Control of tuberculosis in settings with high HIV prevalence

Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. Corbett and colleagues tested two active case-finding strategies to target long periods of infectiousness before diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission. Clusters of neighbourhoods in the high-density residential suburbs of Harare, Zimbabwe, were randomised to receive six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits. Randomisation was done by selection of discs of two colours from an opaque bag, with one disc to represent every cluster, and one colour allocated to each intervention group before selection began. In both groups, adult (≥ 16 years) residents volunteering chronic cough (≥ 2 weeks) had two sputum specimens collected for fluorescence microscopy. Community health workers and cluster residents were not masked to intervention allocation, but investigators and laboratory staff were masked to allocation until final analysis. The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents, compared between intervention groups; analysis was by intention to treat. The secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to before round six of intervention in 12% of randomly selected households from the two intervention groups combined; analysis was based on participants who provided sputum in the two prevalence surveys. Forty-six study clusters were identified and randomly allocated equally between intervention groups, with 55 741 adults in the mobile van group and 54,691 in the door-to-door group at baseline. HIV prevalence was 21% (1916/9060) and in the 6 months before intervention the smear-positive case notification rate was 2·8 per 1000 adults per year. The trial was completed as planned with no adverse events. The mobile van detected 255 smear-positive patients from 5466 participants submitting sputum compared with 137 of 4711 participants identified through door-to-door visits (adjusted risk ratio 1·48, 95% CI 1·11-1·96, p=0·0087). The overall prevalence of culture-positive tuberculosis declined from 6·5 per 1000 adults (95% CI 5·1-8·3) to 3·7 per 1000 adults (2·6-5·0; adjusted risk ratio 0·59, 95% CI 0·40-0·89, p=0·0112). Wide implementation of active case finding, particularly with a mobile van approach, could have rapid effects on tuberculosis transmission and disease.

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Editors’ note: People living with HIV are more susceptible to tuberculosis and the time period from infection to diagnosis or death is shorter than in HIV-negative people, whose tuberculosis is often not diagnosed for a year or more during which time they are infectious to others. In high HIV prevalence areas, early identification of people with active tuberculosis through active case finding can benefit those with and without HIV infection and provoke drops in community incidence. Recently transmitted tuberculosis is the most common source of infections in endemic areas where the bulk of transmission is from casual rather from close household contacts. This study compared two strategies for active case finding – a mobile van that stayed in a study cluster for 5 days announcing free sputum tests for anyone with chronic cough through a loudspeaker versus door-to-door visits asking for those with chronic cough and providing specimen containers along with leaflets stressing the benefits of early diagnosis and the important role of HIV-negative tuberculosis in transmission. Overall, active case finding provided the first investigation for 77% of smear-positive patients despite the fact that they were all symptomatic and lived within 2 km of a primary clinic. A random sample of 12% of households in all 46 clusters was surveyed before the intervention and before the 6th six-monthly intervention. This revealed that the mobile van approach produced more smear-positive tuberculosis cases despite the finding that HIV prevalence was similar (72% of cases in the mobile van group versus 67% of cases in the door-to-door group). Overall 41% of new TB cases diagnosed in the study area over the 3-year period were identified through these two active case finding approaches and infectious TB in the community fell by more than 40%. Active case finding played a major role in bringing TB under control in industrialised countries so why not now, particularly in high HIV prevalence countries?