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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.

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