Comparative Meta-Analysis of Tuberculosis Contact Investigation Interventions in Eleven High Burden CountriesPLOS ONE


Lucie Blok, Suvanand Sahu, Jacob Creswell, Sandra Alba, Robert Stevens, Mirjam I. Bakker
Agricultural and Biological Sciences (all) / Medicine (all) / Biochemistry, Genetics and Molecular Biology (all)


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Comparative Meta-Analysis of Tuberculosis

Contact Investigation Interventions in Eleven

High Burden Countries

Lucie Blok1*, Suvanand Sahu2, Jacob Creswell2, Sandra Alba3, Robert Stevens4, Mirjam

I. Bakker3 1 Koninklijk Instituut voor de Tropen (KIT) Health, 1090HA Amsterdam, Netherlands, 2 Stop TB Partnership,

Geneva 1211, Switzerland, 3 Koninklijk Instituut voor de Tropen (KIT) Biomedical Research, 1105 AZ

Amsterdam, Netherlands, 4 Mott-MacDonald, London EC4M 7RB, United Kingdom *



Screening of household contacts of tuberculosis (TB) patients is a recommended strategy to improve early case detection. While it has been widely implemented in low prevalence countries, the most optimal protocols for contact investigation in high prevalence, low resource settings is yet to be determined. This study evaluated contact investigation interventions in eleven lower and middle income countries and reviewed the association between context or program-related factors and the yield of cases among contacts.


We reviewed data from nineteen first wave TB REACH funded projects piloting innovations to improve case detection. These nineteen had fulfilled the eligibility criteria: contact investigation implementation and complete data reporting. We performed a cross-sectional analysis of the percentage yield and case notifications for each project. Implementation strategies were delineated and the association between independent variables and yield was analyzed by fitting a random effects logistic regression.


Overall, the nineteen interventions screened 139,052 household contacts, showing great heterogeneity in the percentage yield of microscopy confirmed cases (SS+), ranging from 0.1% to 6.2%). Compared to the most restrictive testing criteria (at least two weeks of cough) the aOR’s for lesser (any TB related symptom) and least (all contacts) restrictive testing criteria were 1.71 (95%CI 0.94−3.13) and 6.90 (95% CI 3.42−13.93) respectively.

The aOR for inclusion of SS- and extra-pulmonary TB was 0.31 (95% CI 0.15−0.62) compared to restricting index cases to SS+ TB. Contact investigation contributed between<1% and 14% to all SS+ cases diagnosed in the intervention areas.

PLOS ONE | DOI:10.1371/journal.pone.0119822 March 26, 2015 1 / 18


Citation: Blok L, Sahu S, Creswell J, Alba S, Stevens

R, Bakker MI (2015) Comparative Meta-Analysis of

Tuberculosis Contact Investigation Interventions in

Eleven High Burden Countries. PLoS ONE 10(3): e0119822. doi:10.1371/journal.pone.0119822

Academic Editor: Stefano Merler, Fondazione Bruno

Kessler, ITALY

Received: July 10, 2014

Accepted: January 16, 2015

Published: March 26, 2015

Copyright: © 2015 Blok et al. This is an open access article distributed under the terms of the Creative

Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability Statement: All relevant data are within the paper and its supporting Information files.

Funding: All projects included in the study were implemented with funding from TB REACH. HLSP and KIT were contracted by TB REACH as independent monitoring and evaluation agencies.

However, the analysis presented in this paper was not part of the contracted work. The authors received no funding for this additional analysis work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


This study confirms that high numbers of active TB cases can be identified through contact investigation in a variety of contexts. However, design and program implementation factors appear to influence the yield of contact investigation and its concomitant contribution to TB case detection.


It is estimated that tuberculosis affected 8.6 million people around the world in 2012, leading to 1.3 million deaths.[1] Despite successful initiation and expansion of DOTS and the Stop TB

Strategy in most parts of the world, early and effective identification of TB remains a challenge.

The World Health Organization (WHO) estimates that in 2012 approximately 35% of the incident cases of TB were missed.[1]

Active case finding (ACF) approaches within population groups believed to be at higher risk of developing TB are increasingly being used by TB control programs across a spectrum of settings.[2;3] Although the exact contribution of these approaches to improving case detection in different target populations is unclear, as is how best to optimize their effectiveness, [4;5] the ample evidence indicating that close contacts of people with active TB are at high risk of infection and disease justifies special attention.[6] Two meta-analyses of contact investigation studies found a pooled prevalence of active TB (all forms) among close contacts of 3.1% (95% CI 2.2–4.4) and 4.5% (95% CI 4.3–4.8), and a pooled prevalence of microbiological confirmed TB of 1.2% (95% CI 0.9–1.8) and 2.3% (95% CI 2.1–2.5) respectively.[7;8] Largely based on these findings, screening of household contacts has now been recommended by WHO in all settings. [9]

Since ACF requires additional resources and has opportunity costs, the expected yield for a chosen strategy in a given setting and the impact on overall case notification are important considerations for policy formation.[4] The systematic reviews cited above found a strong heterogeneity in percentage of contacts identified with active TB. A number of factors were identified as potentially influencing yield of screening, including contextual aspects such as background prevalence of TB or HIV infection, as well as those related to the design and implementation of the intervention. The latter might encompass timing of screening, the strategy employed to identify and trace contacts, the operative definitions for index case and contact, criteria for testing and the diagnostic tests used. While the reviews under discussion focused on yield of active or latent TB through contact investigation, evidence on how these various cited factors contribute to higher or lower yield is still lacking.[5;7;8;10] Consequently, the international guidelines on contact investigation stress the need for further research as a basis for firm operational recommendations.[9]