Therapeutic Responses to Different Antimalarial Drugs in Vivax Malaria

Abstract

The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients with Plasmodium vivax malaria. This parasite does not cause marked sequestration, so parasite clearance can be used as a direct measure of antimalarial activity. The activities of these drugs in descending order were artesunate, artemether, chloroquine, mefloquine, quinine, halofantrine, primaquine, and pyrimethamine-sulfadoxine (PS). Therapeutic responses to PS were poor; parasitemias did not clear in 5 of the 12 PS-treated patients, whereas all the other patients made an initial recovery. Of 166 patients monitored for >28 days, 35% had reappearance of vivax malaria 11 to 65 days later and 7% developed falciparum malaria 5 to 21 days after the start of treatment. There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine, in which all vivax malaria reappearances developed >28 days after treatment, suggesting suppression of the first relapse by these slowly eliminated drugs. There was no evidence of chloroquine resistance. The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action.Plasmodium vivax affects millions of people living in tropical areas and is an important cause of morbidity in Central and South Americas and Asia. Until recently, P. vivax has remained uniformly sensitive to chloroquine, and this cheap and widely available antimalarial agent has been the treatment of choice for the past 50 years. Although P. vivax developed resistance to the dihydrofolate reductase inhibitors within a few years of their initial deployment as single drugs (7), chloroquine resistance has developed only in the last decade. High-level chloroquine resistance has been well documented on the northern part of the island of New Guinea and in Sumatra, Indonesia, and there have been sporadic reports from other geographic locations (1). The evaluation of alternative antimalarial drugs for the treatment of vivax malaria is therefore needed.Most research on the efficacies of antimalarial drug treatments concerns Plasmodium falciparum, the most dangerous and the most drug resistant of the four human malaria parasites. P. vivax is less virulent than P. falciparum because it does not reach high parasite densities and it does not sequester in the capillaries and venules. As all stages of asexual development are present in the peripheral blood, the initial decline in the level of parasitemia following drug treatment of P. vivax malaria reflects antimalarial activity and not a combination of accelerated parasite clearance and sequestration (13). This allows a direct comparison of the antimalarial activities of different antimalarial agents, including drugs which act predominantly in the second half of the asexual life cycle. In contrast, in falciparum malaria comparison of the pharmacodynamic properties of antimalarial agents in vivo is confounded by the sequestration of parasiti...

Microgeographical Differences of Plasmodium vivax Relapse and Re-Infection in the Peruvian Amazon

“…Although some recrudescences could result from inadequate drug absorption or unusual disposition kinetics, recurrent infections in this study were newly acquired infections or relapses. 26,27 The Pvmsp-3a polymorphism analysis has been an important molecular epidemiological tool for distinguishing P. vivax infections in malaria-endemic areas. 18,28,29 This study used Pvmsp-3a PCR-RFLP and TR-PCR analysis as tools for differentiating primary from subsequent P. vivax infections.…”

Diagnosis and Treatment of Plasmodium vivax Malaria

“…41,42 Mefloquine, 43 atovaquone + proguanil, 44 halofantrine, 45 piperaquine, 46 artesunate, 47,48 and pyronaridine, 49 all show good efficacy against chloroquine-resistant (CQR) P. vivax in clinical trials.…”

Antiprotozoal compounds: state of the art and new developments

“…Nevertheless, quinine is not considered an ideal treatment owing to its toxicity. Furthermore, it was found that treatment of P. vivax infections with quinine might lead to early relapses owing to the short half-life of quinine [36].…”

“…A treatment success of 100% has been reported [36]. Doxycycline monotherapy applied in 100 mg oral doses twice a day for 7 days shows poor cure rates in P. vivax infections [37], however quinine given in doses of 10 mg salt/kg three times a day for 7 days is also effective against CQ-resistant P. vivax strains [38].…”