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Malaria Deaths Following Inappropriate Malaria Chemoprophylaxis ---United States, 2001

During January--March 2001, two U.S. citizens died from malaria after taking chloroquine alone or with proguanil for malaria chemoprophylaxis in countries with known chloroquine-resistant Plasmodium falciparum malaria. Chloroquine-containing chemoprophylaxis regimens are not recommended by CDC for persons traveling to areas with known chloroquine-resistant P. falciparum. This report summarizes the investigation of the two cases and underscores the need for clinicians and travelers to know the recommended options for malaria chemoprophylaxis when traveling to locations with chloroquine-resistant malaria.

Case Reports

Case 1. On January 11, 2001, a 12-year-old resident of Michigan was taken to a clinic with a 2-day history of fever with chills, malaise, fatigue, cough, and one episode of vomiting. At the clinic, the patient had a temperature of 102 F (39 C). The clinician noted that the patient had returned from Africa on January 6. Upper respiratory tract infection was diagnosed with nausea and vomiting, and the patient was prescribed an oral cephalosporin antibiotic and an antiemetic agent. The symptoms continued, and on January 14, the patient collapsed, was transported to a local hospital, and died in the emergency department shortly thereafter. Examination of a peripheral blood film on stored blood from January 11 and a film from blood taken January 14 demonstrated P. falciparum parasites with 0.8% parasitemia and 14.0%, respectively.

The patient had been born in Nigeria, had emigrated to the United States in 1991, and had returned to Nigeria for 3 weeks during December 2000--January 2001. The patient and five other family members who had traveled to Nigeria had been prescribed weekly chloroquine for malaria chemoprophylaxis. On December 1, the patient had taken the initial 500 mg dose and subsequently had followed the weekly regimen; the last dose was taken January 11. A blood sample taken postmortem revealed a chloroquine level of 1782 ng/ml whole blood, a level consistent with recent ingestion of chloroquine and sufficient to inhibit P. falciparum parasites sensitive to the drug (1,2). The patient's mother also had taken chloroquine for chemoprophylaxis, had P. falciparum malaria diagnosed in January, and later recovered.

Case 2. On March 7, 2001, a 47-year-old resident of Minnesota returned to the United States after 11 days in east Africa. Chloroquine was taken before and during the trip and proguanil was added on arrival in Africa. On returning to the United States, proguanil was discontinued, and on March 11, the scheduled dose of chloroquine was taken. On March 17, the patient developed a persistent headache, and on March 19, sought care for headache and dark urine at a Florida hospital emergency department. On admission, the patient's temperature was 102 F (39 C); physical examination did not reveal any abnormalities. A thick blood film obtained on admission initially was read as Plasmodium species (P. falciparum versus P. malariae), and later was confirmed as P. falciparum. The patient was admitted and treated with oral quinine and doxycycline; however, the patient developed cerebral edema and respiratory failure and died 6 days after admission. The patient had traveled to Africa with a group of 13 persons; nine had taken mefloquine for prophylaxis and four had followed the same regimen as the patient. No other malaria cases were reported from the group.

Reported by: J Landgraf, Lakeland Hospital, Niles; MG Stobierski, G Stoltman, M Boulton, Michigan Dept of Community Health. S Wiersma, JR South, Florida Dept of Health. D Neitzel, H Hull, K Smith, Minnesota Dept of Health. Malaria Epidemiology Br and Entomology Br, Div of Parasitic Diseases, National Center for Infectious Diseases; and EIS officers, CDC.

Editorial Note:

Seven malaria-related deaths among U.S. citizens who had traveled abroad following inappropriate chemoprophylaxis regimens have been reported to CDC since 1992. In all cases, the travelers received prescriptions for chloroquine compounds to be taken for travel to sub-Saharan Africa, where antimalarial resistance to this drug is widespread. The geographic spread of P. falciparum resistance to chloroquine is increasing. Chloroquine resistance exists throughout sub-Saharan Africa, southeast Asia, the Indian subcontinent, and over large portions of South America, including the Amazon basin (3). Among 4685 cases of imported malaria in U.S. civilian travelers during 1992--2001, 893 (19%) took an inappropriate chemoprophylaxis regimen and 2616 (56%) took no chemoprophylaxis. Among 505 persons who took an inappropriate chemoprophylaxis regimen during 1995--2001, 351 (70%) took chloroquine for travel to an area with known chloroquine resistance.

Since 1990, CDC has recommended mefloquine as antimalarial prophylaxis in regions with chloroquine-resistant malaria; doxycycline has been the recommended alternative (4). Chloroquine, ideally taken with daily proguanil (an antimalarial not marketed in the United States except in co-formulation with atovaquone), had been recommended only for persons unable to take mefloquine or doxycycline. In July 2000, Malarone* (Glaxo Wellcome Inc., Research Triangle Park, North Carolina), a combination of atovaquone and proguanil, was approved for use in the United States. Since November 2000, CDC has recommended Malarone, mefloquine, or doxycycline as options for malaria chemoprophylaxis in areas with chloroquine-resistant malaria and no longer recommends chloroquine combined with proguanil (5).

Travelers and health-care workers who provide medical advice to travelers should be aware that chloroquine is effective for malaria prophylaxis only in a few areas of the world. Recommending and prescribing inappropriate chemoprophylaxis can result in travelers becoming ill or dying from malaria. Information on malaria prevention and chemoprophylaxis is available in Health Information for International Travel, CDC's handbook for travelers, which is published biannually and is available and updated online at http://www.cdc.gov/travel. Information also is available by telephoning (877) FYI-TRIP ([877] 394-8747).

References

  1. Hellgren U, Kihamia CM, Mahikwano LF, Björkman A, Eriksson Ö, Rombo L. Response of Plasmodium falciparum to chloroquine treatment: relation to whole blood concentrations of chloroquine and desethylchloroquine. Bull World Health Organ 1989;67:197--202.
  2. Krishna S, White NJ. Pharmacokinetics of quinine, chloroquine, and amodiaquine: clinical implications. Clin Pharmacokinet 1996;30:263--92.
  3. CDC. Health information for international travel 1989. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, 1989.
  4. CDC. Information for health care providers: Malarone for malaria treatment and prophylaxis, October 2000. Available at http://www.cdc.gov/travel/diseases/malaria/malarone.htm. Accessed January 3, 2001.
  5. CDC. Health information for international travel 2001--2002. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, 2001.

*Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services.

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