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The mosquito transmission of malaria: the effects of atovaquone-proguanil (Malarone) and chloroquine.

Abstract
Despite its recognized importance, the prevention of patients with malaria from continuing to infect mosquitoes after treatment is not always achieved in practice. An inevitable consequence of the prolonged life-span and relative metabolic stasis of the mature gametocytes of Plasmodium falciparum is that they are not cleared by most antimalarials, and few antimalarials block infection in the mosquito vector. Previous research on the constituents of Malarone, a new 'combined antimalarial', suggested that the active components, atovaquone and proguanil, might inhibit infectivity of gametocytes to mosquitoes. We contrast here the impact of atovaquone-proguanil and chloroquine on the transmission of P. falciparum and P. berghei. While chloroquine enhanced infectivity of P. falciparum, atovaquone-proguanil caused a significant reduction. Surprisingly, sporontocidal activity against the rodent parasite persisted long after the levels of the constituent drugs would have been expected to have fallen below effective plasma concentrations on the basis of the established pharmacokinetics of atovaquone and proguanil. The P. berghei model may thus have provided a sensitive bioassay, detecting drug(s) at levels below that normally found with the usual chemical assays.
AuthorsS Enosse, G A Butcher, G Margos, J Mendoza, R E Sinden, B Høgh
JournalTransactions of the Royal Society of Tropical Medicine and Hygiene (Trans R Soc Trop Med Hyg) 2000 Jan-Feb Vol. 94 Issue 1 Pg. 77-82 ISSN: 0035-9203 [Print] England
PMID10748906 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimalarials
  • Drug Combinations
  • Naphthoquinones
  • atovaquone, proguanil drug combination
  • Chloroquine
  • Proguanil
  • Atovaquone
Topics
  • Animals
  • Antimalarials (therapeutic use)
  • Atovaquone
  • Chloroquine (therapeutic use)
  • Culicidae
  • Drug Combinations
  • Humans
  • Insect Vectors
  • Malaria (parasitology, prevention & control, transmission)
  • Mice
  • Naphthoquinones (therapeutic use)
  • Plasmodium berghei (drug effects)
  • Plasmodium falciparum (drug effects)
  • Proguanil (therapeutic use)
  • Statistics, Nonparametric

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