SummaryBackgroundControl of tuberculosis in settings with high HIV prevalence is a pressing public health priority. We 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.MethodsClusters 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. This trial is registered, number ISRCTN84352452.Findings46 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).InterpretationWide implementation of active case finding, particularly with a mobile van approach, could have rapid effects on tuberculosis transmission and disease.FundingWellcome Trust.

Unrecognized HIV infection was a common cause of primary care attendance. Routine HIV counseling and testing implemented at the primary care level may provide a simple and effective way of identifying older long-term survivors of mother-to-child transmission before the onset of severe immunosuppression and irreversible complications.

BackgroundDirectly observed treatment short course (DOTS), the global control strategy aimed at controlling tuberculosis (TB) transmission through prompt diagnosis of symptomatic smear-positive disease, has failed to prevent rising tuberculosis incidence rates in Africa brought about by the HIV epidemic. However, rising incidence does not necessarily imply failure to control tuberculosis transmission, which is primarily driven by prevalent infectious disease. We investigated the epidemiology of prevalent and incident TB in a high HIV prevalence population provided with enhanced primary health care.Methods and FindingsTwenty-two businesses in Harare, Zimbabwe, were provided with free smear- and culture-based investigation of TB symptoms through occupational clinics. Anonymised HIV tests were requested from all employees. After 2 y of follow-up for incident TB, a culture-based survey for undiagnosed prevalent TB was conducted. A total of 6,440 of 7,478 eligible employees participated. HIV prevalence was 19%. For HIV-positive and -negative participants, the incidence of culture-positive tuberculosis was 25.3 and 1.3 per 1,000 person-years, respectively (adjusted incidence rate ratio = 18.8; 95% confidence interval [CI] = 10.3 to 34.5: population attributable fraction = 78%), and point prevalence after 2 y was 5.7 and 2.6 per 1,000 population (adjusted odds ratio = 1.7; 95% CI = 0.5 to 6.8: population attributable fraction = 14%). Most patients with prevalent culture-positive TB had subclinical disease when first detected.ConclusionsStrategies based on prompt investigation of TB symptoms, such as DOTS, may be an effective way of controlling prevalent TB in high HIV prevalence populations. This may translate into effective control of TB transmission despite high TB incidence rates and a period of subclinical infectiousness in some patients.

BackgroundHIV counselling and testing is a key component of both HIV care and HIV prevention, but uptake is currently low. We investigated the impact of rapid HIV testing at the workplace on uptake of voluntary counselling and testing (VCT).Methods and FindingsThe study was a cluster-randomised trial of two VCT strategies, with business occupational health clinics as the unit of randomisation. VCT was directly offered to all employees, followed by 2 y of open access to VCT and basic HIV care. Businesses were randomised to either on-site rapid HIV testing at their occupational clinic (11 businesses) or to vouchers for off-site VCT at a chain of free-standing centres also using rapid tests (11 businesses). Baseline anonymised HIV serology was requested from all employees.HIV prevalence was 19.8% and 18.4%, respectively, at businesses randomised to on-site and off-site VCT. In total, 1,957 of 3,950 employees at clinics randomised to on-site testing had VCT (mean uptake by site 51.1%) compared to 586 of 3,532 employees taking vouchers at clinics randomised to off-site testing (mean uptake by site 19.2%). The risk ratio for on-site VCT compared to voucher uptake was 2.8 (95% confidence interval 1.8 to 3.8) after adjustment for potential confounders. Only 125 employees (mean uptake by site 4.3%) reported using their voucher, so that the true adjusted risk ratio for on-site compared to off-site VCT may have been as high as 12.5 (95% confidence interval 8.2 to 16.8).ConclusionsHigh-impact VCT strategies are urgently needed to maximise HIV prevention and access to care in Africa. VCT at the workplace offers the potential for high uptake when offered on-site and linked to basic HIV care. Convenience and accessibility appear to have critical roles in the acceptability of community-based VCT.

Highly acceptable VCT did not reduce HIV incidence in this predominantly male cohort. HIV incidence was highest in the high uptake VCT arm, lending support to a US trial in which rapid testing appeared to have adverse behavioural consequences in some HIV-negative clients. Careful comparison of outcomes under different counselling and testing strategies is needed to maximize HIV prevention from global scale-up of VCT.