Actively hunting down undiagnosed cases of tuberculosis (TB) in the community —especially using a mobile van approach—is an effective way to bring down rates of undiagnosed TB in areas of high HIV prevalence. The findings of this Zimbabwe-based study are reported in an Article published Online First (www.thelancet.com) by The Lancet, written by Dr Liz Corbett, London School of Hygiene and Tropical Medicine, UK, and colleagues. The study was funded by The Wellcome Trust.
Especially in patients who are HIV-negative, TB often has a long period before diagnosis, where symptoms can be mild or even absent. Yet these people can still infect others, adding to the TB epidemic in both HIV-negative and HIV-positive patients.
Africa has been in the grip of a severe epidemic of TB since the onset of the HIV epidemic: the region includes all but one of 15 countries with the highest TB incidences and accounts for 79% of the global burden of 1•4 million cases of HIV-related TB. Thus TB control in this region is essential.
Periodic active case finding for tuberculosis was widely implemented, mainly using chest radiography, during a period of rapid decline in TB incidence in the northern hemisphere and some Asian countries, and remains an integral part of TB control in high-risk groups. In this new work (the DETECTB study), the authors tested two active case-finding strategies (mobile van and door-to-door) to target long periods of infectiousness before diagnosis, which is typical of HIV-negative TB 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. In both groups, adult (≥16 years) residents who had had chronic cough for two weeks or more had two sputum specimens collected for fluorescence microscopy. Positive cases were then referred for treatment, with all but a handful of cases treated. The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents, compared between intervention groups. 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.
The researchers randomly allocated 46 study clusters 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% 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 (giving the mobile van a 48% higher detection rate compared to the door-to-door method). Following this intervention undiagnosed culture-positive TB in the community declined by 43% from 6•5 per 1000 adults to 3•7 per 1000 adults.
The authors say: "We have shown that untargeted periodic active case finding for symptomatic smear-positive TB repeated once every 6 months made a substantial contribution to diagnosis of smear-positive TB in an urban population with high HIV prevalence, and to control of infectious TB. The mobile van delivery strategy significantly outperformed door-to-door enquiry for chronic cough, especially in neighbourhoods with high HIV prevalence."
They add: "By the start of intervention round six, infectious TB in the community had fallen by more than 40% from rates before intervention, to rates well below those reported elsewhere in the region. This major improvement in TB control in a population with high HIV prevalence suggests that such an intervention could provide rapid reductions in TB transmission in the community, and could lead to declining rates of new TB cases in individuals with and without HIV infection within a few years."
The authors note that active case finding for TB in the general community was discouraged for several decades because of high costs of implementation and insufficient strength of treatment programmes. With the successful global scale-up of effective TB treatment, however, they say their results suggest that active case finding needs re-evaluation in general populations wherever TB incidence or prevalence is high.
They conclude: "The effect on HIV-negative TB that we report is in the range needed for countries to meet the Millennium Development Goal relating to tuberculosis prevalence, and was achieved in under 3 years. Interventions should aim to effectively engage men, and, in settings of high HIV prevalence, should ideally be accompanied by interventions promoting HIV diagnosis linked to intensified TB prevention with antiretroviral therapy and isoniazid preventive therapy."
In a linked Comment, Dr Mario Raviglione (director) and Dr Haileyesus Getahun, Stop TB Department, WHO, Geneva, Switzerland, say that it is vital to make sure patients identified are followed-up to ensure they receive the correct treatment. They also highlight another vital issue preventing progress in active case finding: a rapid, accurate, and simple diagnostic test.
They conclude: "At present no rapid point-of-care test is available to identify latent or recent infection, or active disease. Any attempt to scale up active case-finding and to do research to fill the evidence gap is therefore compromised. The call to scale up active case-finding outside health facilities needs to be paired with increased scientific interest, research investment, and political commitment for high-quality basic and operational research. Such research will contribute to the development of a rapid point-of-care diagnostic test that will ultimately revolutionise tuberculosis care and control, and foster progress towards elimination."
Dr Elizabeth Corbett, London School of Hygiene and Tropical Medicine, UK. T) +44 7702798687 E) liz.corbett@lshtm.ac.uk / lizcorbett04@gmail.com
Dr Haileyesus Getahun, Stop TB Department, WHO, Geneva, Switzerland. E) getahunh@who.int
For full Article and Comment, see attached PDF
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Journal
The Lancet