Epidemiology of Tuberculosis in a High HIV Prevalence Population Provided with Enhanced Diagnosis of Symptomatic Disease

Background: Directly 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 Findings: Twenty-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. Conclusions: Strategies 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. When occupational clinics provide free smear and culture-based investigation of tuberculosis symptoms, it can lead to prompt investigation and may aid TB control in high HIV-prevalence populations. Background.: Around eight million people develop tuberculosis (TB) disease every year and of these nearly two million die. However, many more people are infected than have symptoms; perhaps one-third of the world's population is currently infected with TB. Most people infected with TB have what is termed “latent infection,” or in other words they are infected with the bacterium but do not experience any symptoms of disease. Individuals infected with TB who also have a weakened immune system, for example through HIV/AIDS, are much more likely to develop TB disease. In some regions HIV is very common—for example, approximately 11% of sub-Saharan African adults are HIV positive—and because of this cases of TB disease have risen substantially as HIV spreads. The Word Health Organization has a recommended international strategy for control of TB called “DOTS” (Directly Observed Therapy, Shortcourse). Among the five main elements of DOTS are mechanisms for promptly diagnosing and treating people who have TB disease. It is hoped that this strategy will help to reduce the number of new cases of TB diagnosed each year, because individuals promptly diagnosed and treated will then be less likely to transmit the disease to others. Why Was This Study Done?: In this study the investigators wanted to find out if intensive DOTS, combined with giving people better access to test facilities to diagnose TB disease, could be effective in reducing the spread of TB from one person to another in Africa. It is not clear whether DOTS alone can control the spread of TB in populations with high numbers of HIV-positive people already infected with TB and so at high risk of going on to develop TB disease. Specifically, they wanted to collect data on the number of new TB cases being diagnosed per year and how that related to the proportion of the overall population that had infectious undiagnosed TB at any given point in time. They also wanted to find out whether providing good access to services for diagnosis and treatment of TB would affect either the number of new TB cases or the proportion of a given population that had infectious undiagnosed TB. What Did the Researchers Do and Find?: This research study was carried out as part of a trial in which two different strategies for providing testing and counseling for HIV in the workplace were being compared. The trial took place within 22 companies in Harare, Zimbabwe, where HIV is very common in the adult population. Along with HIV testing and counseling, the trial provided for close follow-up and testing of anyone presenting with TB-like symptoms, with the aim of detecting as many cases in the population as possible. At the end of the two-year period, all workers were checked for undiagnosed TB disease, and cultures were carried out to find out how many of these people had infectious TB (but who might not necessarily have had symptoms). 6,440 workers were recruited into the study, of whom 19% were HIV positive. During the period of follow-up, 106 cases of TB were seen, and HIV-positive workers were far more likely than HIV-negative workers to experience TB disease. At the end of the study, 4,668 workers were checked for the presence of undiagnosed TB and 27 individuals were found to be affected, but not all of these people experienced any symptoms of disease. What Do These Findings Mean?: At the end of this study, the proportion of workers found to have undiagnosed TB was fairly low—lower than the level found in other studies carried out in other parts of the world with a high burden of TB disease but low burden of HIV. The researchers therefore concluded that the systems set up within the trial (for close follow-up and testing for TB disease) were an effective way of controlling the overall proportion with infectious TB, even though HIV infection rates were also high. This is likely to mean that the spread of TB infection to others—a prerequisite for achieving TB disease control—was also well controlled. However, more intensive efforts to reduce the risk of TB disease in HIV-positive Africans already infected with TB are also needed, although this study did not aim to find out about the impact of such strategies. Additional Information.: Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040022.