- Open Access
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?
Tropical Diseases, Travel Medicine and Vaccines volume 5, Article number: 1 (2019)
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 . While most cases are self-limited and do not require targeted therapy, enteric illnesses account for an estimated annual cost of $93.2 billion . 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 . 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 , we previously reported unchanged rates of disease among long-term travelers .
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 . 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 . 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 . 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 .
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 .
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.
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.
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).
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.
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).
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).
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 . 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 . 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 . 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 .
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 . 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 . 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 .
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 . 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 . 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.
Scallan E, et al. Foodborne illness acquired in the United States--major pathogens. Emerg Infect Dis. 2011;17(1):7–15.
Riddle MS, et al. Incidence, etiology, and impact of diarrhea among long-term travelers (US military and similar populations): a systematic review. Am J Trop Med Hyg. 2006;74(5):891–900.
Shah N, DuPont HL, Ramsey DJ. Global etiology of travelers’ diarrhea: systematic review from 1973 to the present. Am J Trop Med Hyg. 2009;80(4):609–14.
Kollaritsch H, Paulke-Korinek M, Wiedermann U. Traveler’s diarrhea. Infect Dis Clin N Am. 2012;26(3):691–706.
Al-Abri SS, Beeching NJ, Nye FJ. Traveller’s diarrhoea. Lancet Infect Dis. 2005;5(6):349–60.
Steffen R, Hill DR, DuPont HL. Traveler’s diarrhea: a clinical review. JAMA. 2015;313(1):71–80.
Connor P, Farthing MJ. Travellers’ diarrhoea: a military problem? J R Army Med Corps. 1999;145(2):95–101.
Sanders JW, et al. Impact of illness and non-combat injury during operations Iraqi freedom and enduring freedom (Afghanistan). Am J Trop Med Hyg. 2005;73(4):713–9.
Riddle MS, et al. Past trends and current status of self-reported incidence and impact of disease and nonbattle injury in military operations in Southwest Asia and the Middle East. Am J Public Health. 2008;98(12):2199–206.
Riddle MS, Savarino SJ, Sanders JW. Gastrointestinal infections in deployed forces in the Middle East theater: an historical 60 year perspective. Am J Trop Med Hyg. 2015;93(5):912–7.
Kendall ME, et al. Travel-associated enteric infections diagnosed after return to the United States, foodborne diseases active surveillance network (FoodNet), 2004-2009. Clin Infect Dis. 2012;54(Suppl 5):S480–7.
Greenwood Z, et al. Gastrointestinal infection among international travelers globally. J Travel Med. 2008;15(4):221–8.
Centers for Disease, C. and Prevention. Outbreak of acute gastroenteritis associated with Norwalk-like viruses among British military personnel--Afghanistan, May 2002. MMWR Morb Mortal Wkly Rep. 2002;51(22):477–9.
Thornton SA, et al. Gastroenteritis in US marines during operation Iraqi freedom. Clin Infect Dis. 2005;40(4):519–25.
Bailey MS, et al. Gastroenteritis outbreak in British troops, Iraq. Emerg Infect Dis. 2005;11(10):1625–8.
Egger MS, Davey-Smith G, Altman DG. Systematic Reviews in Health Care. London: BMJ Publishing Group; 2001.
Kaveh GS, Duncan BW, McDonald KM, Wachter RM. Evidence-Based Review Methodology. Making Health Care Safer: A Critical Analysis of Patient Safety Practices. San Francisco, CA: University of California at San Francisco (UCSF)-Stanford University; 2001.
Sanchez JL, et al. Diarrheal disease incidence and morbidity among United States military personnel during short-term missions overseas. Am J Trop Med Hyg. 1998;58(3):299–304.
Black RE. Epidemiology of travelers’ diarrhea and relative importance of various pathogens. Rev Infect Dis. 1990;12(Suppl 1):S73–9.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.
Adachi JA, et al. Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis. 2003;37(9):1165–71.
Adkins H, et al. Travelers’ diarrhea among U.S. navy and marine corps personnel during a Western Pacific deployment. Mil Med. 1990;155(3):111–6.
Armstrong AW, et al. A randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of rifaximin for the prevention of travelers’ diarrhea in US military personnel deployed to Incirlik Air Base, Incirlik, Turkey. J Travel Med. 2010;17(6):392–4.
Arthur JD, et al. A comparative study of gastrointestinal infections in United States soldiers receiving doxycycline or mefloquine for malaria prophylaxis. Am J Trop Med Hyg. 1990;43(6):608–13.
Beecham HJ 3rd, Lebron CI, Echeverria P. Short report: impact of traveler’s diarrhea on United States troops deployed to Thailand. Am J Trop Med Hyg. 1997;57(6):699–701.
Bourgeois AL, et al. Etiology of acute diarrhea among United States military personnel deployed to South America and West Africa. Am J Trop Med Hyg. 1993;48(2):243–8.
Brown JA, et al. Outcomes of diarrhea management in operations Iraqi freedom and enduring freedom. Travel Med Infect Dis. 2009;7(6):337–43.
Buma AH, van Ameijden E, Huyboom M. Morbidity surveillance among Dutch troops during a peace support operation in Cambodia. Mil Med. 1999;164(2):107–11.
Chen LH, et al. Illness in long-term travelers visiting GeoSentinel clinics. Emerg Infect Dis. 2009;15(11):1773–82.
Cohen D, et al. Pilot study of an extended range of potential etiologic agents of diarrhea in the Israel defense forces. Isr J Med Sci. 1992;28(1):49–51.
Cohen D, et al. Prospective cohort studies of shigellosis during military field training. Eur J Clin Microbiol Infect Dis. 2001;20(2):123–6.
Cohen D, et al. Phenotypic characteristics of enterotoxigenic Escherichia coli associated with acute diarrhea among Israeli young adults. Foodborne Pathog Dis. 2010;7(10):1159–64.
DuPont HL, et al. Five versus three days of ofloxacin therapy for traveler’s diarrhea: a placebo-controlled study. Antimicrob Agents Chemother. 1992;36(1):87–91.
DuPont HL, et al. Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers’ diarrhea. Digestion. 1998;59(6):708–14.
DuPont HL, et al. A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers’ diarrhea. Ann Intern Med. 2005;142(10):805–12.
Echeverria P, et al. Diarrhea in U.S. troops deployed to Thailand. J Clin Microbiol. 1993;31(12):3351–2.
Ericsson CD, DuPont HL, Mathewson JJ. Optimal dosing of ofloxacin with loperamide in the treatment of non-dysenteric travelers’ diarrhea. J Travel Med. 2001;8(4):207–9.
Frickmann H, et al. Surveillance of food- and smear-transmitted pathogens in European soldiers with diarrhea on deployment in the tropics: experience from the European Union training Mission (EUTM) Mali. Biomed Res Int. 2015;2015:573904.
Haberberger RL Jr, et al. Etiology of acute diarrhea among United States embassy personnel and dependents in Cairo, Egypt. Am J Trop Med Hyg. 1994;51(6):870–4.
Haberberger RL Jr, et al. Travelers’ diarrhea among United States military personnel during joint American-Egyptian armed forces exercises in Cairo, Egypt. Mil Med. 1991;156(1):27–30.
Haberberger RL, et al. Diarrheal disease aboard a U.S. navy ship after a brief port visit to a high risk area. Mil Med. 1994;159(6):445–8.
Heck JE, Cohen MB. Traveler’s diarrhea. Am Fam Physician. 1993;48(5):793–800 805-6.
Herwaldt BL, et al. A multiyear prospective study of the risk factors for and incidence of diarrheal illness in a cohort of peace corps volunteers in Guatemala. Ann Intern Med. 2000;132(12):982–8.
Hillel O, Potasman I. Correlation between adherence to precautions issued by the WHO and diarrhea among long-term travelers to India. J Travel Med. 2005;12(5):243–7.
Hoge CW, et al. Epidemiology of diarrhea among expatriate residents living in a highly endemic environment. JAMA. 1996;275(7):533–8.
Hyams KC, et al. The navy forward laboratory during Operations Desert shield/desert storm. Mil Med. 1993;158(11):729–32.
Hyams KC, et al. Diarrheal disease during operation desert shield. N Engl J Med. 1991;325(20):1423–8.
Hyams KC, et al. The impact of infectious diseases on the health of U.S. troops deployed to the Persian Gulf during operations desert shield and desert storm. Clin Infect Dis. 1995;20(6):1497–504.
Jiang X, et al. Diagnosis of human caliciviruses by use of enzyme immunoassays. J Infect Dis. 2000;181(Suppl 2):S349–59.
Johnson GP, Weston TD, Ward JE. Treatment of acute diarrhea with norfloxacin during desert storm deployment. Aviat Space Environ Med. 1992;63(8):717–20.
Kasper MR, et al. Diarrhea outbreak during U.S. military training in El Salvador. PLoS One. 2012;7(7):e40404.
Kuschner RA, et al. Use of azithromycin for the treatment of campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent. Clin Infect Dis. 1995;21(3):536–41.
Lesho EP. Supply consumption and disease surveillance during an overseas training exercise in Southeast Asia. Mil Med. 1994;159(1):53–5.
Letizia A, et al. Effects of pre-deployment loperamide provision on use and travelers’ diarrhea outcomes among U.S. military personnel deployed to Turkey. Travel Med Infect Dis. 2014;12(4):360–3.
Marimoutou C, et al. Self-reporting compared to prospective surveillance to evaluate the incidence of diarrhea among French Army personnel deployed to N’djamena, Chad. J Travel Med. 2011;18(3):217–20.
Miser WF, Doukas WC, Lillegard WA. Injuries and illnesses incurred by an army ranger unit during operation just cause. Mil Med. 1995;160(8):373–80.
Monteville MR, et al. Incidence, etiology, and impact of diarrhea among deployed US military personnel in support of operation Iraqi freedom and operation enduring freedom. Am J Trop Med Hyg. 2006;75(4):762–7.
Murphy GS Jr, et al. Ciprofloxacin- and azithromycin-resistant Campylobacter causing traveler’s diarrhea in U.S. troops deployed to Thailand in 1994. Clin Infect Dis. 1996;22(5):868–9.
Oyofo BA, et al. A survey of enteropathogens among United States military personnel during operation bright star ’94, in Cairo, Egypt. Mil Med. 1995;160(7):331–4.
Oyofo BA, et al. Enteropathogens associated with diarrhea among military personnel during operation bright star 96, in Alexandria, Egypt. Mil Med. 1997;162(6):396–400.
Oyofo BA, et al. Norwalk-like virus and bacterial pathogens associated with cases of gastroenteritis onboard a US navy ship. Am J Trop Med Hyg. 1999;61(6):904–8.
Paparello SF, et al. Diarrheal and respiratory disease aboard the hospital ship, USNS-mercy T-AH 19, during operation desert shield. Mil Med. 1993;158(6):392–5.
Pazzaglia G, Escamilla J, Batchelor R. The etiology of diarrhea among American adults living in Peru. Mil Med. 1991;156(9):484–7.
Petruccelli BP, et al. Treatment of traveler’s diarrhea with ciprofloxacin and loperamide. J Infect Dis. 1992;165(3):557–60.
Piyaphanee W, et al. Incidence and impact of travelers’ diarrhea among foreign backpackers in Southeast Asia: a result from Khao san road, Bangkok. J Travel Med. 2011;18(2):109–14.
de Santi VP, et al. Incidence, etiology, and determinants associated with acute diarrhea among French forces deployed to Chad. J Travel Med. 2011;18(2):115–20.
Porter CK, et al. Risk of functional gastrointestinal disorders in U.S. military following self-reported diarrhea and vomiting during deployment. Dig Dis Sci. 2011;56(11):3262–9.
Porter CK, et al. The incidence and gastrointestinal infectious risk of functional gastrointestinal disorders in a healthy US adult population. Am J Gastroenterol. 2011;106(1):130–8.
Porter CK, et al. The epidemiology of travelers’ diarrhea in Incirlik, Turkey: a region with a predominance of heat-stabile toxin producing enterotoxigenic Escherichia coli. Diagn Microbiol Infect Dis. 2010;66(3):241–7.
Putnam SD, et al. Self-reported description of diarrhea among military populations in operations Iraqi freedom and enduring freedom. J Travel Med. 2006;13(2):92–9.
Reaves EJ, et al. Outbreak of gastrointestinal illness during operation new horizons in Pisco, Peru, July 2012. MSMR. 2012;19(11):17–9.
Riddle MS, et al. A prospective study of acute diarrhea in a cohort of United States military personnel on deployment to the multinational force and observers, Sinai, Egypt. Am J Trop Med Hyg. 2011;84(1):59–64.
Rudland S, et al. The enemy within: diarrheal rates among British and Australian troops in Iraq. Mil Med. 1996;161(12):728–31.
Salam I, et al. Randomised trial of single-dose ciprofloxacin for travellers’ diarrhoea. Lancet. 1994;344(8936):1537–9.
Sanders JW, et al. Azithromycin and loperamide are comparable to levofloxacin and loperamide for the treatment of traveler’s diarrhea in United States military personnel in Turkey. Clin Infect Dis. 2007;45(3):294–301.
Sanders JW, et al. An observational clinic-based study of diarrheal illness in deployed United States military personnel in Thailand: presentation and outcome of campylobacter infection. Am J Trop Med Hyg. 2002;67(5):533–8.
Sanders JW, et al. Diarrheal illness among deployed U.S. military personnel during operation bright star 2001--Egypt. Diagn Microbiol Infect Dis. 2005;52(2):85–90.
Scott DA, et al. Norfloxacin for the prophylaxis of travelers’ diarrhea in U.S. military personnel. Am J Trop Med Hyg. 1990;42(2):160–4.
Sebeny PJ, et al. Hotel clinic-based diarrheal and respiratory disease surveillance in U.S. service members participating in Operation Bright Star in Egypt, 2009. Am J Trop Med Hyg. 2012;87(2):312–8.
Sharp TW, et al. Illness in journalists and relief workers involved in international humanitarian assistance efforts in Somalia, 1992-93. J Travel Med. 1995;2(2):70–6.
Sharp TW, et al. Diarrheal disease among military personnel during operation restore Hope, Somalia, 1992-1993. Am J Trop Med Hyg. 1995;52(2):188–93.
Shlim DR, et al. Persistent high risk of diarrhea among foreigners in Nepal during the first 2 years of residence. Clin Infect Dis. 1999;29(3):613–6.
Stermer E, et al. Is traveler’s diarrhea a significant risk factor for the development of irritable bowel syndrome? A prospective study. Clin Infect Dis. 2006;43(7):898–901.
Taylor DN, et al. Treatment of travelers’ diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial. Ann Intern Med. 1991;114(9):731–4.
Taylor DN, et al. Helicobacter pylori infection in desert storm troops. Clin Infect Dis. 1997;25(5):979–82.
Thornton SA, et al. Norfloxacin compared to trimethoprim/sulfamethoxazole for the treatment of travelers’ diarrhea among U.S. military personnel deployed to South America and West Africa. Mil Med. 1992;157(2):55–8.
Tribble DR, et al. Diagnostic approach to acute diarrheal illness in a military population on training exercises in Thailand, a region of campylobacter hyperendemicity. J Clin Microbiol. 2008;46(4):1418–25.
Tribble DR, et al. Traveler’s diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen. Clin Infect Dis. 2007;44(3):338–46.
Trivedi KH, et al. The impact of post-infectious functional gastrointestinal disorders and symptoms on the health-related quality of life of US military personnel returning from deployment to the Middle East. Dig Dis Sci. 2011;56(12):3602–9.
Tuteja AK, et al. Development of functional diarrhea, constipation, irritable bowel syndrome, and dyspepsia during and after traveling outside the USA. Dig Dis Sci. 2008;53(1):271–6.
Walz SE, et al. Pre-exposure anti-campylobacter jejuni immunoglobulin a levels associated with reduced risk of campylobacter diarrhea in adults traveling to Thailand. Am J Trop Med Hyg. 2001;65(5):652–6.
Willshaw GA, et al. Isolation of enterotoxigenic Escherichia coli from British troops in Saudi Arabia. Epidemiol Infect. 1995;115(3):455–63.
Velasco JM, Valderamat MT, Nogrado K, et al. Diarrheal and respiratory illness surveillance during US-RP Balikatan 2014. MSMR. 2015;22(6):20–3.
Ajami NJ, et al. Seroepidemiology of norovirus-associated travelers’ diarrhea. J Travel Med. 2014;21(1):6–11.
Chern A, McCoy A, Brannock T, et al. Incidence and risk factors for disease and non-battle injury aboard the hospital ship USNS COMFORT during a Humanitarian Assistance and Disaster Response Mission, Continuing Promise 2011. Trop Dis Travel Med Vaccin. 2016;2(7):1–9.
Sanders JW, Putnam SD, Antosek LE, Rockabrand DM, Hebst J, Tribble DR, Riddle MS, Sharp TW, Monteville MR. A Cross-Sectional Case-Finding Study of Travelers’ Diarrhea Among U.S. Military Personnel Deployed to Iraq. in 54th Annual Meeting of the American Society of Tropical Medicine and Hygiene: Washington, D.C; 2005. https://www.astmh.org/ASTMH/media/Documents/ASTMH_05_FP.pdf.
Hameed JM, et al. Incidence, etiology and risk factors for Travelers’ diarrhea during a hospital ship-based military humanitarian Mission: continuing promise 2011. PLoS One. 2016;11(5):e0154830.
Hill DR, Beeching NJ. Travelers’ diarrhea. Curr Opin Infect Dis. 2010;23(5):481–7.
Youmans BP, et al. Characterization of the human gut microbiome during travelers’ diarrhea. Gut Microbes. 2015;6(2):110–9.
Beckmann C, et al. Gastrointestinal pathogens detected by multiplex nucleic acid amplification testing in stools of pediatric patients and patients returning from the tropics. Infection. 2014;42(6):961–70.
Kotloff KL, et al. Global burden of diarrheal diseases among children in developing countries: Incidence, etiology, and insights from new molecular diagnostic techniques. Vaccine. 2017;35(49 Pt A):6783–9.
De Bruyn G, Hahn S, Borwick A. Antibiotic treatment for travellers’ diarrhoea. Cochrane Database Syst Rev. 2000;3:CD002242.
Riddle MS, et al. Trial evaluating ambulatory therapy of Travelers’ diarrhea (TrEAT TD) study: a randomized controlled trial comparing 3 single-dose antibiotic regimens with Loperamide. Clin Infect Dis. 2017;65(12):2008–17.
Steffen R. Epidemiology of traveler’s diarrhea. Clin Infect Dis. 2005;41(Suppl 8):S536–40.
Lalani T, et al. Epidemiology and self-treatment of travelers’ diarrhea in a large, prospective cohort of department of defense beneficiaries. J Travel Med. 2015;22(3):152–60.
Soonawala D, Vlot JA, Visser LG. Inconvenience due to travelers’ diarrhea: a prospective follow-up study. BMC Infect Dis. 2011;11:322.
Klem F, et al. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis. Gastroenterology. 2017;152(5):1042–54 e1.
Schrader AJ, Tribble DR, Riddle MS. Strategies to improve Management of Acute Watery Diarrhea during a military deployment: a cost effectiveness analysis. Am J Trop Med Hyg. 2017;97(6):1857–66.
Vargas M, et al. Prevalence of diarrheagenic Escherichia coli strains detected by PCR in patients with travelers’ diarrhea. Clin Microbiol Infect. 1998;4(12):682–8.
Jiang ZD, et al. Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay). J Infect Dis. 2002;185(4):497–502.
Mattila L, et al. Seasonal variation in etiology of travelers’ diarrhea. Finnish-Moroccan Study Group. J Infect Dis. 1992;165(2):385–8.
Steffen R, et al. Epidemiology of travelers’ diarrhea: details of a global survey. J Travel Med. 2004;11(4):231–7.
Chapin AR, et al. Prevalence of norovirus among visitors from the United States to Mexico and Guatemala who experience traveler’s diarrhea. J Clin Microbiol. 2005;43(3):1112–7.
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.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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.
This study was reviewed and approved by the Naval Medical Research Center IRB.
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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
- Travelers’ diarrhea
- Long term traveler
- Enterotoxigenic E. coli (ETEC)
- Enteroaggregative E. coli (EAEC)