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Select public health and communicable disease lessons learned during operations Iraqi freedom and enduring freedom.

In the deployed environment, the prevention, identification, and response to communicable disease threats play a critical role in maintaining combat power. The recent wartime experiences in Iraq and Afghanistan provide no shortage of lessons learned in all of these areas of operational public health. Here we will focus on the prevention of and response to select infectious diseases of public health importance in the deployed environment. The lessons learned from these events fall into key areas of disease prevention and control, disease reporting, medical threat assessment, and risk communication. The topics chosen for discussion address lessons learned from multiple focus areas.

IMMUNIZATION

Military science is a powerful force multiplier on the battlefield. Immunization, for example, has been a staple of deployment readiness since General George Washington ordered variolation against smallpox for the Continental Army in 1777. (1) A shining example of the application of military vaccine science to the battlefield is the Hepatitis A vaccine. Hepatitis A has a long history of negatively impacting deployed forces. A successful partnership between the Walter Reed Army Institute of Research and SmithKline brought the first hepatitis A vaccine to Federal Drug Administration approval in 1995.2 In the absence of this immunization, military operations in Southwest Asia would have been at high risk for hepatitis A infection. According to the National Center for Medical Intelligence, hepatitis A virus poses a year round, high operational risk to non-immunized forces. * Despite this endemic disease threat, there were no evacuations of US service members for hepatitis A infection in Operations Iraqi Freedom (OIF) or Enduring Freedom (OEF). This was not the case for other coalition partners who reported hepatitis A infection leading to lost duty time. (3) The lesson learned is that military science is important for disease prevention on the battlefield. Hepatitis A vaccine would not have come to market without the efforts of military scientists. Research and development of vaccines, medications, and military specific health programs are critical for force health protection.

Smallpox vaccine in the recent conflicts provides lessons in threat assessment and vaccine adverse event reporting. During the recent conflicts, approximately 175,000 service members were immunized annually with the current smallpox vaccine. (4) The occurrence of myocardial signs and symptoms secondary to the vaccine were well described in the literature with a reported incidence of 1% to 3%. (5) As increasing numbers of service members received vaccination, case reports of myocarditis and pericarditis increased, leading to a prospective study of the use of smallpox vaccine in the deploying population. (6) This work demonstrated an incidence of myocardial effects at a rate much higher than previously reported (10%). Of note, there was no mortality reported due to myocardial or pericardial effects of smallpox vaccine use, but the overall effect on medical readiness due to unrecognized vaccine side effects could be significant, given the number of doses administered. As the largest user of smallpox vaccine, the DoD has the responsibility to monitor vaccine safety and make recommendations on future use. The identification of higher rates of cardiac effects will lead to improved screening of cardiopulmonary risk factors for those receiving the vaccine. The question as to whether smallpox was ever a credible threat on the battlefield is debatable. However, the time, expense, and high rate of adverse events from smallpox immunization demonstrates a lesson that careful and deliberate risk assessment must be used for force health protection vaccination.

SELECT INFECTIONS OF PUBLIC HEALTH IMPORTANCE

Rabies

In 2011, a Soldier died after contracting rabies from a presumed dog bite in Afghanistan, the first rabies death in a service member since 1974. (7,8) Rabies prevalence among feral dogs and cats was known to be high throughout much of Afghanistan. ** Despite instructions contained in US Central Command (CENTCOM), General Order 01.C, prohibiting the harboring of pets or mascots while in theater, it was not uncommon for service members to keep dogs or cats as companion animals. In addition, risk was assumed in some situations when local dogs were used as sentries in remote outposts and forward operating bases, or when service members were collocated with Afghan police or military units that used canines for such purposes. Anecdotal reports from Soldiers in theater also suggested that some combat stress control officers implied that having pets or mascots was a beneficial form of stress relief and that commanders may have tolerated animal presence for morale and protection purposes. Regardless of the reasons behind such frequent interaction with feral animals, the death of a service member due to rabies made it clear that the risk from this highly lethal infection was largely underappreciated among service members and their supporting medical providers, perhaps due to the rarity of animal-to-human rabies transmission in the United States or a lack of knowledge about the endemic risk in Afghanistan. Nevertheless, emphasis on prevention of exposure must continue to be a priority. Theater directives prohibiting the harboring of pets and mascots remain essential and commanders must ensure compliance though good order and discipline. When operational requirements place personnel at higher risk, service members must be aware of appropriate management of potential exposures, including immediate wound irrigation and medical evaluation. Medical providers must be fully trained on conducting a rabies exposure assessment. This is necessary both in operational setting and the postdeployment setting, as the inclusion of questions specific to rabies risk in the Postdeployment Health Assessment has increased the ability to detect possible exposures following deployment.

Malaria

Malaria is another infection with a historic effect on military operations. The literature is replete with case reports and epidemiologic studies defining the negative impact of malaria on combat operations. It was therefore appropriate that the military health leadership took a conservative approach to malaria prevention in Iraq. Initial prevention policy included 100% chemoprophylaxis at all times in both theaters of operations in the early stages of the Iraq and Afghanistan conflicts. Doxycycline was chosen primarily as it was also being carried as a chemoprophylactic for anthrax. Early negative experiences with this medication due to altitude and sun exposure in Afghanistan led to a curtailment of its use. The medical threat from malaria in Iraq was known to be limited. Saddam Hussain's draining of the swampy areas in Iraq had nearly eliminated the threat. Malaria in Afghanistan was focal and limited to well-defined areas. To complicate the picture, there was no standardized regimen for chemoprophylaxis across the services in the early years of the conflicts, which led to confusion, misunderstanding, or mistrust among unit providers, service members, and commanders. Chemoprophylaxis itself was suboptimal, as the medications available at the outset of combat operations, doxycycline hyclate and mefloquine, both have significant adverse effect profiles. Issues of noncompliance and adverse effects are well documented in the medical literature. (9-12) In Iraq, this led to an under-appreciation of malaria chemoprophylaxis as a Marine unit went from Iraq (very low risk) to Liberia (very high risk) and, in the absence of compliance with chemoprophylaxis, incurred 80 cases of falciparum malaria, leading to multiple hospital ICU admissions and an estimated cost of $1.2 million to the Military Health System (MHS). (13)

By 2006, malaria chemoprophylaxis was removed from the OIF force protection plan, but cases of Plasmodium vivax malaria began to accumulate from OEF. Although vivax malaria poses a readiness threat to deployed forces, the low mortality and absence of drug resistance cloud the direct threat of malaria as a mortal risk to Soldiers deployed to Afghanistan, particularly considering the 30% prevalence of adverse effects from chemoprophylaxis. (12)

Mefloquine was removed as a primary chemoprophylactic medication primarily due to concern for the ability to adequately screen all service members for behavioral health contraindications. (14,15) Fortunately, combination atovaquone/proguanil (Malarone) became readily available for use as primary chemoprophylaxis during that same time period. The low adverse effect profile of atovaquone/proguanil would improve compliance with chemoprophylaxis across the MHS. (16)

Multiple lessons were learned with malaria during OIF/ OEF. Unfortunately, many of these lessons were in fact relearned from previous engagements, such as the notion that compliance with chemoprophylaxis depends largely on command emphasis. A new lesson learned is that being overly risk averse may negatively effect readiness. Better and faster translation of medical intelligence data into deployment policy and the ability to apply malaria prophylaxis policies below the theater level may have reduced both malaria infection and the adverse effects of chemoprophylactic medications on the battlefield. Other malaria lessons including the use of rapid diagnostic tests, empiric therapy, permethrin-treated uniforms, and public health surveillance are all equally important, and will be captured in later articles.

Tuberculosis/Latent Tuberculosis Infection

Rates of active tuberculosis (TB) transmission are high among civilian populations in both Iraq and Afghanistan. Based on this, initial force health protection measures included pre- and postdeployment placement of TB skin tests (TST) in order to identify deployment-related latent TB infection. However, the realized infection risk among US service members during OIF/OEF was quite low. The use of TSTs in low risk populations inevitably results in a large number of false positive cases. In addition, improper placement and interpretation of TSTs and variability in the biologic products used can contribute to false readings. These factors led to a number of pseudo-outbreaks of TB in which significant proportions of redeploying units were misidentified as being infected with Mycobacterium tuberculosis}1 In reality, despite tens of millions of contact hours with local civilians in these countries, very few cases of active TB attributable to exposure in theater were identified. As the wars progressed, the use of risk stratification to conduct targeted testing on only those at high risk was recognized as a more appropriate approach. (18) While this reduced the amount of postdeployment TB testing, returning service members were still frequently misclassified as high risk, resulting in continued testing within a recognized low risk population. MEDCOM policy eventually removed TB risk assessment from the Postdeployment Health Assessment, which proved critical in reducing the over-diagnosis and treatment of those deployed to CENTCOM areas of operation. This evolving policy highlights a misconception and a key lesson learned about tuberculosis in the operational setting. While this highly prevalent and contagious disease must always be a consideration, deployment to a country with high rates of TB on its own does not necessarily place service members at significant risk of infection. Overestimation of TB risk has notable consequences, resulting in unnecessary testing and treatment. While the adage of "a decision to test is a decision to treat" still holds true, the decision of whom to test clearly remains the more critical and difficult decision.

Human Immunodeficiency Virus

Human immunodeficiency virus (HIV) has been of limited risk to Soldiers in theater because of the systematic screening process in garrison and predeployment screening requirements. However, in 2006 and 2001 Army public health officers became aware of an increasing number of cases of HIV diagnosed on the postdeployment HIV screening test. An investigation conducted by the Military HIV Research Program and the Army Public Health Command revealed most of the infections were acquired in the predeployment window between the required predeployment screening test and the actual deployment. Other cases were acquired during mid-tour leave or immediately postdeployment. Most importantly, no infections were due to exposure within CENTCOM, including through the use of blood products in theater, particularly the battlefield blood supply (walking blood bank). (19) The investigation of the HIV cluster revealed a gap in the screening process that led to deployment of HIV-infected service members. Shortening the predeployment screening window did not eliminate but did significantly decrease the risk of deploying HIV-infected service members. There are a few lessons learned from the HIV cluster. First, predeployment screening programs should consider the biology of the disease process. Given that at the time HIV testing was dependent on a positive ELISA test, and tests could have been conducted one year before deployment, exposures up to 14 months prior to deployment could have led to deployment with HIV. In addition, this study suggests an increase in STD risk activity in the predeployment period. This may be a target for risk reduction counseling. Finally, although the assumption is made that no service members with HIV deploy into the operational environment, we know this to not be true. There are, and will continue to be, pathways by which HIV-infected Soldiers end up on the battlefield. Healthcare providers at all levels should keep this in mind in the care they provide in theater.

Q Fever

Coxiella burnetti infection, also known as Q fever, was another communicable disease that should have received greater predeployment consideration. Both Iraq and Afghanistan are countries with documented endemic Q fever risk. Exposure to this zoonotic pathogen typically occurs through the ingestion or inhalation of soil or dust contaminated by the body fluids of infected livestock. With many service members operating in agricultural regions, often in conditions that predispose to dust inhalation such as helicopter rotor wash, exposure for some was conceivable. Q fever first came to the attention of public health officials during an outbreak investigation of severe pneumonia in service members deployed to Iraq in 2003-2004. (20) Diagnosis of Q fever is challenging in the operational setting, as symptoms of acute infection are often nonspecific and diagnostic tests are typically not considered or are not readily available. While acute infection usually resolves spontaneously, there is a risk of chronic infection, which threatens those who remain undiagnosed. Recognition of Q fever in deployed service members led to the development of new military practice guidelines, which subsequently informed new national guidelines published by the US Centers for Disease Control and Prevention. (21,22) The work of clinicians and public health officers led to the identification of over 150 cases of Q fever exposure in service members. Fortunately, there have been no cases of severe outcomes from chronic Q fever in US service members to date. The lesson learned with Q fever is that laboratory-based surveillance can play an important role in identifying endemic disease in deployed service members. However, it can only be useful if medical providers are aware of the endemic disease risks and have the appropriate tests available to make a diagnosis. Current and accurate infectious disease risk assessments are essential for guiding public health efforts, but they are equally important for training medical providers predeployment and identifying key diagnostic capabilities to be made available in theater.

Leishmaniasis

The early OIF experiences with leishmaniasis were well documented in the medical literature as well as in the lay press. Environmental exposure to the sandfly vector in Iraq led to over 800 cases of cutaneous leishmaniasis. The Army Medical Department (AMEDD) struggled with how to manage these cases, including questions about evacuation, treatment, and long-term care. Despite cutaneous disease having few long-term adverse health outcomes, the large number of initial cases in service members, treatment difficulties, and media attention strained the MHS. Delayed diagnosis, delayed treatment, lack of approved diagnostics and treatments in theater led to hundreds of evacuations and lengthy treatments with a toxic investigational new drug (IND). (23,24) The notable rise and fall of leishmaniasis cases among US service members early in OIF contributed to a new understanding about how environmental changes in the operational setting can significantly alter the ecology of this disease. As US Forces entered the country, new construction and human traffic likely contributed to a disruption of sand fly habitats, exposing a large population of immunologically naive service members. However, the trend soon reversed as the maturing theater of operations resulted in more hardened structures and air conditioned lodging for those deployed to the region, reducing their level of exposure. The experience with leishmaniasis in OIF also changed the clinical management of cases in the deployed setting. While early cases were often medically evacuated for treatment, it became clear that conservative management of mild cases, often with a "watch and wait" approach, was a reasonable alternative that allowed many service members to remain in theater with minimal effect on long-term morbidity.

Surveillance

Given the direct relationship between health and operational readiness, accurate and timely information about disease and injury (D&I) data is critical to medical planners as well as commanders. Significant challenges were met as attempts were made to automate the collection of surveillance data. Assumptions about the use of electronic health records, training of medical providers, lack of appropriate denominator data, and bandwidth limitations posed an insurmountable barrier to systematic accurate D&I data collection in theater. Data such as hospital admissions or medical and casualty evacuation data became commonplace in reporting of D&I rates by leadership. Although easy to calculate, these metrics had limited scope and are neither useful nor actionable at the operational level. As each theater matured and medical care moved into brick and mortar structures at all levels of care, electronic health systems allowed for better capture of medical event data. However, these were still plagued by the lack of population data that would allow for the determination of rates of disease and injury.

Lack of training at the Role I level on basic collection of health surveillance data in the absence of electronic systems left a gap in our knowledge of the disease and injury picture from the earlier years of both conflicts. In the same way that Soldiers learn basic land navigation in the era of the GPS, operational medical providers should learn the importance of data collection and reporting in the absence of automated systems to monitor the health of the deployed force.

THE DEPLOYMENT COMMUNITY

The individuals and organizations that interact with the Warfighter in theater make up the deployment community. While much effort is placed on the reduction of communicable disease among service members and other US government personnel, as the theater of operations matures, greater numbers of local nationals, contractors, and third country nationals become an integral part of the deployment occupational environment. In the same way that disease surveillance, prevention, and response are important for force health protection, the same issues within the non-DoD members of the deployment community are important given the close interactions with deployed forces and other US government personnel. As contracts were put in place to hire local nationals to work on US forward operating bases, issues of occupational health screening became apparent. Third country nationals and other contractors may have had organic medical care available, but the extent of that care, the sharing of public health data, or the capacity to respond to communicable disease was unclear to Army public health officers in theater. Army preventive medicine physicians assisted with outbreaks or evaluations for disease clusters among contractors for suspected tuberculosis, varicella, meningitis, and acute diarrheal disease. The different interacting populations with disconnected medical oversight created challenges in the surveillance of diseases. The lesson learned is consideration must be made for the deployment community as a whole. Occupational health controls and disease surveillance must be ensured for all personnel working with or in proximity to US forces as a matter of force health protection.

INTEGRATION OF LESSONS LEARNED

Most of the lessons cited here are related to DOTMLPF *** areas of leadership and training. Decisions about investing or maintaining military science, adherence to or command support for prevention policy, and appropriate use of risk assessments are all themes repeated in the above lessons learned. There is no doubt that Army leaders understand the connection between readiness and disease prevention, but leaders must enforce prevention policy and the associated health behaviors in the deployed force. Additionally, leaders at all levels must use the appropriate resources, including preventive medicine assets at all levels, to make informed decisions about health risk and engage Army technical experts where such expertise exists. Army deployment policy should be based on solid medical evidence and intelligence. Finally, leaders must have the flexibility to adapt to the changing operational environment.

Training opportunities include training for all levels of medical providers in endemic disease risk as highlighted by the above discussion of rabies, malaria, and Q fever. Training medics and medical commanders on basic disease surveillance procedures while in garrison would greatly reduce the surveillance gap that we face during initial phases of deployment.

The Army doctrine related to many of these public health issues is valid, but the application on the battlefield is often difficult. As the Army moves forward towards AMEDD 2025 to support a force that is leaner, more efficient, and more integrated, commanders cannot presume that technology and medical advances will render basic military preventive medicine obsolete. The basic tenants of preventive medicine, including field sanitation, disease surveillance, and reporting, risk communication, and health risk assessment will continue to be critical to mission success. The Army must continue to field a combat force that can identify and prevent or mitigate the effect of disease and injury on deployed forces. When applied correctly, Army doctrine can achieve just that.

REFERENCES

(1.) Artenstein AW, Opal JM, Opal SM, Tramont EC, Peter G, Russell PK. History of US military contributions to the study of vaccines against infectious diseases. Mil Med. 2005;170(suppl 4):3-11.

(2.) Hoke CH Jr, Binn LN, Egan JE, et al. Hepatitis A in the US Army: epidemiology and vaccine development. Vaccine. 1992;10(suppl 1):S75-S79.

(3.) Green CA, Ross DA, Bailey MS. Acute hepatitis A virus infections in British Gurkha soldiers. J R Army Med Corps. 2013;159:240-242.

(4.) Montgomery JR, Engler R, Allan-Martinez F, Morse A, Duran L. Case report: chest pain in service members following smallpox vaccination. MSMR. 2012;19:6-7.

(5.) Halsell JS, Riddle JR, Atwood JE, et al. Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel. JAMA. 2003;289(24):3283-3289.

(6.) Engler RJ, Nelson MR, Collins LC Jr, et al. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination. PLoS One. 2015;10(3):eCollection 2015.

(7.) Fester JM. Public health aspects of rabies. Aviat Space Environ Med. 1975;46:1194-1195.

(8.) US Centers for Disease Control and Prevention. Imported human rabies in a U.S. Army soldier-New York, 2011. MMWR. 2012;61:302-305.

(9.) Saunders D, Garges E, Kosmowski A, et al. Doxy cycline hyclate tolerability and compliance as daily oral malaria prophylaxis in field conditions: experience of the 10th Mountain Division (LI), OEF VII [abstract]. American Journal of Tropical Medicine and Hygiene. Abstract 1008 (page 288). Available at: https://www.astmh.org/ASTMH/media/Docu ments/pages_250-299.pdf. Accessed March 22, 2016.

(10.) Brisson P, Woll M, Brisson M. Improving compliance with malaria chemoprophylaxis in Afghanistan. Mil Med. 2012;177:1539-1542.

(11.) Kotwal RS, Wenzel RB, Sterling RA, Porter WD, Jordan NN, Petruccelli BP. An outbreak of malaria in US Army Rangers returning from Afghanistan. JAMA. 2005;293:212-216.

(12.) Saunders DL, Garges E, Manning JE, et al. Safety, tolerability, and compliance with long-term antimalarial chemoprophylaxis in American Soldiers in Afghanistan. Am J Trop Med Hyg. 2015;93(3):584-590.

(13.) 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;83(2):258-265.

(14.) Nevin RL. Low validity of self-report in identifying recent mental health diagnosis among U.S. service members completing Pre-Deployment Health Assessment (PreDHA) and deployed to Afghanistan, 2007: a retrospective cohort study. BMC Public Health. 2009;9:376.

(15.) Nevin RL, Pietrusiak PP, Caci JB. Prevalence of contraindications to mefloquine use among USA military personnel deployed to Afghanistan. Malar J. 2008;7:30.

(16.) Kersgard CM, Hickey PW. Adult malaria chemoprophylaxis prescribing patterns in the military health system from 2007-2011. Am J Trop Med Hyg. 2013;89:317-325.

(17.) Mancuso JD, Tobler SK, Keep LW. Pseudoepidemics of tuberculin skin test conversions in the U.S. Army after recent deployments. Am J Respir Crit Care Med. 2008;177:1285-1289.

(18.) Sanchez JL, Sanchez JL, Cooper MJ, Hiser MJ, Mancuso JD. Tuberculosis as a Force Health Protection Threat to the United States Military. Mil Med. 2015;180(3):276-284.

(19.) Scott PT, Hakre S, Myles O, et al. Short communication: investigation of incident HIV infections among U.S. Army soldiers deployed to Afghanistan and Iraq, 2001-2007. AIDS Res Hum Retroviruses. 2012;28(10):1308-1312.

(20.) Shorr AF, Scoville SL, Cersovsky SB, et al. Acute eosinophilic pneumonia among U.S. military personnel deployed in or near Iraq. JAMA. 2004;292:2997-3005.

(21.) Hartzell JD, Gleeson T, Scoville S, Massung RF, Wortmann G, Martin GJ. Practice guidelines for the diagnosis and management of patients with Q fever by the Armed Forces Infectious Diseases Society. Mil Med. 2012;177:484-494.

(22.) Anderson A, Bijlmer H, Fournier PE, et al. Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group. MMWR Recomm Rep. 2013;62(RR-03):1-30.

(23.) Weina PJ, Neafie RC, Wortmann G, Polhemus M, Aronson NE. Old world leishmaniasis: an emerging infection among deployed U.S. military and civilian workers. Clin Infect Dis. 2004;39:1674-1680.

(24.) Aronson NE, Sanders JW, Moran KA. In harm's way: infections in deployed American military forces. Clin Infect Dis. 2006;43:1045-1051.

* Internal military document not accessible by the general public.

** Internal military document not accessible by the general public.

*** Doctrine, organization, training, material, leadership, personnel, and facilities.

Authors

LTC Garges is Director, Preventive Medicine Residency Program, US Army Public Health Center, Aberdeen Proving Ground, Maryland.

MAJ Taylor is Associate Director, Preventive Medicine Residency Program, US Army Public Health Center, Aberdeen Proving Ground, Maryland.

LTC Pacha is Director, Epidemiology and Disease Surveillance Portfolio, US Army Public Health Center, Aberdeen Proving Ground, Maryland.
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Title Annotation:Public Health Challenges
Author:Garges, Eric C.; Taylor, Kevin M.; Pacha, Laura A.
Publication:U.S. Army Medical Department Journal
Geographic Code:9AFGH
Date:Apr 1, 2016
Words:4257
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