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Deployment and Travel Related Infections

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.

Research Area Description 

Deployment and travel-related infections account for substantial morbidity with direct negative consequences on military operations and readiness

Military forces are negative impacted by a range of infectious threats during deployment, most commonly travelers’ diarrhea (TD), but also vector-borne (malaria, dengue, and more recently, zika virus) and respiratory spread pathogens. The main goals of the Deployment and Travel-Related Infections Research Area are to 1) provide epidemiologic threat assessment and clinical and operational outcomes, 2) develop rapid diagnostic platforms for pathogen-specific diagnoses in the deployed setting, and 3) execute clinical trials and effectiveness studies to improve prevention and treatment recommendations.

The Deployment and Travel-Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies among DoD Beneficiaries (TravMil) cohort study, led by Dr. Tahaniyat Lalani, is the centerpiece protocol of the research area.  With the Zika epidemic in Central and South America, determining the potential exposure for deployed service members has become vitally important.  As a result, investigators collaborated with Kansas State University and Walter Reed Army Institute of Research to evaluate mosquito exposure (Anopheles and Aedes spp.) using salivary biomarkers in connection with associated illnesses, such as Zika, Chikungunya, dengue, and malaria. 

Prevention and treatment of TD remains a high priority to Combatant Commands (COCOM).  Following an IDCRP and Naval Medical Research Center (NMRC) co-sponsored workshop in 2016, a clinical practice guideline for the management of acute watery diarrhea during deployment was developed and has now been published in a special supplement of Military Medicine.  The guideline is being provided to COCOM and other senior military leadership.  A manuscript with findings from the Trial Evaluating Treatment of Ambulatory Travelers’ Diarrhea (TrEAT TD) study, led by CAPT Mark Riddle, was also published in Clinical Infectious Diseases.  The results of this randomized trial demonstrated that single-dose regimens of azithromycin, levofloxacin, and rifaximin with loperamide were comparable for the treatment of acute watery diarrhea.  As part of TrEAT TD, IDCRP sponsored development of a TD TaqMan PCR assay in collaboration with the University of Virginia for detection of pathogens associated with TD.  Based on analysis of the utility of the assay, use has become widespread within several national and international surveillance and research settings.  In another laboratory analysis, assessment of the impact of TD treatment on gut microbiome and host-pathogen interaction during Escherichia coli infections is expected to be complete by late 2019. 

During the past year, enrollment at U.S. sites continued for the Trial Evaluating Regimens of Rifaximin for Chemoprophylaxis Against Travelers’ Diarrhea (Prevent TD), led by CDR Ramiro Gutierrez at NMRC.  In addition, we received approval from the U.K. Ministry of Defence to enroll British military personnel in the study.  We anticipate all enrollments to be completed by mid-2018. 

The Knowledge, Attitudes, Practice, and Outcomes Study (KAPOS) study, led by COL Patrick Hickey, is evaluating Military Health System providers’ fund of knowledge and practice patterns related to prevention of infectious diseases in the pre-travel and pre-deployment settings, critical issues for optimizing threat mitigation and maximizing force health protection in the expeditionary military.  Currently, data collection is in process with analysis and presentation planned for 2018.

A Peer-Reviewed Medical Research Program proposal was submitted related to a TD prevention clinical trial, which will evaluate the efficacy of three over-the-counter “nutraceutical” products in preventing TD compared with a placebo (P4TD) by Drs. Tahaniyat Lalani and David Tribble.  Another new project, led by Dr. Tribble, aims to provide pathogen-specific diarrhea incidence among military beneficiaries stationed in Oahu with assessment of Pacific region-specific risk based on travel history.  This work will expand understanding of clinical, microbiological, and immunological outcomes and was awarded funds through a Global Emerging Infections Surveillance and Response System (GEIS) proposal.  

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

The Deployment and Travel-Related Infection Research Area focus on disease surveillance and randomized trials has provided an evidence base to develop deployment-related clinical practice guidelines for TD management.  In addition, several protocols in the research area (TrEAT TD, TravMil, Prevent TD and the Stool Card Validation study) evaluate the use of field expedient diagnostics for determining the pathogen-specific epidemiology of illnesses, which will inform the development of effective preventive and treatment measures.   Multiple TravMil substudies are evaluating the incidence of resistant Gram-negative organism acquisition, exposure to mosquito vectors and associated infections during deployment.  Looking forward, the research area will focus on collaborative efforts with GEIS and Center for Global Health Engagement to best address COCOM-specific priority support surveillance efforts, as well as using data-driven guidelines to improve the practice of deployment and travel medicine through our knowledge, attitudes and practices initiatives.

Highlights / Key Findings

  • Clinical practice guideline for TD management in deployed service members developed through an expert consensus panel comprised of IDCRP investigators and subject-matter experts was published in a special supplement of Military Medicine, along with evidence-based review of data supporting the recommendations.  IDCRP investigators also contributed to the development of guidelines for TD prevention and treatment, which was published in the Journal of Travel Medicine.
  • IDCRP-sponsored 2017 American Society of Tropical Medicine and Hygiene symposium included four presentations with findings related to the TaqMan Array Card PCR assay, military TD clinical practice guideline, biomarkers of mosquito exposure, and KAPOS preliminary results
  • In a TravMil  study on self-reported mosquito exposure, 64% of travelers to Chikungunya-outbreak regions reported seeing mosquitos and 53% reported at least one bite
  • TrEAT TD TaqMan PCR analysis demonstrated sensitive and specific detection of diarrheagenic E. coli, a leading cause of diarrhea among deployed troops, making it a promising alternative to conventional methods for diarrheal specimen collection and testing

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.   

Publications

Riddle MS, Connor P, Fraser J, Porter CK, Swierczewski B, Hutley EJ, Danboise B, Simons MP, Hulseberg C, Lalani T, Gutierrez RL, Tribble DR, and the TrEAT TD Study Team. Trial Evaluating Ambulatory Therapy of Travelers’ Diarrhea (TrEAT TD) Study: a randomized controlled trial comparing three single dose antibiotic regimens with loperamide. Clin Infect Dis. 2017 Nov 29;65(12):2008-2017.

Riddle MS, Tribble D. Preface: Guidelines for the Treatment of Travelers' Diarrhea in Deployed Military Personnel. Mil Med. 2017 Sep;182(S2):1-3.

Porter CK, Olson S, Hall A, Riddle MS. Travelers' Diarrhea: An Update on the Incidence, Etiology, and Risk in Military Deployments and Similar Travel Populations. Mil Med. 2017 Sep;182(S2):4-10.

Swierczewski B, Simons M. Diagnostics in a Forward Deployed Setting. Mil Med. 2017 Sep;182(S2):11-16.

Tribble DR. Antibiotic Therapy for Acute Watery Diarrhea and Dysentery. Mil Med. 2017 Sep;182(S2):17-25.

Murray CK, Blyth DM. Acquisition of Multidrug-Resistant Gram-Negative Organisms During Travel. Mil Med. 2017 Sep;182(S2):26-33.

Riddle MS, Martin GJ, Murray CK, Burgess TH, Connor P, Mancuso JD, Schnaubelt ER, Ballard TP, Fraser J, Tribble DR. Management of Acute Diarrheal Illness During Deployment: A Deployment Health Guideline and Expert Panel Report. Mil Med. 2017 Sep;182(S2):34-52.

Riddle MS, Tribble D. Implementation and Evaluation of Deployment Health Guidelines on Acute Diarrhea Management: A Medical Call to Arms. Mil Med. 2017 Sep;182(S2):53-56.

Tribble DR. Resistant pathogens as causes of traveller’s diarrhea globally and impact(s) on treatment failure and recommendations. J Travel Med. 2017 Apr 1;24(suppl_1):S6-S12.

Riddle MS, Connor BA, Beeching NJ, DuPont HL, Hamer DH, Kozarsky P, Libman M, Steffen R, Taylor D, Tribble DR, Vila J, Zanger P, Ericsson CD. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med. 2017 Apr 1;24(suppl_1):S57-S74.

Lindholm DA, Myers T, Widjaja S, Grant EM, Telu K, Lalani T, Fraser J, Fairchok M, Ganesan A, Johnson MD, Kunz A, Tribble DR, Yun HC; Infectious Disease Clinical Research Program TravMil Study Group. Mosquito Exposure and Chikungunya and Dengue Infection among Travelers during the Chikungunya Outbreak in the Americas. Am J Trop Med Hyg. 2017; 96(4): 903-12.

Lalani T, Yun H, Tribble D, Ganesan A, Kunz A, Fairchok M, Schnaubelt E, Fraser J, Mitra I, Kronmann KC, Burgess T, Deiss RG, Riddle MS, Johnson MD. A comparison of compliance rates with anti-vectorial protective measures during travel to regions with dengue or chikungunya activity, and regions endemic for Plasmodium falciparum malaria. J Travel Med. 2016;23(5).

Presentations 

 

ID Week 2016, October 26-30, 2016, New Orleans, LA:

  1. Poster #606: Wood S, Telu K, Tribble D, et al. Influenza-like Illness in Travelers to the Developing World.
  2. Poster #611: Hutter J, Lalani T, Yun H, et al. Acid suppression with histamine (H2) blockers and proton pump inhibitors (PPIs) is not associated with an increased risk of traveler’s diarrhea.

American Society of Tropical Medicine & Hygiene Annual Meeting, November 13-17, 2016, Atlanta, GA:

  1. Oral Presentation: Riddle MS, Connor P, Fraser J, et al. Results from the Trial Evaluating Ambulatory Therapy of Travelers’ Diarrhea (TrEAT TD) Study: a randomized controlled trial comparing three single dose antibiotic regimens with loperamide.
  2. Oral Presentation: Lalani T, Tisdale M, Liu J, et al. Performance characteristics of the Whatman FTA Elute card and TaqMan Array card PCR assay – TrEAT TD study.
  3. Poster #477: Ashley D, Fraser J, Yun H, et al. Pre-travel health care among pediatric US military beneficiaries.

Conference of the International Society of Travel Medicine, May 14-18, 2017, Barcelona, Spain:

  1. Oral Presentation: Riddle MS, Connor P, Fraser J, et al. Results from the Trial Evaluating Ambulatory Therapy of Travelers’ Diarrhea (TrEAT TD) Study: a randomized controlled trial comparing three single dose antibiotic regimens with loperamide.
  2. Poster: Hickey P, Fraser J, Mitra I, et al. Deployment and Travel Health: Knowledge, Attitudes, Practices, and Outcomes Study (KAPOS).

American Society of Tropical Medicine & Hygine Annual Meeting, Novemeber 5-9, 2017, Baltimore, MD:

     1. Symposium: Lalani T, Tribble DR, Tisdale M., Riddle MS, Hickey P. Translational Research                   Initiatives in the Practice of Travel Medicine. 2017.