Severe Cutaneous Reactions among American Travelers Using Pyrimethamine-Sulfadoxine (Fansidar®) for Malaria Prophylaxis

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  • * Malaria Branch, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia 30333
  • ** Epidemiology Development Branch, Division of Drug and Biological Product Experience, Food and Drug Administration, Rockville, Maryland 20857
  • Department of Dermatology, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215

In 1982, the fixed combination of pyrimethamine and sulfadoxine (Fansidar®) became available in the United States, and was recommended for use in travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum. Prior to that time, no reports of severe cutaneous reactions had appeared in the medical literature despite widespread use for more than 8 years in both Europe and malarious areas of the developing world. In the fall of 1984, the Centers for Disease Control received reports of 4 cases of toxic epidermal necrolysis (including 3 fatalities) among Americans who had used pyrimethamine-sulfadoxine (PYR/SDX) for the prevention of malaria. Subsequent investigation into severe cutaneous reactions associated with the use of this drug by American travelers detected 24 cases of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Twenty-three of the 24 patients concurrently used chloroquine. Seven patients died. No risk factors in the development of these reactions other than the use of PYR/SDX could be identified. Among American travelers, we estimate that these reactions occur in 1 per 5,000–8,000 users, and that fatal reactions occur in 1 per 11,000–25,000 users. This higher than expected incidence necessitates that the use of PYR/SDX for the prevention of malaria be reconsidered. In the United States it is now recommended that the routine weekly use of the drug be reserved for those travelers at highest risk of acquiring chloroquine-resistant P. falciparum, when alternate prophylactic regimens are not deemed appropriate.