Frontières, Luxembourg; the World Health Organization Country Office in India, New Delhi, India; the All India Institute of Medical Sciences, New Delhi, India; and ESIC Medical College, Bangalore, India.Funding for the workshop and open access publication was received from the World Diabetes Foundation, Gentofte, Denmark. Conflict of interest: none declared.

TABLE Prevalence of IFG, DM and smoking among a cohort of TB patients in Belgaum, India, January–September 2012

CharacteristicTotal

nIFG

n (%)*DM onlyn (%)*

Smoking only

n (%)*

DM + smoking n (%)*

Total 307 24 (7.8) 109 (35.5) 30 (9.8) 11 (3.6)Age, years

18–24 35 0 5 (14.3) 6 (17.1) 3 (8.6)25–34 84 4 (4.8) 13 (15.5) 12 (14.3) 2 (2.4)35–44 81 9 (11.1) 36 (44.4) 9 (11.1) 1 (1.2)45–54 42 10 (23.8) 33 (78.6) 1 (2.4) 3 (7.1)55–64 43 0 13 (30.2) 1 (2.3) 2 (4.7)⩾65 22 1 (4.6) 9 (40.9) 1 (4.6) 0

SexMale 197 17 (8.6) 73 (37.1) 30 (15.2) 11 (5.6)Female 110 7 (6.4) 36 (32.7) 0 0

Type of TBNew smear-positive 160 8 (5.0) 57 (35.6) 14 (8.8) 5 (3.1)New smear-negative 49 3 (6.1) 29 (59.2) 2 (4.1) 1 (2.0)New extra-pulmonary 36 3 (8.3) 9 (25.0) 3 (8.3) 1 (4.2)Retreatment cases 55 4 (7.3) 13 (23.6) 10 (18.2) 4 (7.3)Multidrug-resistant TB

(resistant to isoniazid and rifampicin) 7 6 (85.7) 1 (14.3) 1 (14.3) 0

* Row percentages with denominator in Total column. IFG = impaired fasting glucose; DM = diabetes mellitus; TB = tuberculosis.

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WHO/HTM/TB/2011.15. Geneva, Switzerland: WHO, 2011. http://whqlibdoc. who.int/publications/2011/9789241502252_eng.pdf Accessed August 2013.

11 World Health Organization/International Union Against Tuberculosis and Lung Disease. A WHO/The Union monograph on TB and tobacco control. Joining efforts to control two related global epidemics. Geneva, Switzer-

land: WHO, 2007. http://www.who.int/tobacco/resources/publications/tb_tob_ control_monograph/en/ Accessed August 2013.

12 World Health Organization. WHO policy on collaborative TB/HIV activities: guidelines for national programmes and other stakeholders. WHO/HTM/TB/2012.1, WHO/HIV/2012.1. Geneva, Switzerland: WHO, 2012.

Le diabète sucré (DM) et le tabagisme sont des facteurs de risque de mauvais résultats dans le traitement de la tuberculose (TB). Dans un hôpital de soins tertiaires à Belgaum dans l’Etat de Karnataka en Inde du Sud, tous les patients TB âgés de ⩾18 ans et diagnostiqués con-sécutivement entre février et septembre 2012 ont été évalués en

matière de DM et de tabagisme. Sur 307 patients TB, on a trouvé un DM chez 35,5%, un tabagisme actuel chez 9,8% et chez 3,6%, à la fois un DM et un tabagisme actuel. Il est indispensable d’incorporer des mesures d’évaluation et de réaction à ces deux facteurs au cours du traitement de la TB.

La diabetes sacarina (DM) y el tabaquismo representan factores de riesgo de alcanzar desenlaces terapéuticos desfavorables en el trata-miento de la tuberculosis (TB). En un hospital de atención terciaria de Belgaum, en el estado de Karnataka del sur de la India, se investigaron el tabaquismo y la DM en todos los pacientes consecutivos de ⩾18 años de edad, en quienes se estableció el diagnóstico de TB

entre febrero y septiembre del 2012. De los 307 pacientes TB, se di-agnosticó DM en el 35,5%, el 9,8% eran fumadores actuales y el 3,6% eran diabéticos y fumadores actuales. Es necesario incorporar medidas de evaluación y de respuesta a estos dos factores durante el tratamiento de la TB.

Public Health Action (PHA) The voice for operational research.Published by The Union (www.theunion.org), PHA provides a platform to fulfi l its mission, ‘Health solutions for the poor’. PHA publishes high-quality scientifi c research that provides new knowledge to improve the accessibility, equity, quality and effi ciency of health systems and services.

e-ISSN 2220-8372Editor-in-Chief: Donald A Enarson, MD, Canada Contact: [email protected] website: http://www.theunion.org/index.php/en/journals/pha Article submission: http://mc.manuscriptcentral.com/pha