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U.S. military personnel must be ready to deploy to locations worldwide, including environments with heightened risk of infectious disease. Diarrheal illnesses continue to be among the most significant infectious disease threats to operational capability. To better prevent, detect, and respond to these threats and improve synchronization across the Department of Defense (DoD) overseas laboratory network, a multisite Global Travelers' Diarrhea protocol was implemented with standardized case definitions and harmonized laboratory methods to identify enteric pathogens. Harmonized laboratory procedures for detection of Norovirus ( NoV ), enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli , Shiga toxin-producing E. coli , enteropathogenic E. coli , Salmonella enterica , Shigella /enteroinvasive E. coli , and Campylobacter jejuni have been implemented at six DoD laboratories with surveillance sites in Egypt, Honduras, Peru, Nepal, Thailand, and Kenya. Samples from individuals traveling from wealthy to poorer countries were collected between June 2012 and May 2018, and of samples with all variables of interest available ( n = 410), most participants enrolled were students (46%), tourists (26%), U.S. military personnel (13%), or other unspecified travelers (11%). One or more pathogens were detected in 59% of samples tested. Of samples tested, the most commonly detected pathogens were NoV (24%), ETEC (16%), and C. jejuni (14%), suggesting that NoV plays a larger role in travelers' diarrhea than has previously been described. Harmonized data collection and methods will ensure identification and characterization of enteric pathogens are consistent across the DoD laboratory network, ultimately resulting in more comparable data for global assessments, preventive measures, and treatment recommendations.

Objective: Stool repositories are a valuable resource for retrospective analyses including quantitative PCR assays to distinguish between asymptomatic shedding and clinical disease. The suitability of archival specimens for this purpose is unclear and requires assessment. We conducted a pilot study to evaluate pathogen detection by TaqMan Array Card (TAC) in travelers' diarrhea (TD) stool specimens stored for 1-13 years, as well as the impact of transporting specimens on Whatman FTA Elute cards (FTA Cards) on detection., Results: The positive percent agreement (PPA) for TAC on stool vs. microbiologic testing was lower than our a priori PPA estimate of 80% for most pathogens: Shigella spp. (100% [95%CI 69-100%]), enterotoxigenic E coli (ETEC) (63% [95%CI 49-75%]), Campylobacter spp. (66% [95%CI 43-85%]) and Norovirus (37% [95%CI 16-61%]). Use of the FTA card resulted in a further reduction of PPA. Our findings suggest that archival specimens may lead to insensitive detection on quantitative PCR assays due to degradation of nucleic acid with prolonged storage, although our limited sample size precluded us from evaluating the impact of storage duration on nucleic acid yield. Additional studies are needed to understand the impact of storage duration on quantitative PCR data.

Exposure to cholera is a risk for individuals and groups travelling to endemic areas, and the bacteria can be imported to cholera-free countries by returning travellers. This systematic review of the literature describes the circumstances in which cholera infection can occur in travellers and considers the possible value of the cholera vaccine for prevention in travellers. PubMed and EMBASE were searched for case reports of cholera or diarrhoea among travellers, with date limits of 1 January 1990-30 April 2018. Search results were screened to exclude the following articles: diarrhoea not caused by cholera, cholera in animals, intentional cholera infection in humans, non-English articles and publications on epidemics that did not report clinical details of individual cases and publications of cases pre-dating 1990. Articles were reviewed through descriptive analytic methods and information summarized. We identified 156 cases of cholera imported as a consequence of travel, and these were reviewed for type of traveller, source country, serogroup of cholera, treatment and outcomes. The case reports retrieved in the search did not report consistent levels of detail, making it difficult to synthesize data across reports and draw firm conclusions from the data. This clinical review sheds light on the paucity of actionable published data regarding the risk of cholera in travellers and identifies a number of gaps that should drive additional effort. Further information is needed to better inform evidence-based disease prevention strategies, including vaccination for travellers visiting areas of cholera risk. Modifications to current vaccination recommendations to include or exclude current or additional traveller populations may be considered as additional risk data become available. The protocol for this systematic review is registered with PROSPERO (registration number: 122797)., (© International Society of Travel Medicine 2019. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

New guidelines on the management of acute diarrhea in adults were promulgated in 2016. The aim of this review was to provide an overview of the context of acute diarrhea and how to generally approach a patient; to present some new areas in the field concerning diagnostics, particularly culture-independent testing, as well as some of the risks and benefits of treatment; and to discuss prevention, particularly in the traveler's diarrhea setting.

Background: Recommended treatment for travelers' diarrhea includes the combination of an antibiotic, usually a fluoroquinolone or azithromycin, and loperamide for rapid resolution of symptoms. However, adverse events, postdose nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and emerging resistance to front-line agents are evidence gaps underlying current recommendations., Methods: A randomized, double-blind trial was conducted in 4 countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and July 2015. US and UK service members with acute watery diarrhea were randomized and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500 mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24 hours and time to last unformed stool., Results: Clinical cure at 24 hours occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07). At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at 48 and 96% at 72 hours). The median time to last unformed stool did not differ between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours; rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There were no differences between treatment arms with postdose nausea, vomiting, or other adverse events., Conclusions: Single-dose azithromycin, levofloxacin, and rifaximin with loperamide were comparable for treatment of acute watery diarrhea., Clinical Trial Registration: NCT01618591., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Travelers' diarrhea (TD) has historically been a common illness among visitors to developing nations. Although recent studies indicate decreasing incidence of TD among short-term travelers, a systematic review of illness among long-term travelers, including deployed military personnel, has not been conducted in more than 10 years. We conducted a literature search of studies published between 2005 and 2015 that evaluated TD in populations of deployed military personnel or similar long-term travelers (travel ≥1 month) to developing nations. Our literature search identified 28 studies for inclusion. We found that the incidence of TD remained high (10% clinical incidence, 30% self-reported incidence), with variability depending on region of travel and similar rates in both military and civilian long-term travelers. Bacteria (Escherichia coli, Campylobacter, Shigella, and Salmonella species) were the most commonly identified enteropathogens. Fifty percent of affected individuals experienced lost ability to work and 5% required hospitalization. This systematic review demonstrates that among deployed military personnel and long-term travelers, TD remains a prevalent disease that can significantly impact individual readiness for duty. These data demonstrate that to maintain operational readiness among deployed personnel, a focus on vigilance for disease and early treatment of cases is vital., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

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., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Background: : Travelers' diarrhea causes significant morbidity including some sequelae, lost travel time and opportunity cost to both travelers and countries receiving travelers. Effective prevention and treatment are needed to reduce these negative impacts., Methods: : This critical appraisal of the literature and expert consensus guideline development effort asked several key questions related to antibiotic and non-antibiotic prophylaxis and treatment, utility of available diagnostics, impact of multi-drug resistant (MDR) colonization associated with travel and travelers' diarrhea, and how our understanding of the gastrointestinal microbiome should influence current practice and future research. Studies related to these key clinical areas were assessed for relevance and quality. Based on this critical appraisal, guidelines were developed and voted on using current standards for clinical guideline development methodology., Results: : New definitions for severity of travelers' diarrhea were developed. A total of 20 graded recommendations on the topics of prophylaxis, diagnosis, therapy and follow-up were developed. In addition, three non-graded consensus-based statements were adopted., Conclusions: : Prevention and treatment of travelers' diarrhea requires action at the provider, traveler and research community levels. Strong evidence supports the effectiveness of antimicrobial therapy in most cases of moderate to severe travelers' diarrhea, while either increasing intake of fluids only or loperamide or bismuth subsalicylate may suffice for most cases of mild diarrhea. Further studies are needed to address knowledge gaps regarding optimal therapies, the individual, community and global health risks of MDR acquisition, manipulation of the microbiome in prevention and treatment and the utility of laboratory testing in returning travelers with persistent diarrhea., (Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.)

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., (Published by Oxford University Press on behalf of International Society of Travel Medicine 2016. This work is written by US Government employees and is in the public domain in the United States.)

Travelers' diarrhea (TD) is the most common ailment affecting travelers, including deployed U.S. military. Continuing Promise 2011 was a 5-month humanitarian assistance/disaster response (HA/DR) military and non-governmental organization training mission aboard the hospital ship USNS Comfort, which deployed to Central and South America and the Caribbean between April and September 2011. Enhanced TD surveillance was undertaken during this mission for public health purposes. Passive surveillance (clinic visits), active surveillance (self-reported questionnaires), and stool samples were collected weekly from shipboard personnel. Descriptive statistics and multivariate-logistic regression methods were used to estimate disease burden and risk factor identification. Two polymerase chain reaction methods on frozen stool were used for microbiological identification. TD was the primary complaint for all clinic visits (20%) and the leading cause of lost duties days due to bed rest confinement (62%), though underreported, as the active self-reported incidence was 3.5 times higher than the passive clinic-reported incidence. Vomiting (p = 0.002), feeling lightheaded or weak (p = 0.005), and being a food handler (p = 0.017) were associated with increased odds of lost duty days. Thirty-eight percent of self-reported cases reported some amount of performance impact. Based on the epidemiological curve, country of exercise and liberty appeared to be temporally associated with increased risk. From the weekly self-reported questionnaire risk factor analysis, eating off ship in the prior week was strongly associated (adjusted odds ratio [OR] 2.4, p<0.001). Consumption of seafood increased risk (aOR 1.7, p = 0.03), though consumption of ice appeared protective (aOR 0.3, p = 0.01). Etiology was bacterial (48%), with enterotoxigenic Escherichia coli as the predominant pathogen (35%). Norovirus was identified as a sole pathogen in 12%, though found as a copathogen in an additional 6%. Despite employment of current and targeted preventive interventions, ship-board HA/DR missions may experience a significant risk for TD among deployed US military personnel and potentially impact mission success.

We evaluated the limits of detection (LoD) for an 11-plex PCR-Luminex assay performed on Whatman(™) FTA Elute cards smeared with stool containing pathogens associated with travelers' diarrhea. LoDs ranged from 10(2) to 10(5)CFU, PFU, or cysts/g for most pathogens except Cryptosporidium. Campylobacter and norovirus LoDs increased with prolonged storage of cards., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Knowledge of disease burden attributable to functional gastrointestinal disorders (FGD) in travelers is lacking, despite the high incidence of travelers' diarrhea (TD) associated with increased FGD risk. One tool for assessing the impact of disease on health-related quality of life is the health utility index (HUI), which values health states based on preferential health outcomes. Health utilities can be used as preference weights in the estimation of quality-adjusted life-years (QALYs)., Methods: Six months following travel to Egypt or Turkey, 120 US military personnel completed a survey on TD during deployment, health-related quality of life (SF-36), and the onset of functional bowel disorders (Rome II). Elements from the SF-36 were used to develop SF-6D values, which were combined with health state valuations to enable calculation of HUI scores for each subject. Mean index scores were compared across functional outcomes, specific symptoms, and demographic profiles., Results: The presence of FGD significantly reduced index scores, with irritable bowel syndrome (IBS) and dyspepsia showing the greatest impact (-0.17 and -0.19, respectively) compared with those with no FGD (p < 0.05). Importantly, however, several individuals met multiple FGD outcome definitions. Additionally, a number of symptoms associated with abnormal bowel habits and abdominal pain were associated with reduced index scores regardless of outcome., Conclusion: FGD are associated with significant morbidity as assessed by HUIs. Given the strong link between TD and FGD as well as the large number of travelers from the developed to the developing world, additional study is needed to further understand this association and efforts aimed at primary disease prevention are warranted., (Published 2015. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: Infectious diarrhea is a common problem among travelers. Expert guidelines recommend the prompt use of antibiotics for self-treatment of moderate or severe travelers' diarrhea (TD). There is limited data on whether travelers follow these self-treatment guidelines. We evaluated the risk factors associated with TD, the use of TD self-treatment, and the risk of irritable bowel syndrome (IBS) during travel., Methods: Department of Defense beneficiaries traveling outside the United States for ≤6.5 months were enrolled in a prospective cohort study. Participants received pre- and post-travel surveys, and could opt into a travel illness diary and follow-up surveys for symptoms of IBS. Standard definitions were used to assess for TD and IBS. Suboptimal self-treatment was defined as the use of antibiotics (with or without antidiarrheal agents) for mild TD, or the use of antidiarrheals alone or no self-treatment in cases of moderate or severe TD., Results: Twenty-four percent of participants (270/1,120) met the criteria for TD. The highest incidence was recorded in Africa [8.6 cases/100 person-weeks, 95% confidence interval (CI): 6.7-10.5]. Two hundred and twelve participants with TD provided information regarding severity and self-treatment: 89 (42%) had mild TD and 123 (58%) had moderate or severe TD. Moderate or severe TD was independently associated with suboptimal self-treatment [OR 10.4 (95% CI: 4.92-22.0)]. Time to last unformed stool did not differ between optimal and suboptimal self-treatment. IBS occurred in 4.5% (7/154) of TD cases and in 3.1% (16/516) of cases without TD (p = 0.39). Among TD cases, a lower incidence of IBS was noted in participants who took antibiotics [4.8% (5/105) vs 2.2% (1/46)] in those who did not, but the difference did not reach statistical significance (p = 0.60)., Conclusions: Our results suggest the underutilization of antibiotics in travelers with moderate or severe TD. Further studies are needed to systematically evaluate pre-travel instruction and traveler adherence to self-treatment guidelines, and the impact of suboptimal self-treatment on outcomes., (© 2014 International Society of Travel Medicine.)

Objective: This study assessed the efficacy of education and self-treatment with loperamide on diarrhea morbidity and healthcare utilization in a deployed military setting., Method: In this prospective, controlled study, volunteers from military personnel deployed to Incirlik Air Base received either travelers' diarrhea education (non-loperamide group) or education plus a supply of loperamide (loperamide group). Volunteers were surveyed to determine frequency and outcomes of diarrheal illness., Results: 109 deployed personnel were enrolled with 48 assigned to the loperamide group, and 61 to the non-loperamide group. Overall, 41 (38%) service members had at least one diarrheal episode. Only 10 (9%) service members sought treatment from a healthcare provider and the distribution was similar in both groups. Loperamide use for self-treatment was more common in the loperamide group (85%) vs. (57%), [p = 0.02]) but use of antibiotics was similar in both groups (loperamide (30%) vs. non-loperamide (20%)., Conclusions: Provision of loperamide and education did not significantly affect healthcare utilization or antibiotic use to manage diarrheal episodes, when compared to education alone. Further prospective studies will either need a very large patient population to power them or should use other primary end points such a functional assessment in addition to seeking care., (Published by Elsevier Ltd.)

Background: Travelers' diarrhea (TD) has generally been considered a self-limited disorder which resolves more quickly with expeditious and appropriate antibiotic therapy given bacteria are the most frequently identified cause. However, epidemiological, clinical, and basic science evidence identifying a number of chronic health conditions related to these infections has recently emerged which challenges this current paradigm. These include serious and potentially disabling enteric and extra-intestinal long-term complications. Among these are rheumatologic, neurologic, gastrointestinal, renal, and endocrine disorders. This review aims to examine and summarize the current literature pertaining to three of these post-infectious disorders: reactive arthritis, Guillain-Barré syndrome, and post-infectious irritable bowel syndrome and the relationship of these conditions to diarrhea associated with travel as well as to diarrhea associated with gastroenteritis which may not be specifically travel related but relevant by shared microbial pathogens. It is hoped this review will allow clinicians who see travelers to be aware of these post-infectious sequelae thus adding to our body of knowledge in travel medicine., Methods: Data for this article were identified by searches of PubMed and MEDLINE, and references from relevant articles using search terms "travelers' diarrhea" "reactive arthritis" "Guillain-Barré syndrome" "Post-Infectious Irritable Bowel Syndrome." Abstracts were included when related to previously published work., Results and Conclusions: A review of the published literature reveals that potential consequences of travelers' diarrhea may extend beyond the acute illness and these post-infectious complications may be more common than currently recognized. In addition since TD is such a common occurrence it would be helpful to be able to identify those who might be at greater risk of post-infectious sequelae in order to target more aggressive prophylactic or therapeutic approaches to such individuals. It is hoped this review will allow clinicians who see travelers to be aware of these post-infectious sequelae thus adding to our body of knowledge in travel medicine., (© 2013 International Society of Travel Medicine.)

Background: Recent developments related to a safe and effective nonabsorbable antibiotic, rifaximin, and identification of postinfectious irritable bowel syndrome as a frequent sequela call for a need to reconsider the value of primary prevention of traveler's diarrhea (TD) with antibiotics., Methods: Randomized, placebo-controlled, double-blind studies evaluating the effectiveness and safety of rifaximin or a fluoroquinolone chemoprophylaxis against TD were pooled using a random effects model and assessed for heterogeneity., Results: The nine studies (four rifaximin and five fluoroquinolone) included resulted in pooled relative risk estimates of 0.33 (95% CI = 0.24-0.45, I2 = 3.1%) and 0.12 (95% CI = 0.07-0.20, I2 =0.0%), respectively. Similar rates of treatment emergent adverse events were found between antibiotic and placebo groups., Conclusions: This meta-analysis supports the effectiveness of antibiotics in preventing TD. However, further studies that include prevention of secondary chronic health outcomes among travelers to different geographic regions, and a formal risk-benefit analysis for antibiotic chemoprophylaxis, are needed.

The Current Topics in Military Tropical Medicine series provides focused reviews addressing specific questions faced by operational military medical personnel. This issue in the series explores the diagnosis and management of persistent diarrhea in deployed service members.

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.

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., (© 2011 International Society of Travel Medicine.)

Background: Infectious diarrhea is an important problem among travelers and deployed US military overseas causing substantial morbidity due to acute illness and may result in burdensome postinfectious sequelae., Methods: The nonsystemic antibiotic rifaximin was evaluated for prevention of travelers' diarrhea (TD) in a US military and civilian adult beneficiary population in a randomized, double-blind, placebo-controlled clinical trial. In all, 100 volunteers deployed to Incirlik Air Base, Turkey, received rifaximin 1,100 mg once daily or placebo for 2 weeks, and participants were followed daily for 2 weeks., Results: In an intention to treat analysis (n = 95), TD (based on subjects meeting case definition or early treatment) developed in 6.3% (3 of 48) of the rifaximin group compared with 19.2% (9 of 47) in the placebo group (Fisher's exact test p = 0.07). Rifaximin provided 67% (95% confidence interval, -13% to 91%, p = 0.07) protection against TD. Rifaximin 1,100 mg once daily was well tolerated with no observed differences in adverse events, whether solicited or unsolicited among the two treatment groups., Conclusions: Rifaximin may represent an option among military personnel on deployment for prevention of TD with supportive future studies that consider deployment length, settings, and operational situations where widespread use of chemoprophylaxis may increase force health protection without undue risk during critical deployments., (Published 2010. This article is a US Government work and is in the public domain in the USA.)

Background: Transmission of tuberculosis (TB) during travel is a significant potential infectious disease threat to travelers. However, there is uncertainty in the travel medicine community regarding the evidence base for both estimates of risk for latent TB infection (LTBI) in long-term travelers and for information regarding which travelers may benefit from pre- or post-travel TB screening. The purpose of this study was to determine the risk for tuberculin skin test (TST) conversion, used as a surrogate for LTBI, in long-term travelers from low- to high-risk countries., Methods: We performed a systematic review to acquire all published and unpublished data on TST conversion in long-term civilian and military travelers from 1990 to June 2008. Point estimates and confidence intervals (CIs) of the incidence of TST conversion were combined in a random effects model and assessed for heterogeneity., Results: The cumulative risk with CI for LTBI as measured by TST conversion was 2.0% (99% CI: 1.6%-2.4%). There was a marked heterogeneity (chi(2) heterogeneity statistic, p < 0.0001) which could not be explained by evaluable study characteristics. When stratifying by military and civilian studies, the cumulative risk estimate was 2.0% (99% CI: 1.6-2.4) for military and 2.3% (99% CI: 2.1-2.5) for civilian studies., Conclusion: The overall cumulative incidence of 2.0% is what could be expected to occur among the local population in many developing-country settings, though TST conversion likely overestimates the risk of TB infection because of the low positive predictive value (PPV) of the TST in low-prevalence populations such as travelers. To maximize the PPV of a screening test for LTBI, a targeted testing strategy for long-term military and civilian travelers is recommended, based on exposures known to increase the risk of TB. Studies to better define higher risk groups, activities, and locations are needed.

This study evaluated travelers' diarrhea among US military personnel on short-term deployment to Incirlik Air Base, Turkey, from June through September 2002. Upon reporting for care for travelers' diarrhea, subjects were enrolled into the study and completed a series of questionnaires and provided stool specimens for pathogen identification and antimicrobial susceptibility testing. Fifty-three percent of the 202 participating subjects had a pathogen isolated from their stool. Enterotoxigenic Escherichia coli (ETEC) was the predominant pathogen (41%), followed by Campylobacter spp. (12%). The most common ETEC phenotype recovered was stable toxin (ST) CS6 (47% of all ETEC). Most (91.1%) of the cases presented with water diarrhea regardless of isolated pathogen. However, there were some differences in nongastrointestinal symptoms among subjects with Campylobacter spp. All illnesses were well managed with antibiotics with or without loperamide with a median time to the last unformed stool of 9 h (interquartile range, 1-32 h). We found no food or environmental factors associated with a differential risk of infection with a specific pathogen. Travelers' diarrhea among a US military population in and around Incirlik, Turkey, can commonly be attributed to ETEC and Campylobacter spp. The high proportion of ST-only-producing CS6 ETEC in this region highlights the pathogen's worldwide diversity. Future studies of travelers' diarrhea in this population should adapt more novel microbiologic techniques such as polymerase chain reaction and enhanced culture methods to increase the likelihood of identifying pathogenic E. coli., (Published by Elsevier Inc.)

Background: A previous Cochrane Collaboration review established an effective advantage of antibiotic therapy, compared with placebo, for treatment of traveler's diarrhea. The goal of the present study was to conduct a systematic review of the literature to establish the effect on treatment outcomes of using antimotility agents in conjunction with antibiotic therapy., Methods: The meta-analysis was conducted through searches of electronic databases and pertinent reference lists (including other review articles) and consultation with experts in the field. Clinical trials on therapy of infectious diarrhea in adult populations that met eligibility criteria were studied. Data were extracted and verified by 2 independent investigators and were analyzed for outcomes of clinical cure at 24 h, 48 h, and 72 h and time to last unformed stool. Study quality, heterogeneity, and publication bias were assessed. When appropriate, effect estimates among studies were pooled and sensitivity analyses were performed., Results: Nine studies consisting of 12 different adjunctive loperamide antibiotic regimens were included for analysis. Among 6 paired studies comparing antibiotics alone versus antibiotics in combination with loperamide, the odds of clinical cure at 24 h and 48 h favored combination therapy, with summary odds ratios of 2.6 (95% confidence interval, 1.8-3.6; P = .20 by chi(2) heterogeneity statistic) and 2.2 (95% confidence interval, 1.5-3.1; P = .20, by chi(2) heterogeneity statistic), respectively, with no evidence of heterogeneity. Factors that possibly affect advantage of combination therapy over solo therapy included increased frequency of pretreatment diarrhea and higher prevalence of noninvasive pathogens., Conclusion: Antibiotic therapy with adjunctive loperamide offers an advantage over antibiotics alone by decreasing the illness duration and increasing the probability of early clinical cure.

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.

Background: The recommended treatment for traveler's diarrhea is the combination of an appropriate antibiotic (usually a fluoroquinolone) and loperamide. Azithromycin compared favorably with fluoroquinolones in trials that did not include the use of loperamide, but combination therapy has not, to our knowledge, been studied to date., Methods: A randomized, double-blind trial was conducted at Incirlik Air Base, Turkey, fromJ une 2003 through August 2004. Adults from the United States with noninflammatory diarrhea were randomized to receive a single dose of azithromycin (1000 mg; 106 persons) or levofloxacin (500 mg; 101 persons) plus loperamide (4 mg initially and as needed thereafter). Volunteers maintained a symptom diary and were evaluated on days 1, 3, and 7 after treatment., Results: No differences were noted with respect to pretreatment symptoms or pathogen distribution. Enterotoxigenic Escherichia coli was the most common pathogen isolated (from 45% of patients in the azithromycin group and 42% of patients in the levofloxacin group), and Campylobacter species was the second most common pathogen isolated (from 6% of patients in the azithromycin group and 9% of patients in the levofloxacin group). Median time to last diarrheal stool (azithromycin group, 13 h; levofloxacin group, 3 h), median time to resolution of associated symptoms (2 days), and additional loperamide usage (azithromycin group, 39% of patients; levofloxacin group, 34% of patients) were similar between groups. Azithromycin use was associated with more nausea in the 30 min after dosing (azithromycin group, 8% of patients; levofloxacin group, 1% of patients; Pp.004), but no vomiting or other adverse events were noted in either group., Conclusions: Single-dose treatment with azithromycin (1000 mg) and loperamide is as effective as single-dose treatment with levofloxacin (500 mg) and loperamide for noninflammatory diarrhea. Although nausea after dosing is uncommon, it is more frequently associated with azithromycin than with levofloxacin. Future studies should focus on determining whether lower doses of azithromycin would decrease the frequency of nausea and decrease treatment costs without affecting efficacy.

To determine regional estimates of pathogen-specific prevalence and incidence, as well as, describe morbidity associated with diarrhea among deployed US military and similar populations, a systematic review was conducted for publications between January 1990 to June 2005. Point estimates and confidence intervals of pathogen prevalence and travelers' diarrhea incidence were combined in a random effects model and assessed for heterogeneity. In total, 262 studies were identified for potential inclusion, of which 52 fulfilled inclusion criteria. Overall, 38% were from the Middle East, 29% from Southeast Asia, 27% from Latin America/Caribbean, and 6% from sub-Saharan Africa. Median duration of travel was 1.5 months (interquartile range, 1-3 months). Enterotoxigenic Escherichia coli (ETEC), Campylobacter, and Shigella were identified as causing 38-45% of diarrhea, with regional and population differences. Incidence based on self-report was higher than studies using passive surveillance or clinic-based methods (29 versus 7 versus 6 episodes per 100 person-months, respectively) without regional differences.

Background: Travellers' diarrhoea (TD) is the most common travel-related illness with an estimated 10 million people afflicted annually. Outcome measures to assess the efficacy of primary and secondary TD interventions were historically based on diarrhoea frequency with ≥1 associated gastrointestinal symptom. Furthermore, efficacy determination is often made on the presence or absence of TD, rather than on TD illness severity. Current severity classifications are based on subjective consideration of impact of illness on activity. We sought to develop a standardized scoring system to characterize TD severity to potentially apply as a secondary outcome in future field studies.Methods: Data on multiple signs and symptoms were obtained from a previously published multisite TD treatment trial conducted by the US Department of Defense (TrEAT TD). Correlation, regression and multiple correspondence analyses were performed to assess impact on activity and a TD severity score was established.Results: Numerous signs and symptoms were associated with impaired function, with malaise and nausea most strongly associated [odds ratio (OR) 5.9-44.3, P < 0.0001 and OR 2.8-37.1, P < 0.0001, respectively). Based on co-varying symptomatology, a TD severity score accounting for diarrhoea frequency in addition to several signs and symptoms was a better predictor of negative impact on function than any single sign/symptom (X2 = 127.16, P < 0.001). Additionally, there was a significant difference (P < 0.0001) in the mean TD severity score between those with acute watery diarrhoea (3.9 ± 1.9) and those with dysentery or acute febrile illness (6.2 ± 2.0).Conclusions: The newly developed disease severity score better predicted a negative impact on activity due to TD than did any single sign or symptom. Incorporating multiple parameters into the TD severity score better captures illness severity and moves the field towards current recommendations for TD management by considering symptoms with high functional impact. Further validation of this score is needed in non-military travellers and other settings. [ABSTRACT FROM AUTHOR]

Background: Travellers' diarrhoea (TD) is the most common clinical syndrome affecting travellers. This narrative review summarizes key discoveries reported in the last two years related to TD and suggests areas for future research.Methods: A PubMed literature search was conducted for novel data in TD research published between 12 January 2018 and 12 January 2020. Inclusion was based on contribution to epidemiology, aetiology, diagnostics, management and long-term consequences and relevance to public health, discovery and clinical practice.Results: The initial literature search yielded 118 articles. We retrieved 72 and reviewed 31 articles for inclusion. The findings support our understanding that TD incidence varies by traveller group and environment with students and military-travel remaining moderately high risk, and control of food and water in mass gathering events remain an important goal. The growth of culture-independent testing has led to a continued detection of previously known pathogens, but also an increased detection frequency of norovirus. Another consequence is the increase in multi-pathogen infections, which require consideration of clinical, epidemiological and diagnostic data. Fluoroquinolone resistant rates continue to rise. New data on non-absorbable antibiotics continue to emerge, offering a potential alternative to current recommendations (azithromycin and fluoroquinolones), but are not recommended for febrile diarrhoea or dysentery or regions/itineraries where invasive pathogens are likely to cause illness. Recent studies investigated the interaction of the microbiome in TD prevention and consequences, and while discriminating features were identified, much uncertainty remains. The prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and carriage is increasing. Finally, continued research documents the post-infectious consequences, whereas mechanisms of reactive arthritis and post-infectious IBS necessitate further investigation.Conclusions: Globally, TD remains an important travel health issue and advances in our understanding continue. More research is needed to mitigate risk factors where possible and develop risk-based management strategies to reduce antibiotic usage and its attendant consequences. [ABSTRACT FROM AUTHOR]

An editorial is presented on the potential role of antibiotics for diarrhea in travelers for the development of the antibiotic Rifamycin SV formulated with an enteric coating and a patented multimatrix technology which targets the delivery of the antibiotic to the distal small bowel and colon. It expresses the view that there remains a continued need for novel travel medicine antibiotic therapy.