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Africa, home to 11% of the world's population, carries 29% of the global burden of tuberculosis cases and 34% of related deaths, and the challenges of controlling the disease in the region have never been greater. The World Health Organization (WHO) estimates that the average incidence of tuberculosis in African countries more than doubled between 1990 and 2005, from 149 to 343 per 100,000 population (see maps)1 — a stark contrast to the stable or declining rates in all other regions during this period. In 1990, two African countries, Mali and Togo, had an incidence greater than 300 per 100,000; by 2005, 25 countries had reached that level, and 8 of them had an incidence at least twice that high.
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The association between HIV infection and tuberculosis stems from two distinct processes. In some cases, populations with latent tuberculosis acquire HIV infection, which increases 100-fold the risk of reactivation of tuberculosis. In other cases, people with HIV-induced immunosuppression acquire new tuberculosis infections and are at extraordinarily high risk for active tuberculosis. This cycle of infection and disease is amplified by the interaction between patients with active tuberculosis and those with HIV infection in clinics, hospitals, and the broader community.
The ability of African health care systems to respond to, manage, and contain the growing number of cases of tuberculosis is constrained by limitations of funding, facilities, personnel, drug supplies, and laboratory capacity. Although the President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis, and Malaria have donated large sums of money to help address Africa's health problems, most of the money has been earmarked for HIV, with a lesser focus on tuberculosis.
Another critical factor concerns early diagnosis and treatment of tuberculosis, which limits the spread of the disease and reduces deaths. Throughout Africa, diagnosis rests on the microscopical detection of acid-fast bacilli in sputum, an insensitive technique that is particularly ill suited to the detection of tuberculosis in HIV-infected patients, who have fewer bacilli in their sputum and have more extrapulmonary tuberculosis than HIV-negative patients; the WHO estimates that only half of all persons with smear-positive tuberculosis are identified. Modern culture and nucleic acid–amplification systems are rarely available. As a result, many people remain ill and contagious for prolonged periods before the disease is detected, and thousands die without ever having received a diagnosis of tuberculosis. Unfortunately, even with diagnosis, the average rate of successful treatment is less than 70%, far below the WHO target of 85%, making both relapse and the emergence of drug resistance common.
The emergence of drug resistance has been a largely neglected aspect of Africa's epidemic; although multidrug-resistant (MDR) tuberculosis has been present for some time, the number of cases was thought to be low. A 2006 outbreak of extensively drug-resistant (XDR) tuberculosis in South Africa, however, has highlighted this serious problem. In KwaZulu-Natal Province, half the XDR cases in patients with HIV infection were acquired in hospitals or clinics, and several occurred in health care workers. Mortality exceeded 95% — chilling evidence of the critical importance of preventing the nosocomial spread of tuberculosis. XDR tuberculosis will undoubtedly continue to emerge elsewhere in Africa: Botswana's first two cases were reported in early 2008.
In the midst of this bleak situation, there is a glimmer of hope. In 2005, the African ministers of health declared a "TB Emergency," promising swift and concerted action to combat the disease. And the global health community has increased its investment in tuberculosis control and research. HIV activists, having achieved success in their AIDS awareness and funding efforts, have set their sights on tuberculosis. At an international tuberculosis conference in South Africa in November 2007, more than 3000 delegates brought a new level of attention and urgency to Africa's unprecedented health problems.
Achieving results, however, requires enormous investment and commitment, particularly to the development of new biomedical tools. The availability of point-of-care diagnostic tests could substantially reduce the incidence of and mortality from tuberculosis and prompt earlier treatment, thus limiting transmission. Rapid detection of drug-resistant strains would facilitate earlier access to appropriate therapy. New drugs that shorten cure times would reduce transmission, improve treatment outcomes, and prevent the emergence of drug resistance. And a new vaccine could protect future generations. (Although bacille Calmette–Guérin is the world's most widely used vaccine, there is little evidence that it is effective in adults.) Fortunately, research in these areas is under way, led by innovative partnerships funded largely by the Bill and Melinda Gates Foundation and European countries.
In the meantime, Africa's health care systems can adopt new strategies for improving disease-control outcomes. Better use of existing, highly sensitive culture techniques could reduce mortality rates associated with tuberculosis by 20% or more,4 and implementation of treatment programs that meet WHO targets could have a substantial effect on survival and transmission rates. Interventions directed at people with the highest risk, including families of patients with tuberculosis or HIV infection, could be extremely effective.
The WHO, for its part, is promoting various interventions, including supplementation of sputum smears with liquid tuberculosis-culture systems for patients with HIV, increased investments in laboratory services, surveillance of drug resistance, and widespread use of preventive therapy for HIV-infected persons. A new initiative launched by the WHO's Stop TB and HIV departments emphasizes the three I's: intensified case finding, isoniazid preventive therapy, and infection control.
Early identification of symptomatic people with active tuberculosis is an important strategy for the reduction of transmission and mortality (see photo). Studies in Africa show that the prevalence of undetected tuberculosis ranges from 2 to 3% among HIV-infected pregnant women to 8 to 10% among people with a new diagnosis of HIV infection. Preventive therapy with isoniazid can reduce tuberculosis incidence, yet less than 1% of all HIV-infected people worldwide who could benefit from this intervention receive it.1 Antiretroviral therapy alone is insufficient to control tuberculosis, but analyses suggest that isoniazid significantly augments the effect of HIV drugs.5 Ongoing trials are testing community-wide preventive therapy and new combinations of drugs that might shorten the course of preventive therapy and extend its durability.
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No potential conflict of interest relevant to this article was reported.
Source Information
Dr. Chaisson is the director of the Center for Tuberculosis Research at the Johns Hopkins University School of Medicine, Baltimore. Dr. Martinson is the deputy director of the Perinatal HIV Research Unit, University of the Witwatersrand, Soweto, South Africa.
A slide presentation on tuberculosis and HIV in Africa may be seen at www.nejm.org.
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