Chemotherapy of Drug‐Resistant Malaria

Abstract

KC KAIN. Chemotherapy of drug-resistant malaria. Can J Infect Dis 1996;7(1):25-33. OBJECTIVE:To review the impact of drug-resistant malaria on current management of plasmodial infections. DATA SOURCES: A MEDLINE search of the English-language medical literature from 1985 to 1995; bibliographies of selected papers; international malaria advisory experts. DATA SYNTHESIS: Combinations of artemisinin derivatives and mefloquine or atovaquone plus proguanil appear to be the most active drug regimens against multidrug-resistant falciparum malaria from Southeast Asia. The optimal therapy for chloroquine-resistant Plasmodium vivax is unknown, but recent data indicate that halofantrine or chloroquine plus high doses of primaquine are efficacious. CONCLUSIONS:The incidence of drug-resistant malaria continues to increase at a rate that exceeds new drug development. Ultimately the control of malaria will require more creative approaches than just the development of additional inhibitory drugs. These might include the identification of biochemical pathways unique to the parasite (such as drug efflux and heme polymerization), making it possible to design new classes of antimalarial agents that are selectively toxic to the parasite; methods to block parasite development in the mosquito vector; and multistage vaccines against asexual and sexual stages to block both the pathophysiology and the transmission of disease. Key Words: Drug-resistant malaria, Plasmodium falciparum, Plasmodium vivaxTraitement pharmacologique du paludisme réfractaire OBJECTIF : Passer en revue l'impact du paludisme réfractaire aux médicaments sur le traitement courant des infections plasmodiales. SOURCES DES DONNÉES :Une interrogation du Réseau MEDLINE sur la littérature médicale de langue anglaise publiée entre 1985 et 1995, bibliographies d'articles sélectionnés, experts-conseils internationnaux sur le paludisme. SYNTHÈSE DES DONNÉES : Les associations de dérivés d'artémisinine, de méfloquine ou d'atovaquone plus proguanil semblent être les schémas médicamenteux les plus efficaces contre le paludisme à falciparum résistant à plusieurs médicaments, en provenance de l'Asie du sud-est. Le traitement optimal dans les cas de Plasmodium vivax résistant à la chloroquine est inconnu, mais selon des données récentes, l'halofantrine ou la chloroquine avec dose élevée de primaquine sont efficaces. CONCLUSIONS : L'incidence du paludisme résistant aux médicaments continue d'augmenter à un taux qui excède la vitesse de mise au point de nouveaux médicaments. Éventuellement, la maîtrise du paludisme exigera des approches plus créatrices que le simple développement d'autres médicaments inhibiteurs. Parmi ces approches, l'identification des voies biochimiques empruntées par ce parasite (comme l'efflux des médicaments et la polymérisation de l'hème) rendra possible la conception de nouvelles classes d'agents antipaludéens sélectivement toxiques à l'endroit du parasite, de méthodes en vue de bloquer le développement du parasite dans le vecteur même et de vaccins à plusieur...

Reemergence of Established Pathogens in the 21st Century

“…Mefloquine alone (15 mg/kg) has low cure rates in regions of Thailand but it remains efficacious in much of Africa and South America (>90% efficacy) (Kain, 1996). When studied in 94 Brazilian patients with falciparum malaria, mefloquine (1,000 mg single dose) had a reported cure rate of 99% (95% Confidence Interval, CI 94.2-99.7%) (Cerutti et al, 1999).…”

“…Patients who relapse following a standard course of primaquine should receive two times the standard dose (30 mg base/day for 14 days) or a total dose of 6 mg/kg of primaquine to prevent further relapse (Kain, 1996).…”

Educating travelers about malaria: dealing with resistance and patient noncompliance.

“…Because approximately 90% of travelers who contract malaria do not become ill until returning home, it is up to us-in an area where malaria is not common-to recognize malaria, make the laboratory diagnosis, and treat it. 44,45 About 1,500 cases of malaria are diagnosed in the United States each year, 99.7% in travelers. 10 Approximately 90% of travelers who contract malaria become ill after returning home.…”

Evaluation of rapid immunocapture assays for diagnosis of Plasmodium vivax in Korea

“…Moreover, malaria is becoming increasingly prevalent, including in Korea. A number of factors have contributed to the global resurgence of malaria, including insecticide resistance in the Anopheles mosquito, rapid spread of antimalarial-drug resistance, and increased movement of human populations consequent on increases in international travel and immigration (Collins and Jeery 1996;Freedman 1992;Kain 1996;Lackritz et al 1991;Molyneux and Fox 1993).…”