HUMAN immunodeficiency virus (HIV) infection is a potent risk factor for tuberculosis (TB). Not only does HIV increase the risk of reactivating latent Mycobacterium tuberculosis (MTB) infection,¹ it also increases the risk of rapid TB progression soon after infection or reinfection with MTB.^2,3 In persons infected with MTB only, the lifetime risk of developing TB ranges between 10% and 20%.^4,5 In persons coinfected with MTB and HIV, however, the annual risk can exceed 10%.^1,6,7 The TB burden in countries with a generalized HIV epidemic has therefore increased rapidly over the past decade, especially in the severely affected countries of eastern and southern Africa.^8-12 Tuberculosis is one of the most common causes of morbidity and the most common cause of death in HIV-positive adults living in less-developed countries,^13-26 yet it is a preventable and treatable disease.

The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory.

More than 36 million patients have been successfully treated via the World Health Organization’s strategy for tuberculosis (TB) control since 1995. Despite predictions of a decline in global incidence, the number of new cases continues to grow, approaching 10 million in 2010. Here we review the changing relationship between the causative agent, Mycobacterium tuberculosis , and its human host and examine a range of factors that could explain the persistence of TB. Although there are ways to reduce susceptibility to infection and disease, and a high-efficacy vaccine would boost TB prevention, early diagnosis and drug treatment to interrupt transmission remain the top priorities for control. Whatever the technology used, success depends critically on the social, institutional, and epidemiological context in which it is applied.