Correspondence

Failure of Mefloquine Chemoprophylaxis for Malaria in Somalia

N Engl J Med 1993; 329:1206October 14, 1993

Article

To the Editor:

A weekly dose of 250 mg of mefloquine (Lariam) is being used by U.S. forces for chemoprophylaxis against malaria in Somalia. We report two cases of malaria caused by Plasmodium falciparum in U.S. soldiers who were taking mefloquine.

A 23-year-old man was admitted on March 3, 1993, with a seven-day history of fever, chills, and headache. A blood smear showed P. falciparum. The serum mefloquine level in blood drawn when the patient's smear was positive was 1067 ng per milliliter for the parent compound and 4014 ng per milliliter for the primary metabolite. He had been taking mefloquine since December 17, 1992. He reported that he had not missed any doses.

A 21-year-old man was seen on March 29, 1993, with a two-day history of fever, severe frontal headache, aching knees, and malaise. A peripheral-blood smear showed P. falciparum. The serum mefloquine level in blood obtained when the patient's smear was positive was 830 ng per milliliter for the parent compound and 2627 ng per milliliter for the primary metabolite. He had initially taken 100 mg of doxycycline by mouth daily for chemoprophylaxis, starting on December 15, 1992. He switched to mefloquine in mid-January 1993; during one week he was taking both drugs. He reported that he had not missed any doses.

Both patients were successfully treated with oral quinine and pyrimethamine-sulfadoxine (Fansidar); no resistance to therapeutic doses was observed. Serum mefloquine levels were measured at the Centers for Disease Control and Prevention by high-performance liquid chromatography1. At steady-state plasma concentrations, the level of the primary metabolite of mefloquine is at least twice that of the parent compound (Lobel HO: personal communication). The serum levels of mefloquine and its primary metabolite suggest that both patients complied with their chemoprophylactic regimens. A serum mefloquine level of more than 650 ng per milliliter is thought to prevent malaria in 95 percent of people who use mefloquine for chemoprophylaxis2.

Reduced susceptibility to mefloquine in vitro has been documented in West African isolates of P. falciparum3. Although resistance to chloroquine has been documented in Somalia,4 resistance to mefloquine has not. Physicians seeing soldiers or others returning from Somalia must suspect malaria in all febrile patients, regardless of their history of chemoprophylaxis. The clinical presentation of malaria may be milder and atypical in patients undergoing chemoprophylaxis. Despite case reports of mefloquine resistance from West Africa and these failures of chemoprophylaxis, mefloquine is an effective and well-tolerated agent2 and should be recommended as chemoprophylaxis for travelers to Africa5.

Alan J. Magill, M.D., Maj., M.C.
Bonnie L. Smoak, M.D., Ph.D., Maj., M.C.
Walter Reed Army Institute of Research, Washington, DC 20307-5100

5 References

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   Warsame M, Wernsdorfer WH, Willcox M, Kulane AA, Bjorkman A. The changing pattern of Plasmodium falciparum susceptibility to chloroquine but not to mefloquine in a mesoendemic area of Somalia. Trans R Soc Trop Med Hyg 1991;85:200-203
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   Wyler DJ. Malaria chemoprophylaxis for the traveler. N Engl J Med 1993;329:31-37
   Full Text | Web of Science | Medline

Citing Articles (5)

Citing Articles

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   Watcharapong Piyaphanee, Yupaporn Wattanagoon, Udomsak Silachamroon, Chayasin Mansanguan, Pongdej Wichianprasat, Eric Walker. (2009) Knowledge, Attitudes, and Practices Among Foreign Backpackers Toward Malaria Risk in Southeast Asia. Journal of Travel Medicine 16:2, 101-106
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   COL L. Jose Sanchez, Izidro Bendet, LTC Max Grogl, José B. P. Lima, LTC W. Lorrin Pang, Maj Farm Med Roberto Guimaraes, Cel H. Med Roberto Guedes, COL K. Wilbur Milhous, Michael D. Green, LCDR Daniel G. Todd. (2000) Malaria in Brazilian Military Personnel Deployed to Angola. Journal of Travel Medicine 7:5, 275-282
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3. 3

   Patricia Schlagenhauf. (1999) Mefloquine for Malaria Chemoprophylaxis 1992–1998: A Review. Journal of Travel Medicine 6:2, 122-133
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4. 4

   Alberto Matteelli, Alessandro Chiodera, Francesco Castelli, Silvio Caligaris, Cristina Minardi, Giampiero Carosi. (1995) Failure of Mefloquine Chemoprophylaxis for Malaria in Mozambique. Journal of Travel Medicine 2:4, 260-261
   CrossRef

5. 5

   Mario S. Peragallo, Guido Sabatinelli, Giancarlo Majori, Glauco Calí, Giuseppe Sarnicola. (1995) Prevention of malaria among Italian troops in Somalia and Mozambique (1993–1994). Transactions of the Royal Society of Tropical Medicine and Hygiene 89:3, 302
   CrossRef