Revised Recommendations for Malaria Chemoprophylaxis for Travelers to East Africa

The following statement updates information published in the "East Africa" section of the MMWR supplement, "Prevention of Malaria in Travelers, 1982" (MMWR Vol. 31/No.1S, p. 24S) dated April 16, 1982.

Infections with chloroquine-resistant Plasmodium falciparum malaria acquired by travelers to East Africa were first reported in 1978 (1). Since then, there have been a number of similar case reports in the world literature, all describing chloroquine-prophylaxis and/or -treatment failures in non-immune travelers to East Africa (2-4).

In the past 18 months, an additional 19 such cases of chloroquine-prophylaxis failure among U.S. travelers have been reported to and documented by CDC. When available, chloroquine levels in blood tested at the time of diagnosis have corroborated the history of chloroquine prophylaxis. In several instances, malaria parasites from these patients have been adapted to in vitro culture, and in vitro drug-sensitivity testing has confirmed the parasites' in vivo resistance to chloroquine. To date, the countries in which chloroquine-resistant infections in non-immune travelers have been acquired include: Kenya, Tanzania, Uganda, Madagascar, and Comoros (5). There have been no documented cases from West Africa.

These data offer compelling evidence that chloroquine-resistant P. falciparum transmission is widely dispersed in East Africa, and that there is substantial risk of infection for American travelers, despite chloroquine prophylaxis. Foreign Service officers, Peace Corps volunteers, missionaries, and workers who live for extended periods in areas with high transmission may be at particular risk. Consultation with medical personnel of the U. S. Department of State and of the Peace Corps confirms that cases of chloroquine prophylaxis failure have occurred in these groups within the past year.

Fansidar* is the drug most commonly used to suppress chloroquine-resistant P. falciparum malaria. Each tablet contains a fixed combination of pyrimethamine, 25 mg, and sulfadoxine, 500 mg. Fansidar was licensed for sale in the United States in January 1982.

Chloroquine and the 2 components of Fansidar interrupt different metabolic pathways of the malaria parasite. Therefore, while the risk of acquiring malaria can never be completely eliminated, available information indicates that the combination of chloroquine with Fansidar will be substantially more effective prophylactically than Fansidar alone. When Fansidar prophylaxis is indicated, chloroquine should always be taken concurrently because: 1) Fansidar alone may not always be efficacious (even against sensitive strains of P. falciparum) due to "host failure" (6), 2) the addition of chloroquine may retard the emergence of Fansidar-resistant malaria, and 3) the effectiveness of Fansidar as a prophylaxis for the other species of human malaria in East Africa has not been adequately documented.

On the basis of accumulating evidence and the advice of a recently convened group of experts, CDC's recommendations now are: Fansidar, 1 tablet once weekly PLUS chloroquine 300 mg (base) once weekly. Weekly doses of Fansidar and chloroquine may be taken on the same day, at the same time. Contraindications to Fansidar

1. Pregnant women. Fansidar is not recommended for pregnant women, due to results of animal studies suggesting that pyrimethamine may have teratogenic potential. Pregnant women who cannot avoid travel to areas of the world with chloroquine-resistant malaria should use chloroquine alone as prophylaxis. Health-care providers should advise these patients that they are at increased risk of acquiring malaria, and should be especially alert for the development of a febrile illness.

2. Allergy to sulfonamides. The use of Fansidar is contraindicated for persons allergic to sulfonamides; a pyrimethamine-dapsone combination (marketed overseas as Maloprim) may be useful for individuals who do not have cross-hypersensitivity to sulfones. Of note, hematologic toxicity attributed to dapsone has been reported when it has been taken for malaria prophylaxis (7).

3. Children under 2 months old. Fansidar should not be given to children 2 months of age, as sulfa drugs may induce neonatal jaundice. Chloroquine may be given to newborns, but parents should be aware of the potential for prophylaxis failure in areas where transmission of chloroquine-resistant malaria is known to occur. Long-Term Use of Fansidar.

There have been few studies of the long-term side effects of Fansidar prophylaxis (8,9), and no studies of the side effects of concurrent use of both chloroquine and Fansidar. Long-term administration of pyrimethamine may induce megaloblastic anemia, leukopenia, or other hematologic toxicity. While these side effects are usually reversible, routine hemograms should be obtained from persons on Fansidar prophylaxis for longer than 6 months. Reported by Malaria Br, Div of Parasitic Diseases, Center for Infectious Diseases, CDC.

References

1. CDC. Chloroquine-resistant malaria acquired in Kenya and Tanzania--Denmark, Georgia, New York. MMWR 1978;27:463-4.

2. Faehlmann M, Rombo L, Hedman P. Serum concentrations of chloroquine in a patient with a late recrudescence of Kenyan Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 1981;75:362-4.

3. Gardner AL, Weinstein RA, Lincoln LJ. Failure of chloroquine prophylaxis in Plasmodium falciparum from East Africa. JAMA 1981;246:979-80.

4. Bengtsson E, Bjorkman A, Brohult J, et al. Malaria prophylaxis when visiting areas of East Africa with chloroquine resistance. Lancet 1981;2:249.

5. CDC. Chloroquine-resistant Plasmodium falciparum malaria acquired in East Africa--Pennsylvania. MMWR 1981;30:525-6.

6. CDC. Problems encountered with using Fansidar as prophylaxis for malaria. MMWR 1982;31:232-4.

7. Ognibene, AJ. Agranulocytosis due to dapsone. Ann Intern Med 1970;72:521-4.

8. Ebisawa I, Muto T, Mitsui G, Kameko S. Malaria at Nam Ngum Dam construction site in Laos. Jap J Exp Med 1971;41:209-19.

9. O'Holohan DR, Hugoe-Matthews 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 1971;2:164-8. *Use of trade names is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.

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