Malaria in Peace and War

Abstract and Commentary

Synopsis: Malaria remains a serious threat to both tourists and deployed military personnel. Areas once thought to be relatively risk free may later be associated with transmission of malaria, requiring public health vigilance and regular updating of prophylaxis recommendations.

Sources: CDC Transmission of Malaria in Resort Areas-Dominican Republic, 2004. MMWR. 2005;53:1195-1198; Kotwal RS, et al. An Outbreak of Malaria in US Army Rangers Returning From Afghanistan. JAMA. 2005;293:212-216.

Kay and colleagues from CDC describe 3 cases of falciparum malaria presenting in November 2004 in travelers from the United States returning from resort areas in La Altagracia and Duarte provinces in the Dominican Republic. These areas in the far eastern region of the island of Hispaniola had previously been regarded as nonmalarious. All 3 patients had significant delay in correct diagnosis and suffered severe malaria associated with high level parasitemia, and their clinical courses were complicated by acute respiratory distress syndrome, requiring mechanical ventilation, acute renal failure requiring hemodialysis, and cerebral malaria in at least 1 of the cases. An additional 14 cases of malaria have been reported in European and Canadian travelers returning from La Altagracia Province.

Kotwal et al describe an outbreak of vivax malaria involving 38 soldiers from a 725-man Ranger Task Force which had been deployed to eastern Afghanistan between June and September 2002. Of note, was the delayed presentation of many of these patients with a median duration of 233 days (range, 1-339 days) after return from the malaria endemic region. From a post-deployment survey of 521 members of the task force, it was noted that the self-reported compliance rate was 52% for weekly chemoprophylaxis, 41% for terminal prophylaxis, 31% for both weekly and terminal prophylaxis, 82% for treating uniforms with permethrin, and 29% for application of insect repellant.

Comment by Dean Winslow, MD, FACP

Malaria remains a major infectious disease scourge in the developing world, with up to 500 million estimated cases and several million deaths annually.1 Malaria is largely ignored by the majority of people in the developed world until it strikes home. This most often occurs when we venture forth to malaria endemic regions as either voluntary civilian tourists or as military armed tourists in the service of our country.

The CDC report is of interest for several reasons. The diagnosis appears to have been significantly delayed in all 3 of the cases occurring in US travelers, resulting in multi-organ system complications. The development of malaria in individuals returning from what had been considered to be non-malarious areas, points out the likely influence of climatic events on changes in the regional epidemiology of this disease. In September 2004, Hurricane Jeanne struck the Caribbean islands on its way northward and caused heavy rains and flooding, markedly increasing the risk of transmission due to providing standing water to facilitate the increased breeding of the Anopheles albimanus mosquitoes, the predominant malaria vector in the Dominican Republic. It is of note that a previous outbreak of malaria in European travelers to the eastern part of the Dominican Republic occurred during July 1999-March 2000 in the wake of hurricanes Mitch and George.2 At that time, the CDC temporarily expanded its travel recommendations to recommend chloroquine prophylaxis for all areas of La Altagracia Province; this recommendation was rescinded 2 months later after the Dominican Republic Ministry of Health increased surveillance and controlled the outbreak. In November 2004, the CDC again expanded its recommendations for chloroquine prophylaxis to include both La Altagracia and Duarte Provinces.3

The outbreak of vivax malaria in US Army Rangers returning from deployment to Afghanistan reported by Kotwal et al raises several practical issues for malaria chemoprophylaxis and physical preventive measures. While most individuals taking a 2-3 week vacation to a malarious area will comply with physical preventive measures and chemoprophylaxis, it is much more difficult to do so when one is deployed for 120 days or more. While not specifically addressed by Kotwal et al, the poor compliance with insect repellant (DEET is issued to US military personnel.) may have been related to odor, which could potentially result in tactical compromise of special operations. Additionally, the necessity of conducting night combat operations would be expected to maximize exposure to the mosquito vector. It is not widely appreciated by either commanders or physicians that chemoprophylaxis is not 100% effective, even with good compliance with medication. An outbreak of falciparum malaria in a total of 80 US Marines deployed to Liberia in September 2003 was recently reported.4 This earlier outbreak was closely studied by the team at National Naval Medical Center in Bethesda, and a number of potentially important factors were identified. While most individuals had detectable levels of mefloquine in their blood, compliance was not perfect. In addition, since it was originally anticipated that the marines would be ashore for only 2-3 days (rather than the 10-12 nights they ended up spending in Liberia), they did not deploy with bed nets.

Due to the co-existence of chloroquine resistant P. falciparum in the Indian subcontinent and immediately adjacent areas including Afghanistan, the US military provides mefloquine for non-flying personnel and doxycycline to flyers deployed to the Afghanistan area of operational responsibility (AOR). (In Eastern Turkey and Iraq at least 95% of malaria is vivax, so chloroquine is used in the Iraq AOR.) Unfortunately, mefloquine causes CNS side effects (including dysphoria, dreams, mood changes, and other transient neuropsychiatric reactions) in up to 5% of individuals. From personal experience while deployed with the US Air Force during this latest war, doxycycline malaria chemoprophylaxis, when taken daily for weeks at a time, frequently causes nausea, bloating, and loose stools. If taken on an empty stomach, especially before going to bed, severe esophagitis may occur. In addition, photosensitivity can be a significant problem with doxycycline.

An earlier outbreak of malaria reported among US military personnel returning from Somalia in 1993 is also illustrative of the importance of the use of terminal prophylaxis in areas where vivax (and ovale) malaria risk is high.5 The major malaria threat in Somalia was judged to be P. falciparum, so only chemoprophylaxis with either mefloquine or doxycycline was given in most cases. Terminal prophylaxis with primaquine was rarely given and not supervised after redeployment in the cases where it was prescribed. As a result, of the 83 Army and Marine Corps personnel with documented malaria infections, 77% had vivax, 17% falciparum, 4% had mixed vivax and falciparum infection, and ovale was detected in 1 patient.

These reports remind us of the importance of malaria as a cause of fever and severe illness in travelers. Accurate and up-to-date medical intelligence is critical so that appropriate chemoprophylaxis can be prescribed. Prevention of malaria in travelers and military personnel is, also, more than just compliance with chemoprophylaxis.

It is multilayered and must include bed nets and personal protective measures including using DEET, treating uniforms/clothes with permethrin, and such seemingly unimportant measures as keeping sleeves rolled down.

Dr. Winslow, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor of Infectious Disease Alert.

References

1. Greenwood B. Malaria Mortality and Morbidity in Africa. Bull World Health Organ. 1999;77:617-618.

2. Jelinek T, et al. Falciparum Malaria in European Tourists to the Dominican Republic. Emerg Infect Dis. 2000;6:537-538.

3. CDC. Outbreak Notice: Advice For Travelers About Revised Recommendations For Malaria Prophylaxis in Dominican Republic; updated December 17, 2004.

4. Martin GJ. Lack of Preparation Led to Malaria Outbreak Among Marines. US Medicine Information Central 2003; (online citation) December 2003.

5. CDC. Malaria Among US Military Personnel Returning From Somalia, 1993. MMWR. 1993;42:524-526.