Infectious diseases are not only a significant threat to the health of service members, but also greatly impact the readiness of military wartime operations, as well as peacekeeping and training activities.
United States military combat, humanitarian assistance and other activities in developing countries expose forward deployed troops to infectious diseases that can significantly and negatively affect operations. Travel medicine has become an increasingly important discipline in the civilian and military sectors with the rapid growth in international travel, particularly to the developing world. The IDCRP has focused efforts on describing the epidemiology of deployment and travel related infections, evaluating pre-travel health care and developing novel methodologies for identifying enteropathogens and pathogens associated with febrile disease. Efforts have also focused on developing effective treatment strategies for travelers’ diarrhea in deployed troops. Most recently, DoD encountered several emerging infectious disease threats relating to deployment health, including the spread of chikungunya virus within South/Central America and Florida with expected expansion into the eastern US, and the Ebola epidemic in West Africa leading to a large-scale deployment of troops into the region as part of Operation United Assistance. IDCRP launched several initiatives through ongoing protocols as well as new studies aimed at providing valuable epidemiologic and outcome data related to these infections.
With worldwide deployment of U.S. service members, the improved understanding of the epidemiology of infectious disease threats and identification of optimal preventive and treatment approaches is a high priority of the Military Health System (MHS). The most frequently reported infections include travelers’ diarrhea (TD), vector-borne illnesses (e.g., malaria, Dengue virus, Zika virus, and Chikungunya virus), and respiratory diseases. Mitigating the impact of these infections requires comprehensive surveillance efforts and high-quality research. The overarching goal of the Deployment and Travel- Related Infections Research Area is to enhance infectious disease preparedness and Force Health Protection of U.S. military forces prior to and during deployment.
The Deployment and Travel-Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies among DoD Beneficiaries (TravMil) cohort study, led by Dr. Tahaniyat Lalani, remains the centerpiece protocol of the research area and has enrolled more than 4,500 travelers and deployed service members. During the past year, infectious disease surveillance efforts focused on deployments to regions considered high-risk for infections by Combatant Commands (COCOMs) and the DoD Global Emerging Infections Surveillance (GEIS) network and enrollment in these populations was successful with 30-50% reporting TD and 10- 40% with an influenza-like-illness. As the occurrence of TD in deployed personnel has a substantial impact on operational readiness, improved prevention and treatment remains a priority for COCOMs. A significant achievement in 2019 was the completion of enrollment and followup for the Trial Evaluating Regimens of Rifaximin for Chemoprophylaxis against Travelers’ Diarrhea (Prevent TD), led by CAPT Ramiro Gutierrez, which is a collaborative effort with the United Kingdom Ministry of Defence (U.K. MOD). Overall, 449 subjects were enrolled in the clinical trial and data analysis is expected to be completed in 2020. A difference in the TD incidence between the U.S.and U.K. personnel was observed, likely due to the varying risk of TD at their destinations. For example, the risk of TD is low while the U.K. Army personnel were within the barracks at British Army Training Unit in Nanyuki, Kenya, and increased during exercises in the austere environment at Archers Post and during travel into the local community. This finding is being used to inform the study design for an upcoming placebo-controlled clinical trial, P4TD, which is a collaborative effort with the U.K. MOD to evaluate the clinical efficacy of different nutraceutical products for the prevention of TD (i.e., probiotic, prebiotic, and passive immunoprophylaxis). This clinical study, led by Dr. Lalani and Dr. David Tribble, will also involve a collaboration with the New York Center for Travel and Tropical Medicine.
In 2017, the Trial Evaluating Ambulatory Therapy of Travelers’ Diarrhea (TrEAT TD) study was completed and the findings demonstrated that a single highdose of rifaximin (1650 mg) with loperamide was effective at treating acute watery diarrhea. As a follow-on clinical trial, and in collaboration with the U.K. MOD, TrEAT TD 2.0 will examine the efficacy of rifaximin at a lower dose (550 mg) compared to azithromycin. Another protocol is the Knowledge, Attitudes, Practice, and Outcomes Study (KAPOS), led by COL Patrick Hickey, which aims to evaluate knowledge of infectious disease threats and prescription practices of travel medicine and deployment health providers. These are critical issues for mitigating infectious disease threats and optimizing Force Health Protection in the expeditionary military. Presently, differences in malaria chemoprophylaxis and TD self-treatment prescription patterns among travel medicine specialists and non-specialists are being evaluated with regards to outcomes.
An anonymous post-deployment survey for high-priority infections among Marines serving in the Indo-Pacific Command is planned. Samples will be collected from deployments with high infection rates to identify specific pathogens. A survey-based approach will also be used, along with collection of serum samples, to assess the leptospirosis incidence and operational impact in jungle warfare training settings in Camp Gonsalves, Okinawa, Japan, and Schofield Barracks, Hawaii.
Key Studies
IDCRP-037: Deployment and Travel Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies Among Department of Defense Beneficiaries (TravMil)
IDCRP-065: A Randomized, Double-Blind, Clinical Trial Evaluating the Equivalency of Three Single Dose Regimens with Loperamide for Treatment of Ambulatory Watery Travelers' Diarrhea, and Azithromycin with and without Loperamide for Treatment of Ambulatory Dysentery/Febrile Diarrhea (TrEAT Travelers’ Diarrhea)
IDCRP-076: Development of multiplex PCR assay using stool smears obtained on filter paper cards for detection of pathogens associated with travelers’ diarrhea
IDCRP-080: A randomized, double-blind, placebo-controlled study evaluating rifaximin for the prevention of travelers’ diarrhea in TravMil deployment population (Prevent TD)
Military Impact
Surveillance of high-priority infectious disease threats and militarily-relevant clinical trials conducted by the Deployment and Travel-Related Infections Research Area add to the evidence base for deployment-related clinical practice guidelines. Findings from TravMil have been used to develop infectious disease threat assessment reports, which are provided to COCOMs, medical support teams of the deployed units, and GEIS. Data from multiple protocols (i.e., Stool Card Validation, TrEAT TD, and TravMil) confirmed the value of filter paper-based stool collection combined with TaqMan® Array Card PCR-based assay as an alternative approach (or supplemental when performed in conjunction with conventional methods) for collection of diarrheal specimens in an austere environment with limited storage and laboratory capabilities. As the research area continues to move forward, the successful partnerships with DoD research laboratories both within and outside of the United States and with the U.K. MOD will be further leveraged to address specific COCOM priority surveillance efforts and utilize findings of clinical trials to improve the practice of deployment and travel medicine within the MHS.
Highlights / Key Findings
- TaqMan® Array Card PCR assay was used to evaluate changes in pathogen detection in stool specimens from subjects who participated in the TrEAT TD clinical trial. Between Day 0 and Day 21, there was a significant decrease in pathogen detection (77% to 25%). Changes in virulence gene profiles for pathogens detected at both time points suggest acquisition of a new strain rather than persistence of the initial pa thogen.
- P4TD will be the first time there has been a head-tohead placebo-controlled comparison of nutraceutical products (i.e., probiotic, prebiotic, and passive immunoprophylaxis) within a single clinic al trial.
- Pediatric travelers more frequently reported mosquito bites and contact with wild or domesticated animals than adult military dependent travelers. Also, travelers <10 years old were less commonly prescribed antibiotics and antidiarrheals for TD self-treatment.
- Data collected through KAPOS will be used for the FDArequired post-licensure safety surveillance study of Tafenoquine, which was recently approved for malaria chemoprophylaxis and radical cure of Plasmodium vivax in the MHS.
Partners and Collaborators
The Deployment and Travel-Related Infections Research Area has developed strong partnerships with institutions within the DoD including the overseas labs (e.g., AFRIMS, NAMRU-6, USAMRU-K), NMRC, and WRAIR, with foreign militaries (UK Ministry of Defence), as well as academia including Kansas State University, University of Virginia, and University of Vermont. Funding support for projects in the research area have been provided by multiple sponsors including NIAID, GEIS, MRMC, USU, BUMED, Navy CSI, and Navy Advanced Development.