Malaria and Travelers

Abstract & Commentary

By Philip Fischer, MD, DTM&H

Dr. Fischer is Professor of Pediatrics, Division of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.

Dr. Fischer reports no financial relationship relevant to this field of study.

Synopsis: Helpful summary information can guide travel medicine practitioners through a maze of controversy toward appropriate use of incompletely understood malaria chemoprophylactic agents as well as toward evidence-based treatment of patients with malaria.

Sources: Chen LH et al. Controversies and misconceptions in malaria chemoprophylaxis for travelers. JAMA 2007; 297:2251-2263.

Griffith KS et al. Treatment of malaria in the United States. JAMA 2007; 297:2264-2277.

The May 23/30, 2007, issue of JAMA was devoted to malaria and contained an informative selection of papers. In particular, two articles were of particular interest to practitioners of travel medicine. Travel Medicine Advisor associate editor, Lin Chen, joined with collaborators on each side of the Atlantic to discuss myths and controversies about malaria chemoprophylaxis. While the prevention of malaria in travelers requires detailed knowledge of malaria epidemiology and host-vector-parasite interactions, they wrote, decisions are also complicated by lack of standardized recommendations. The Centers for Disease Control and Prevention's (CDC's) Monica Parise MD and some of her public health colleagues suggested that U.S. clinicians' unfamiliarity with malaria and drug resistance patterns have contributed to delays in diagnosis and treatment with resulting poor outcomes. Then, with text, tables, and a helpful algorithm, they systematically reviewed the details of medications used in the treatment of malaria.

Commentary

Chemoprophylaxis: Data are not complete, and various national groups have offered differing recommendations in regard to the use of chemoprophylaxis for travelers. In addition, travelers and public media sometimes share misconceptions. Thus, health care providers providing pre-travel care must be aware of factual material while being ready to discuss controversies - particularly in regard to mefloquine and to primaquine.

Since it became available in Europe in 1985, mefloquine has been used by more than 30 million individuals. Many individual reports document both serious and minor adverse events, but larger studies are not completely comparable due to variations in design, methods, and study populations. Some studies have shown similar rates of abnormal dreams and insomnia between travelers taking mefloquine and those taking other antimalarials such as chloroquine. Recent studies, however, show more sleep trouble, headache, and psychological disturbance in travelers, especially women, taking mefloquine. While disabling adverse reactions are uncommon (less than 1%) with mefloquine, they are even less common for individuals taking other medications. Mefloquine does not cause difficulty with driving, concentration, balance, or diving.

Malaria chemoprophylaxis is designed to prevent life-threatening disease but does not effectively prevent later illness due to recrudescence of Plasmodium vivax. Even atovaquone-proguanil, which has some activity against liver stages of malaria, does not prevent hypnozoites from causing later bouts of vivax malaria. Primaquine also offers the potential for providing both primary and post-exposure prevention of malaria and is effective against all species of human malaria. Prior to even prophylactic treatment with primaquine, however, glucose-6-phosphate dehydrogenase (G6PD) deficiency must be ruled out. Until primaquine becomes routinely recommended, travelers to areas endemic for Plasmodium vivax or ovale must be warned that febrile illness, even up to a year or more after return from the endemic area, should prompt a diagnostic evaluation for malaria.

Treatment

Prompt diagnosis of malaria is the key to effective treatment, and clinicians in all settings should consider the diagnosis of malaria in febrile patients who have visited malaria endemic areas within the past year. Blood smears should be obtained and examined promptly; the CDC provides a telediagnosis service as well as physician consultation (770-488-7788 during regular working hours and 770-488-7100 after normal working hours).

Oral quinine (in combination with either tetracycline, doxycycline, or clindamycin), atovaquone-proguanil, and mefloquine are effective in most cases of uncomplicated malaria. Mefloquine use is limited by resistance of malaria parasites originating in some parts of southeast Asia and by its association, in treatment doses, with adverse neuropsychiatric events. Resistance to atovaquone-proguanil has only been reported in 12 patients, but is certainly possible. The combination of atovaquone and proguanil is also probably the best choice for treatment of chloroquine-resistant P. vivax malaria from Papua New Guinea and Indonesia. Primaquine can prevent P. vivax relapses and is now recommended in a dose of 0.5 mg primaquine base/kg by mouth daily for 14 days with a maximum daily dose of 30 mg. Because of either resistance or toxicity, the use of sulfadoxine-pyrimethamine, amodiaquine, and halofantrine is not recommended in the United States.

Treatment of severe malaria should be initiated with parenteral therapy, and quinidine is the only parenteral product available in the U.S. Artemisinin derivatives are effective in cases of severe malaria and will likely be available in the U.S. through the CDC by later this year. Exchange transfusions seem beneficial in some cases of severe malaria. Other treatment modalities including prophylactic phenobarbital, dexamethasone, heparin, and iron chelators are either unproven or harmful and are not recommended.

Children less than 8 years of age should not receive doxycycline or tetracycline due to effects on bone and teeth. Clindamycin is, however, effective in combination with quinine and can replace tetracycline for the treatment of young children. Mefloquine is adequately tolerated in children as small as 5 kg. Primaquine can be used at any age, as long as G6PD testing has been normal.

Atovaquone-proguanil and mefloquine are not currently recommended at treatment doses during pregnancy but can be considered if quinine and clindamycin are not available or are not tolerated. Primaquine should not be used during pregnancy due to the potential risk of undiagnosed G6PD deficiency in the pre-born child.