Expanded Sexually Transmitted Infection Surveillance Efforts in the United States Military: A Time for Action

The U.S. military is composed primarily of persons less than 35 years of age. These young, healthy people are at great risk for contracting sexually transmitted infections (STIs), which have been a threat to military service members (SM) throughout history.1 Although influenced by screening policies in place, reportable STI rates for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in the U.S. military almost always exceed those in the civilian setting, even after adjusting for age, race, and U.S. geographic region of origin.2,–4 Furthermore, the threat posed by STI to military populations is magnified by assignment to areas where hazardous pathogens such as antimicrobial-resistant NG may be prevalent.5,–7 According to the World Health Organization (WHO) 2008 estimates, the total global number of new cases of four of the curable STI—CT, NG, syphilis, and Trichomonas vaginalis—was nearly 500 million cases in adults aged 15 to 49 years.8 These four STIs are responsible for considerable morbidity, above and beyond that attributable to human immunodeficiency virus (HIV) infection. If left untreated, NG and CT among women often lead to pelvic inflammatory disease (PID), which can lead to infertility, ectopic pregnancy, and chronic pain. In men, they are a cause of epididymitis, a painful condition that can also lead to infertility. Syphilis remains an important cause of mortality, particularly in congenital cases where the infection is passed from mother to infant. STIs also increases the risk for transmission of HIV,9,10 and treatment of STIs has been shown to reduce the risk of HIV acquisition in HIV-endemic areas.11,12 Although many STIs in the fighting forces are presently curable or can be suppressed, some still result in significant morbidity (e.g., recurrent herpes simplex virus [HSV] genital lesions; chronic hepatitis B and C virus infections; recurrent vaginitis; human papillomavirus [HPV]-induced genital warts; and cervical, vulvar, anal, and oropharyngeal cancers), serious complications (e.g., PID, infertility, complications of pregnancy, and congenital syphilis), and some can limit SM routine day-to-day duties, travel, and deployability (e.g., HIV infection, chronic hepatitis). The impact of non-HIV STI has recently been reviewed as part of a Global Burden of Diseases, Injuries, and Risk Factors enterprise that examined 291 diseases in 21 regions of the world and found that these infections accounted for upward of 159 disability-adjusted life years per 100,000 in the year 2010, a significant burden worldwide.13 A robust and active surveillance program to monitor STI incidence and prevalence and antimicrobial susceptibilities is essential to assess risks and morbidity and to inform policies and interventions. The successful HIV surveillance and research initiatives, developed by the U.S. military in 1985, were recently expanded to include monitoring of the incidence and prevalence of STIs other than HIV infection, oversight of antimicrobial resistance in NG, and evaluation of risk behaviors, systems, and social structures associated with STI acquisition and spread. Particularly relevant is the increasing threat of multidrug-resistant NG.14,15 Antimicrobial-resistant NG has affected the military since early antimicrobial use. Military researchers in the late 1960s documented the emergence of penicillin resistance16,17and later in the 1970s and 1980s, decreased susceptibility to tetracycline and spectinomycin5; around the same time that penicillin resistance was detected in parts of Europe and Africa.7 By the early 1990s, resistance to the fluoroquinolones (e.g., ciprofloxacin, ofloxacin) had developed and subsequent resistance to the macrolide azithromycin emerged in many parts of the world in the late 1990s.18,19 Because of the rise in fluoroquinolone-resistant NG in the United States, the Centers for Disease Control and Prevention (CDC) national guidelines in 2007 limited the empiric first-line treatment of gonorrhea to a single class of drugs, the extended-spectrum cephalosporins (ESCs).20,21 However, in the past 5 years, the CDC has published updated guidelines22,23 emphasizing the limited treatment options now available, given increasing resistance to ESCs. For NG treatment, CDC now recommends an increased dose of ceftriaxone plus either azithromycin or doxycycline for concurrent CT, and has relegated cefixime to a secondary therapy. CDC also recommends culture and resistance testing for patients with apparent treatment failure, as well as continued surveillance for NG resistance. This expansion of surveillance and research activities is supported by the Armed Forced Health Surveillance Center and its Division of Global Emerging Infections Surveillance and Response Systems (AFHSC-GEIS) program. Here we present a review of advances made during the period of October 2010 through May 2013; a summary is provided in Table I. Summary of STI Surveillance and Research Initiatives in October 2010 Through May 2013 STI, sexually transmitted infections; NG, Neisseria gonorrhoeae; DoD, U.S. Department of Defense; ESC, extended-spectrum cephalosporin; AD, active duty; CT, Chlamydia trachomatis; HIV, human immunodeficiency virus; HSV, herpes simplex virus types 1 or 2 (HSV-1 or HSV-2); DoDSR, DoD Serum Repository; HPV, human papillomavirus; CDC, U.S. Centers for Disease Control and Prevention. Summary of STI Surveillance and Research Initiatives in October 2010 Through May 2013 STI, sexually transmitted infections; NG, Neisseria gonorrhoeae; DoD, U.S. Department of Defense; ESC, extended-spectrum cephalosporin; AD, active duty; CT, Chlamydia trachomatis; HIV, human immunodeficiency virus; HSV, herpes simplex virus types 1 or 2 (HSV-1 or HSV-2); DoDSR, DoD Serum Repository; HPV, human papillomavirus; CDC, U.S. Centers for Disease Control and Prevention. The mission of the AFHSC-GEIS program is to develop, implement, support, and evaluate an integrated global emerging infectious disease surveillance and response system that contributes to the enhancement of the overall health of U.S. Forces, the global Military Health System, and the public health of the community at large. Emerging and re-emerging STI pathogens that have the potential to affect U.S. military forces are the focus of AFHSC-GEIS STI initiatives. Goals and plans have been developed through consultations with major domestic and international stakeholders. The AFHSC-GEIS STI initiatives were reviewed from the beginning of fiscal year 2011 (October 1, 2010) through mid-fiscal year 2013 (May 31, 2013), to include a review of plans, goals, and objective progress reports for projects, which were discussed with stakeholders. Initiatives in U.S. Forces and facilities and in partner countries fell into four areas of emphasis: (1) surveillance for antimicrobial-resistant NG; (2) screening for STI in U.S. military recruits and other troops; (3) seroepidemiologic studies of HSV, HPV, and syphilis (Treponema pallidum) infections in U.S. Forces and foreign military; and (4) educational efforts for U.S. military health care providers. Recognizing that a successful global STI surveillance and research network requires engagement of all parties in support of the WHO's 2005 International Health Regulations (IHR 2005),24 we assessed incorporation of IHR goals into the STI pillar initiatives. NG is able to develop antimicrobial resistance within a relatively short timeframe, and spread of antimicrobial-resistant strains can occur very quickly.25,26 Thus, establishment and maintenance of NG surveillance systems with reference laboratory capability in U.S. Forces was given a high priority. In addition, research needs were identified to support special military needs. Continued surveillance for antimicrobial-resistant NG in the military is of the utmost importance to adequately address treatment and prevention strategies among military groups. The key components of the plans for antimicrobial-resistant NG surveillance consist of: (1) development of a surveillance network that includes important U.S.-based military sites as well as sites in seven partner countries; (2) establishment of a reference laboratory at the Uniformed Services University of the Health Sciences (USU), Bethesda, MD; and (3) special studies to improve specimen collection in field or deployed settings and on ships. In the continental United States (CONUS) and Europe, the USU Infectious Disease Clinical Research Program (IDCRP) has been established and is expanding an integrated network of military health care sites to conduct surveillance and clinical research. Initially, U.S. Army sites were selected based on reported numbers of cases and to provide geographic diversity. These included military medical treatment facility (MTF)-based clinics at Fort Bragg, NC; Fort Sam Houston, TX; Fort Carson, CO; and Fort Lewis, WA. Additional U.S. military MTF sites in Portsmouth, VA; San Diego, CA; and Bethesda, MD, are expected to open soon. Initial studies by this IDCRP group include the following: (1) determining NG and CT prevalence among symptomatic men and women presenting for care, (2) characterization of antimicrobial resistance patterns among NG isolates, (3) assessment of novel approaches to isolation or identification of NG resistance, and (4) pilot studies to better define behavioral risk factors and potential interventions. Antimicrobial-resistant NG surveillance activities are also being supported in seven partner countries: Peru, Ghana, Cameroon, Kenya, Djibouti, Georgia, and Thailand (see Figure 1). These countries were selected based on existing collaborations with U.S. military research laboratories overseas and pre-existing AFHSC-GEIS supported surveillance efforts. The main effort is aimed at identifying circulating NG strain genotypes associated with clinically apparent antimicrobial resistance. Secondary objectives include assessment of risk factors, sexual networks, and other pathogens as well as future diagnostic, therapeutic, and prevention trials. In addition, efforts will be made to coordinate domestic STI surveillance activities with those by overseas military and civilian collaborators to better understand transmission networks and facilitate investigations of the propagation of antimicrobial resistance, efforts that are intended to complement those underway by the CDC, WHO, and others.26 2011–2013 STI surveillance, country partners. STI, sexually-transmitted infections. Ongoing STI surveillance in Europe at Landstuhl Regional Medical Center in Germany is not shown as it is not yet coordinated with AFHSC-GEIS. Antimicrobial-resistant NG surveillance efforts have been undertaken since April 2013 among U.S. military personnel in CONUS as well as among high-risk groups such as female commercial sex workers (FCSW), men who have sex with men (MSM), and heterosexually active host-country military and civilians in Peru, Djibouti, Ghana, and Kenya since October 2010. Work overseas is being conducted by collaborators at the U.S. Naval Medical Research Unit No. 6 (NAMRU-6) in Lima, Peru; at the U.S. Naval Medical Research Unit No. 3 (NAMRU-3) and the Global Disease Detection Regional Center; U.S. CDC in Cairo, Egypt, and Accra, Ghana; and at the U.S. Army Medical Research Unit-Kenya (USAMRU-K) in Nairobi, Kenya. A preliminary summary of findings from CONUS as well from the four additional countries is presented in Table II. A total of 3,314 subjects were enrolled and tested between October 2010. and May 2013 with 139 (4.2%) subjects found NG positive. Of these 139 subjects, 58 (42%) had isolates and have undergone antimicrobial susceptibility testing (AST) and determination of minimum inhibitory concentration (MIC) breakpoints by Etest.27 Preliminary Results on October 2010 Through May 2013 A in Peru, of was also NG, Neisseria gonorrhoeae; female commercial sex men who have sex with of NG strains that were or had decreased susceptibility to the antimicrobial is based on the minimum inhibitory concentration breakpoints for resistance as by the Clinical and with the of and azithromycin for which are breakpoints and the per U.S. Surveillance were cefixime ceftriaxone penicillin tetracycline azithromycin was culture identification by testing and susceptibility testing (AST) was conducted on isolates and testing all were by all In addition, for in the of the of NG in was in Preliminary Results on October 2010 Through May 2013 A in Peru, of was also NG, Neisseria gonorrhoeae; female commercial sex men who have sex with of NG strains that were or had decreased susceptibility to the antimicrobial is based on the minimum inhibitory concentration breakpoints for resistance as by the Clinical and with the of and azithromycin for which are breakpoints and the per U.S. Surveillance were cefixime ceftriaxone penicillin tetracycline azithromycin was culture identification by testing and susceptibility testing (AST) was conducted on isolates and testing all were by all In addition, for in the of the of NG in was in In subjects were enrolled and tested at Fort Bragg, with 5 found to be NG positive. was on of was also for and 3 and significant resistance was not the number of isolates is to to In Peru, has with STI clinics that high-risk populations in and have been monitoring STI disease behaviors, and NG antimicrobial resistance have been from symptomatic and patients with for NG by Initial as well as testing for in the of the has shown high rates of as well as resistance, in all of surveillance efforts into military clinics in the as well as among heterosexually active civilians in is underway and will be reported In Ghana, laboratory was established at the for Medical and in A total of heterosexually active military and civilian patients at four military in have been enrolled and found to be NG positive. has been on seven isolates and significant resistance has been azithromycin as well as to and penicillin Additional efforts are underway to surveillance to other sites in the of later in In Kenya, surveillance activities by among heterosexually active military and have at civilian A total of subjects have been enrolled and of which have been found to be NG positive. Preliminary findings on these isolates have shown significant resistance to tetracycline fluoroquinolones and penicillin with from an resistance to azithromycin as well as high to ceftriaxone and cefixime This preliminary recently published on NG strains in Kenya, and may emerging resistance to azithromycin to Thus, continued surveillance efforts among patients and high-risk groups of in as well as in the of and Kenya will in the to include testing for NG and CT infections as In Djibouti, laboratory for NG and CT surveillance was established in late 2010 at the Center for and Clinical and and and have been from patients presenting with or of culture and are in isolates and for the year have been to for additional and A total of subjects have been enrolled and of which have been found to be NG positive. isolates resistance has been to fluoroquinolones tetracycline and penicillin with preliminary findings of decreased susceptibility to such as and ceftriaxone Preliminary of resistance in Kenya and is and testing testing and additional specimen These findings to be through susceptibility testing at and as well as collection of additional in patients to treatment (e.g., at and the importance of monitoring and active surveillance for STI, NG, which is to development of antimicrobial resistance. NG surveillance initiatives are being also among foreign military and in the region in Military as well as in the region in and military and civilian in is also expected that of surveillance for antimicrobial-resistant NG will with the military in the to additional sites in and are being for later in A U.S. Department of reference laboratory and NG is being developed by at the which will as a reference laboratory in with the University of NG reference laboratory and the Surveillance The USU laboratory will and for U.S. Forces and international and NG strains will be and tested for antimicrobial susceptibilities and by strains will be and be made to researchers within and the to monitoring NG antimicrobial resistance in the military field is the development of collection and for with laboratory for and other for and resistance at the U.S. Naval Unit No. 2 are the of as a for and genital as an to provided in surveillance Preliminary is in are and on at studies are its for field medical of and this can be integrated in other NG surveillance efforts in the U.S. it is surveillance efforts include and surveillance on the and is on the collection of NG isolates from patients who have antimicrobial to other sites in the antimicrobial-resistant NG surveillance network are isolates will be tested for antimicrobial susceptibility by and will be by Etest.27 Antimicrobial-resistant isolates will be and to responsible for resistance. these are and can be on and for will published for fluoroquinolones and azithromycin resistance in NG strains and will to develop an additional for associated with resistance to ESCs. NG and CT are the reported STIs in the U.S. is for to the burden of all Because the military surveillance system on surveillance, reported STI rates are to be as a number of who are not and some are to care the military medical the prevalence of all and of behavioral and treatment initiatives, is to develop a for and the impact of during military are sites where treatment, and can be conducted and CT screening for all female military recruits has been by the Armed Forces has been by the Health since In addition, the U.S. Services recommends screening women less than years of to provide the screening for women with the of the all also female recruits during expansion of STI screening to recruits less than years of also be as per CDC is and additional may from screening of recruits provide a of STIs in the U.S. the military studies among recruits have reported CT infection rates among female recruits to the U.S. significant morbidity in the as well as CT rates among and U.S. Army personnel in the U.S. and These are by military and civilian public health in the United better assess STI patterns in the it will be to existing screening to military members with symptomatic or infection and those who are at and in other selected military with and culture the STI includes STI to include a condition in the U.S. military (e.g., cases reported per of per and a with high prevalence with million cases million of which occur in the United at the in with have to patterns of STI in the U.S. military the past Preliminary review of medical for a of SM for the period of that or STIs are within military service with as high as for women and for men among those with or years of as well as rates during the period of to and Surveillance supported by AFHSC-GEIS from the DoD Serum for military personnel provide a for identifying infection with STI such as 2 HPV, and HIV, as well as or past infection with The impact that such has on U.S. military personnel is In to be very among as well as among In addition, is the major cause of genital as well as of the STIs in the United States and infection has also been reported as a significant risk for HIV acquisition and and a significant cause of morbidity in the U.S. being in reported incidence by HPV, CT, and In the U.S. is routine or screening program. In an effort to define such a program be a among U.S. military active personnel is being conducted by IDCRP and SM within 1 year of active and years between 2005 and are being tested for the of to and The support assessment of prevalence on into the military and subsequent and inform policies and HPV, the cause of genital and a major risk for cervical, vulvar, anal, and oropharyngeal has recently been found to be and associated with health care than other STI in the U.S. In the U.S. and the which and the cause of and and the cause of genital warts; a that and was by the in October In the Services policies the of these as by the U.S. is to these policies have been and such will have on infection rates among military In an effort to inform DoD policies and the the is rates and of and the of that the is among to or of the is a of among military recruits to assess the needs of this and as a for the of the program with and are also rates among as well as the and of the to SM to the impact of of the rates on around of have been documented to the within 1 year with between and of 3 and Thus, and rates have been In addition, have documented that of may be genital among service women in the since the IDCRP have been prevalence and among military and findings have a of for of the in the and to or of these after years, who infection with of the new infections of an Although of the now to these support the potential of routine of to military and to as by national guidelines from the on these initiatives will also the for an DoD that to a in assessment of the and incidence for STIs other than HIV infection among host-country military recruits is being as an pilot at of to STI such as and as well as to The Armed Forces Research of Medical Sciences is to conduct and studies of foreign military are AFHSC-GEIS in and STI among these is the for the and continued conduct clinically relevant and educational efforts for U.S. military health care providers. In with this military at the Army of in with the U.S. Health and the University of and the of Prevention Centers developed a on as part of a on the 2010 CDC The was developed for a of military health care and civilian who care of military areas included of STIs in the Armed of and and an of prevention strategies for military personnel and This open has been as a educational through the CDC be that is a research in of treatment and as with to NG treatment, and evaluation of treatment that are beginning to be by this program and which will continued in the The of the AFHSC-GEIS STI pillar is a for surveillance and and that will provide DoD and service with a of STI of approaches to STI surveillance is a that is in all and The AFHSC-GEIS is to with who are to efforts in STI surveillance, antimicrobial resistance surveillance, and are being developed and to define and address goals and as well as review in support of this enhancement of STI surveillance and research initiatives has in the U.S. in October 2010, a network has been established with the of a in countries in a significant expansion of STI initiatives in the United States and program areas have included the following: (1) surveillance for emergence of antimicrobial-resistant NG, (2) screening and assessment of the impact of STIs among recruits and other (3) seroepidemiologic studies of non-HIV STIs as and and syphilis, and (4) conduct of clinically relevant educational efforts for U.S. military health care providers. Initial progress has been through a network of that and a and surveillance is that these surveillance activities will partner countries and the U.S. military to STI and to reduce incidence and morbidity, as well as global health This effort many For from in surveillance in areas (e.g., and we have in from to for in those less than years of age, as well as from the to that to of from or and a that the successful isolation of NG isolates, of resistance and contributes to resistance. the and as all STIs have the same of transmission and is between a surveillance program that the and the has is that this effort will a to better STIs in the military and and support development of policies to to at AFHSC-GEIS to and for development and subsequent support, to and for support, and to for and in support of STI initiatives. we to all subjects, field and country civilian and military collaborators for and