Is primaquine useful and safe as true exo-erythrocytic merontocidal, hypnozoitocidal and gametocidal antimalarial drug?

Résumé 0

"The main objective of this paper is to make available in asingle document, a sequence of events that have beenpublished on the biology of malaria parasites and theirinteraction with the human host, looking for arguments foreffective and save treatment: what we know and what wewould like to know about the effects of primaquine in orderto justify its use in clinical and public health practice. Thepracticioner should be aware that the antimalarial activity,hemolytic and methemoglobinemic side effects, anddetoxification of primaquine are all thought to depend onvarious biotransformation products of the drug. In spite ofthe universal use during over six decades, their site andmechanism of formation and degradation and their specificbiologic effects remain very poorly understood in humanbeings. The mature gametocytes of P. falciparum are naturallyresistant to chloroquine and other blood merontocides, butthey are usually eliminated with a single dose of 1.315 mg/kgper os (p.o.) of primaquine phosphate (equivalent to 0.75mg-base). Rather than empirically, related with relapsesfrequency, dosage schedules should only be determinedthrough consideration of the kinetics and dynamics of thedrug and its effect on sporozoites, pre and exo-erythrocyticmerontes, hypnozoites and gametocytes of P. vivax. Wheremedical care services are not available or not capable to detectglucose -6- phosphate dehydrogenese- (G-6-PD) deficienciesand deleterious effects of the drug, we recommend not touse primaquine. Both, P. vivax primary clinical attack and P.vivax relapses, as and when they occur should be treated witha course of 10 mg/kg chloroquine-base p.o. Prevention ofrelapses is probably related to strain characteristics of P. vivaxhypnozoites populations envolved. If well informed and qualified medical care workers decide to use primaquine inthe absence of enzime defficiencies and are able to follow-upthe clinical, toxicological and parasitic results, a daily dose of0.25 mg/kg primaquine-base during 14 days could beadministered safety for possible prevention of P. vivax relapses."