HIGH TUBERCULOSIS INCIDENCE AMONG

PEOPLE LIVING WITH DIABETES IN

BANDUNG, INDONESIA (TINDER STUDY)

Otago Global Health Institute (OGHI)

12th Annual Conference, Wellington

6-7 November 2019

Sue McAllister1, Raspati C. Koesoemadinata2, Prayudi Santoso2, Nanny N.M. Soetedjo2,

Abdul Kamil2, Hikmat Permana2, Rovina Ruslami2, Julia A. Critchley3, Reinout van Crevel4,

Philip C. Hill1, Bachti Alisjahbana2

1. Centre for International Health, University of Otago, Dunedin, New Zealand

2. Infectious Disease Research Centre, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia

3. Population Health Research Institute, St Georges, University of London, UK

4. Radboud University Medical Centre, Nijmegen, The Netherlands

Background

• People living with diabetes mellitus (DM) are approximately

3 times more likely to develop tuberculosis (TB) than those

without DM.

• Indonesia TB incidence:

319 per 100,000 population (291-348) World Health Organization, 2017

• DM prevalence:

6.7% (total adult cases 10,276,100) https://idf.org/our-network/regions-members/western-pacific/members/104-indonesia.html

2

Background, cont’d

Patients with diabetes

% (95% CI)

Household contacts

% (95% CI)

Latent TB positive 38.6% (30.5-46.6) 68.6% (60.9-72.3)

Active TB 4.9% (1.6-8.2) 1.2% (-0.5-2.9)

3

Current WHO guidelines – screening & preventive treatment

of people with latent TB infection for:

- HIV-positive individuals

- children who are household contacts of a TB patient

Background cont’d and Study Aim

• Data regarding TB incidence among people with DM in

TB-endemic settings are scarce.

• Cohort of people with DM from previous study in 2014

who were tested for latent TB and were TB disease-free

4

To estimate the incidence rate of TB disease

in people with diabetes

Bandung

5

Bandung

city

Population ~2.5 million

Methods• Baseline:

o Diabetes mellitus

o >18 years of age

o Recruited via Community Health

Centres & tertiary referral hospital

6

Interview & clinical examination

Chest x-ray

(if suggestive of pulmonary TB &/or symptoms of cough)

Sputum test for acid-fast bacilli (AFB) & Mycobacterium

tuberculosis culture

TB

category

Definition

Definite M. Tuberculosis culture or Xpert MTB/RIF

positive or on anti-TB medication/already

treated for TB

Probable TB symptoms, chest x-ray suggestive of

TB and AFB positive but culture negative

Possible TB symptoms and/or chest x-ray

suggestive of TB but AFB and culture

negative

No TB No evidence of TB on symptom review or

investigations

Follow-up: contact by phone,

clinic appointment or home visit

Methods, cont’d

• Analysis: o Incidence rates and 95% confidence intervals calculated per 1000

person-years.

o Chi-squared test for comparison of groups

• Ethical approval:o The baseline study - Health Research Ethics Committee, Faculty of

Medicine, Universitas Padjadjaran, and the Research Ethics Committee,

London School of Hygiene & Tropical Medicine.

o The follow-up study - University of Otago Human Ethics Committee, and

the Health Research Ethics Committee, Faculty of Medicine, Universitas

Padjadjaran.

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Diabetes patients

eligible for follow-up

(n=590)

Follow-up

examination done

(n=326; 67%)

Did not attend clinic

• Refused (n=85)

• Died (n=101)

Unable to be

contacted

(n=78)

Patient or family

contacted

(n=512)

Flow chart of participant follow-up

Characteristics at baseline of patients followed-up

(n=326)

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• Time from baseline to follow up mean=3.43 years (range 1.94 – 4.31)

• Female – 71%

• Age – mean=58 years (range 23 – 81)

• DM duration <5 years – 57%

• HbA1c <7% – 29%

• Metformin – 62%

TB case definition of patients followed-up (n=326)

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TB case definition category Cases % (95% CI)

Definite TB 4 1.2 (0.34-3.1)

Probable TB 1 0.3 (0.008-1.7)

Possible TB 33 10.1 (7.1-13.9)

Already diagnosed 6 1.8 (0.7-4.0)

Not TB 282 86.5 (82.3-90.0)

Definite, probable or already

diagnosed

11 3.4 (1.7-6.0)

TB case definition of patients followed-up (n=326)

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TB case definition category Cases % (95% CI)

Definite TB 4 1.2 (0.34-3.1)

Probable TB 1 0.3 (0.008-1.7)

Possible TB 33 10.1 (7.1-13.9)

Already diagnosed 6 1.8 (0.7-4.0)

Not TB 282 86.5 (82.3-90.0)

Definite, probable or already

diagnosed

11 3.4 (1.7-6.0)

Baseline latent TB status

Positive (n=138) 8 5.8 (2.5-11.1)

Negative (n=181) 3 1.7 (0.3-4.8)

TB case definition of patients followed-up (n=326)

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TB case definition category Cases % (95% CI)

Definite TB 4 1.2 (0.34-3.1)

Probable TB 1 0.3 (0.008-1.7)

Possible TB 33 10.1 (7.1-13.9)

Already diagnosed 6 1.8 (0.7-4.0)

Not TB 282 86.5 (82.3-90.0)

Definite, probable or already

diagnosed

11 3.4 (1.7-6.0)

Baseline latent TB status

Positive (n=138) 8 5.8 (2.5-11.1)

Negative (n=181) 3 1.7 (0.3-4.8)

Cases per 1000 person-years

(95% CI)

Definite, probable or already

diagnosed

11 9.85 (4.03-15.68)

Baseline latent TB status

Positive 8 17.13 (5.25-29.00)

Negative 3 4.79 (-0.63-10.21)

Incidence rate ratio 3.57; 95% CI 0.86-20.92, p=0.054

Characteristics of patients who died (n=101) vs.

those who were followed-up (n=326)

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Reason for death – diabetes complications (86%)

0%

10%

20%

30%

40%

50%

60%

70%

Aged >70 Primaryeducation or

less

Smoker HbA1c >10% Hospitalisedin year before

baseline

Normal chestx-ray

Possible TBat baseline

Died Followed up

Incidence rate compared with other countries

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Country Incidence rate per 100,000

person years

Our study 985

China1 120

Hong Kong2 295

Taiwan (on Metformin)3 127

Taiwan (not on Metformin)3 140

1. Qiu H, Shi Y, Li Y, et al. Incident rate and risk factors for tuberculosis among patients with type 2 diabetes:

retrospective cohort study in Shanghai, China. Trop Med & Intl Health. 2017; 22(7): 830-8..

2. Leung CC, Lam TH, Chan WM, et al. Diabetic control and risk of tuberculosis: a cohort study. Am J Epidemiol.

2008;167(12):1486-94.

3. Lee MC, Chiang CY, Lee CH, et al. Metformin use is associated with a low risk of tuberculosis among newly diagnosed

diabetes mellitus patients with normal renal function: A nationwide cohort study with validated diagnostic criteria.

PLoS One. 2018;13(10):e0205807.

Strengths and limitations

• Baseline sample size restricted the number available for follow-up, limiting study power

• 28% of participants could not be contacted or refused

• Verbal report from family on reason of death

Possible underestimate of incidence

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• Complete baseline information & able to confirm TB and LTBI status

• Active case finding approach

Summary and conclusions

• High TB incidence in diabetes patients

• Higher TB incidence in those who had latent TB infection at

baseline (but not statistically significant)

• People with diabetes could benefit from preventive therapy

• PROTID Africa (Uganda & Tanzania): Randomised controlled

trial of TB preventive therapy for DM patients (Rifapentine &

Isoniazid 1x week for 12 weeks vs. placebo)

• PROTID Asia

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Acknowledgements

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• Fundingo The baseline cross-sectional study was supported by the TANDEM

project, which is funded by the European Union’s Seventh Framework Programme (FP7/2007–2013) under Grant Agreement Number 305279.

o The follow-up study was funded by a University of Otago Research Grant and a Department of Preventive and Social Medicine Strategic Grant.

• Study participants

• Staff at the Endocrine Clinic,

Hasan Sadikin Hospital,

Bandung