Editorial Notes Chemoprophylaxis of Malaria I N JULY 1977, three persons in a group of 20 American tourists to Africa developed malaria. The infection contributed to the death of one, nearly killed the second, and led to hospitalization in a foreign country for the third. All of the uninfected tourists and none of those infected were taking prophylaxis. Two of those who developed malaria had discussed chemoprophylaxis with their physicians and decided against chloroquine because of possible toxicity and eye damage. The third had discussed immunizations but not malaria prophylaxis with his physician. This true story (1) is not unique. Every year thousands of Americans travel to malarious parts of the world unaware of the risk of malaria, of the need for malaria chemoprophylaxis, or of how long they will need medication after they return home. This low level of awareness by travelers, many of whom have sought a physician's advice for immunization, examination, and medication before traveling, undoubtedly reflects inadequate advice from physicians. This poor advice is, at least in part, a consequence of the low priority for tropical medicine in most medical schools in the United States. A recent survey showed that 70% of American medical schools give less than 16 hours to teaching tropical medicine (2). To help fill the gap in physician-patient education about malaria prevention, the Center for Disease Control has published a special supplement to the Morbidity and Mortality Weekly Report (3). These recommendations were drafted at the Center for Disease Control and discussed and modified at the annual meeting of the American Society of Tropical Medicine and Hygiene. This invaluable supplement includes information on malaria risk in diverse geographic areas and appropriate drugs and regimens for malaria chemoprophylaxis. It should be in every physician's office. Copies can be obtained without charge from the Center for Disease Control, 1600 Clifton Road, N.E., Atlanta, G A 30333. The need for, and choice of, an antimalarial depends

on the intensity of the exposure, the presence or absence of chloroquine-resistant malaria, and host characteristics such as age, pregnancy, and previous drug intolerance. These considerations are clearly outlined in the supplement; space does not permit their review here. The main thrust of the supplement is the choice and use of agents to prevent malaria. Chloroquine is the preferred drug for the chemoprophylaxis of all forms of malaria except those strains of Plasmodium falciparum that are resistant to it. The recommended adult dose is 500 mg (300-mg base) taken orally once a week beginning 1 to 2 weeks before entering the malarious area and continuing for at least 6 weeks after the last exposure. Chloroquine is safe for children and pregnant women. Smaller doses recommended for children are detailed in the supplement. There is little risk of any untoward serious reactions in the suppressive doses recommended. Retinopathy has never been reported with the doses of chloroquine used for malaria prophylaxis. (For those few patients who cannot tolerate chloroquine, alternate chemoprophylactic drugs are outlined in the supplement.) Because chloroquine is active only against the erythrocytic stages of Plasmodium infection, chloroquine alone will not always prevent initial attacks or relapses of those malarial infections that persist in the liver (Plasmodium vivax and Plasmodium ovale). Primaquine is active against the exoerythrocytic stages, but the routine use of primaquine for prophylaxis is controversial. Different experts place different values on the potential risk of subsequent malaria, delayed diagnosis, illness, and dollar costs as compared with the potential risk of primaquine toxicity—primarily hemolytic anemia and methemoglobinemia in glucose-6-phosphate dehydrogenase-deficient persons. Therefore, whereas chloroquine can be recommended to all travelers to a malarious area, the decision to administer primaquine should be made for each traveler. Primaquine is given as 15-mg base daily for 15 days and is begun after the traveler has left the malarious area. Primaquine can also be given as 45-mg base once weekly for 8 weeks; this regimen is less apt to induce hemolysis in Editorial Notes

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persons with enzyme-deficient erythrocytes. Malaria chemoprophylaxis in areas with chloroquineresistant strains of P. falciparum requires the use of potentially toxic agents. The need for chemoprophylaxis must be individualized according to the risk of exposure for each traveler. The largest experience with a chemoprophylactic combination in nonimmune North Americans exposed to chloroquine-resistant falciparum malaria has been with a combination of chloroquine, primaquine, and dapsone. This combination was used extensively during the Vietnam conflict, and I recommended it for exposed travelers despite the risk of drug-associated, sometimes fatal, agranulocytosis (4). Several recent studies have suggested that a fixed combination of pyrimethamine and sulfadoxine, a long-acting sulfonamide, is more effective for the suppression of chloroquine-resistant falciparum malaria (5-8). The recommended regimen of pyrimethamine-sulfadoxine is 60 mg of pyrimethamine and 1000 mg of sulfadoxine once every 2 weeks. This drug is active primarily against the erythrocytic stages of malaria parasites and when continued for 6 weeks after returning from a malarious area will produce a suppressive cure of most chloroquine-sensitive and chloroquine-resistant falciparum infections. (Pyrimethamine-resistant strains of P. vivax will not be suppressed; therefore some authorities suggest adding weekly chloroquine to this regimen.) Experience with pyrimethamine-sulfadoxine in nonimmune North Americans is limited, as are toxicity data. N o information is available on the safety of continued use for periods exceeding 6 months. Although no serious untoward effects have been noted, the combination should not be given to patients with sulfonamide drug allergy, and physicians should be alert to the possibility of serious reactions—similar to those associated with the use of other sulfonamides. The drug is not available in the United States but is available in single-tablet form under the trade names Fansidar, Falcidar, or Antemal in most countries with known chloroquine-resistant malaria. The physician must ask, "Where are you going," and advise appropriately about malaria chemoprophylaxis. Failure to do so is a potentially costly, if not fatal, mistake. The current in-hospital cost of treating one patient with this preventable disease is nearly $2000 (9). The potential risk of inadequate antimalarial prophylaxis includes death. The scenario of the patient whose influenza-like illness has not responded to aspirin and orange juice and who is subsequently admitted with irreversible falciparum malaria is all too tragically familiar (10). With increasing numbers of Americans traveling to remote parts of the globe, clinicians in the United States need to increase their competence in tropical medicine, particularly in the prevention of malaria. (ELIZABETH BARRETT-CONNOR, M.D.; Department of Community Medicine, University of California, San Diego; La Jolla, California)

Dam construction site in Laos. I. Suppression with combinations of sulfonamides and pyrimethamine. Jpn J Exp Med 41:209-219, 1971 6. O ' H O L O H A N DR, H U G O E - M A T T H E W S J: Malaria suppression and prophylaxis on a Malaysian rubber estate: sulformethoxine-pyrimethamine single monthly dose vs chloroquine single weekly dose. Southeast Asian J Trop Med Public Health 2:164-168, 1971 7. L E W I S AN, PONNAMPALAM JT: Suppression of malaria with monthly administration of combined sulphadoxine and pyrimethamine. Ann Trop Med Parasitol 69:1-12, March 1975 8. P E A R L M A N EJ, L A M P E RM, T H I E M A N U N W, K E N N E D Y RS: Chemo-

suppressive field trials in Thailand. III. The suppression of Plasmodium falciparum and Plasmodium vivax parasitemias by a sulfadoxine-pyrimethamine combination. Am J Trop Med Hyg 26:1108-1115, 1977 9. K E A N BH, REILLY PC JR.: Malaria—the mime. Recent lessons from a group of civilian travellers. Am J Med 61:159-164, 1976 10.

N E V A FA, S H E A G R E N JN, S H U L M A N NR, C A N F I E L D CJ: Malaria:

host-defense mechanisms and complications. Ann Intern Med 73:295306, 1970 ©1978 American College of Physicians

References 1. S T A T E OF C A L I F O R N I A , D E P A R T M E N T OF H E A L T H : Malaria encounters

of a deadly kind. Calif Morbid Weekly Rep Infect Dis Section No. 17, 5 May 1978 2. SCHULTZ MG: Current concepts in parasitology. Parasitic diseases. N Engl J Med 297:1259-1261, 1977 3. C E N T E R FOR DISEASE CONTROL: Chemoprophylaxis of malaria. Morbid Mortal Weekly Rep 27(10)(suppl):81-90, 10 March 1978 4. BARRETT-CONNOR E: Chemoprophylaxis of malaria for travelers. Ann Intern Med 81:219-224, 1974 5. E B I S A W A I, M U T O T, M I T S U I G, K A M E K O S: Malaria at Nam Ngum

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September 1978 • Annals of Internal Medicine • Volume 89 • Number 3

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Chemoprophylaxis of malaria.

Editorial Notes Chemoprophylaxis of Malaria I N JULY 1977, three persons in a group of 20 American tourists to Africa developed malaria. The infection...
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