The resistance of falciparum malaria in Africa to 4-aminoquinolines and antifolates.
Falciparum malaria cannot be eradicated from sub-Saharan Africa with present technology. The mainstay of malaria control in this situation is treatment of fever cases with chloroquine, aiming principally at reduction of mortality. The efficacy of this policy is now endangered because of the appearance and spread of chloroquine-resistance on the African continent. The present review examines laboratory and field research on the resistance of African P.falciparum to chloroquine, amodiaquine, pyrimethamine, proguanil, chlorproguanil and the combination sulfadoxine-pyrimethamine. Drug-resistance in malaria may be assessed with in vivo and in vitro technology. In vivo tests are simple, but the results are difficult to compare because of the influence of immunity. In vitro tests provide a more precise epidemiological tool, but their analysis should be undertaken with consideration of their technical limitations. For parasitological, immunological and epidemiological reasons, a one-to-one correlation between in vivo and in vivo grading of resistance is usually not found. Extended in vivo tests may be at least as sensitive as in vitro tests for detecting rare resistant parasites. On the other hand, the standardized grading of higher levels of in vivo resistance is arbitrary, and it is doubtful, whether such distinction has any clinical relevance. The 4-aminoquinolines (chloroquine and amodiaquine) presumably act by interfering with vital functions in the acid vesicles of parasites. Recent experiments indicate that resistance may be related to an increased rate of efflux of chloroquine from the parasite. It is caused by mutation, and at least three genetic levels of resistance have been identified. The blood stages of resistant plasmodia seem to have a biological advantage over sensitive ones, an observation that raises some hitherto unanswered questions. In the 1970s, a low degree of resistance to chloroquine was found in African P. falciparum in several localities. Resistance to the standard dose of chloroquine of 25 mg/kg was found in 1978 in tourists, who had sojourned in Kenya and Tanzania. Since then, chloroquine-resistance has spread centrifugally with increasing rapidity from an original focus in Northern Tanzania or Southern Kenya. The rate of increase in the proportion of resistant infections has generally been more rapid in the areas, where resistance has been introduced recently than in the original epifocus. The rate of increase is also generally more rapid in urban than in rural areas, an observation that can be ascribed to differences in drug pressure.(ABSTRACT TRUNCATED AT 400 WORDS)
Schapira
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Instituto Nacional de Saúde, Maputo, Mozambique.
D000634:Aminoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D005493:Folic Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000187:drug effects*
D000634:Aminoquinolines; D000962:Antimalarials; D005493:Folic Acid Antagonists