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Primaquine phosphate has been used for preventing relapse of Plasmodium vivax and P. ovale malaria since the early 1950s, based on its ability to kill latent (hypnozoite) and developing liver stages of these parasites. There are three uses for primaquine in malaria: radical cure of established infection with P. vivax or P. ovale malaria; presumptive anti-relapse therapy (PART; terminal prophylaxis) in persons with extensive exposure to these parasites; and primary prophylaxis against all malaria species. All persons for whom primaquine is being considered must have a glucose-6-phosphate dehydrogenase (G6PD) enzyme level checked before use, and persons who have a deficiency of G6PD must not take primaquine for prophylaxis or PART. The recommended adult dose for PART based on clinical trials and expert opinion is 30 mg base daily for 14 days, started on return from a malarious region and overlapping with a blood schizonticide. The adult dose for primary prophylaxis is 30 mg daily begun 1 day before travel and continued for 7 days after return. This review will examine the evidence for these recommendations.
Received July 27, 2005. Accepted for publication April 13, 2006.
Acknowledgments: The findings and conclusions expressed are the personal views of the authors do not reflect the official views of the Department of Defense, Department of the Army, the Department of the Navy, or the Centers for Disease Control and Prevention. Presented at the Centers for Disease Control and Prevention Expert Meeting on Malaria Prevention, 29-30 January, 2003, Atlanta, Georgia.
Disclaimer: None of the authors has a conflict of interest to declare.
* Address correspondence to David R. Hill, MD, DTM&H, National Travel Health Network and Centre and London School of Hygiene & Tropical Medicine Mortimer Market Centre, Capper Street, London WC1E 6AU, UK. E-mail: david.hill{at}uclh.org
Authors’ addresses: David R. Hill, MD, DTM&H, FRCP National Travel Health Network and Centre and London School of Hygiene & Tropical Medicine Mortimer Market Centre, Capper Street, London WC1E 6AU, UK, E-mail: david.hill{at}uclh.org. J. Kevin Baird, PhD, Director, ALERTAsia Foundation The Eijkman Institute Jalan Diponegoro No. 69, Jakarta 10430, Indonesia, E-mail: alerta{at}alertasia.org. Capt. Monica E. Parise, MD, Chief, U.S. Public Health Service, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway, MS F22, Atlanta, GA 30341, E-mail: mparise{at}cdc.gov. Linda S Lewis, DVM, MPVM, Epidemiologist, Butte County Department of Public Health, 202 Mira Loma Drive, Oroville, CA 95965, E-mail: llewis{at}buttecounty.net. Edward T. Ryan, MD, DTM&H, Director, Tropical & Geographic Medicine Center, Division of Infectious Diseases, Massachusetts General Hospital, Jackson 504, 55 Fruit Street, Boston, MA 02114, E-mail: etryan{at}partners.org. Col. Alan J. Magill, MD, FACP, Director, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, E-mail: alan.magill{at}na.amedd.army.mil.
Infectious Diseases Society of America-United States Public Health Service Grading System for ranking recommendations in clinical guidelines.1 Strength of recommendation: A, good evidence to support a recommendation for use; B, moderate evidence to support a recommendation for use; C, poor evidence to support a recommendation; D, moderate evidence to support a recommendation against use; E, good evidence to support a recommendation against use. Quality of evidence: I, evidence from one or more properly randomized, controlled trials; II, evidence from one or more well-designed clinical trials, without randomization; from cohort or case-controlled analytic studies (preferably from > 1 center); from multiple time-series; or from dramatic results from uncontrolled experiments; III, evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
15 mg daily for 14 days is the current FDA-approved regimen; 30 mg daily for 14 days is not currently an FDA-approved regimen, although clinical trials data (A-II) and current expert opinion (C-III) support the use of the higher dose.
Mild/moderate ADRs enumerated if reported in at least two studies at > 2% frequency; ordered according to number of studies that reported this ADR.
Severe ADRs may be defined in various ways in different studies, but include ADRs interfering with activities of daily living or prompting the seeking of medical attention. Severe ADRs may also include any of the reactions listed under mild to moderate ADRs if they are severe in intensity.
1 Chemotherapeutic index is the ratio of the largest tolerated dose divided by the smallest effective dose (in this case the dose capable of preventing nearly all relapses).
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