INT J TUBERC LUNG DIS 18(6):640–646 Q 2014 The Union http://dx.doi.org/10.5588/ijtld.13.0486

Predictors of contact tracing completion and outcomes in tuberculosis: a 21-year retrospective cohort study M. J. Saunders,* G. C. K. W. Koh,†‡ A. D. Small,§ M. Dedicoat‡ *Department of Respiratory Medicine, The Royal Liverpool and Broadgreen University Hospitals, Liverpool, † Warwick Medical School, University of Warwick, Coventry, ‡Department of Infection & Tropical Medicine, Heart of England National Health Service Foundation Trust, Birmingham, §Department of Intensive Care, Sandwell and West Birmingham Hospitals Trust, Birmingham, UK SUMMARY

Birmingham, UK, 1990–2010. To identify predictors in contacts for completion of screening and of a positive screening outcome, i.e., a diagnosis of latent tuberculous infection (LTBI) or active tuberculosis (TB). D E S I G N : A retrospective cohort study of TB notifications for a European city. R E S U LT S : A total of 46 158 contacts were identified from 7365 index cases. Over the study period 17 471 (40.9%) failed to complete screening. Active TB or LTBI was diagnosed in 2220 (7.0%) contacts of cases of pulmonary TB (PTB) and in 222 (2.7%) contacts of cases of extra-pulmonary TB (EPTB). The proportion of contacts offered LTBI treatment increased (P , 0.001) over the study period. Age, ethnicity, sex and use of

interferon-gamma release assays (IGRA) were the most important predictors of screening completion, with working age adult males who were Black or from the Indian subcontinent least likely to complete. Age, smear positivity status of the index case and IGRA usage were the most important predictors of a positive screening outcome (active TB or LTBI diagnosed). C O N C L U S I O N : Contact tracing of both PTB and EPTB index cases is useful for active case finding. The findings of this study can be used to target screening and improve the effectiveness and efficiency of local contact tracing programmes. K E Y W O R D S : infectious disease reporting; screening; interferon-gamma release tests; logistic regression

TUBERCULOSIS (TB) remains a worldwide public health challenge despite efforts to reduce transmission and treat infection.1 In the United Kingdom, TB incidence has stabilised at 14 per 100 000 population.2 However, during the 1990s and 2000s, TB incidence increased faster in Birmingham than in England. Birmingham is the second largest city in the United Kingdom, with a population of approximately one million that is ethnically very diverse.3 The annual incidence of TB is 35/100 000,4 and is as high as 99.3/100 000 in the centre.4 This has been attributed to the reactivation of latent tuberculous infection (LTBI) in persons born in high-incidence areas outside of the United Kingdom.5 In Birmingham 73% of cases occur in patients born outside the United Kingdom.4 Contact tracing involves the evaluation of contacts of TB patients to identify and treat active TB and LTBI. This has been standard practice for decades, as contacts of TB cases are at a higher risk of infection than the public.6–9 Although expensive, screening is effective and forms an essential part of TB pro-

grammes in many countries, including the United Kingdom, where national guidance recommends assessing the need for screening in any case of active TB.6,7,10,11 In Birmingham, contact tracing for all types of TB has been standard practice since 1980. The purpose of the present study was to evaluate screening outcomes and identify predictors of screening completion and positive screening outcomes, i.e., the identification of a contact with either LTBI or active TB.

SETTING:

OBJECTIVE:

STUDY POPULATION AND METHODS The cohort All TB cases in Birmingham are reported to the Birmingham Chest Clinic, which performs contact tracing for the city. This study was performed on anonymised data during the period from 1 January 1990 to 31 December 2010. Data were collected by the Birmingham TB Nursing Service on index cases with both pulmonary (PTB) and extra-pulmonary TB (EPTB). PTB was

Correspondence to: Matthew Saunders, Royal Liverpool University Hospital, Prescot Street, Liverpool L78XP, UK. Tel: (þ44) 78 1745 5461. e-mail: [email protected] Article submitted 4 July 2013. Final version accepted 9 February 2014.

TB contact tracing in Birmingham

defined as involvement of the lung parenchyma, mediastinal lymph nodes or pleura. EPTB was defined as TB of any other site. PTB cases were further stratified into smear-positive or -negative, as determined by Ziehl-Neelsen staining (until 1994), or fluorescence microscopy using auramine (after 1994) in accordance with national guidelines.12 Contacts of index cases were then identified by interview of the index case following notification. Two study outcomes of interest were identified. The first was the completion of screening, defined as positive if the contact attended a screening appointment, completed the diagnostic tests and attended a notification appointment, if required. The second was a positive screening outcome, defined as the contact being diagnosed with and offered treatment for either LTBI or active TB. Details of the contact screening procedure and data collection are described in the Appendix.* Statistical analysis Data were analysed using SPSS, version 19 (Statistical Product and Service Solutions, Chicago, IL, USA) and Stata, version 12 (Stata Corp, College Station, TX, USA). Contacts were stratified by whether the index case had PTB or EPTB. The v2 test for trend was used to identify trends in the number of contacts screened annually, the number of contacts completing screening and overall screening outcomes. Multivariate logistic regression models were constructed to estimate the contribution of each of the variables to the outcomes of interest. We considered separately models that include the degree of relationship (i.e., partner, school, etc.) and models that divide contacts according to whether they are in the first ring (a contact with 78 h exposure/day), as there is a large overlap in the two definitions, and models that contain both variables would be extremely difficult to interpret. We confined discussion to those variables with an odds ratio (OR) of ,0.8 or .1.25. We also discussed variables we felt were clinically relevant in that they alter the way we run our service.

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1542 (30.5%) were smear-positive; 2309 (31.4%) had EPTB; 5580 index cases (75.8%) had at least one contact identified and 46 158 contacts were identified in total. For index cases with PTB, 35 098 (76.0%) contacts were identified; for index cases of EPTB, 10 164 (22.0%) contacts were identified: 23 372 (50.6%) were females and 21 955 (47.6%) males. The median age was 22 years (interquartile range [IQR] 10–37.1) for females and 21 (IQR 9–36) for males. Data on ethnicity were available for 33 319 contacts (72.2%), of whom 4395 (13.2%) were White, 3532 (10.6%) were Black, 24 055 (72.2%) were from the Indian subcontinent and 1337 (4.0%) were of other ethnicity (including mixed race). Screening outcomes Screening outcomes were available for 42 613 contacts (92.3%); of these, 17 471 (40.9%) failed to complete screening. There were considerable differences in screening outcomes over the study period (Figures 1 and 2), but there was no evidence of a trend in completion rates (P ¼ 0.20) or for an overall trend in the number of contacts screened each year (P ¼ 0.12, Figure 1). There was no overall change in the proportion of contacts who were offered bacille Calmette-Gu´erin vaccination (P ¼ 0.35) or offered anti-tuberculosis treatment (P ¼ 0.67), although there was a significant increase in the proportion of contacts who were offered chemoprophylaxis for LTBI (P , 0.001, Figure 2). Pulmonary tuberculosis Outcomes were available for 16 034 (34.7%) contacts of smear-positive cases and 15 335 (33.2%) contacts of smear-negative cases (Table 1). The total number of positive screening outcomes for PTB was

Ethics The data analysed in this report were collected for public health purposes and were anonymised before analysis. Ethical approval for the analysis was not needed in accordance with national guidance.

RESULTS Characteristics of study subjects A total of 7365 index cases were diagnosed between 1990 and 2010: 5056 (68.6%) had PTB, of whom *The Appendix is available in the online version of this article, at http://www.ingentaconnect.com/content/iuatld/ijtld/2014/ 00000018/00000006/art00005

Figure 1 Screening completion rates in contacts of tuberculosis cases, Birmingham, 1990–2010. There was no evidence for a change in completion rates over the study period (P ¼ 0.20) or for a change in the number of contacts screened each year (P ¼ 0.12).

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Contacts who were Black were less likely to complete than those who were White. When the index case had PTB, contacts were more likely to complete if they were aged 765 years or if they were a school contact. They were more likely to complete if interferon-gamma release assays (IGRAs) had been used and if they had been screened at a time when staff workload was lower. Contacts were less likely to complete if they were male or from the Indian subcontinent. Contacts of PTB were less likely to complete than those of EPTB (OR 0.291, 95% confidence interval [CI] 0.276–0.307, P ,0.001).

Figure 2 Screening outcomes in contacts of tuberculosis, Birmingham, 1990–2010. There was no change in the proportion of contacts who were offered BCG (P ¼ 0.35) or diagnosed with active TB (P ¼ 0.67). There was a significant increase in the proportion of contacts who were offered chemoprophylaxis for LTBI (P , 0.001). BCG ¼ bacille Cal´ mette-Guerin; LTBI ¼ latent tuberculous infection; TB ¼ tuberculosis.

2220 (7.0%) and the number of contacts of PTB cases screened for each positive screening outcome was 15. Extra-pulmonary tuberculosis Outcomes were available for 9875 contacts (21.4%) (Table 1). The total number of positive screening outcomes was 222 (2.27%) and the number of EPTB contacts needed to screen for each positive screening outcome was 45.

Positive screening outcome Factors associated with increased odds of a positive screening outcome are listed in Tables 4 and 5 and Appendix Tables A.3 and A.4. In the multivariate analysis, contacts of PTB were more likely to screen positive if they were aged ,16 years, Black or if they were a contact of a smear-positive index case. Contacts of PTB who had been screened using an IGRA and those from the first ring of screening were more likely to screen positive. Contacts were less likely to screen positive if they were aged .65 years, male, from the Indian subcontinent, or if they were a friend, other relative or school contact of the index. Contacts of EPTB cases were more likely to screen positive if they were aged ,16 years, or a partner or in-law of the index case. Contacts aged .65 years and those from the Indian subcontinent were less likely to screen positive. Contacts of PTB were more likely to screen positive than those of EPTB (OR 2.10, 95%CI 1.92–2.30, P ,0.001).

Screening completion All the predictors examined were associated with screening completion in the univariate analysis (Tables 2 and 3, Appendix Tables A.1 and A.2). In the multivariate analysis, contacts of both PTB and EPTB cases were less likely to complete screening if they came from the first ring of contacts. Contacts were more likely to complete if they were aged ,16 years or if they were a partner of the index case. Table 1

DISCUSSION Screening outcomes The rates of screening outcomes were similar in 1990 and 2010, and there were no overall trends in the data. There were, however, large differences in the number of contacts screened and the number of contacts completing screening, as well as differences in rates of screening outcomes. These are probably

Contacts of index cases (outcomes of screening)

EPTB Smear-positive PTB Smear-negative PTB Contacts of PTB with missing smear positivity status Contacts with missing site data Total

Contacts n

Failed to complete n (%)

Negative screen n (%)

BCG given n (%)

LTBI n (%)

Active TB n (%)

Positive screening rate (active TB or LTBI) n (%)

9 875 16 034 15 335

2049 (20.7) 7319 (45.6) 7565 (49.3)

7216 (73.1) 6282 (39.2) 6391 (41.7)

388 (3.93) 857 (5.34) 758 (4.94)

165 (1.67) 1044 (6.51) 440 (2.87)

57 (0.58) 532 (3.32) 181 (1.18)

222 (2.27) 1576 (9.83) 621 (4.05)

483 886 42 613

201 (41.6) 337 (38.0) 17 471

222 (46.0) 476 (53.7) 20 587

37 (7.67) 50 (5.64) 2090

18 (3.73) 20 (2.26) 1687

5 (1.04) 3 (0.34) 778

23 (4.76) 23 (2.56) 2465

´ BCG ¼ bacille Calmette-Guerin; LTBI ¼ latent tuberculous infection; TB ¼ tuberculosis; EPTB ¼ extra-pulmonary TB; PTB ¼ pulmonary TB.

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TB contact tracing in Birmingham

Table 2 cases*

Univariate analysis and multivariate regression identifying determinants for completion of screening in contacts of PTB Univariate analysis

Multivariate analysis

Frequency n (%)

OR (95%CI)

P value

aOR (95%CI)

P value

Age, years 0–15 16–64 765

13 548 (38.6) 19 938 (56.8) 1 456 (4.2)

2.01 (1.91–2.10) — 1.58 (1.40–1.77)

,0.001 — ,0.001

2.22 (2.09–2.36) — 1.61 (1.39–1.86)

,0.001 — ,0.001

Male sex‡

16 452 (46.9)

0.863 (0.825–0.902)

,0.001

0.858 (0.810–0.909)

,0.001

Ethnicity§ White Black Indian subcontinent Other

3 900 (11.1) 2 548 (7.3) 17 016 (48.5) 845 (2.4)

— 0.667 (0.602–740) 0.567 (0.526–0.610) 0.968 (0.826–1.13)

— ,0.001 ,0.001 0.685

— 0.554 (0.492–0.624) 0.547 (0.503–0.596) 0.880 (0.734–1.06)

— ,0.001 ,0.001 0.169

Index case is smear-positive¶

17 597 (50.1)

1.16 (1.11–1.21)

,0.001

0.986 (0.930–1.05)

3 722 (10.6)

1.38 (1.29–1.48)

,0.001

1.30 (1.18–1.42)

,0.001

Risk factor †

IGRA#

0.631

Lower staff workload#

12 058 (34.4)

1.19 (1.14–1.25)

,0.001

1.21 (1.14–1.1.28)

,0.001

First ring contact**

28 264 (80.5)

0.290 (0.265–0.317)

,0.001

0.377 (0.318–0.446)

,0.001

* This table lists the independent contribution of seven predictors for the completion of screening as described using a logistic regression model. For age, workingage adults (age 16–64 years) were the comparator. For ethnicity, the White group was the comparator (n ¼ 35 098). 19 724 contacts were included in the regression analysis; 15 374 (43.8%) were excluded, as they contained missing data. We also performed a sensitivity analysis by excluding ethnicity and relation. This included 27 007 (76.9%) contacts and did not materially affect any of the results. † 156 (0.4%) contacts had no age recorded. ‡ 694 (2.0%) contacts had no sex recorded. § 10 789 (30.7%) contacts had no ethnicity recorded. ¶ 488 (1.4%) contacts had no smear status recorded. # 0 contacts contained missing data on these two fields. ** 3954 (11.3%) contacts had no data recorded on ‘first ring’. We performed a sensitivity analysis that did not materially affect any of the results. PTB ¼ pulmonary tuberculosis; OR ¼ odds ratio; aOR ¼ adjusted OR; CI ¼ confidence interval; IGRA ¼ interferon-gamma release assay.

due to variations in staffing over time. The results suggest that contacts of PTB were more likely to complete screening when staff workload was lower and more contacts were screened (Figure 1). Although the models presented showed no association between workload and positive screening outcomes, Table 3

the variable is a crude measure of workload and may not account for all aspects of staffing. The proportion of contacts with LTBI was dependent on the number of contacts investigated. This was, in turn, dependent on the proportion testing positive in the first ring and meant that the overall

Univariate and multivariate regression identifying determinants for completion of screening in contacts of EPTB cases* Frequency n (%)

Risk factor

Univariate analysis

Multivariate analysis

OR (95%CI)

P value

aOR (95%CI)

P value

,0.001 — 0.007 ,0.001

3.25 (2.74–3.84) — 1.41 (0.995–2.00) 0.787 (0.698–0.888)

,0.001 — 0.054 ,0.001

— 0.062 0.71 0.026

— 0.581 (0.417–0.811) 0.924 (0.696–1.23) 1.13 (0.768–1.66)

— 0.001 0.583 0.537 0.073

†

Age, years 0–15 16–64 765 Male sex‡

5483 4253 356 5069

(53.9) (41.8) (3.50) (49.9)

2.69 (2.40–3.01) — 1.46 (1.11–1.91) 0.822 (0.745–0.906)

Ethnicity§ White Black Indian subcontinent Other

414 849 6732 468

(4.10) (8.40) (66.2) (4.6)

— 0.760 (0.570–1.01) 1.05 (0.817–1.34) 1.49 (1.05–2.12)

IGRA¶

1121 (11.0)

1.02 (0.880–1.20)

0.73

1.18 (0.985–1.41)

Lower staff workload¶

3053 (30.0)

0.823 (0.742–0.912)

,0.001

0.919 (0.801–1.05)

0.23

First ring contact#

8396 (82.6)

0.838 (0.680–1.03)

0.626 (0.460–0.852)

0.003

0.097

* This table lists the independent contribution of six predictors for the completion of screening as described using a logistic regression model. For age, working-age adults (age 16–64 years) were the comparator. For ethnicity, the White group was the comparator (n ¼ 10 164). 7112 contacts were included in the regression analysis; 3052 (30.0%) were excluded, as they contained missing data. We also performed a sensitivity analysis by excluding ethnicity and relation, which therefore included 8598 (84.6%) contacts. The aOR for lower staff workload changed to 0.859 (0.759–0.972). There were no other material changes to the results. † 72 (0.7%) contacts had no age recorded. ‡ 122 (1.2%) contacts had no sex recorded. § 1701 (16.7%) contacts had no ethnicity recorded. ¶ 0 contacts contained missing data on these two fields. # 1117 (11.0%) contacts had no data recorded on ‘first ring’. We performed a sensitivity analysis. When all missing contacts were attributed to being in the first ring, the aOR for lower staff workload changed to 0.835 (95%CI 0.742–0.940). When all missing contacts are attributed to not being in the first ring the aOR for lower staff workload changed to 0.812 (95%CI 0.719–0.917). EPTB ¼ extra-pulmonary tuberculosis; OR ¼ odds ratio; aOR ¼ adjusted OR; CI ¼ confidence interval; IGRA ¼ interferon-gamma release assay.

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Table 4 cases*

Univariate analysis and multivariate regression identifying determinants of a positive screening episode in contacts of PTB Univariate analysis

Multivariate analysis

Frequency n (%)

OR (95%CI)

P value

aOR (95%CI)

P value

Age, years 0–15 16–64 765

13 548 (38.6) 19 938 (56.8) 1 456 (4.1)

4.68 (4.34–5.04) — 0.303 (0.200–0.460)

,0.001 — ,0.001

4.86 (4.43–5.34) — 0.267 (0.164–0.435)

,0.001 — ,0.001

Male sex‡

16 452 (46.9)

0.988 (0.923–1.06)

0.72

0.855 (0.811–0.966)

0.006

Ethnicity§ White Black Indian subcontinent Other

3 900 (11.1) 2 548 (7.3) 17 016 (48.5) 845 (2.4)

— 1.70 (1.50–1.91) 0.515 (0.467–0.568) 1.37 (1.14–1.65)

— ,0.001 ,0.001 0.001

— 1.24 (1.01–1.43) 0.391 (0.347–0.440) 1.11 (0.887–1.40)

— 0.005 ,0.001 0.357

Index is smear-positive¶

17 597 (50.1)

1.81 (1.69–1.94)

,0.001

2.20 (2.01–2.41)

,0.001

3 722 (10.6)

1.37 (1.25–1.51)

,0.001

1.31 (1.15–1.45)

,0.001

Lower staff workload#

12 058 (34.4)

1.07 (0.995–1.14)

First ring contact**

28 264 (80.5)

2.96 (2.49–3.53)

Risk factor †

IGRA#

0.071 ,0.001

1.06 (0.963–1.16) 3.26 (2.38–4.46)

0.249 ,0.001

* This table lists the independent contribution of seven predictors for a positive screening episode as described using a logistic regression model. For age, workingage adults (age 16–64 years) were the comparator. For ethnicity, the White group was the comparator (n ¼ 35 098); 19 724 contacts were included in the regression analysis; 15 374 (43.8%) were excluded, as they contained missing data. We also performed a sensitivity analysis by excluding ethnicity and relation. This included 27 007 (76.9%) of contacts and did not materially affect any of the results. † 156 (0.4%) contacts had no age recorded. ‡ 694 (2.0%) contacts had no sex recorded. § 10 789 (30.7%) contacts had no ethnicity recorded. ¶ 488 (1.4%) contacts had no smear positivity recorded. # 0 contacts contained missing data on these two fields. ** 3954 (11.3%) contacts had no data recorded on ‘first ring’. We performed a sensitivity analysis that did not materially affect any of the results. PTB ¼ pulmonary tuberculosis; OR ¼ odds ratio; aOR ¼ adjusted OR; CI ¼ confidence interval; IGRA ¼ interferon-gamma release assay.

proportion of LTBI in the first and second rings together may have decreased when the proportion was high (.10%) in the first ring. This could have led to artefactual changes in the proportion of screening outcomes. Furthermore, contacts who failed to complete screening may have been less likely to have Table 5 cases*

TB, as contacts are less likely to attend if they have no symptoms, potentially falsely increasing the proportion of contacts screening positive. The overall failure rate of 40.9% remained unacceptably high. The proportion of contacts receiving chemoprophylaxis increased. This could

Univariate analysis and multivariate regression identifying determinants of a positive screening episode in contacts of EPTB Univariate analysis

Multivariate analysis

Risk factor

Frequency n (%)

OR (95%CI)

P value

aOR (95%CI)

P value

Age, years† 0–15 16–64 765

5483 (53.9) 4253 (41.8) 356 (3.50)

3.71 (3.09–4.46) — 0.091 (0.013-0.653)

,0.001 — 0.003

3.48 (2.81–4.32) — 0.127 (0.018-0.913)

,0.001 — 0.04

Male sex‡

5069 (49.9)

0.823 (0.698–0.972)

0.021

0.706 (0.578–0.862)

0.001

Ethnicity§ White Black

414 (4.10) 849 (8.40)

— 1.83 (1.22–2.75)

— 0.003

— 1.38 (0.861–2.22)

— 0.180

6732 (66.2)

0.512 (0.352–0.746)

Other

Indian subcontinent

468 (4.6)

1.99 (1.29–3.08)

0.002

1.72 (1.05–2.81)

0.031

IGRA¶

1121 (11.0)

1.31 (1.04–1.67)

0.024

1.04 (0.760–1.41)

0.829

Lower staff workload¶

3053 (30.0)

1.22 (1.02–1.44)

0.026

1.21 (0.967–1.51)

0.096

First ring contact#

8396 (82.6)

1.01 (0.721–1.41)

0.960

0.966 (0.619–1.51)

0.878

,0.001

0.473 (0.310–0.722)

,0.001

* This table lists the independent contribution of six predictors for a positive screening episode as described using a logistic regression model. For age, working-age adults (age 16–64 years) were the comparator. For ethnicity, the White group was the comparator (n ¼ 10 164); 7112 contacts were included in the regression analysis; 3052 (30.0%) were excluded, as they contained missing data. We also performed a sensitivity analysis by excluding ethnicity and relation which therefore included 8598 (84.6%) contacts. The aOR for lower staff workload changed to 1.5 (1.24–1.83). There were no other material changes. † 72 (0.7%) contacts had no age recorded. ‡ 122 (1.2%) contacts had no sex recorded. § 1701 (16.7%) contacts had no ethnicity recorded. ¶ 0 contacts contained missing data on these two fields. # 1117 (11.0%) contacts had no data recorded on ‘first ring’. We performed a sensitivity analysis that did not materially affect any of the results. EPTB ¼ extra-pulmonary tuberculosis; OR ¼ odds ratio; aOR ¼ adjusted OR; CI ¼ confidence interval; IGRA ¼ interferon-gamma release assay.

TB contact tracing in Birmingham

be due to an increase in the awareness of LTBI as a diagnostic entity. Screening completion The study identified a number of variables associated with screening completion for both contacts of PTB and EPTB. Contacts of PTB were less likely to complete screening than contacts of EPTB. This is probably because contacts of EPTB patients are more commonly closer family contacts who are more likely to be engaged with the process. In both groups, contacts were less likely to complete screening if they were of working age. Clinics often run during working hours, which makes it difficult for working adults to attend: one solution may be to run evening or weekend clinics to target this population. Interestingly, contacts from the first ring were less likely to complete screening than later rings. The reasons for this are unclear, but important, as contacts of PTB in the first ring were more likely to screen positive and thus require strict efforts to improve completion rates. Among contacts, males were less likely to complete screening, but there was no clinically relevant difference between the sexes in the odds of a positive screening episode. Contacts of active TB who were Black were less likely to complete screening, as were contacts of PTB who were from the Indian subcontinent. This is worrying, as the highest rates of TB in the United Kingdom are currently in the Indian, Pakistani and Black ethnic groups.2 Further research is needed to examine the reasons behind this: it is possible to speculate that language and cultural factors may contribute, and this will be important when engaging with these communities. Positive screening outcome The results confirm the findings of previous research in that positive screening outcomes are more common in contacts of PTB and that smear positivity of the index case is the most important predictor after contact ring.13,14 The current guidance of the National Institute for Clinical Excellence (NICE) in the United Kingdom recommends contact tracing in schools for PTB cases. 10 We demonstrate that although contacts aged ,16 years were more likely to have a positive screening episode compared to those of working age, those who were identified through school were much less likely to screen positive. This has important ramifications, as contact tracing in schools can be time-consuming and expensive. Interestingly, contacts of PTB who were from the Indian subcontinent were less likely to screen positive. These contacts were also less likely to complete screening, a finding that may have biased the results, as infected contacts from the subcontinent may have been from poorer backgrounds than contacts who were well, and may have been lost to

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follow-up due to an inability to speak English and problems accessing services. Contact tracing of EPTB cases also revealed a significant burden of active TB and LTBI, which is consistent with previous reports.13,14 This corroborates current guidance from NICE, which recommend assessing the need for contact tracing in all active TB cases, irrespective of site.10,13,14 Although EPTB cases are not infectious, it is likely that transmission occurs in high-risk communities, such as ethnic groups and communities residing in high density housing, where both the contact and index cases may have been infected by a third individual.13 As for PTB, children aged ,16 years who were contacts of EPTB were more likely to have a positive screening episode than those of working age. The finding that child contacts of any active TB case were more likely to be infected is significant, and reinforces the emphasis the World Health Organization has given to the growing burden of TB in childhood.15 An encouraging finding is that contacts of PTB who were tested using IGRAs were more likely both to complete screening and to have a positive screening episode. This is probably because IGRAs require only one clinic attendance by the contact and are therefore less time-intensive than the tuberculin skin test. IGRAs may also be more sensitive at detecting active TB and LTBI, and they have been endorsed by NICE in situations where they may increase completion of contact tracing.10,16,17 Furthermore, the results of this study suggest that more distant contacts are less likely to screen positive than closer contacts. In accordance with various guidelines, risk should be assessed on a case-by-case basis depending on the infectiousness of the index case, duration of exposure to the index and risk of TB among contacts.8,10,18 Limitations The data were analysed retrospectively, meaning that some data were missing and could not be recovered, particularly for ethnicity and relation. In a sensitivity analysis excluding these variables, these missing data did not affect the significance of the other variables. Importantly, we could not audit retrospectively how closely screening guidelines were adhered to. The data analysed were routinely collected and were not part of a specific research database, which may also have led to data inaccuracies. We cannot exclude confounding by factors that were not measured in our study. Furthermore, changes in practice and personnel over time may have affected the results. Importantly, the number of people who were true contacts of an index case, but who were not identified during the contact tracing process, cannot be known.

CONCLUSION TB remains a problem in Birmingham, and contact

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tracing in both PTB and EPTB cases is useful in case finding. Contact tracing programmes should aim to improve completion rates in the working age population and in the Black and Subcontinent population, using IGRAs where possible. Our results may be used to improve the effectiveness and efficiency of local programmes, which are essential to meet the aim of TB elimination in low-incidence countries by 2050.1 Acknowledgements The authors wish to thank the patients and staff of the Birmingham TB clinic, and in particular J Innes, who collected the majority of this data and designed and maintained the database. We would also like to thank M Munang who contributed to the initial stages of the study design and checking of the primary data. All authors are salaried employees of the National Health Service. No specific funding for this project was gained. Conflict of interest: None declared

References 1 World Health Organization. The Stop TB Strategy: building on and enhancing DOTS to meet the TB-related Millennium Development Goals. WHO/HTM/STB/2006.37. Geneva, Switzerland: WHO, 2006. 2 Pedrazzoli D, Fulton N, Anderson L, Lalor M, Abubakar I, Zenner D. Tuberculosis in the UK: 2012 report. London, UK: Health Protection Agency, 2012. http://www.hpa.org.uk/ w e b w / H PAw e b & H PAw e b S t a n d a r d / H PAw e b _ C / 1317134916916 Accessed March 2014. 3 Birmingham City Council. Demographic briefing 2011/02 — ethnicity in Birmingham. Birmingham, UK: Birmingham City Council, 2011. 4 Birmingham City Council. Report of the Health and Adults Overview and Scrutiny Committee: tuberculosis in Birmingham. Birmingham, UK: Birmingham City Council, 2012. 5 Abubakar I, Stagg H, Cohen T et al. Controversies and unresolved issues in tuberculosis prevention and control: a low burden-country perspective. J Infect Dis 2012; 205 (Suppl 2): S293–S300.

6 Fox G J, Barry S E, Britton W J, Marks G B. Contact investigation for tuberculosis: a systematic review and metaanalysis. Eur Respir J 2013; 41: 140–156. http://www. pubmedcentral.nih.gov/articlerender.fcgi?artid¼3533588&tool ¼pmcentrez&rendertype¼abstract Accessed March 2014. 7 Joint Tuberculosis Committee of the British Thoracic Society. Control and prevention of tuberculosis in the United Kingdom:Code of Practice 2000. Thorax 2000; 55: 887–901. 8 Erkens C G M, Kamphorst M, Abubakar I, et al. Tuberculosis contact investigation in low-prevalence countries: a European consensus. Eur Respir J 2010; 36: 925–949. 9 Reichler M R, Reves R, Bur S, et al. Evaluation of investigations conducted to detect and prevent transmission of tuberculosis. JAMA 2002; 287: 991–995. 10 National Institute for Clinical Excellence. Clinical diagnosis and management of tuberculosis, and measures for its prevention and control. London, UK: NICE, 2011. 11 Pisu M, Gerald J, Shamiyeh J E, Bailey W C, Gerald L B. Targeted tuberculosis contact investigation saves money without sacrificing health. J Public Health Manag Pract 2013; 15: 319–327. 12 Health Protection Agency. Investigation of specimens for Mycobacterium species. London, UK: HPA, 2006. 13 Underwood B R, White V L C, Baker T, Law M, Moore-Gillon J C. Contact tracing and population screening for tuberculosis who should be assessed? J Public Health 2003; 25: 59–61. 14 Mandal P, Craxton R, Chalmers J D et al. Contact tracing in pulmonary and non-pulmonary tuberculosis. QJM 2012; 105: 741–747. 15 World Health Organization. Global tuberculosis report, 2012. WHO/HTM/TB/2012.6. Geneva, Switzerland: WHO, 2012. 16 Diel R, Goletti D, Ferrara G, et al. Interferon-c release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J 2011; 37: 88–99. 17 Sester M, Sotgiu G, Lange C, et al. Interferon-c release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J 2011; 37: 100–111. 18 Taylor Z, Nolan C M, Blumberg H M. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Recomm Rep 2005; 54 (RR-12): 1–81.

TB contact tracing in Birmingham

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APPENDIX

were managed in accordance with national guidelines.1

Contact screening

Data collection Data were collected on a number of factors hypothesised to affect the two outcomes. These data included demographics such as age, sex and ethnicity. Age was categorised into three groups, 0–15 (dependent), 16–64 (working adults) and 765 (retired) years. As TB is more common in people born overseas, data were collected on ethnicity.2,3 Ethnicity was categorised as White, Black (Afro-Caribbean and sub-Saharan African), Indian subcontinent (India, Pakistan and Bangladesh) and Other. Data were collected on type of contact (first degree relative, partner, other relative, in-law, friend, school contact or other) to assess the hypothesis that closer contacts of index cases are more likely to complete screening.4,5 Data were also collected on whether the contact was screened using TST or IGRA; for contacts of cases of pulmonary TB, data on index case smear positivity were collected. To assess the effect of human resources on screening completion, a ratio of contacts identified to nurse numbers was calculated and transformed into a binary variable, with work-

A contact with 78 h of exposure per day was defined as a close contact, and invited to be included in the first ‘ring’ of contacts. The first ring generally included relatives, partners and school contacts. If .10% of the first ring of contacts screened had a positive tuberculin skin test (TST), the screening team invited a second ring of contacts to participate (usually friends, work place colleagues and more distant relatives). Active tuberculosis (TB) was screened using chest radiograph and sputum examination for acid-fast bacilli, as well as microbiological sampling or imaging of other sites as indicated clinically. Latent tuberculous infection (LTBI) was diagnosed in those contacts without evidence of active TB with TST or interferon-gamma release assay (IGRA) positivity (after 2009). Screening outcomes (failure to complete screening, negative screen, bacille Calmette-Gu´erin [BCG] offered, LTBI treatment offered and active TB treatment offered) were recorded on a database and active TB and LTBI

Table A.1 Univariate analysis and multivariate regression identifying determinants for completion of screening in contacts of cases of pulmonary TB* Univariate analysis Risk factor

Multivariate analysis

Frequency (%)

OR (95%CI)

P value

aOR (95%CI)

P value

Age, years 0–15 16–64 765

13 548 (38.6) 19 938 (56.8) 1 456 (4.1)

2.01 (1.91–2.10) — 1.58 (1.40–1.77)

,0.001 — ,0.001

2.85 (2.63–3.08) — 1.36 (1.15–1.60)

,0.001 — ,0.001

Male sex‡

16 452 (46.9)

0.863 (0.825–0.902)

,0.001

0.872 (0.815–0.934)

,0.001

3 900 2548 17 016 845

(11.1) (7.3) (48.5) (2.4)

— 0.667 (0.602–740) 0.567 (0.526–0.610) 0.968 (0.826–1.13)

— ,0.001 ,0.001 0.685

— 0.575 (0.503–0.658) 0.639 (0.575–0.711) 0.884 (0.722–1.08)

— ,0.001 ,0.001 0.23

(18.7) (4.0) (15.2) (5.7) (3.5) (2.7) (8.9) (50.1)

1.06 0.874 0.657 0.679 4.01 2.46 1.16

— (0.936–1.19) (0.811–0.941) (0.592–0.729) (0.599–0.771) (3.34–4.81) (2.24–2.71) (1.11–1.21)

— 0.382 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001

1.45 0.655 0.933 0.823 4.06 1.53 1.03

— (1.27–1.65) (0.601–0.715) (0.830–1.05) (0.699–0.970) (3.07–5.36) (1.31–1.78) (0.963–1.11)

— ,0.001 ,0.001 0.25 0.02 ,0.001 ,0.001 0.37

†

Ethnicity§ White Black Indian subcontinent Other Relation¶ First degree relative Partner Other relative In-law Friend School Other Index is smear-positive# IGRA** Lower staff workload**

6 1 5 2 1

552 420 351 003 212 952 3 130 17 597

3 722 (10.6)

1.38 (1.29–1.48)

,0.001

1.29 (1.18–1.41)

,0.001

12 058 (34.4)

1.19 (1.14–1.25)

,0.001

1.01 (0.942–1.08)

0.79

* This table lists the independent contribution of seven predictors for the completion of screening as described using a logistic regression model. For age, working age adults (16 – 64 years) were the comparator. For ethnicity, the White group was the comparator. For relationships, first degree relatives were the comparator (n ¼ 35 098); 14 733 contacts were included in the regression analysis, 20 365 (58.0%) were excluded, as they contained missing data. We also performed a sensitivity analysis by excluding ethnicity and relation. This included 27 007 (76.9%) contacts and did not materially affect any of the results. † 156 (0.4%) contacts had no age recorded. ‡ 694 (2.0%) contacts had no sex recorded. § 10 789 (30.7%) contacts had no ethnicity recorded. ¶ 14 478 (41.2%) contacts had no relation status recorded. # 488 (1.4%) contacts had no smear positivity recorded. ** No contacts contained missing data on these two fields. TB ¼ tuberculosis; OR ¼ odds ratio; CI ¼ confidence interval; aOR ¼ adjusted OR; IGRA ¼ interferon-gamma release assay.

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Table A.2 Univariate analysis and multivariate regression identifying determinants for completion of screening in contacts of cases of extra-pulmonary TB* Univariate analysis Risk factors

Multivariate analysis

Frequency (%)

OR (95%CI)

P value

aOR (95%CI)

P value

Age, years 0–15 16–64 765

5483 (53.9) 4253 (41.8) 356 (3.50)

2.69 (2.40–3.01) — 1.46 (1.11–1.91)

,0.001 — 0.007

3.25 (2.74–3.84) — 1.41 (0.995–2.00)

,0.001 — 0.054

Male sex‡

5069 (49.9)

0.822 (0.745–0.906)

,0.001

0.722 (0.629–0.828)

,0.001

Ethnicity§ White Black Indian subcontinent Other

414 849 6732 468

(4.10) (8.40) (66.2) (4.6)

— 0.760 (0.570–1.01) 1.05 (0.817–1.34) 1.49 (1.05–2.12)

— 0.062 0.71 0.026

— 0.608 (0.416–0.888) 0.960 (0.680–1.36) 1.39 (0.869–2.21)

— 0.010 0.82 0.17

Relation¶ First degree relative Partner Other relative In-law Friend School Other

3315 781 1215 608 117 2 112

(32.6) (7.7) (12.0) (6.0) (1.2) (0.02) (1.10)

— (0.724–1.06) (1.03–1.46) (0.488–0.718) (0.258–0.555) — 0.863 (0.543–1.37)

— 0.17 0.020 ,0.001 ,0.001 — 0.53

— (1.08–1.65) (0.856–1.27) (0.643–0.995) (0.321–0.844) — 0.855 (0.459–1.98)

— 0.007 0.68 0.045 0.08 — 0.62

IGRA#

1121 (11.0)

1.02 (0.880–1.20)

0.73

1.18 (0.985–1.41)

0.073

Lower staff workload#

3053 (30.0)

0.823 (0.742–0.912)

,0.001

0.919 (0.801–1.05)

0.23

†

0.875 1.23 0.592 0.378

1.33 1.04 0.800 0.521

* This table lists the independent contribution of six predictors for the completion of screening as described using a logistic regression model. For age, working-age adults (16 – 64 years) were the comparator. For ethnicity, the White group was the comparator. For relationships, first degree relatives were the comparator. The model was unable to calculate ORs for school contacts of cases of extra-pulmonary TB due to the low number of contacts available for analysis (n ¼ 10 164); 5398 contacts were included in the regression analysis. 4766 (46.9%) were excluded, as they contained missing data. We also performed a sensitivity analysis by excluding ethnicity and relation which therefore included 8598 (84.6%) contacts. The aOR for lower staff workload changed to 0.859 (0.759-0.972). There were no other material changes. † 72 (0.7%) contacts had no age recorded. ‡ 122 (1.2%) contacts had no sex recorded. § 1701 (16.7%) contacts had no ethnicity recorded. ¶ 4014 (39.5%) contacts had no relation status recorded. # 0 contacts contained missing data on these two fields. TB ¼ tuberculosis; OR ¼ odds ratio; CI ¼ confidence interval; aOR ¼ adjusted OR; IGRA ¼ interferon-gamma release assay.

load defined as lower when there were ,500 contacts to 1 nurse per year. Missing data Table A.5 details all missing data for those contacts who had an outcome available. Contacts who had data missing on any variable included in the regression models were excluded from the analysis. For sex, age, TB site, smear positivity, IGRA and staff workload, the proportion of missing data was ,2% and not felt to be significant. For ethnicity, relation and first ring contact, the proportion of missing data was .2%. A sensitivity analyses for first ring contact was performed and the results highlighted in the legend of each table. We conducted a further sensitivity analysis in which we excluded both the relation and ethnicity field from the models.

References 1 National Institute for Clinical Excellence. Clinical diagnosis and management of tuberculosis, and measures for its prevention and control. London, UK: NICE, 2006. 2 Pedrazzoli D, Fulton N, Anderson L, Lalor M, Abubakar I, Zenner D. Tuberculosis in the UK: 2012 report. London, UK: Health Protection Agency, 2012. http://www.hpa.org.uk/webw/ HPAweb&HPAwebStandard/HPAweb_C/1317134916916 Accessed March 2014. 3 Cain K P, Haley C A, Armstrong L R, et al. Tuberculosis among foreign-born persons in the United States: achieving tuberculosis elimination. Am J Respir Crit Care Med 2007; 175: 75–79. 4 Fok A, Numata Y, Schulzer M, FitzGerald M J. Risk factors for clustering of tuberculosis cases: a systematic review of population-based molecular epidemiology studies. Int J Tuberc Lung Dis 2008; 12 : 480–492. 5 Kenyon T A, Valway S E, Ihle W W, Onorato I M, Castro K G. Transmission of multidrug-resistant Mycobacterium tuberculosis during a long airplane flight. N Engl J Med 1996; 334: 933– 938.

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iii

Table A.3 Univariate analysis and multivariate regression identifying determinants of a positive screening episode in contacts of cases of pulmonary TB* Univariate analysis Risk factors

Multivariate analysis

Frequency (%)

OR (95%CI)

P value

aOR (95%CI)

P value

Age, years 0–15 16–64 765

13 548 (38.6) 19 938 (56.8) 1 456 (4.1)

4.68 (4.34–5.04) — 0.303 (0.200–0.460)

,0.001 — ,0.001

5.87 (5.21–6.61) — 0.257 (0.150–0.441)

,0.001 — ,0.001

Male sex‡

16 452 (46.9)

0.988 (0.923–1.06)

0.72

0.916 (0.826–1.01)

Ethnicity§ White Black Indian subcontinent Other

3 900 (11.1) 2 548 (7.3) 17 016 (48.5) 845 (2.4)

— 1.70 (1.50–1.91) 0.515 (0.467–0.568) 1.37 (1.14–1.65)

— ,0.001 ,0.001 0.001

— 1.16 (0.98–1.36) 0.422 (0.366–0.486) 1.34 (1.05–1.71)

— 0.086 ,0.001 0.019

— (0.308–0.485) (0.839–1.03) (0.313–0.462) (0.713–1.03) (0.367–0.616) (0.586–0.768)

— ,0.001 0.18 ,0.001 0.090 ,0.001 ,0.001

1.05 0.581 1.05 0.730 0.417 0.913

— (0.811–1.35) (0.513–0.658) (0.843–1.31) (0.578–0.921) (0.305–0.571) (0.826–1.01)

— 0.733 ,0.001 0.67 0.008 ,0.001 0.36

†

Relation¶ First degree relative Partner Other relative In-law Friend School Other Index is smear-positive# IGRA** Lower staff workload**

6 1 5 2 1

552 420 351 003 212 952 3130

(18.7) (4.0) (15.2) (5.7) (3.5) (2.7) (8.9)

0.386 0.931 0.380 0.855 0.476 0.671

0.074

17 597 (50.1)

1.81 (1.69–1.94)

,0.001

2.36 (2.12–2.63)

,0.001

3 722 (10.6)

1.37 (1.25–1.51)

,0.001

1.39 (1.23–1.57)

,0.001

12 058 (34.4)

1.07 (0.995–1.14)

0.974 (0.880–1.07)

0.60

0.071

* This table lists the independent contribution of seven predictors for a positive screening episode as described using a logistic regression model. For age, workingage adults (16 – 64 years) were the comparator. For ethnicity, the White group was the comparator. For relationships, first degree relatives were the comparator (n ¼ 35 098); 14 733 contacts were included in the regression analysis, 20 365 (58.0%) were excluded, as they contained missing data. We also performed a sensitivity analysis by excluding ethnicity and relation. This included 27 007 (76.9%) of contacts and did not materially affect any of the results. † 156 (0.4%) contacts had no age recorded. ‡ 694 (2.0%) contacts had no sex recorded. § 10 789 (30.7%) contacts had no ethnicity recorded. ¶ 14 478 (41.2%) contacts had no relation status recorded. # 488(1.4%) contacts had no smear positivity recorded. ** No contacts contained missing data on these two fields. TB ¼ tuberculosis; OR ¼ odds ratio; CI ¼ confidence interval; aOR ¼ adjusted OR; IGRA ¼ interferon-gamma release assay.

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Table A.4 Univariate analysis and multivariate regression identifying determinants of a positive screening episode in contacts of cases of extra-pulmonary TB Univariate analysis Risk factors

Multivariate analysis

Frequency (%)

OR (95%CI)

P value

aOR (95%CI)

P value

Age, years 0–15 16–64 765

5483 (53.9) 4253 (41.8) 356 (3.50)

3.71 (3.09–4.46) — —

,0.001 — —

3.99 (2.97–5.34) — —

,0.001 — —

Male sex‡

5069 (49.9)

0.823 (0.698–0.972)

0.021

Ethnicity§ White Black Indian subcontinent Other

414 849 6732 468

(4.10) (8.40) (66.2) (4.60)

— 1.83 (1.22–2.75) 0.512 (0.352–0.746) 1.99 (1.29–3.08)

— 0.003 ,0.001 0.002

Relation¶ First degree relative Partner Other relative In-law Friend School Other

3315 781 1215 608 117 2 112

(32.6) (7.7) (12.0) (6.0) (1.2) (0.02) (1.10)

— (0.379–0.807) (0.748–1.26) (0.431–0.951) (0.306–1.62) — 1.33 (0.686–2.59)

— 0.002 0.82 0.026 0.41 — 0.40

IGRA#

1121 (11.0)

1.31 (1.04–1.67)

Lower staff workload#

3053 (30.0)

1.22 (1.02–1.44)

†

0.553 0.970 0.640 0.704

0.809 (0.647–1.01) — 1.02 (0.617–1.69) 0.306 (0.189–0.494) 1.58 (0.922–2.70)

0.065 — 0.94 ,0.001 0.096

— (1.14–2.82) (0.775–1.39) (1.18–3.10) (0.324–2.66) — 2.13 (0.940–4.81)

— 0.012 0.81 0.009 0.89 — 0.090

0.024

1.24 (0.945–1.63)

0.12

0.026

1.02 (0.812–1.28)

0.86

1.79 1.04 1.91 0.928

* This table lists the independent contribution of six predictors for a positive screening episode as described using a logistic regression model. For age, working-age adults (16 – 64 years) were the comparator. For ethnicity, the White group was the comparator. For relationships, first degree relatives were the comparator. The model was unable to calculate ORs for school contacts of cases of extra-pulmonary TB due to the low number of contacts available for analysis. For adults aged 765 years, the model was unable to calculate ORs due to the low number of positive screening episodes in this population (n ¼ 10 164); 5398 contacts were included in the regression analysis; 4766 (46.9%) were excluded, as they contained missing data. We also performed a sensitivity analysis by excluding ethnicity and relation, which therefore, included 8598 (84.6%) contacts. The aOR for lower staff workload changed to 1.5 (1.24-1.83). There were no other material changes. † 72 (0.7%) contacts had no age recorded. ‡ 122 (1.2%) contacts had no sex recorded. § 1701 (16.7%) contacts had no ethnicity recorded. ¶ 4014 (39.5%) contacts had no relation status recorded. # No contacts contained missing data on these two fields. TB ¼ tuberculosis; OR ¼ odds ratio; CI ¼ confidence interval; aOR ¼ adjusted OR; IGRA ¼ interferon-gamma release assay.

Table A.5 Summary of missing data for all contacts who had available outcomes Variable

Frequency (%)

Sex Age Ethnicity Relation IGRA Lower staff workload First ring contact TB site Smear positivity (for pulmonary TB)

831 235 12 839 18 765 0 0 5541 896 488

IGRA ¼ interferon-gamma release assay; TB ¼ tuberculosis.

(1.80) (0.50) (27.8) (40.7) (0) (0) (12.0) (2.0) (1.4)

TB contact tracing in Birmingham

v

RESUME

Birmingham, Royaume-Uni, 1990–2010. Identifier les facteurs pr e´ dictifs d’ach`evement et de r´esultat positif du d´epistage (par exemple, diagnostic d’une infection tuberculeuse latente [LTBI] ou une tuberculose [TB] active). S C H E´ M A : Etude r e´ trospective de cohorte des d´eclarations de TB dans une ville europ´eenne. R E´ S U L T A T S : A partir de 7365 cas index, 46 158 contacts ont e´ t´e identifi´es. Au cours de la p´eriode d’´etude, 17 471 (40,9%) n’ont pas termin´e le d´epistage. Une TB active ou LTBI a e´ t´e diagnostiqu´e chez 2220 (7,0%) contacts de cas de TB pulmonaire (TBP) et chez 222 (2,7%) contacts de cas de TB extra-pulmonaire (TBEP). La proportion de contacts auxquels on a propos´e un traitement de LTBI a augment´e (P , CONTEXTE : OBJECTIF :

0,001) au long de l’´etude. L’age, ˆ l’origine ethnique, le sexe et le recours aux tests de lib´eration de l’interf´erongamma (IGRA) ont e´ t´e les facteurs pr´edictifs les plus importants de la compl´etude du d´epistage ; les hommes adultes de race noire ou venant du sous-continent indien e´ taient les moins susceptibles de terminer le d´epistage. L’age, ˆ le r´esultat du frottis des cas index et l’utilisation de l’IGRA ont e´ t´e les facteurs pr´edictifs les plus importants de r´esultats positifs du d´epistage (diagnostic de TB active ou LTBI). C O N C L U S I O N : La recherche de contacts de cas index de TBP et TBEP est utile en termes de d´epistage actif de cas. Les r´esultats de cette e´ tude peuvent servir a` cibler le d´epistage et am´eliorer l’efficacit´e et la rentabilit´e des programmes locaux de recherche des contacts. RESUMEN

M A R C O D E R E F E R E N C I A: La ciudad de Birmingham en el Reino Unido de 1990 al 2010. O B J E T I V O: Determinar los factores pronosticos ´ de la complecion ´ de la investigacion ´ de contactos y la obtencion ´ de un resultado positivo de la misma (es decir, un diagnostico ´ de infeccion ´ tuberculosa latente [LTBI] o de tuberculosis [TB] activa). M E´ T O D O: Fue este un estudio retrospectivo de cohortes sobre la notificacion ´ de casos de TB en una ciudad europea. R E S U LT A D O S: Se detectaron 46 158 contactos de 7365 casos iniciales de TB. Durante el estudio 17 471 personas no completaron la investigacion ´ de contactos (40,9%). Se diagnostico´ TB activa o LTBI en 2220 contactos de casos de TB pulmonar (TBP) (7,0%) y en 222 contactos de TB extrapulmonar (TBEP) (2,7%). La proporcion ´ de contactos a quienes se propuso el tratamiento de la LTBI

aumento´ durante el lapso del estudio (P , 0,001). Los principales factores pronosticos ´ de la complecion ´ de la investigacion ´ de contactos fueron la edad, la etnia, el sexo y el uso de las pruebas de liberacion ´ de interferon ´ gama (IGRA) y fue menos probable que la completaran los hombres adultos de etnia negra o procedentes del subcontinente indio. Los principales factores pronosticos ´ de un resultado positivo de la investigacion ´ de contactos (TB activa o LTBI) fueron la edad, la baciloscopia positiva del esputo del caso inicial y el uso de las pruebas de IGRA. ´ N: La investigacion CONCLUSIO ´ de contactos de los casos iniciales de TBP y TBEP es util ´ en la busqueda ´ activa de casos. Los resultados del presente estudio se pueden utilizar con el fin de orientar las investigaciones y mejorar la eficacia y la eficiencia de los programas locales de investigacion ´ de contactos.