Should household contacts and other close contacts of a · PDF fileShould household contacts and other close contacts of a person with active TB be systematically screened for active

Should household contacts and other close contacts of a person with active TB be systematically screened for active TB?

Patients:

Screening intervention:

Comparison:

Close contacts of active TB cases

Symptom screening, chest X-ray screening, or both

Passive case-finding

Implied purpose: Linked treatment:

Reducing TB morbidity, mortality and transmission Treatment of active TB and treatment of TB infection in children aged <5 years

Note: See the systematic reviews for full references to cited papers.

1 Fox G et al. Contact investigation for tuberculosis: a systematic review and meta analysis. European Respiratory Journal, 2013, 4:140–156.

DO

MA

I

N

CRITERIA JUDGEMENT EVIDENCE COMMENTS

Bu

rde

n o

f ill

ne

ss o

r p

rob

lem

Is it frequent? Very

infrequent Infrequent

Moderately frequent

frequent Very

frequent

Across 95 studies in low-income and middle-income countries, the weighted mean prevalence of all types of active TB among household contacts and other close contacts of a person with active TB was 3.1% (95% confidence interval [CI], 2.2–4.4%), and the weighted-mean prevalence of microbiologically proven TB was 1.2% (95% CI, 0.9–1.8%). In 108 studies in high-income settings, the weighted-average prevalence of all types of active TB among close contacts or household contacts was 1.4% (95% CI, 1.1–1.8%). In children aged <5 years in low-income and middle-income countries, the weighted-average prevalence of all types of active TB was 10% (95% CI, 5.0–18.9%).1

Across 89 studies, the weighted mean number needed to screen (NNS) for all types of active TB in household contacts was 40 (range, 2–568) (Shapiro 2012). The weighted average NNS ranged from 54 in low-incidence settings to 17 in high-incidence settings (Shapiro 2012).

Is it severe?

Very mild

mild moderate severe Very

severe*

*e.g. life threatening or disabling

Hosehold contacts and other close contacts of a person with active TB have a high risk of becoming infected. People who have been recently infected with TB have a higher risk of progressing to active disease in the near future compared with people who have distant latent TB infection. Household contacts who are aged <5 years, have HIV, or have other diseases that impair their immune system are at a particularly high risk of developing active TB, and are also at high risk for poor disease outcomes.

3a

Co

nfi

de

nce

In

acc

ura

cy o

f th

e d

iag

no

stic

te

st

What is the confidence in the accuracy of the diagnostic test ?

Very low

Low Moderate High

Sensitivity and specificity (based on van’t Hoog et al 2012)

Outcome Any cough Cough lasting >2

weeks

Any symptom Chest X-ray (any

abnormality)

Chest X-ray (TB-

related

abnormality)

Effect Quality Effect Quality Effect Quality Effect Quality Effect Quality

TP Sensiti

vity

56% (40–74%)

OO Low

35% (24–46%)

OOO Very low

77% (68–86%)

OOO Very low

98% (95–

100%)

O Moderate

87% (79–95%)

OO Low FP

TN Specifi

city

80% (69–90%)

OO Low

95% (93–97%)

OO Low

68% (50–85%)

OOO Very low

75% (72–79%)

O Moderate

89% (87–92%)

OO Low FP

TP, true positive; FP, false positive; TN, true negative.

For further details see the GRADE tables on the accuracy of diagnostic tests.

Be

ne

fits

an

d

ha

rms

Overall, are the anticipated desirable effects large?

No Yes

Modelled yeild of different algorithms based on point estimates from the systematic review of the accuracy of screening tools (van’t Hoog et al 2012) and systematic reviews of the accuracy of sputum-smear microscopy2 and the Xpert MTB/RIF test3

Screening

Diagnosi

s

Prevalence 0.5% (500/100 000)

Prevalence 1% (1 000/100 000)

Prevalence 2% (2 000/100 000)

TP FP TN FN TP FP TN FN TP FP TN FN

Chest X-ray: any

abnormality

SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623

XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197

Chest X-ray: TB

abnormalities

SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778

XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399

Cough lasting >2–3 weeks

SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506

XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353

Any symptom SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916

XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580

1. Cough lasting >2–3

weeks. 2. Chest X-ray

SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555

XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417

1. Any symptom. 2. Chest X-ray

SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024

XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722

TP, true positive; FP, false positive; TN, true negative; FN, false negative; SSM, sputum-smear microscopy; XP, Xpert MTB/RIF test; CD, clinical diagnosis.

Overall, are the anticipated undesirable effects small?

No Yes

Overall, is there certainty of the link between the accuracy of the diagnostic test and the consequences?

Very uncertain

uncertain Moderately

certain Certain

Very certain

2 Approaches to improve sputum smear microscopy for tuberculosis diagnosis: expert group meeting report. Geneva, World Health Organization, 2009. 3 Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system. Policy statement. Geneva, World Health Organization, 2011 (WHO/HTM/TB/2011.4).

Direct assessment of outcomes of screening (Kranzer 2012)

For further details see the GRADE tables.

Co

nfi

de

nc

e i

n b

en

efi

ts

an

d

ha

rms

What is the overall confidence in the estimates of effect for benefits and harms?

Very low

Low Moderate High

There is VERY LOW QUALITY evidence that investigating contacts could improve case-detection rates for the population where the investigation is carried out. There is VERY LOW QUALITY evidence that investigating contacts could identify cases earlier than passive case-finding. There is LOW QUALITY evidence that investigating contacts may influence the epidemiology of TB.

Va

lue

s

What is the confidence in the values that patients place on the benefits and harms?

Very low

Low Moderate High

Very high

In 24 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening during investigation of household contacts was 80%; the range was 39–99%; and the median proportion was 85%.

Re

so

urc

e

s

Is the cost low

relative to the net

benefits?

No Uncertain Yes

No cost–effectiveness analysis of contact tracing has been published.

Diagnostic category Potential effect Summary of findings

Effect No. of studies Quality

True positives

Benefit on case detection Contact tracing contributed 2 to 19% of all cases

5 cross-sectional studies

OOO Very low

Benefit on time to diagnosis - 0 studies OOO Very low

Benefit on severity at diagnosis Risk of severe x-ray changes at diagnosis RR 0.38

1 cross sectional study

OOO Very low

Benefit on treatment outcome - 0 studies OOO Very Low

Benefit on transmission 15% reduction in incidence 22% reduction in

prevalence

2 cluster RCTs OO Low

False negatives Harm from missed diagnosis - Not reviewed -

True negatives Benefit from reassurance - Not reviewed -

Harm from unnecessary screening - Not reviewed -

False positives Harm from unnecessary treatment - Not reviewed -

Overall balance of consequences

Undesirable consequences clearly outweigh desirable consequences

Undesirable consequences probably outweigh desirable consequences

Desirable and undesirable consequences

closely balanced or uncertain

Desirable consequences probably outweigh undesirable consequences

Desirable consequences clearly outweigh undesirable consequences

Recommendation Strongly recommend

against Conditionally recommend

against Do not make recommendation (use this

option very rarely if evidence is too sparse) Conditionally recommend

Strongly recommend

Proposed recommendation for discussion Household contacts and other close contacts of someone with active TB should be systematically screened for active TB. (This is a strong recommendation with very low quality evidence. )

Remarks Contacts may be investigated either by invitation to a clinic or through a household visit. No empirical data are available on the relative effectiveness and cost effectiveness of each type of investigation. The panel believes that household visits are more effective but also more resource intensive. For details on prioritizing index cases for investigation, operational aspects of contact investigations, and monitoring and evaluating of contact investigation, see WHO’s guidelines on contact investigations.4 Contact investigations should always be done when the index case has any of the following: sputum smear-positive pulmonary TB; proven or suspected multidrug-resistant TB (MDR-TB) or extensively drug-resistant TB (XDR-TB); is a person living with HIV; is a child aged <5 years. In addition, resources permitting, investigations of household contacts and close contacts may be performed for all index cases with pulmonary TB.4 For those whose screening is positive, whether further diagnostic evaluation is undertaken depends on the profile of the contact and the index case.4 For individuals who are contacts of a patient with MDR-TB or at high risk of MDR-TB for other reasons,5 the primary diagnostic test should be the Xpert MTB/RIF test.6 All persons living with HIV who have signs or symptoms of TB, persons who are seriously ill and suspected of having TB regardless of their HIV status, and persons whose HIV status is unknown who present with strong clinical evidence of HIV infection in settings where there is a high prevalence of HIV should have as their primary diagnostic test an Xpert MTB/RIF test. In settings where there is a high prevalence of HIV, all household contacts and close contacts should be counselled and tested for HIV. When an index case is a person living with HIV, all household contacts should be counselled and tested for HIV. All household contacts and close contacts who have symptoms compatible with active TB should receive counselling and testing for HIV as part of their clinical evaluation. People living with HIV who are household contacts or close contacts of someone with TB and who after an appropriate clinical evaluation have been found not to have active TB should be treated for presumed latent TB infection following WHO’s guidelines.7 Children who are younger than 5 years and who are household contacts or close contacts of someone with TB and who after an appropriate clinical evaluation have been found not to have active TB should be treated for presumed latent TB infection following WHO’s guidelines.3 Contacts should have a nutrition assessment as part of the investigation. If malnutrition is identified, it should be managed according to WHO’s recommendations.8

4 Recommendations for investigating the contacts of persons with infectious tuberculosis in low- and middle-income countries. Geneva, World Health Organization, 2012

(WHO/HTM/TB/2012.9). 5 Guidelines for the programmatic management of drug-resistant tuberculosis: emergency update 2008. Geneva, World Health Organization, 2008 (WHO/HTM/TB/2008.402).

6 Rapid implementation of the Xpert MTB/RIF diagnostic test: technical and operational ’how-to’. Practical considerations. Geneva, World Health Organization, 2011 (WHO/HTM/TB/2011.2).

7 Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva, World Health Organization, 2011.

8 Guideline: Nutritional care and support for patients with Tuberculosis. WHO 2013 (draft guideline)

Should people living with HIV be systematically screened for active TB at each

visit to a health facility in all settings?


Patients: Screening intervention:

Comparison:

People with HIV Symptom screening and chest X-ray screening Passive case-finding


Reducing TB morbidity, mortality and transmission Chemotherapy for active TB Chemoprophylaxis for latent TB infection

1 Getahun H et al. HIV infection-associated tuberculosis: the epidemiology and the response. Clinical Infectious Diseases, 2010, 50 (Suppl. 3):S201–S207. Cox JA et al. Autopsy causes of death in HIV-positive individuals in sub-Saharan Africa and correlation with clinical diagnoses. AIDS Reviews, 2010, 12:183–194. 2 Global tuberculosis control: WHO report 2011. Geneva, World Health Organization, 2011. Sanchez M et al. Outcomes of TB treatment by HIV Status in national recording systems in Brazil, 2003–2008. PLoS One, 2012, 7(3): e33129 (doi:10.1371/journal.pone.0033129). Farley JE et al. Outcomes of multi-drug resistant tuberculosis (MDR-TB) among a cohort of South African patients with high HIV prevalence. PLoS ONE, 2011, 6(7): e20436 (doi:10.1371/journal.pone.0020436). Gandhi NR et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet, 2006, 368 :1575–1580. Gandhi NR et al. HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality. American Journal of Respiratory and Critical Care Medicine, 2010, 181:80–86. 3 Timothy R et al. HIV infection–related tuberculosis: clinical manifestations and treatment. Clinical Infectious Diseases, 2010, 50(Suppl. 3):S223–S230. Getahun H et al. Diagnosis of smear negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet 2007, 369:2042–2049. Chaisson RE et al.. Tuberculosis in patients with the acquired immunodeficiency syndrome: clinical features, response to therapy, and survival. American Review of Respiratory Disease, 1987, 136:570–574.

DO

MA

IN


Bu

rde

n o

f ill

ne

ss o

r p

rob

lem



Moderately frequent

frequent Very

frequent

The review of the number needed to screen (NNS) found that the average NNS among people with HIV in low-incidence countries is 30 (range, 8–391); in countries with a moderate incidence it is 61 (5–316); in countries with a medium incidence it is 13 (2–120); and in countries with a high incidence it is 10 (3–64) (Shapiro 2012).

Is it severe?

Very mild


severe*


TB is responsible for more than one quarter of deaths occurring in people living with HIV.1 Among people who are HIV-positive, outcomes from treatment for TB are much worse than in other people with TB.2 Delayed diagnosis of TB in people living with HIV is associated with an increased risk of poor treatment outcomes and death.3

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Sanchez%2BM%5bauth%5d

http://www.thelancet.com/search/results?fieldName=Authors&searchTerm=Neel%20R+Gandhi

http://www.thelancet.com/journals/lancet/issue/vol368no9547/PIIS0140-6736(06)X6218-9

4 Getahun H et al. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Medicine, 2011, 8(1):e1000391 (doi: 10.1371/journal.pmed.1000391). 5 Song R et al. Evaluation of tuberculosis screening approaches among HIV-infected children in Rwanda, 2008 [Abstract no. TUPEB132]. Geneva, International AIDS Society, 2013 (http://www.iasociety.org/Abstracts/A200721790.aspx, accessed 15.09.2012[ 6 Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva, World Health Organization, 2011.

Co

nfi

de

nce

in

acc

ura

cy o

f th

e d

iag

no

stic

te

st


Very low

Low Moderat

e High

A systematic review found that the best symptom-based screening tool for HIV-positive people used four symptoms, and had a sensitivity of 79% and a specificity of 50%.4 At a 5% prevalence of TB among people living with HIV, the negative predictive value was 97.7% (95% confidence interval, 97.4–98.0). Adding abnormal findings on chest X-ray to the screening for four symptoms increased the sensitivity from 79% to 91% but there was a drop in specificity, from 50% to 39%. At a 5% prevalence of TB among people living with HIV, augmenting the symptom-based screening with abnormal findings seen on chest X-ray increased the negative predictive value by a margin of 1% (98.7% versus 97.8%). Adding abnormal findings on chest X-ray to the symptom-based screening at a TB prevalence of 20% among people living with HIV increased the negative predictive value by almost 4% (94.3% versus 90.4%). One study5 assessed a screening algorithm for HIV-positive children. The presence of cough lasting >2 weeks, fever or failure to thrive had a sensitivity of 95% and specificity 59%. The absence of these symptoms had a negative predictive value of 99%. GRADE table from the guideline on intensified case-finding in people living with HIV.6

http://www.iasociety.org/Abstracts/A200721790.aspx

Be

ne

fits

a

nd

h

arm

s


No Yes

Impact on case detection No published controlled trial has assessed the impact of screening HIV-positive people on changes in overall case detection. One cross-sectional study in India from a setting with a low prevalence of HIV found that 1% of the total cases detected came from screening people with HIV (Shetty 2008). Impact on time to diagnosis and severity at diagnosis No studies were found. Impact on treatment outcomes No published study has compared treatment outcomes between HIV-positive TB patients detected through screening with outcomes among those detected through other methods. Three studies reported TB treatment outcomes only in cohorts with TB detected through screening. One study from Botswana (Agizew 2010) reported a treatment success rate of 85% and a death rate of 12% in a cohort in which all patients were HIV-positive. One study from Ivory Coast (Koffi 1997) reported a treatment success rate of 74% and a death rate of 26% in a cohort of patients identified through screening in prisons, among whom 30% were HIV-positive (data were not disaggregated by HIV status). One study from South Africa (Kranzer 2012) reported a treatment success rate of 81% and a death rate of 5% in a cohort of patients screened for TB as part of a mobile HIV testing programme; 54% of patients were HIV-positive (data were not disaggregated by HIV status). Impact on epidemiology No published trial has assessed the epidemiological impact of screening for TB specifically in people who are HIV-positive.


No Yes

Overall, is there certainty about the link between the accuracy of the diagnostic test and the consequences?

Very uncertain


certain Certain

Very certain

Co

nfi

de

nc

e i

n b

en

efi

ts

an

d h

arm

s


Very low

Low Moderate High

There is VERY LOW QUALITY direct evidence on the impact of screening on morbidity and transmission specifically among people with HIV. However, TB is a cause of death and suffering among people with HIV, and delayed diagnosis of TB in HIV-positive people is associated with an increased risk of poor outcomes from treatment, including death. It is therefore plausible that screening HIV-positive people for TB will be beneficial. An additional benefit is that screening for active TB can identify people who are eligible for treatment of latent TB infection; treating latent TB infection has been shown to be effective in reducing the incidence of TB and death from TB.

Va

lue

s


Very low

Low Moderate High

Very high

In 17 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among people living with HIV was 78%; the range was 52–99%; and the median proportion was 83%.

Re

so

urc

es

Is the cost low

relative to the

net benefits?

No Uncertain Yes

No cost–effectiveness analysis has been published.








Recommendation Strongly recommend against

Conditionally recommend against

Do not make recommendation (use this option very rarely if evidence is too sparse)

Conditionally recommend

Strongly recommend

We decide People living with HIV should be systematically screened for active TB at each visit to a health facility in all settings. This is a strong recommendation with very low quality evidence.

Remarks This recommendation is fully consistent with previous WHO guidelines on intensified case finding in people with HIV.7


Should systematic screening for active TB be done in miners?

Patients:

Diagnostic intervention:

Comparison:

People working in mines

Chest X-ray



Reducing TB morbidity, mortality and transmission Treatment of active TB


1 Barboza CEG et al. Tuberculosis and silicosis: epidemiology, diagnosis and chemotherapy. Jornal Brasileiro de Pneumologia, 2008, 34:959–966. 2 Churchyard GJ et al. Silicosis prevalence and exposure-response relations in South African gold miners. Occupational and Environmental Medicine, 2004, 61: 811–816. 3 Hnizdo E, Murray J. Risk of pulmonary tuberculosis relative to silicosis and exposure to silica dust in South African gold miners. Occupational and Environmental Medicine, 1998, 55:496–502. Erratum in: Occupational and Environmental Medicine, 1999, 56:215–216. Corbett EL et al. Risk factors for pulmonary mycobacterial disease in South African gold miners. A case-control study. American Journal of Respiratory and Critical Care Medicine, 1999, 159:94–99. Cowie RL. The epidemiology of tuberculosis in gold miners with silicosis. American Journal of Respiratory and Critical Care Medicine,1994, 150:1460–1402. te Waternaude JM et al. Tuberculosis and silica exposure in South African gold miners. Occupational and Environmental Medicine, 2006, 63:187–192. 4 Corbett EL et al. HIV infection and silicosis: the impact of two potent risk factors on the incidence of mycobacterial disease in South African mines. AIDS, 2000, 14:2759–2768. 5 Churchyard GJ et al. Factors associated with an increased case-fatality rate in HIV-infected and non-infected South African gold miners with pulmonary tuberculosis. International Journal of Tuberculosis and Lung Disease, 2000, 4:705–712.

Do

ma

in


Bu

rde

n o

f ill

ne

ss o

r p

rob

lem

Is it frequent?

Very infrequen

t

Infrequent

Moderately frequent

frequent Very

frequent

A systematic review of eight studies (Shapiro 2012) of the number needed to screen (NNS) to detect a previously undetected case of TB found that for miners the mean weighted NNS was 87 (range, 20–233); all of the high-incidence countries represented in these studies are known to have a high prevalence of HIV among miners. For low-incidence countries the mean NNS was 48; for moderate-incidence countries, the mean NNS was 154; and for high-incidence countries the mean NNS was 37.

Is it severe?

Very mild

mild moderat

e severe

Very severe

*


Exposure to silica dust and silicosis are among the strongest risk factors for TB, with a relative risk of 2.8–39 for silicosis, depending on the severity of the disease.1 Silicosis is common in miners,2 which is the main reason for the high incidence of TB among them.3 In some countries, such as those in southern Africa, the prevalence of HIV is high among miners, which further increases their risk of TB and poor outcomes from TB treatment if diagnosis is delayed. The combined increase in risk for silicosis and HIV infection is multiplicative.4 TB patients with silicosis have an increased risk of death (adjusted relative risk [RR], 3.0; 95% confidence interval [CI],1.4–6.3).5

6 Godfrey-Faussett P et al. Tuberculosis control and molecular epidemiology in a South African gold-mining community. Lancet,. 2000, 356:1066–1071. 7 Girdler-Brown BV et al. The burden of silicosis, pulmonary tuberculosis and COPD among former Basotho gold miners. American Journal of Industrial Medicine, 2008, 51:640–647. 8 Stuckler D et al. Mining and risk of tuberculosis in sub-Saharan Africa. American Journal of Public Health, 2011, 101:524–530.

Though data are scarce on the prevalence of silicosis in most low-income and middle-income settings, it is plausible that silicosis is particularly common in settings where working conditions are poor, such as in many low-income countries. Delayed diagnosis of TB leads to an increased risk of transmission, especially in crowded settings, such as mines, and especially where miners both work and live in crowded conditions.6 In some middle-income countries, the mining industry attracts migrant workers from countries with a high burden of TB, and there is migratioin into and out of mining communitiies.7 In theory, mines can amplify TB transmission, leading to increased transmission both within and outside mining communities. Mining is a significant determinant of countrywide variation in the incidence of TB in sub-Saharan nations.8

Co

nfid

en

ce in

acc

ura

cy o

f th

e d

iag

no

stic

t

est


Very low

Low Moderat

e High


weeks


abnormality)

Chest X-ray (TB-

related

abnormality)


TP Sensitivity

56% (40–74%)

OO Low

35% (24–46%)

OOO Very low

77% (68–86%)

OOO Very low

98% (95–

100%)

O Moderate

87% (79–95%)

OO Low FP

TN Specificity

80% (69–90%)

OO Low

95% (93–97%)

OO Low

68% (50–85%)

OOO Very low

75% (72–79%)

O Moderate

89% (87–92%)

OO Low FP

Sensitivity and specificity (based on van’ t Hoog et al 2012)

TP, true positive; FP, false positive; TN, true negative. For further details see the GRADE tables on the accuracy of diagnostic tests. (One study – Lewis 2009 – evaluating different algorithms for symptom screening in gold miners, reported a sensitivity of <10% for chronic cough, and a sensitivity of 29% for any symptom in a population already undergoing annual screening with chest X-ray.)

B

en

efi

ts

an

d h

arm

s


No Yes

Modelled yield of different algorithms based on point estimates from the systematic review of the accuracy of screening tools (van’t Hoog et al 2012) and systematic reviews of the accuracy of sputum-smear microscopy9 and the Xpert MTB/RIF test10

Screening Diagnosi

s

Prevalence 0.5% (500/100 000)

Prevalence 1% (1 000/100 000)

Prevalence 2% (2 000/100 000)


Chest X-ray: any

abnormality

SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623

XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197

Chest X-ray: TB

abnormalities

SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778

XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399


SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506

XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353


XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580



SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555

XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417


SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024

XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722



No Yes



Very uncertain

uncertain

Moderately certain

Certain Very

certain


Impact on case detection No studies.

Impact on time to diagnosis and severity at diagnosis No studies. Impact on treatment outcomes One cohort study (Churchyard 2000) assessing risk factors for case-fatality in HIV-negative miners and HIV-positive miners with TB found that the adjusted relative risk of death (controlling for HIV status, sputum status, treatment category, age, extent of disease, silicosis and drug resistance) was 5.6 (95% CI, 2.6–12.2) for people identified through passive case-finding compared with those identified through a routine screening programme using chest X-ray. The adjusted RR for HIV-positive miners was 4.3 (95% CI, 1.9–9.6); for HIV-negative miners it was 8.0 (95% CI, 1.8–36.5). The case-fatality rate in HIV-negative miners detected through passive case-finding was low (2.0%); the case-fatality rate in those who were screened was even lower (0.4%). The case-fatality rate in HIV-positive miners detected through passive case-finding was high (16%); it was 3% for those who had been screened. Thus, while the reduction in relative risk was higher for HIV-negative miners than it was for HIV-positive miners who had been screened, the absolute decrease in risk was much larger for HIV-positive miners who had been screened. Impact on TB epidemiology No studies. Screening interval



True positives

Benefit on case detection - 0 studies OOO Very low


Benefit on severity at diagnosis - 0 studies OOO Very low

Benefit on treatment outcome Fewer deaths (See text)

1 cohort OOO Very Low

Benefit on transmission - 0 studies OOO Very low





One randomized controlled trial (Churchyard 2011) compared miners who had 6-monthly screening by chest X-ray with miners who had 12-monthly screening by chest X-ray. There was no difference in the number of cases detected, but miners identified by 6-monthly screening had significantly less extensive disease at the time of diagnosis and a lower case-fatality rate than those identified by 12-monthly screening, although only the reduction in case-fatality rate at 2 months was significantly lower.

Co

nfi

de

nc

e

in b

en

efi

ts

an

d h

arm

s What is the overall

confidence in the estimates of effect for benefits and harms?

Very low

Low Moderate High

There is VERY LOW QUALITY evidence that screening for TB among miners reduces the case-fatality rate. There is no evidence from published studies on the impact of screening miners for TB on case detection, delay in diagnosis and severity of disease at diagnosis, or on the epidemiology of TB.

Va

lue

s


Very low

Low Moderate High Very

high

In six studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening in miners was 70%; the range was 66–93%; and the median proportion was 84%.

Re

so

urc

es

Is the cost low

relative to the net

benefits?

No Uncertain Yes

No cost or cost–effectiveness analysis has been published.




Desirable and undesirable consequences closely

balanced or uncertain




Conditionally recommend Against



Strongly recommend

Options for recommendation and for discussion Option 1: There is not enough evidence to make a recommendation. Option 2: Systematic screening for active TB should be done in miners. Option 3: Systematic screening for active TB should be done in miners in settings with a moderate-to-high burden (prevalence >100/100 000) or where the prevalence of TB in miners is very high (>1%). For options 2 and 3: These are conditional recommendations with very low quality evidence.

Remarks Screening miners should be a high priority, particularly in settings with a high prevalence of HIV and a high prevalence of silicosis. It may not be possible to implement this recommendation in resource-constrained settings. However, mining companies tend to be resource-rich and could probably afford to offer screening. When the prevalence of rifampicin resistance in the screened population is <10% , an Xpert MTB/RIF result that is positive for rifampicin should be confirmed by conventional drug-susceptibility testing or line probe assay.11 In settings with a high prevalence of HIV, counselling and testing for HIV should be offered to all people whose screening is positive for TB.12 The screening interval should be ≤1 year. Screening miners for TB should be combined with general health screening.

11

Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system. Policy statement. Geneva, World Health Organization, 2011 (WHO/HTM/TB/2011.4). 12

Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva, World Health Organization, 2011.

Should systematic screening for active TB be done routinely in prisons?

Patients:


Comparison:

People in prisons

Symptom screening or chest X-ray screening, or both



Reducing TB morbidity, mortality and transmission Anti-TB chemotherapy


D O M A I N


Bu

rde

n o

f ill

ne

ss o

r p

rob

lem



Moderately frequent

frequent Very

frequent

A systematic review found that the incidence of TB in prisoners averages 23 times higher than in the general population (Baussano et al 2010). This review reported a median incidence of 1943/100 000 population in middle-income and low-income countries, and an incidence of 238/100 000 in high-income countries. A systematic review of the number needed to screen (NNS) in different risk groups (Shapiro et al 2012) reported a mean weighted NNS from 44 studies of prisoners in all countries of 315 (range, 4–2945). In low-incidence countries the weighted mean NNS was 1180 (range 4-2945) ; in medium-incidence countries the weighted mean NNS was 155 (range 19-191); and in countries with a moderate incidence or a high incidence it was 110 (range 7-2762). TB transmission rates are high in prisons because there is often a high prevalence of TB among people who are incarcerated, and living conditions are often crowded. Prisons can amplify community transmission of TB. In high-income countries Baussano (2010) estimated that the population-attributable fraction of TB in prisons was 8.5%; in middle-income and low-income countries it was estimated to be 6.3%.

Is it severe?

Very mild


severe*


The prevalence of risk factors for poor treatment outcomes may be high in prisons; these risk factors include HIV infection, undernutrition, and drug abuse and alcohol abuse.

Co

nfid

enc

e in

acc

ura

cy o

f th

e d

iag

nost

ic

tes

t

What is the confidence in the accuracy of the diagnostic test?

Very low

Low Moderate High




weeks

Any symptom Chest x-ray (any

abnormality)

Chest X-ray (TB-

related

abnormality)


TP Sensiti

vity

56% (40–74%)

OO Low

35% (24–46%)

OOO Very low

77% (68–86%)

OOO Very low

98% (95–

100%)

O Moderate

87% (79–95%)

OO Low FP

TN Specifi

city

80% (69–90%)

OO Low

95% (93–97%)

OO Low

68% (50–85%)

OOO Very low

75% (72–79%)

O Moderate

89% (87–92%)

OO Low FP


Be

ne

fits

an

d h

arm

s


No Yes


Screening

Diagnosis

Prevalence 0.5% (500/100 000)

Prevalence 1% (1 000/100 000)

Prevalence 2% (2 000/100 000)


Chest X-ray: any abnormality

SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623

XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197

Chest X-ray: TB abnormalities

SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778

XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399


SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506

XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353


XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580

1. Cough lasting >2–3 weeks. 2. Chest X-ray

SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555

XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417


SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024

XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722



No Yes


Very uncertain


certain Certain

Very certain




Impact on case detection There are no studies assessing the impact of screening in prisons on overall case detection.

Impact on time to diagnosis and severity at diagnosis One study has compared delay in people screened vs. passively detected among various high risk groups in London, including prisoners. The delay to diagnosis was three time longer on average in those detected passively. The data is from a published conference abstract and does not provide disaggregated delay data by risk groups, nor details about study methodology. Impact on treatment outcomes Two studies have reported treatment outcomes among prisoners with TB detected through screening, but no study has compared outcomes between screened and passively detected prisoners. One study from Ivory Coast (Koffi 1997) reported treatment success rate 74% and death rate 26%. The other study, from Malawi (Harrier 2004) reported treatment success rate 61% and death rate 12% while 7% defaulted before treatment started.



True positives

Benefit on case detection - 0 studies OOO Very low

Benefit on time to diagnosis Delay 3xlonger with passive detection


OOO Very low

Benefit on severity at diagnosis Less likely to be smear positive at diagnosis


OOO Very low

Benefit on treatment outcome No control group 2 cross sectional studies

OOO Very Low

Benefit on transmission Reduction in incidence over time (10 years)

1 longitudinal study OOO Very low





Impact on TB epidemiology One study from Mongolia3 reported declining TB incidence in a prison over a ten year period (from about 2,500/100,000 notified cases in prisoners in 2001 to less than 900/100,000 in 2010 across 23 prisons and 16 detention centres with a total of about 6000 prisoners), associated with the introduction of systematic screening at both detention and conviction combined with improved TB management and improved living conditions in the prisons. The national TB notification rate in Mongolia fluctuated between 142 and 194/100,000 during the same time period without any clear downward trend. Results may be interpreted as screening having an effect on reducing transmission and thus reducing incidence within prisons, while this did not have an impact on the national level. This was however not a controlled study, and therefore it was not included in the systematic review by Kranzer (2012).

co

nfi

de

nc

e i

n b

en

efi

ts

an

d h

arm

s


Very low

Low Moderate High

There is VERY LOW QUALITY evidence that screening prisoners could detect cases of TB earlier and affect the epidemiology of TB within prisons.

Va

lue

s


Very low

Low Moderate High

Very high

In 16 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening in prisons was 72%; the range was 18–98%; and the median proportion was 86%.

Re

so

urc

es

Is the cost low

relative to the net

benefits?

No Uncertain Yes

No cost-effectiveness analysis has been published.




Desirable and undesirable consequences closely balanced or uncertain







Strongly recommend

3 Yanjindulam et al. Reduction of tuberculosis burden among prisoners in Mongolia: review of case notification, 2001-2010. INT J TUBERC LUNG DIS 16(3):327–329

Options for recommendations and for discussion Option 1: There is not enough evidence to make a recommendation. Option 2: Screening for active TB at the time a person enters prison should be followed by yearly screening and screening when a prisoner is released; this strategy should be implemented in prisons and other penitentiary institutions in all settings. Option 3: Screening for active TB at the time a person enters prison should be followed by yearly screening and screening when a prisoner is released; this strategy should be implemented in prisons and other penitentiary institutions in moderate–to-high burden settings (>100/100 000).

For options 2 and 3: These are conditional recommendations with very low-quality evidence. Notes: While direct evidence of the impact on morbidity from and transmission of TB from screening prisoners is very weak, there are several reasons to conditionally recommend such screening:

prisoners are among the highest risk group for TB in all settings, although the NNS is high in low-burden settings;

transmission in prisons is believed to be high, especially where living conditions are crowded; additionally, prisons can amplify transmission. The population-attributable fraction of TB in prisoners has been estimated to be 8.5% in high-income countries, and 6.3% in middle-income and low-income countries;

screening in prisons is feasible in many settings, and general health screening is already taking place in many prisons.

Remarks

It may not be possible to implement these recommendations in resource-constrained settings.

When the prevalence of rifampicin resistance in the screened population is <10% , an Xpert MTB/RIF result that is positive for rifampicin should be confirmed by conventional drug-susceptibility testing or line probe assay.2

In settings with a high prevalence of HIV, counselling and testing for HIV should be offered to all people whose screening for TB is positive.4

For recommendations on managing TB in prisons and other penitentiary institutions, and for advice on managerial and administrative issues, see Guidelines for the control of tuberculosis in prisons.5

Screening for TB in prisons and other penitentiary institutions should be combined with general health screening.


5 Guidelines for the control of tuberculosis in prisons. The Hague, Tuberculosis Coalition for Technical Assistance (TBCTA), 2009.

Should systematic screening for active TB be done routinely in settings with a moderate-to-high prevalence of TB (>100/100 000 population) among people seeking care for any reason who:

(i) belong to one of the following risk groups for TB – people older than 60 years, with previously known or suspected TB, who are undernourished, who smoke, who have chronic obstructive pulmonary disease, who have diabetes, with alcohol or substance abuse disorders, with a disease or undergoing treatment that impairs their immune system, who are pregnant, or who work in health care; or who work in health care. and

(ii) have not been screened for TB during the preceding 6–12 months?

Patients:


Comparison:

People living in areas with a moderate–to-high prevalence of TB who

attend for health-care services and belong to special risk groups




Reducing TB morbidity, mortality and transmission Anti-TB chemotherapy


DO

MA

IN


Bu

rde

n o

f ill

ne

ss o

r p

rob

lem



Moderately frequent

frequent Very

frequent

In 5 studies from low-incidence countries (Shapiro et al 2012) the average number needed to screen (NNS) in people with diabetes was 1 276; in 5 studies from countries with a medium-to-high incidence it was 40 (Shapiro et al 2012). A systematic review of screening for TB in people with diabetes also reported a lower NNS in settings with a high background prevalence of TB and a tendency towards a lower NNS in people with more severe diabetes (Jeon et al 2010). The NNS for people who abuse drugs or alcohol ranged from 151 in 7 studies from settings with a low-to--moderate incidence to 20 in 2 studies from medium-incidence settings (Shapiro et al 2012); no study has been done in a setting with a high incidence . The weighted average NNS for people with a lesion previously identified by chest X-ray was 75 in 3 studies (Shapiro 2012). Recent prevalence surveys have consistently found that the prevalence of active TB increases with age, and the prevalence is higher in people older than 50-60 years than in the rest of the population (surveys from Bangladesh, China, Myanmar, Pakistan, the Philippines and Viet Nam). Elderly people account for a large proportion of the prevalence, and increase the total burden of TB in countries undergoing rapid demographic transition. However, there are no studies on the yield and impact of screening among elderly people attending health clinics. The incidence of TB in people with previous TB or a lesion seen on chest X-ray is much higher than in the general population. Okada (2012) found that the incidence of smear-positive TB was 0.67%/year in people with an abnormality seen on chest X-ray compared with 0.08%/year in people with a normal chest X-ray at baseline (relative risk, 8). Four studies (Shapiro 2012) looking

1 Baker MA et al. Systematic review: the impact of diabetes on tuberculosis treatment outcomes. BMC Medicine, 2011, 9:81 (doi:10.1186/1741-7015-9-81). 2 Hanrahan CF et al. Body mass index and risk of tuberculosis and death. AIDS, 2010, 24:1501–1508. Khan A et al. Lack of weight gain and relapse risk in a large tuberculosis treatment trial. American Journal of Respiratory and Critical Care Medicine, 2006, 174:344–348. Krapp F et al., Bodyweight gain to predict treatment outcome in patients with pulmonary tuberculosis in Peru. International Journal of Tuberculosis and Lung Disease, 2008, 12:1153–1159. Zachariah R et al., Moderate to severe malnutrition in patients with tuberculosis is a risk factor associated with early death. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2002, 96:291–294. Cegielski JP, McMurray DN. The relationship between malnutrition and tuberculosis: evidence from studies in humans and experimental animals. International Journal of Tuberculosis and Lung Disease, 2004, 8:286–298. 3 Rehm J et al. Alcohol consumption, alcohol use disorders and incidence and disease course of tuberculosis (TB) – is there a causal connection? BMC Public Health, 2009, 9:450 (doi:10.1186/1471-2458-9-450). 4 Waitt CJ, Squire SB. A systematic review of risk factors for death in adults during and after tuberculosis treatment. International Journal of Tuberculosis and Lung Disease, 2011, 15:871–885. 5 Figueroa-Damian R, Arredondo-Garcia JL. Neonatal outcome of children born to women with tuberculosis. Archives of Medical Research, 2001, 32:66–69. Bjerkedal T, Bahna SL, Lehmann EH. Course and outcome of pregnancy in women with pulmonary tuberculosis. Scandinavian Journal of Respiratory Diseases, 1975, 56:245–250.

Nhan-Chang CL, Jones TB. Tuberculosis in pregnancy. Clinical Obstetrics and Gynecology, 2010, 53: 311–321.

at other disease risk groups in low-incidence settings found an average NNS of 510 (range, 36–2846).

Is it severe?

Very mild


severe*


People with diabetes,1 people who are undernourished,2 people who abuse alcohol,3 injecting drug users ,4 patients with diseases that impair their immune system,4 and elderly people4 all have an increased risk of poor outcomes from TB treatment. Pregnant women with TB have a higher risk of complications for themselves and their infants than other pregnant women.5

Co

nfi

de

nce

in a

ccu

racy

of

the

dia

gn

ost

ic

te

st

What is the confidence in the accuracy of the diagnostic test?

Very low

Low Moderate High


weeks


abnormality)

Chest X-ray (TB-

related

abnormality)


TP Sensiti

vity

56% (40–74%)

OO Low

35% (24–46%)

OOO Very low

77% (68–86%)

OOO Very low

98% (95–

100%)

O Moderate

87% (79–95%)

OO Low FP

TN Specifi

city

80% (69–90%)

OO Low

95% (93–97%)

OO Low

68% (50–85%)

OOO Very low

75% (72–79%)

O Moderate

89% (87–92%)

OO Low FP


TP, true positive; FP, false positive; TN, true negative. For further details see the GRADE tables on the accuracy of diagnostic tests.

Be

ne

fits

an

d

ha

rms


No Yes


Screening

Diagnosi

s

Prevalence 0.5% (500/100 000)

Prevalence 1% (1 000/100 000)

Prevalence 2% (2 000/100 000)


Chest X-ray: any

abnormality

SSM+CD 1890 97610 156 688 1881 97119 312 1377 1862 96138 623

XP 245 99255 49 902 244 98756 98 1803 241 97759 197 197

Chest X-ray: TB

abnormalities

SSM+CD 815 98685 195 611 810 98190 389 1222 802 97198 778

XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399


SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506

XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353


XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580



SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555

XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417


SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024

XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722



No Yes



Very uncertain


certain Certain

Very certain


For further details see the GRADE tables. Impact on case detection Meijer (1971) reported on the contribution to overall case detection of routine screening with chest X-ray in chest clinics; screening included people with fibrotic lesions previously seen on X-ray and contacts of people with TB and people whose tuberculin skin test (TST) had recently converted. The studies were done in Canada (Ontario), the former Czechoslovakia (Kolin district) and the Netherlands at various times during the 1950s and 1960s. The proportion of all notified, bacteriologically confirmed cases detected through such screening was 10% (96/1020) in Canada, 34% (109/319) in the former Czechoslovakia and 20% (981/4872) in the Netherlands. The contribution of screening among people with a lesion seen previously on chest X-ray was not reported separately. Okada (2012) reported on the contribution of rescreening 2 years after a prevalence survey of people who had been identified with active TB and people with abnormalities seen on chest X-ray but without active TB in the initial survey. Among the 35 notified smear-positive cases (from 22 160 persons in the survey clusters) during the 2 years after the initial survey, 21 (60%) were identified by rescreening, including 1 (3%) relapsed case of cured TB and 20 (57%) cases among people who had had an abnormal chest X-ray but did not have active TB at the time of the initial survey. The weighted average contribution to overall case detection across all of the studies above is 19% of all bacteriologically confirmed, notified cases. There are no published studies on the contribution from screening to overall case detection in other risk groups within health facilities.



True positives

Benefit on case detection See text 4 cross-sectional OO Low




Benefit on transmission - 0 studies OOO Very low





Impact on time to diagnosis and severity at diagnosis No studies. Impact on treatment outcomes No studies. Impact on TB epidemiology No studies.

Co

nfi

de

nc

e i

n b

en

efi

ts

an

d

ha

rms


Very low

Low Moderate High

There is LOW QUALITY evidence that screening people with a previous lesion seen on chest X-ray contributes to overall case-detection rates. There is no such evidence for other clinical risk groups. There is no evidence about the impact of screening on delay to diagnosis and treatment outcomes. There is no evidence from published trials demonstrating an impact on case detection or on the epidemiology of TB. A GRADE table is presented only for people with a lesion previously seen on chest X-ray.

Va

lue

s


Very low

Low Moderate High

Very high

In two studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among people with diabetes was 94%; the range was 94–98%; and the median proportion was 96%. In six studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among pregnant women was 94%; the range was 68–96%; and the median proportion was 90%. In two studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among elderly people living in institutions was 72%; the range was 72–95%; and the median proportion was 83%. In three studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among people with drug dependencies was 93%; the range was 69–94%; and the median proportion was 89%. No studies assessed consent for screening among people with alcohol use disorders, malnourished people, smokers, and people with diseases that impair their immune system.

Re

so

urc

es

Is the cost low

relative to the

net benefits?

No Uncertain Yes

No cost–effectiveness analysis has been published.












Strongly recommend

Proposed options for recommendations and for discussion Option 1: There is no evidence to make a recommendation. Option 2: People with a known lesion seen on chest X-ray should be screened annually for active TB in settings with a moderate-to-high prevalence of TB (>100/100 000). Option 3: Systematic screening for active TB should be done in settings with a moderate-to-high TB prevalence (>100/100 000) among people seeking care for any reason who: (i) belong to one of the following risk groups for TB – people older than 60 years,; with previously known or suspected TB (including a lesion previously seen on chest X-ray), who are undernourished, who smoke, who have chronic obstructive pulmonary disease , who have diabetes; with alcohol or substance abuse disorders, with a disease or undergoing treatment that impairs their immune system, who are pregnant, or who work in health care; and (ii) have not been screened for TB during the preceding 6–12 months. These are conditional recommendations with very low quality evidence. NOTE: The only published evidence about the impact of screening in these risk groups concerns the contribution to case detection made by screening people with a lesion seen on a previous chest X-ray. Thus, there is an argument for making a recommendation only for this risk group. However, there are six reasons for recommending screening in all of these groups in settings where the burden of TB is very high despite a lack of evidence of an impact on morbidity and transmission:

1. early diagnosis and treatment of TB are essential parts of infection control in health facilities;8 2. the burden of undiagnosed TB among these risk groups is high in settings with a moderate-to-high prevalence of TB, and the NNS is therefore low, especially if a sensitive algorithm is

used for screening and diagnosis; 3. several of these groups are at higher risk of having poor outcomes from TB treatment; 4. the additional cost of screening is small in comparison with the additional cost of screening outside health-care facilities; 5. the acceptability of screening is likely to be high among patients; 6. access to further tests and specialist clinical evaluation is good when compared with screening done outside health facilities.

8 WHO policy on TB infection control in health-care facilities, congregate settings and households. Geneva, World Health Organization, 2009 (WHO/HTM/TB/2009.419).

Remarks for option 3

This recommendation concerns interventions that should be undertaken in addition to passive case-finding and the standard diagnostic work-up of people seeking care for symptoms compatible with TB.9 It may not be possible to implement this recommendation in resource-constrained settings. Individuals known to have TB or suspected of having TB and who are at a high risk for multidrug-resistant TB (MDR-TB) should have as their primary diagnostic test the Xpert MTB/RIF test. This group includes persons suspected of having pulmonary TB and considered to be at risk of harbouring MDR-TB bacilli (risk groups defined by national policies or as defined in WHO’s Guidelines for the programmatic management of drug-resistant TB,10 and persons who have been treated with anti-TB chemotherapy and in whom pulmonary TB has again been diagnosed – that is, patients in all retreatment categories (failure, default, relapse).11 All persons living with HIV who have signs or symptoms of TB, persons who are seriously ill and suspected of having TB regardless of their HIV status, and persons whose HIV status is unknown but who present with strong clinical evidence of HIV infection in settings where the prevalence of HIV is high should have as their primary diagnostic test the Xpert MTB/RIF.8 In settings with a high prevalence of HIV, counselling and testing for HIV should be offered to all people whose screening is positive for TB.12 There is no evidence on the appropriate interval between screenings. The suggested 6–12 month interval is arbitrary, and a different interval may be applied, or people may be eligible for screening at each health-care visit, a strategy that would simplify implementation. Screening people with lesions seen on chest X-ray can be done either in a chest clinic or specialist TB clinic, or in a general health facility. Other risk groups should be targeted within the clinic where their care is managed – for example, pregnant women can be screened at antenatal clinics or people with diabetes can be screened at the endocrinology department. Screening for TB in people with diabetes should be complemented by screening for diabetes in people with TB, see the Collaborative framework for care and control of TB and diabetes.13 Screening for TB in in smokers or people with chronic obstructive pulmonary disease should be complemented by screening for smoking in people with TB, see the monograph by WHO and the International Union Against Tuberculosis and Lung Disease.14 Screening for TB in people who abuse drugs or alcohol should be complemented by HIV screening in these groups and with screening for alcohol and drug abuse in people with TB, see the Policy guidelines for collaborative TB and HIV services for injecting and other drug users.15 Screening for TB in health facilities should be offered to all health-care staff and combined with other infection-control interventions, see the guidelines on infection control in health facilities.16 Concerning children: see remarks to Recommendation 7 in Section 8 in the guidelines.

9 Implementing the WHO Stop TB Strategy: a handbook for national tuberculosis control programmes. Geneva, World Health Organization, 2008 (WHO/HTM/TB/2008.401).

10 Guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update. Geneva, World Health Organization, 2011 (WHO/HTM/TB/2011.6). 11

Rapid implementation of the Xpert MTB/RIF diagnostic test: technical and operational ‘how-to’. Practical considerations. Geneva, World Health Organization, 2011 (WHO/HTM/TB/2011.2). 12

Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva, World Health Organization, 2011. 13

Collaborative framework for care and control of tuberculosis and diabetes. Geneva, World Health Organization, 2011 (WHO/HTM/TB/2011.15). 14

A WHO/The Union monograph on TB and tobacco control: joining efforts to control two related global epidemics. Geneva, World Health Organization, 2008 (WHO/TB/2007.390). 15 Policy guidelines for collaborative TB and HIV services for injecting and other drug users: an integrated approach. Geneva, World Health Organization, 2008 (WHO/HTM/TB/2008.404). 16

WHO policy on TB infection control in health-care facilities, congregate settings and households. Geneva, World Health Organization, 2009 (WHO/HTM/TB/2009.419).

Should screening for active TB be done in communities with a high burden of TB through door-to-door screening or through invitation for chest X-ray screening (high-intensity community screening)?

Patients:

Intervention:

Comparison:

Population in communities with a very high burden of TB

Door-to-door symptom screening or invitation for chest X-ray screening



Reducing TB morbidity, mortality and transmission Chemotherapy for active TB


DO

MA

IN


Bu

rde

n o

f ill

ne

ss o

r p

rob

lem



Moderately frequent

frequent Very

frequent

A systematic review of the number needed to screen (NNS) (Shapiro 2012) reported for community screening an average NNS (range) of:

3922 (137–30 865) in countries with a low incidence;

669 (15–5594) in countries with a moderate incidence;

601 (138–618) in countries with a medium incidence; and

100 (16–6355) in countries with a high incidence.

Is it severe?

Very mild


severe*


In principle, screening an entire community targets people who have an average risk of adverse outcomes and consequences from TB.If screening focuses on particularly vulnerable communities, it is likely to target people with TB who have a higher-than-average risk of both delayed diagnosis and adverse outcomes (including health, social and economic consequences) related to undiagnosed TB or to late diagnosis and treatment. In communities with high prevalences of both TB and HIV, a large proportion of people with TB are HIV-positive and therefore are particularly vulnerable to the negative effects of late diagnosis and treatment of TB.

Be

ne

fits

an

d

ha

rms


No Yes

Co

nfi

de

nce

In

acc

ura

cy o

f th

e d

iag

no

stic

te

st


Very low

Low Moderate High



weeks


abnormality)

Chest X-ray (TB-

related

abnormality)


TP Sensiti

vity

56% (40–74%)

OO Low

35% (24–46%)

OOO Very low

77% (68–86%)

OOO Very low

98% (95–

100%)

O Moderate

87% (79–95%)

OO Low FP

TN Specifi

city

80% (69–90%)

OO Low

95% (93–97%)

OO Low

68% (50–85%)

OOO Very low

75% (72–79%)

O Moderate

89% (87–92%)

OO Low FP




No Yes


Screening

Diagnosi

s

Prevalence 0.5% (500/100 000)

Prevalence 1% (1 000/100 000)

Prevalence 2% (2 000/100 000)


Chest X-ray: any

abnormality

SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623

XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197

Chest X-ray: TB

abnormalities

SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778

XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399


SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506

XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353


XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580



SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555

XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417


SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024

XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722


Overall, is there certainty about the link between the accuracy of the diagnostic test and the conquences?

Very uncertain


certain Certain

Very certain



RCT, randomized controlled trial.


Impact on case detection

Two randomized controlled trials have assessed the impact of community screening using door-to-door screening of households on the change in overall case detection. A trial in Brazil (Miller 2010) increased the case yield during the intervention but not overall during the entire period of the study, so the intervention seemed to affect the delay in diagnosis rather than the total number diagnosed. A trial in South Africa (Moyo 2012) followed a cohort of infants randomized to screening or passive case-finding, and found that case-finding was 2.6 times higher in the screened group.

Nine studies (Kranzer 2013) assessed the proportion of cases identified through screening on the total number of notified cases in the same population; the proportion identified through screening ranged from 14% to 85%.



True positives

Benefit on case detection See text 2 cluster RCTs 9 cross sectional

OO Low

Benefit on time to diagnosis See text 2 RCTs

OOO Very low


7 cross sectional OOO Very low

Benefit on treatment outcome No differences have been shown

3 cross sectional studies

OOO Very Low

Benefit on transmission See text 1 RCT I Longitudinal study

OOO Very low





Impact on delay in diagnosis and severity of disease at diagnosis

Two studies assessed different aspects of the impact of screening on the delay in diagnosis. A randomized controlled trial (RCT) from Brazil (Miller 2010) found no difference in the median delay in diagnosis between the intervention arm and the control arm. An RCT of household screening of infants found that the time to diagnosis was on average 3.4 months shorter in the screening arm (Moyo 2012).

Seven studies (den Boon 2008, Meijer 1971a, Meijer 1971, Meijer 1971c, Krivinka 1974, Meijer 1971, Moyo 2012) reported a lower proportion of sputum smear-positive cases in patients identified through screening compared with those identified by passive case detection; the difference in the percentage of smear-positive cases ranged from 10% to 27% fewer among those who had been screened.

Impact on treatment outcomes

Three studies – in India, Nepal and South Africa (Cassels 1982, Santha 2003, den Boon 2008) -- presented comparable data on treatment outcomes from cases identified through community screening compared with those identified through passive detection. In all studies the outcomes were similar.

Impact on epidemiology

Two studies assessed the epidemiological impact of door-to-door community screening. A community-based RCT in Zimbabwe (Corbett 2010) used door-to-door screening for symptoms. There was no control group without an intervention, so the comparison is the prevalence of TB in the communities before and after the intervention as assessed by surveys. The prevalence fell by 44% over 3 years in the door-to-door arm but the reduction was not statistically significant. The reduction was similar in areas covered by the different interventions, although the cumulative yield of cases during the intervention was higher in the mobile-van arm of this trial (see the Decision table on symptom screening by invitation to mobile or stationary units).The population of the area increased by 10% during the study period which may have affected the prevalence.

Okada (2012) reported on a follow-up study conducted in Cambodia 2 years after a national TB prevalence survey to capture incident TB cases in communities previously screened for TB as part of the national survey. The standardized TB notification ratio was 0.38 (95% confidence interval, 0.27–0.52) in the 2012 study, showing a two thirds reduction in notification in the study areas compared with what would have been expected if the communities had followed the national notification trend.

Co

nfi

de

nc

e I

n b

en

efi

ts

an

d

ha

rms


Very low

Low Moderate High

There is LOW QUALITY evidence that door-to-door and other intensive community screening interventions lead to increased case detection; and there is VERY LOW QUALITY evidence that these interventions reduce the delay in diagnosis. There is VERY LOW QUALITY evidence that treatment outcomes are similar among those screened compared with those identified by passive case-finding; and there is VERY LOW QUALITY evidence that intense community screening could have an impact on TB epidemiology.

Va

lue

s


Very low

Low Moderate High

Very high

In 11 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among residents in poor urban areas was 91%; the range was 59–99%; and the median proportion was 88%. In nine studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening in indigenous populations was 69%; the range was 40–97%; and the median proportion was 89%.

RE

SO

UR

CE

S

Is the cost low

relative to the

net benefits?

No Uncertain Yes

No cost–effectiveness analysis of community screening has been published.












Strongly recommend

Proposed options for discussion Option 1: There is insufficient evidence to make any recommendation. Option 2: Door- to-door screening or other intense community screening should be considered in subpopulations estimated to have a very high prevalence of undetected TB (>0.5–1%) if other interventions have been shown to be insufficient to improve early detection of TB. For option2: This is a conditional recommendation with very low quality evidence.

Remarks for proposed option 2 In order to improve the efficiency of screening and reduce the risk of high numbers of false-positive cases even in settings with a high prevalence of TB only the highest risk subpopulations should be targeted; these subpopulations include residents of urban slums, homeless people, people living in remote areas, indigenous populations, migrants and other vulnerable groups,. It may not be possible to implement this recommendation in resource-constrained settings.

Community members may be screened for symptoms, or offered a chest X-ray. In settings with a high prevalence of HIV, counselling and testing for HIV should be offered to all people who are screened and found positive for TB.

Children aged ≥10 years should be screened using the algorithm for adults. No study has specifically assessed the sensitivity and specificity of screening algorithms for children and adolescents who are not contacts of people with TB. The panel believes that the screening algorithm for adults is likely to have similar precision in adolescents. However, the prevalence of undiagnosed TB is likely to be lower, thereby adversely affecting the test’s performance and the risk–benefit ratio. Screening for symptoms and using chest X-rays in children aged <10 years is likely to have low specificity since pulmonary TB is a relatively rare cause of lower respiratory symptoms and signs, which are common in this age group. A large number of young children who do not have TB would need further investigations for TB if they were systematically screened as part of general screening in their community. Furthermore, since most confirmatory, diagnostic TB tests have a lower sensitivity in young children than in adults, the final diagnosis would be uncertain for many of the children who had further evaluations, likely resulting in a high number of false-positive cases. The panel thus judges that there is a risk of doing more harm than benefit in children aged <10 years. The situation is different when contacts are being investigated, since this type of investigation targets children with a higher prevalence of TB and also aims to rule out TB in children aged <5 years who are eligible for treatment of latent TB infection (see WHO’s recommendations on contact investigations).3 To the extent possible, community screening should be combined with other screening, health-promotion activities or social support . When screening is done in refugee camps among displaced populations, consult the guidelines on tuberculosis care and control in refugee and displaced populations for recommendations on TB management and operational aspects.4


(WHO/HTM/TB/2012.9). 4 Tuberculosis care and control in refugee and displaced populations: an interagency field manual, 2nd ed. Geneva, World Health Organization, 2007 (WHO/HTM/TB/2007.377).

Should screening for active TB be done in communities that have a high burden of TB by inviting people to mobile or stationary facilities to be screened for symptoms and for sputum collection (low- to moderate-intensity community screening)?

Patients:

Intervention:

Comparison:

Populations in communities with a very high burden of TB

Symptom screening and sputum collection





DO

MA

IN


Bu

rde

n o

f Il

lne

ss o

r pr

ob

lem



Moderately frequent

frequent Very

frequent

A systematic review of the number needed to screen (NNS) (Shapiro 2012) reported for community screening an average NNS (range) of:

3922 (137–30865) in countries with a low incidence;


601 (138–618) in countries with a medium incidence; and

100 (16–6355) in countries with a high incidence.

Is it severe?

Very mild


severe*


In principle, screening an entire community targets people who have an average risk of adverse outcomes and consequences from TB. If screening focuses on particularly vulnerable communities, it is likely to target people with TB who have a higher-than-average risk of both delayed diagnosis and adverse outcomes (including health, social and economic consequences) related to undiagnosed TB or to late diagnosis and treatment. In communities with high prevalences of both TB and HIV, a large proportion of people with TB are HIV-positive and therefore are particularly vulnerable to the negative effects of late diagnosis and treatment of TB.

Co

nfi

de

nce

In

acc

ura

cy o

f th

e d

iag

no

stic

te

st


Very low

Low Moderate High

Sensitivity and specificity (based on van’ t Hoog et al 2012) Outcome Any cough Cough lasting >2

weeks Any symptom Chest X-ray (any

abnormality) Chest X-ray (TB-

related abnormality)


TP Sensiti

vity

56% (40–74%)

OO Low

35% (24–46%)

OOO Very low

77% (68–86%)

OOO Very low

98% (95–

100%)

O Moderate

87% (79–95%)

OO Low FP

TN Specifi

city

80% (69–90%)

OO Low

95% (93–97%)

OO Low

68% (50–85%)

OOO Very low

75% (72–79%)

O Moderate

89% (87–92%)

OO Low FP



Be

ne

fits

an

d

ha

rms


No Yes


Screening

Diagnosi

s

Prevalence 0.5% (500/100 000)

Prevalence 1% (1 000/100 000)

Prevalence 2% (2 000/100 000)


Chest X-ray: any

abnormality

SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623

XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197

Chest X-ray: TB

abnormalities

SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778

XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399


SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506

XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353


XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580



SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555

XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417


SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024

XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722



No Yes


Very uncertain


certain Certain

Very certain



RCT, randomized controlled trial. For further details see the GRADE tables.


Three randomized controlled trials (RCTs) have assessed the impact on the change in overall case detection using outreach clinics or outreach workers to identify people who have symptoms of TB and to collect sputum samples in health facilities or in the community. One trial showed a positive and statistically significant impact (Datiko 2009); one showed a positive but not statistically significant impact (Shargie 2006b); and one showed no impact (Ayles 2012). One observational study assessed the proportion of cases identified through temporary camps set up to perform microscopy in remote villages; these camps accounted for 6% of the total cases notified (Harper 1996). Impact on delay in diagnosis and severity of disease at diagnosis One cross-sectional study from Ethiopia (Shargie 2006a) found a 4% lower proportion of participants who had a delay in diagnosis >90 days among those who were screened (54% of those who were screened had a delayed diagnosis versus 58% of those who were not screened). The difference was not statistically significant. A community-based RCT from Ethiopia (Shargie 2006b) found that the proportion of participants whose diagnosis was delayed by >90 days was 22% lower in communities where screening took place (41% had a delay in screened communities versus 63%), and the difference was statistically significant. Impact on treatment outcomes Two studies -- one in Nepal and one in Zambia (Harper 1996, Ayles 2012) -- presented comparable data on treatment outcomes from cases found through community screening compared with those identified by passive detection. There was no difference in outcomes in either of the studies.



True positives

Benefit on case detection Not pooled 3 RCTs OOO Very low

Benefit on time to diagnosis Reduced in both studies 1 cluster RCT 1 cross sectional

OO Low


Benefit on treatment outcome Neither study found a difference

2 cross sectional studies

OOO Very Low

Benefit on transmission One study found a reduction and one did not

2 cluster RCTs OOO Very low





Impact on epidemiology Two studies assessed the epidemiological impact of community screening. A community-based RCT in Zimbabwe (Corbett 2010) used mobile vans to make public announcements inviting people with cough to be tested. Testing used sputum-smear microscopy. There was no control group that did not receive an intervention, so the comparison is the prevalence of TB in communities before and after the intervention as assessed by surveys. There was a 38% reduction in prevalence over 3 years, but the decline was not statistically significant. The population of the area increased by 10% during the study period, which may have affected the prevalence. A community-based RCT in Zambia found no impact from providing health information with decentralized sputum-collection points, symptom screening and sputum collection during health camps (Ayles 2012).

Co

nfi

de

nc

e i

n b

en

efi

ts

an

d

ha

rms


Very low

Low Moderate High

There is VERY LOW QUALITY evidence that community screening leads to increased case detection; there is LOW QUALITY evidence that community screening may reduce the delay in diagnosis. There is VERY LOW QUALITY evidence that treatment outcomes are similar in those screened compared with those detected by passive case-finding; there is MODERATE QUALITY evidence that providing health information along with decentralized sputum-collection points, symptom screening and sputum collection during health camps has no impact on the epidemiology of TB. There is VERY LOW QUALITY evidence that more intense symptom screening through use of mobile vans may have an impact on the epidemiology of TB.

Va

lue

s


Very low

Low Moderate High

Very high

In 11 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among residents in poor urban areas was 91%; the range was 59–99%; and the median proportion was 88%. In nine studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo screening in indigenous populations was 69%; the range was 40–97%; and the median proportion was 89%.

Re

so

urc

es

Is the cost low

relative to the

net benefits?

No Uncertain Yes









Recommendation Strongly recommend

against Conditionally recommend

against Do not make recommendation (use this

option very rarely if evidence is too sparse) Conditionally recommend

Strongly recommend

Proposed options for discussion Option 1: There is insufficient evidence to make any recommendation. Option 2: Inviting people to TB screening at a mobile facility or fixed facility should be considered in subpopulations estimated to have a very high prevalence of undetected TB (>0.5–1%) if other interventions have been shown to be insufficient to improve the early detection of TB. For both options: This is a conditional recommendation with very low-quality evidence.

Remarks for proposed option 2 To improve the efficiency of screening and reduce the risk of high numbers of false-positives even in settings with a high prevalence of TB, only the highest risk subpopulations should be targeted; these settings include urban slums, areas where homeless people congregate, remote areas with difficult access, and areas with indigenous populations, migrants or other vulnerable groups. Even if highly focused, it may not be possible to implement this recommendation in resource-constrained settings.

People can be invited for screening by providing general health information or through face-to-face interaction (by going door to door, by establishing health camps and through other outreach activities). If people are invited through face-to-face interaction, screening for cough lasting >2 weeks or haemoptysis, as well as collecting sputum for sputum-smear microscopy or Xpert MTB/RIF testing, can be done at the place of interaction. A second screening with a chest X-ray, as well as diagnosis using the Xpert MTB/RIF test, can be done in mobile facilities or fixed facilities. In settings with a high prevalence of HIV, counselling and testing for HIV should be offered to all people who are screened and found positive for TB. Children aged ≥10 years should be screened using the algorithm for adults. No study has specifically assessed the sensitivity and specificity of screening algorithms for children and adolescents who are not contacts of people with TB. The panel believes that the screening algorithm for adults is likely to have similar precision in adolescents. However the prevalence of undiagnosed TB is likely to be lower, thereby adversely affecting the test’s performance and the risk–benefit ratio. Screening for symptoms and using chest X-rays in children aged <10 years is likely to have low specificity since pulmonary TB is a relatively rare cause of lower respiratory symptoms and signs, which are common in this age group. A large number of young children who do not have TB would need further investigations for TB if they were systematically screened as part of general screening in their community. Furthermore, since most confirmatory, diagnostic TB tests have a lower sensitivity in young children than in adults, the final diagnosis would be uncertain for many of the children who had further evaluations, likely resulting in a high number of false-positive cases. The panel thus judges that there is a risk of doing more harm than benefit in children aged <10 years. The situation is different when contacts are being investigated, since this type of investigation targets children with a higher prevalence of TB and also aims to rule out TB in children aged <5 years who are eligible for treatment of latent TB infection (see WHO’s recommendations on contact investigations).3


(WHO/HTM/TB/2012.9).

Should screening for active TB be undertaken in communities with a very high burden of TB?

Note: This Decision table combines door-to-door screening and screening by inviting people to mobile or stationary facilities to be screened for symptoms and for sputum collection and, in communities with a high burden of TB. The panel may develop a combined recommendation for the two approaches, separate recommendations, recommendations for either, both, or none of the approaches.

Patients:

Intervention:

Comparison:

Population in communities with a very high burden of TB

Symptom screening, chest X-ray screening, or both; door-to-door or by

invitation




Note: See systematic reviews for full references to cited papers

DO

MA

IN


Bu

rde

n o

f ill

ne

ss o

r p

rob

lem



Moderately frequent

frequent Very

frequent

A systematic review of the number needed to screen (NNS) (Shapiro 2012) reported for community screening an NNS (range) of:

3922 (137–30 865) in countries with a low incidence;


601 (138–618) in countries with a medium incidence ; and

100 (16–6355) in countries with a high incidence .

Is it severe?

Very mild


severe*


In principle, screening an entire community targets people who have an average risk of adverse outcomes and consequences from TB. If screening focuses on particularly vulnerable communities, it is likely to target people with TB who have a higher-than-average risk of both delayed diagnosis and adverse outcomes (including health, social and economic consequences) related to undiagnosed TB or to late diagnosis and treatment. In communities with high prevalences of both TB and HIV, a large proportion of people with TB are HIV-positive and therefore are particularly vulnerable to the negative effects of late diagnosis and treatment of TB.

Co

nfi

de

nce

in

acc

ura

cy o

f th

e

dia

gn

ost

ic

te

st


Very low

Low Moderate High

Sensitivity

and

specificity

(based on

van t’Hoog

et al 2012)

Outcome

Any cough Cough lasting >2

weeks


abnormality)

Chest X-ray (TB-

related

abnormality)


TP Sensitivity

56% (40-

OO [Should

35% (24–

OOO Very low

77% (68–

OOO Very low

98% (95–

O Moderate

87% (79–

OO Low FP

Be

ne

fits

an

d

ha

rms


No Yes

Modelled yiled of different algorithms based on point estimates from the systematic review of accuracy of screening tools (van’t Hoog et al 2012), and systematic reviews of accuracy of sputum-smear microscopy1 and the Xpert MTB/RIF test.2

Screening

Diagnosi

s

Prevalence 0.5% (500/100 000)

Prevalence 1% (1 000/100 000)

Prevalence 2% (2 000/100 000)


Chest X-ray: any

abnormality

SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623

XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197

Chest X-ray: TB

abnormalities

SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778

XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399


SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506

XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353


74%) [95% CI?]

this designation be explain

ed anywhe

re?] Low

46%) 86%) 100%) 95%)

TN Specifi

city

80% (69–90%)

OO Low

95% (93–97%)

OO Low

68% (50–85%)

OOO Very low

75% (72–79%)

O Moderate

89% (87–92%)

OO Low FP


For further details see GRADE tables on the accuracy of diagnostic tests.


No Yes


XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580

Cough lasting >2–3 weeks plus [OK?] chest X-ray

SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555

XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417

Any symptom plus [OK?] chest X-ray

SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024

XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722


Direct assessment of outcomes fof screening (Kranzer 2012)

RCT, randomized controlled trial.



Four randomized controlled trials (RCTs) have assessed the impact of community screening on changes in the overall case-detection rate; two used door-to-door screening of households and two used outreach clinics or outreach workers to identify people with TB symptoms and collect sputum samples in health facilities or in the community. All four showed a positive impact on case-detection rates. A trial in Brazil (Miller 2010)using door-to-door screening increased the case yield during the intervention but not overall during the entire period of the study so the intervention seemed to affect the delay in diagnosis rather than the total number diagnosed. A

Overall, is there certainty of the link between the diagnostic test accuracy information and the con-sequences?

Very uncertain


certain Certain

Very certain



True positives

Benefit on case detection All four trials showed a benefit

4 cluster RCTs 10 cross-sectional

O Moderate

Benefit on time to diagnosis See text 3 cluster RCTs 1 cross sectional

OOO Very low


9 cross sectional OOO Very low

Benefit on treatment outcome No benefits seen 6 cross sectional OOO Very Low

Benefit on transmission See text 2 RCTs 1 Cohort

OO Low





trial in South Africa (Moyo 2012) followed a cohort of infants randomized to screening or passive case–finding, and found that case-finding was 2.6 times higher in the screened group. Two Ethiopian studies used community health-workers in different ways to increase case-finding and diagnosis. One of the Ethiopian studies (Shargie 2006) used preadvertised outreach clinics; the other (Datiko 2009) worked to increase awareness of TB and TB symptoms and make it easier to collect sputum samples. Both studies found higher case rates in the intervention communities: 27 more cases were detected per 100 000 population in the first study and 53 more cases were detected in the second study. However in the study by Shargie (2006) the difference was not statistically significant. The two Ethiopian studies focused primarily on delivering health information and decentralizing sputum collection; the actual method of identifying people with TB symptoms was not clearly described. Impact on delay in diagnosis and severity of disease at diagnosis Four studies have assessed different aspects of the impact of screening on the delay in diagnosis. Two studies assessed the difference in self-reported delay between patients identified through screening and those identified through passive detection. One cross-sectional study from Ethiopia (Shargie 2006a) found a 4% decrease in the proportion of participants who had a delay in diagnosis >90 days among those who were screened (54% of those who were screened had a delayed diagnosis versus 58% of those who were not screened). The difference was not statistically significant. A community-based RCT from Ethiopia (Shargie 2006b) found that the proportion of participants whose diagnosis was delayed by >90 days was 22% lower in communities where screening took place (41% in screened communities versus 63%), and the difference was statistically significant. An RCT from Brazil (Miller 2010) found no difference in median delay between the intervention arm and the control arm. An RCT of household screening in infants found that the time to diagnosis was on average 3.4 months shorter in the screening arm (Moyo 2012). Two studies – one from South Africa (den Boon 2008) and one from Cambodia (Eang 2012) – reported a lower proportion of sputum smear-positive cases in patients identified through screening than in patients detected through passive case-finding: 67% versus 94% in the South African study, and 29% versus 60% in the Cambodian study. These studies also assessed smear grade in smear-positive cases, and found that the proportion of cases with smears graded 3+ was 57% lower in South Africa and 11% lower in Cambodia among those detected through screening than in other smear-positive patients. A lower proportion of smear-positive cases may reflect the use of screening and diagnostic tools that are more sensitive in diagnosing culture-positive TB rather than the impact of community screening itself. Furthermore, smear-positive TB does not necessarily indicate that a patient had a longer delay before being diagnosed than someone with smear-negative TB: the difference in smear grade is more likely to reflect the impact of community screening on early detection. Impact on treatment outcomes Six studies -- two in Nepal, one in Cambodia, one in India, one in South Africa and one in Zambia (Cassels 1982, Harper 1996, Eang 2012, Santha 2003, den Boon 2008, and Ayles 2012) -- presented comparable data on treatment outcomes in cases found through community screening and those identified through passive detection. In all six studies, the outcomes were similar, and a meta-analysis of these studies gave a pooled relative risk of 1.0 (95% confidence interval, 0.98-1.02) (Kranzer 2012) with low heterogeneity (I2, 0%). Impact on epidemiology Three studies assessed the epidemiological impact of community screening.

A community-based RCT [OK to say RCT?] in Zimbabwe (Corbett 2010) used two different case-finding interventions (mobile vans or door-to-door screening for symptoms). There was no control group that did not receive an intervention, so the comparison is the prevalence of TB in the communities before and after the interventions; this was assessed by surveys. The prevalence fell by 40% over 3 years for both arms combined but the reduction was not statistically significant. The reduction was similar in areas covered by the different interventions, although the cumulative yield of cases during the intervention was higher in the mobile-van group. The population of the area increased by 10% during the study period which may have affected the prevalence. Okada (2012) reported on a follow-up study conducted in Cambodia 2 years after a national TB prevalence survey to capture incident TB cases in communities previously screened for TB as part of the national survey. The standardized TB notification ratio was 0.38 (95% confidence interval, 0.27–0.52) in the 2012 study, showing a two thirds reduction in notification in the study areas compared with what would have been expected if the communities had followed the national notification trend. A community-based RCT in Zambia found no impact on TB epidemiology of an intervention delivering health information that was combined with decentralized sputum-collection points and sputum collection during health camps (Ayles 2012).

Co

nfi

de

nc

e i

n b

en

efi

ts

an

d h

arm

s


Very low

Low Moderate High

There is MODERATE QUALITY evidence that community screening leads to increased case detection; and there is VERY LOW QUALITY evidence that community screening reduces the delay in diagnosis. There is VERY LOW QUALITY evidence that treatment outcomes are similar among those screened compared with those identified by passive case-finding. There is MODEARTE evidence that health information with decentralized sputum-collection points, symptom screening and sputum collection during health camps has no impact on the epidemiology of TB; and there is LOW QUALITY evidence that more intense community screening may have an impact on the epidemiology of TB.

Va

lue

s


Very low

Low Moderate High

Very high

Community-based screening had high participation rates, ranging from 2% to 99% of eligible individuals. The average participation rate was 82% ± 0.2 (interquartile range, 80–95%). Acceptability ranged from 12% to 100%, with a median of 90%. In 47 studies (Mitchell 2012), the weighted average of eligible persons who consented to undergo TB screening in the general community was 82%; the range was 2–99%; and the median proportion was 90%. In 11 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among residents in poor urban areas was 91%; the range was 59–99%; and the median proportion was 88%. In nine studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening in indigenous populations was 69%; the range was 40–97%; and the median proportion was 89%.

Re

so

urc

es

Is the cost small

[low?] relative to

the net benefits?

No Uncertain Yes











Do not make recommendation (use this option rarely if evidence is sparse)


Strongly recommend

We decide – Proposed options for discussions: option 1: There is insufficient evidence to make any recommendation; option 2: Community screening for active TB should be considered in subpopulation estimated to have a very high prevalence of undetected TB (>0.5–1%) if other interventions have been shown to be insufficient to improve the early detection of TB. For option 2: This is a conditional recommendation with very low quality evidence.

Remarks for option 2 To improve the efficiency of screening and reduce the risk of high numbers of false-positives even in settings with a high prevalence of TB only the highest risk subpopulations should be targeted; these settings include urban slums, areas where homeless people congregate, remote areas with difficult access, and areas with indigenous populations, migrants or other vulnerable groups. Even if highly focused it may not be possible to implement this recommendation in resource-constrained settings.

People can be invited for screening by providing general health information or through face-to-face interaction (by going door to door, by establishing health camps, and through other outreach activities). If people are invited through face-to-face interaction, screening for symptoms , as well as collecting sputum for sputum-smear microscopy or Xpert MTB/RIF testing, can be done at the place of interaction. A second screening with a chest X-ray, as well as diagnosis using Xpert MTB/RIF testing, can be done in mobile facilities or fixed facilities.

When the prevalence of rifampicin resistance in the screened population is <10% , an Xpert MTB/RIF result that is positive for rifampicin should be confirmed by conventional drug-susceptibility testing or line probe assay.3 In settings with a high prevalence of HIV, counselling and testing for HIV should be offered to all people who are screened and found positive for TB.

Children aged ≥10 years should be screened using the algorithm for adults. No study has specifically assessed the sensitivity and specificity of screening algorithms for children and

adolescents who are not contacts of people with TB. The panel believes that the screening algorithm for adults is likely to have similar precision in adolescents. However the prevalence of undiagnosed TB is likely to be lower, thereby adversely affecting the test’s performance and the risk–benefit ratio. Screening for symptoms and using chest X-rays in children aged <10 years is likely to have low specificity since pulmonary TB is a relatively rare cause of lower respiratory symptoms and signs, which are common in this age group. A large number of young children who do not have TB would need further investigations for TB if they were systematically screened as part of general screening in their community. Furthermore, since most confirmatory, diagnostic TB tests have a lower sensitivity in young children than in adults, the final diagnosis would be uncertain for many of the children who had further evaluations, likely resulting in a high number of false-positive cases. The panel thus judges that there is a risk of doing more harm than benefit in children aged <10 years. The situation is different when contacts are being investigated, since this type of investigation targets children with a higher prevalence of TB and also aims to rule out TB in children aged <5 years who are eligible for treatment of latent TB infection (see WHO’s recommendations on contact investigations).4 To the extent possible, community screening should be combined with other screening, health-promotion activities or social support. When screening is done in refugee camps among displaced populations, consult the guidelines on tuberculosis care and control in refugees and displaced populations for recommendations on TB management and operational aspects.5

3 Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF system. Policy statement: Geneva, World Health Organization, 2011 (WHO/HTM/TB/2011.4). 4 Recommendations for investigating the contacts of persons with infectious tuberculosis in low- and middle-income countries. Geneva, World Health Organization, 2012

(WHO/HTM/TB/2012.9). 5 Tuberculosis care and control in refugee and displaced populations: an interagency field manual, 2nd ed. Geneva, World Health Organization, 2007 (WHO/HTM/TB/2007.377).

Should systematic screening for active TB be done routinely in homeless people and people in shelters, including drug users?

Patients:


Comparison:

Homeless people and people in shelters, including drug users




Reducing TB morbidity, mortality and transmission Treatment of active TB; treatment of latent TB infection in countries where this is the policy for homeless people who are contacts of someone with active TB


1 Beijer U, Wolf A, Fazel S. Prevalence of tuberculosis, hepatitis C virus, and HIV in homeless people: a systematic review and meta-analysis. Lancet Infectious Diseases, 2012, 12:859–870.

DO

MA

IN


Bu

rde

n o

f ill

ne

ss o

r p

rob

lem



Moderately frequent

frequent Very

frequent

From 18 studies in countries with a low incidence of TB Shapiro (2012) reported a weighted mean number needed to screen (NNS) of 133 (range, 22–1778). Screening programmes using chest X-rays reported significantly higher prevalences than those using other screening tools. A systematic review of 17 studies of the prevalence of TB in homeless people as reported by TB-screening programmes targeting this group1 reported a range of 0.2–7.7% in low-incidence settings. The weighted average was 1.1% (95% confidence interval, 0.8–1.5%), but there was significant heterogeneity.

Is it severe?

Very mild


severe*


There is a high prevalence of risk factors for TB transmission in this group, as well as a high risk of progression to active TB and poor treatment outcomes. Homeless people are among the groups with the poorest access to health services.

C

on

fid

en

ce i

n a

ccu

racy

of

the

dia

gn

ost

ic

te

st


Very low

Low Moderate High



weeks


abnormality)

Chest X-ray (TB-

related

abnormality)


TP Sensiti

vity

56% (40–74%)

OO Low

35% (24–46%)

OOO Very low

77% (68–86%)

OOO Very low

98% (95–

100%)

O Moderate

87% (79–95%)

OO Low FN

TN Specifi

city

80% (69–90%)

OO Low

95% (93–97%)

OO Low

68% (50–85%)

OOO Very low

75% (72–79%)

O Moderate

89% (87–92%)

OO Low FP

TP, true positive; FP, false positive; TN, true negative. For further details see the GRADE tables on the accuracy of diagnostic tests.

Be

ne

fits

an

d h

arm

s


No Yes


Screening

Diagnosi

s

Prevalence 0.5% (500/100 000)

Prevalence 1% (1 000/100 000)

Prevalence 2% (2 000/100 000)


Chest X-ray: any

abnormality

SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623

XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197

Chest X-ray: TB

abnormalities

SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778

XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399


SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506

XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353


XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580



SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555

XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417


SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024

XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722



No Yes


Be

ne

fits

an

d

ha

rms


Very uncertain


certain Certain

Very certain


For further details see the GRADE tables. Impact on case detection A study in Rotterdam (de Vries 2007) reported that 5% of all notified cases were detected by screening homeless people. There are no published controlled trials assessing the impact of screening homeless people on overall case detection. Impact on time to diagnosis and severity at diagnosis Three studies, all conducted in low-burden settings, reported between 32% and 55% fewer smear-positive cases among homeless people who had been screened than among homeless people with TB detected through passive case-finding (Ross 1977, Capewell 1986, Story 2008). Ross (1977) also reported 58% fewer patients with severe findings on chest X-ray among homeless people who had been screened. Impact on treatment outcomes No study was identified. Impact on epidemiology A study in the United States evaluated a programme of mandatory screening combined with mandatory prophylaxis and treatment for people wanting to use homeless shelters (Rendelman 1999). Trends in TB in the district studied fell by almost 90% over 10 years. The incidence of TB statewide was much lower, but the incidence did not fall during the same period as the intervention. It was not possible to isolate the effect of screening for active TB from the effect of chemoprophylaxis. The population of the district



True positives

Benefit on case detection 5% of all detected cases 1 cross-sectional OOO Very low

Benefit on time to diagnosis Delay 3x longer with passive detection

0 studies OOO Very low

Benefit on severity at diagnosis Less likely to be smear-positive at diagnosis

3 cross-sectional OOO Very low


Benefit on transmission Reduction in incidence over time

2 longitudinal OOO Very low





changed during the study period as a result of gentrification, and this may have contributed to some of the fall in incidence. One study (de Vries 2007) reported trends in TB after mobile chest X-ray screening was introduced for homeless people and drug users in Rotterdam between 2002 and 2005; this was initiated after a rapid increase in the incidence of TB in these groups. The incidence within the risk group fell by 54%; and the proportion of cases contributed to the overall incidence from homeless people and drug users in the city fell from 16% to 8% (de Vries 2007).

Co

nfi

de

nc

e i

n b

en

efi

ts

an

d h

arm

s


Very low

Low Moderate High

There is VERY LOW QUALITY evidence that screening homeless people could improve case detection, identify cases earlier and reduce the burden of TB within the risk group and in the general community.

All evidence is from low-burden settings.

va

lue

s


Very low

Low Moderate High

Very high

In five studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among homeless people was 96%; the range was 41–97%; and the median proportion was 75%.

Re

so

urc

es

Is the cost low

relative to the

net benefits?

No Uncertain Yes

No cost–effectiveness analysis based on empirical data has been published.












Strongly recommend

Options for recommendations and for discussion Option 1: There is not enough evidence to make a recommendation. Option 2: Systematic screening for active TB should be done in homeless people and people in shelters, and should include drug users, in intermediate-to-low burden settings where these risk groups contribute a significant proportion to the notified cases or when there are indications of an outbreak among these groups. For option 2: This is a conditional recommendation with very low quality evidence. NOTE: While direct evidence is very weak about the impact of screening in homeless people on morbidity and transmission, there are several reasons to conditionally recommend such screening:

homeless people are among the highest risk group for TB in all settings, and in low-burden settings with a concentrated TB epidemic they may account for a significant proportion of all cases;

homeless people are at particularly high risk of having poor access to health services, and may not use the services that are available. For many health conditions, they are among the most vulnerable groups;

in some countries, homeless people who are a close contact of someone with active TB are eligible for treatment of latent TB infection. Screening for active disease would have the added benefit of identifying people eligible for treatment of latent infection.

Remarks

This recommendation applies to settings with an intermediate burden or a low burden where these risk groups account for a significant proportion of notified cases or when there are indications of an outbreak occurring among them. In settings with a very high prevalence of TB, homeless people should be prioritized for screening (see Recommendation 7 in Section 8 in the guidelines). In settings with high a prevalence of HIV, counselling and testing for HIV should be offered to all people whose screening is positive for TB).4 There is no evidence on the appropriate interval between screenings. Screening may done continually, at time of entry into a homeless shelter, or through outreach campaigns at annual or other intervals. To the extent possible, screening should be integrated with other outreach screening, health-promotion activities and social support.


Documents

Should household contacts and other close contacts of a · PDF fileShould household contacts and other close contacts of a person with active TB be systematically screened for active