should systematic screening for active tb be done in household … · 9 borderline statistical...

Should systematic screening for active TB be done in household contacts and other close contacts?

Note: For full references to cited studies, see systematic review 1 (Kranzer K et al. A systematic literature review of the benefits to communities and individuals of active screening for tuberculosis disease. International Journal of Tuberculosis and Lung Disease, 2013, 17:432–446.)

Quality assessment Summary of findings

Importance No of cases/population Effect Quality

No of studies Design Limitations Inconsistency Indirectness Imprecision Other Intervention Control Relative (95%CI) Absolute

1. Impact on case detection

Cross sectional studies assessing proportion of detected cases through screening vs. all notified cases

5 studies: Lee 2008 Ottmani 2009 Capewell 1984

Ormerod 1993 Jereb 1999

Cross-sectional Not serious Not serious Serious1 Not serious None 31 NA 78

50 561

1635 NA 816

649 9199

2% of all notified cases 4.5% ≥10 years, 19% of <10 years 9% of all notified cases

7% of all notified cases 6% of all notified cases

VERY LOW

IMPORTANT

2. Impact on time to diagnosis and severity at diagnosis:

2.1. Studies on delay: No studies

2.2. Studies of severity of disease at time of diagnosis

IMPORTANT Proportion sputum smear positive in screening compared to passive case finding

1 (Eang 2012) Cross sectional Not serious Not serious Serious2 Not serious 116/405(29%) 358/602(59%) 0.48(0.41;0.57) 31/100 fewer in screening (25-35 lower) LOW

Smear grade among sputum smear positive cases, reporting percentage scanty, proportion 2+ or 3+ out of all smear positive

1 (Eang 2012) Cross sectional Not serious Not serious Not serious Not serious 50/116(0.43) 203/354(0.57) 0.75(0.60;0.94) 14/100 fewer (3/100 to 23/100 fewer) LOW

Chest X-ray indicating severe disease

1 (Wang 2000) Cross sectional Not serious Not serious Serious3 Not serious 17/284(6%) 620/3903(16%) 0.38 (0.23;0.60) 10/100 fewer severe (6-12/100 fewer) VERY LOW

3. Impact on treatment outcomes: no studies CRITICAL

4. Impact on TB epidemiology

Cluster RCT of screening of household TB contacts, including chemoprophylaxis for those with likely latent infection, over 5 years, in a high incidence area of Rio de Janeiro. Comparing TB notification in intervention and control areas

CRITICAL

1 (Cavalcante

2010)

Cluster RCT Not serious Only one study Serious4 Serious5 Incidence decr.

10%, from 339 to 305/100,0006

Incidence increased

5%from 340 to 358/100,0005

15% difference in change of incidence

(p for difference=0.04)

LOW

Cluster RCT of household intervention (3 visits per household, including screening of household contacts) vs. no household intervention in very high burden setting, comparing prevalence of active TB incidence of TB infection

1 (Ayles 2012)7 Cluster RCT Not serious Only one study Serious8 Serious9 TB prevalence 746/100,000

Infection incidence 0.87%

TB prevalence 883/100,000


Adj RR TB: 0.78 (0.61-1.00)

Adj RR infection: 0.45 (0.20-1.05)

194 fewer prevalent TB cases/100,000 in the intervention areas

0.9 less TB infections/100 population in the intervention areas

LOW

1 The study design does not allow conclusion if detected cases are additional and the reported percentages are only indirect measures of increase in case detection 2 Only one study in one setting 3 Only one study in one setting. 4 Not possible to separate the effect of contact screening for active TB from the other co-interventions; treatment of latent TB. Only one study. 5 Borderline statistical significance 6 Absolute number of cases by year not reported. 7 The household intervention also included HIV counselling, testing and management. The study also included an arm of enhanced case finding, results are not included here 8 Not possible to separate the effect of contact tracing from the other co-interventions; treatment of latent TB, HIV counselling and testing. Only one study. 9 Borderline statistical significance for impact on prevalance of active TB and not statistically significant difference in TB infection prevalance

Should systematic screening for active TB be done in miners?



Importance No of cases/population Effect

Quality No of studies Design Limitations Inconsistency Indirectness Imprecision

Other considerations

Intervention Control Relative (95%CI)

Absolute


No studies IMPORTANT

2. Impact on time to diagnosis and severity at diagnosis


3. Impact on treatment outcomes

11 Cohort No No Serious2 No - 12/1225 (1.0%) 69/1011 (6.8%) Adjusted RR: 5.6(2.6-12.2)

5.5 fewer deaths per 100 treated ( 4.2 to 6.3 fewer per 100 treated)

VERY LOW CRITICAL


No studies CRITICAL

1 Churchyard 2000. Study population: miners. 2 Only one study

Should systematic screening for active TB be done in prisoners?







Absolute


No studies


2.1. Studies of delay from reported onset of symptoms to start of treatment IMPORTANT

1 Story 20081 Cross sectional

Serious2 Only one study Serious3 Serious4 - - 3 time longer

average delay in passive case finding group

- VERY LOW

2.2.Proportion sputum smear positive in screening compared to passive case finding

1 Story 2008

Cross sectional

Serious Only one study Serious Serious4 44%4 66% 0.67 22/100 fewer in screening groups VERY LOW


2 studies Koffi 1997 Harries 2004

Cross-sectional Serious5 Not serious Serious5 Not serious 80/108=74%

181/296=61%

NA

NA

NA

VERY LOW CRITICAL


1 study6 Yanjindulam 2012

Longitudinal surveillance

Serious7 Only one study Serious8 Serious9 900/100,000 in prisons 201010

2,500/100,000 in prisons in 2001

0.36 1600/100,000 notified cases less after ten years implementation

VERY LOW CRITICAL

1 This study screened hard-to-reach groups, including homeless, drug users, in shelters, and prisoners 2 Only a conference abstract is available so design details cannot be assessed. 3 The study did not report results separately for the different subgroups. 4 Absolute numbers not available 5None of the studies compared change in treatment success rate when introducing screening or through a trial design comparing screening vs. no screening. 6Yanjindulam 2012. Introduction of systematic screening at both detention and conviction combined with improved TB management and improved living conditions in the prisons, between 2001 and 2010, across 23 prisons and 16 detention centres with a total of about 6000 prisoners. Assessed trend in TB notification within prisons and compared to national trend. 7 No control group, only compared before and after in prisons and with national trend during the same time period 8 Only one study in one setting. It is not possible to separate the impaxct of screening from the impact of improved living conditions and improved TB treatment. 9 Avaiable data do not allow calculation of statistical uncertainty. 10 Absolute numbers not reported

Stable national notification in same period

Should systematic screening for active TB be done in people with previously untreated fibrotic CXR lesion?



Importance No of cases Effect



Screening in risk group

Other case detection Relative (95%CI)

Absolute


Studies of contribution to overall case detection IMPORTANT

4 studies1:

Ontario Kolin Netherlands Cambodia

Cross sectional

Not serious Serious Not serious Not serious 1206

96 109 981 20

6246

1020 319

4872 35

19% of all notified bacteriological positive cases

10% of all notified bacteriological positive 34% of all notified bacteriological positive

20% of all notified bacteriological positive 57% of all notified bacteriological positive

LOW




1202/1496

No studies CRITICAL


No studies CRITICAL

1 Meijer (1971) reported contribution from routine CXR screening in chest clinics, including people with previous fibrotic lesions on CXR, but also contacts and recent TST converters, from Canada (Ontario), Czechoslovakia (Kolin district) and The Netherlands in various time periods in the 1950s and 60s. Okada (2012) reported contribution of re-screening two years after a prevalence survey, of people who had been identified with active TB and people with CXR abnormalities but no active TB, in the initial survey.

Should systematic screening for active TB be done in communities with high TB burden?



Importance No of cases Effect



Through screening

Total in same population

Relative (95%CI)

Absolute


1.1. Studies assessing proportion of detected cases through screening out of all notified cases

Cross sectional studies

10 studies Meijer 1971a1 Meijer 1971b2

Meijer 1971c3 Krivinka 19744 Meijer 1971d5 Aneja 19846 Santha 20037

Harper 19968 Gonzalez 20099 Garcia 200010

Cross-sectional11

Serious12 Serious13 Serious14 Not serious None 90

140

229 19

1682 26

211

71 24 92

646

1020

618 96

4872 13

508

1175 19 15

NA Proportion of cases through screening: 14% of bacteriologically positive cases 14% of bacteriologically positive cases

37% of bacteriologically positive cases 20% of bacteriologically positive cases 35% of bacteriologically positive cases

67% of all notifies cases 25% of all notified cases

6% of all notified cases 56% of all notified cases 86% of all notified cases

VERY LOW IMPOPRTANT

1 Canada 1960-69. Mass miniature radiography screening in selected communities with a previous known case of TB , excluding in those <30 years who were TST negative, covering 18% of the population annually. Numbers do not include the reported routine hospital admission screening, covering 4% of the population, which yielded additional 66 (10%) of the total cases. 2 Canada 1967-68. MMR screening in community, industries, pre-employment and “others”, reaching about 10% of the population. Numbers in the table do not include yield from other than community screening, hospital admission screening (90 cases), “routione Xray” in hospitals , private clinics and chest clinics (136 cases) prison screening (16), contact investigation (35 cases). These cvases constitute an additional 277 (27%) of all bacteriologically positive cases. 3 Czechoslovakia 1961-69. MMR community screening in Kolin district, every 2-3 years, reaching 95% of population >15 years. Screening of people with known fibrotic lung lesions (191 cases) not included here. 4 Czechoslovakia 19729. MMR community screening in Kolin district, reaching 95% of population >15 years. Screening of people with known fibrotic lung lesions (8 cases) cases) not included here. 5 Netherlands 1951-67. MMR screening in community, people >14 years, covering ¼-1/3 of population each year 6 Lay health care workers identified TB suspects in the community, prepared microscopy slides and facilitated transport to microscopy centres. 7 Door-door in approx one third of the population 8 Temporary microscopy camps were put up in remote villages 9 Home visits only to specific risk groups (elderly, heavy alcohol users, ex-prisoners, HIV positive, socio-economically vulnerable) 10 Screening in mixed risk groups on community level or institutions: jails, shelters, orphanages, alcohol support groups and other risk groups. 11 Comparing number of TB cases detected through screening with total number of TB detected through screening and passive case f inding combined in the intervention area. 12 None of the studies compared screening with an alternative intervention since in settings screening was combined with passive case detection. It is unknown in all studies if cases detected through screening would have been detected through

passive case finding had screening not been done. The study design does not allow a direct assessment of effect of screening on additional case detection. Many studies are from the pre-DOTS era 13 Large variation in proportion of cases detected through screening, related to the differences across studies in type and size of target population and differences in screening method. 14 Due to inherent limitation of study design






Absolute


1.2. Community randomized trials

CRITICAL

Health extension workers informed community about TB and identified TB symptomatics and collected sputum samples at health posts once a month over 20 months. Sputum smear positive notification detection rate

1 (Datiko 2009)

RCT Serious15 Only one trial Serious16 Not serious None 230/178138

(129/100,000)

88/118673

(74/100,000)

RR 1.5517

Case detection rate 53% higher in

intervention clusters (95% CI; 40 to 65%)18

LOW

Community promoters informed about TB symptoms, sputum collection in monthly outreach clinics in rural areas over 1 year. Sputum smear positive case notification rate

1 (Shargie 2006)

RCT Serious19 Only one trial Serious16 Serious8 None 159/127607 (125/100,000)

221/225284 (98/100,000)

RR 1.27 (0.81;1.72)

27 more cases detected per 100,000 population

(from 19 fewer to 72 more)

VERY LOW

Door-to-door screening for symptomatics in poor urban areas

1 (Miller 2010) During intervention 27d Intervention +60d

RCT Not serious Only one trial Serious16 Serious20 None N=11249 19: 934/100000 32: 516/100000

N=12304 16: 604/100,000 41: 493/100,000

Rate Ratio 1.55(1.10;1.99) 1.05(0.56;1.54)

330 more cases detected per 100,000 population per year (from 60 more to 598

more) during intervention, no difference 60 days after

LOW

Infants screened 3 monthly through household visits; suspected TB disease was investigated as inpatient

1 (Moyo 2012) RCT Serious21 Only one trial Serious22 Not serious None 89/4109 PY (2166/100000)

36/4372 PY (823/100,000)

2.6 (1.8-4.0) 1,317 more cases detected per 100,000 population per year (from 659 more to 2470

more per 100,000)

LOW

Repeat information campaigns about TB to the community, decentralised sputum collection points with easy access, sputum collection in health camps, over 3 years

1 (Ayles 2012) RCT Not serious Only one trial Serious23 Serious None Cases at 0 vs.

3 years 875/946 (0.92)

Cases at 0 vs. 3 years

2024/2181 (0.93)

1.0 No difference in the change in case

notification between intervention and control

LOW

15 Method of calculating the main outcome is unclear. The actual method of screening/identification of TB symptomatic is not clearly described. Randomization is described, but little baseline data is provided 16 only been assessed in one setting 17 Crude ratio of case notification rates. Not enough data to calculate CI, adjusted for clustering 18 Authors only report difference in mean case detection rate, which conventionally is the ratio of case notification to the estimated TB incidence, though it is not stated in the paper exactly how it has been calculated 19 The method for choosing which communities received the intervention is not described. Few baseline comparison data are given, but the map suggests a non-random selection and differences between intervention and control communities. The communities were contiguous so there could be contamination. 20 Borderline significance for short term impact and no significant impact after 60 days. 21 Case definition includes main criteria for positive screen. Overdiagnosis possible 22 Only been assessed in one setting, and concerns young children only. 23 Only been assessed in one setting.


Importance Cases/population, mean or median Effect Quality

No of studies Design Limitations Inconsistency Indirectness Imprecision Other Intervention Control Relative (95%CI) Absolute


2.1. Studies of delay from reported onset of symptoms to start of treatment

Studies of proportion of patients with delay more than 90 days, general community screening

1 (Shargie 2006a) Cross sectional Serious 24 Only one study Serious25 Serious 7/13(54%) 14/24(58%) 0.93 4% less in the screening group VERY LOW

MPORTANT

Studies of median delay, door-to-door, RCT community screening

1 (Miller 2010) RCT Serious24 Only one study Serious25 No serious 56 days 56 days No difference LOW

Studies of mean time from birth to diagnosis in cohort of newborn children

1 (Moyo 2012) RCT Serious26 Only one study Serious25 No serious 13.2 months 16.6 months 3.4 months shorter in screening group (0.3 to 6.5 months shorter)

LOW

Study of proportion of patients with delay more than 90 days, RCT community screening

1 (Shargie 2006b) RCT Serious Only one study Serious25 No serious 65/159 (41%) 139/221 (63%) 0.65 (0.49- 0.81 22% less in the screening arm (12-32% less) LOW

Proportion with cough <3 weeks at time of diagnosis, community screening

1 (Santha 2003 Cross sectional Serious Only one study Serious No serious 37% 58% 2.06 19/100 more with short duration in screened VERY LOW


Proportion sputum smear positive in screening compared to passive case finding

7 studies Den Boon 2008 Meijer 1971a27 Meijer 1971b28

Meijer 1971c29 Krivinka 197430 Meijer 1971d31 Moyo 2012

Cross sectional

Not serious Not serious Serious32 Not serious 813/2128 (0.38) 18/27(67%) 47/90(52%)

63/140(45%)

25/81(31%) 4/19(21%)

646/1682(38%) 10/89 (11%)

2479/3865(0.64) 446/473(94%) 265/425(62%) 420/603(70%)

44/98(45%) 8/21(38%)

1288/2209(58%) 8/36(22%)

0.60(0.56;0.63) 0.71 0.84 0.64

0.69 0.55 0.65 0.46

40/100 lower in screening 27/100 lower in screening 10/100 lower in screening 25/100 lower in screening

14/100 lower in screening 17/100 lower in screening 20/100 lower in screening 11/100 lower in screening

VERY LOW

IMPORTANT

Smear grade among sputum smear positive cases, reporting percentage scanty, proportion 2+ or 3+ out of all smear positive IMPORTANT

2 studies: Den Boon 2008 Shetty

Cross sectional

Not serious Not serious Not serious Not serious 97/229 (0.42) 10/18(0.56)

87/211(0.41)

665/954(0.79) 314/446 (0.70) 351/508(0.69)

0.61(0.52;0.71)

30/100 fewer smear grade 2+ or 3+ in screened (122/100 to 36/100 lower)

LOW

24 Self reported onset of disease may not be reliable, and recall bias may vary between screened cases and those passively detected. No study assessed changed in delay after introduction of screening 25 Only one study 26 Most cases were diagnosed on the bases of symptoms and not on the bases of microbiology, and case definition thus included the maincriteria for positive screen. Overdiagnosis is likely. 27 Canada 1960-69. Mass miniature radiography screening in selected communities with a previous known case of TB , excluding in those <30 years who were TST negative, covering 18% of the population annually. The passive case detection group does not include patients detected through routine hospital admission screening. 28 Canada 1967-68. MMR screening in community, industries, pre-employment and “others”, reaching about 10% of the population. The passive case detection group does not include patients detected through hospital admission screening, “routine Xray” in hospitals , private clinics and chest clinics, prison screening, contact investigation.. 29 Czechoslovakia 1961-69. MMR community screening in Kolin district, every 2-3 years, reaching 95% of population >15 years. The passive case detection group does not include patients detected through screening of people with known fibrotic lung lesions. 30 Czechoslovakia 19729. MMR community screening in Kolin district, reaching 95% of population >15 years. The passive case detection group does not include patients detected through screening of people with known fibrotic lung lesions. 31 Netherlands 1951-67. MMR screening in community, people >14 years, covering ¼-1/3 of population each year 32 Method of diagnosis not necessarily the same in screened and non-screened groups.



Quality No of studies Design Limitations Inconsistency Indirectness Imprecision Other Intervention Control Relative (95%CI) Absolute


633

den Boon 2008 Ayles 2012

Santha 2003 Cassles 1982 Harper 1996 Eang 2012

Cross-sectional Serious34 Not serious Serious35 Not serious Treatment success

16/20 (80%) 597/771(77%)

107/153(70%) 62/100(62%) 50/68(74%)

370/384(96%)

Treatment success

380/473(80%) 2406/3151(77%)

361/508(71%) 110/159(69%)

997/1306(76%) 573/602(95%)

Pooled 1.00(.98;1.02)

RR=1.0 (0.83;1.2) RR=0.98 (0.95;1.01)

RR=0.99 (0.91;1.08) RR=0.95 (0.83;1.08) RR=0.98 (0.87;1.09 RR=1.01 (0.99;1.04)

Same number of successfully treated

patients among those identified through screening and those

identified through passive case finding

VERY LOW CRITICAL


4.1. One time household screening in randomly selected clusters in high burden setting, comparing smear-positive notification rate in intervention clusters with baseline and national rate two years after screening

CRITICAL

1 (Okada 2012) Cohort study Serious Only one study Serious Not serious 34 (154/100,000)

89.5 (404/100,000) Standardized notification rate

0.38 (0.27-

0.52)

250 less smear positive cases per 100,000 population 2 years after one-off screening

VERY LOW

4.2. 6-mothly community screening with mobile van or door-door vs. baseline pre-intervention, in a high burden setting, over 3 years, comparing TB prevalence before and after intervention

1 (Corbett 2010) Cluster randomised trial

Serious36 Only one study Serious Not serious 3.7/1000 (2.6-5.0)

(41 cases)

Baseline prevalence 6.5/1000 (5.1-8.3)

(66 cases)

Adj RR 0.59 (0.40-0.89)

p=0.01

280 fewer prevalent cases per 100,000 population after 3 years

LOW

Repeat information campaigns about TB to the community, decentralised sputum collection points with easy access, sputum collection in health camps, over 3 years

1 Ayles 2012 RCT No serious Only one study Serious37 Serious38 TB prevalence 927/100,000


TB prevalence 711/100,000


Adj RR TB: 1.11 (0.87-1.42)

Adj RR infection: 1.36 (0.59-3.14)

216/100,000 higher prevalance in the intervention are (from 92 less to 299 more)

3.6/1000 higher infection incidence in the intervention arm (from 4.3/1000 less to

22/1000 more)

LOW

33 Only including studies comparing a cohort of patients among identified through screening and a cohort of patients identified through passive case finding 34 Not controlled for severity at time of diagnosis and other patient related factors 35None of the studies compared change in treatment success rate when introducing screening. 36 No control area without intervention, only two different interventions. Difficult to control for secular trend. 37 Only studies in one setting. The major part of the intervention is information campaign combined with decentralized sputum collection points 38 Not powered to detect small difference in prevalance or infection incidence

Should systematic screening for active TB be done among homeless, in shelters, or among drugusers?





Other

considerations Intervention Control

Relative

(95%CI) Absolute


1.1. Cross sectional studies assessing proportion of detected cases through screening vs. all notified cases

1.1.1. Community-based screening, including screening in specific risk populations

1 (de Vries 2007)

Cross-sectional1

Serious Only one study Serious Serious None 28 562 5% of all notified cases VERY LOW IMPORTANT



IMPORTANT

2.2.1. Proportion sputum smear positive in screening compared to passive case finding

3: Ross 1977

Capewell 1986 Story 2008

Cross sectional

Not Serious Not Serious Serious Not Serious 58/131(0.44) 31/54(0.58)

10/41(0.26) 15/25(0.44)

220/337(0.65) 46/71(0.85)

15/26(0.58) 158/240(0.66)

0.67(0.55;0.83) 0.68

0.45 0.67

21/100 fewer in screening (From 11/100 to 35/100 fewer)

VERY LOW

2.2.3. Chest X-ray indicating severe disease

1 Ross 1977 Cross sectional

Serious Not Serious Serious Not Serious 7/54 (0.13) 22/71(0.31) 0.51(0.24;1.10) 15/100 fewer severe in screening group (24/100 fewer to 3/100 more)


No study


Impact on TB in the general community, incidence decline

1 (Rendelman 1999)

Secular trend, before-after

1985-1995

Serious2 Only one study Serious3 Not serious 29/100,000 (5 cases)

227/100,000 (39 cases)

0.13 (0.05 to 0.32)

34 fewer cases, or 198/100,000 pop. In the intervention district 10 years after screening

was introduced (between 154 and 215/100,000 fewer) No downward trend in

other districts.

VERY LOW

CRITICAL

Impact within the risk group, incidence decline

1 (De Vries 2007) Secular trend,

before-after 2002-2005

Serious4 Only one study Serious5 Not serious 11/4500

244/100,000

24/4500:

553/100,000

0.46

(0.22 to 0.93)

309/100,000 fewer incident cases after

intervention. (between 34 and 431 fewer)

1 Comparing number of TB cases detected through screening with total number of TB detected through screening and passive case f inding in the intervention area. All studies targeted specific subpopulations, none covered the whole population. The

proportion of the population covered varied but was not consistently reported in the studies. 2 No control group, only before after and compared with overall trend in the state of Oregon. No control for other possible confounding events 3 Only one study in one setting. 4 No control group, only before after with the risk group. 5 Only one study in one setting.

should systematic screening for active tb be done in household … · 9 borderline statistical...

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