al., 1991). Currently, there is no evidence of person-to-person spread of this drug-resistant virus.

Zidovudine and Human Immunodeficiency Virus-1

Zidovudine, also known as azidothymidine (AZT), is effective in prolonging the survival and improving the quality of life of those infected with HIV-1, including those with AIDS, those with symptomatic HIV infection, and HIV-infected asymptomatic individuals. Zidovudine works by inhibiting the viral enzyme reverse transcriptase (RNA-dependent DNA polymerase) (Hayden and Douglas, 1990).

Unfortunately, resistance to the drug has been documented and appears to be associated with length of treatment (most isolates demonstrate reduced drug susceptibility after six months of treatment) and CD4-lymphocyte counts of less than 200 per cubic milliliter (Laughlin et al., 1991). Resistance develops gradually as the result of point mutations in the gene for reverse transcriptase; multiple mutations are necessary to confer high-level resistance (Laughlin et al., 1991).

RESISTANCE TO ANTIMALARIALS

Over the past 15 years, there has been a tremendous resurgence of malaria around the world and an increase in the percentage of cases caused by Plasmodium falciparum, the most virulent of the four human malaria parasites (Institute of Medicine, 1991a). Worldwide, as many as 2 million people will die from malaria in 1992, most of them children in Africa.

The seriousness of the worldwide increase in malaria incidence is heightened by the spread of parasites resistant to the available assortment of antimalarial drugs. Malaria parasites, like bacteria and viruses, can develop resistance to the drugs used to prevent or treat infection. And, as is the case with antibiotics, resistance is often the result of overuse or misuse of antimalarial drugs. However, unlike the case for antibiotics, the development of antimalarial drugs is not a high priority for U.S. pharmaceutical companies. Within the United States, this task is almost entirely the domain of the Walter Reed Army Institute of Research. Globally, the Special Programme for Research and Training in Tropical Diseases, a joint project of the United Nations Development Programme, the World Bank, and the World Health Organization, is an important participant in antimalarial drug development.

Resistance to quinine, the first antimalarial drug ever marketed, was initially reported in 1910 in Germans who developed malaria while working in Brazil (Peters, 1987). Since then, a number of other antimalarials have been developed, the most notable of which is chloroquine.

Resistance to chloroquine in P. falciparum was first reported in 1961 in



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