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Am. J. Trop. Med. Hyg., 39(1), 1988, pp. 15-20
Copyright © 1988 by The American Society of Tropical Medicine and Hygiene

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Ultrastructural Study of the Effects of Chloroquine and Verapamil on Plasmodium Falciparum

Gretta H. Jacobs*, Ayo M. J. Oduola, Dennis E. Kyle, Wilbur K. Milhous, Samuel K. Martin AND Masamichi Aikawa*
* Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, and Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307

Verapamil, a calcium antagonist, has recently been shown to reverse chloroquine resistance in malarial parasites in vitro. We report the first ultrastructural morphological changes associated with this phenomenon using chloroquine-sensitive and -resistant clones of Plasmodium falciparum. While the administration of 6.3 x 10-8 M chloroquine had little morphological effect on the chloroquine-resistant strain, the combination of chloroquine and verapamil resulted in typical chloroquine-related food vacuolar swelling with increased amounts of granular matrix. Secondary morphological changes included degeneration of nuclei, mitochondria, and other organelles. These effects appeared similar to those in the chloroquine-sensitive strain of P. falciparum treated with chloroquine alone or with the chloroquine/verapamil combination. Furthermore mild food vacuolar changes were seen in a small number of parasites (from both chloroquine-sensitive and -resistant groups) exposed to high concentrations (1 x 10-4 M) of verapamil alone.

Accepted for publication December 11, 1987.






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Copyright © 1988 by the American Society of Tropical Medicine and Hygiene.