The US military, as a matter of policy, follows most of the recommendations in the CDC Yellow Book. However, certain situations 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 predeployment medicine, but civilian physicians may interact with people who are on reserve status, home on leave, recently discharged from active duty, or veterans. Predeployment and postdeployment 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. An additional purpose is to provide civilian clinicians who frequently see military personnel with background and available information sources regarding these differences and to emphasize their role in informing relevant findings to military care providers.
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 that may differ from those of civilian travelers. This section focuses on the unique aspects of using pretravel vaccines and malaria chemoprophylaxis in the military population and on special considerations relevant to returning service members with health concerns. The specific examples will be from the US military, but the concepts may be applicable to other militaries. In 2016, approximately 1.3 million US military members were on active duty, and approximately 800,000 were in the reserve forces.
Several characteristics of the military force differ from those of the civilian population (Table 8-5). In general, the active duty military population is younger, in better health than the population at large, and predominately male.
|Characteristic||Travel Medicine||Military Medicine|
|Goal||Optimizing advice and interventions for individual travelers||Ensuring mission success; optimizing advice and interventions for each person is difficult|
|Adherence||Strongly encouraged but travelers are free to choose||Required; vaccines and malaria chemoprophylaxis are part of force health protection (FHP)|
|Education||One-on-one encounters||Unit education|
|Population||Not prescreened; travel health providers see all ages and people with preexisting medical conditions||Prescreened; people with serious medical problems are not allowed to join the military or be deployed|
|Special populations||Infants, children, pregnant women, elderly people, people with renal or hepatic impairment and often taking other medications||Less frequent in military population or deployments|
|Disease comorbidity||Similar to civilian population||Limited, generally healthy|
|Sex||50% male, 50% female||85% male|
|Unusual activities||Adventure activities, such as trekking, climbing, scuba diving, spelunking||Housed in barracks or other group settings, aviators, Special Forces, operating complex weapons systems, hostile and extreme environments, stress of combat operations, night operations, and use of night-vision goggles|
|Duration of malaria chemoprophylaxis use||Mostly short term, 2–3 weeks||The US military often uses chemoprophylaxis for longer periods of time than do short-term travelers. Many deployments are for 1 year or longer.|
Force health protection (FHP) is an important concept in military medicine. FHP is defined as all measures taken by commanders, supervisors, individual service members, and the military health system to promote, protect, improve, conserve, and restore the mental and physical well-being of service members across the range of military activities and operations. Delivery of vaccines and the use of malaria chemoprophylaxis agents are 2 aspects of FHP.
Medical interventions for FHP are the responsibility of the unit commander, with advice from the unit medical officer. When predeployment vaccines or malaria chemoprophylaxis are indicated, the commander includes such requirements in the mission plan. Service members are then required to receive these interventions under proper medical supervision. If a particular vaccine or drug is medically contraindicated, alternative agents may be employed if 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 www.dtic.mil/whs/directives. The Policy and Program for Immunizations to Protect the Health of Service Members and Military Beneficiaries is found in directive 6205.O2E (September 19, 2006) at 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. In certain circumstances, individual service members may be exempt from vaccination. There are 2 types of exemptions from immunization: medical and administrative. Granting medical exemptions is a medical function that can only be validated by a health care professional. Granting administrative exemptions is a nonmedical function, usually controlled by the person’s unit commander.
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 Defense Health Agency (DHA) Immunization Healthcare Branch (IHB) [formerly the Military Vaccine Agency (MILVAX)] supports 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 DHA IHB website (www.health.mil/vaccines).
The US military issues FHP recommendations based on geographic areas of responsibility (AOR) (www.vaccines.mil/QuickReference). 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 personnel on orders to deploy or travel to Afghanistan should receive the vaccines listed in the “Vaccine Recommendations” tab of the above quick reference web page unless there is a medical contraindication.
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) use of personal protection measures, which include individual bed nets, permethrin-impregnated uniforms, and insect repellents; and 3) use of chemoprophylaxis where indicated. The joint instruction on immunization and chemoprophylaxis stipulates that medical commanders designate trained staff to provide comprehensive malaria prevention counseling to military and civilian personnel considered to be at risk of contracting malaria and that such counseling “include instruction on how to take prescribed antimalarial medications, the importance of compliance with the prescribed medication schedule, information about potential adverse effects, and the need to seek medical care if these adverse effects occur.”
Malaria cases seen in returning US military personnel reflect the current deployments around the world. In 2015, the number of malaria cases was the lowest in >20 years (30 cases). The number of cases declined with the continued drawdown of deployed personnel to Afghanistan from 2012 through 2015. The risk of Plasmodium falciparum malaria, which accounted for 43% of cases in 2015, is substantial for people with frequent training and development missions to sub-Saharan Africa (www.afhsc.mil/documents/pubs/msmrs/2016/v23_n01.pdf).
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 antimalarial 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 use is 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 2011, United States Africa Command (AFRICOM) issued a policy change recommending atovaquone-proguanil (Malarone) as the recommended malaria chemoprophylaxis option for all personnel for both short- and long-term deployments in high-transmission areas of Africa. High-transmission areas for the purpose of this policy are defined by the National Center for Medical Intelligence. For practical purposes, this includes most of sub-Saharan Africa. For people who are unable to receive atovaquone-proguanil because of intolerance or contraindication, doxycycline is the preferred second-line therapy. Use of mefloquine as prophylaxis is a third-line recommendation for those unable to receive either atovaquone-proguanil or doxycycline. Before prescribing mefloquine for prophylaxis, absolute and relative contraindications as described in the approved product label must be considered.
In April 2013, the Assistant Secretary of Defense (Health Affairs) issued new guidance on medications to prevent malaria. Atovaquone-proguanil and doxycycline are both first-line choices in areas other than sub-Saharan Africa. Mefloquine should be reserved for people with intolerance or contraindications to both first-line medications. Before using mefloquine for prophylaxis, care should be taken to identify any contraindications on an individual basis and ensure required FDA mefloquine medication guide (www.accessdata.fda.gov/drugsatfda_docs/label/2013/076523s007lbl.pdf) is given to people prescribed mefloquine.
As a matter of policy, 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. PART is also referred to as “terminal prophylaxis.” In PART, primaquine is given to otherwise healthy people on their departure 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 the weight of the patient; 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 for PART 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 continue to occur in returning military personnel. Use of the higher-dose primaquine regimen for PART is now recommended for military personnel. This recommendation is consistent with the spirit of DoD issuance 6200.02 (February 17, 2008), in that the higher-dose recommendation for primaquine when used as PART is “standard medical practice in the United States.”
Although primaquine is included as an acceptable alternative by CDC for primary prophylaxis in some countries where the risk of malaria is exclusively or mostly P. vivax malaria, primaquine is not FDA-approved for primary prophylaxis. Because use of primaquine for primary prophylaxis constitutes off-label use, it cannot be prescribed for a deploying group under FHP, but it can be prescribed by a licensed medical provider on an individual basis as part of medical practice.
The most important risk of using primaquine is hemolytic anemia in those who are deficient in G6PD. Current policy is for all US military personnel to be screened for 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.
A recurrent issue for military medicine is the correct timing of primaquine when given as PART in conjunction with the standard chemoprophylaxis drug being taken. Primaquine can be given at any time after personnel leave an endemic area. For convenience and for enhancing adherence to the 14-day regimen of primaquine, it is often best for military units to prescribe primaquine in the immediate 2 weeks after return. During this time, the units are often still at their home base completing their in-processing before block leave. Once personnel depart on leave, adherence and monitoring for side effects are more difficult.
Under FHP, military personnel 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 8-6.
|CDC Recommendation||US Military Policy|
|Choice of malaria chemoprophylaxis agent||Chemoprophylaxis guidelines do not recommend one drug versus another, but rather emphasize the goal of tailoring the recommendation for the individual traveler on the basis of past experience, itinerary, possible drug interaction, potential side effects, costs, and medical contraindications such as drug allergies.||Individualizing advice and recommendations for large military deployments is rarely logistically possible or feasible. Recognizing this reality, in April 2013, the US military adopted a new policy on the use of malaria chemoprophylaxis in the US military. Atovaquone-proguanil and doxycycline are now the first-line drugs of choice to prevent malaria in deployed US military forces in all areas other than sub-Saharan Africa. Atovaquone-proguanil is the drug of choice for short-term travel (up to 2 or 3 weeks) and for people who travel frequently, to minimize long postexposure prophylaxis treatment courses. In September 2011, AFRICOM policy changed to recommending atovaquone-proguanil for most destinations in sub-Saharan Africa.|
|Doxycycline||An option for chemoprophylaxis in all areas.||Recommended first-line chemoprophylaxis choice in all areas other than sub-Saharan Africa.|
|Mefloquine||An option for chemoprophylaxis in all areas except Southeast Asia.||Mefloquine is not recommended as a primary option. It should be reserved for people with intolerance or contraindications to atovaquone-proguanil and doxycycline. Before using mefloquine for prophylaxis, care should be taken to identify any contraindications on an individual basis and ensure the required FDA mefloquine medication guide (www.accessdata.fda.gov/drugsatfda_docs/label/2013/076523s007lbl.pdf) is given to people prescribed mefloquine.|
|Atovaquone-proguanil||An option for chemoprophylaxis in all areas.||Atovaquone-proguanil is the drug of choice for sub-Saharan Africa and a first-line option in all other areas.|
|Primaquine chemoprophylaxis||CDC recommends the use of primaquine as primary chemoprophylaxis in geographic areas with mainly Plasmodium vivax malaria.||There is no FDA-approved indication for the use of primaquine to prevent malaria. Therefore, the US military cannot use primaquine as a chemoprophylaxis agent under current FHP guidelines.|
|PART||Primaquine at 30 mg (base) for 14 days.||There is no FDA-approved indication for the use of primaquine at the higher dose of 30 mg (base) for 14 days. However, primaquine is an FDA-approved drug with an indication for PART. The CDC-recommended (higher) dose is recommended, as it is the standard of medical practice in the United States.|
|Abbreviations: AFRICOM, African Command; FDA, Food and Drug Administration; FHP, Force Health Protection; PART, presumptive antirelapse treatment.|
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 potential to affect national security.
Symptoms and health concerns after a deployment may be similar to health issues reported from nonmilitary returning travelers. However, deployment presents a different set of circumstances from the civilian traveler such as differential vaccination recommendations, physical and psychological stress and trauma of combat, environmental exposures, and infections that may cause unique health concerns. In 2002, the US Department of Defense developed and mandated the use of the Post-Deployment Health Clinical Practice Guideline (PDH-CPG) under Health Affairs Policy 02-007. The PDH-CPG is designed to help clinicians implement specific approaches to address these distinctive experiences and exposures and includes clinical tools and resources to evaluate and manage patients with the full spectrum of deployment-related concerns. The goal of the PDH-CPG is to promote evidence-based management of people with postdeployment health concerns, identify the critical decision points in managing patients with postdeployment health concerns, allow flexibility so that local policies or procedures such as those regarding referrals to or consultation with specialists, and improve local management of patients with postdeployment health concerns and thereby improve patient outcomes.
Drs. Forgione, Fukuda, and Riddle are employees of the Department of Defense and as such, the views expressed in this section are those of the authors and do not necessarily reflect the official policy or position of the Departments of the Air Force, Army, or Navy, nor the Department of Defense.
Mark Fukuda, Gregory A. Raczniak, Mark S. Riddle, Michael Forgione, Alan J. Magill