Chapter 002. Global Issues in Medicine (Part 6) Tuberculosis Chapter 158 offers a concise overview of the pathophysiology and treatment of TB, which is closely linked to HIV infection in much of the world. Indeed, a substantial proportion of the resurgence of TB registered in southern Africa may be attributed to HIV co-infection. Even before the advent of HIV, however, it was estimated that fewer than half of all cases of TB in developing countries were ever diagnosed, much less treated. Primarily because of the common failure to diagnose and treat TB, international authorities devised a single strategy to reduce the burden of disease. The DOTS strategy (directly observed therapy using short-course isoniazid- and rifampin-based regimens) was promoted in the early 1990s as highly cost-effective by the World Bank, the WHO, and other international bodies. Passive case-finding of smear-positive patients was central to the strategy, and an uninterrupted drug supply was, of course, deemed necessary for cure. DOTS was clearly effective for most uncomplicated cases of drug-susceptible TB, but it was not long before a number of shortcomings were identified. First, the diagnosis of TB based solely on smear microscopy—a method dating from the late nineteenth century—is not sensitive. Many patients with pulmonary TB and all patients with exclusively extrapulmonary TB are missed by smear microscopy, as are most children with active disease. Second, passive case-finding relies on the availability of health care services, which is uneven in settings where TB is most prevalent. Third, patients with multidrug-resistant (MDR) TB are by definition infected with strains of Mycobacterium tuberculosis resistant to isoniazid and rifampin; thus exclusive reliance on these drugs is ineffective in settings in which drug resistance is an established problem. The crisis of antibiotic resistance registered in U.S. hospitals is not confined to the industrialized world or to bacterial infections. In some settings, a substantial minority of patients with TB are infected with strains resistant to at least one first-line anti-TB drug. As an effective DOTS-based response to MDR TB, global health authorities adopted DOTS-Plus, which adds the diagnostics and drugs necessary to manage drug-resistant disease. Even before DOTS-Plus could be brought to scale in resource-constrained settings, however, new strains of extensively drug-resistant (XDR) M. tuberculosis began to threaten the success of TB control programs in already-beleaguered South Africa, for example, where high rates of HIV infection have led to a doubling of TB incidence over the past decade. Tuberculosis and AIDS as Chronic Diseases: Lessons Learned Strategies effective against MDR TB have implications for the management of drug-resistant HIV infection and even drug-resistant malaria, which, through repeated infections and a lack of effective therapy, has become a chronic disease in parts of Africa. Indeed, examining AIDS and TB together as chronic diseases allows us to draw a number of conclusions, many of them pertinent to global health in general (Fig. 2-3). First, charging fees for AIDS prevention and care will pose insurmountable problems for people living in poverty, many of whom will always be unable to pay even modest amounts for services or medications. Like efforts to battle airborne TB, such services might best be seen as a public good for public health. Initially, this approach will require sustained donor contributions, but many African countries have recently set targets for increased national investments in health—a pledge that could render ambitious programs sustainable in the long run. Meanwhile, as local investments increase, the price of AIDS care is decreasing. The development of generic medications means that ART can now cost <$0.50 (U.S.) per day, and costs continue to decrease to affordable levels for public health bodies in developing countries. Second, the effective scale-up of pilot projects will require the strengthening and sometimes rebuilding of health care systems, including those charged with delivering primary care. In the past, the lack of health care infrastructure has been cited as a barrier to providing ART in the world's poorest regions; however, AIDS resources, which are at last considerable, may be marshaled to rebuild public health systems in sub-Saharan Africa and other HIV- burdened regions—precisely the settings in which TB is resurgent. Third, a lack of trained health care personnel, most notably doctors, is invoked as a reason for the failure to treat AIDS in poor countries. The lack is real, and the "brain drain," which is discussed below, continues. However, one reason doctors leave Africa is that they lack the tools to practice their trade there. AIDS funding provides an opportunity not only to recruit physicians and nurses to underserved regions but also to train community health workers to supervise care for AIDS and many other diseases within their home villages and neighborhoods. Such training should be undertaken even in places where physicians are abundant, since community-based, closely supervised care represents the highest standard of care for chronic disease, whether in the First World or the Third. Fourth, extreme poverty makes it difficult for many patients to comply with therapy for chronic diseases, whether communicable or not. Indeed, poverty in its many dimensions is far and away the greatest barrier to the scale-up of treatment and prevention programs. It is possible to remove many of the social and economic barriers to adherence, but only with what are sometimes termed "wrap- around services": food supplements for the hungry, help with transportation to clinics, child care, and housing. In many rural regions of Africa, hunger is the major coexisting condition in patients with AIDS or TB, and these consumptive diseases cannot be treated effectively without adequate caloric intake. Finally, there is a need for a renewed basic-science commitment to the discovery and development of vaccines; of more reliable, less expensive diagnostic tools; and of new classes of therapeutic agents. This need applies not only to the three leading infectious killers—against none of which an effective vaccine exists—but also to many other neglected diseases of poverty. . Chapter 002. Global Issues in Medicine (Part 6) Tuberculosis Chapter 158 offers a concise overview of the pathophysiology and treatment of TB, which is closely linked to HIV infection in. registered in U.S. hospitals is not confined to the industrialized world or to bacterial infections. In some settings, a substantial minority of patients with TB are infected with strains resistant. rebuilding of health care systems, including those charged with delivering primary care. In the past, the lack of health care infrastructure has been cited as a barrier to providing ART in the