Monday, February 6, 2012

Malaria in the U.S. Armed Forces: a Persistent but Preventable Threat

Colonel Mark M. Fukuda, MD, is the assistant chief and program director for malaria surveillance of the Global Emerging Infections Surveillance & Response System division at the Armed Forces Health Surveillance Center.

The potential impact of malaria on military populations is highlighted by General Douglas MacArthur, who in referring to malaria’s impact on World War II forces, famously lamented: “This will be a long war, if for every division I have facing the enemy, I must count on a second division in the hospital with malaria, and a third division convalescing from this debilitating disease”.1 Today’s deployment patterns, though different from those of MacArthur’s time, continue to pose the threat of malaria to members of U.S. armed forces.

This issue of the  Medical Surveillance Monthly Report (MSMR) reports the latest trends in malaria among U.S. military members. Of particular note, the 91 cases of malaria that were considered acquired in Afghanistan in 2011 was the highest number recorded among U.S. military members serving in that country in the last nine years; moreover, the Afghanistan-acquired cases constituted 73 percent of all documented malaria cases last year. Unfortunately, after ten years of U.S. military presence in Afghanistan, and despite the availability of effective prevention measures and a long organizational history of fighting the disease, malaria remains a threat to U.S. forces and their operations in Afghanistan.

The U.S. military’s persistent and perhaps worsening malaria experience in Afghanistan is not inevitable. Foreign militaries’ recent experiences in malaria endemic settings have shown that malaria burdens can be reduced to negligible levels by the consistent application of proper control measures. Of note, during a series of Swedish military deployments to Liberia from 2004 to 2006, no cases of Plasmodium falciparum malaria were reported among the 1,170 soldiers whose total malaria exposure spanned approximately 7,000 person-months.2 According to the report, all soldiers were instructed prior to deployment to use a DEET-containing repellent and bed nets. In addition, the use of anti-malarial drugs to prevent the disease, such as mefloquine or atovoquone-proguanil (Malarone®), was “encouraged” by both command and health personnel and “soldiers took their tablets together and at the same time of the day.”

In contrast, during a short operation carried out by U.S. military forces in Liberia in 2003, there was a 36 percent P. falciparum (the most severe form of malaria) attack rate among those spending time ashore.3 Among participants in the operation, malaria chemoprophylaxis was administered via an “honor system;” the self-reported compliance with the indicated prophylaxis was only 55 percent. In addition, compliance with recommendations for use of insect repellent was low, and the unit had no bed nets.3 The divergent Swedish and U.S. military experiences in Liberia highlight the effectiveness of currently available countermeasures against malaria when used as indicated – even while conducting operations in hyper-endemic settings.

There are other lessons to learn from the Swedish military experience in Liberia. No doubt, emphasis by command and medical personnel on compliance with personal protective measures and the chemoprophylaxis regimen was critical to the prevention of P. falciparum infections during periods of intense exposure to mosquito vectors of the life-threatening parasite. Furthermore, despite the complete prevention of P. falciparum cases, the authors reported 14 cases of relapsing P. ovale malaria ( a relatively mild form of malaria) diagnosed between 2.5 and 12 months after returning to Sweden. This was not unexpected since “terminal prophylaxis” to prevent relapsing forms of malaria had not been employed. The authors noted that the P. ovale infections (acquired in Liberia and clinically manifested in Sweden) were further evidence of the specific chemoprophylactic effectiveness of mefloquine and atovoquone-proguanil against P. falciparum because P. falciparum is far more prevalent than P. ovale in Liberia.

Human behavioral factors and the multiple competing demands of deployment operations hamper perfect compliance with malaria prevention measures. In this context, the pharmacology of chemoprophylaxis agents matters. In the Swedish military report, approximately 4 out of every 5 soldiers initially received mefloquine for chemoprophylaxis while the remaining one-fifth received atovoquone-proguanil. For those receiving mefloquine, it is likely that the required weekly dosing schedule not only fostered greater compliance, but also provided greater tolerance for missed or delayed doses. Those receiving atovoquone-proguanil may have similarly benefitted from a more forgiving drug. In a recent report from the Walter Reed Army Institute of Research,4 atovaquone-proguanil, administered as a single dose, provided prolonged protection against experimentally inoculated P. falciparum infections, supporting the premise that daily atovaquone-proguanil likely provides a margin of error when doses are missed.

It would be overly simplistic to conclude that the U.S. military’s malaria problem could be eliminated simply by choosing the right chemoprophylaxis agent. Personal protective measures (i.e., use of DEET-containing repellent, proper wear of the uniform, use of impregnated bed nets) capable of preventing not only malaria but also other vector borne infectious diseases, will always be required. But in settings with high transmission of potentially deadly P. falciparum infections, the choice of and level of compliance with taking the proper chemoprophylaxis agent can make a crucial difference—in enhancing military operational effectiveness and saving lives.

1. Fukuda MM, Klein TA, Kochel T, et al. Malaria and other vector-borne infection surveillance in the U.S. Department of Defense Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance program: review of 2009 accomplishments. BMC Public Health. 2011 Mar 4;11 Suppl 2:S9.

2. Andersson, H, Askling H, Falck B, Rombo L. Well-tolerated chemoprophylaxis uniformly prevented Swedish soldiers from Plasmodium falciparum malaria in Liberia, 2004-2006. Mil Med. 173, 12:1194,2008.

3. Whitman TJ, Coyne PE, Magill AJ, et al. An outbreak of Plasmodium falciparum malaria in U.S. Marines deployed to Liberia. Am J Trop Med Hyg. 2010 Aug;83(2):258-65.

4. Deye GA, Miller RS, Miller L, et al. Prolonged protection provided by a single dose of atovaquone-proguanil for the chemoprophylaxis of Plasmodium falciparum malaria in an human challenge model. Clin Infect Dis. 2012 Jan;54(2):232-9. Epub 2011 Nov 3.

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