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Travelers' diarrhea: update on the incidence, etiology and risk in military and similar populations – 1990-2005 versus 2005–2015, does a decade make a difference?
Scott Olson1,
Alexis Hall1,
Mark S. Riddle2 &
Chad K. Porter1
Tropical Diseases, Travel Medicine and Vaccines volume 5, Article number: 1 (2019) Cite this article
Travelers' diarrhea remains a prevalent illness impacting individuals visiting developing countries, however most studies have focused on this disease in the context of short term travel. This study aims to determine the regional estimates of travelers' diarrhea incidence, pathogen-specific prevalence, and describe the morbidity associated with diarrheal disease among deployed military personnel and similar long term travelers.
We updated a prior systematic review to include publications between January 1990 and June 2015. Point estimates and confidence intervals of travelers' diarrhea and pathogen prevalence were combined in a random effects model and assessed for heterogeneity. Eighty-two studies were included in the analysis, including 29 new studies since the prior systematic review.
Military personnel were evaluated in 69% of studies and non-military long term travelers in 34%, with a median duration of travel of 4.9 months, and travel predominantly to the Middle East, Southeast Asia, and Latin America and the Caribbean. Sixty-two percent of tested cases were due to bacterial pathogens, with enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC), and Campylobacter predominating, and significant regional variability. The incidence of TD from studies with longitudinal data was 36.3 cases per 100 person-months, with the highest rates in Southeast Asia, Latin America and the Caribbean, and the Middle East, with higher estimates from those studies using self-reporting of disease. Morbidity remained significant, with 21% being incapacitated or placed sick in quarters (SIQ) by their illness, 15% requiring intravenous fluids, and 3% requiring hospitalization.
In comparison to results from the prior systematic review, there were no significant differences in incidence, pathogen prevalence, or morbidity; however there was a trend toward improved care-seeking by sick individuals.
In the United States foodborne disease affects 1 in 6 individuals per year, and while the majority (80%) of cases are due to unidentified causes, among diagnosed etiologies in this setting, viruses predominate [1]. While most cases are self-limited and do not require targeted therapy, enteric illnesses account for an estimated annual cost of $93.2 billion [1]. In contrast, among travelers to developing countries, the rate of acute enteric disease has been historically much higher, with an estimated attack rate of 29% per month [2]. In addition, bacteria predominate as the cause of acute illness, with diarrheagenic E. coli, Campylobacter spp., and Shigella spp. representing the most commonly isolated pathogens [3,4,5]. And while rates of travelers' diarrhea (TD) among short-term travelers (less than one month) may be decreasing [6], we previously reported unchanged rates of disease among long-term travelers [2].
Deployed military personnel represent a unique subset of travelers, among whom TD historically has caused significant morbidity and mortality. Throughout recorded history, the importance of infectious enteric disease has been noted, with mentions of diarrheal illness among troops as early as the Peloponnesian War [7]. In American history, acute enteric illness has been noted to hinder military operations in every major war, from the Civil War through the Vietnam War [7]. More recently, data from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) highlight that acute diarrheal illness has remained the most common non-combat disease among deployed US personnel, with incidence as high as 45 episodes per 100 person-months [8,9,10].
The risks for developing acute TD are similar between military and non-military long-term travelers, with first time travel or deployment, travel or deployment to developing nations, younger age, and lack of dietary discretion being common risk factors [5, 6, 11, 12]. Among both military and non-military travelers, individuals afflicted by TD during their travel are often precluded from participation in daily activities and work. This scenario in the military can result in potentially high numbers of lost duty days across an entire deployed population, and close living conditions can lead to large outbreaks [10, 13,14,15].
Our 2006 systematic review highlighted the incidence, etiology, and impact of travelers' diarrhea among US military personnel and similar travelers [2]. Since that time major changes to the pattern and tempo of military deployment and multiple new studies of TD in this population necessitate an update to the prior systematic review to include studies published since 2005 and better describe regional estimates of diarrheal disease incidence, pathogen-specific prevalence, and management options and morbidity among long-term travelers, including deployed US military personnel and similar populations. In updating the prior systematic review, we demonstrate how diarrheal illness has changed among long term travelers in the past decade, so that in both the civilian and military populations providers can better manage this prevalent disease using the most current data.
We performed a systematic review of the scientific literature published between July 1, 2005 and June 30, 2015, based on accepted principles of methodological design [16, 17], including eligibility criteria for available evidence, standardized data abstraction, critical appraisal of the evidence, and standardized methods of data analysis. These data were then combined with data from our previous 2006 study.
Search strategy and study selection
We conducted our review initially by performing a comprehensive search of electronic bibliographic databases (including MEDLINE, EMBASE, CINAHL, and the Cochrane Library). Additionally manual searches of bibliographies of identified studies, technical reports, and doctoral dissertations were performed. All searches were performed by pairing keyword(s) [travelers' diarrhea or diarrhea] with each of the following terms eliminating duplicates: epidemiology, etiology, military, Peace Corps, expatriate, incidence, burden, morbidity, and treatment. In addition, MEDLINE searches were conducted using major MeSH headings (medical subject headings) determined from articles known to be eligible. One reviewer screened all publications and reports for possible inclusion based on eligibility criteria. If eligibility could not be determined from title and/or abstract alone, the full-text was retrieved and evaluated. Data from retrieved articles, technical reports, and doctoral dissertations were abstracted based on inclusion and exclusion criteria then verified. All review articles were obtained for hand searching bibliographies to identify further potential articles for inclusion.
Original research in the form of observational cohorts, surveys, database analyses, or clinical trials published in English were considered for inclusion. Publications classified as review, in non-English language, editorials, case-reports, or irrelevant were excluded, and reasons for exclusion were recorded. Studies on US military and other similar or long-term travel populations were reviewed for inclusion criteria. Similar traveler populations were defined as expatriates of a developed country traveling or living abroad in a developing country. Long-term travel was defined as travel for ≥1 month. All studies involving US military, regardless of travel duration, were considered for inclusion. Studies involving tourists and short-term (< 1 month of travel abroad) business travelers were excluded. Studies with duplicate study populations were also excluded. Studies were categorized to geographic regions of sub-Saharan Africa, Latin America and the Caribbean, Southeast Asia, and the Middle East based on reported geographic regions of travel. Only publications reporting information for variables of interest to this study were included.
Data abstraction and validation
Using the same pre-tested, standardized abstraction form (included in Additional file 1) that was used for our prior systematic review, we abstracted data from retrieved articles and reports. Bibliographic information, study design description, study years, geographic location, and population characteristics (e.g., follow-up period, case definition, etc.) necessary to answer key questions and to evaluate heterogeneity of studies were included in the data abstraction form [2].
The primary outcomes of interest included quantitative and qualitative measures of etiology and incidence of TD and its associated treatment and morbidity. Pathogen prevalence was abstracted as a percentage of total cases reported, along with the study denominator that was used to calculate the prevalence. Because of the difficulty in determining the causality of disease when multiple pathogens are isolated, pathogen prevalence was reported as the number of cases infected with a specific agent inclusive of cases with multiple organisms. The total number of diarrheal cases was abstracted along with the size of the study population and study period used to compute diarrheal prevalence/incidence for each separate study. Incidence was abstracted as an event number, with person-time as the denominator when available. In prophylaxis trials, estimates were only abstracted for the placebo group. Estimates were stratified based on self-reporting, clinic-based case series, or disease and non-battle injury (DNBI) reports. Data were then combined with the 2006 review data.
Pathogen prevalence and incidence were stratified by region as geographic differences as previously described [18, 19]. Because of known variations in study design, methodologies, population characteristics, and other factors, heterogeneity of prevalence and incidence estimates across studies was expected and assessed graphically with Forest plots and statistically through the use of heterogeneity statistics and non-parametric methods. For the purpose of summary, point estimates and 95% confidence intervals were calculated using a random effects model with methodology developed by DerSimonian and Laird [20].
In the case of parameters where only a few studies were found (e.g., probabilities and outcomes associated diarrhea and treatment), a median and range of estimates are reported. Publication bias was not assessed, because the concern of non-published findings caused by negative studies or disappointing results was considered to be minimal, given the objective of summarizing pathogen prevalence and disease incidence.
All analyses were conducted using Stata V13 (StataCorp, College Station, TX).
Our initial search of the literature identified 454 eligible articles. Of those studies 273 were rejected on review of abstracts due to being duplicate studies (n = 18), reviews (n = 53), case reports or editorials (n = 36), or finding inappropriate titles or abstracts (n = 161), with an additional 164 studies excluded after full review due to ineligible populations (n = 92), non-extractable data (n = 52), or being reviews or editorials (n = 12). Twelve additional studies were identified from the references of retrieved articles. Following evaluation for suitability, 29 articles were identified for final inclusion, abstracted, scored for quality, and combined with data from the precursor review (n = 52). Results from an additional unpublished study were also identified and included following review of the available draft manuscript, yielding a total of 82 included studies in the updated systematic review [9, 14, 18, 21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96]. The study selection process is detailed further in Fig. 1.
Flow diagram of study selection for inclusion in the updated systematic review. We identified 454 candidate studies for inclusion since the last systematic review by query of electronic bibliographic databases. After review of titles and abstracts, 193 studies were identified for full review, with 164 studies excluded. Thirty studies were identified for inclusion in the final systematic review, with a total of 82 studies when those from the prior review were included
As shown in Table 1, the median sample size of the studies included in this systematic review was 240 travelers (interquartile range [IQR] 114, 1529). The travel population identified in these studies was primarily composed of deployed US military personnel (54 studies, 69%), with non-US military populations evaluated in 28 studies (34%). The median duration of travel to developing nations was 4.9 months (IQR 1, 5.7), with travel predominantly to the Middle East/North Africa region (52% of travelers), followed by S.E. Asia and Latin America/Caribbean (each 14%) and Sub-Saharan Africa and "Multiple regions" (each 10%). The included studies ranged in study design, with descriptive studies (n = 25, 30%), clinical trials (n = 16, 19%), and cohort studies (n = 12, 15%) representing the most common designs. A majority of studies (n = 59, 72%) included the standard definition of travelers' diarrhea (at least three loose stools in a 24-h period or at least two loose-stools in a 24-h period with associated symptoms). The median year of all studies was 1999.
Table 1 Studies included in current systematic review of diarrheal illness among long term travelers since 2006
Pathogen prevalence
Fifty-two studies (63%) reported etiologies of acute TD, with the majority of cases (64% of 11,613 total) having an identified pathogen recovered. Bacterial pathogens were identified in 62% of cases where testing was performed (10,552 tested), with viral (7% of 5443 tested) and parasitic (4% of 5905 tested) pathogens being detected at much lower frequencies (Fig. 2). Recovery of multiple pathogens was found in 11% of tested TD cases, and no pathogens were detected in 36% of cases. There was marked heterogeneity among studies estimating prevalence for individual pathogens across all regions (χ2 heterogeneity statistic, P < 0.001); pathogens included in the analysis were those listed in Table 2, and regions included were defined as SE Asia, Africa, Middle East, and Latin America/Caribbean. Among identified bacterial causes, enterotoxigenic E. coli (ETEC, 44% of bacterial cases), enteroaggregative E. coli (EAEC, 21%), and Campylobacter spp. (19%) were most commonly reported. Other bacterial pathogens reported at lower rates include enteropathogenic E. coli (EPEC, 6% of bacterial cases), Shigella (6%), and Salmonella spp. (3%). There were no significant differences in prevalence of various pathogens between studies before and after 2006 (Table 2).
Pathogen prevalence of diarrheal illness among long term travelers, 1990–2015. Of those cases for which diagnostic testing was performed, 62% were positive for bacterial pathogens, with viruses (7%) and parasites (4%) being detected at lower rates. ETEC was the most commonly isolated bacterial etiology (44%), followed by EAEC (21%) and Campylobacter spp. (19%). Multiple pathogens were detected in 11% of tested cases and no identified pathogens in 36%
Table 2 Comparison of pathogen prevalence between prior review and update
There was notable variability in the prevalence of specific pathogens between regions. ETEC and EAEC were predominant pathogens in Africa (36% each of total identified causes) and ETEC in the Middle East (39%), while Campylobacter (63%) and Salmonella (16%) were the most commonly isolated pathogens in SE Asia. Although viruses were less frequently identified pathogens, norovirus represented a higher proportion of cases in Latin America/Caribbean (14%) than other regions (Fig. 3). The rates of multiple pathogen recovery ranged from 7% of cases in the Middle East to 16% in SE Asia. Across regions, there was also variability in the rates of successful pathogen identification, with no identified pathogen found in 20% of tested subjects in SE Asia compared to 51% in Africa.
Region specific pathogen prevalence of diarrheal illness among long term travelers, 1990–2015. We identified variability of pathogen prevalence across studies from different regions. In Latin America/Caribbean, Africa, and the Middle East, the most common identified pathogen was ETEC, while in SE Asia Campylobacter spp. predominated
Pathogen prevalence also varied depending on the type of traveler assessed. In US military populations (5520 cases tested), ETEC (28% of identified pathogens), Campylobacter (15%), and EAEC (9%) were most commonly detected, with multiple pathogens detected in 9% of cases and no identified pathogen in 35%. Among non-US military populations (6093 cases tested) EAEC (36% of identified pathogens), ETEC (19%), and norovirus (15%) predominated, with multiple pathogens identified in 16% of cases and no identified pathogen in 51%.
Fifty-three studies (64%) reported incidence of TD among 65,555 long-term travelers. As with pathogen prevalence there was considerable heterogeneity between studies used to estimate diarrhea incidence (χ2 heterogeneity statistic, P < 0.001). We estimated a pooled incidence of TD among long-term travelers of 36.3 cases per 100 person-months (95% confidence interval [CI] 29.2–43.4, 26 included studies) (Fig. 4). The incidence of TD appeared to be greatest within the first month of travel (48.9 per 100 person-months before 1 month vs. 31.3 after 1 month; p < 0.001). There was heterogeneity in TD incidence across regions, with the highest incidence experienced by travelers to SE Asia (41 cases per 100 person-months, 5 studies), Latin America/Caribbean (39.4, 3 studies), and the Middle East (35.2, 14 studies) (p < 0.001). Lower incidence of TD was found in S. Asia (33.3, 2 studies) and Africa (27.4, 1 study). Because it represented the largest regional dataset, we evaluated the subset of long-term travelers to the Middle East for any temporal trends in incidence and found TD had not changed significantly from 2006 (29.4, IQR 13.6, 45.2; 14 studies) to 2015 (27.2, IQR 20, 36.2; 12 studies).
Incidence of diarrheal illness among long-term travelers, 1990–2016. We found an estimated overall pooled incidence of TD among long-term travelers of 36.3 cases per 100 person-months. Studies included in the prior systematic review (AJTMH, 64(5), 2006) are listed at the top of the forest plot, with studies since that time included at the bottom of the figure (2018 Update). Weights calculated by random effects model
Among the 53 studies, twenty-seven studies estimated TD incidence by clinic-based reporting of subjects presenting to care for acute illness. The overall pooled estimate based on these studies was 7.7 cases per 100 person-months (95% CI 6.5–9.0), with no significant differences noted between US military populations (7.6, 95% CI 6.2–8.9) and other travelers (7.4, 95% CI 5.5–9.3). Twenty-six studies estimated incidence by either self-reporting of symptoms or cohort study design with an overall pooled estimate of 36.3 cases per 100 person-months (95% CI 39.9–41.7), and no significant differences between US military (37.5, 95% CI 30.7–44.4) and other travelers (33.2, 95% CI 27.7–38.8).
The rate of seeking care appeared to have increased since the 2006 review. Within the subset of studies from 1990 to 2005 that reported care-seeking behaviors, only 16% of sick individuals (95% CI 12–21%, 7 studies) sought medical care, while from 2006 to 2015 38% sought care (95% CI 32–45%, 7 studies; p = 0.012). The cumulative rates of care-seeking across all included studies was 25% (95% CI 22–29%).
Thirty-five studies (43%) had extractable information that described the parameters of disease morbidity, including disease severity and treatment outcomes. A total of 21% of subjects reported being sick-in-quarters (SIQ) or incapacitated by their illness, 15% required IV fluids, and 3% required inpatient hospital admission for treatment (Table 3). Additionally there appeared to be a higher rate of travelers placed SIQ or incapacitated by their acute illness when Shigella or Campylobacter spp. were isolated compared to other bacterial etiologies, though this was not a statistically significant finding. Nine studies reported the probability of treatment failure among travelers reporting for care, with a median rate of failure of 9%. Thirty-six included studies (44%) reported the morbidity of treated and/or untreated disease. For travelers with TD who did not seek care or receive treatment, the median duration of symptoms was 3.0 (IQR 2.4–3.5) days. Those who did seek care reported a median of 1.4 days of symptoms before presenting to medical care, and 1.5 days of symptoms after treatment. Of those who presented to care, 85% received an anti-motility agent (loperamide), while 57% received antibiotic medications. The time to last unformed stool was shorter for travelers administered antibiotics plus loperamide versus those receiving antibiotics alone (9.6 vs. 21.8 h), though this difference was not statistically significant (p = 0.2).
Table 3 TD associated outcomes ('90 – '15)
This updated review reveals that travelers' diarrhea remains a major medical concern among deployed US military and other long-term travelers, with a pooled incidence of over 30 cases per 100 person-months, and the highest incidence in the first month of travel. In addition to this high rate of illness, we found no notable change in incidence over the last 25 years of available data. This finding differs from previous reviews of TD among all travelers that suggest a decrease in incidence over the past two decades [6]. Since one could assume that eating local fare or consuming improperly treated water while traveling would drive the continued high rate of diarrheal disease while traveling, the restricted access of military personnel deployed to active theaters (Middle East) should preclude eating food or drinking water locally acquired. Our finding that the rate of TD among US military personnel is similar to other long term travelers would contradict this conclusion, suggesting that off base exposures are ubiquitous and food and water control is difficult [10]. Given that the incidence of disease remains high despite pre-travel education and counseling, other preventative measures, namely development of successful vaccines against the most common pathogens, should remain a focus in ongoing research. In addition to the continued high rates of disease, we found that incidence is much higher when studies use self-reporting, reflecting that studies relying on active surveillance (clinic or DNBI-based) likely underestimate the true incidence of TD [97]. And while our last systematic review found that there was no appreciable difference in incidence across different regions, in this update we found that incidence of disease was higher in SE Asia than all other included regions. Prior reviews have also noted regional variability, with higher rates of TD in SE Asia, South Asia, Northern and Sub-Saharan Africa, and the Middle East compared to other travel destinations, with an overall trend of decreasing rates of TD in South America and East and Southeast Asia [4, 6, 12, 98].
We found that in those studies where evaluation for specific infectious etiologies was performed, a majority of subjects had at least one pathogen identified, a finding consistent with other reviews that have reported pathogen recovery ranging from 50 to 94% of TD cases [3, 4, 6]. Consistent with estimates from our prior systematic review, diarrheagenic E. coli (particularly ETEC and EAEC) and Campylobacter remained the most common pathogens causing TD in aggregate. As was demonstrated in the prior review, we again note significant variability of enteropathogens across geographic regions, with SE Asia experiencing the highest prevalence of Campylobacter and Salmonella infections, and higher rates of norovirus recovery in South America. Our findings correspond with an epidemiologic survey by Shah et al., in which ETEC was the predominant enteropathogen across all regions, found in 30% of all subjects studied, followed by EAEC, with higher prevalence of norovirus and rotavirus in Latin America and Africa, and Campylobacter and Salmonella in Southeast Asia [3].
In addition to the variability of specific etiologies, we also found that the rates of successful isolation of pathogens varied by region, ranging from only about 50% in Africa up to almost 80% in SE Asia. This finding likely reflects the heterogeneity of study designs. And while improvements in storage and processing (including culture-independent detection methods) have occurred in the last two decades, we did not note any apparent improvement in pathogen recovery over this time period. Shah et al. noted that while use of PCR diagnostics resulted in a higher rate of detection of diarrheagenic E. coli species not detected on routine culture, this finding has not been replicated in larger epidemiologic studies [3]. We anticipate studies utilizing molecular diagnostics for pathogen identification will reveal whether viral pathogens such as norovirus represent a large proportion of the unidentified cases. While recent studies have found norovirus to be the second leading cause of TD after ETEC, analysis of samples in the Global Enteric Multicenter Study (GEMS) comparing culture-based and culture-independent molecular diagnostic methods found higher estimates of incidence of disease from ST-ETEC and Shigella with PCR-based diagnostics, but similar estimates of viral (Norovirus) and parasitic (Cryptosporidium) pathogens [99,100,101]. As the GEMS study aimed to characterize diarrheal illness among children less than 5 years old in developing countries, it is possible that pathogen prevalence will inherently differ from our findings, largely due to the difference between local children and international travelers in epidemiologic exposures within the same geographic location.
Based on reported duration of symptoms from subjects not seeking care, we found that the total duration of symptoms of uncomplicated disease is around three days. Interestingly, we found that duration of symptoms among individuals seeking care was similar (1.4 days before treatment and 1.5 days after). It is likely that as TD is routinely a self-limited disease, treatment may mitigate severity but not duration of symptoms. While we did not find a difference in duration of symptoms between treated and untreated travelers, within the group of travelers who received treatment, data on time to last unformed stool (TLUS) demonstrates that subjects administered a combination of loperamide plus antibiotic reported more rapid recovery than those using only antibiotics, with a difference of almost 20 h. In contrast to our findings, a Cochrane review of TD found quicker resolution of symptoms with antibiotic therapy [102]. In addition a recent study of single-dose antibiotic treatment of TD among deployed military personnel found that treated individuals experienced TLUS of around 12 h compared to greater than 72 h in historically untreated controls [103].
Despite this relative short duration of symptoms, there remains a significant burden of morbidity due to more severe cases, with a high rate of individuals being incapacitated as a result of their illness or requiring IV rehydration. Our results are consistent with previous studies that found approximately 20–50% of subjects altered plans or were incapacitated due to TD, 10–20% being confined to accommodations, and 1% requiring hospitalization [37, 104,105,106]. While only 3% of TD cases were admitted for treatment, the high incidence of disease among long term travelers suggests that in situations such as large scale deployment of troops, severe, debilitating disease can be a large medical threat to operational readiness.
While the incidence of diarrheal disease and its associated morbidity among long term travelers does not appear to have changed since the original systematic review, there has been some improvement in the rates of care seeking. Compared to reported care seeking behavior described in 2006, subjects since that time have been roughly twice as likely to seek care for an acute gastrointestinal illness. It is uncertain what might explain this change, whether due to study differences or actual increasing awareness by service members of the potential effectiveness of therapies available over the course of a prolonged operational effort. Presenting to care early may lead to mitigation of morbidity from more severe cases and could potentially decrease the risk of developing post-infectious sequelae, such as irritable bowel syndrome, which is estimated to occur in up to 10% of cases. Observational studies show that illness duration and severity are independently associated with increased risk of PI-IBS [107]. Despite the finding that care-seeking behavior is improving, and at higher rates than reported in prior studies (5–15%), the overall rate of presenting to medical attention remains sub-optimal, at only about one in three cases, and remains a target for improvement [4, 98, 105, 106]. From a systematic standpoint, a recent cost effectiveness analysis of models to improve care seeking behaviors and optimize treatment among deployed military personnel demonstrated that modest cost increases could result in significant decreases in duty days lost to TD [108]. If applied across the military and civilian sector, this analysis demonstrates that time lost to illness could be decreased, and productivity of travelers increased, by focusing on encouraging sick individuals to seek care and optimizing treatment by providers.
This review includes a comprehensive literature search, prospective inclusion and exclusion criteria, standardized data abstraction, and current analytic methods, all of which reduce the potential bias in the resultant population of studies used for analysis. Limitations of this study include the heterogeneity of prevalence and incidence across the different included study designs, populations included, regions of study, and sparseness of data for some measures, particularly pathogen-specific outcomes of disease. While a small number of independent variables were found to explain some of the heterogeneity among included studies, small study numbers precluded further analysis of what factors may be associated with differential pathogen prevalence and disease incidence. Because several of the included studies in this review were performed in serial assessment from the same specific location within a region (e.g., military exercises in Thailand, student populations in Mexico), caution should be taken in generalizing these findings across an entire region. In addition the study excluded individuals traveling for business, leisure, or to visit friends and relatives (VFR), so our findings may not be applicable to these populations of travelers, though prior evaluation of excluded studies based on population non-eligibility did not find any appreciable differences in estimates of disease [109,110,111,112,113]. Our findings also highlight that there are significant differences in the etiology of diarrheal disease between deployed US military personnel and other long-term travelers, so collapsing the findings may not reflect the true epidemiology of disease in each population; however, as previously stated this finding may simply represent differing travel destinations and not an inherent difference in populations. The paucity of studies reporting epidemiologic data from important regions such as India, China, Oceana, and Sub-Saharan Africa is a major limitation of our systematic review. Lastly, this review focused primarily on endemic (sporadic) diarrheal illness occurring in long-term travel populations. Because pathogens associated with epidemic diarrheal illness also cause significant morbidity and can impact military operations, epidemiologic data on epidemic disease would be helpful, but is outside the scope of this review.
This updated systematic review of studies on diarrheal illness among US military personnel and similar long-term travelers provides some important conclusions. Diarrheal disease among long-term travelers remains a frequent occurrence, and the associated morbidity is significant. While care-seeking behaviors have been improving over the last ten years, a high percentage of cases of diarrheal disease are not brought to medical attention. While it is unclear if these missed cases represent milder illnesses that are managed with self-treatment, capturing these cases could potentially result in decreased time spent incapacitated by illness or associated morbidity. Diarrheagenic E. coli (ETEC and EAEC, particularly), Campylobacter, and Shigella species remain significant diarrheal pathogens globally, with some variations in prevalence geographically. Among long-term travelers, a number of other bacterial, viral, and parasitic pathogens, though not encountered as frequently, need to be considered in cases of diarrheal disease. Lastly, because diarrheal disease remains frequent in this population, the high incidence of cases not seeking care remains high, and the associated morbidity of disease can be significant, diarrheal disease should be considered an important health threat and be investigated further with further well-designed studies, including those focused on timely and effective treatment strategies and preventative measures including behavioral or hygiene interventions and vaccine development.
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The authors would like to acknowledge the support of the Naval Medical Research Center leadership.
Salary support for the investigators came from the Military Infectious Disease Research Program.
The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. This is a US Government work. There are no restrictions on its use. There were no financial conflicts of interests among any of the authors.
Some of the authors are employees of the U.S. Government or military service members. This work was prepared as part of official duties. Title 17 U.S.C. §105 provides that 'Copyright protection under this title is not available for any work of the United States Government.' Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties.
Enteric Disease Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA
Scott Olson, Alexis Hall & Chad K. Porter
Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Mark S. Riddle
Scott Olson
Alexis Hall
Chad K. Porter
Scott Olson assisted in analysis and interpretation of data, and drafted and edited the final manuscript. Alexis Hall was involved in developing the concept and design of the study and performed a majority of the data collection. Mark Riddle assisted in developing the study design, interpreting the results, and drafting and editing the final manuscript. Chad Porter developed the study concept and design, participated in analysis of data and interpretation of results, and contributed to the final manuscript.
Correspondence to Chad K. Porter.
This study was reviewed and approved by the Naval Medical Research Center IRB.
As the data for this systematic review lack subject identifiers or other personal identifying information (PII), consent from individual subjects is not required.
Systematic review of travelers' diarrhea--data abstraction form. (DOC 69 kb)
Olson, S., Hall, A., Riddle, M.S. et al. Travelers' diarrhea: update on the incidence, etiology and risk in military and similar populations – 1990-2005 versus 2005–2015, does a decade make a difference?. Trop Dis Travel Med Vaccines 5, 1 (2019). https://doi.org/10.1186/s40794-018-0077-1
Long term traveler
Enterotoxigenic E. coli (ETEC)
Enteroaggregative E. coli (EAEC)


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redpajama_set_name: RedPajamaStackExchange


These Snuggle Bugs are cozy and relaxing. They are filled with wheat. Warm them in the microwave for up to 3 minutes. When you take them out you can hold them by the wings and give it a good shake to mix the warmed wheat.
Our kids use them at night mostly, but I also find them in the car on cold days, on their laps on chilly mornings, stuffed down their coats waiting at the bus stop, at school on cold days (yes, they even take them to school and use their teachers microwaves to warm them throughout the day). We love to warm them up and stick them in the bed while we are getting ready for bed, then your bed is already nice and cozy warm to climb into.
Homemade. I do my best to look over the work of each Bug that we make, But there is always a chance of there being a problem. If you come across one please let me know.


Mock Trial is both a classroom strategy and an extracurricular competition that high school students have loved for decades. Using a mock court case, students play the roles of attorneys, witnesses, and court officers while learning the lasting skills of public speaking, teamwork, research, collaboration, civil and criminal legal concepts, and civic engagement. It is a way to bring the law alive for students and to give them a voice in what otherwise might seem a very distant judicial system.
Oregon has been participating in the National High School Mock Trial Competition (NHSMTC) since 1987, and Classroom Law Project is proud to carry that legacy for Oregon high schools into the 21st century! Every March, over 70 teams from high schools all around the state compete in 8 different regional competitions. The winners of those regionals compete at the State Competition and that winner goes on to Nationals. Check out all our past winners!
Classroom Law Project coordinates the high school mock trial competitions in Oregon and also provides workshops for teachers on how to implement mock trial strategies in their classrooms.
Check our upcoming events for learning opportunities. To see historical materials — including past case packets — visit our resources page and filter the PROGRAM by "Mock Trial".


Anybody watch the Martinsville finish?
Joey "The Joker" Logano drives his way to Miami through the rear bumper of the #78.
Truex runs him clean, side by side for the last 10 laps... Could have taken the #22 out multiple times... Continued to race him clean... Made the clean pass on Logano on the last lap... Logano runs it hard into turn 3, and solidly pushes Truex up the track, and goes on to take the win.
Curious that Logano didn't stop on the frontstretch and grab the checkered flag as has become the norm for cup winners. Looked like he stopped on the backstretch maybe? Not sure why, but I'm thinking that it would have been pretty hostile over by where the remaining crowd was booing. Think there's quite a few more Truex fans out there than Logano fans, and there's probably even less Logano fans after today's event.
Truex ends up 3rd, and all Logano can say is, "I'm on my way to Miami!"
They say that rivalries are good for the sport.
In the post race, Junior said, "I tell Martin that he's too nice..."
I always liked the rule that you race others the way they race you. Based on that, I think it was a pretty chicken shi+ move on Logano's part, but I'm not a racer, and maybe that no longer holds true for some.
I don't know if Truex can win the championship, but I know that he can make it difficult for Logano to win.


DALLAS (AP) - United and Continental airlines are reducing flights between the U.S. and Japan because of a drop in demand since the March 11 earthquake and tsunami.
The sister airlines will cut their combined passenger-carrying capacity on U.S.-Japan flights by 10 percent in April and 14 percent in May.
Spokeswoman Julie King said Thursday the airlines will drop a few flights a week between four U.S. cities and Tokyo, and will delay adding a second daily flight between San Francisco and Tokyo by a month, until April 27.
King said the moves were made "because of the measurable decline in demand for travel between the two countries," but she wouldn't put a percentage figure on the drop-off.
The news from United Continental Holdings Inc. came one day after AMR Corp.'s American Airlines said it will suspend two of its six daily flights to Japan next week until late April. Delta Air Lines Inc. said last week it will suspend service to Haneda Airport in Tokyo, although it will keep flying to the other big Tokyo airport, Narita.
Travel to, from and within Japan has slumped as the nation deals with power shortages and fear of radiation leaks from a damaged nuclear power plant.
King said United will drop some flights each week between Tokyo Narita and Los Angeles, Seattle and Washington's Dulles International Airport. Continental will do the same on its Narita-Newark, N.J., route, which will lose seven round trips in May.
United also is switching to smaller planes - Boeing 777s instead of 747s - on its Chicago-Narita route because of the weak demand.
Continental previously announced it stopped flights from Guam to Sendai, Japan, because of damage to the Sendai airport.
Together, United and Continental have 1,000 employees at nine airports in Japan.


At Freedman & Lorry, P.C. we take great pride in the attention to detail and dedication provided by our attorneys to all our clients.
Your comments and experiences with our legal services are vital in ensuring that we uphold our reputation as lawyers who fight to protect the rights of men and women – both in and out of the workplace. Following are some of the testimonials we have received from clients.
Court, Custody, and lawyers are all very intimidating but when you have Rebecca in your corner, you know she will advocate for you as if you were her closest friend. She cares about me, and most importantly, my children. If your expectations or requests are unlikely, she will be honest with you. She does not waste your time or your money. She works for every penny and is relentless in her efforts to achieve the best outcome possible for her client. I am forever grateful that I am lucky enough to call her my attorney and would recommend her to anyone in need of an advocate who will know your case and fight for you. The woman will sacrifice sleep for days because she cannot rest unless she knows she is fully prepared to represent her client in court. You will not regret hiring Rebecca and once you see her in action you will be grateful that you were smart enough to choose her to represent you.
Rebecca is beyond a lawyer! She helped me and my fiancé get full custody of both of our children in what was a very complex and complicated situation in a very short period of time. Rebecca was always available, reliable, gave great advice, and was a "Jedi Knight" in the courtroom. I highly recommend Rebecca for custody matters – no matter how complex. I also recommend her for PFA and eviction matters. Can't thank her enough!
I want to thank Paul he is great! Totally made me feel at ease at once always told me to call him or his paralegal Megan, she is such a sweetheart and very calm,she and Paul are the Greatest!!!! Thank you so much for everything!!!!
Thank you for taking my case and getting me the settlement you did. To think that I might have forfeited that sum of money if you hadn't had your website out there, educating me on what I was entitled to for my injuries under the Defense Base Act. Certainly, neither my employer nor the insurance company ever told me I was entitled to anything more than coverage while I was off work. Actually, I wish I'd seen your site sooner, and then contacted you immediately. Because you already had a long established relationship with the individual best positioned to ensure insurance companies fulfill their obligations under this particular act, I'd have saved myself some major headaches and probably received more compensation.
It was a pleasure to work with you. I had some concerns about signing on with an attorney I discovered through the Internet. But after talking to attorneys here and then in Dallas, Texas where I'd lived before going overseas, it seemed obvious you were the best choice due to your familiarity with the Defense Base Act and the players. The others despite specializing in personal injury and workers compensation cases knew nothing about how to handle people like me who fell under the Defense Base Act. And as it turned out, it was easy working by phone and e-mail.
I'm grateful you were out there and supported me, and are out there willing to support others, especially in these difficult times where so many are sustaining life-changing injuries while working on behalf of the military. I just hope they discover you, and sooner than later, too. May I share your name with a friend with the Red Cross who is currently in Iraq, just in case she comes across civilians there who could use your help?
RELIABLE. AFFORDABLE. ON POINT. These were the initial qualities I was looking for in a Lawyer. However, as Rebecca Kolsky helped me with my divorce in the past 7 months, it was very well-evident that she far surpassed my expectations. Here is why I have found her so UNIQUE….
1.RELATABLE: MAKES YOU FEEL AT EASE. PATIENT. EMPATHIZES.
Most times, lawyers time you at your initial consultation, and often charge you as well. Rebecca doesn't do this. She gives you as much time as you need. You're already scattered and nervous. But now you're tongue-tied and forgot what you were going to say. Rebecca RESPECTS YOU REGARDLESS OF YOUR FAUX PAS. SHE GETS YOU. You can feel it, and you can see it in her expressions. This mentality and level of respect will carry into her working rapport with you throughout your entire case. It is very relieving.
2. SOLUTION-CENTERED: PROVIDES OPTIONS. POSITIVE.
The other Lawyers I talked to made it sound like there was only one way to proceed. They didn't initiate options unless you knew what to ask. Rebecca not only initiates options, but she GOES THE EXTRA MILE to CUSTOMIZE YOUR OPTIONS based on your SITUATION. Just let her know what you need and how you feel. She's also patient in helping you understand the legal whys and hows. She puts herself in the client's shoes and gets that we won't always grasp things the first time around.
3. RESPONSIVE: REPLIES QUICKLY. COVERS ALL BASES.
Rebecca is incredibly quick to respond to your inquiries and answer your questions. She provides in-depth explanations and offers additional nuggets of wisdom to consider to help you make your decisions. She also follows up with all parties to make sure they received everything they should. She doesn't assume things are going smoothly; she MAKES SURE they are.
4. NO SURPRISES! GREAT CONNECTIONS.
Itemization was fair and there weren't any surprises. Rebecca tells you her thoughts up front, alerts you to any court fees you'll need to pay, and lets you know in advance the status of your retainer and upcoming bills. She also has really great connections with third parties, her team is very nice, and she's genuinely happy for you when you are happy.
My divorce went incredibly smoothly, and it is all thanks to Rebecca. I highly recommend her!!!!!!!!!!!!
I'm happy to report, that once again we have prevailed in an unjust firing at the Philadelphia Inquirer. Arbitrator Richard Kasher ruled on August 31st that the employer did not have good and reasonable cause to demote, and then terminate sports columnist Stephen A. Smith in January of 2008.
This continues our undefeated winning streak in arbitrations against PMH, and our counsel Neal Goldstein has taken the title of "Lights Out" away from Phillies closer Brad Lidge. We have not lost any arbitration to the Tierney team, and with back pay may be closing in on a million dollars total.
I want to personally thank our brilliant legal team of good Neal, and evil Neal, and our executive committee for backing us when we ask for your approval to move cases to arbitration. Quite frankly, today is a good day at the Guild!!
Neal Goldstein and his Band of Lawyers represent Philadelphia's finest, the hourly work force.
F&L was established years ago to represent labor unions, union members and their families, and continues to serve this community. The firm supports labor organizations that represent workers in local court, negotiations, at arbitrations, if unjustly fired, and at the National Labor Relations Board.
Employers fear them because they know the attorneys at Freedman & Lorry know how to protect working men and women.
Need a Good Lawyer call the firm your Union calls and trusts.
Freeman & Lorry Labor Law Firm.


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Why VCs should care about trade mark due diligence
Alasdair MacQuarrie
Industry Analysis / Tue 6 Mar 2018
Investors cannot afford to go wrong in their approach to trade mark due diligence prior to startup investment, writes Alasdair MacQuarrie, partner at IP law firm Gill Jennings & Every.
VC investment is all about identifying startups with terrific growth potential and funding them to accelerate that growth to generate bigger returns sooner.
When it comes to identifying growth potential, a couple of things are known to be key decision factors for investors: is the founder or managing team "investable", and is the business built on a solid idea and viable brand?
VCs have a clear framework for evaluating the former, based on years of experience of seeing who is and isn't successful. They can usually quite quickly determine which founders or management teams have the potential to be great entrepreneurs and leaders, even when they don't yet have a solid track record.
But they can be less good at assessing the IP protection that safeguards a startup's innovation and brand. Too often, a VC's IP due diligence amounts to little more than a cursory check of public records to confirm a startup has filed for protection at all. Their corporate lawyers run a tick-box due diligence exercise that approaches IP from a purely technical, rather than commercial, perspective.
Often, those checks prioritise existing patents and other protection safeguarding the company's core offering, and treat trade marks as the poor relation.
There is some irony in this approach. Because growth acceleration is key in the early stages of any startup, early funding tends to be used for marketing and PR aimed at building a strong brand that people can buy into and that offers instant recognition. A trade mark protects the startup's brand, and can include a product name, a logo, or a slogan, not to mention the name of the startup itself, which is often overlooked; in other words, everything that customers see when interacting with the brand. Failure to protect these assets can put the startup's future at risk.
For investors, a lack of deep understanding of the importance of including trade mark protection in a solid IP strategy can lead to tricky situations. This is especially the case if they end up investing in startups whose IP isn't commercially and legally robust.
If this happens, instead of early investment being spent on marketing and PR, money might be redirected to fight a trade mark lawsuit or for a complete rebrand. Both can be expensive and completely avoidable. Still, if it has to come to this, it's better to deal with the issue in the early stages of a startup when adjustments are relatively easy to make. Companies can have their exit valuations slashed by as much as 70 per cent if gaps in their IP strategy exist.
Freedom to operate
International expansion is a common route to growth, but can be problematic if a startup hasn't established its freedom to operate under its chosen brand in its new target markets. IP rights are specific to different jurisdictions. Investors supporting international business growth must be confident that the startup is able to commercialise a product in a new country or region without infringing IP rights of others.
All sorts of things could get in the way here, from existing companies in the new markets that have a similar or identical brand to trade mark "squatters", who register other people's trade marks as their own in other countries or regions, thereby limiting or delaying a startup's growth potential.
The cost of getting this wrong can be severe. Not all companies are as lucky as Monzo (née Mondo), which made a virtue of falling foul of a (now all but forgotten) trade mark dispute. Instead of a lengthy and expensive legal battle, Monzo opted for a rebrand in order to continue building and scaling its business. It even turned the rebrand into a customer engagement exercise, capitalising on the goodwill of its early adopters and fans to invite suggested new names for consideration. Monzo has of course gone from strength to strength since then, but the cost and disruption of such a situation could have a severe negative impact on the prospects of a less well-established startup.
Investors need to be checking for potential situations like this, aligning IP due diligence to their scrutiny of a startup's business plan and being just as rigorous with the former as they are with the latter. Investors in particular take the long view, which is why it's vitally important that solid IP checks at the outset consider a startup's current position and market, as well as its growth ambitions. This will likely mean consulting specialists in IP law who are equipped to look strategically and commercially at a startup's assets, now and in the future.
Want to learn more about Intellectual Property? Download the 'IP Law: The Startup and Scaleup Guide', produced in partnership with GJE.
Partner at Gill Jennings & Every
IPlegaltrade markVC
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