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Sexually Transmitted Infections

STIs were a significant cause of morbidity and mortality before the advent of penicillin treatment. With new medications and treatment options available in the 1940s, the Department of Defense (DoD) shifted its focus away from STIs and turned to other more militarily impactful diseases. However, with the development of antibiotic resistant gonorrhea, there has been a renewed global interest in STIs. The Armed Forces Health Surveillance Center (AFHSC) has examined data to show that CT and HPV infections are on the rise among military personnel. IDCRP has developed an STI clinical research network to create research opportunities at various military installations and expand the knowledge base of these infections.

Service members are often young, active and may engage in risky behaviors at any point during their military career, including international deployment. Prior to the repeal of Don’t Ask Don’t Tell, STI research in the military was limited due to the inability to ask sensitive risk-behavior questions. Since then, STI research in the military has begun to examine these sensitive issues, which can lead to a better understanding of the difference between STI rates among service members and civilians.

Research Area Description

Sexually-transmitted infections (STIs) are among the most common infections in military populations and represent a threat to medical readiness, force health protection, and significant morbidity with the potential to introduce clinically problematic infections into civilian communities.

Although the U.S. military is largely comprised of the same risk groups described in civilian populations, multiple studies have shown higher rates of STIs in the military.  In recent years, interest in sexually-transmitted infections (STIs) and their relevance to the military intensified with the inclusion of Neisseria gonorrhea (GC) by the Centers for Disease Control and Prevention as one of the top three urgent drug-resistant U.S. threats. The intersection of deployment health and STIs became even more apparent with the demonstration of sexual transmission of the Zika virus along with ongoing research into long-term genital carriage of Ebola virus.

The GC Resistance Study and Repository, led by LTC Eric Garges and Dr. Ann Jerse, remains the backbone of the research portfolio with 77 new GC isolates added to the repository.   The domestic GC surveillance program was maintained at four U.S. military hospitals and inclusion/reengagement of additional sites are being planned for the upcoming year.  We have also continued to develop a role in support of the Global Emerging Infections Surveillance and Response System (GEIS) global GC surveillance effort, largely as a coordinating center for the newly established DoD Gonococcal Reference Laboratory and Repository at USU (located in the lab of Dr. Ann Jerse).  Upcoming analyses will incorporate whole genome sequencing to provide genetic epidemiologic data to compare determinants of resistance to phenotypes from GC isolates from around the globe. 

With the goal of examining prevalence and risk factors for GC and chlamydia (CT) infections, two additional protocols are underway.  The 3 Site GC/CT Testing Among HIV+ DoD Beneficiaries study, led by Dr. Anuradha Ganesan, has enrolled 450 HIV-infected subjects and the self-testing portion of the study was completed.  Findings indicate that self-testing is a feasible and acceptable method for collection of extra-genital samples within the military health system.  Molecular testing of the CT specimens is forthcoming, which will provide information on transmission networks and support preventive efforts.  Risk factors for extragential CT and GC infections among asymptomatic active-duty women is the focus of the second protocol (3 Site GC/CT Testing Among Women study), led by CAPT Mary Bavaro and Dr. Robert Deiss.  Presently, the study has completed enrollment and data analysis is underway.

In the upcoming year, we will see the further expansion of the domestic GC surveillance program and extra-genital testing in high-risk HIV-negative populations.  Additionally, we will begin screening clinical samples collected from our CT studies for M. genitalium, which is prevalent in civilian populations, but surveillance efforts in military populations have been limited.  The Sexual and Social Network Study, led by LTC Garges, recently completed a pilot study and the protocol is being refined based on the findings.   Enrollment will start in early 2018 at four sites with the potential to expand to any clinical site currently enrolling in the GC Resistance Protocol.  This study will be used to identify risk reduction targets for interventions beyond traditional individual risk factors.  Research concepts in development include a multi-component approach to evaluating sexual transmission of Zika virus, as well as conducting studies to evaluate a Meningitis B vaccine (4cMenB, Bexsero) for prevention efficacy and host response against GC. 

Military Impact

The IDCRP is uniquely positioned to address sexually-transmitted threats to service member health from clinical prevention through therapy.  Our goal is to support DoD STI prevention, diagnosis, and treatment to reduce STIs among active-duty members and beneficiaries.  In our role as the GC Resistance Coordinating Center, providing support and standardization across all sites involved in efforts in this area, we have demonstrated regional resistance patterns from locations with no other available data.  This information is valuable to the DoD for mission planning, but is also critical in assessing the global antimicrobial resistance risk for GC.  Ongoing surveillance efforts have also monitored the resistance patterns at U.S.-based treatment facilities, directly affecting force health.

Looking forward, a new strategic plan is being developed for the research area, which will outline the current disease trends within the military population, define unique advantages and disadvantages of STI study within the DoD, and identify clinical research targets that are (1) relevant to the DoD, (2) appropriate for burden and risk assessment and, (3) support clinical research goals of our stakeholders, collaborators, and the global community.  We will also continue to maintain a comprehensive survey of new STI vaccines and diagnostic platforms that may be of interest to the DoD, with the long-term goal of planning prevention studies, including behavioral interventions and STI vaccines.

Highlights / Key Findings

  • 22% of women and 3.3% of men received a pathogen-specific STI diagnosis during military service; lower rates for men may indicate under-diagnosis and need for enhanced male-directed screening and diagnostic interventions
  • Self-collection of extra-genital samples provided more positive results than provider-collected samples; adoption of self-testing could improve compliance with guidelines
  • Country specific GC antimicrobial resistance patterns have demonstrated regional resistance patterns and unique NG-MAST types.
  • Whole genome sequencing of GC specimens will be conducted in collaboration at Dr. Patrick McGann’s Lab at Walter Reed Army Institute of Research Multidrug-resistant Organism Repository and Surveillance Network
  • Site in the Philippines being discussed for inclusion in GC surveillance program; will be a first-time collaboration with the CDC Global Surveillance Program
  • Initiation of observational and laboratory based studies evaluating a protective effect of the  4CMenB Meningitis B vaccine against genital Neisseria infection will begin in 2018

Publications 

Deiss R, Bower RJ, Co E, et al. The association between sexually transmitted infections, length of service and other demographic factors in the U.S. military. PLoS One. 2016 Dec 9;11(12):e0167892.

Presentations

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

  1. Poster #1303: Macalino G, Kluz N, Rahman N, et al. Gonococcal Resistance in a Population of at-risk U.S. DoD Beneficiaries.
  2. Poster #478: Macalino G, Wang X, Ganesan G, et al. How does changing sexual risk behaviors impact incident sexually transmitted infections (STIs) in a cohort of HIV+ military beneficiaries?
  3. Poster #474: Byrne M, Kluz N, Sanchez J, et al. Characterizing Self-reported Sexual Risk Behaviors and STIs among High Risk Military Populations who Utilize Social Networking Sites to Seek Sexual Partners.

International Society for STD Research Meeting, 2017, July 9-12, Rio de Janeiro, Brazil, South America:

  1. Poster: Rahman N, Kluz N, Puplampu-Attram N, et al. Antibiotic Resistance and Molecular Typing of Neisseria gonorrhoeae Isolated from the Three Overseas Sites through the Global Emerging Infections Surveillance and Response System (GEIS)
  2. Podium: Garges, E., Rahman, N., Jerse, A. Establishing a DoD Gonococcal Resistance Surveillance Effort, Reference Laboratory and Repository from a population of at-risk U.S. DoD beneficiaries