Decision Tables Screening PDF

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

Screening intervention: Symptom screening, chest X-ray screening, or both
Comparison: Passive case-finding
Implied purpose: Reducing TB morbidity, mortality and transmission

Linked treatment: 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.
DOMAI
CRITERIA JUDGEMENT EVIDENCE COMMENTS

N
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
Very
Infrequent
Moderately
frequent
Very
settings, the weighted-average prevalence of all types of active TB among close contacts or household contacts was 1.4% (95%
Is it frequent? infrequent frequent frequent
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
Burden of illness or problem
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).
Hosehold contacts and other close contacts of a person with active TB have a high risk of becoming infected. People who have
Very
mild moderate severe
Very been recently infected with TB have a higher risk of progressing to active disease in the near future compared with people who
mild severe*
have distant latent TB infection.
Is it severe?     
*e.g. life threatening or disabling
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.
1
Fox G et al. Contact investigation for tuberculosis: a systematic review and meta analysis. European Respiratory Journal, 2013, 4:140–156.
Sensitivity and specificity (based on van’t Hoog et al 2012)
Confidence In accuracy of the diagnostic
Outcome Any cough Cough lasting >2 Any symptom Chest X-ray (any Chest X-ray (TB-
weeks abnormality) related
What is the Very
Low Moderate High abnormality)
low
confidence in the
test
    Effect Quality Effect Quality Effect Quality Effect Quality Effect Quality
accuracy of the
diagnostic test ? TP
Sensiti
56%
OO
35%
OOO
77%
OOO
98%
O
87%
OO
(40– (24– (68– (95– (79–
FP vity Low Very low Very low Moderate Low
74%) 46%) 86%) 100%) 95%)
TN 80% 95% 68% 89%
Specifi OO OO OOO 75% O OO
(69– (93– (50– (87–
FP city Low Low Very low (72–79%) Moderate Low
90%) 97%) 85%) 92%)
TP, true positive; FP, false positive; TN, true negative.
For further details see the GRADE tables on the accuracy of diagnostic tests.
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
Prevalence 0.5% Prevalence 1% Prevalence 2%

Screening Diagnosi (500/100 000) (1 000/100 000) (2 000/100 000)
Overall, s TP FP TN FN TP FP TN FN TP FP TN FN
are the No Yes Chest X-ray: SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623
anticipated   any
desirable effects abnormality XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197
large?
Chest X-ray: SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778
TB
abnormalities XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399
Cough lasting SSM+CD 124 407 99093 376 247 405 98595 753 494 401 97599 1506
>2–3 weeks XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353
B enefi ts a nd har m s
SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916
Any symptom
XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580
Overall,
are the No Yes 1. Cough SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555
anticipated   lasting >2–3
undesirable weeks. 2. XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417
effects small? Chest X-ray
1. Any SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024
symptom. 2.
Chest X-ray 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
Overall, is there MTB/RIF test; CD, clinical diagnosis.
certainty of the
link between the Very
uncertain
Moderately
Certain
Very
uncertain certain certain
accuracy of the
diagnostic test     
and the
consequences?
2Approaches to improve sputum smear microscopy for tuberculosis diagnosis: expert group meeting report. Geneva, World Health Organization, 2009.
3Automated 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)
Summary of findings
Diagnostic category Potential effect
Effect No. of studies Quality
Benefit on case detection Contact tracing contributed 5 cross-sectional OOO
2 to 19% of all cases studies Very low
Benefit on time to diagnosis - 0 studies OOO
Very low
Benefit on severity at diagnosis Risk of severe x-ray changes 1 cross sectional OOO
True positives at diagnosis RR 0.38 study Very low
Benefit on treatment outcome - 0 studies OOO
Very Low
Benefit on transmission 15% reduction in incidence 2 cluster RCTs OO
22% reduction in Low
prevalence
False negatives Harm from missed diagnosis - Not reviewed -
Benefit from reassurance - Not reviewed -
True negatives
Harm from unnecessary screening - Not reviewed -
False positives Harm from unnecessary treatment - Not reviewed -
For further details see the GRADE tables.
What is the
There is VERY LOW QUALITY evidence that investigating contacts could improve case-detection rates for the population where
Confi dence i n benefi ts
overall Very
the investigation is carried out. There is VERY LOW QUALITY evidence that investigating contacts could identify cases earlier
and harm s
confidence in the Low Moderate High

low
estimates of than passive case-finding. There is LOW QUALITY evidence that investigating contacts may influence the epidemiology of TB.
effect for benefits    
and harms?
What is the
confidence in the Very High In 24 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening during
values that Low Moderate Very high
V al ues
low
patients place on investigation of household contacts was 80%; the range was 39–99%; and the median proportion was 85%.
the benefits and     
harms?
Is the cost low

No cost–effectiveness analysis of contact tracing has been published.
Res our c e
relative to the net No Uncertain Yes

s
benefits?   
Overall balance of Undesirable consequences clearly Undesirable consequences probably Desirable and undesirable Desirable consequences probably Desirable consequences clearly
consequences outweigh desirable consequences outweigh desirable consequences consequences outweigh undesirable consequences outweigh undesirable consequences
closely balanced or uncertain
    
Recommendation Strongly recommend Conditionally recommend Do not make recommendation (use this Conditionally recommend Strongly recommend
against against option very rarely if evidence is too sparse)
    
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
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: People with HIV

Screening intervention: Symptom screening and chest X-ray screening

Linked treatment: Chemotherapy for active TB
Note: See the systematic reviews for full references to cited papers. Chemoprophylaxis for latent TB infection
DOMAIN
Very
Infrequent
Moderately
frequent
Very
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).
Very
mild
Very
severe*
TB is responsible for more than one quarter of deaths occurring in people living with HIV.1 Among people who are HIV-positive,
Is it severe?      outcomes from treatment for TB are much worse than in other people with TB.2 Delayed diagnosis of TB in people living with HIV
*e.g. life threatening or disabling is associated with an increased risk of poor treatment outcomes and death.3
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.
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
Confidence in accuracy of the diagnostic
What is the
Very Moderat
confidence in the Low High
low e
test
accuracy of the
diagnostic test ?    
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
Impact on case detection
Overall, No published controlled trial has assessed the impact of screening HIV-positive people on changes in overall case detection. One
are the No Yes
anticipated  
cross-sectional study in India from a setting with a low prevalence of HIV found that 1% of the total cases detected came from
desirable effects screening people with HIV (Shetty 2008).
large?
Impact on time to diagnosis and severity at diagnosis
No studies were found.
Overall,
are the No Yes

anticipated   Impact on treatment outcomes
undesirable No published study has compared treatment outcomes between HIV-positive TB patients detected through screening with
effects small? 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-
Overall, is there
certainty about positive (data were not disaggregated by HIV status). One study from South Africa (Kranzer 2012) reported a treatment success
the link between Very
uncertain
Moderately
Certain
Very 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
the accuracy of uncertain certain certain
patients were HIV-positive (data were not disaggregated by HIV status).
the diagnostic     
test and the

consequences?
Impact on epidemiology
No published trial has assessed the epidemiological impact of screening for TB specifically in people who are HIV-positive.
There is VERY LOW QUALITY direct evidence on the impact of screening on morbidity and transmission specifically among
people with HIV.
C onfi dence i n benefi ts and harm s
What is the
overall
confidence in Very
Low Moderate High
However, TB is a cause of death and suffering among people with HIV, and delayed diagnosis of TB in HIV-positive people is
low
the estimates of associated with an increased risk of poor outcomes from treatment, including death. It is therefore plausible that screening HIV-
effect for     positive people for TB will be beneficial.
benefits and
harms?
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.
What is the
confidence in Very High
the values that Low Moderate Very high In 17 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among people
V al ues
low
patients place
     living with HIV was 78%; the range was 52–99%; and the median proportion was 83%.
on the benefits
and harms?
Is the cost low

Res our c
relative to the No Uncertain Yes No cost–effectiveness analysis has been published.

es
net benefits?   
closely
balanced or uncertain
    
    
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
7
Should systematic screening for active TB be done in miners?
Patients: People working in mines

Diagnostic intervention: Chest X-ray

Linked treatment: Treatment of active TB
Domain
COMMEN
CRITERIA JUDGEMENT EVIDENCE
TS
Very Very A systematic review of eight studies (Shapiro 2012) of the number needed to screen (NNS) to detect a previously undetected
Infrequ Moderatel
Is it frequent?
infrequen
ent y frequent
frequent freque case of TB found that for miners the mean weighted NNS was 87 (range, 20–233); all of the high-incidence countries represented
t nt
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.
Exposure to silica dust and silicosis are among the strongest risk factors for TB, with a relative risk of 2.8–39 for silicosis,
Very 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
Very moderat
mild
mild
e
severe severe among them.3 In some countries, such as those in southern Africa, the prevalence of HIV is high among miners, which further
*
Is it severe? 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
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.
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
Sensitivity and specificity (based on van’ t Hoog et al 2012)

abnormality)
Effect Quality Effect Quality Effect Quality Effect Quality Effect Quality
What is the Very Moderat TP 56% 35% 77% 98% 87%
confidence in the Low High Sensiti OO OOO OOO O OO
test
low e (40– (24– (68– (95– (79–

accuracy of the FP vity Low Very low Very low Moderate Low
74%) 46%) 86%) 100%) 95%)
diagnostic test ?    
TN 80% 95% 68% 89%
(69– (93– (50– (87–
90%) 97%) 85%) 92%)
(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.)
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.
Modelled yield of different algorithms based on point estimates from the systematic review of the accuracy of screening
Overall,
are the anticipated No Yes tools (van’t Hoog et al 2012) and systematic reviews of the accuracy of sputum-smear microscopy9 and the Xpert
desirable effects   MTB/RIF test10
large?
Screening Prevalence 0.5% Prevalence 1% Prevalence 2%

Diagnosi (500/100 000) (1 000/100 000) (2 000/100 000)
s TP FP TN FN TP FP TN FN TP FP TN FN
Chest X-ray: SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623
any
abnormality XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197
Chest X-ray: SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778
TB
Benefits and harms
>2–3 weeks XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353
Overall,
No Yes SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916
are the anticipated
undesirable   Any symptom
effects small? XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580
1. Cough SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555
lasting >2–3
weeks. 2. XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417
Chest X-ray
1. Any SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024
symptom. 2.
Chest X-ray XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722
MTB/RIF test; CD, clinical diagnosis.
Summary of findings
Benefit on case detection - 0 studies OOO
Very low
Very low
Benefit on severity at diagnosis - 0 studies OOO
True positives
Very low
Benefit on treatment outcome Fewer deaths 1 cohort OOO
(See text) Very Low
Benefit on transmission - 0 studies OOO
Very low
True negatives
Overall, is there
certainty about
the link between Very uncert Moderatel
Certain
Very Impact on case detection
the accuracy of uncertain ain y certain certain No studies.
the diagnostic test     
and the
consequences? 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
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.
What is the overall

Confidence
There is VERY LOW QUALITY evidence that screening for TB among miners reduces the case-fatality rate. There is no evidence from
and harms
in benefits
confidence in the Very

Low Moderate High
estimates of effect low published studies on the impact of screening miners for TB on case detection, delay in diagnosis and severity of disease at diagnosis,
for benefits and or on the epidemiology of TB.
   
harms?
What is the
confidence in the Very High Very
In six studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening in miners was 70%; the
Values
values that Low Moderate

low high
patients place on
    
range was 66–93%; and the median proportion was 84%.
the benefits and
harms?
Resources
Is the cost low

relative to the net No Uncertain Yes No cost or cost–effectiveness analysis has been published.
Overall balance of Undesirable consequences clearly outweigh Undesirable consequences probably outweigh Desirable and undesirable consequences Desirable consequences probably outweigh Desirable consequences clearly outweigh
consequences desirable consequences desirable consequences closely undesirable consequences undesirable consequences
    
Recommendation Strongly recommend Conditionally recommend Do not make recommendation (use this option very Conditionally recommend Strongly recommend
against Against rarely if evidence is too sparse)
    
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
Should systematic screening for active TB be done routinely in prisons?
Patients: People in prisons

Screening intervention: Symptom screening or chest X-ray screening, or both

Linked treatment: Anti-TB chemotherapy

M
O
D
N
A
I
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
Very
Infrequent
Moderately
frequent
Very 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%.
Very Very
mild severe* The prevalence of risk factors for poor treatment outcomes may be high in prisons; these risk factors include HIV infection,
*e.g. life threatening or disabling undernutrition, and drug abuse and alcohol abuse.
Outcome Any cough Cough lasting >2 Any symptom Chest x-ray (any Chest X-ray (TB-
abnormality)
TP 56% 35% 77% 98% 87%
Sensiti OO OOO OOO O OO
(40– (24– (68– (95– (79–
FP vity Low Very low Very low Moderate Low
74%) 46%) 86%) 100%) 95%)

TN 80% 95% 68% 89%
(69– (93– (50– (87–
90%) 97%) 85%) 92%)
What is the
confidence in Very For further details see the GRADE tables on the accuracy of diagnostic tests.
Low Moderate High
test
the accuracy of low

the diagnostic
test?    
Overall, MTB/RIF test2
are the No Yes Screening Diagnosi (500/100 000) (1 000/100 000) (2 000/100 000)
anticipated   s TP FP TN FN TP FP TN FN TP FP TN FN
desirable Chest X-ray: SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623
effects large? any
abnormality XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197
Chest X-ray: SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778
TB
>2–3 weeks XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353
Benefits and harms
SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916
Overall, Any symptom
are the No Yes XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580
anticipated 1. Cough SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555
undesirable lasting >2–3
effects small?   weeks. 2. XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417
Chest X-ray
1. Any SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024
symptom. 2.
Chest X-ray XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722
Overall, is there
certainty about
uncertain
Moderately
Certain
Very
the accuracy of
test and the

consequences?
Summary of findings
Benefit on case detection - 0 studies OOO
Very low
Benefit on time to diagnosis Delay 3xlonger with passive 1 cross sectional OOO
detection study Very low
Benefit on severity at diagnosis Less likely to be smear 1 cross sectional OOO
True positives
positive at diagnosis study Very low
Benefit on treatment outcome No control group 2 cross sectional OOO
studies Very Low
Benefit on transmission Reduction in incidence over 1 longitudinal study OOO
time (10 years) Very low
True negatives

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

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.

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.
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).
What is the
confi dence i n benef it s
overall Very
There is VERY LOW QUALITY evidence that screening prisoners could detect cases of TB earlier and affect the epidemiology of
and harm s

low
estimates of TB within prisons.
effect for benefits    
and harms?
What is the
confidence in the Very High In 16 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening in prisons was
values that Low Moderate Very high
V al ues
low
patients place on 72%; the range was 18–98%; and the median proportion was 86%.
harms?
Is the cost low

No cost-effectiveness analysis has been published.
Res our c
relative to the net No Uncertain Yes

es
Overall balance of Undesirable consequences clearly Undesirable consequences probably Desirable and undesirable consequences Desirable consequences probably Desirable consequences clearly
consequences outweigh desirable consequences outweigh desirable consequences closely balanced or uncertain outweigh undesirable consequences outweigh undesirable consequences
     
Recommendation Strongly recommend Conditionally recommend Do not make recommendation (use this option Conditionally recommend Strongly recommend
against Against very rarely if evidence is too sparse)
    
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 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.
4
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 Patients: People living in areas with a moderate–to-high prevalence of TB who
years, with previously known or suspected TB, who are undernourished, who attend for health-care services and belong to special risk groups
smoke, who have chronic obstructive pulmonary disease, who have diabetes, Screening intervention: Symptom screening or chest X-ray screening, or both
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. Linked treatment: Anti-TB chemotherapy
and
(ii) have not been screened for TB during the preceding 6–12 months?
DOMAIN
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 .
Very
Infrequent
Moderately
frequent
Very The weighted average NNS for people with a lesion previously identified by chest X-ray was 75 in 3 studies (Shapiro 2012).
infrequent frequent frequent
Is it frequent?
    
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
at other disease risk groups in low-incidence settings found an average NNS of 510 (range, 36–2846).
Very
mild
Very
severe*
People with diabetes,1 people who are undernourished,2 people who abuse alcohol,3 injecting drug users ,4 patients with
Is it severe?      diseases that impair their immune system,4 and elderly people4 all have an increased risk of poor outcomes from TB treatment.
*e.g. life threatening or disabling Pregnant women with TB have a higher risk of complications for themselves and their infants than other pregnant women.5


abnormality)
What is the
Very TP 56% 35% 77% 98% 87%
confidence in the Low Moderate High Sensiti OO OOO OOO O OO
test
low
accuracy of the (40– (24– (68– (95– (79–
    FP vity Low Very low Very low Moderate Low
diagnostic test? 74%) 46%) 86%) 100%) 95%)
TN 80% 95% 68% 89%
(69– (93– (50– (87–
90%) 97%) 85%) 92%)
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.
MTB/RIF test7
Overall,
are the No Yes Chest X-ray: SSM+CD 1890 97610 156 688 1881 97119 312 1377 1862 96138 623
anticipated any
  XP 245 99255 49 902 244 98756 98 1803 241 97759 197 197
desirable effects abnormality
large? Chest X-ray: SSM+CD 815 98685 195 611 810 98190 389 1222 802 97198 778
TB
>2–3 weeks XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353
SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916
Any symptom
XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580
1. Cough SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555
lasting >2–3
Overall, weeks. 2.
are the No Yes XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417
Chest X-ray
anticipated  
undesirable 1. Any SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024
effects small? symptom. 2.
Chest X-ray XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722
Summary of findings
Benefit on case detection See text 4 cross-sectional OO
Low
Very low
True positives
Very low
Very Low
Benefit on transmission - 0 studies OOO
Very low
Overall, is there Benefit from reassurance - Not reviewed -
True negatives
certainty about Harm from unnecessary screening - Not reviewed -
uncertain
Moderately
Certain
Very False positives Harm from unnecessary treatment - Not reviewed -
the accuracy of
test and the
consequences?
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.
No studies.

No studies.
No studies.
What is the
overall There is LOW QUALITY evidence that screening people with a previous lesion seen on chest X-ray contributes to overall case-
confidence in Very
and harm s
low
Low Moderate High detection rates. There is no such evidence for other clinical risk groups. There is no evidence about the impact of screening on
the estimates of
effect for delay to diagnosis and treatment outcomes. There is no evidence from published trials demonstrating an impact on case
   
benefits and detection or on the epidemiology of TB. A GRADE table is presented only for people with a lesion previously seen on chest X-ray.
harms?
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
What is the
women was 94%; the range was 68–96%; and the median proportion was 90%.
confidence in Very High
the values that Low Moderate Very high In two studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among elderly
V al ues
low
patients place
     people living in institutions was 72%; the range was 72–95%; and the median proportion was 83%.
on the benefits
and harms?
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.
Is the cost low

Res our c es
No Uncertain Yes
relative to the No cost–effectiveness analysis has been published.
closely
     
    
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
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: Population in communities with a very high burden of TB

Intervention: Door-to-door symptom screening or invitation for chest X-ray screening
Passive case-finding
Comparison:

DOMAIN
A systematic review of the number needed to screen (NNS) (Shapiro 2012) reported for community screening an average NNS
(range) of:
Very
infrequent
Infrequent
Moderately
frequent
frequent
Very
frequent
 3922 (137–30 865) in countries with a low incidence;
Is it frequent?
      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.
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
Very
Very undiagnosed TB or to late diagnosis and treatment.
mild severe*
*e.g. life threatening or disabling 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.

abnormality)
What is the
Very
confidence in the Low Moderate High TP 56%
OO
35%
OOO
77%
OOO
98%
O
87%
OO
test
low Sensiti
accuracy of the (40– (24– (68– (95– (79–
diagnostic test ?
    FP vity
74%)
Low
46%)
Very low
86%)
Very low
100%)
Moderate
95%)
Low
TN 80% 95% 68% 89%
(69– (93– (50– (87–
90%) 97%) 85%) 92%)
Overall,
are the No Yes
anticipated  
desirable effects
large?
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 microscopy1 and the Xpert MTB/RIF test2
Overall,
undesirable abnormality XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197
effects small? Chest X-ray: SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778
TB
>2–3 weeks XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353
SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916
Any symptom
XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580
1. Cough SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555
lasting >2–3
weeks. 2. XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417
Chest X-ray
1. Any SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024
symptom. 2.
Overall, is there Chest X-ray XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722
certainty about
the link between Very Moderately Very
uncertain Certain
the accuracy of uncertain certain certain MTB/RIF test; CD, clinical diagnosis.
test and the

conquences?
Summary of findings
Benefit on case detection See text 2 cluster RCTs OO
9 cross sectional Low
Benefit on time to diagnosis See text 2 RCTs OOO
Very low
True positives
positive at diagnosis Very low
Benefit on treatment outcome No differences have been 3 cross sectional OOO
shown studies Very Low
Benefit on transmission See text 1 RCT OOO
I Longitudinal study Very low
True negatives
RCT, randomized controlled trial.

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%.
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.
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.
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.
What is the
There is LOW QUALITY evidence that door-to-door and other intensive community screening interventions lead to increased case
Confi dence I n benefit s
overall
confidence in Very detection; and there is VERY LOW QUALITY evidence that these interventions reduce the delay in diagnosis. There is VERY
and harm s
Low Moderate High

low
the estimates of LOW QUALITY evidence that treatment outcomes are similar among those screened compared with those identified by passive
effect for     case-finding; and there is VERY LOW QUALITY evidence that intense community screening could have an impact on TB
benefits and
harms?
epidemiology.
What is the In 11 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among residents
confidence in High
in poor urban areas was 91%; the range was 59–99%; and the median proportion was 88%.
Very
the values that Low Moderate Very high
V al ues
low
patients place In nine studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening in indigenous
on the benefits     
and harms?
populations was 69%; the range was 40–97%; and the median proportion was 89%.
RE S O URCE S
Is the cost low

relative to the No Uncertain Yes No cost–effectiveness analysis of community screening has been published.
closely
    
    
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
3
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: Populations in communities with a very high burden of TB

Intervention: Symptom screening and sputum collection


MA
DO
IN
A systematic review of the number needed to screen (NNS) (Shapiro 2012) reported for community screening an average NNS
(range) of:
Very
infrequent
Infrequent
Moderately
frequent
frequent
Very
frequent
 3922 (137–30865) in countries with a low incidence;
Is it frequent?
Burden of Illness or problem
      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.
In principle, screening an entire community targets people who have an average risk of adverse outcomes and consequences from
Very
mild
Very
severe*
TB. If screening focuses on particularly vulnerable communities, it is likely to target people with TB who have a higher-than-average
Is it severe?      risk of both delayed diagnosis and adverse outcomes (including health, social and economic consequences) related to undiagnosed
*e.g. life threatening or disabling 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.


abnormality)
What is the
Very TP 56% 35% 77% 98% 87%
confidence in the Low Moderate High Sensiti OO OOO OOO O OO
test
low (40– (24– (68– (95– (79–

accuracy of the FP vity Low Very low Very low Moderate Low
    74%) 46%) 86%) 100%) 95%)
diagnostic test ?
TN 80% 95% 68% 89%
(69– (93– (50– (87–
90%) 97%) 85%) 92%)
Overall, MTB/RIF test2
are the No Yes
anticipated   Prevalence 0.5% Prevalence 1% Prevalence 2%
desirable effects Screening Diagnosi (500/100 000) (1 000/100 000) (2 000/100 000)
large? s TP FP TN FN TP FP TN FN TP FP TN FN
Chest X-ray: SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623
any
XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197
abnormality
Chest X-ray: SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778
TB
XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399
abnormalities
>2–3 weeks XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353
SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916
Any symptom
Overall, XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580
are the No Yes 1. Cough SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555
anticipated   lasting >2–3
undesirable weeks. 2. XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417
effects small? Chest X-ray
1. Any SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024
symptom. 2.
XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722
Chest X-ray
Overall, is there
certainty about
uncertain
Moderately
Certain
Very
the accuracy of
test and the

consequences?
Summary of findings
Benefit on case detection Not pooled 3 RCTs OOO
Very low
Benefit on time to diagnosis Reduced in both studies 1 cluster RCT OO
1 cross sectional Low
True positives
Very low
Benefit on treatment outcome Neither study found a 2 cross sectional OOO
difference studies Very Low
Benefit on transmission One study found a 2 cluster RCTs OOO
reduction and one did not Very low
True negatives
RCT, randomized controlled trial.


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).

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.

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.
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).
What is the There is VERY LOW QUALITY evidence that community screening leads to increased case detection; there is LOW QUALITY
overall evidence that community screening may reduce the delay in diagnosis. There is VERY LOW QUALITY evidence that treatment
confidence in Very
a n d harm s
low
Low Moderate High outcomes are similar in those screened compared with those detected by passive case-finding; there is MODERATE QUALITY
the estimates of
effect for evidence that providing health information along with decentralized sputum-collection points, symptom screening and sputum
   
benefits and collection during health camps has no impact on the epidemiology of TB. There is VERY LOW QUALITY evidence that more
harms? intense symptom screening through use of mobile vans may have an impact on the epidemiology of TB.
What is the In 11 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among residents
confidence in Very High in poor urban areas was 91%; the range was 59–99%; and the median proportion was 88%.
V al ues
low
patients place
on the benefits      In nine studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo screening in indigenous
and harms? populations was 69%; the range was 40–97%; and the median proportion was 89%.
Is the cost low
No cost–effectiveness analysis of community screening has been published.
Res our c
relative to the No Uncertain Yes

es
closely balanced or uncertain
    
    
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.
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
3
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 Patients: Population in communities with a very high burden of TB
by inviting people to mobile or stationary facilities to be screened for Intervention: Symptom screening, chest X-ray screening, or both; door-to-door or by
symptoms and for sputum collection and, in communities with a high invitation
burden of TB. The panel may develop a combined recommendation for the Comparison: Passive case-finding
two approaches, separate recommendations, recommendations for either,
both, or none of the approaches. Implied purpose: Reducing TB morbidity, mortality and transmission
Note: See systematic reviews for full references to cited papers

DOMAIN
C R IT ER IA JU D GEM EN T EVIDENCE C OM M EN T S
A systematic review of the number needed to screen (NNS) (Shapiro 2012) reported for community screening an NNS (range) of:
Very Moderately Very
 3922 (137–30 865) in countries with a low incidence;
Infrequent frequent
 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 .
In principle, screening an entire community targets people who have an average risk of adverse outcomes and consequences
Very Very from TB. If screening focuses on particularly vulnerable communities, it is likely to target people with TB who have a higher-than-
mild severe* average risk of both delayed diagnosis and adverse outcomes (including health, social and economic consequences) related to
*e.g. life threatening or disabling 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.
Sensitivity Any cough Cough lasting >2 Any symptom Chest X-ray (any Chest X-ray (TB-
and weeks abnormality) related
Confidence in accuracy of the
specificity abnormality)
What is the (based on Effect Quality Effect Quality Effect Quality Effect Quality Effect Quality
diagnostic
Very
test
accuracy of the
low van t’Hoog
diagnostic test ?     et al 2012)
Outcome
TP Sensiti 56% OO 35% OOO 77% OOO 98% O 87% OO
FP vity (40- [Should (24– Very low (68– Very low (95– Moderate (79– Low
74%) this 46%) 86%) 100%) 95%)
[95% designa
CI?] tion be
explain
ed
anywhe
re?]
Low
TN 80% 95% 68% 89%
(69– (93– (50– (87–
90%) 97%) 85%) 92%)
For further details see GRADE tables on the accuracy of diagnostic tests.
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
B enef it s and har m s

Overall, s TP FP TN FN TP FP TN FN TP FP TN FN
desirable effects XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197
abnormality
large? Chest X-ray: SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778
TB
XP 400 105 99395 100 800 105 98895 200 1601 104 97896 399
abnormalities
>2–3 weeks XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353
SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916
Any symptom
XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580
Cough lasting SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555
>2–3 weeks
Overall, plus [OK?] XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417
are the No Yes chest X-ray
anticipated   Any symptom SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024
undesirable plus [OK?] XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722
effects small? chest X-ray
Direct assessment of outcomes fof screening (Kranzer 2012)
Summary of findings
Benefit on case detection All four trials showed a 4 cluster RCTs O
benefit 10 cross-sectional Moderate
Benefit on time to diagnosis See text 3 cluster RCTs OOO
1 cross sectional Very low
True positives
Benefit on treatment outcome No benefits seen 6 cross sectional OOO
Very Low
Benefit on transmission See text 2 RCTs OO
1 Cohort Low
Overall, is there False negatives Harm from missed diagnosis - Not reviewed -
certainty of the Benefit from reassurance - Not reviewed -
link between the True negatives
Very Moderately Very Harm from unnecessary screening - Not reviewed -
diagnostic test uncertain
uncertain
certain
Certain
certain
accuracy False positives Harm from unnecessary treatment - Not reviewed -
    
information and
the con-
sequences? 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
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.

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.

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%).
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).
What is the There is MODERATE QUALITY evidence that community screening leads to increased case detection; and there is VERY LOW
Co n fi de nc e in b en ef i ts
overall QUALITY evidence that community screening reduces the delay in diagnosis. There is VERY LOW QUALITY evidence that
confidence in Very
treatment outcomes are similar among those screened compared with those identified by passive case-finding. There is
a nd h ar ms
Low Moderate High

low
the estimates of
effect for MODEARTE evidence that health information with decentralized sputum-collection points, symptom screening and sputum
   
benefits and collection during health camps has no impact on the epidemiology of TB; and there is LOW QUALITY evidence that more intense
harms? community screening may have an impact on the epidemiology of TB.
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%.
What is the In 47 studies (Mitchell 2012), the weighted average of eligible persons who consented to undergo TB screening in the general
confidence in High
community was 82%; the range was 2–99%; and the median proportion was 90%.
Very
V alues
low
patients place In 11 studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among residents
on the benefits     
and harms?
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%.
Is the cost small
Res our c es
[low?] relative to No Uncertain Yes No cost–effectiveness analysis of community screening has been published.
the net benefits?   
closely
    
against against option rarely if evidence is sparse)
    
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
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
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: Homeless people and people in shelters, including drug users

Screening intervention: Symptom screening or chest X-ray screening, or both

Linked treatment: 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
DOMAIN
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
Very
Infrequent
Moderately
frequent
Very using other screening tools.
infrequent frequent frequent
Is it frequent?
    
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.
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
Very Very
mild
severe* poor treatment outcomes.
Homeless people are among the groups with the poorest access to health services.
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.
abnormality)
TP 56% 35% 77% 98% 87%
Sensiti OO OOO OOO O OO
(40– (24– (68– (95– (79–
What is the FN vity
74%)
Low
46%)
Very low
86%)
Very low
100%)
Moderate
95%)
Low
Very
test
low TN 80% 95% 68% 89%

accuracy of the Specifi OO OO OOO 75% O OO
diagnostic test ?
    (69– (93– (50– (87–
90%) 97%) 85%) 92%)
MTB/RIF test3
Overall, Prevalence 0.5% Prevalence 1% Prevalence 2%
are the No Yes Screening Diagnosi (500/100 000) (1 000/100 000) (2 000/100 000)
anticipated s TP FP TN FN TP FP TN FN TP FP TN FN
 
desirable effects Chest X-ray: SSM+CD 344 1890 97610 156 688 1881 97119 312 1377 1862 96138 623
large? any
abnormality XP 451 245 99255 49 902 244 98756 98 1803 241 97759 197
Chest X-ray: SSM+CD 305 815 98685 195 611 810 98190 389 1222 802 97198 778
TB
>2–3 weeks XP 162 53 99447 338 324 52 98948 676 647 52 97948 1353
SSM+CD 271 2482 97018 229 542 2470 96530 458 1084 2445 95555 916
Any symptom
XP 355 321 99179 145 710 320 98680 290 1420 317 97683 580
1. Cough SSM + CD 111 179 99321 389 222 178 98822 778 445 177 97823 1555
lasting >2–3
weeks. 2. XP 146 23 99477 354 291 23 98977 709 583 23 97977 1417
Overall, Chest X-ray
are the No Yes
anticipated   1. Any SSM + CD 244 1092 98408 256 488 1087 97913 512 976 1076 96924 1024
undesirable symptom. 2.
effects small? Chest X-ray XP 319 141 99359 181 639 141 98859 361 1278 139 97861 722
Summary of findings
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 0 studies OOO
detection Very low
Benefit on severity at diagnosis Less likely to be smear- 3 cross-sectional OOO
True positives
Very Low
Benefit on transmission Reduction in incidence over 2 longitudinal OOO
time Very low
True negatives
Overall, is there Harm from unnecessary screening - Not reviewed -
certainty about False positives Harm from unnecessary treatment - Not reviewed -
uncertain
Moderately
Certain
Very
the accuracy of
the diagnostic      For further details see the GRADE tables.
test and the
consequences? 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.

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.

No study was identified.
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
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).
What is the
overall
confidence in Very There is VERY LOW QUALITY evidence that screening homeless people could improve case detection, identify cases earlier
and harm s
Low Moderate High

the estimates of low and reduce the burden of TB within the risk group and in the general community.
effect for    
benefits and All evidence is from low-burden settings.
harms?
What is the
confidence in Very High In five studies (Mitchell 2012) the weighted average of eligible persons who consented to undergo TB screening among homeless
v al ues
low
patients place on people was 96%; the range was 41–97%; and the median proportion was 75%.
harms?
Is the cost low No cost–effectiveness analysis based on empirical data has been published.
Res our c
relative to the No Uncertain Yes

es
closely
     
    
Options for recommendations and for discussion

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.
4

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Should household contacts and other close contacts of a person

with active TB be systematically screened for active TB?

Patients: Close contacts of active TB cases

Implied purpose: Reducing TB morbidity, mortality and transmission

CRITERIA JUDGEMENT EVIDENCE COMMENTS

Prevalence 0.5% Prevalence 1% Prevalence 2%

For further details see the GRADE tables.

confidence in the Low Moderate High

Is the cost low

relative to the net No Uncertain Yes

Patients: People with HIV

Implied purpose: Reducing TB morbidity, mortality and transmission

CRITERIA JUDGEMENT EVIDENCE COMMENTS

are the No Yes

test and the

Is the cost low

relative to the No Uncertain Yes No cost–effectiveness analysis has been published.

This is a strong recommendation with very low quality evidence.

Patients: People working in mines

Implied purpose: Reducing TB morbidity, mortality and transmission

Environmental Medicine, 1999, 56:215–216.

weeks abnormality) related

low e (40– (24– (68– (95– (79–

Screening Prevalence 0.5% Prevalence 1% Prevalence 2%

Impact on treatment outcomes

What is the overall

confidence in the Very

values that Low Moderate

Is the cost low

Option 1: There is not enough evidence to make a recommendation.

Patients: People in prisons

Implied purpose: Reducing TB morbidity, mortality and transmission

CRITERIA JUDGEMENT EVIDENCE COMMENTS

74%) 46%) 86%) 100%) 95%)

the accuracy of low

test and the

For further details see the GRADE tables.

Impact on case detection

Impact on time to diagnosis and severity at diagnosis

Impact on treatment outcomes

confidence in the Low Moderate High

Is the cost low

relative to the net No Uncertain Yes

Option 1: There is not enough evidence to make a recommendation.

CRITERIA JUDGEMENT EVIDENCE COMMENTS

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

weeks abnormality) related

Impact on treatment outcomes

Is the cost low

Proposed options for recommendations and for discussion

Option 1: There is no evidence to make a recommendation.

These are conditional recommendations with very low quality evidence.

It may not be possible to implement this recommendation in resource-constrained settings.

Concerning children: see remarks to Recommendation 7 in Section 8 in the guidelines.

Patients: Population in communities with a very high burden of TB

Implied purpose: Reducing TB morbidity, mortality and transmission

CRITERIA JUDGEMENT EVIDENCE COMMENTS

weeks abnormality) related

test and the

RCT, randomized controlled trial.

For further details see the GRADE tables.

Impact on case detection

Low Moderate High