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MALARIA: Obstacles and Opportunities
The situation for drug treatment and prophylaxis of P. falciparum malaria is desperate (Payne, 1987; Moran and Bernard, 1989). Given the toxicity and scarcity of primaquine, causal prophylaxis is not a viable option. Daily doses of proguanil provide causal prophylaxis in areas where resistance to this drug is not present, but the compound is not marketed in the United States.
Since this species of parasite does not cause relapse, suppressive prophylaxis should be able to prevent the disease. However, strains of P. falciparum resistant to one or more of the available antimalarial drugs have been documented throughout the world. Resistance to the dihydrofolate reductase inhibitors pyrimethamine and proguanil is widespread, and the potential for serious toxicity with the para-aminobenzoic acid (PABA) anti-metabolites sulfadoxine, sulfalene, and dapsone has limited their use in combination with reductase inhibitors for this purpose.
The nearly global spread of chloroquine resistance precludes its routine use for suppressive prophylaxis. In the worst situations, such as along the Thailand-Cambodia border, parasite strains resistant to mefloquine and/or quinine are also disturbingly common, and few viable prophylactic regimens exist.
Among the antibiotics with antimalarial activity, most attention is currently focused on doxycycline, a tetracycline derivative suitable for once-daily dosing (Pang et al., 1987, 1988). Concerns about the widespread use of doxycycline or other tetracyclines for prophylaxis of malaria include the emergence of drug-resistant strains of P. falciparum, potentially eroding the clinical utility of these drugs in combination with quinine for the treatment of severe malaria (Bruce-Chwatt, 1987). In addition, there are concerns that doxycycline prophylaxis could select drug-resistant strains of pathogenic bacteria (Peters, 1990a,b). Tetracyclines are broadly available in many malarious areas, however, and the impact on resistance patterns from the use of tetracyclines for malaria prophylaxis is unclear. A recent report suggests that the use of doxycycline for malaria prophylaxis in Thailand was not associated with an increased risk of diarrhea from drug-resistant strains of enteric pathogens (Arthur et al., 1990). Furthermore, tetracyclines are often taken as prophylaxis against “travelers' diarrhea” by visitors to less-developed countries. The safety of these drugs is remarkable. Given these considerations, it is appropriate to use doxycycline, at least for travelers in regions where chloroquine resistance is a problem, for malaria prophylaxis.
That there are more treatment options for falciparum malaria than prophylactic regimens is not cause for optimism. The problem of drug resis-