Research on Implementation of Interventions in Tuberculosis Control in Low- and Middle-Income Countries: A Systematic Review

Cobelens and colleagues systematically reviewed research on implementation and cost-effectiveness of the WHO-recommended interventions for tuberculosis. Background: Several interventions for tuberculosis (TB) control have been recommended by the World Health Organization (WHO) over the past decade. These include isoniazid preventive therapy (IPT) for HIV-infected individuals and household contacts of infectious TB patients, diagnostic algorithms for rule-in or rule-out of smear-negative pulmonary TB, and programmatic treatment for multidrug-resistant TB. There is no systematically collected data on the type of evidence that is publicly available to guide the scale-up of these interventions in low- and middle-income countries. We investigated the availability of published evidence on their effectiveness, delivery, and cost-effectiveness that policy makers need for scaling-up these interventions at country level. Methods and Findings: PubMed, Web of Science, EMBASE, and several regional databases were searched for studies published from 1 January 1990 through 31 March 2012 that assessed health outcomes, delivery aspects, or cost-effectiveness for any of these interventions in low- or middle-income countries. Selected studies were evaluated for their objective(s), design, geographical and institutional setting, and generalizability. Studies reporting health outcomes were categorized as primarily addressing efficacy or effectiveness of the intervention. These criteria were used to draw landscapes of published research. We identified 59 studies on IPT in HIV infection, 14 on IPT in household contacts, 44 on rule-in diagnosis, 19 on rule-out diagnosis, and 72 on second-line treatment. Comparative effectiveness studies were relatively few (n = 9) and limited to South America and sub-Saharan Africa for IPT in HIV-infection, absent for IPT in household contacts, and rare for second-line treatment (n = 3). Evaluations of diagnostic and screening algorithms were more frequent (n = 19) but geographically clustered and mainly of non-comparative design. Fifty-four studies evaluated ways of delivering these interventions, and nine addressed their cost-effectiveness. Conclusions: There are substantial gaps in published evidence for scale-up for five WHO-recommended TB interventions settings at country level, which for many countries possibly precludes program-wide implementation of these interventions. There is a strong need for rigorous operational research studies to be carried out in programmatic settings to inform on best use of existing and new interventions in TB control. Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is curable and preventable, but according to the World Health Organization (WHO), in 2011, 8.7 million people had symptoms of TB (usually a productive cough and fever) and 1.4 million people—95% from low- and middle-income countries—died from TB. TB is also the leading cause of death in people with HIV worldwide, and in 2010 about 10 million children were orphaned as a result of their parents dying from TB. To help reduce the considerable global burden of TB, a global initiative called the Stop TB Partnership, led by WHO, has implemented a strategy to reduce deaths from TB by 50% by 2015—even greater than the target of Millennium Development Goal 6 (to reverse the increase in TB incidence by 2015). Why Was This Study Done?: Over the past few years, WHO has recommended that countries implement several interventions to help control the spread of tuberculosis through measures to improve prevention, diagnosis, and treatment. Five such interventions currently recommended by WHO are: treatment with isoniazid to prevent TB among people who are HIV positive, and also among household contacts of people infected with TB; the use of clinical pathways (algorithms) for diagnosing TB in people accessing health care who have a negative smear test—the most commonly used diagnostic test, which relies on sputum samples—(“rule-in algorithms”); screening algorithms for excluding TB in people who have HIV (“rule-out algorithms”); and finally, provision of second-line treatment for multidrug-resistant tuberculosis (a form of TB that does not respond to the most commonly used drugs) under programmatic conditions. The effectiveness of these interventions, their costs, and the practicalities of implementation are all important information for countries seeking to control TB following the WHO guidelines, but little is known about the availability of this information. Therefore, in this study the researchers systematically reviewed published studies to find evidence of the effectiveness of each of these interventions when implemented in routine practice, and also for additional information on the setting and conditions of implemented interventions, which might be useful to other countries. What Did the Researchers Do and Find?: Using a specific search strategy, the researchers comprehensively searched through several key databases of publications, including regional databases, to identify 208 (out of 11,489 found initially) suitable research papers published between January 1990 and March 2012. For included studies, the researchers also noted the geographical location and setting and the type and design of study. What Do These Findings Mean?: These findings suggest that there is limited evidence on effectiveness, delivery, and cost-effectiveness to guide the scale-up of five WHO recommended interventions to control tuberculosis in the countries and settings, despite the urgent need for such interventions to be implemented. The poor evidence base identified in this review highlights the tension between the decision to adopt the recommendation and its implementation adapted to local circumstances, and may be an important reason as to why these interventions are not implemented in many countries. This study also suggests creative thinking is necessary to address the gaps between WHO recommendations and global health policy on new interventions and their real-world implementation in country-wide TB control programs. Future research should focus more on operational studies, the results of which should be made publicly available, and researchers, donors, and medical journals could perhaps re-consider their priorities to help bridge the knowledge gap identified in this study. Additional Information: Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001358.