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Problem New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. Approach We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization -- Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Local setting Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Relevant changes Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Lessons learnt Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional researchcapacity strengthening. Such capacity-building approaches pr [ABSTRACT FROM AUTHOR]

The article presents a study on the effectiveness of extended isoniazid therapy as treatment for tuberculosis in adults with HIV infection in Botswana. The study uses a randomized and placebo-controlled trial in which Cox regression analysis is used to estimate the effect of antiretroviral therapy and compare incident tuberculosis in groups. It is inferred that 36 months' isoniazid prophylaxis is effective for the prevention of tuberculosis than in 6-month prophylaxis in individuals with HIV.

Antiretroviral therapy (ART) is lifesaving in patients with advanced HIV infection, but the magnitude of benefit in HIV-infected patients receiving tuberculosis (TB) treatment remains uncertain, and population-based data from developing countries are limited. We prospectively collected data about HIV-infected TB patients from February 2003 through January 2004 in Ubon-ratchathani, Thailand. During 12 months, HIV was diagnosed in 329 (14%) of 2,342 patients registered for TB treatment. Of patients with known outcomes, death during TB treatment occurred in 5 (7%) of 71 who received ART and 94 (43%) of 219 who did not. Using multivariate analysis, we found a large reduction in the odds of death for patients receiving ART before or during TB treatment (odds ratio, 0.2; 95% confidence interval, 0.1-0.5), adjusting for CD4 count, smear status, co-trimoxazole use, and treatment facility. ART is associated with a substantial reduction in deaths during TB treatment for HIV-infected TB patients in Thailand. [ABSTRACT FROM AUTHOR]

Summary Background The burden of tuberculosis is compounded by drug-resistant forms of the disease. This study aimed to analyse data on antituberculosis drug resistance gathered by the WHO and International Union Against Tuberculosis and Lung Disease Global Project on Anti-tuberculosis Drug Resistance Surveillance. Methods Data on drug susceptibility testing for four antituberculosis drugs-isoniazid, rifampicin, ethambutol, and streptomycin-were gathered in the third round of the Global Project (1999-2002) from surveys or ongoing surveillance in 79 countries or geographical settings. These data were combined with those from the first two rounds of the project and analyses were done. Countries that participated followed a standardised set of guidelines to ensure comparability both between and within countries. Findings The median prevalence of resistance to any of the four antituberculosis drugs in new cases of tuberculosis identified in 76 countries or geographical settings was 10·2% (range 0·0-57·1). The median prevalence of multidrug resistance in new cases was 1·0% (range 0·0-14·2). Kazakhstan, Tomsk Oblast (Russia), Karakalpakstan (Uzbekistan), Estonia, Israel, the Chinese provinces Liaoning and Henan, Lithuania, and Latvia reported prevalence of multidrug resistance above 6·5%. Trend analysis showed a significant increase in the prevalence of multidrug resistance in new cases in Tomsk Oblast (p<0·0001). Hong Kong (p=0·01) and the USA (p=0·0002) reported significant decreasing trends in multidrug resistance in new cases of tuberculosis. Interpretation Multidrug resistance represents a serious challenge for tuberculosis control in countries of the former Soviet Union and in some provinces of China. Gaps in coverage of the Global Project are substantial, and baseline information is urgently required from several countries with high tuberculosis burden to develop appropriate control interventions. [ABSTRACT FROM AUTHOR]