Adequate Primaquine for Vivax Malaria

Scott Kitchener; Peter Nasveld; Sonya Bennett; Joseph Torresi

Disclosures

J Travel Med. 2005;12(3):133-135. 

In This Article

Abstract and Introduction

Abstract

Background: Treatment of vivax malaria with primaquine prevents the relapse of infection from residual liver stages of the parasite. Inadequate dosage is related to a higher relapse risk.
Methods: A comparison was made of vivax malaria relapse-prevention treatments with primaquine 22.5 mg or 30 mg daily for 14 days on 146 reports to the Australian Army Central Malaria Register.
Results: The lower dose of primaquine was found to carry a relative risk of 6.63 for a relapse of vivax malaria compared with the higher dose.
Conclusions: The available data presented here suggest that vivax malaria in this region is increasingly tolerant of the 22.5 mg daily treatment regimen of primaquine and that the greater dose of at least 30 mg daily is more effective.

Introduction

Following an outbreak of primarily falciparum malaria among Australian Defence Force (ADF) personnel during the InterFET (International Force, East Timor) operation in East Timor (September 1999-February 2000), 267 vivax malaria cases and relapses were reported to the Central Malaria Register (CMR) of the Army Malaria Institute by September the following year.[1]

To prevent vivax (and ovale) malaria, primaquine postexposure prophylaxis (PEP) may be used following travel to malarial areas.[2] In the ADF, primaquine PEP is not directly observed by routine. Nevertheless, for almost 10 years, this has been found to be effective against malaria exposures in the regions to the near north of Australia.[3] Prior to the ADF involvement in East Timor, the policy for the primaquine PEP dose for this region was raised from 15 mg daily to 22.5 mg daily for 14 days.

Initial investigations of primaquine during the 1950s were conducted using the Chesson strain from the southwest Pacific. Investigators found 30 mg/d for 14 days was effective,[4,5] whereas 15 mg daily of primaquine was only 70 to 80% effective. Later the total dose of primaquine was suggested as the salient feature of treatment,[6] and 6 mg/kg was ultimately recommended for effective treatment.[7]

In recent studies of primaquine efficacy among Australians being treated for vivax malaria, resistance was suggested by a relapse rate of infections from Papua New Guinea in returning Australians that was eight times the relapse rate of infections contracted elsewhere.[8] It was further noted that for these infections, 30 mg primaquine daily for 14 days (420 mg total) was probably inadequate treatment to prevent relapses in this group of Australians. The total dose of 315 mg (22.5 mg daily for 14 days) used by our study population for PEP would only be satisfactory to treat those individuals weighing < 52.5 kg. In a sample of 1,557 Australian soldiers completing deployments from operations in Bougainville and East Timor, the average weight was 79 kg (SD 12 kg); therefore, the existing dose would be inadequate for most.

The conventional treatment of vivax malaria in the ADF is 1,500 mg chloroquine orally over 3 days followed by 14 days of primaquine at 7.5 mg three times a day (315 mg). However, during the study period 15 mg twice daily for 14 days (420 mg) began to be used for treatment, providing the opportunity for a retrospective analysis of the effectiveness of the larger dose.

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