Search

Background: The Joint Trauma System (JTS) is a DoD Center of Excellence for Military Health System trauma care delivery and the DoD's reference body for trauma care in accordance with National Defense Authorization Act for Fiscal Year 2017. Through the JTS, evidence-based clinical practice guidelines (CPGs) have been developed and subsequently refined to standardize and improve combat casualty care. Data are amassed through a single, centralized DoD Trauma Registry to support process improvement measures with specialty modules established as the registry evolved. Herein, we review the implementation of the JTS DoD Trauma Registry specialty Infectious Disease Module and the development of infection-related CPGs and summarize published findings on the subsequent impact of the Infectious Disease Module on combat casualty care clinical practice and guidelines.Methods: The DoD Trauma Registry Infectious Disease Module was developed in collaboration with the Infectious Disease Clinical Research Program (IDCRP) Trauma Infectious Disease Outcomes Study (TIDOS). Infection-related information (e.g., syndromes, antibiotic management, and microbiology) were collected from military personnel wounded during deployment June 1, 2009 through December 31, 2014 and medevac'd to Landstuhl Regional Medical Center in Germany before transitioning to participating military hospitals in the USA.Results: To support process improvements and reduce variation in practice patterns, data collected through the Infectious Disease Module have been utilized in TIDOS analyses focused on assessing compliance with post-trauma antibiotic prophylaxis recommendations detailed in JTS CPGs. Analyses examined compliance over three time periods: 6 months, one-year, and 5 years. The five-year analysis demonstrated significantly improved adherence to recommendations following the dissemination of the 2011 JTS CPG, particularly with open fractures (34% compliance compared to 73% in 2013-2014). Due to conflicting recommendations regarding use of expanded Gram-negative coverage with open fractures, infectious outcomes among patients with open fractures who received cefazolin or expanded Gram-negative coverage (cefazolin plus fluoroquinolones and/or aminoglycosides) were also examined in a TIDOS analysis. The lack of a difference in the proportion of osteomyelitis (8% in both groups) and the significantly greater recovery of Gram-negative organisms resistant to aminoglycosides or fluoroquinolones among patients who received expanded Gram-negative coverage supported JTS recommendations regarding the use of cefazolin with open fractures. Following recognition of the outbreak of invasive fungal wound infections (IFIs) among blast casualties injured in Afghanistan, the ID Module was refined to capture data (e.g., fungal culture and histopathology findings, wound necrosis, and antifungal management) needed for the TIDOS team to lead the DoD outbreak investigation. These data captured through the Infectious Disease Module provided support for the development of a JTS CPG for the prevention and management of IFIs, which was later refined based on subsequent TIDOS IFI analyses.Conclusions: To improve combat casualty care outcomes and mitigate high-consequence infections in future conflicts, particularly in the event of prolonged field care, expansion, refinement, and a mechanism for sustainability of the DoD Trauma Registry Infectious Disease Module is needed to include real-time surveillance of infectious disease trends and outcomes. [ABSTRACT FROM AUTHOR]

The article presents the discussion on longest period of war for the USA accompanied by unprecedented advances in combat casualty care. Topics include survivability of battlefield wounds increased resulting in a greater incidence of trauma related infections and creating new challenges for clinicians caring for the wounded; and threat of multidrug-resistant organisms associated with battlefield wound colonization.

Background: We assessed the compliance with self-collection of stool smears on Whatman® FTA® Elute Card (FTA Card) and detection of travellers' diarrhoea (TD)-associated pathogens by using a quantitative Polymerase Chain Reaction (PCR) assay [customized TaqMan® array card (TAC)] in a prospective, observational cohort of travellers.Methods: Enrolled travellers documented symptoms on a travel diary and collected an FTA Card during a diarrhoeal episode, or at the end of travel if they remained asymptomatic. TAC testing was performed on FTA Cards from TD cases and 1:1 matched asymptomatic controls and 1:1 matched loose stool cases that did not meet TD criteria. Odds ratios were used to determine the association between detected pathogens and TD.Results: Of 2456 travellers, 484 (19.7%) completed an illness diary and met TD criteria, and 257 (53.1%) collected an FTA Card during the TD episode. FTA Cards were stored for a median of 2 years at room temperature (IQR: 1-4 years) before extraction and testing. The overall TAC detection rate in TD cases was 58.8% (95% CI: 52.5-64.8). Enterotoxigenic Escherichia coli was the most common pathogen in TD cases (26.8%), and 3.5% of samples were positive for norovirus. The odds of detecting TD-associated pathogens in 231 matched cases and asymptomatic controls were 5.4 (95% CI: 3.6-8.1) and 2.0 (95% CI: 1.1-3.7) in 121 matched TD and loose stool cases (P < 0.05). Enteroaggregative E. coli was the most common pathogen detected in asymptomatic controls and loose stool cases. Detection of diarrhoeagenic E. coli, Shigella/enteroinvasive E. coli and Campylobacter spp. was significantly associated with TD.Conclusion: FTA Cards are a useful adjunct to traditional stool collection methods for evaluating the pathogen-specific epidemiology of TD in austere environments. Qualitative detection of pathogens was associated with TD. Measures to improve compliance and quality of FTA Card collection with decreased storage duration may further optimize detection. [ABSTRACT FROM AUTHOR]

Background Antibiotic stewardship in the pretravel care of older adults is important to effectively treat infections while minimizing harm from side effects and unnecessary antibiotic use. The objective of this study was to compare the characteristics, risk behaviors, infectious diseases, and antibiotic use between older (≥60 years) and younger (18–59 years) travelers. Methods TravMil is a prospective, observational cohort of United States (US) Department of Defense beneficiaries traveling outside the continental US for ≤6.5 months. For this analysis, we included adults enrolled pretravel between January 2010 and August 2018 and excluded active duty personnel on deployment. Pre and post-travel surveys captured trip characteristics, exposures, illnesses, and antibiotic use. Results A total of 1742 travelers were analyzed: 747 (42.9%) were aged ≥60 years and 995 (57.1%) were aged 18–59 years. Older travelers were less likely to engage in high-risk dietary behaviors and experience travelers' diarrhea than younger travelers (18.2% vs 22.9%; P  < .05). Influenza-like illness (12.5%) and febrile illness (3.4%) occurred less frequently in the older cohort. Antibiotic use for self-treatment was common in both age groups (25.7% vs 26.7%) and often inappropriate, for example, for treatment of occasional loose stool or mild travelers' diarrhea (67.0% [67/100] in older adults vs 57.6% [83/144] in younger adults; P  < .05), and influenza-like illness (63.4% [64/101] vs 58.6% [68/116], respectively; P  < .05). Conclusions Older travelers were less likely to engage in high-risk behaviors and experience travelers' diarrhea, and both age groups experienced mild, self-limited infections. Inappropriate use of antibiotics was common, suggesting that antimicrobial stewardship should be emphasized at pretravel counseling with international travelers. [ABSTRACT FROM AUTHOR]

Introduction: During recent wars in Iraq and Afghanistan, improved survivability in severe trauma corresponded with a rise in the proportion of trauma-related infections, including those associated with multidrug-resistant organisms (MDROs). Significant morbidity was reported in association with the infections. There is also concern regarding potential long-term impacts of the trauma-related infectious complications. Therefore, to meet the critical need of prospective collection of standardized infection-related data to understand the disease burden and improve outcomes of wounded personnel, the Trauma Infectious Disease Outcomes Study (TIDOS) was developed. Herein, we review accomplishments and key peer-reviewed findings of TIDOS.Methods: The TIDOS project is a multicenter observational study of short- and long-term infectious complications following deployment-related trauma. Wounded military personnel medevac'd to Landstuhl Regional Medical Center (LRMC; Germany) before transfer to a participating US military hospital between June 2009 and December 2014 were eligible for inclusion. An infectious disease module to supplement the Department of Defense Trauma Registry by collecting infection-related data from all trauma patients admitted to participating hospitals was developed. Specimens from trauma patients were also collected and retained in a microbiological isolate repository. During the initial hospitalization, patients were given the opportunity to enroll in a prospective follow-up cohort study. Patients who received Department of Veterans Affairs (VA) care were also given the opportunity to consent to ongoing VA follow-up.Results: A total of 2,699 patients transferred to participating military hospitals in the USA, of which 1,359 (50%) patients enrolled in the TIDOS follow-up cohort. In addition, 638 enrolled in the TIDOS-VA cohort (52% of TIDOS enrollees who entered VA healthcare). More than 8,000 isolates were collected from infection control surveillance and diagnostic evaluations and retained in the TIDOS Microbiological Repository. Approximately 34% of the 2,699 patients at US hospitals developed a trauma-related infection during their initial hospitalization with skin and soft-tissue infections being predominant. After discharge from the US hospitals, approximately one-third of TIDOS cohort enrollees developed a new trauma-related infection during follow-up and extremity wound infections (skin and soft-tissue infections and osteomyelitis) continued to be the majority. Among TIDOS cohort enrollees who received VA healthcare, 38% developed a new trauma-related infection with the incident infection being diagnosed a median of 88 days (interquartile range: 19-351 days) following hospital discharge. Data from TIDOS have been used to support the development of Joint Trauma System clinical practice guidelines for the prevention of combat-related infections, as well as the management of invasive fungal wound infections. Lastly, due to the increasing proportion of infections associated with MDROs, TIDOS investigators have collaborated with investigators across military laboratories as part of the Multidrug-Resistant and Virulent Organisms Trauma Infections Initiative with the objective of improving the understanding of the complex wound microbiology in order to develop novel infectious disease countermeasures.Conclusions: The TIDOS project has focused research on four initiatives: (1) blast-related wound infection epidemiology and clinical management; (2) DoD-VA outcomes research; (3) Multidrug- Resistant and other Virulent Organisms Trauma Infections Initiative; and (4) Joint Trauma System clinical practice guidelines and antibiotic stewardship. There is a continuing need for longitudinal data platforms to support battlefield wound research and clinical practice guideline recommendation refinement, particularly to improve care for future conflicts. As such, maintaining a research platform, such as TIDOS, would negate the lengthy time needed to initiate data collection and analysis. [ABSTRACT FROM AUTHOR]

Background: During recent wars, 26% of combat casualties experienced open fractures and these injuries frequently are complicated by infections, including osteomyelitis. Risk factors for the development of osteomyelitis with combat-related open tibia fractures have been examined, but less information is known about recurrence of this infection, which may result in additional hospitalizations and surgical procedures.Questions/purposes: (1) What is the risk of osteomyelitis recurrence after wartime open tibia fractures and how does the microbiology compare with initial infections? (2) What factors are associated with osteomyelitis recurrence among patients with open tibia fractures? (3) What clinical characteristics and management approaches are associated with definite/probable osteomyelitis as opposed to possible osteomyelitis and what was the microbiology of these infections?Methods: A survey of US military personnel injured during deployment between March 2003 and December 2009 identified 215 patients with open tibia fractures, of whom 130 patients developed osteomyelitis and were examined in a retrospective analysis. No patients with bilateral osteomyelitis were included. Twenty-five patients meeting osteomyelitis diagnostic criteria were classified as definite/probable (positive bone culture, direct evidence of infection, or symptoms with culture and/or radiographic evidence) and 105 were classified as possible (bone contamination, organism growth in deep wound tissue, and evidence of local/systemic inflammation). Patients diagnosed with osteomyelitis were treated with débridement and irrigation as well as intravenous antibiotics. Fixation hardware was retained until fracture union, when possible. Osteomyelitis recurrence was defined as a subsequent osteomyelitis diagnosis at the original site ≥ 30 days after completion of initial treatment. This followup period was chosen based on the definition of recurrence so as to include as many patients as possible for analysis. Factors associated with osteomyelitis recurrence were assessed using univariate analysis in a subset of the population with ≥ 30 days of followup. Patients who had an amputation at or proximal to the knee after the initial osteomyelitis were not included in the recurrence assessment.Results: Of 112 patients meeting the criteria for assessment of recurrence, 31 (28%) developed an osteomyelitis recurrence, of whom seven of 25 (28%) had definite/probable and 24 of 87 (28%) had possible classifications for their initial osteomyelitis diagnosis. Risk of osteomyelitis recurrence was associated with missing or devascularized bone (recurrence, 14 of 31 [47%]; nonrecurrence, 22 of 81 [28%]; hazard ratio [HR], 3.94; 1.12-13.81; p = 0.032) and receipt of antibiotics for 22-56 days (recurrence, 20 of 31 [65%]; nonrecurrence: 37 of 81 [46%]; HR, 2.81; 1.05-7.49; p = 0.039). Compared with possible osteomyelitis, definite/probable osteomyelitis was associated with localized swelling at the bone site (13 of 25 [52%] versus 28 of 105 [27%]; risk ratio [RR], 1.95 [1.19-3.19]; p = 0.008) and less extensive skin and soft tissue injury at the time of trauma (9 of 22 [41%; three definite/probably patients missing data] versus 13 of 104 [13%; one possible patient missing data]; RR, 3.27 [1.60-6.69]; p = 0.001). Most osteomyelitis infections were polymicrobial (14 of 23 [61%; two patients with missing data] for definite/probable patients and 62 of 105 [59%] for possible patients; RR, 1.03 [0.72-1.48]; p = 0.870). More of the definite/probable patients received vancomycin (64%) compared with the possible patients (41%; p = 0.046), and the duration of polymyxin use was longer (median, 38 days versus 16 days, p = 0.018). Time to definitive fracture fixation was not different between the groups.Conclusions: Recurrent osteomyelitis after open tibia fractures is common. In a univariate model, patients with an intermediate amount of bone loss and those treated with antibiotics for 22 to 56 days were more likely to experience osteomyelitis recurrence. Because only univariate analysis was possible, these findings should be considered preliminary. Osteomyelitis recurrence rates were similar, regardless of initial osteomyelitis classification, indicating that diagnoses of possible osteomyelitis should be treated aggressively.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Invasive fungal wound infections (IFIs) were an unexpected complication associated with blast-related wounds during Operation Enduring Freedom. Between 2010 and 2012, IFI incidence rates were as high as 10-12% for patients injured during Operation Enduring Freedom and admitted to the intensive care unit at the Landstuhl Regional Medical Center. Independent risk factors for the development of IFIs include dismounted blast injuries, above knee amputations and massive (>20 units) packed red blood cell transfusions within 24 hours after injury. The Joint Trauma System developed a Clinical Practice Guideline on IFI prevention, identification and management. Aggressive and frequent surgical debridement remains the primary therapy accompanied by topical antifungal therapy (e.g., Dakins solution). Empiric systemic antifungal therapy with both liposomal amphotericin B and an intravenous broad-spectrum triazole (e.g., voriconazole or posaconazole) should be administered when there is strong suspicion of IFI based on the occurrence of recurrent wound necrosis following serial surgical debridements, since many cases involve multiple fungal species. Other recommendations include: (1) early tissue sampling for wound histopathology and fungal cultures, (2) early consultation with infectious disease specialists, and (3) coordination with surgical pathology and clinical microbiology. [ABSTRACT FROM AUTHOR]

Wound infections play an important role in the morbidity and mortality of service members injured in combat. The exigent and often long road to recovery can be complicated by healthcare-associated infections caused by multidrug-resistant organisms. The outcome is not only financially taxing but also can be life threatening. This Clinical Practice Guideline (CPG) will provide the reader with a brief overview of this topic, easy and equitable strategies to implement, and significantly reduce the exposure and possible contamination and spread of life threatening organisms in combat wounds. The table and guidance will provide easy step-wise approach in management of different challenging scenarios to help control spread of infection down range and at every level of medical treatment facility involved in patient transport to the ultimate institution. [ABSTRACT FROM AUTHOR]

Background: The Trauma Infectious Disease Outcomes Study (TIDOS) cohort follows military personnel with deployment-related injuries in order to evaluate short- and long-term infectious complications. High rates of infectious complications have been observed in more than 30% of injured patients during initial hospitalization. We present data on infectious complications related to combat trauma after the initial period of hospitalization.Patients and Methods: Data related to patient care for military personnel injured during combat operations between June 2009 and May 2012 were collected. Follow-up data were captured from interviews with enrolled participants and review of electronic medical records.Results: Among 1,006 patients enrolled in the TIDOS cohort with follow-up data, 357 (35%) were diagnosed with one or more infection during their initial hospitalization, of whom 160 (45%) developed a trauma-related infection during follow-up (4.2 infections per 10,000 person-days). Patients with three or more infections during the initial hospitalization had a significantly higher rate of infections during the follow-up period compared with those with only one inpatient infection (incidence rate: 6.6 versus 3.1 per 10,000 days; p < 0.0001). There were 657 enrollees who did not have an infection during initial hospitalization, of whom 158 (24%) developed one during follow-up (incidence rate: 1.6 per 10,000 days). Overall, 318 (32%) enrolled patients developed an infection after hospital discharge (562 unique infections) with skin and soft-tissue infections being predominant (66%) followed by osteomyelitis (16%). Sustaining an amputation or open fracture, having an inpatient infection, and use of anti-pseudomonal penicillin (≥7 d) were independently associated with risk of an extremity wound infection during follow-up, whereas shorter hospitalization (15-30 d) was associated with a reduced risk.Conclusions: Combat-injured patients have a high burden of infectious complications that continue long after the initial period of hospitalization with soft-tissue and osteomyelitis being predominant. Further research on the long-term impact and outcomes of combat-associated infection is needed. [ABSTRACT FROM AUTHOR]

The article provides information on deployment of health guidelines for managing acute diarrhea including its evaluation and implementation. Topics discussed include optimization of operations for health and promotions for healthy lifestyle, infectious diseases that affect travellers, and diarrhea development.

Diarrheal disease affects a large proportion of military personnel deployed to developing countries, resulting in decreased job performance and operational readiness. Travelers’ diarrhea is self-limiting and generally resolves within 5 days; however, antibiotic treatment significantly reduces symptom severity and duration of illness. Presently, azithromycin is the preferred first-line antibiotic for the treatment of acute watery diarrhea (single dose 500 mg), as well as for febrile diarrhea and dysentery (single dose 1,000 mg). Levofloxacin and ciprofloxacin are also options for acute watery diarrhea (single dose 500 mg and 750 mg, respectively) and febrile diarrhea/dysentery in areas with high rates of Shigella (500 mg once for 3 days [once daily with levofloxacin and twice daily with ciprofloxacin]), but are becoming less effective because of increasing fluoroquinolone resistance, particularly among Campylobacter spp. Another alternate for acute watery diarrhea is rifaximin (200 mg 3 times per day for 3 days); however, it should not be used with invasive illness. Use of loperamide in combination with antibiotic treatment is also beneficial as it has been shown to further reduce gastrointestinal symptoms and duration of illness. Because of regional differences in the predominance of pathogens and resistance levels, choice of antibiotic should take travel destination into consideration. [ABSTRACT FROM AUTHOR]

Diarrheal disease affects a large proportion of military personnel deployed to developing countries, resulting in decreased job performance and operational readiness. Travelers' diarrhea is self-limiting and generally resolves within 5 days; however, antibiotic treatment significantly reduces symptom severity and duration of illness. Presently, azithromycin is the preferred first-line antibiotic for the treatment of acute watery diarrhea (single dose 500 mg), as well as for febrile diarrhea and dysentery (single dose 1,000 mg). Levofloxacin and ciprofloxacin are also options for acute watery diarrhea (single dose 500 mg and 750 mg, respectively) and febrile diarrhea/dysentery in areas with high rates of Shigella (500 mg once for 3 days [once daily with levofloxacin and twice daily with ciprofloxacin]), but are becoming less effective because of increasing fluoroquinolone resistance, particularly among Campylobacter spp. Another alternate for acute watery diarrhea is rifaximin (200 mg 3 times per day for 3 days); however, it should not be used with invasive illness. Use of loperamide in combination with antibiotic treatment is also beneficial as it has been shown to further reduce gastrointestinal symptoms and duration of illness. Because of regional differences in the predominance of pathogens and resistance levels, choice of antibiotic should take travel destination into consideration. [ABSTRACT FROM AUTHOR]

The Trauma Infectious Disease Outcomes Study began in June 2009 as combat operations were decreasing in Iraq and increasing in Afghanistan. Our analysis examines the rate of infections of wounded U.S. military personnel from operational theaters in Iraq and Afghanistan admitted to Landstuhl Regional Medical Center between June 2009 and December 2013 and transferred to a participating U.S. hospital. Infection risk factors were examined in a multivariate logistic regression analysis (expressed as odds ratios [OR]; 95% confidence intervals [CI]). The study population includes 524 wounded military personnel from Iraq and 4,766 from Afghanistan. The proportion of patients with at least one infection was 28% and 34% from the Iraq and Afghanistan theaters, respectively. The incidence density rate was 2.0 (per 100 person-days) for Iraq and 2.7 infections for Afghanistan. Independent risk factors included large-volume blood product transfusions (OR: 10.68; CI: 6.73-16.95), high Injury Severity Score (OR: 2.48; CI: 1.81-3.41), and improvised explosive device injury mechanism (OR: 1.84; CI: 1.35-2.49). Operational theater (OR: 1.32; CI: 0.87-1.99) was not a risk factor. The difference in infection rates between operational theaters is primarily a result of increased injury severity in Afghanistan from a higher proportion of blast-related trauma during the study period. [ABSTRACT FROM AUTHOR]

During the recent war in Afghanistan (2001-2014), invasive fungal wound infections (IFIs) among US combat casualties were associated with risk factors related to the mechanism and pattern of injury. Although previous studies recognized that IFI patients primarily sustained injuries in southern Afghanistan, environmental data were not examined. We compared environmental conditions of this region with those of an area in eastern Afghanistan that was not associated with observed IFIs after injury. A larger proportion of personnel injured in the south (61%) grew mold from wound cultures than those injured in the east (20%). In a multivariable analysis, the southern location, characterized by lower elevation, warmer temperatures, and greater isothermality, was independently associated with mold contamination of wounds. These environmental characteristics, along with known risk factors related to injury characteristics, may be useful in modeling the risk for IFIs after traumatic injury in other regions. [ABSTRACT FROM AUTHOR]

Diarrheal disease frequently affects military personnel deployed to developing countries, resulting in decreased job performance and potential negative impacts on military operational readiness. Travelers’ diarrhea is a self-limiting illness; however, antibiotic treatment (with and without use of adjunct loperamide therapy) has been shown to significantly reduce clinical presentation of symptoms and duration of illness. Nonetheless, the choice of first-line antibiotics must be carefully considered as increasing resistance of enteric pathogens in endemic regions has rendered many first-line antibiotics ineffective (e.g., Campylobacter spp. are resistant to fluoroquinolones in Southeast Asia). Presently, there are no standardized recommendations for the treatment of travelers’ diarrhea among deployed military personnel. Therefore, an expert panel was convened to develop evidence-based, consensus-driven guidelines that address key clinical issues related to self-treatment, antibiotic treatment for acute watery diarrhea and febrile diarrhea/dysentery, and diagnostics. These guidelines “Management of Acute Diarrheal Illness during Deployment” are published in this supplement along with articles reviewing the evidence-based data that supported their development. [ABSTRACT FROM AUTHOR]

Diarrheal disease frequently affects military personnel deployed to developing countries, resulting in decreased job performance and potential negative impacts on military operational readiness. Travelers' diarrhea is a self-limiting illness; however, antibiotic treatment (with and without use of adjunct loperamide therapy) has been shown to significantly reduce clinical presentation of symptoms and duration of illness. Nonetheless, the choice of first-line antibiotics must be carefully considered as increasing resistance of enteric pathogens in endemic regions has rendered many first-line antibiotics ineffective (e.g., Campylobacter spp. are resistant to fluoroquinolones in Southeast Asia). Presently, there are no standardized recommendations for the treatment of travelers' diarrhea among deployed military personnel. Therefore, an expert panel was convened to develop evidence-based, consensus-driven guidelines that address key clinical issues related to self-treatment, antibiotic treatment for acute watery diarrhea and febrile diarrhea/dysentery, and diagnostics. These guidelines "Management of Acute Diarrheal Illness during Deployment" are published in this supplement along with articles reviewing the evidence-based data that supported their development. [ABSTRACT FROM AUTHOR]

Background. Many studies have found acute gastrointestinal infections to be among the most likely reason for clinic visits among forward deployed soldiers and are considered a significant contributor to morbidity in this population. This occurs despite the controlled food and water distribution systems under which military populations operate. Furthermore, recent studies have indicated that providers often fail to appropriately identify and treat the typical causes of these infections. To adequately address this issue, an assessment of gaps in knowledge, practice, and management of acute diarrhea in deployed troops was conducted. Methods. A multiple-choice survey was developed by clinical researchers with expertise in travelers' diarrhea (TD) and provided to a convenience sample of clinical providers with a broad range of training and operational experience. The survey evaluated provider's knowledge of TD along with their ability to identify etiologies of various syndromic categories of acute gastrointestinal infections. Providers were also queried on selection of treatment approaches to a variety of clinical-based scenarios. Results. A total of 117 respondents completed the survey. Most were aware of the standard definition of TD (77%); however, their knowledge about the epidemiology was lower, with less than 24% correctly answering questions on etiology of diarrhea, and 31% believing that a viral pathogen was the primary cause of watery diarrhea during deployment. Evaluation of scenario-based responses showed that 64% of providers chose not to use antibiotics to treat moderate TD. Furthermore, 19% of providers felt that severe inflammatory diarrhea was best treated with hydration only while 25% felt hydration was the therapy of choice for dysentery. Across all provider types, three practitioner characteristics appeared to be related to better scores on responses to the nine management scenarios: having a Doctor of Medicine or Doctor of Osteopathy degree, greater knowledge of TD epidemiology, and favorable attitudes toward antimotility or antibiotic therapy. Conclusion. Results from this survey support the need for improving knowledge and management of TD among deploying providers. The information from this study should be considered to support the establishment and dissemination of military diarrhea-management guidelines to assist in improving the health of military personnel. [ABSTRACT FROM AUTHOR]

Background. The interferon-γ release assays (IGRAs) are increasingly being used as an alternative to the tuberculin skin test (TST). Although IGRAs may have better specificity and certain logistic advantages to the TST, their use may contribute to overtesting of low-prevalence populations if testing is not targeted. The objective of this study was to evaluate the accuracy of a risk factor questionnaire in predicting a positive test result for latent tuberculosis infection using the 3 commercially available diagnostics. Methods. A cross-sectional comparison study was performed among recruits undergoing Army basic training at Fort Jackson, South Carolina, from April through June 2009. The tests performed included: (1) a risk factor questionnaire; (2) the QuantiFERON Gold In-Tube test (Cellestis Limited, Carnegie, Victoria, Australia); (3) the T-SPOT.TB test (Oxford Immunotec Limited, Abingdon, United Kingdom); and (4) the TST (Sanofi Pasteur Ltd., Toronto, Ontario, Canada). Prediction models used logistic regression to identify factors associated with positive test results. RFQ prediction models were developed independently for each test. Results. Use of a 4-variable model resulted in 79% sensitivity, 92% specificity, and a c statistic of 0.871 in predicting a positive TST result. Targeted testing using these risk factors would reduce testing by >90%. Models predicting IGRA outcomes had similar specificities as the skin test but had lower sensitivities and c statistics. Conclusions. As with the TST, testing with IGRAs will result in false-positive results if the IGRAs are used in low-prevalence populations. Regardless of the test used, targeted testing is critical in reducing unnecessary testing and treatment. [ABSTRACT FROM AUTHOR]

The Infectious Diseases Clinical Research Program (IDCRP) at the Uniformed Services University of the Health Sciences (USU) is a National Institute of Allergy and Infectious Diseases (NIAID)-funded network of military treatment and research facilities coordinated through USU and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF). IDCRP functions in collaboration with the NIAID, universities, and industry to address infectious diseases threats to the U.S. military and to the nation. Although IDCRP has projects in diseases from HIV to tuberculosis, a major focus has been on skin, soft-tissue, and war-related infections. [ABSTRACT FROM AUTHOR]

Skin grafting of traumatic finger amputations and concave raw surfaces poses special problems for skin grafting. In grafting finger amputations, oozing of blood tends to form a film of blood separating the graft from the raw amputation site. In concave raw surfaces, the skin must be made to conform to the concave surface. A technique of secure fixation of the graft allowing for frequent irrigation of the graft affords a better chance for a good skin graft take. [ABSTRACT FROM AUTHOR]

(n = 150) Nonbattle injury (NBI) continues to be a leading cause of morbidity among troops currently deployed to Iraq and Afghanistan. To assess NBI incidence, impact, and risk factors, a survey was given to soldiers during mid- or postdeployment from Iraq, Afghanistan, and surrounding region, from January 2005 through May 2006. Among 3,367 troops completing a survey, 19.5% reported at least one NBI, and 85% sought care at least once for their symptoms. Service component, rank, and unit type were among factors associated with differential NBI risk. Twenty percent stated that NBI resulted in back-up personnel being called or shift change to cover impacted duties, and among those reported having been grounded from flight status, a third were the result of NBI. NBI continues to be a problem in recent deployments, and given the findings on individual and potential operational impact indicators. NBI should be viewed as a primary force health protection problem. [ABSTRACT FROM AUTHOR]

Background. A robust human challenge model for Campylobacter jejuni is an important tool for the evaluation of candidate vaccines. The previously established model conveys a potential risk of Guillain-Barre syndrome attributable to lipooligosaccharide ganglioside mimicry. This work establishes a new C. jejuni human challenge model that uses a strain (CG8421) without ganglioside mimicry and that applies Campylobacter-specific cellular immunity screening to achieve high attack rates at lower inoculum doses. Methods. Healthy Campylobacter-naive adults participated in an open-label challenge trial. Participants were dosed with C. jejuni CG8421 and followed as inpatients. Pattern of illness, bacterial shedding, and immunologic responses were determined. Results. Following screening, 23 subjects received 1×106 or 1×105 colony-forming units of C. jejuni, with attack rates (percentage of patients who became ill) of 100% (1×106 colony-forming units) or 93% (1×105 colony-forming units). Every subject shed CG8421; the median time to diarrhea onset was 72.3 h (interquartile range, 53.9-99.9 h). Symptoms included abdominal cramps (74%), nausea (65%), and fever (39%). No major safety concerns occurred, including bacteremia, hypotension, or postinfectious sequelae. Unexpectedly, recrudescent infection occurred in 2 subjects (1 subject without Campylobacter-specific adaptive immune responses and 1 with azithromycin resistance acquired in vivo); both infections cleared after receipt of additional antibiotics. Cumulative Campylobacter-specific immune responses were as follows: serologic response occurred in 87% (immunoglobulin [Ig] A) and 48% (IgG) of subjects, in vitro interferon-g production occurred in 91% of subjects, and 96% of subjects had IgA antibody-secreting cells and fecal IgA detected. Conclusions. The C. jejuni CG8421 challenge model provides a safe and effective tool, without the risk of Guillain-Barre syndrome. The model demonstrates high attack rates after lower doses of challenge inoculum, provides further understanding of immunologic responses, and permits future investigation of candidate Campylobacter vaccines. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the evolutional changes in disease and nonbattle injury in a long-term deployment setting, we investigated trends of selected disease and nonbattle injury NBI) incidence among US military personnel deployed in ongoing military operations in Southwest Asia and the Middle East. Methods. Participants completed an anonymous questionnaire concerning diarrhea, acute respiratory illness (ARI), and NBIs. We compared incidence, morbidity, and risk associations of disease and NBI incidence with historical data. We analyzed a clinic screening form to describe trends in diarrhea incidence over a 3-year period. Results. Between April 2006 and March 2007, 3374 troops completed deployment questionnaires. Incidence of diarrhea was higher than that of ARI and NBI (12.1, 7.1, and 2.5 episodes per 100 person-months, respectively), but ARI and NBI resulted in more-frequent health system utilization (both P<.001) and de creased work performance (P<.001 and P = .05, respectively) than did diarrhea. Compared with historical disease and NBI incidence rates, diarrhea and NBI incidence declined over a 4-year period, whereas ARI remained relatively constant. Conclusions, Diarrhea, ARI, and NBI are important health concerns among deployed military personnel. Public health and preventive measures are needed to mitigate this burden. {Am J Public Health. 2008;98:2199-2206. doi:10.2105/ AJPH.2007.131680) [ABSTRACT FROM AUTHOR]

Background and Methods: Vector-borne diseases are known threats to deployed troops. We performed a cross-sectional study of troops deployed to Southwest Asia between January 2005 and February 2007 to evaluate practices of personal protective measures and their relationship to self-report of Old World cutaneous leishmaniasis (CL), a marker of vector-borne disease threat. Results: Regular or always N, N-diethyl-m-toluamide (DEET) use was low (2-5%). Associations for DEET use were command emphasis, branch of service, uniform treatment with permethrin, and duty station. Uniform treatment with permethrin was associated with branch of service, command emphasis, and use of DEET. We identified 22 cases of CL (incidence density of 1.8-3.7 per 100 person-years) with increased risk among Reserve/National Guard components, Air Force and Marine personnel. Conclusions: Commanders can influence the use of the military insect repellent system. Unit-based treatment of uniforms improves prevalence. CL incidence may be higher than previously reported. [ABSTRACT FROM AUTHOR]

Summary: Infectious diarrhea is one of the many threats to the deployed military, and given limited resources, a decision to pursue a vaccine acquisition strategy should be based on best evidence that weighs costs and benefits compared to alternatives. An economic model was developed to estimate the marginal cost to avert a duty day lost due to diarrhea for a vaccine acquisition strategy compared to current clinical management, for both multiplex and pathogen-specific vaccines. Vaccines against Campylobacter and enterotoxigenic Escherichia coli appeared to be more favorable than a Shigella vaccine. This model provides an evidence-based decision tool to support prioritization in vaccine development. [Copyright &y& Elsevier]

Rationale, aims and objectives This study is part of a research effort to identify and quantify factors related to the cost-effectiveness of a vaccine acquisition strategy to reduce the burden of infectious diarrhoea on US military personnel deployed overseas. Where evidence is lacking in the scientific literature, or considerable uncertainty exists, it is often necessary to develop best estimates with ranges of certainty. To this end, a modified ‘Delphi’ survey technique to obtain the best estimates for uncertain parameters including clinical care-seeking behaviour for acute diarrhoea, routine diarrhoea management in a deployed setting, and vaccine development time frames and costs were developed from a diverse panel of experts. Methods The study was conducted in three survey iterations. During each iteration, participants were contacted and given 2–3 weeks to complete a web-based survey designed to ascertain estimates, ranges of variability, and level of certainty for these estimates. Results In all, 25 of 43 solicited experts agreed to participate in the study. These included three (12%) experts who identified themselves primarily as being currently involved in Vaccine Industry, six (24%) Academic/Military Diarrheal Vaccine Development, five (20%) Military Product Acquisition, five (20%) Military Preventive Medicine, two (8%) Tropical/Travel Medicine and four (16%) Military Clinical Infectious Disease. Management practices in deployed military populations (for both provider and self-treatment) were consistent with recently published literature. Similar target time frames for vaccine licensure were established for Enterotoxigenic E. coli, Campylobacter, Shigella and Norovirus of around 9–11 years. Targets for vaccine efficacy appear to be lower than currently licensed travel vaccines (60–80%), and there was consensus on more conservative adverse event rates. Conclusions These data should prove useful to researchers and policy makers working in the area of vaccine acquisition for the US military and provide continued information on the gap in optimal travellers’ diarrhoea management practices in a deployed setting. [ABSTRACT FROM AUTHOR]

Background. Traveler's diarrhea in Thailand is frequently caused by Campylobacter jejuni. Rates of fluoroquinolone (FQ) resistance in Campylobacter organisms have exceeded 85% in recent years, and reduced fluoroquinolone efficacy has been observed. Methods. Azithromycin regimens were evaluated in a randomized, double-blind trial of azithromycin, given as a single 1-g dose or a 3-day regimen (500 mg daily), versus a 3-day regimen of levofloxacin (500 mg daily) in military field clinics in Thailand. Outcomes included clinical end points (time to the last unformed stool [TLUS] and cure rates) and microbiological end points (pathogen eradication). Results. A total of 156 patients with acute diarrhea were enrolled in the trial. Campylobacter organisms predominated (in 64% of patients), with levofloxacin resistance noted in 50% of Campylobacter organisms and with no azithromycin resistance noted. The cure rate at 72 h after treatment initiation was highest (96%) with single-dose azithromycin, compared with the cure rates of 85% noted with 3-day azithromycin and 71% noted with levofloxacin (P = .002). Single-dose azithromycin was also associated with the shortest median TLUS (35 h; P = .03, by log-rank test). Levofloxacin's efficacy was inferior to azithromycin's efficacy, except in patients with no pathogen identified during the first 24 h of treatment or in patients with levofloxacin-susceptible Campylobacter isolates, in whom it appeared to be equal to azithromycin. The rate of microbiological eradication was significantly better with azithromycin-based regimens (96%–100%), compared with levofloxacin (38%) (P =.001); however, this finding was poorly correlated with clinical outcome. A higher rate of posttreatment nausea in the 30 min after receipt of the first dose (14% vs. <6%; P = .06) was observed as a mild, self-limited complaint associated with single-dose azithromycin. Conclusions. Single-dose azithromycin is recommended for empirical therapy of traveler's diarrhea acquired in Thailand and is a reasonable first-line option for empirical management in general. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between medical knowledge and clinical practice, a survey on travelers' diarrhea was administered to military health care providers attending a professional development and trauma management conference. The survey was administered at the beginning of the conference and 58 of the 76 attendees participated by completing a questionnaire. Respondents were aware of the standard definition of travelers' diarrhea; however, their knowledge about the epidemiology and management of travelers' diarrhea was low. Less than one-third correctly answered questions on etiology and more than two-thirds made incorrect management choices in treatment of mild to moderate watery diarrhea and dysentery. Important knowledge gaps about gastroenteritis were identified, and should serve as a basis to develop military-specific clinical guidelines and training programs. [ABSTRACT FROM AUTHOR]

Background Among combat injured, invasive fungal infections (IFIs) result in significant morbidity. Cultures and histopathology are the primary diagnostic methods for IFIs, but they have limitations. We previously evaluated a panfungal polymerase chain reaction assay, which was 83% sensitive and 99% specific for angioinvasive IFIs. Here, we evaluated 3 less resource-intensive seminested assays targeting clinically relevant fungi in the order Mucorales and genera Aspergillus and Fusarium. Methods Formalin-fixed paraffin-embedded tissue specimens from a multicenter trauma IFI cohort (2009-2014) were used. Cases were US military personnel injured in Afghanistan with histopathologic IFI evidence. Controls were patients with similar injury patterns and no laboratory IFI evidence (negative culture and histopathology). Seminested assays specific to Mucorales (V4/V5 regions of 18S rDNA), Aspergillus (mitochondrial tRNA), and Fusarium (internal transcribed spacer [ITS]/28A regions of DNA) were compared with a panfungal assay amplifying the internal transcribed spacer 2 region of rDNA and to histopathology. Results Specimens from 92 injury sites (62 subjects) were compared with control specimens from 117 injuries (101 subjects). We observed substantial agreement between the seminested and panfungal assays overall, especially for the order Mucorales. Moderate agreement was observed at the genus level for Aspergillus and Fusarium. When compared with histopathology, sensitivity and specificity of seminested assays were 67.4% and 96.6%, respectively (sensitivity increased to 91.7% when restricted to sites with angioinvasion). Conclusions Prior studies of seminested molecular diagnostics have focused on culture-negative samples from immunocompromised patients. Our findings underscore the utility of the seminested approach in diagnosing soft-tissue IFIs using formalin-fixed paraffin-embedded tissue samples, especially with angioinvasion. [ABSTRACT FROM AUTHOR]

Introduction Battlefield-related wound infections are a significant source of morbidity among combat casualties. Seasonality of these infections was demonstrated in previous conflicts (e.g. Korea) but has not been described with trauma-related health care–associated infections from the war in Afghanistan. Methods The study population included military personnel wounded in Afghanistan (2009-2014) medevac'd to Landstuhl Regional Medical Center and transitioned to participating military hospitals in the United States with clinical suspicion of wound infections and wound cultures collected ≤7 days post-injury. Analysis was limited to the first wound culture from individuals. Infecting isolates were collected from skin and soft-tissue infections, osteomyelitis, and burn soft-tissue infections. Data were analyzed by season (winter [ December 1-February 28/29], spring [March 1-May 31], summer [June 1-August 31], and fall [September 1-November 30]). Results Among 316 patients, 297 (94.0%) sustained blast injuries with a median injury severity score and days from injury to initial culture of 33 and 3.5, respectively. Although all patients had a clinical suspicion of a wound infection, a diagnosis was confirmed in 198 (63%) patients. Gram-negative bacilli (59.5% of 316) were more commonly isolated from wound cultures in summer (68.1%) and fall (67.1%) versus winter (43.9%) and spring (45.1%; P  < .001). Multidrug-resistant (MDR) Gram-negative bacilli (21.8%) were more common in summer (21.8%) and fall (30.6%) versus winter (7.3%) and spring (19.7%; P  = .028). Findings were similar for infecting Gram-negative bacilli (72.7% of 198)—summer (79.5%) and fall (83.6%; P  = .001)—and infecting MDR Gram-negative bacilli (27.3% of 198)—summer (25.6%) and fall (41.8%; P  = .015). Infecting anaerobes were more common in winter (40%) compared to fall (11%; P  = .036). Gram-positive organisms were not significantly different by season. Conclusion Gram-negative bacilli, including infecting MDR Gram-negative bacilli, were more commonly recovered in summer/fall months from service members injured in Afghanistan. This may have implications for empiric antibiotic coverage during these months. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) commonly cause diarrhea in children living in developing countries and in travelers to those regions. ETEC are characterized by colonization factors (CFs) that mediate intestinal adherence. We assessed if bovine colostral IgG (bIgG) antibodies against a CF, CS17, or antibodies against CsbD, the minor tip subunit of CS17, would protect subjects against diarrhea following challenge with a CS17-expressing ETEC strain.Methods: Adult subjects were randomized (1:1:1) to receive oral bIgG against CS17, CsbD, or placebo. Two days prior to challenge, subjects began dosing 3 times daily with the bIgG products (or placebo). On day 3, subjects ingested 5 × 109 cfu ETEC strain LSN03-016011/A in buffer. Subjects were assessed for diarrhea for 120 hours postchallenge.Results: A total of 36 subjects began oral prophylaxis and 35 were challenged with ETEC. While 50.0% of the placebo recipients had watery diarrhea, none of the subjects receiving anti-CS17 had diarrhea (P = .01). In contrast, diarrhea rates between placebo and anti-CsbD recipients (41.7%) were comparable (P = 1.0).Conclusions: This is the first study to demonstrate anti-CS17 antibodies provide significant protection against ETEC expressing CS17. More research is needed to better understand why anti-CsbD was not comparably efficacious. Clinical Trials Registration. NCT00524004. [ABSTRACT FROM AUTHOR]

Background We evaluated the impact of infectious disease (ID) syndromes on US active duty (AD) servicemembers returning from overseas deployment (DEP), military training exercises (EXR), or short-term military travel (eg, temporary assignment of duty [TDY]). Methods We conducted a survey-based assessment of US AD servicemembers returning from DEP, EXR, or TDY between 2015 and 2019. Subjects completed a post-travel survey capturing symptoms of travelers' diarrhea (TD), influenza-like illness (ILI), and febrile illness (FI). Risk factors associated with any ID syndrome (ie, either TD, ILI, or FI) that impacted daily activities were assessed using a logistic regression model with backward selection. Results One-third of servicemembers (654/1822) experienced an ID syndrome, and 26% (471/1822) reported a ≥50% reduction in activity level due to an ID syndrome (median duration, 3 days). TD was the most common ID syndrome experienced and accounted for 73% (346/471) of ID syndromes impacting daily activities. The greatest impact of ID syndromes was observed in servicemembers on DEP. Compared with servicemembers on EXR or TDY, those on DEP had a longer duration of travel and a delayed period of risk for ID syndromes. Multivariate analysis identified high-risk exposures (ie, environmental exposures, close contact with locals, consuming food from street vendors) and behaviors (ie, inability to sanitize hands before meals) that could be used to inform mitigation strategies. Conclusions ID syndromes result in a significant loss of productivity during military travel. Addressing modifiable risk factors and access to TD self-treatment in high-risk settings may help mitigate the impact of ID threats during military travel. [ABSTRACT FROM AUTHOR]

Enterobacter cloacae is a Gram-negative rod with multidrug-resistant potential due to chromosomally-induced AmpC β-lactamase. We evaluated characteristics, antibiotic utilization, and outcomes associated with battlefield-related E. cloacae infections (2009–2014). Single initial and serial E. cloacae isolates (≥24 hours from initial isolate from any site) associated with a clinical infection were examined. Susceptibility profiles of initial isolates in the serial isolation group were contrasted against last isolate recovered. Characteristics of 112 patients with E. cloacae infections (63 [56%] with single initial isolation; 49 [44%] with serial isolation) were compared to 509 patients with bacterial infections not attributed to E. cloacae. E. cloacae patients sustained more blast trauma (78%) compared to non-E. cloacae infections patients (75%; p<0.001); however, injury severity scores were comparable (median of 34.5 and 33, respectively; p = 0.334). Patients with E. cloacae infections had greater shock indices (median 1.07 vs 0.92; p = 0.005) and required more initial blood products (15 vs. 14 units; p = 0.032) compared to patients with non-E. cloacae infections. Although E. cloacae patients had less intensive care unit admissions (80% vs. 90% with non-E. cloacae infection patients; p = 0.007), they did have more operating room visits (5 vs. 4; p = 0.001), longer duration of antibiotic therapy (43.5 vs. 34 days; p<0.001), and lengthier hospitalizations (57 vs. 44 days; p<0.001). Patients with serial E. cloacae had isolation of infecting isolates sooner than patients with single initial E. cloacae (median of 5 vs. 8 days post-injury; p = 0.046); however, outcomes were not significantly different between the groups. Statistically significant resistance to individual antibiotics did not develop between initial and last isolates in the serial isolation group. Despite current combat care and surgical prophylaxis guidelines recommending upfront provision of AmpC-inducing antibiotics, clinical outcomes did not differ nor did significant antibiotic resistance develop in patients who experienced serial isolation of E. cloacae versus single initial isolation. [ABSTRACT FROM AUTHOR]

Background and Aim: Mental and physical health-related quality of life (HRQOL) are important health impact measures following military deployment. While conditions such as post-traumatic stress disorder (PTSD) are known to adversely affect QOL, little is known about the effect of post-infectious functional gastrointestinal disorders (PI-FGID). Our aim was to evaluate the risk of PI-FGID and its impact on HRQOL among military personnel returning from deployment.Methods: A cross-sectional cohort of active-duty military deployed to Egypt or Turkey between 2004 and 2005 was asked to complete a questionnaire (Rome II and SF-36 instruments) on travelers' diarrhea (TD) during deployment and FGID symptoms and HRQOL 6 months after returning from deployment.Results: A total of 121 military personnel returning from Egypt (n = 33) and Turkey (n = 88) completed the post-deployment questionnaire. Nearly half (48.3%) met the definition for an FGID at the time of the survey, and 53% of individuals reporting one or more episodes of TD during deployment developed an FGID, compared to 33% of those not reporting TD (odds ratio [OR] 2.2, P = 0.08). Compared to those not meeting the FGID criteria, those with post-deployment FGID had lower mean mental HRQOL scores (-13.4%, P < 0.0001) and lower physical HRQOL scores (-7.2%, P = 0.004).Conclusions: There was a high prevalence of FGID symptoms in military personnel returning from deployment, and TD was a noted risk factor. FGID and symptoms decreased QOL, with mental HRQOL being affected more than physical HRQOL. These findings require further research in order to assess the long-term impact of these and other post-infectious sequela related to TD during deployments among returning veterans. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the letter on the treatment of traveler's diarrhea published in June 2007 issue.

Background: Tip-localized adhesive proteins of bacterial fimbriae from diverse pathogens confer protection in animal models, but efficacy in humans has not been reported. Enterotoxigenic Escherichia coli (ETEC) commonly elaborate colonization factors comprising a minor tip adhesin and major stalk-forming subunit. We assessed the efficacy of antiadhesin bovine colostral IgG (bIgG) antibodies against ETEC challenge in volunteers.Methods: Adults were randomly assigned (1:1:1) to take oral hyperimmune bIgG raised against CFA/I minor pilin subunit (CfaE) tip adhesin or colonization factor I (CFA/I) fimbraie (positive control) or placebo. Two days before challenge, volunteers began a thrice-daily, 7-day course of investigational product administered in sodium bicarbonate 15 minutes after each meal. On day 3, subjects drank 1 × 109 colony-forming units of colonization factor I (CFA/I)-ETEC strain H10407 with buffer. The primary efficacy endpoint was diarrhea within 120 hours of challenge.Results: After enrollment and randomization, 31 volunteers received product, underwent ETEC challenge, and were included in the per protocol efficacy analysis. Nine of 11 placebos developed diarrhea, 7 experiencing moderate to severe disease. Protective efficacy of 63% (P = .03) and 88% (P = .002) was observed in the antiadhesin bIgG and positive control groups, respectively.Conclusions: Oral administration of anti-CFA/I minor pilin subunit (CfaE) antibodies conferred significant protection against ETEC, providing the first clinical evidence that fimbrial tip adhesins function as protective antigens. [ABSTRACT FROM AUTHOR]

Background: Infection is a frequent and serious complication after combat-related trauma. The Sequential Organ Failure Assessment (SOFA) score has been shown to have predictive value for outcomes, including sepsis and mortality, among various populations. We evaluated the prognostic ability of SOFA score in a combat-related trauma population. Methods: Combat casualties (2009-2014) admitted to Landstuhl Regional Medical Center (LRMC; Germany) intensive care unit (ICU) within 4 days post-injury followed by transition to ICUs in military hospitals in the United States were included. Multivariate logistic regression was used to determine predictive effect of selected variables and receiver operating characteristic (ROC) curve analysis was used to evaluate overall accuracy of SOFA score for infection prediction. Results: Of the 748 patients who met inclusion criteria, 436 (58%) were diagnosed with an infection (32% bloodstream, 63% skin and soft tissue, and 40% pulmonary) and were predominantly young (median 24 years) males. Penetrating trauma accounted for 95% and 86% of injuries among those with and without infections, respectively (p < 0.001). Median LRMC admission SOFA score was 7 (interquartile range [IQR]: 4-9) in patients with infections versus 4 (IQR: 2-6) in patients without infections (p < 0.001). Thirty-day mortality was 2% in both groups. On multivariate regression, LRMC SOFA score was independently associated with infection development (odds ratio: 1.2; 95% confidence interval: 1.1-1.3). The ROC curve analysis revealed an area under the curve of 0.69 for infection prediction, and 0.80 for mortality prediction. Conclusions: The SOFA scores obtained up to 4 days post-injury predict late onset infection occurrence. This study revealed that for every 1 point increase in LRMC SOFA score, the odds of having an infection increases by a factor of 1.2, controlling for other predictors. The use of SOFA score in admission assessments may assist clinicians with identifying those at higher risk of infection following combat-related trauma. [ABSTRACT FROM AUTHOR]

Background: There is limited information on compliance rates with anti-vectorial protective measures (AVPMs) during travel to countries with risk of dengue and chikungunya. We evaluated differences in mosquito exposures, and factors associated with AVPM compliance in travellers going to countries where the principal mosquito-borne infectious disease threat is falciparum malaria and those where risk of dengue or chikungunya predominates.Methods: Department of Defence beneficiaries with planned travel to regions where the predominant mosquito-borne infection is falciparum malaria, and those with predominantly dengue or chikungunya risk, were included. Regions were divided into three groups: 'high-risk falciparum malaria', 'low-risk falciparum malaria' and 'chikungunya/dengue risk'. Demographics, trip characteristics, arthropod exposure and AVPM compliance were captured using pre- and post-travel surveys. Skin repellent compliance was defined as self-reported use, categorized as 'often/every day'. A logistic regression model was used to estimate factors associated with AVPM compliance.Results: 183 (9%), 185 (9%) and 149 (7%) travelled to high and low falciparum malaria risk regions, and chikungunya/dengue risk regions, respectively. Overall, 53% (95% CI: 48-57%) and 16% (95% CI: 12-19%) were compliant with repellent use on skin and clothing, respectively. Daytime bites were reported more frequently in chikungunya/dengue risk regions than high malaria risk regions (37% vs. 10%), while night time bites were frequently in high malaria risk regions (53% vs 20%; P < 0.001). Compliance with skin repellents was associated with female gender [RR: 1.54 (95% CI: 1.05-2.28)], observing mosquitoes during travel [RR: 2.77 (95% CI: 1.76-4.36)] and travel during the rainy season [RR: 2.45 (95% CI: 1.66-3.71)]).Conclusions: Poor AVPM compliance was observed in the overall cohort. Compliance with skin repellent use was associated with female gender, observing mosquitoes and travelling during the rainy season, and was not associated with the risk of malaria or chikungunya/dengue at the travel destination. [ABSTRACT FROM AUTHOR]

The human microbiome is comprised of a complex and diverse community of organisms that is subject to dynamic changes over time. As such, cross-sectional studies of the microbiome provide a multitude of information for a specific body site at a particular time, but they fail to account for temporal changes in microbial constituents resulting from various factors. To address this shortcoming, longitudinal research studies of the human microbiome investigate the influence of various factors on the microbiome of individuals within a group or community setting. These studies are vital to address the effects of host and/or environmental factors on microbiome composition as well as the potential contribution of microbiome members during the course of an infection. The relationship between microbial constituents and disease development has been previously explored for skin and soft tissue infections (SSTIs) within congregate military trainees. Accordingly, approximately 25% of the population carries Staphylococcus aureus within their nasal cavity, and these colonized individuals are known to be at increased risk for SSTIs. To examine the evolution of the nasal microbiota of U.S. Army Infantry trainees, individuals were sampled longitudinally from their arrival at Fort Benning, Georgia, until completion of their training 90 days later. These samples were then processed to determine S. aureus colonization status and to profile the nasal microbiota using 16S rRNA gene-based methods. Microbiota stability differed dramatically among the individual trainees; some subjects exhibited great stability, some subjects showed gradual temporal changes and some subjects displayed a dramatic shift in nasal microbiota composition. Further analysis utilizing the available trainee metadata suggests that the major drivers of nasal microbiota stability may be S. aureus colonization status and geographic origin of the trainees. Nasal microbiota evolution within the congregate setting imposed by military training is a complex process that appears to be affected by numerous factors. This finding may indicate that future campaigns to prevent S. aureus colonization and future SSTIs among high-risk military trainees may require a 'personalized' approach. [ABSTRACT FROM AUTHOR]

Background: In the aftermath of wars, there is a surge in the number of wounded service members who leave active duty and become eligible for healthcare through the Department of Veterans Affairs (VA). Collaborations between the Department of Defense (DoD) and VA are crucial to capture comprehensive data and further understand the long-term impact of battlefield trauma. We provide a summary of the development, methodology, and status of an effective collaboration between the Infectious Disease Clinical Research Program and the St. Louis VA Health Care System with the multicenter, observational Trauma Infectious Disease Outcomes Study (TIDOS), which examines the short- and long-term outcomes of deployment-related trauma.Methods: As part of TIDOS, wounded service members who transitioned to participating military hospitals in the United States (2009-2014) were given the opportunity to enroll in a prospective follow-up cohort study to continue to capture infection-related data after their hospital discharge. Enrollees in the TIDOS cohort who left military service and received health care through the VA also had the option of consenting to have relevant VA medical records abstracted and included with the study data. Infections considered to be complications resulting from the initial trauma were examined.Results: Among 1,336 TIDOS enrollees, 1,221 (91%) registered and received health care through the VA with 633 (47%) consenting to follow-up using VA records and comprising the TIDOS-VA cohort. Of the first 337 TIDOS-VA cohort enrollees, 38% were diagnosed with a new trauma-related infection following hospital discharge (median: 88 days; interquartile range: 18-351 days). Approximately 71% of the infections were identified through DoD sources (medical records and follow-up) and 29% were identified through VA electronic medical records, demonstrating the utility of DoD-VA collaborations. The TIDOS DoD-VA collaboration has also been utilized to assess intermediate and long-term consequences of specific injury patterns. Among 89 TIDOS-VA cohort enrollees with genitourinary trauma, 36% reported sexual dysfunction, 21% developed at least one urinary tract infection, 14% had urinary retention/incontinence, and 8% had urethral stricture. The rate of urinary tract infections was 0.05/patient-year during DoD follow-up time and 0.07/patient-year during VA follow-up time.Conclusions: Wider capture of infection-related outcome data through the DoD-VA collaboration provided a clearer picture of the long-term infection burden resulting from deployment-related trauma. Planned analyses include assessment of osteomyelitis among combat casualties with amputations and/or open fractures, evaluation of mental health and social factors related to injury patterns, and examination of health care utilization and cost in relation to infectious disease burdens. [ABSTRACT FROM AUTHOR]

Introduction: During Operation Enduring Freedom in Afghanistan, an outbreak of combat-related invasive fungal wound infections (IFIs) emerged among casualties with dismounted blast trauma and became a priority issue for the Military Health System.Methods: In 2011, the Trauma Infectious Disease Outcomes Study (TIDOS) team led the Department of Defense IFI outbreak investigation to describe characteristics of IFIs among combat casualties and provide recommendations related to management of the disease. To support the outbreak investigation, existing IFI definitions and classifications utilized for immunocompromised patients were modified for use in epidemiologic research in a trauma population. Following the conclusion of the outbreak investigation, multiple retrospective analyses using a population of 77 IFI patients (injured during June 2009 to August 2011) were conducted to evaluate IFI epidemiology, wound microbiology, and diagnostics to support refinement of Joint Trauma System (JTS) clinical practice guidelines. Following cessation of combat operations in Afghanistan, the TIDOS database was comprehensively reviewed to identify patients with laboratory evidence of a fungal infection and refine the IFI classification scheme to incorporate timing of laboratory fungal evidence and include categories that denote a high or low level of suspicion for IFI. The refined IFI classification scheme was utilized in a large-scale epidemiologic assessment of casualties injured over a 5.5-year period.Results: Among 720 combat casualties admitted to participating hospitals (2009-2014) who had histopathology and/or wound cultures collected, 94 (13%) met criteria for an IFI and 61 (8%) were classified as high suspicion of IFI. Risk factors for development of combat-related IFIs include sustaining a dismounted blast injury, experiencing a traumatic transfemoral amputation, and requiring resuscitation with large-volume (>20 units) blood transfusions. Moreover, TIDOS analyses demonstrated the adverse impact of IFIs on wound healing, particularly with order Mucorales. A polymerase chain reaction (PCR)-based assay to identify filamentous fungi and support earlier IFI diagnosis was also assessed using archived formalin-fixed, paraffin-embedded tissue specimens. Although the PCR-based assay had high specificity (99%), there was low sensitivity (63%); however, sensitivity improved to 83% in tissues collected from sites with angioinvasion. Data obtained from the initial IFI outbreak investigation (37 IFI patients) and subsequent TIDOS analyses (77 IFI patients) supported development and refinement of a JTS clinical practice guideline for the management of IFIs in war wounds. Furthermore, a local clinical practice guideline to screen for early tissue-based evidence of IFIs among blast casualties at the Landstuhl Regional Medical Center was critically evaluated through a TIDOS investigation, providing additional clinical practice support. Through a collaboration with the Uniformed Services University Surgical Critical Care Initiative, findings from TIDOS analyses were used to support development of a clinical decision support tool to facilitate early risk stratification.Conclusions: Combat-related IFIs are a highly morbid complication following severe blast trauma and remain a threat for future modern warfare. Our findings have supported JTS clinical recommendations, refined IFI classification, and confirmed the utility of PCR-based assays as a complement to histopathology and/or culture to promote early diagnosis. Analyses underway or planned will add to the knowledge base of IFI epidemiology, diagnostics, prevention, and management. [ABSTRACT FROM AUTHOR]

Introduction: During the wars in Iraq and Afghanistan, increased incidence of multidrug-resistant (MDR) organisms, as well as polymicrobial wounds and infections, complicated the management of combat trauma-related infections. Multidrug resistance and wound microbiology are a research focus of the Trauma Infectious Disease Outcomes Study (TIDOS), an Infectious Disease Clinical Research Program, Uniformed Services University, research protocol. To conduct comprehensive microbiological research with the goal of improving the understanding of the complicated etiology of wound infections, the TIDOS MDR and Virulent Organisms Trauma Infections Initiative (MDR/VO Initiative) was established as a collaborative effort with the Brooke Army Medical Center, Naval Medical Research Center, U.S. Army Institute of Surgical Research, and Walter Reed Army Institute of Research. We provide a review of the TIDOS MDR/VO Initiative and summarize published findings.Methods: Antagonism and biofilm formation of commonly isolated wound bacteria (e.g., ESKAPE pathogens-Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), antimicrobial susceptibility patterns, and clinical outcomes are being examined. Isolates collected from admission surveillance swabs, as part of infection control policy, and clinical infection workups were retained in the TIDOS Microbiological Repository and associated clinical data in the TIDOS database.Results: Over the TIDOS study period (June 2009 to December 2014), more than 8,300 colonizing and infecting isolates were collected from military personnel injured with nearly one-third of isolates classified as MDR. At admission to participating U.S. military hospitals, 12% of wounded warriors were colonized with MDR Gram-negative bacilli. Furthermore, 27% of 913 combat casualties with ≥1 infection during their trauma hospitalization had MDR Gram-negative bacterial infections. Among 335 confirmed combat-related extremity wound infections (2009-2012), 61% were polymicrobial and comprised various combinations of Gram-negative and Gram-positive bacteria, yeast, fungi, and anaerobes. Escherichia coli was the most common Gram-negative bacilli isolated from clinical workups, as well as the most common colonizing MDR secondary to extended-spectrum β-lactamase resistance. Assessment of 479 E. coli isolates collected from wounded warriors found 188 pulsed-field types (PFTs) from colonizing isolates and 54 PFTs from infecting isolates without significant overlap across combat theaters, military hospitals, and study years. A minority of patients with colonizing E. coli isolates developed subsequent infections with the same E. coli strain. Enterococcus spp. were most commonly isolated from polymicrobial wound infections (53% of 204 polymicrobial cultures). Patients with Enterococcus infections were severely injured with a high proportion of lower extremity amputations and genitourinary injuries. Approximately 65% of polymicrobial Enterococcus infections had other ESKAPE organisms isolated. As biofilms have been suggested as a cause of delayed wound healing, wound infections with persistent recovery of bacteria (isolates of same organism collected ≥14 days apart) and nonrecurrent bacterial isolates were assessed. Biofilm production was significantly associated with recurrent bacteria isolation (97% vs. 59% with nonrecurrent isolates; P < 0.001); however, further analysis is needed to confirm biofilm formation as a predictor of persistent wound infections.Conclusions: The TIDOS MDR/VO Initiative provides comprehensive and detailed data of major microbial threats associated with combat-related wound infections to further the understanding of wound etiology and potentially identify infectious disease countermeasures, which may lead to improvements in combat casualty care. [ABSTRACT FROM AUTHOR]

Introduction: Extremity trauma is the most common battlefield injury, resulting in a high frequency of combat-related extremity wound infections (CEWIs). As these infections are associated with substantial morbidity and may impact wounded warriors long after initial hospitalization, CEWIs have been a focus of the Infectious Disease Clinical Research Program (IDCRP). Herein, we review findings of CEWI research conducted through the IDCRP and discuss future and ongoing analyses.Methods: Military personnel with deployment-related trauma sustained between 2009 and 2014 were examined in retrospective analyses through the observational Trauma Infectious Disease Outcomes Study (TIDOS). Characteristics of wounded warriors with ≥1 open extremity wound were assessed, focusing on injury patterns and infection risk factors. Through a separate trauma-associated osteomyelitis study, military personnel with combat-related open fractures of the long bones (tibia, femur, and upper extremity) sustained between 2003 and 2009 were examined to identify osteomyelitis risk factors.Results: Among 1,271 wounded warriors with ≥1 open extremity wound, 16% were diagnosed with a CEWI. When assessed by their most severe extremity injury (i.e., amputation, open fracture, or open soft-tissue wound), patients with amputations had the highest proportion of infections (47% of 212 patients with traumatic amputations). Factors related to injury pattern, mechanism, and severity were independent predictors of CEWIs during initial hospitalization. Having a non-extremity infection at least 4 days before CEWI diagnosis was associated with reduced likelihood of CEWI development. After hospital discharge, 28% of patients with extremity trauma had a new or recurrent CEWI during follow-up. Risk factors for the development of CEWIs during follow-up included injury pattern, having either a CEWI or other infection during initial hospitalization, and receipt of antipseudomonal penicillin for ≥7 days. A reduced likelihood for CEWIs during follow-up was associated with a hospitalization duration of 15-30 days. Under the retrospective osteomyelitis risk factor analysis, patients developing osteomyelitis had higher open fracture severity based on Gustilo-Anderson (GA) and the Orthopaedic Trauma Association classification schemes and more frequent traumatic amputations compared to open fracture patients without osteomyelitis. Recurrence of osteomyelitis was also common (28% of patients with open tibia fractures had a recurrent episode). Although osteomyelitis risk factors differed between the tibia, femur, and upper extremity groups, sustaining an amputation, use of antibiotic beads, and being injured in the earlier years of the study (before significant practice pattern changes) were consistent predictors. Other risk factors included GA fracture severity ≥IIIb, blast injuries, foreign body at fracture site (with/without orthopedic implant), moderate/severe muscle damage and/or necrosis, and moderate/severe skin/soft-tissue damage. For upper extremity open fractures, initial stabilization following evacuation from the combat zone was associated with a reduced likelihood of osteomyelitis.Conclusions: Forthcoming studies will examine the effectiveness of common antibiotic regimens for managing extremity deep soft-tissue infections to improve clinical outcomes of combat casualties and support development of clinical practice guidelines for CEWI treatment. The long-term impact of extremity trauma and resultant infections will be further investigated through both Department of Defense and Veterans Affairs follow-up, as well as examination of the impact on comorbidities and mental health/social factors. [ABSTRACT FROM AUTHOR]

The author reflects on an article published within the issue of the journal on the results of a phase 3 randomized double-blind placebo-controlled trial evaluating a non-absorbable antibiotic Rifamycin SV targeting the delivery of the antibiotic to the distal small bowel and colon. He notes the identification of the potential safety issues with systemic antibiotics and the need for novel antibiotics in travelers' diarrhea (TD) management. He also concludes the effectiveness of Rifamycin SV.

Campylobacter jejuni is a leading cause of human gastroenteritis worldwide; however, our understanding of the human immune response to C. jejuni infection is limited. A previous human challenge model has shown that C. jejuni elicits IFNγ production by peripheral blood mononuclear cells, a response associated with protection from clinical disease following re-infection. In this study, we investigate T lymphocyte profiles associated with campylobacteriosis using specimens from a new human challenge model in which C. jejuni-naïve subjects were challenged and re-challenged with C. jejuni CG8421. Multiparameter flow cytometry was used to investigate T lymphocytes as a source of cytokines, including IFNγ, and to identify cytokine patterns associated with either campylobacteriosis or protection from disease. Unexpectedly, all but one subject evaluated re-experienced campylobacteriosis after re-challenge. We show that CD4+ T cells make IFNγ and other pro-inflammatory cytokines in response to infection; however, multifunctional cytokine response patterns were not found. Cytokine production from peripheral CD4+ T cells was not enhanced following re-challenge, which may suggest deletion or tolerance. Evaluation of alternative paradigms or models is needed to better understand the immune components of protection from campylobacteriosis. [ABSTRACT FROM AUTHOR]