TY - JOUR
T1 - The mosquito transmission of malaria
T2 - the effects of atovaquone-proguanil (Malarone) and chloroquine
AU - Enosse, S
AU - Butcher, G A
AU - Margos, G
AU - Mendoza, J
AU - Sinden, R E
AU - Høgh, B
PY - 2000/4/5
Y1 - 2000/4/5
N2 - 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.
AB - 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.
KW - Animals
KW - Antimalarials/therapeutic use
KW - Atovaquone
KW - Chloroquine/therapeutic use
KW - Culicidae
KW - Drug Combinations
KW - Humans
KW - Insect Vectors
KW - Malaria/parasitology
KW - Mice
KW - Naphthoquinones/therapeutic use
KW - Plasmodium berghei/drug effects
KW - Plasmodium falciparum/drug effects
KW - Proguanil/therapeutic use
KW - Statistics, Nonparametric
M3 - Journal article
C2 - 10748906
SN - 0035-9203
VL - 94
SP - 77
EP - 82
JO - Transactions of the Royal Society of Tropical Medicine and Hygiene
JF - Transactions of the Royal Society of Tropical Medicine and Hygiene
IS - 1
ER -
