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Contact Investigation for Tuberculosis: a Systematic Review and Meta-Analysis

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Contact Investigation for Tuberculosis: a Systematic Review and Meta-Analysis Eur Respir J 2013; 41: 140–156 DOI: 10.1183/09031936.00070812 CopyrightßERS 2013 ERJ Open articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 3.0 Contact investigation for tuberculosis: a systematic review and meta-analysis Gregory J. Fox*, Simone E. Barry#, Warwick J. Britton#," and Guy B. Marks*,+ ABSTRACT: Investigation of contacts of patients with tuberculosis (TB) is a priority for TB control AFFILIATIONS in high-income countries, and is increasingly being considered in resource-limited settings. This *Woolcock Institute of Medical Research, University of Sydney, review was commissioned for a World Health Organization Expert Panel to develop global contact #Centenary Institute of Cancer investigation guidelines. Medicine and Cell Biology, University We performed a systematic review and meta-analysis of all studies reporting the prevalence of of Sydney, " TB and latent TB infection, and the annual incidence of TB among contacts of patients with TB. Discipline of Medicine, Sydney Medical School, University of After screening 9,555 titles, we included 203 published studies. In 95 studies from low- and Sydney, and middle-income settings, the prevalence of active TB in all contacts was 3.1% (95% CI 2.2–4.4%, +Dept of Respiratory Medicine, I2599.4%), microbiologically proven TB was 1.2% (95% CI 0.9–1.8%, I2595.9%), and latent TB Liverpool Hospital, Sydney, Australia. infection was 51.5% (95% CI 47.1–55.8%, I2598.9%). The prevalence of TB among household 2 CORRESPONDENCE contacts was 3.1% (95% CI 2.1–4.5%, I 598.8%) and among contacts of patients with multidrug- G.J. Fox 2 resistant or extensively drug-resistant TB was 3.4% (95% CI 0.8–12.6%, I 595.7%). Incidence was Woolcock Institute of Medical greatest in the first year after exposure. In 108 studies from high-income settings, the prevalence Research of TB among contacts was 1.4% (95% CI 1.1–1.8%, I2598.7%), and the prevalence of latent University of Sydney 431 Glebe Point Road 25 infection was 28.1% (95% CI 24.2–32.4%, I 99.5%). There was substantial heterogeneity among Glebe published studies. Sydney 2037 Contacts of TB patients are a high-risk group for developing TB, particularly within the first year. Australia Children ,5 yrs of age and people living with HIV are particularly at risk. Policy recommendations E-mail: [email protected] must consider evidence of the cost-effectiveness of various contact tracing strategies, and also Received: incorporate complementary strategies to enhance case finding. May 03 2012 Accepted after revision: KEYWORDS: Contact tracing, early diagnosis, human, Mycobacterium tuberculosis, systematic Aug 10 2012 First published online: review, tuberculosis Aug 30 2012 uberculosis (TB) remains a major global strategies that have been proposed to increase case The online version of this article has been health challenge, affecting 8.8 million detection [4]. Active case finding may be worth- amended. The amendment is outlined in the T people each year, most of whom live in while in contacts of patients with TB because they correction published in the August 2015 low- and middle-income countries [1]. The are at higher risk of exposure to the causative issue of the European Respiratory Journal importance of TB control in social and economic organism than members of the general population [DOI: 10.1183/13993003.50708-2012]. development has been widely acknowledged, [5]. After exposure to airborne droplets containing including in the Millennium Development Mycobacterium tuberculosis, some contacts will be Goals. In this context, the World Health infected and some of these will go on to develop Organization (WHO) STOP TB Partnership has disease. The risk of a contact becoming infected set two targets: 1) to reduce prevalence and relates to the infectiousness of the TB patient, the deaths by 50% by 2015, relative to 1990 levels; duration and proximity of the contact [6, 7], and and 2) to eliminate TB as a public health problem susceptibility of the contact [8, 9]. The onset of by 2050 [2]. In order to achieve these targets, disease may occur early, within 6 weeks, or many healthcare systems will need to identify more years later [10]. Contact investigations are under- cases of TB at an earlier stage of the illness [3]. taken to prevent or detect these cases. Contact investigation involves the systematic Contact investigation has been standard practice evaluation of the contacts of known TB patients for decades in high-income countries, where the to identify active disease or latent TB infection incidence of TB in the general population is low (LTBI). It is one of a number of active case-finding [11]. It may involve clinical assessment, chest European Respiratory Journal Print ISSN 0903-1936 This article has supplementary material available from www.erj.ersjournals.com Online ISSN 1399-3003 140 VOLUME 41 NUMBER 1 EUROPEAN RESPIRATORY JOURNAL G.J. FOX ET AL. TUBERCULOSIS radiography, microbiological evaluation of sputum or a test to patients) had been identified before screening was conducted. detect LTBI, such as a tuberculin skin test (TST) or an We excluded studies where the diagnosis of TB was not made interferon-c release assay. There has been a growing interest according to clinical, radiological or microbiological criteria or in contact investigation in resource-limited settings as national where there were less than 10 index patients or contacts programmes seek new methods for improving case detection identified in the study. [12]. The WHO currently recommends contact investigation in Cross-sectional, case–control studies and cohort studies were two high-risk populations: children aged ,5 yrs [13] and included. We also sought evidence from any published people living with, or at high risk of, HIV infection [14]. randomised controlled trials. We excluded editorials, confer- Recently, the WHO has also launched the first international ence abstracts and systematic reviews. standards for the investigation of contacts of patients with infectious TB [15]. Data extraction and definitions Two reviewers (G.J. Fox and C. Dobler (Woolcock Institute of One previous meta-analysis examined data from 41 household Medical Research, University of Sydney, Sydney, Australia)) contact investigation studies in low–middle-income countries independently screened all titles identified in the database up to 2005 [16]. However, there has not yet been an analysis of searches. The full-text of all articles included by either reviewer contact investigation beyond the household setting or in high- on the basis of abstract was obtained. To determine eligibility income countries. Furthermore, the previous meta-analysis for inclusion, one author reviewed all full-text articles. A was limited to cases of TB that were diagnosed at the time of second author (W.J. Britton) repeated this assessment inde- the initial contact investigation. There has not yet been a meta- pendently for a random selection of 10% of full-text articles analysis of data on the incidence of TB among contacts during and there was complete agreement about excluded articles. the 5 yrs following exposure. Nor has there been an analysis of key risk groups, such as contacts of patients with multidrug- Two authors independently extracted data from all of the resistant (MDR)-TB. Therefore, the aim of the analysis included studies. One author (G.J. Fox) extracted all data from presented here is to systematically review and quantify data all studies, and the other authors (S.E. Barry, W.J. Britton and on the prevalence of TB and LTBI and the subsequent G.B. Marks) independently re-extracted data for six key data incidence of TB in contacts of patients with TB in household fields from all of the included studies between them. and non-household settings in high-, middle- and low-income Disagreements were resolved by consensus. countries and in various risk groups. Where data from the same contact cohort were included in This systematic review and meta-analysis was conducted as a multiple papers, we included the study with the most part of a GRADE (Grading of Recommendations Assessment, complete data. If the reviewers were certain the two studies Development and Evaluation) [17] review for an Expert Panel had the same participants and there were different sets of data that was convened to contribute to the development of in two papers then the results were merged into one entry. If a international guidelines on contact investigation for the paper described outcomes in two countries, the data from each WHO [15]. were reported separately. METHODS Data extracted from selected studies included: 1) study design, country, location of exposure, selection criteria for index Search strategy and study selection patients and contacts; 2) screening methods employed; and This review followed the methods described in the PRISMA 3) outcomes including number of contacts screened, the statement for the reporting of systematic reviews and meta- number of cases of TB and microbiologically proven disease analyses [18]. First, we searched the literature for available among contacts, the number of contacts with LTBI, and the systematic reviews and meta-analyses, identifying a Cochrane number of incident cases each year during the first 5 yrs. review [19], a systematic review of household contact investiga- Subgroup data were extracted for outcomes of TB, micro- tion [16], and two reviews focusing on specific populations [20, biologically proven TB and LTBI among contacts of acid-fast 21]. We then designed a search for all published studies that bacilli (AFB) smear-positive and AFB smear-negative source provided a measure of prevalence or incidence of TB or LTBI patients (index patients), index patients with HIV, and MDR- among contacts of patients with new or recurrent TB. We or extensively drug-resistant (XDR)-TB.
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