TY - JOUR
T1 - Chronotherapy of malaria
T2 - identification of drug-sensitive stage of parasite and timing of drug delivery for improved therapy.
AU - Cambie, G.
AU - Caillard, V.
AU - Beauté-Lafitte, A.
AU - Ginsburg, H.
AU - Chabaud, A.
AU - Landau, I.
PY - 1991
Y1 - 1991
N2 - The cyclic nature of malarial fever in conjunction with the pharmacokinetic characteristics of antimalarial drugs, call for the conception of a chrono-therapeutic approach for the treatment of the disease. An experimental murine malarial model was devised using the highly synchronous species Plasmodium vinckei petteri to test this rationale. Sub-curative doses of chloroquine were injected sub-cutaneously to mice either during the prepatent period or during patent infection. Inspection of the effect of drug applied at different stages of the parasitic cycle, revealed that medium size trophozoites (MT) were the most susceptible stage to chloroquine, while ring and young trophozoite stages were refractory to the drug. Chloroquine given during these latter stages, affected the parasites when they developed into the MT stage. Drug treatment during the MT stage phase-shifted the schizogonic cycle by 18 hours. Hence, treatment with two consecutive injections given 18 hours apart, i.e. timed to the overwhelming presence of the MT stage in the circulation, gave the best therapeutic results.
AB - The cyclic nature of malarial fever in conjunction with the pharmacokinetic characteristics of antimalarial drugs, call for the conception of a chrono-therapeutic approach for the treatment of the disease. An experimental murine malarial model was devised using the highly synchronous species Plasmodium vinckei petteri to test this rationale. Sub-curative doses of chloroquine were injected sub-cutaneously to mice either during the prepatent period or during patent infection. Inspection of the effect of drug applied at different stages of the parasitic cycle, revealed that medium size trophozoites (MT) were the most susceptible stage to chloroquine, while ring and young trophozoite stages were refractory to the drug. Chloroquine given during these latter stages, affected the parasites when they developed into the MT stage. Drug treatment during the MT stage phase-shifted the schizogonic cycle by 18 hours. Hence, treatment with two consecutive injections given 18 hours apart, i.e. timed to the overwhelming presence of the MT stage in the circulation, gave the best therapeutic results.
UR - http://www.scopus.com/inward/record.url?scp=0026039460&partnerID=8YFLogxK
U2 - 10.1051/parasite/199166114
DO - 10.1051/parasite/199166114
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C2 - 1883151
AN - SCOPUS:0026039460
SN - 0003-4150
VL - 66
SP - 14
EP - 21
JO - Parasite
JF - Parasite
IS - 1
ER -