Chapter 8Advising Travelers with Specific Needs

Alan J. Magill, Steven B. Cersovsky, Robert F. DeFraites*

OVERVIEW

The US military, as a matter of policy, follows most of the recommendations in the CDC Yellow Book. However, there are unique situations that apply only to the US military, and some policies or recommendations differ from what is recommended in the Yellow Book for civilian travel. Active-duty military physicians generally manage pre-deployment medicine, but civilian physicians may interact with people who are on reserve status, home on leave, recently discharged from active duty, or veterans. Pre-deployment and post-deployment information, policies, and guidelines for clinicians, service members and their families, and veterans can be found on the Deployment Health Clinical Center website (www.pdhealth.mil).  The purpose of this section is to inform US military medical corps officers, who routinely consult the Yellow Book, about these differences and also make civilian clinicians, who frequently see military personnel, aware of these differences.

In many countries, one of the largest traveling populations is their military personnel. The military should be considered a special population with demographics, destinations, and needs different from civilian travelers. This section focuses on the unique aspects of using pre-travel vaccines and malaria chemoprophylaxis in the military population. The specific examples will be from the US military, but the concepts may be applicable to other militaries, as well. In 2010, approximately 1.5 million US military members were on active duty and approximately 1.0 million were in the reserve forces.

Several characteristics of the military force differ from those of the civilian population (Table 8-10). The active duty military is younger, in better health, and predominately male.

FORCE HEALTH PROTECTION

Force Health Protection (FHP) is an important concept in military medicine. FHP is broadly defined as a strategy that applies preventive health techniques and emerging technologies to environmental surveillance and combat medicine to protect all service members before, during, and after deployment. Delivery of vaccines and the appropriate use of malaria chemoprophylaxis agents are 2 aspects of FHP.

Medical countermeasures for FHP are the responsibility of the unit commander, with advice from the unit medical officer. When pre-deployment vaccines or malaria chemoprophylaxis are indicated, the commander includes such requirements in the mission plan. Service members are then required to receive the interventions under medical supervision. People who have a medical contraindication to a vaccine or drug receive alternative agents, when they are available. The unit medical officer documents which military personnel have not received standard preventive measures, so these people may receive additional monitoring or treatment if they become ill.

FHP policy positions in the Department of Defense (DoD) are issued as directives and instructions. All directives and instructions can be found online at Policy and Program for Immunizations to Protect the Health of Service Members and Military Beneficiaries is found in directive 6205.O2E (September 19, 2006) (www.dtic.mil/whs/directives/corres/pdf/620502p.pdf).  Although policy may be made at higher levels in Washington, DC, the final decision to use vaccines or malaria chemoprophylaxis under FHP is made by commanders in the field, guided by their medical staff.

ROUTINE AND TRAVEL-RELATED IMMUNIZATIONS

DoD policy states that the recommendations for immunization from CDC and the Advisory Committee for Immunization Practices shall generally be followed, consistent with requirements and guidance of the Food and Drug Administration (FDA) and with consideration for the unique needs of military settings and exposure risks. The Military Vaccine Agency (MILVAX) supports all 5 branches of the US Armed Services to enhance military medical readiness by coordinating DoD immunization (vaccination) programs worldwide. A valuable source of service- specific information on immunizations for all branches of the US military is found at the MILVAX website (www.vaccines.mil/default.aspx).

In particular, the quick reference section of the MILVAX website (www.vaccines.mil/default.aspx?cnt=resource/qr)  provides an easily accessible and complete source of information with product specifics and policy documents that both military and civilian providers will find useful. DoD and service-specific policies for vaccines and geographic-specific vaccine recommendations can be also be downloaded from this site.

GEOGRAPHIC AREAS OF RESPONSIBILITY

The US military issues FHP recommendations based on geographic areas of responsibility (AOR) (www.vaccines.mil/default.aspx?cnt=resource/qr).   Command and control over US military personnel in each AOR are under a unified combatant command, which is a joint (all branches of the US military) command that provides recommendations for all service members being deployed to that AOR. For example, Afghanistan is in the Central Command (CENTCOM) AOR. All people on orders to deploy or travel to Afghanistan should receive the vaccines listed in the above web page under the CENTCOM tab of the vaccine recommendations page, unless there is a medical contraindication.

MALARIA CHEMOPROPHYLAXIS

Preventing malaria in military units deployed to endemic areas is an essential objective of FHP. Malaria can be prevented through 1) education and training, 2) appropriate use of personal protection measures that include individual bed nets, permethrin-impregnated uniforms, and insect repellents, and 3) use of chemoprophylaxis where indicated.

Malaria cases seen in returning US military personnel reflect the current deployments around the world. In 2010, the highest risk was in Afghanistan, with exposures to chloroquine-resistant Plasmodium falciparum and P. vivax malaria. There is also significant risk from frequent training and development missions to sub-Saharan Africa.

Several features of malaria chemoprophylaxis under FHP that are unique to the US military are derived from the activities and stressors of military deployments. When anti-malarial drugs are used for chemoprophylaxis as part of FHP, the military can only use FDA-approved chemoprophylaxis agents in accordance with the specific FDA-approved indications. Off-label use of drugs is not allowed when given under FHP. If off-label indications are felt to be in the best interest of the person or unit, trained and knowledgeable clinicians must provide one-on-one medical evaluations, document in the medical record the rationale for such use, and provide a by-name prescription for the drug or vaccine to each person.

In September 2009, the Assistant Secretary of Defense (Health Affairs) issued a policy memorandum on the use of mefloquine in malaria chemoprophylaxis throughout the DoD. In chloroquine-resistant areas in which doxycycline and mefloquine are equally efficacious in preventing malaria, doxycycline is the drug of choice for malarial chemoprophylaxis. Those personnel with a history of neurobehavioral disorders who cannot take doxycycline should be prescribed atovaquone-proguanil for travel to chloroquine-resistant areas.

The rationale for recommending doxycycline over mefloquine is as follows:

• With the increasing recognition of possible neuropsychiatric side effects of mefloquine in some people, new relative contraindications have been added to the product label since 2003. In addition, each person prescribed mefloquine must be given an FDA-approved medication guide. Complying with this guidance requires a one-on-one encounter with a knowledgeable provider, which can be difficult with large deployments.
• Neuropsychiatric side effects may confound the diagnosis and management of posttraumatic stress disorder and traumatic brain injury, which makes the continued routine use of mefloquine less desirable.

The US military routinely uses primaquine for presumptive antirelapse treatment (PART) in returning military populations to prevent the late relapse of P. vivax malaria or P. ovale malaria as a matter of policy. PART is also referred to as “terminal prophylaxis.” In PART, primaquine is given to otherwise healthy people on their return from an endemic area. Primaquine is used for this indication much more frequently in the military than in most civilian travelers.

The FDA-approved regimen for PART is 15 mg (base) given daily for 14 days. This regimen was approved in 1952 and has not been revisited since. In the intervening decades, an overwhelming amount of data has accumulated to show that the total dose of primaquine to eliminate the dormant hypnozoite stages responsible for late relapses is dependent on the infecting P. vivax strain, and therefore, the optimal human dose should be based on weight and adjusted for the infecting P. vivax strain.

In 2003, CDC recommended 30 mg (base) of primaquine daily for 14 days based on available evidence, but the FDA-approved regimen remains the lower dose. Adherence to the daily 14-day regimen is poor unless primaquine is given under directly observed therapy, which is rarely done. As a result of noncompliance and subtherapeutic dosing with the 15 mg (base) for 14 days regimen, periodic outbreaks of relapsed P. vivax malaria occur in returning military personnel.

Current policy is for all US military personnel to be screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency on entry into military service. However, some people, such as reservists, may have deployed without testing, or clinicians may not be able to confirm results for all people in a unit requiring PART. Clinicians should be aware that hemolytic reactions to primaquine may occur in those with unrecognized G6PD deficiency.

Under FHP, people are required to take their chemoprophylaxis agents as prescribed to maintain mission readiness. Individual soldiers do not have the right to refuse an order given under FHP. There is great variability in practice as to how seriously individual commanders enforce these policies, however, and continued outbreaks of malaria occur in military populations because of poor compliance.

Differences between civilian and US military use of chemoprophylaxis drugs are summarized in Table 8-11.

UNIQUE NEEDS FOR THE MILITARY

US military personnel may encounter threats, such as biological warfare agents, that are not usually considered for civilian travelers. Vaccines, immunoglobulins, drug prophylaxis, and drug treatment regimens can be given under FHP but only in accordance with FDA-licensed products and regimens and for FDA-approved indications.

Products not approved by the FDA are given to soldiers only with voluntary informed consent under an institutional review board–approved protocol and in accordance with a current and FDA-approved investigational new drug application.

Only under exceptional circumstances would products not approved by the FDA be given to soldiers without informed consent. This circumstance is governed by emergency use authorization procedures. Section 564 of the Federal Food, Drug, and Cosmetic Act (21 USC 360bbb-3), as amended by the Project BioShield Act of 2004 (Public Law 108-276), permits the FDA commissioner to authorize the use of an unapproved medical product or an unapproved use of an approved medical product during a declared emergency involving a heightened risk of attack on the public or US military forces, or when there is a significant potential to affect national security.

BIBLIOGRAPHY

1. Carr ME Jr, Fandre MN, Oduwa FO. Glucose-6-phosphate dehydrogenase deficiency in 2 returning Operation Iraqi Freedom soldiers who developed hemolytic anemia while receiving primaquine prophylaxis for malaria. Mil Med. 2005 Apr;170(4):273–6.
2. Food and Drug Administration. Emergency use authorization of medical products. Rockville, MD: Food and Drug Administration; 2007 [updated 2010 Mar 1; cited 2010 Oct 26]. Available from: http://www.fda.gov/RegulatoryInformation/Guidances/ucm125127.htm.
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