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Recommendations for Investigating Contacts of Persons with Infectious Tuberculosis in Low- and Middle-Income Countries. Geneva: World Health Organization; 2012.

Cover of Recommendations for Investigating Contacts of Persons with Infectious Tuberculosis in Low- and Middle-Income Countries

Recommendations for Investigating Contacts of Persons with Infectious Tuberculosis in Low- and Middle-Income Countries.

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This chapter describes the areas in which information is lacking, as identified by the expert panel.


The panel identified major gaps in the evidence for use of contact investigation as a routine intervention in TB control. There is no evidence that identification and evaluation of contacts reduces TB incidence or mortality. Although studies of the impact of the intervention would be difficult, a cluster randomized or step-wedge design would be a reasonable approach. In addition, mathematical modelling, including cost–effectiveness estimates, would provide useful information. A comparison of contact investigation with other forms of active case finding could provide information to guide the choice of interventions, although contact investigation is best implemented by TB control programmes.

A major weakness in the literature is the lack of standardized protocols for studies. Such standardization would allow comparisons of use of the same approach under different conditions and enable identification of country-specific barriers to implementation. Different approaches to contact investigation, in particular use of an active versus a passive approach, have not been evaluated. Moreover, different screening and clinical evaluation algorithms have not been compared.

There is limited information on approaches to and the value of contact investigation in settings with a high prevalence of HIV infection, including testing of contacts as part of routine evaluation. Undertaking contact investigations in such settings would require overcoming significant operational and technical barriers. The current recommendation is to test new cases of TB for HIV. Ideally, contacts in settings with a high prevalence of HIV infection should also be tested. It is clear that treatment of LTBI in people with HIV infection reduces their risk for TB, but it has not been established whether treatment of contacts with HIV infection, regardless of whether they have been infected, is beneficial. Both operational investigations and clinical trials will be necessary to answer these questions.

There is also insufficient information on the yield of contact investigations when the index case has TB caused by drug-resistant M. tuberculosis. Systematic investigation of contacts of known or suspected cases of MDR-TB and XDR-TB may be effective for reducing transmission of drug-resistant strains of M. tuberculosis in a community, although this is not proven. In addition, contact investigation may reduce morbidity and mortality by shortening the time to diagnosis and initiation of effective treatment. There has been little systematic investigation of the epidemiology of MDR-TB and XDR-TB, and the potential role of transmission to adults and children who are household contacts has not been well quantified. Operational investigations, clinical trials and mathematical modelling will be necessary to prove this presumed benefit.

More generally, the use of any of the treatment regimens for LTBI in high-incidence, low-income settings in the framework of contact investigation requires further investigation. Smieja et al. (41) in 1999 systematically reviewed 11 randomized controlled clinical trials of isoniazid preventive therapy for 6–12 months and found that treatment resulted in a relative risk for active TB of 0.40 (95% confidence interval, 0.31–0.52) over 2 years or longer. Only two of these studies, however, were conducted in high-burden, low-income countries, and many other factors, such as feasibility, drug availability and cost, must be considered before recommending routine treatment for LTBI as a component of contact investigation in such settings.

Although interferon-gamma release assays, now commonly used in high-income areas, are currently too costly for routine use in high-burden settings, they may prove valuable for identifying LTBI in places where coverage with bacillus Calmette-Guérin is high, if or when the price drops (42). Use of this category of tests should be evaluated under programme conditions in high-burden settings to determine their performance, practicality and feasibility in contact investigations.

There is little information on the long-term benefits of treating LTBI in children, and long-term follow-up is needed. This will require a link between data on exposure and the development of active TB, which should be incorporated into national TB programme databases.

Copyright © World Health Organization 2012.

All rights reserved. Publications of the World Health Organization are available on the WHO web site ( or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: tni.ohw@sredrokoob).

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Bookshelf ID: NBK179069


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