TY - JOUR
T1 - Modelling the chloroquine chemotherapy of falciparum malaria
T2 - The value of spacing a split dose
AU - Hoshen, M. B.
AU - Stein, W. D.
AU - Ginsburg, H.
PY - 1998
Y1 - 1998
N2 - We have attempted to provide a rational basis for improving the protocols for chemotherapy of malaria. We model the regression of parasitaemia by Plasmodium falciparum its subsequent elimination from the body, or recrudescence, for populations of cells treated with chloroquine. Our model assumes that the drug forms a complex with some receptor in the parasite and that parasites possessing this complex die at a defined rate. We take into account that chloroquine is eliminated exonentially from the body. We show how the parameters of the model can be derived from observations in the field. The model correctly predicts the effects of drug dose, degree of initial parasitaemia, rate of parasite multiplication and degree of drug resistance to chloroquine chemotherapy. The level of parasitaemia will reduce to a minimum at sufficiently high concentrations of chloroquine, but only if the parasitaemia is reduced to below that of 1 parasite per infected person will a cure of malaria be obtained. Otherwise, recrudescence will, sooner or later, occur. We show that, even for drug-resistant malaria, if 2 doses of chloroquine are given to a patient with an interval of some 10 days between them, parasites can be eliminated from the body without toxic levels of chloroquine being reached.
AB - We have attempted to provide a rational basis for improving the protocols for chemotherapy of malaria. We model the regression of parasitaemia by Plasmodium falciparum its subsequent elimination from the body, or recrudescence, for populations of cells treated with chloroquine. Our model assumes that the drug forms a complex with some receptor in the parasite and that parasites possessing this complex die at a defined rate. We take into account that chloroquine is eliminated exonentially from the body. We show how the parameters of the model can be derived from observations in the field. The model correctly predicts the effects of drug dose, degree of initial parasitaemia, rate of parasite multiplication and degree of drug resistance to chloroquine chemotherapy. The level of parasitaemia will reduce to a minimum at sufficiently high concentrations of chloroquine, but only if the parasitaemia is reduced to below that of 1 parasite per infected person will a cure of malaria be obtained. Otherwise, recrudescence will, sooner or later, occur. We show that, even for drug-resistant malaria, if 2 doses of chloroquine are given to a patient with an interval of some 10 days between them, parasites can be eliminated from the body without toxic levels of chloroquine being reached.
KW - Chemotherapy
KW - Chloroquine
KW - Drug resistance
KW - Plasmodium falciparum
UR - http://www.scopus.com/inward/record.url?scp=0031897710&partnerID=8YFLogxK
U2 - 10.1017/S0031182098002480
DO - 10.1017/S0031182098002480
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 9614323
AN - SCOPUS:0031897710
SN - 0031-1820
VL - 116
SP - 407
EP - 416
JO - Parasitology
JF - Parasitology
IS - 5
ER -