Background: Infectious gastroenteritis (IGE) is caused by numerous bacterial, viral, and parasitic pathogens. A history of IGE has been shown in previous studies to increase the risk of developing chronic gastrointestinal disorders and other chronic conditions. As bacteria and viruses represent the majority of pathogen-specific causes of IGE, post-infectious studies have primarily focused on these organisms. The objective of this study was to investigate an association between a history of parasite-associated IGE and the subsequent development of chronic post-infectious gastrointestinal and non-gastrointestinal disorders in a military population.
Abstract Background Clostridium difficile associated disease (CDAD) has risen in incidence and the experience in the US military has not been described. Methods We evaluated the U.S. military's database and identified CDAD cases and demographic characteristics among affected military personnel from 1998 to 2010. Results 2,423 cases were identified. CDAD incidence was 13.2 cases (95% CI: 12.7-13.7) per 100 K p-yr and increased over study years. CA-CDAD and HA-CDAD incidence was 5.5 (95% CI: 5.2, 5.9) per 100 K p-y and 1.3 (95% CI: 1.2, 1.4) per 1,000 hospitalizations respectively. Females comprised a larger proportion of CA-CDAD than HA-CDAD (25.5% vs. 19.3%; p < 0.001) cases as did Air Force service (29% vs. 23.4%; p < 0.01). On multivariate analysis female gender, Coast Guard or Air Force service, and a married status was associated with CA-CDAD whereas Male gender and Marine Corps service were associated with HA-CDAD cases. Conclusions CDAD has increased among military personnel, with female cases more likely to be community associated. Gender, marital status and branch of service had the strongest association with CDAD subtype. Further work is needed to evaluate the epidemiologic factors that have led to these increased rates in otherwise low-risk populations and associated sequelae.
Objectives The aim of this study was to assess the risk of incident rheumatological diagnoses (RD) associated with self-reported diarrhoea and vomiting during a first-time deployment to Iraq or Afghanistan. Such an association would provide evidence that RD in this population may include individuals with reactive arthritis (ReA) from deployment-related infectious gastroenteritis. Design This case–control epidemiological study used univariate and multivariate logistic regression to compare the odds of self-reported diarrhoea/vomiting among deployed US military personnel with incident RD to the odds of diarrhoea/vomiting among a control population. Setting We analysed health records of personnel deployed to Iraq or Afghanistan, including responses on a postdeployment health assessment and medical follow-up postdeployment. Participants Anonymous data were obtained from 891 US military personnel with at least 6 months of medical follow-up following a first-time deployment to Iraq or Afghanistan in 2008–2009. Cases were defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes; controls had an unrelated medical encounter and were representative of the study population. Main outcome measures The primary measure was an association between incident RD and self-reported diarrhoea/vomiting during deployment. A secondary measure was the overall incidence of RD in this population. Results We identified 98 cases of new onset RD, with a total incidence of 161/100 000 persons. Of those, two participants had been diagnosed with Reiter's diseasei (3.3/100 000 persons) and the remainder with non-specific arthritis/arthralgia (157.5/100 000 persons). The OR for acute diarrhoea was 2.67 (p=0.03) after adjusting for important covariates. Conclusions Incident rheumatological conditions, even those classified as 'non-specific,' are significantly associated with prior severe diarrhoea in previously deployed military personnel, potentially indicating ReA and need for ...
ObjectivesThe aim of this study was to assess the risk of incident rheumatological diagnoses (RD) associated with self-reported diarrhoea and vomiting during a first-time deployment to Iraq or Afghanistan. Such an association would provide evidence that RD in this population may include individuals with reactive arthritis (ReA) from deployment-related infectious gastroenteritis.DesignThis case-control epidemiological study used univariate and multivariate logistic regression to compare the odds of self-reported diarrhoea/vomiting among deployed US military personnel with incident RD to the odds of diarrhoea/vomiting among a control population.SettingWe analysed health records of personnel deployed to Iraq or Afghanistan, including responses on a postdeployment health assessment and medical follow-up postdeployment.ParticipantsAnonymous data were obtained from 891 US military personnel with at least 6 months of medical follow-up following a first-time deployment to Iraq or Afghanistan in 2008-2009. Cases were defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes; controls had an unrelated medical encounter and were representative of the study population.Main outcome measuresThe primary measure was an association between incident RD and self-reported diarrhoea/vomiting during deployment. A secondary measure was the overall incidence of RD in this population.ResultsWe identified 98 cases of new onset RD, with a total incidence of 161/100 000 persons. Of those, two participants had been diagnosed with Reiter's disease (i) (3.3/100 000 persons) and the remainder with non-specific arthritis/arthralgia (157.5/100 000 persons). The OR for acute diarrhoea was 2.67 (p=0.03) after adjusting for important covariates.ConclusionsIncident rheumatological conditions, even those classified as 'non-specific,' are significantly associated with prior severe diarrhoea in previously deployed military personnel, potentially indicating ReA and need for preventive measures to reduce diarrhoeagenic bacterial exposures in military personnel and other travellers to the developing regions.
Abstract Background Reactive arthritis (ReA) is a recognized sequela of infectious gastroenteritis (IGE). However, the population-based incidence of IGE-related ReA is poorly defined, and the risk of disease has not previously been characterized in a military population. The intent of this study was to provide estimates of the incidence and morbidity associated with IGE-related ReA in the U.S. military population. Methods Using active duty US military medical encounter data from the Defense Medical Surveillance System, we conducted a matched case-control study to assess the risk of ReA following IGE. Both specific and nonspecific case definitions were utilized to address ICD-9 coding limitations; these included specific ReA (Reiter's Disease or postdysenteric arthritis) and nonspecific arthritis/arthralgia (N.A.A) (which included several related arthropathy and arthralgia diagnoses). Incidence was estimated using events and the total number of active duty personnel for each year. Results 506 cases of specific ReA were identified in active duty personnel between 1999 and 2007. Another 16,365 cases of N.A.A. were identified. Overall incidence was 4.1 (95% CI: 3.7, 4.5) and 132.0 (95% CI, 130.0-134.0) per 100,000 for specific ReA and N.A.A, respectively. Compared to the youngest age category, the incidence of both outcomes increased 7-fold with a concurrent increase in symptom duration for cases over the age of 40. Specific IGE exposures were documented in 1.4% of subjects. After adjusting for potential confounders, there was a significant association between IGE and ReA (specific reactive arthritis OR: 4.42, 95% CI: 2.24, 8.73; N.A.A OR: 1.76, 95% CI: 1.49, 2.07). Conclusions Reactive arthritis may be more common in military populations than previously described. The burden of ReA and strong association with antecedent IGE warrants continued IGE prevention efforts.
Background The US CDC estimates over 2 million foodborne illnesses are annually caused by 4 major enteropathogens: non-typhoid Salmonella spp., Campylobacter spp., Shigella spp. and Yersinia enterocoltica. While data suggest a number of costly and morbid chronic sequelae associated with these infections, pathogen-specific risk estimates are lacking. We utilized a US Department of Defense medical encounter database to evaluate the risk of several gastrointestinal disorders following select foodborne infections. Methods We identified subjects with acute gastroenteritis between 1998 to 2009 attributed to Salmonella(nontyphoidal) spp., Shigella spp., Campylobacter spp. or Yersinia enterocolitica and matched each with up to 4 unexposed subjects. Medical history was analyzed for the duration of military service time (or a minimum of 1 year) to assess for incident chronic gastrointestinal disorders. Relative risks were calculated using modified Poisson regression while controlling for the effect of covariates. Results A total of 1,753 pathogen-specific gastroenteritis cases (Campylobacter: 738, Salmonella: 624,Shigella: 376, Yersinia: 17) were identified and followed for a median of 3.8 years. The incidence (per 100,000 person-years) of PI sequelae among exposed was as follows: irritable bowel syndrome (IBS), 3.0; dyspepsia, 1.8; constipation, 3.9; gastroesophageal reflux disease (GERD), 9.7. In multivariate analyses, we found pathogen-specific increased risk of IBS, dyspepsia, constipation and GERD. Conclusions These data confirm previous studies demonstrating risk of chronic gastrointestinal sequelae following bacterial enteric infections and highlight additional preventable burden of disease which may inform better food security policies and practices, and prompt further research into pathogenic mechanisms.
BackgroundThe US CDC estimates over 2 million foodborne illnesses are annually caused by 4 major enteropathogens: non-typhoid Salmonella spp., Campylobacter spp., Shigella spp. and Yersinia enterocoltica. While data suggest a number of costly and morbid chronic sequelae associated with these infections, pathogen-specific risk estimates are lacking. We utilized a US Department of Defense medical encounter database to evaluate the risk of several gastrointestinal disorders following select foodborne infections.MethodsWe identified subjects with acute gastroenteritis between 1998 to 2009 attributed to Salmonella (nontyphoidal) spp., Shigella spp., Campylobacter spp. or Yersinia enterocolitica and matched each with up to 4 unexposed subjects. Medical history was analyzed for the duration of military service time (or a minimum of 1 year) to assess for incident chronic gastrointestinal disorders. Relative risks were calculated using modified Poisson regression while controlling for the effect of covariates.ResultsA total of 1,753 pathogen-specific gastroenteritis cases (Campylobacter: 738, Salmonella: 624, Shigella: 376, Yersinia: 17) were identified and followed for a median of 3.8 years. The incidence (per 100,000 person-years) of PI sequelae among exposed was as follows: irritable bowel syndrome (IBS), 3.0; dyspepsia, 1.8; constipation, 3.9; gastroesophageal reflux disease (GERD), 9.7. In multivariate analyses, we found pathogen-specific increased risk of IBS, dyspepsia, constipation and GERD.ConclusionsThese data confirm previous studies demonstrating risk of chronic gastrointestinal sequelae following bacterial enteric infections and highlight additional preventable burden of disease which may inform better food security policies and practices, and prompt further research into pathogenic mechanisms.
BackgroundThe US CDC estimates over 2 million foodborne illnesses are annually caused by 4 major enteropathogens: non-typhoid Salmonella spp., Campylobacter spp., Shigella spp. and Yersinia enterocoltica. While data suggest a number of costly and morbid chronic sequelae associated with these infections, pathogen-specific risk estimates are lacking. We utilized a US Department of Defense medical encounter database to evaluate the risk of several gastrointestinal disorders following select foodborne infections.MethodsWe identified subjects with acute gastroenteritis between 1998 to 2009 attributed to Salmonella (nontyphoidal) spp., Shigella spp., Campylobacter spp. or Yersinia enterocolitica and matched each with up to 4 unexposed subjects. Medical history was analyzed for the duration of military service time (or a minimum of 1 year) to assess for incident chronic gastrointestinal disorders. Relative risks were calculated using modified Poisson regression while controlling for the effect of covariates.ResultsA total of 1,753 pathogen-specific gastroenteritis cases (Campylobacter: 738, Salmonella: 624, Shigella: 376, Yersinia: 17) were identified and followed for a median of 3.8 years. The incidence (per 100,000 person-years) of PI sequelae among exposed was as follows: irritable bowel syndrome (IBS), 3.0; dyspepsia, 1.8; constipation, 3.9; gastroesophageal reflux disease (GERD), 9.7. In multivariate analyses, we found pathogen-specific increased risk of IBS, dyspepsia, constipation and GERD.ConclusionsThese data confirm previous studies demonstrating risk of chronic gastrointestinal sequelae following bacterial enteric infections and highlight additional preventable burden of disease which may inform better food security policies and practices, and prompt further research into pathogenic mechanisms.
Though no avian influenza vaccine currently exists, development efforts have increased. Given recent reports of suboptimal vaccination rates among US military personnel, we sought to assess factors associated with a willingness to receive a hypothetical avian influenza vaccine. A self-administered questionnaire was completed by US military personnel during mid-deployment to Iraq, Afghanistan, and surrounding regions. Respondents were predominately male (86.2%), Army (72.1%), and enlisted (86.3%) with a mean age of 29.6 y. The majority (77.1%) agreed to receive an avian influenza vaccine if available. Exploratory factor analysis (EFA) identified two factors, vaccine importance and disease risk, that best described the individual perceptions and both were associated with an increased willingness to receive the hypothetical vaccine (OR: 8.2 and 1.6, respectively). Importantly, after controlling for these factors differences in the willingness to receive this hypothetical vaccine were observed across gender and branch of service. These results indicated that targeted education on vaccine safety and efficacy as well as disease risk may modify vaccination patterns in this population.
We used a seroepidemiologic study to estimate Q fever (Coxiella burnetii) seroprevalence, seroincidence, and risk factors for seroconversion in two deployed military populations in 2005. The first study group resided in an area with a known Q fever outbreak history (Al Asad, Iraq). Of this population, 7.2% seroconverted for an incidence rate of 10.6 seroconversions per 1,000 person-months. The second population included personnel transiting through Qatar on mid-deployment leave from southwest/central Asia. In this group, we found 2.1% prevalence with 0.92 seroconversions per 1,000 person-months. However, no significant risk factors for Q fever seroconversion were found in either population.
Abstract Background The US CDC estimates over 2 million foodborne illnesses are annually caused by 4 major enteropathogens: non-typhoid Salmonella spp., Campylobacter spp., Shigella spp. and Yersinia enterocoltica . While data suggest a number of costly and morbid chronic sequelae associated with these infections, pathogen-specific risk estimates are lacking. We utilized a US Department of Defense medical encounter database to evaluate the risk of several gastrointestinal disorders following select foodborne infections. Methods We identified subjects with acute gastroenteritis between 1998 to 2009 attributed to Salmonella (nontyphoidal) spp., Shigella spp., Campylobacter spp. or Yersinia enterocolitica and matched each with up to 4 unexposed subjects. Medical history was analyzed for the duration of military service time (or a minimum of 1 year) to assess for incident chronic gastrointestinal disorders. Relative risks were calculated using modified Poisson regression while controlling for the effect of covariates. Results A total of 1,753 pathogen-specific gastroenteritis cases ( Campylobacter : 738, Salmonella : 624, Shigella : 376, Yersinia : 17) were identified and followed for a median of 3.8 years. The incidence (per 100,000 person-years) of PI sequelae among exposed was as follows: irritable bowel syndrome (IBS), 3.0; dyspepsia, 1.8; constipation, 3.9; gastroesophageal reflux disease (GERD), 9.7. In multivariate analyses, we found pathogen-specific increased risk of IBS, dyspepsia, constipation and GERD. Conclusions These data confirm previous studies demonstrating risk of chronic gastrointestinal sequelae following bacterial enteric infections and highlight additional preventable burden of disease which may inform better food security policies and practices, and prompt further research into pathogenic mechanisms.
PURPOSE: The etiology of several autoimmune disorders, including rheumatoid arthritis, remains unknown. While there are clear phases of disease progression, the mechanisms of transition between these phases are poorly understood. Additionally, treatment focuses on an alteration of the biological processes to prevent joint damage and functional decline. A goal is to potentially treat the disease during the preclinical phase to mitigate the disease process. Reactive arthritis is another rheumatologic condition known to be secondary to a distal infection. While prevention of infection would mitigate risk, serologic profiling patients with the disease may assist in the elucidation of potential disease risk factors. This study was initiated to enable an assessment of pre-disease biomarkers in patients newly diagnosed with rheumatoid arthritis and reactive arthritis. PARTICIPANTS: A retrospective cohort of 500 rheumatoid and 500 reactive arthritis cases with 500 matched controls was drawn from a population of active component US military personnel. Appropriate inclusion criteria limited subject selection. Additionally, 4 serum samples (3 pre-disease and 1 disease-associated) were obtained for each case and control. FINDINGS TO DATE: The established cohort provides the framework for novel exploration of the host response through serum profiling and seroepidemiology prior to disease onset. FUTURE PLANS: This study establishes the framework for the evaluation of novel serum biomarkers enabling the identification of signals prior to clinical disease that may enable disease prediction, elucidate disease pathogenesis and identify novel exposures leading to increased disease risk and/or disease severity.
PURPOSE: The etiology of Inflammatory Bowel Disease (IBD) remains currently unknown but evidence would suggest that it results from a complex interplay between genetic susceptibility genes, the intestinal microbiome and the environment, resulting in an increased response towards microbial and self-antigens, followed by the development of pre-clinical intestinal inflammation as a precursor to overt clinical disease. Efforts are needed to provide insights into the characterization of the disease, the possible prediction of complications, and the detection of a pre-clinical disease state where, through early screening and intervention, disease course can be reversed, attenuated or even prevented. A consortium of academic, industry and governmental organization investigators initiated this study to enable an assessment of pre-disease biomarkers in patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC). PARTICIPANTS: A retrospective cohort of 1000 UC and 1000 CD cases with 500 matched controls was drawn from an active duty US military personnel population with relevant inclusion criteria with three associated pre-disease and a single disease-associated archived serum samples. FINDINGS TO DATE: The PREDICTS study has been established as a biorepository platform study to perform novel discovery and analysis efforts in the field of IBD and proteomic systems biology. FUTURE PLANS: This study is poised to enable the assessment of novel biomarkers within the serum compartment to be analyzed with the goal of identifying pre-disease signals that ultimately predict disease risk, and further elucidate disease pathogenesis in the early stages of the disease process, and identify novel exposures that increase disease risk.
Campylobacter jejuni infection is a leading cause of foodborne disease, common to children, adult travelers, and military populations in low- to middle-income countries. In the absence of a licensed vaccine, efforts to evaluate prophylactic agents are underway. The prophylactic efficacy of a twice-daily, 550 mg dose of the antibiotic rifaximin demonstrated no efficacy against campylobacteriosis in a controlled human infection model (CHIM); however, samples from the CHIM study were utilized to assess how the human gut microbiome responds to C. jejuni infection, and if a 'protective' microbiota exists in study participants not developing campylobacteriosis. Statistically significant, but minor, differences in study participant beta diversity were identified during the challenge period (p = 0.002, R(2) = 0.042), but no significant differences were otherwise observed. Pre-challenge alpha diversity was elevated in study participants who did not develop campylobacteriosis compared to those who did (p < 0.001), but alpha diversity declined in all study participants from the pre-challenge period to post-discharge. Our work provides insight into gut microbiome shifts observed during a C. jejuni CHIM and following antibiotic treatment. This study utilized a high dose of 1.7 x 10(5) colony-forming units of C. jejuni; future work could include CHIM studies performed with inocula more closely mimicking natural exposure as well as field studies involving naturally-occurring enteric infections.
INTRODUCTION: Enterotoxigenic Escherichia coli (ETEC) is a common cause of infectious diarrhoea and a leading cause of morbidity and mortality in children living in resource-limited settings. It is also the leading cause of travellers' diarrhoea among civilian and military travellers. Its dual importance in global public health and travel medicine highlights the need for an effective vaccine. ETEC express colonization factors (CFs) that mediate adherence to the small intestine. An epidemiologically prevalent CF is coli surface antigen 6 (CS6). We assessed the safety and immunogenicity of a CS6-targeted candidate vaccine, CssBA, co-administered intramuscularly with the double-mutant heat-labile enterotoxin, dmLT [LT(R192G/L211A)]. METHODS: This was an open-label trial. Fifty subjects received three intramuscular injections (Days 1, 22 and 43) of CssBA alone (5 µg), dmLT alone (0.1 µg) or CssBA (5, 15, 45 µg) + dmLT (0.1 and 0.5 µg). Subjects were actively monitored for adverse events for 28 days following the third vaccination. Antibody responses (IgG and IgA) were characterized in the serum and from lymphocyte supernatants (ALS) to CS6 and the native ETEC heat labile enterotoxin, LT. RESULTS: Across all dose cohorts, the vaccine was safe and well-tolerated with no vaccine-related severe or serious adverse events. Among vaccine-related adverse events, a majority (98%) were mild with 79% being short-lived vaccine site reactions. Robust antibody responses were induced in a dose-dependent manner with a clear dmLT adjuvant effect. Response rates in subjects receiving 45 µg CssBA and 0.5 µg dmLT ranged from 50 to 100% across assays. CONCLUSION: This is the first study to demonstrate the safety and immunogenicity of CssBA and/or dmLT administered intramuscularly. Co-administration of the two components induced robust immune responses to CS6 and LT, paving the way for future studies to evaluate the efficacy of this vaccine target and development of a multivalent, subunit ETEC vaccine.
