VIEWPOINT

Is Africa lost?

In 1992, less than 20 countries were implementing a sound TB control strategy. At the same time, TB was being resurrected as a major public health problem world-wide after two decades of neglect. Awareness of upward trends in the industrialized countries and MDR-TB outbreaks in large cities were driving forces behind the re-emergence of TB in the international health agenda. New evidence, and consequent estimates, suggested that the situation in developing countries, especially in sub-Saharan Africa, was deteriorating rapidly. Similarly, major increases were observed in the former USSR. It was estimated that some 7–8 million new cases and 2–3 million deaths were occurring annually in the world. The global targets of reaching 85% cure rates and 70% case detection among infectious cases were established by the World Health Assembly in 1991. Both the WHO declaration of TB as a global emergency in 1993 and the launch of the five-element DOTS strategy in 1994–1995 resulted in countries adopting DOTS in encouraging numbers. In fact, in 2000, 148 countries including all 22 highest burden countries (HBC) responsible for 80% of cases world-wide, had adopted the new DOTS strategy. Nevertheless, progress in case detection remained slow due to incomplete geographical coverage or need to widen detection and notification capacity with innovative schemes. The major constraints to TB control became increasingly clear, and a global Stop TB Partnership was eventually established to address such constraints. A Global DOTS Expansion Plan revealed the needs and the gaps to achieve the global targets in 2005. Today, in 2002, the top priority remains that of expanding DOTS, as rapidly as possible, using a number of new approaches to increase case detection and notification while maintaining high cure rates. These must involve collaboration with the private sector and communities, as well as strengthening of primary care services. Similarly, crucial is the rapid identification of solutions to TB/HIV and MDR-TB.

At the end of the 20th century, tuberculosis remains a major public health issue. In developing countries tuberculosis is a leading cause of morbidity and mortality, and the spread of the HIV epidemic contributes significantly to the worsening of the situation. Coinfection with tuberculosis and HIV results in special diagnostic and therapeutic problems and uses up larger amounts of medical resources in developing countries. Outbreaks of multidrug resistant tuberculosis (MDR-TB) were first reported from US-American centers caring for HIV patients, but have now been observed in many other countries. In Western Europe the tuberculosis epidemic is under control, but increasing incidence rates in migrants raise new problems in these countries. Tuberculosis is uncontrolled in large parts of the former Soviet Union due to the socio-economic break-down in these countries. Only rigorous infection control measures on a world-wide scale will prevent further detoriation of this situation. Therefore, the extension of surveillance systems, and sufficient funding for the prevention, diagnosis, and treatment of tuberculosis by national governments and international organizations are all urgently needed.

The thioredoxin (Trx) and thioredoxin reductase (TR) ofMycobacterium tuberculosishave been expressed inEscherichia coliand shown to reduce peroxides and dinitrobenzenes. The reduction of H₂O₂requires both Trx and TR and is more efficient under anaerobic than aerobic conditions. In contrast, cumene hydroperoxide is reduced to cumyl alcohol and acetophenone in a process that requires NADPH and TR but not Trx. Cumene hydroperoxide reduction is partially inhibited by chelation of trace metals in the medium. The reduction of cumene hydroperoxide by TR is more effective under anaerobic than aerobic conditions due to a competing oxidase reaction in which electrons are transferred from TR to O₂. Under anaerobic conditions, dinitrobenzenes also serve as electron acceptors and are reduced by TR to nitroanilines, but the enzyme does not reduce mononitrobenzenes or mononitroimidazoles such as metronidazole. The reductive activity of the Trx–TR system may modify the antioxidant defenses ofM. tuberculosis.