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Inhibitory action of the anti-malarial compound atovaquone (566C80) against Plasmodium berghei ANKA in the mosquito, Anopheles stephensi

Published online by Cambridge University Press:  06 April 2009

R. E. Fowler ,
P. F. Billingsley ,
M. Pudney  and
R. E. Sinden
R. E. Fowler
Affiliation:
Molecular and Cellular Parasitology Research Group, Department of Biology, Imperial College of Science, Technology and Medicine, London SW7 2BB
P. F. Billingsley
Affiliation:
Molecular and Cellular Parasitology Research Group, Department of Biology, Imperial College of Science, Technology and Medicine, London SW7 2BB
M. Pudney
Affiliation:
Department of Molecular Sciences, Wellcome Research Labs, Langley Court, Beckenham, Kent BR3 3BS
R. E. Sinden
Affiliation:
Molecular and Cellular Parasitology Research Group, Department of Biology, Imperial College of Science, Technology and Medicine, London SW7 2BB
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Summary

The activity of atovaquone against Plasmodium berghei ANKA during sporogonic development has been examined. Anopheles stephensi mosquitoes were fed on gametocyte infected mice which had been treated 8 h previously with atovaquone or diluent alone. Mosquito midguts were examined for oocysts, and salivary gland infections were estimated using an ELISA for the circumsporozoite protein (CSP). The number of oocysts per midgut fell by at least 97% when mosquitoes were fed on mice dosed with 0·1–10 mg atovaquone/kg body weight. This was paralleled by a decrease in the prevalence of oocyst-infected mosquitoes from 70–90% in controls to 40% or 10% respectively. No oocysts were observed at a dose of 100 mg/kg. CSP ELISA results indicated that mosquitoes fed on atovaquone failed to produce sporozoites. Mosquitoes which fed on gametocytaemic, atovaquone-treated mice (0·1–100 mg/kg) did not transmit malaria to naive mice. These results demonstrate that atovaquone has a highly potent inhibitory activity against the mosquito stages of P. berghei.

Keywords

sporonticidechemotherapyhydroxynaphthoquinone
Type
Research Article
Information
Parasitology , Volume 108 , Issue 4 , May 1994 , pp. 383 - 388
Copyright
Copyright © Cambridge University Press 1994

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References

REFERENCES

Beier, J. C., Perkins, P. V., Wirtz, R. A., Whitmire, R. E., Mugambi, M. & Hockmeyer, W. T. (1987). Field evaluation of an enzyme-linked immunosorbent assay (ELISA) for Plasmodium falciparum sporozoite detection in anopheline mosquitoes from Kenya. American Journal of Tropical Medicine and Hygiene 36, 459–68.CrossRefGoogle ScholarPubMed
Bray, R. S., Burgess, R. W., Fox, R. M. & Miller, M. J. (1959). Effect of pyrimethamine upon sporogony and pre-erythrocytic schizogony of Laverania falciparum. Bulletin of the World Health Organization 21, 233–8.Google ScholarPubMed
Burkot, T. R. & Wirtz, R. A. (1986). Immunoassays of malaria sporozoites in mosquitoes. Parasitology Today 2, 155–7.CrossRefGoogle ScholarPubMed
Chutmongkonkul, M., Maier, W. A. & Seitz, H. M. (1992). Plasmodium falciparum: effect of chloroquine, halofantrine and pyrimethamine on the infectivity of gametocytes for Anopheles stephensi mosquitoes. Annals of Tropical Medicine and Parasitology 86, 103–10.CrossRefGoogle ScholarPubMed
Coleman, R. E., Clavin, A. M. & Milhous, W. K. (1992). Gametocytocidal and sporontocidal activity of antimalarials against Plasmodium berghei ANKA in ICR mice and Anopheles stephensi mosquitoes. American Journal of Tropical Medicine and Hygiene 46, 169–82.CrossRefGoogle ScholarPubMed
Davies, C. S., Pudney, M., Matthews, P. J. & Sinden, R. E. (1989). The causal prophylactic activity of the novel hydroxynaphthoquinone 566C80 against Plasmodium berghei infections in rats. Acta Leidensa 58, 115–28.Google ScholarPubMed
Davies, C. S., Pudney, M., Nicholas, J. C. & Sinden, R. E. (1993). The novel hydroxynaphthoquinone 566C80 inhibits the development of liver stages of Plasmodium berghei cultured in vitro. Parasitology 106, 1–6.CrossRefGoogle ScholarPubMed
Do Rosario, V. E., Vaughan, J. A., Murphy, M., Harrod, V. & Coleman, R. (1988). Effect of chloroquine on the sporogonic cycle of Plasmodium falciparum and Plasmodium berghei in anopheline mosquitoes. Acta Leidensa 57, 53–60.Google Scholar
Hudson, A. T. (1993). Atovaquone – a novel broad spectrum anti-infective drug. Parasitology Today 9, 66–8.CrossRefGoogle ScholarPubMed
Hudson, A. T., Dickins, M., Ginger, C. D., Gutteridge, W. E., Holdich, T., Hutchinson, D. B. A., Pudney, M., Randall, A. W. & Latter, V. S. (1991). 566C80 – a potent broad spectrum anti-infective agent with activity against malaria and opportunistic infections in AIDS patients. Drug and Experimental Clinical Research 17, 427–35.Google ScholarPubMed
Hutchinson, D. B. A., Looareesuwan, S. & Farquhar, J. (1992). Evaluation of the hydroxynaphthoquinone, 566C80, in the treatment of uncomplicated Plasmodium falciparum malaria. Abstracts of the 4th Malaria meeting, BSPFeb 1992.Google Scholar
Ichimori, K., Curtis, C. F. & Targett, G. A. T. (1990). The effects of chloroquine on the infectivity of chloroquine-sensitive and -resistant populations of Plasmodium yoelii nigeriensis to mosquitoes. Parasitology 100, 377–81.CrossRefGoogle ScholarPubMed
James, D. M. & Gilles, H. M. (1985). Malaria. In Human Antiparasitic Drugs: Pharmacology and Usage, pp. 120–164. Chichester: John Wiley and Sons.Google Scholar
Jeffrey, G. m. (1958). Infectivity to mosquitoes of Plasmodium vivax following treatment with chloroquine and other antimalarials. American Journal of Tropical Medicine and Hygiene 7, 207–11.CrossRefGoogle Scholar
Klein, T. A., Tada, M. S., Lima, J. B. P. & Katsuragawa, T. H. (1991). Infection of Anopheles darlingi fed on patients infected with Plasmodium vivax before and during treatment with chloroquine in Costa Marques, Rondonia, Brazil. American Journal of Tropical Medicine and Hygiene 45, 471–8.CrossRefGoogle Scholar
McGhee, M. w. (1985). Introductory Statistics. St Paul: West Publishing Co.Google Scholar
Medley, G. F., Sinden, R. E., Fleck, S., Billingsley, P. F., Tirawanchai, N. & Rodriguez, M. H. (1993). Heterogeneity in patterns of malarial oocyst infections in the mosquito vector. Parasitology 106, 441–9.CrossRefGoogle ScholarPubMed
Omar, M. S., Collins, W. E. & Contacos, P. G. (1974). Gametocytocidal and sporontocidal effects of antimalarial drugs on malaria parasites. II. Action of the folic reductase inhibitors, chloroguanide and pyrimethamine against Plasmodium cynomolgi. Experimental Parasitology 36, 167–77.CrossRefGoogle ScholarPubMed
Ozaka, L. S., Gwadz, R. W. & Godson, G. N. (1984). Simple centrifugation method for rapid separation of sporozoites from mosquitoes. Journal of Parasitology 70, 831–3.CrossRefGoogle Scholar
Peters, W. (1987). Chemotherapy and Drug Resistance in Malaria. London: Academic Press.Google Scholar
Pudney, M., Chapman, A., Nights, C. J., Fry, M., Webb, E., Pearce, J. L. & Drakeley, C. J. (1990). Potential mechanisms of experimentally produced resistance to the new antimalarial hydroxynaphthoquinone 566C80. Abstracts of the 2nd Malaria Meeting, BSPFebruary 1990.Google Scholar
Ranawaka, G., Alejo-Blanco, R. & Sinden, R. E. (1993). Studies on the effect of transmission-blocking antibody ingested in primary and secondary blood feeds, upon the development of Plasmodium berghei in the mosquito vector. Parasitology 107, 225–31.CrossRefGoogle Scholar
Shute, P. G. & Maryon, M. (1954). The effect of pyrimethamine (Daraprim) on the gametocytes and oocysts of Plasmodium falciparum and Plasmodium vivax. Transactions of the Royal Society of Tropical Medicine and Hygiene 48, 50–63.CrossRefGoogle ScholarPubMed
Sinden, R. E. (1982). Gametocytogenesis of Plasmodium falciparum in vitro: ultrastructural observations on the lethal action of chloroquine. Annals of Tropical Medicine and Parasitology 76, 15–23.CrossRefGoogle ScholarPubMed
Teklehaimanot, A., Nguyen-Dinh, P., Collins, W. E., Barber, A. M. & Campbell, C. C. (1985). Evaluation of sporontocidal compounds using Plasmodium falciparum gametocytes produced in vitro. American Journal of Tropical Medicine and Hygiene 34, 429–34.CrossRefGoogle ScholarPubMed
Vinke, I. H. (1970). The effects of pyrimethamine and sulphormethoxine on the pre-erythrocytic and sporogonous cycle of Plasmodium berghei berghei. Annates de la Société belge de Medecine tropicale 50, 339–58.Google Scholar
Whitman, L. (1948). The effect of artificial blood meals containing the hydroxynaphthoquinone M2279 on the developmental cycle of Plasmodium gallinaceum in Aedes aegypti. Journal of Infectious Diseases 82, 251–5.CrossRefGoogle ScholarPubMed
Wirtz, R. A., Burkot, T. R., Andre, R. G., Rosenberg, R., Collins, W. E. & Roberts, D. R. (1985). Identification of Plasmodium vivax sporozoites in mosquitoes using an enzyme linked immunosorbent assay. American Journal of Tropical Medicine and Hygiene 30, 1048–54.CrossRefGoogle Scholar
Wirtz, R. A., Burkot, T. R., Graves, P. M. & Andre, R. G. (1987). Field evaluation of enzyme-linked immunosorbent assays for Plasmodium falciparum and Plasmodium vivax sporozoites in mosquitoes (Diptera: Culicidae) from Papua New Guinea. Journal of Medical Entomology 24, 433–7.CrossRefGoogle ScholarPubMed