No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Traveler's Diarrhea
Abstract
Travelers' diarrhea (TD) is the most important health issue among international travelers. In high risk areas, 50-90% of travelers may experience an episode of TD. The risk of acquiring TD is influenced by factors such as the destination, duration of stay, standard of accommodation, type of travel, age of the traveler, and also by individual risk factors. Most cases of TD are caused by bacteria; treatment for TD are loperamide and antibiotics. Preventive strategies such as hygiene measures have limited impact. Prophylactic intake of antibiotics or vaccines to prevent from TD can be considered in special situations.
... 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]. ...
... 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]. ...
... 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. ...
Background
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.
Methods
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.
Results
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.
Conclusions
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.
... However, it should be pointed out that the clinical picture of the disease caused by different pathogens may vary. Campylobacter has been associated with more severe TD including fever and abdominal pain [28,29] and ETEC with acute watery diarrhoea [29]. One study suggests similar clinical pictures for EPEC and ETEC [28]. ...
... However, it should be pointed out that the clinical picture of the disease caused by different pathogens may vary. Campylobacter has been associated with more severe TD including fever and abdominal pain [28,29] and ETEC with acute watery diarrhoea [29]. One study suggests similar clinical pictures for EPEC and ETEC [28]. ...
Objectives:
Eighty million travellers visiting (sub)tropical regions contract travellers' diarrhoea (TD) each year, yet prospective data comparing the prevalence of TD pathogens in various geographical regions are scarce. Our recent study employing modern molecular methods found enteropathogenic (EPEC) and enteroaggregative (EAEC) Escherichia coli to be the most frequent pathogens, followed by enterotoxigenic E. coli (ETEC) and Campylobacter. We revisited our data to compare the findings by geographical region.
Methods:
A total of 459 prospectively recruited travellers provided stool samples and completed questionnaires before and after visiting destinations in various geographical regions. A multiplex qPCR assay was used to analyse Salmonella, Yersinia, Campylobacter jejuni /Campylobacter coli, Shigella, Vibrio cholerae, EPEC, EAEC, ETEC, EHEC (enterohaemorrhagic E. coli) and EIEC (enteroinvasive E. coli).
Results:
TD was contracted by 69% (316/459) of the subjects; EPEC and EAEC outnumbered ETEC and Campylobacter in all regions. Multiple pathogens were detected in 42% (133/316) of the samples. The proportions of all pathogens varied by region. The greatest differences were seen for Campylobacter: while relatively frequent in South Asia (n=11; 20% of those 55 with TD during travel) and Southeast Asia (15/84; 15%), it was less common in East and West Africa (5/71; 7% and 1/57; 2%), and absent in South America and the Caribbean (0/40; 0%).
Conclusion:
EPEC and EAEC outnumbered ETEC and Campylobacter everywhere, yet the proportions of pathogen findings varied by region, ETEC and Campylobacter rates showing the greatest differences. The high frequency of multibacterial findings in many regions indicates a need for further investigating the clinical role of each pathogen.
... 24 Infectious disease accounts for about 2.8% to 4% of deaths during/from travel. [1][2][3][4]7,25,26 In terms of morbidity, traveler's diarrhea is the most common problem encountered. 25,26 ...
... [1][2][3][4]7,25,26 In terms of morbidity, traveler's diarrhea is the most common problem encountered. 25,26 ...
We present 2 anonymized cases to identify issues and challenges associated with long-haul in-flight medical emergencies. The first case involved a middle-aged man with a history of carditis on a systemic steroid who developed vomiting and rigor. Four physicians, including a pediatric intensivist, responded to the emergency call. In the second case, a pediatric trainee who was the only onboard medical personnel was summoned for help when a middle-aged man developed acute shortness of breath while traveling on a commercial flight. The cases illustrate the challenges and issues on the critical decisions of diagnosis, resuscitation, and whether the flight had to be returned or diverted. An extensive literature search is made to summarize the evidence available for these decisions and challenges. Epidemiology and outcomes associated with these medical emergencies are reviewed. In-flight medical emergencies are not rare. Physicians of all disciplines should be prepared to deal with these emergencies and make sensible decisions when equipment and resources are likely to be limited.
... In our case, potential problems that may arise during travel include cardiopulmonary disease mortality, injury, and accident. Infectious disease accounts for about 2.8-4% of deaths during/from travel [1][2][3][4][8][9][10]. In terms of morbidity, traveler's diarrhea is the most common problem encountered [9,10]. ...
... Infectious disease accounts for about 2.8-4% of deaths during/from travel [1][2][3][4][8][9][10]. In terms of morbidity, traveler's diarrhea is the most common problem encountered [9,10]. ...
Aim
. We presented the case of a child with central hypoventilation syndrome (CHS) to highlight issues that need to be considered in planning long-haul flight and problems that may arise during the flight.
Case
. The pediatric intensive care unit (PICU) received a child with central hypoventilation syndrome (Ondine’s curse) on nocturnal ventilatory support who travelled to Hong Kong on a make-a-wish journey. He was diagnosed with central hypoventilation and had been well managed in Canada. During a long-haul aviation travel, he developed respiratory symptoms and desaturations. The child arrived in Hong Kong and his respiratory symptoms persisted. He was taken to a PICU for management. The child remained well and investigations revealed no pathogen to account for his respiratory infection. He went on with his make-a-wish journey.
Conclusions
. Various issues of travel medicine such as equipment, airline arrangement, in-flight ventilatory support, travel insurance, and respiratory infection are explored and discussed. This case illustrates that long-haul air travel is possible for children with respiratory compromise if anticipatory preparation is timely arranged.
... Travelers' diarrhea is the most common health impairment in persons visiting developing countries affecting up to 50-90% of travelers in high-risk areas. 21 ETEC is the leading bacterial cause of diarrhea in the developing world, as well as the most common cause of travelers' diarrhea. 22 ETEC infection is characterized by profuse and watery diarrhea lasting several days with abdominal cramp, malaise, vomiting and low-grade fever. ...
... 23 Although it is rare in developed countries and usually benign, travelers' diarrhea represents a considerable socioeconomic burden for both the traveler and the host country. 21 For these reasons, much effort has been dedicated to finding a way of preventing such ailment. 22 As several probiotic strains have been shown to enhance human resistance to infectious disease 4-6 by excretion of antimicrobial components, by competing with pathogens for intestinal nutrients and mucosal adhesion sites, by strengthening gut barrier integrity and/or by modulating the immune system, the aim of the present study was to investigate whether a probiotic could increase resistance to ETEC. ...
Background:
Several probiotic strains have been shown to enhance human resistance to infectious disease. It is speculated that these strains may impose this effect by excretion of anti-microbial components, by competing with pathogens for intestinal nutrients and/or mucosal adhesion sites or modulating the immune system.
Objective:
A parallel, double-blind, placebo-controlled 4-week intervention was performed in healthy males, to study the effect of a blend of probiotic bacteria (Lactobacillus helveticus Rosell-52, Lactobacillus rhamnosus Rosell-11, Bifidobacterium longum ssp. longum Rosell-175) and a probiotic yeast (Saccharomyces cerevisiae var boulardii CNCM I-1079) on enterotoxigenic Escherichia coli (ETEC) challenge. Primary outcomes studied were fecal ETEC excretion and total fecal output per day.
Subjects/methods:
Subjects were randomized to the probiotic (5 × 10(9) colony-forming units (CFUs); twice daily; n=30) or placebo group (twice daily; n=30). After 2 weeks, subjects were orally challenged with a live attenuated ETEC (3 × 10(9) CFU), previously demonstrated to induce mild, short-lived symptoms of a foodborne infection. Before and after ETEC challenge, subjects collected 24 h fecal samples. Compliance to study guidelines, stool consistency (Bristol Stool Score), stool frequency, and frequency and severity of gastrointestinal (GI) complaints were recorded by the subjects on a Daily Record Questionnaire.
Results:
ETEC challenge induced a significant increase in fecal ETEC excretion in both groups. However, a statistically significant increase in fecal output was only observed in the probiotic group. ETEC challenge resulted in a decrease in the percentage of fecal dry weight, and an increase in reported Bristol Stool Score, stool frequency and GI complaints. Dietary probiotics significantly decreased the percentage of fecal dry weight. In addition, ETEC increased C-reactive protein, total secretory Immunoglobulin A (IgA) and Immunoglobulin G Colonization Factor Antigen II.
Conclusion:
Dietary probiotics did not increase resistance to oral attenuated ETEC challenge in human subjects.
... Foodborne diarrhea primarily affects inhabitants of developing countries with low sanitary standards and also affects visitors to these endemic areas, resulting in travelers' diarrhea. Etiologically, diarrheagenic Escherichia coli (DEC) -and most prominently enterotoxigenic E. coli (ETEC)-is the primary cause of these diarrheal diseases [2][3][4]. These ETEC strains can survive gastrointestinal digestion and transit successfully via the gastrointestinal tract to enter the intestine [5,6]. ...
The experimental challenge with attenuated enterotoxigenic E . coli strain E1392/75-2A prevents diarrhea upon a secondary challenge with the same bacteria. A dose-response pilot study was performed to investigate which immunological factors are associated with this protection. Healthy subjects were inoculated with increasing E . coli doses of 1E6-1E10 CFU, and three weeks later, all participants were rechallenged with the highest dose (1E10 CFU). Gastrointestinal discomfort symptoms were recorded, and stool and blood samples were analyzed. After the primary challenge, stool frequency, diarrhea symptom scores, and E . coli -specific serum IgG (IgG-CFA/II) titer increased in a dose-dependent manner. Fecal calprotectin and serum IgG-CFA/II response after primary challenge were delayed in the lower dose groups. Even though stool frequency after the secondary challenge was inversely related to the primary inoculation dose, all E . coli doses protected against clinical symptoms upon rechallenge. Ex vivo stimulation of PBMCs with E . coli just before the second challenge resulted in increased numbers of IL-6 ⁺ /TNF-α ⁺ monocytes and mDCs than before the primary challenge, without dose-dependency. These data demonstrate that primary E . coli infection with as few as 1E6 CFU protects against a high-dose secondary challenge with a homologous attenuated strain. Increased serum IgG-CFA/II levels and E . coli -induced mDC and monocyte responses after primary challenge suggest that protection against secondary E . coli challenges is associated with adaptive as well as innate immune responses.
... La pathologie la plus fréquente rencontrée sur place ou lors du retour de voyage est indéniablement celle des diarrhées du voyageur. Toute une série d'articles récents ont été publiés sur ce thème et c'est donc l'occasion de faire un point de situation (6,(7)(8)(9)(10). ...
Un sujet passionnant, fréquemment rencontré en pratique courante Diarrhées pendant ou après retour de voyage Les diarrhées du voyageur sont un sujet passionnant, fré-quemment rencontrées en pratique courante, souvent passées sous silence par nos patients sans sollicitation de notre part (question à ne pas oublier: « Avez-vous fait récemment un voyage à l'étranger? »). Elles méritent une attention dédiée notamment grâce à l'arrivée de nouveaux moyens diagnostics (par ex. multiplex d'entéropathogènes par PCR) et afin d'évi-ter l'effet tunnel «exotique» (se méfier de l'exacerbation d'une pathologie sous-jacente type maladie de Crohn suite à une infection «banale et auto-résolutive»). P lus d'un milliard de personnes ont voyagé et traversé une fron-tière en 2012, avec un pourcentage non négligeable allant d'un pays développé vers un pays en voie de développement pour dif-férentes raisons (tourisme, voyage d'affaires, visite d'amis et de proches, etc.) (1). Les voyages dans des « destinations à risque » augmentent donc toujours plus, ainsi que la typologie variée des voyageurs (cf. plus loin). Les études épidémiologiques s'intéressent à cette situation déjà depuis la fin des années '50, mais se sont net-tement mieux précisées depuis les années '80 (2, 3). Ces 10 der-nières années, des études multicentriques par le biais de réseaux de surveillance, se sont intéressées l aux voyageurs en partance et leur préparation au voyage (par ex.
... La pathologie la plus fréquente rencontrée sur place ou lors du retour de voyage est indéniablement celle des diarrhées du voyageur. Toute une série d'articles récents ont été publiés sur ce thème et c'est donc l'occasion de faire un point de situation (6,(7)(8)(9)(10). ...
Les diarrhées du voyageur sont un sujet passionnant, fréquemment rencontrées en pratique courante, souvent passées sous silence par nos patients sans sollicitation de notre part (question à ne pas oublier : "Avez-vous fait récemment un voyage à l'étranger ?"). Elles méritent une attention dédiée notamment grâce à l'arrivée de nouveaux moyens diagnostics (par ex. multiplex d'entéropathogènes par PCR) et afin d'éviter l'effet tunnel "exotique" (se méfier de l'exacerbation d'une pathologie sous-jacente type maladie de Crohn suite à une infection "banale et auto-résolutive").
... followed by the diarrheagenic E. coli. 26,27 Previous analysis of TAC determined a pathogen-specific odds ratio, with Ct values of each pathogen detected in diarrhea samples demonstrating an increased strength of association with clinical presentation of diarrhea as the specific pathogen load increased. 16 Specifically, Cryptosporidium was reported to have a significant increase in association with diarrhea at Ct <30. ...
Background:
Military personnel are vulnerable to diarrhea. Diarrheal disease is common when deployed for operations or exercise in developing countries. Although diarrheal disease is transient, cumulative time lost and medical asset can have a significant impact on military operations. Currently, diagnostics of diarrheal etiology typically relies on a mixture of conventional bacteriology, enzyme-linked immunosorbent assay, and polymerase chain reaction (PCR)-based methods including real-time PCR. These methods, however, can be time and labor intensive, although the identification of diarrheal etiology needs to be informative and rapid for treatment and prevention. Real-time PCR has been increasingly used to identify pathogens. Real-time PCR panels of common diarrheal pathogens have been developed, but several diarrheal pathogens are not included in the panel. An expanded and customizable panel to detect diarrhea etiology has been developed employing TaqMan Array Card (TAC) technology. TAC performs 384 real-time PCR reactions simultaneously. As currently configured for diarrheal disease by the University of Virginia, a maximum of 8 samples can be tested simultaneously with approximately 48 target pathogens per sample including bacteria, fungi, helminths, protozoan parasites, and viruses. TAC diarrheal disease panels have been successfully applied to detect pathogens in acute diarrheal stool samples from young children in several international multicenter diarrhea studies.
Methods:
In this study, TAC was applied to stool samples collected under an approved human use protocol from military personnel with acute diarrhea participating in the annual joint military exercise, Balikatan, between the Republic of the Philippines and the United States in 2014. Several established pathogen-specific real-time PCR detection assays were also performed in parallel for comparative purposes.
Findings:
TAC was applied to 7 stool samples. Campylobacter spp. was the most common diarrheal disease pathogen detected. Results from TAC matched 5 out of 6 pathogen specific real-time PCR assays. TAC required a total of 5-6 hours to complete all the procedures from nucleic acid extraction and data analysis, whereas a minimum of 18 hours and 4 hours are required for conventional bacteriology and enzyme-linked immunosorbent assay, respectively, per pathogen.
Discussion:
With TAC, pathogen load can be estimated from the amount of nucleic acid present for each pathogen, which can be analyzed further to better determine pathogen attribution and to compare pathogen load between case and control samples. Unfortunately, such correlative analysis was not possible because of the limited sample size available in this study. A larger sample size is needed for further evaluation of TAC on a specific population set, including military personnel. Regardless, TAC was found to be a useful and functional diagnostic platform that is less time-consuming, easy to use with high reproducibility, and costs less per sample compared to the current typically employed methods. The successful application of TAC in acute diarrhea stool samples from a US military population in the Philippines demonstrates its versatility as a potential candidate for a next-generation diagnostics platform.
... Travelers' Diarrhea (TD) is the most common illness reported in international travelers from industrialized nations to low-income, developing nations [1,2]. TD can be caused by multiple etiologic agents to include enteric bacteria (diarrheagenic Escherichia coli, Shigella spp., Campylobacter spp.), viruses (noroviruses, adenoviruses, astroviruses) and parasites (Giardia lamblia, Entamoeba histolytica, Cryptosporidium parvum) [3,4]. ...
Noroviruses are the leading cause of acute gastroenteritis in the United States and are responsible for at least 50 % of acute gastroenteritis outbreaks occurring worldwide each year. In addition, noroviruses have caused outbreaks on cruise ships, in nursing homes and hospitals, and in deployed military personnel, but its role in the etiology of travelers’ diarrhea is not well defined. The aim of this review is to describe the role of noroviruses in travelers’ diarrhea in terms of epidemiology, current diagnostics, treatment and vaccine development efforts. Studies have shown prevalence rates of noroviruses in travelers’ diarrhea cases ranging from 10–65 %. It is likely that norovirus prevalence rates are highly underestimated in travelers’ diarrhea due to rapid onset, short duration of the illness, limited availability of laboratory facilities, and the fact that most clinical laboratories lack the diagnostic capability to detect noroviruses in stool. Further, additional studies are needed to accurately determine the true prevalence rates of norovirus as an etiologic agent of diarrhea among travelers to different regions around the world. With the rapid progress in the development of a norovirus vaccine, travelers could serve as an ideal population for future norovirus clinical trials.
... Yet, in 25-40% of cases, no etiologic agent can be correlated with disease. 1,6,7 TD studies include research on the identification and diagnosis of etiologic agents, epidemiology, treatments, and preventative measures. A critical component that has been overlooked is the gut microbiome and how it is affected by TD. ...
Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.
... In our study, antibiotics were generally taken for the treatment of TD, the disease most commonly encountered abroad. While TD with severe symptoms undoubtedly requires antimicrobial treatment, antibiotics are usually not needed for moderate and mild cases, as these usually resolve spontaneously [27]. In reality, however, a substantial proportion of travelers with mild diarrhea do take antibiotics [28]. ...
Background. More than 300 million travelers visit regions with poor hygiene annually. A significant percentage of them become colonized by resistant intestinal bacteria such as extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-PE) and may transmit the strains to others and to medical care settings when they return home. Despite the threats to global healthcare caused by an upsurge in antimicrobial resistance, no effort has been centered on prevention of colonization while traveling.
Methods. Stool samples were collected from 430 Finns before and after traveling outside Scandinavia. All specimens were analyzed for ESBL- and carbapenemase-producing Enterobacteriaceae (CPE). Questionnaires were used to survey volunteers about use of antimicrobials as well as other potential risk factors. The results were subjected to multivariable analysis.
Results. Twenty-one percent (90/430) of the travelers became colonized by ESBL-PE and none by CPE. Geographic region, occurrence of travelers' diarrhea (TD), age, and use of antimicrobial (AB) for TD were identified as independent risk factors predisposing to contracting ESBL-PE. Eleven percent of those in subgroup TD−AB−, 21% in TD+AB−, and 37% in TD+AB+ acquired ESBL-PE. The risk proved to be highest in South Asia (46%); 23% became colonized in subgroup TD−AB−, 47% in TD+AB−, and 80% in TD+AB+. In Southeast Asia, the rates were 14%, 37%, and 69%, respectively.
Conclusions. TD and antimicrobials for TD proved to be independent risk factors, with up to 80% of TD+AB+ travelers contracting ESBL-PE. In modern pre-travel counseling for those visiting high-risk regions, travelers should be advised against taking antibiotics for mild or moderate TD.
... Adsorbents Adsorbents such as bismuth subsalicylate and attapulgite act by adsorbing fluids and compounds to improve stool consistency (see Table 4) [67]. This approach for managing HIVassociated noninfectious diarrhea has been considered based on the high degree of success observed in some patients using adsorbents to treat travelers' diarrhea [68,69]. However, the etiology and pathophysiology of travelers' diarrhea is distinct from that of HIV-associated noninfectious diarrhea, and the success of therapies for travelers' diarrhea has not transferred to the setting of HIV [70]. ...
Introduction:
Diarrhea poses a substantial burden for patients with human immunodeficiency virus (HIV), negatively impacting quality-of-life (QoL) and adherence to antiretroviral therapy. During the combination antiretroviral therapy (cART) era, as incidence of opportunistic infection as a cause of diarrhea decreased, incidence of noninfectious diarrhea (including diarrhea as an adverse event [AE] of cART and HIV enteropathy) increased proportionately. A literature search was conducted for information on prevalence, etiology, and treatment options for noninfectious diarrhea in patients with HIV.
Results:
For marketed antiretroviral therapies, up to 28% of patients live with >4 loose or watery stools per day. The US Food and Drug Administration (FDA) does not require pharmaceutical manufacturers to include, within approved prescribing information, prevalence rates for all grades of diarrhea. Traditionally, noninfectious diarrhea management focused on avoiding use of diarrhea-associated cART; symptom management (nonpharmacologic and/or pharmacologic); and, as a last resort, changing cART. Examining the evidence upon which this approach is based reveals that most strategies rely upon anecdotal information and case reports. This review summarizes the literature and updates clinicians on the most recent options for management of noninfectious diarrhea in patients with HIV.
Conclusion:
Diarrhea in patients with HIV is a significant unmet clinical need that contributes to worsening QoL and complicates medical management. Approaching management using a stepwise method of nonpharmacologic (diet), nonprescription (over-the-counter) and, finally, prescription agent changes (modification of cART or addition of an evidence-based antidiarrheal) appears reasonable, despite a lack of clear scientific evidence to support the initial two steps of this approach. If diet modifications, including psyllium and fiber introduction, fail to resolve noninfectious diarrhea in patients with HIV, loperamide followed by crofelemer should be considered. Clinicians are encouraged to review the most recent literature, not rely upon prescribing information. Continued vigilance by HIV providers to the presence of gastrointestinal AEs, even in patients taking the most recently approved antiretroviral agents, is warranted. Additional research is justified in identifying the etiology and management of HIV-associated diarrhea in patients on successful cART regimens.
... Although not all travel-related illness is foodborne, many disease episodes, in particular diarrhea, result from eating food contaminated with bacterial, protozoal, and viral pathogens. 44 Younger travelers, on limited budgets, extended trips, and more likely to engage in risky behavior, experience frequent episodes of diarrhea and other foodborne infections. 45 Cruise ships have been the scene and source of outbreaks of diarrheal disease affecting the more affluent, often older traveler, frequently caused by norovirus but also associated with a variety of bacterial and other enteric pathogens. ...
This article provides a historical framework on food safety for more contemporary details to rest on, focusing primarily on the past 100 years or so (with a touch of ancient history) as particular issues that affect how the safety of the food we eat have been appreciated, have evolved or at times have been successfully dealt with, or have newly emerged or reemerged, in large part because of the impact of technology, trade, and travel.
Background:
Tropical infectious diseases and vaccine-preventable emergencies are the mainstay of pre-travel consultations. However, non-communicable diseases, injuries, and accidents that occur during travel are not emphasized enough in these settings.
Methods:
We performed a narrative review based on a literature search of PubMed, Google Scholar, UpToDate, DynaMed, and LiSSa and on reference textbooks and medical journals dedicated to travel, emergency, and wilderness medicine. Relevant secondary references were extracted. We also aimed to discuss newer or neglected issues, such as medical tourism, COVID-19, exacerbations of comorbidities associated with international travel, insurance coverage, health care seeking abroad, medical evacuation or repatriation, and tips for different types of travellers' emergency medical kits (personal, group, physician handled).
Results:
All sources reviewed led to the selection of more than 170 references. Among epidemiological data on morbidity and deaths while abroad, only retrospective data are available. Deaths are estimated to occur in 1 in 100 000 travellers, with 40% caused by trauma and 60% by diseases, and less than 3% linked to infectious diseases. Trauma and other injuries acquired during travel, such as traffic accidents and drowning, can be reduced by up to 85% with simple preventive recommendations such as avoiding simultaneous alcohol intake. In-flight emergencies occur on 1 in 604 flights on average. Thrombosis risk is 2 to 3 times greater for travellers than for non-travellers. Fever during or after travel can occur in 2-4% of travellers, but in up to 25-30% in tertiary centers. Traveller's diarrhoea, although rarely severe, is the most common disease associated with travel. Autochthonous emergencies (acute appendicitis, ectopic pregnancy, dental abscess) can also occur.
Conclusions:
Pre-travel medicine encounters must include the topic of injuries and medical emergencies, such as the risk-taking behaviours and foster better planning in a comprehensive approach along with vaccines and infectious diseases advices.
Traveling is common in the modern world, and the risk of infection for travelers varies according to several factors. Chief among these are previous medical conditions, travel destination, geographical characteristics of that destination, the time spent traveling, the type of tourist activities, and the accommodation used. There have been few studies regarding travel and the risk of infection in recipients of biologic and targeted therapies, with much of the existing data being extrapolated from studies in all travelers. The most frequent clinical syndromes among travelers worldwide are systemic febrile illness, acute diarrhea, respiratory infections, and dermatological disorders. Before departure, travelers should be counseled about the risk of disease in the country or countries they plan to visit, including the recommendations for preventing illness. Pre-travel services, including vaccines, should be readily available to all travelers. In this chapter we review the most relevant infectious etiologies in travelers, together with the related features that modify the risk of infection.
Relevance . Travel diarrhea is the most common health problem in travelers, affecting up to 70% of travelers, especially when traveling to developing countries. Research and development of scientific and practical approaches to the prevention, risk assessment and treatment of travelers' diarrhea continues to be the focus of attention of specialists in the field of epidemiology, infectious diseases and travel medicine around the world.
Aim of the study : systematization and synthesis of new data on various clinical and epidemiological aspects of travelers' diarrhea.
Conclusion . Analysis of modern scientific literature has made it possible to identify the risks for travelers associated with the direction of travel and the state of their own health. The highest risk of developing traveler's diarrhea (from 20% to 90%) is recorded in people visiting the countries of the Middle East, South and Southeast Asia, Central and South America, and Africa. There is a high risk of developing traveler's diarrhea in children under 4 years of age. The causative agents of acute bacterial intestinal infections can account for up to 80% -90% of all cases of travelers' diarrhea. In most cases, travelers' diarrhea is mild. Seeking medical care is observed from 5% to 15% of cases. For etiotropic therapy, the use of azithromycin, ciprofloxacin and other drugs is recommended. Recommendations for self-management of traveler's diarrhea have been formulated. Pre-trip travel advice will help reduce the risks of travelers' diarrhea.
An experimental human challenge model with an attenuated diarrheagenic Escherichia coli (E. coli) strain has been used in food intervention studies aimed to increase resistance to E. coli infection. This study was designed to refine and expand this challenge model. In a double-blind study, healthy male subjects were orally challenged with 1E10 or 5E10 colony-forming units (CFU) of E. coli strain E1392/75-2A. Three weeks later, subjects were rechallenged with 1E10 CFU of E. coli . Before and after both challenges, clinical symptoms and infection- and immune-related biomarkers were analyzed. Subset analysis was performed on clinically high- and low-responders. Regardless of inoculation dose, the first challenge induced clinical symptoms for 2–3 days. In blood, neutrophils, CRP, CXCL10, and CFA/II-specific IgG were induced, and in feces calprotectin and CFA/II-specific IgA. Despite clinical differences between high- and low-responders, infection and immune biomarkers did not differ. The first inoculation induced protection at the second challenge, with a minor clinical response, and no change in biomarkers. The refined study design resulted in a larger dynamic range of symptoms, and identification of biomarkers induced by a challenge with the attenuated E. coli strain E1392/75-2A, which is of value for future intervention studies. Addition of a second inoculation allows to study the protective response induced by a primary infection.
Clinicaltrials.gov registration: NCT02541695 (04/09/2015).
The number of children accompanying their parents in international travel is increasing steadily, and with the rising global migration, children more frequently accompany their parents or caregivers for visiting friends or relatives (VFR). As compared to travel for tourism, VFR children are at higher risk of acquiring local diseases, as they more often stay in rural areas in resource-poor locations, have longer periods of visit, are less likely to attend pre-travel consultations, and less frequently adhere to recommended precautions.
Travelers's diarrhea (TD) is the most common travel-associated illnesses in children. This review updates the existing knowledge on TD in children, regarding its distinctive epidemiology, risk factors, preventive measures, clinical manifestations, complications, causative microorganisms and management. Despite the limited focused research on pediatric TD, which challenges the formulation of children-oriented evidence-based guidelines, practical recommendations are suggested.
Enterohemorrhagic Escherichia coli (EHEC) is a strain of the human pathogenic E. coli bacteria that can cause serious foodborne diseases. Many probiotics have antagonistic effects on EHEC, but few studies have examined the interactions between probiotics and EHEC in vivo. To investigate the colonization of Lactobacillus casei LC2W and its inhibitory effect on E. coli O157: H7 in vivo, these strains labelled with different fluorescent proteins were monitored in the intestinal tracts of live mice using in vivo imaging system. The results showed L. casei LC2W inhibited the colonization of O157: H7 in mice. Further research found LC2W had both prevention and treatment effects on the colitis severity of mice infected by O157:H7, where the prevention effect dominated over the treatment one. This study demonstrates a feasible method for studying the interactions between probiotics and pathogens, and the mechanisms by which probiotics reduce colitis induced by O157: H7.
Pharmacists play an important role in the assessment and management of diarrhea. By obtaining a focused clinical history from the patient, they can identify patients who need to be referred to their physician or to the emergency room, as well as which patients can be managed at home with oral rehydration therapy (ORT) and sometimes symptomatic therapy. Red flags that prompt referral include severe diarrhea (characterized by one or more of the following: ≥6 stools/day, fever, severe abdominal cramping, bloody stools, dehydration, or symptom duration >7 days), and high-risk patient factors (young children or age > 65, chronic medical conditions, immunosuppression, frailty, or pregnancy). Understanding the categorizations and etiologies of diarrhea is essential for proper assessment and management. Acute diarrhea is defined as diarrhea with <14 days duration. Persistent diarrhea lasts 14–30 days, and chronic diarrhea is defined as >30 days duration of symptoms. Acute diarrhea is most often caused by infection, whereas persistent and chronic diarrhea are more likely to be drug or disease-related. Diarrhea-associated mortality in high-risk individuals is largely due to dehydration. Preventing and treating dehydration is the cornerstone of management for all patients. Most patients can be managed with ORT, either with oral fluids and salty foods, or with oral rehydration solutions (ORS) that are formulated to maximize rehydration. Moreover, intravenous fluids are needed in patients with severe dehydration.
Background:
Most travellers' diarrhea (TD) infections occur during travel to low- and middle-income countries. Type of travel, duration of stay, age of traveller and presence of certain medical conditions are important factors to consider for risk of TD. The Committee to Advise on Tropical Medicine and Travel (CATMAT) assembled a TD working group to develop recommendations on prevention and treatment of TD in travellers. This document is a summary of the Statement on Travellers' Diarrhea.
Methods:
Following a systematic review of the literature, recommendations on the prevention and treatment of TD were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to evaluate data quality, benefits and harms of the intervention, and values and preferences of the traveller. Other recommendations were based on a review of the literature and expert opinion.
Recommendations:
Using the GRADE methodology, CATMAT concluded that oral cholera vaccine should not be routinely recommended to prevent TD in Canadian travellers. This recommendation was based on moderate quality data that showed this vaccine was not effective in preventing TD in travellers compared to placebo. Bismuth subsalicylate (BSS), fluoroquinolones or rifaximin are options for the prevention of TD based on high-quality data for BSS and fluoroquinolones and moderate evidence for rifaximin. For the treatment of TD, loperamide (alone or in combination with antibiotics), fluoroquinolones, azithromycin and rifaximin are all options, with varying degrees of data quality. Based on available evidence and expert opinion, CATMAT recommends handwashing or the use of hand sanitizer, as well as prudent choice and preparation of food and beverages as best practices for preventing diarrhea while travelling. At this time, a recommendation cannot be made for either the use of probiotics and prebiotics to prevent TD or the use of BSS to treat TD due to insufficient available evidence.
Conclusion:
With the exception of BSS for prevention of TD (strong recommendation for use), CATMAT conditionally recommends the use of each of the other GRADE-evaluated preventive and therapeutic products assessed in this Statement. These CATMAT recommendations should be considered as options in the prevention and treatment of TD based on the particular situation of the traveller.
Background:
Travelers' diarrhea (TD) is a common illness experienced by travelers from developed countries visiting developing countries. Recent questionnaire-based surveillance studies reported that approximately 6-16% of travelers experienced TD while visiting Thailand; however, a majority of TD information was limited mainly to US military populations.
Methods:
A TD surveillance study was conducted at Bumrungrad International Hospital in 2012-2014 in Bangkok, Thailand. Enteropathogens were identified by conventional methods and TaqMan® Array Card (TAC) which employs real-time PCR for the simultaneous detection of multiple pathogens. Analyses to determine pathogen-disease and symptoms association were performed to elucidate the clinical relevance of each enteropathogen.
Results:
TAC identified more pathogens per sample than conventional methods. Campylobacter spp. were the most prevalent, followed by the diarrheagenic Escherichia coli, and norovirus GII. These agents had significant pathogen-disease associations as well as high attributable fractions (AF) among diarrheal cases. A wide range of pathogen loads for Campylobacter spp. was associated with TD, while heat-labile toxin enterotoxigenic Escherichia coli (LT-ETEC) was associated with an increased pathogen load. Most cases were associated with inflammatory diarrhea while Campylobacter spp. and Shigella spp. were associated with dysentery.
Conclusion:
A pan-molecular diagnostic method such as TAC produces quantifiable and comparable results of all tested pathogens, thereby reducing the variability associated with multiple conventional methods. This allows better determination of the clinical relevance of each diarrhea etiologic agent, as well as their geographical relevance in Thailand.
Als Reiseimpfungen für Kinder sind Cholera, Gelbfieber, japanische Enzephalitis, Tollwut, Tuberkulose und Typhus hinsichtlich der Zulassung für das entsprechende Alter des Kindes und des Reiseziels zu berücksichtigen. Die epidemiologische Situation am Reiseziel kann aus Internetquellen zeitnah ermittelt werden.
Introduction: Diarrhea is a common illness among travelers to developing countries. Located in a tropical region, Bali has a potentially high prevalence of travelers diarrhea. This hospital-based cross-sectional study was carried out to assess the clinical and microbiological profiles of diarrhea among travelers admitted to Kasih Ibu hospital, Denpasar-Bali. Methods: This study enrolled a total of 71 patients at Kasih Ibu hospital between April 2015 and August 2016. All patients completed an epidemiologic questionnaire; their clinical histories were taken, and physical examinations were performed. Stool samples were collected for bacterial and parasitologic studies and susceptibility testing. Results: Most patients were female (70.4%), and the nationality of most patients was Dutch (15.5%). Secretory diarrhea was the most frequently found diarrheal type (88.7%), with only 5.6% of cases having severe dehydration which developed into acute kidney injury. A high percentage of Entamoeba spp. was also seen in this study (54.9%). Of the 37 stool samples available for microbiological testing, 62.2% showed growth; Escherichia coli was the most commonly isolated bacteria (54.1%). Patients not infected by Entamoeba spp. were found more likely to experience nausea and vomiting (P
This prospective cohort study describes travelers' diarrhea (TD) and non-TD gastrointestinal (GI) symptoms among international travelers from the Boston area, the association of TD with traveler characteristics and dietary practices, use of prescribed antidiarrheal medications, and the impact of TD and non-TD GI symptoms on planned activities during and after travel. We included adults who received a pre-travel consultation at three Bostonarea travel clinics and who completed a three-part survey: pre-travel, during travel, and post-travel (2-4 weeks after return). TD was defined as self-reported diarrhea with or without nausea/vomiting, abdominal pain, or fever. Demographic and travel characteristics were evaluated by χ2 test for categorical and Wilcoxon rank-sum test for continuous variables. Analysis of dietary practices used logistic generalized estimating equation models or logistic regression models. Of 628 travelers, 208 (33%) experienced TD and 45 (7%) experienced non-TD GI symptoms. Of 208 with TD, 128 (64%), 71 (36%), and 123 (62%) were prescribed ciprofloxacin, azithromycin, and/or loperamide before travel, respectively. Thirty-nine (36%) of 108 took ciprofloxacin, 20 (38%) of 55 took azithromycin, and 28 (28%) of 99 took loperamide during travel. Of 172 with TD during travel, 24% stopped planned activities, and 2% were hospitalized. Of 31 with non-TD GI symptoms during travel, six (13%) stopped planned activities. International travelers continue to experience diarrhea and other GI symptoms, resulting in disruption of planned activities and healthcare visits for some. Although these illnesses resulted in interruption of travel plans, a relatively small proportion took prescribed antibiotics. Copyright © 2017 by The American Society of Tropical Medicine and Hygiene.
Acute diarrhea is a common, primarily self-limited illness, which can be managed most often with supportive care. Stool cultures are rarely indicated early on, unless the patient has fever, abdominal pain, or bloody diarrhea, suggestive of a bacterial etiology. The focus of treatment should be on replacement of fluid and electrolytes, especially in the young and the elderly, who are at increased risk of excessive morbidity and mortality. Empiric antibiotic therapy, with few exceptions, should be given in the setting of severe dysentery or in patients with significant comorbidities. Specific antibiotic therapy is determined by the organism identified. Any decision to treat must carefully weigh the potential benefits and risks, particularly if the patient is at risk for Shiga toxin-producing Escherichia coli.
Background: International tourism is increasing. Preventive Medicine remains important, especially the Pre-Travel Consultation (PTC). Objective: To determinate, the characteristics of tourists associated with PTC in tourists at Cuzco, Peru. Methods: A cross-sectional, analytical study, a secondary analysis of data from a database generated by survey of foreign tourists who visited Cuzco, in the waiting room of the airport was performed. The main variable was to have had a PTC at the tourist's country of residence, the area of residence was categorized according to health/risk of acquiring infectious diseases as traveler's diarrhea during their stay. These and other variables were analyzed and statistical association with generalized linear models were done. Results: Of the 1827 tourists, 875 (48%) were men, with a median age of 33 years (range 18-88 years); 42% had a PTC. In the multivariate analysis, it was found that a PTC lower frequency was associated with male gender (aPR: 0.84; 95% CI: 0.75-0.94), and a higher frequency was associated with have born (aPR: 1.77; 95% CI: 1.39-2.27) and reside in an area of low risk of acquiring infectious diseases (aPR: 1.95; 95% CI: 1.26-3.00), adjusted for the history of a disease. Conclusions: Sex, region of birth and residence of tourists (as risk of acquiring infectious diseases) are associated with having a PTC. These findings may serve the health and government attending tourists who come to our country.
Background. Enterotoxigenic Escherichia coli (ETEC) and non-O157 Shiga toxin-producing E. coli (STEC) are not detected by conventional culture methods. The prevalence of ETEC infections in the United States is unknown, and recognized cases are primarily associated with foreign travel. Gaps remain in our understanding of STEC epidemiology.
Methods. Two sentinel surveillance sites were enrolled: an urban health maintenance organization laboratory (Laboratory A) and a rural hospital laboratory (Laboratory B). Residual sorbitol MacConkey (SMAC) plates from stool cultures performed at Laboratory A (1996–2006) and Laboratory B (2000–2008) were collected. Colony sweeps from SMAC plates were tested for genes encoding STEC toxins stx1 and stx2 (1996–2008) and ETEC heat-labile and heat-stable toxins eltB, estA 1, 2 and 3 (2000–2008) by polymerase chain reaction (PCR)-based assays.
Results. In Laboratory A, a bacterial pathogen was identified in 7.0% of 21 970 specimens. During 1996–2006, Campylobacter was the most common bacterial pathogen (2.7% of cultures), followed by Salmonella (1.2%), Shigella (1.0%), and STEC (0.9%). Among STEC (n = 196), O157 was the most common serogroup (31%). During 2000–2006, ETEC (1.9%) was the second most common bacterial pathogen after Campylobacter (2.6%). In Laboratory B, of 19 293 specimens tested, a bacterial pathogen was identified for 5.5%, including Campylobacter (2.1%), STEC (1.3%), Salmonella (1.0%), and ETEC (0.8%). Among STEC (n = 253), O157 was the leading serogroup (35%). Among ETEC cases, 61% traveled internationally.
Conclusions. Enterotoxigenic E. coli and STEC infections were as common as most other enteric bacterial pathogens, and ETEC may be detected more frequently by culture-independent multiplex PCR diagnostic methods. A high proportion of ETEC cases were domestically acquired.
Diarrhea is the most common health issue affecting travelers to destinations across the world. This paper reviews the options for initial treatment of acute traveler’s diarrhea (TD). Its prevention, including but not limited to vaccines and safe travel and eating habits, is an important consideration but is beyond the scope of this paper. Treatment of TD has three arms: volume repletion, antibiotics, and antimotility/antisecretory agents. Patients should be advised to continue a diet that they can tolerate and maintain adequate fluid intake. In most cases, neither oral rehydration therapy nor dietary restrictions are likely to provide significant benefit. As yet, there is no evidence to support probiotic use for treatment of this type of diarrhea. Given that bacteria are the most frequent cause of TD, adult patients with moderate to severe disease should be treated empirically with a short course of antibiotics. In many instances, these will be prescribed pre-travel with instructions for proper usage when typical symptoms occur while abroad. However, such travelers should be advised to see a physician or seek emergency treatment if symptoms are severe or persist beyond 3 days. Antibiotic selection must take into account the epidemiology of resistant enteric pathogens. Fluoroquinolones are usually effective, although resistance of Campylobacter to this class of drugs in South and Southeast Asia warrants azithromycin as first-line empiric therapy in travelers to those regions. One day of therapy is often sufficient but can be extended to 3 days. Rifaximin is an alternative in non-invasive disease only. The antimotility agent loperamide is safe and effective and should be considered as adjunctive therapy in most cases of TD and can similarly be prescribed pre-travel. In non-pregnant adults, bismuth subsalicylate can also provide some symptomatic relief. Where available, racecadotril may be a safe alternative in both adults and children, although never specifically studied in TD. In cases of severe symptoms, or those lasting longer than 3 days, the patient should be evaluated for non-bacterial etiologies as well as possible Clostridium difficile infection. Certain travelers are more vulnerable to severe complications related to TD. Children, particularly infants, may need more aggressive fluid resuscitation with oral rehydration therapy. Several of the antidiarrheal agents must be avoided. Elderly patients and those with impaired cardiovascular reserve or immune-deficient states are more prone to complications as well. Treatment recommendations also differ for pregnant women. We generally advise adult non-pregnant travelers to follow smart eating and drinking practices and to bring a supply of bismuth subsalicylate and loperamide. We also prescribe an empiric antibiotic course (ciprofloxacin or azithromycin for up to 3 days) that is to be used for moderate to severe cases of TD.
Traveler’s diarrhea is usually short-lasting (about 3–5 days) and self-limiting. Apart from oral rehydration, no special treatment is necessary for the otherwise healthy traveler. However, in order to avoid a ruined vacation, treatment must provide quick relief from diarrhea and concomitant symptoms. To meet this need, travelers must be equipped with suitable medication for self-treatment. Three options are available. Oral rehydration is harmless but does not significantly shorten the disease, although it prevents complications caused by dehydration and loss of electrolytes. Loperamide is an antimotility agent which significantly shortens diarrhea but will not be a causative treatment, and may even be dangerous if used in cases of potentially invasive diarrhea. Additionally, loperamide can be used only for a short period of time. Antibiotics, which are the only causative treatment option, shorten the duration of symptoms and eliminate the causative bacteria, and are therefore recommended for treatment of moderate and severe traveler’s diarrhea. However, antibiotics often have a negative risk-benefit ratio when weighing potential side effects versus treatment need for a short-lasting and self-limiting disease like traveler’s diarrhea. Azithromycin has several advantages over other antibiotics. It is taken only once (1000 mg), the rate of antimicrobial resistance is low, and it has a good safety profile. Furthermore, in contrast to rifaximin, it can be used in severe cases of diarrhea with fever or bloody stools and can even be administered in children. Optionally, azithromycin can be combined with antimotility medications such as loperamide. Travelers should be reminded that diarrhea can be a symptom of other severe diseases, such as malaria. Therefore, if diarrhea persists or additional symptoms such as fever occur, travelers should seek medical advice.
Nervous system infections are among the most important diseases in travellers. Healthy travellers might be exposed to infectious agents of central nervous system, which may require in-patient care. Progressive course is not uncommon in this family of disorders and requires swift diagnosis. An overview of the available evidence in the field is, therefore, urgent to pave the way to increase the awareness of travel-medicine practitioners and highlights dark areas for future research. In November 2013, data were collected from PubMed, Scopus, and Web of Knowledge (1980 to 2013) including books, reviews, and peer-reviewed literature. Works pertained to pre-travel care, interventions, vaccinations related neurological infections were retrieved. Here we provide information on pre-travel care, vaccination, chronic nervous system disorders, and post-travel complications. Recommendations with regard to knowledge gaps, and state-of-the-art research are made. Given an increasing number of international travellers, novel dynamic ways are available for physicians to monitor spread of central nervous system infections. Newer research has made great progresses in developing newer medications, detecting the spread of infections and the public awareness. Despite an ongoing scientific discussion in the field of travel medicine, further research is required for vaccine development, state-of-the-art laboratory tests, and genetic engineering of vectors.
In healthy adults and children in developed countries, most foodborne and water-borne infections are short-lived and resolve without specific treatment. In developing areas, these infections may produce acute mortality and chronic morbidity caused by developmental impairment. Immune-compromised hosts are at increased risk of life-threatening complications. This article reviews recommendations for the treatment of the most common and important foodborne illnesses, focusing on those caused by infections or toxins of microbial origin. The cornerstone of life-saving treatment remains oral rehydration therapy, although the use of other supportive measures as well as antibiotics for certain infections is also recommended.
Shigellosis is a global human health problem causing an important morbidity among travellers returning from tropical areas. This study was aimed to describe the evolution of antimicrobial resistance profile in Shigella spp. isolated between the years 1995-2010 in patients with traveller's diarrhoea (TD) returning from tropical areas.
The levels of antimicrobial resistance were tested in a total of 191 Shigella spp. isolated during the period from 1995 to 2010.
A decrease of cases of diarrhoea caused by Shigella has been observed in recent years. A wide spectrum of antibiotic resistance was observed among Shigella spp. These isolates showed high levels of resistance to tetracycline (84%), co-trimoxazole (75.5%), and ampicillin (45.5%). The resistance was low to ciprofloxacin (2.1%), azithromycin (3.9%) and furazolidone (8.4%). According to the period, in the case of ampicillin, amoxicillin plus clavulanic acid, chloramphenicol, values of resistance were significantly decreasing from 1995-2000 to 2001-2010, (62.5% vs. 28.4%, 19.8% vs. 6.6%, 23.4 vs. 10.4%, respectively). Meanwhile in nalidixic acid and tetracycline the evolution of resistance has increased over time.
A decrease in the isolation number of Shigella spp. causing TD has been observed. Differential trends in the evolution of the levels of resistance to the tested antibacterial agents have been observed.
Probiotics and prebiotics have a major influence on gastrointestinal flora composition. This review analyses the relationship between this change in flora composition and health benefits in children. Literature databases were searched for relevant articles. Despite exhaustive research on the subject in different indications, such as prevention and treatment of acute gastroenteritis, antibiotic associated diarrhea (AAD), traveler's diarrhea, inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori, necrotizing enterocolitis, constipation, allergy and atopic dermatitis, colic and extraintestinal infections, reports of clear benefits for the use of prebiotics and probiotics in pediatric disorders remain scarce. The best evidence has been provided for the use of probiotics in acute gastroenteritis and in prevention of AAD. However, AAD in children is in general mild, and only seldom necessitates additional interventions. Overall, the duration of acute infectious diarrhea is reduced by approximately 24 hours. Evidence for clinically relevant benefit in all other indications (inflammatory bowel disease, irritable bowel syndrome, constipation, allergy) is weak to nonexistent. Selected probiotic strains given during late pregnancy and early infancy decrease atopic dermatitis. Adverse effects have very seldom been reported. Since the risk seems minimal to nonexistent, prebiotics and probiotics may be helpful in the prevention and treatment of some disorders in children, although the evidence for benefit is limited. The best evidence has been accumulated for some lactobacilli strains and for Saccharomyces boulardii in the reduction of the duration of acute diarrhea due to gastroenteritis and prevention of AAD.
Malaria, diarrhea, respiratory infections, and cutaneous larva migrans are common travel-related infections observed in children and adolescents returning from trips to developing countries. Children visiting friends and relatives are at the highest risk because few visit travel clinics before travel, their stays are longer, and the sites they visit are more rural. Clinicians must be able to prepare their pediatric-age travelers before departure with preventive education, prophylactic and self-treating medications, and vaccinations. Familiarity with the clinical manifestations and treatment of travel-related infections will secure prompt and effective therapy.
Travellers' diarrhoea (TD) is the most common infectious disease among travellers. In the Netherlands, stand-by or prophylactic antibiotics are not routinely prescribed to travellers. This study prospectively assessed the incidence rate, risk factors, and treatment of TD among immunocompetent travellers.
Persons who attended the travel clinic of the Public Health Service Amsterdam in 2006-2007 before short-term travel to tropical and subtropical countries were invited to answer a questionnaire regarding sociodemographics and travel purpose; they were also asked to keep a daily structured travel diary, recording their itinerary, symptoms, and self-medication or consultation with a doctor. Diarrhoea episodes containing blood or mucous were considered severe.
Of 1202 travellers, the median age was 38 years, and the median travel duration 3 weeks. Of all episodes, 96% were mild. The median duration of TD was 2 days and significantly shorter in subsequent episodes compared to first episodes (p < 0.0005). Of first episodes 38% started in the first travel week. The incidence rate (IR) for first episodes was 2.49 (95% confidence interval [CI], 2.30-2.70) per 100 travel days, with the highest IR among travellers to South-Central and West Asia. The IR for first and subsequent episodes was comparable. Risk factors for first episodes included female sex, a Western country of birth, and tourism as the purpose of travel. The lowest risk was in travellers to South America. An independent risk factor for subsequent episodes was female sex. In total, 5% of travellers used antibiotics; of those, 92% had mild diarrhoea, and 53% received antibiotics over the counter.
TD is common among travellers, but the overall course is mild, not requiring treatment. The incidence rates for first and second episodes are comparable. Female sex is a risk factor for the first episode, as well as subsequent ones. Prescription antibiotics are not needed in short-term healthy travellers.
Noroviruses (NoVs) are increasingly being recognized as an important enteric pathogen of gastroenteritis worldwide. The prevalence of NoVs as a cause of diarrhea acquired by travelers in developing countries is not well known. We examined the prevalence and importance of NoV infection in three international traveler cohorts with diarrhea acquired in three developing regions of the world, Mexico, Guatemala, and India. We also characterized the demographics and symptoms associated with NoV diarrhea in these travelers. Stool samples from 571 international travelers with diarrhea were evaluated for traditional enteropathogens. NoVs were identified using reverse transcription-PCR and probe hybridization. NoVs were identified in 10.2% of cases of travelers' diarrhea and, overall, was the second most common pathogen, following diarrheagenic Escherichia coli. The detection of NoV diarrhea significantly varied over the three study time periods in Guadalajara, Mexico, ranging from 3 of 98 (3.0%) diarrheal stools to 12 of 100 (12.0%) fecal specimens (P=0.03). The frequency of NoV diarrhea was also dependent upon the geographic region, with 17 of 100 (17.0%) travelers to Guatemala, 23 of 194 (11.9%) travelers to India, and 3 of 79 (3.8%) travelers to Mexico testing positive for NoVs from 2002 to 2003 (P=0.02). NoVs are important pathogens of travelers' diarrhea in multiple regions of the world. Significant variation in the prevalence of NoV diarrhea and in the predominant genogroup infecting travelers was demonstrated, dependent upon the specific geographic location and over time.
This study examined established enteric pathogens, Arcobacter species and enterotoxigenic Bacteroides fragilis (ETBF), in 201 U.S. and European travelers with acute diarrhea acquired in Mexico, Guatemala, and India. Arcobacter butzleri and ETBF were detected in 8% and 7% of diarrhea cases, respectively.
Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS) in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published.
A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS), Dukoral for the prevention of traveller's diarrhoea (TD) was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005.
The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days) subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 euro per traveller.
According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.
Campylobacter is a leading foodborne bacterial pathogen, which causes gastroenteritis in humans. This pathogenic organism is increasingly resistant to antibiotics, especially fluoroquinolones and macrolides, which are the most frequently used antimicrobials for the treatment of campylobacteriosis when clinical therapy is warranted. As a zoonotic pathogen, Campylobacter has a broad animal reservoir and infects humans via contaminated food, water or milk. Antibiotic usage in both animal agriculture and human medicine, can influence the development of antibiotic-resistant Campylobacter. This review will describe the trend in fluoroquinolone and macrolide resistance in Campylobacter, summarize the mechanisms underlying the resistance to various antibiotics and discuss the unique features associated with the emergence, transmission and persistence of antibiotic-resistant Campylobacter. Special attention will be given to recent findings and emphasis will be placed on Campylobacter resistance to fluoroquinolones and macrolides. A future perspective on antibiotic resistance and potential approaches for the control of antibiotic-resistant Campylobacter, will also be discussed.
A previous Cochrane Collaboration review established an effective advantage of antibiotic therapy, compared with placebo, for treatment of traveler's diarrhea. The goal of the present study was to conduct a systematic review of the literature to establish the effect on treatment outcomes of using antimotility agents in conjunction with antibiotic therapy.
The meta-analysis was conducted through searches of electronic databases and pertinent reference lists (including other review articles) and consultation with experts in the field. Clinical trials on therapy of infectious diarrhea in adult populations that met eligibility criteria were studied. Data were extracted and verified by 2 independent investigators and were analyzed for outcomes of clinical cure at 24 h, 48 h, and 72 h and time to last unformed stool. Study quality, heterogeneity, and publication bias were assessed. When appropriate, effect estimates among studies were pooled and sensitivity analyses were performed.
Nine studies consisting of 12 different adjunctive loperamide antibiotic regimens were included for analysis. Among 6 paired studies comparing antibiotics alone versus antibiotics in combination with loperamide, the odds of clinical cure at 24 h and 48 h favored combination therapy, with summary odds ratios of 2.6 (95% confidence interval, 1.8-3.6; P = .20 by chi(2) heterogeneity statistic) and 2.2 (95% confidence interval, 1.5-3.1; P = .20, by chi(2) heterogeneity statistic), respectively, with no evidence of heterogeneity. Factors that possibly affect advantage of combination therapy over solo therapy included increased frequency of pretreatment diarrhea and higher prevalence of noninvasive pathogens.
Antibiotic therapy with adjunctive loperamide offers an advantage over antibiotics alone by decreasing the illness duration and increasing the probability of early clinical cure.
To determine if loperamide is effective and safe in treating watery diarrhoea, we randomly assigned 50 adult expatriates in Bangladesh with more than three unformed stools in the previous 24 hours and illness of less than 72 hours to receive loperamide or a placebo. On entry into the five day study patients took two capsules (one loperamide capsule = 2 mg) and one after each unformed stool up to a maximum of eight per day. The groups did not significantly differ in pretreatment features or pathogens identified. Mean number of stools on study day 1 was 2.6 in the loperamide group and 4.0 in the placebo group (p = 0.035); on day 2 it was 1.3 versus 3.4 (p less than 0.001). Differences in stool frequencies during the final three study days, or proportion of patients with cramps, nausea, or vomiting on any study day, were not significant. No serious side effects occurred in either group. We conclude that loperamide, by decreasing stool frequency during the early part of illness, may have a role in the symptomatic treatment of this self-limiting disease.
Basic remarks: Among travellers to distant countries with a low socioeconomic status and poor hygiene, traveller's diarrhea is a major problem. Once this epidemiological fact had been recognized, intensive efforts were made to reduce the incidence of this illness by prophylactic medication. Among non-antibiotic substances investigated, Saccharomyces boulardii (SB) appeared to show promising results in earlier studies. Method: In a placebo-controlled, double-blind study, various dosages (250 mg and 1,000 mg SB) were administered prophylactically to 3,000 Austrian travellers to distant regions. Results: A significant reduction in the incidence of diarrhea was observed, with succcess depending directly on the rigorous use of the preparation. A tendency was noted for SB to have a varying regional effect, which was particularly marked in North Africa and in the Near-east (Turkey!); in addition, the effect also proved to be dose-dependent. The medication can be classified as low on side effects.
AIM: To purify anticoagulation protein from human placental and study the biochemical characterization. METHODS: The placental anticoagulation protein was purified from human placenta by ammonium sulfate precipitation, negative ion exchange chromatography on DEAE Sepharose CL-6B, gel filtration on Sephadex G-75 and Heparin Sepharose CL-6B affinity chromatography. Its anticoagulant activities in vitro were assayed by Activated partial thromboplastin time (APTT); its molecular weight was calculated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and its isoelectric point was estimated by the isoelectric focusing electrophoresis. RESULTS: A kind of protein was purified from human placenta that was able to prolong APTT. The purified protein accounted for 0.1% of the total placenta. SDS-PAGE showed that it was a single polypeptide and its molecular weight was 34. 9KD. The isoelectric point was pH4. 9 by the isoelectric focusing electrophoresis. Its effect on APTT was stronger with increasing its concentration. CONCLUSION: The method proued to be sucessful for of the purification of anticoagulation protein from the placental.
Twenty-five men with induced shigellosis received a mixture of diphenyoxylate hydrochloride with atropine (Lomotil), placebo and oxolinic acid (Oxabid), or a second placebo in four randomly assigned treatment groups. Diarrhea was decreased by oxolinic acid or Lomotil therapy, while fever was prolonged in the group receiving only Lomotil. Two men who received Lomotil alone had fever until the drug regimen was discontinued five days later. Shigellae were eradicated from stool in four of six men treated with oxolinic acid alone, but in only one of six men receiving oxolinic acid and Lomotil.Lomotil may be contraindicated in shigellosis. Diarrhea may represent a defense mechanism when disease is caused by a bacterial pathogen that must penetrate the intestinal epithelium to produce illness where increased intestinal motility (diarrhea) may decrease contact time between the invasive bacteria and mucosal cells.
Context Traveler's diarrhea (TD) can incapacitate travelers.
Characteristics of TD could be helpful in identifying individuals who
might benefit from a vaccine against TD.Objective To determine epidemiology, etiology, and impact of TD in
Jamaica.Design Two-armed, cross-sectional survey conducted between March
1996 and May 1997.Setting Sangster International Airport and 10 hotels in Montego
Bay area, Jamaica.Subjects To investigate epidemiology and impact, 30,369
short-term visitors completed a questionnaire just before boarding
their homebound aircrafts. To investigate etiology, 322 patients (hotel
guests) with TD provided stool samples.Main Outcome Measures Attack and incidence rates of reported
diarrhea and of classically defined TD (≥3 unformed stool samples in
24 hours and ≥1 accompanying symptom), incapacity, risk factors, and
etiology.Results The attack rate for diarrhea was 23.6% overall, with
11.7% having classically defined TD. For a mean duration of stay of 4
to 7 days, the incidence rate was 20.9% (all TD) and 10.0% (classic
TD). Among airport respondents, the incapacity lasted a mean of 11.6
hours. Less than 3% of all travelers avoided potentially high-risk
food and beverages. The most frequently detected pathogens were
enterotoxigenic Escherichia coli, Rotavirus, and
Salmonella species.Conclusions A realistic plan for reducing TD is needed. Preventive
measures such as the improvement of hygienic conditions at the
destination, and/or the development of vaccines against the most
frequent pathogens associated with TD may contribute toward achieving
this goal.
OBJECTIVE:The study was designed to evaluate the effectiveness of SP-303 (Provir), a plant-derived product with novel antisecretory properties, in the treatment of travelers’ diarrhea.METHODS:A total of 184 persons from the United States who acquired diarrhea in Jamaica or Mexico were enrolled in a double-blind, placebo-controlled study examining the effectiveness of three doses of SP-303 in reducing illness. Subjects were treated with 125 mg, 250 mg, or 500 mg SP-303 or a matching placebo four times a day for 2 days. Subjects kept daily diaries of symptoms and were seen each day for 3 days. Of the subjects, 169 (92%) were included in the efficacy analysis.RESULTS:The most common etiological agent identified was enterotoxigenic Escherichia coli, found in 19% of subjects. The mean time interval from taking the first dose of medication until passage of the last unformed stool during 48 h therapy (TLUS48) was 38.7 h for the placebo group. TLUS48 was shortened by SP-303: 30.6 h for the 125-mg dose group (p = 0.005); 30.3 h for the 250-mg group; and 32.6 h for the 500-mg group (p = 0.01). Treatment failures were seen in 29.3% in the placebo group compared with 7.3% (p = 0.01), 4.3 (p = 0.002), and 9.8 (p = 0.026) in the three treatment groups. SP-303 was well tolerated at all doses.CONCLUSIONS:SP-303 was effective in shortening the duration of travelers’ diarrhea by 21%. This antisecretory approach works directly against the pathophysiology of travelers’ diarrhea and is not likely to potentiate invasive forms of diarrhea or to produce posttreatment constipation.
Bacterial enteropathogens, the major cause of travelers' diarrhea, are customarily treated with antibacterial drugs. Rifaximin, a nonabsorbed antimicrobial was examined as treatment for travelers' diarrhea.
A randomized, prospective, double-blind clinical trial was carried out in 72 US adults in Mexico. Patients with acute diarrhea received one of three doses of rifaximin (200, 400 and 600 mg t.i.d.) or trimethoprim/sulfamethoxazole (TMP/SMX, 160 mg/800 mg b.i.d.) for 5 days. Results were compared with data from 2 placebo-treated historical control populations.
The shortest duration of treated diarrhea was seen in the group receiving 200 mg rifaximin t. i.d (NS). Clinical failure to respond to treatment occurred in 6 of 55 (11%) rifaximin-treated subjects versus 5 of 17 (29%) of TMP/SMX-treated subjects (NS). Sixteen of twenty (80%) of the enteropathogens isolated from the rifaximin-treated subjects and 7 of 7 (100%) from the TMP/SMX group were eradicated by treatment (NS). Sixteen of twenty-four (67%) enteropathogens identified were susceptible to TMP and all 24 were inhibited by</=50 microgram/ml of rifaximin. Rifaximin reduced the number of unformed stools passed during the first 24 h of treatment when compared with 2 control placebo groups (3.3 versus 5.1; p = 0.008 and 0.0001) and led to a reduced duration of post-enrollment diarrhea (mean values of 43.1 versus 68.1 and 81.9 h; p = 0.001).
Rifaximin shortened the duration of travelers' diarrhea compared with TMP/SMX and 2 earlier studied placebo-treated groups. A poorly absorbed drug if effective in treating bacterial diarrhea has pharmacologic and safety advantages over the existing drugs.
Aliment Pharmacol Ther 2011; 34: 1269–1281
Background The use of proton pump inhibitors (PPIs) is increasing worldwide. Suppression of gastric acid alters the susceptibility to enteric bacterial pathogens.
Aim This systematic review was undertaken to examine the relationship between PPI use and susceptibility to enteric infections by a specific pathogen based on published literature and to discuss the potential mechanisms of PPI enhanced pathogenesis of enteric infections.
Methods PubMed, OVID Medline Databases were searched. Search terms included proton pump inhibitors and mechanisms of, actions of, gastric acid, enteric infections, diarrhoea, Clostridium difficile, Salmonella, Shigella and Campylobacter.
Results The use of PPIs increases gastric pH, encourages growth of the gut microflora, increases bacterial translocation and alters various immunomodulatory and anti-inflammatory effects. Enteric pathogens show variable gastric acid pH susceptibility and acid tolerance levels. By multiple mechanisms, PPIs appear to increase susceptibility to the following bacterial enteropathogens: Salmonella, Campylobacter jejuni, invasive strains of Escherichia coli, vegetative cells of Clostridium difficile, Vibrio cholerae and Listeria. We describe the available evidence for enhanced susceptibility to enteric infection caused by Salmonella, Campylobacter and C. difficile by PPI use, with adjusted relative risk ranges of 4.2–8.3 (two studies); 3.5–11.7 (four studies); and 1.2–5.0 (17 of 27 studies) for the three respective organisms.
Conclusions Severe hypochlorhydria generated by PPI use leads to bacterial colonisation and increased susceptibility to enteric bacterial infection. The clinical implication of chronic PPI use among hospitalized patients placed on antibiotics and travellers departing for areas with high incidence of diarrhoea should be considered by their physicians.
Rifaximin has been shown to be effective in treating and preventing travelers' diarrhea (TD) during the summer season.
The goal of this double-blinded multicenter trial was to assess the efficacy and safety of rifaximin 550 mg administered once daily for 14 days compared with placebo in the prevention of TD during the dry season in Mexico.
There were 101 participants randomized. Overall, 25 participants developed TD during the 3 weeks of the study: 22% from the rifaximin group and 29% from the placebo group (p = 0.4). Mild diarrhea (defined as only one or two unformed stools during a 24-h period plus at least one abdominal symptoms) developed in only 3 (6%) participants taking rifaximin compared with 10 (21%) taking placebo during the first week of study (p = 0.03). No clinically significant or serious adverse events were reported.
Antibiotic prophylaxis of TD in Mexico during the dry season needs to be further studied and its benefits weighed against the benefits of self-treatment.
Recent epidemiologic data on travelers' diarrhea (TD) are essential for the evaluation of conventional and future prophylactic and therapeutic measures.
To determine the epidemiology, including risk factors, impact and quality-of-life evaluation of TD, a cross-sectional survey was conducted over 12 months at the airports of Mombasa (Kenya), Goa (India), Montego Bay (Jamaica) and Fortaleza (Brazil) by distributing questionnaires to visitors just prior to their flying home. The study period was March 1996 to July 1998.
Overall, 73,630 short-term visitors completed a questionnaire. The total diarrhea attack rate varied between a high of 54.6% in Mombasa and a low of 13.6% in Fortaleza, but only between 31.5% and 5.4% of all travelers had classic TD. The 14-day incidence rates varied between 19.5% and 65.7%. Few travelers meticulously avoided potentially dangerous food items, although in India and Kenya most travelers avoided those considered most dangerous. Risk factors were stays exceeding 1 week, age between 15 and 30 years, and residence in the UK. The impact, measured as incapacity or quality-of-life scores, was very considerable.
TD continues to affect vacationers and business travelers as frequently as it did some 20 years ago. Compliance with recommendations to reduce exposure to pathogens by avoiding dangerous food items is poor among travelers from all countries. Implementation of food safety education programs may be difficult to achieve.
Diarrhea is the most common illness among travelers and expatriates in Nepal. Published data on the etiology of travelers' diarrhea (TD) in Nepal are over 13 years old and no prior data exist on antibiotic susceptibility for currently used drugs. We investigated the etiology of diarrhea and antimicrobial susceptibility pattern of bacterial pathogens and compared the results to previous work from the same clinical setting.
A total of 381 cases and 176 controls were enrolled between March 2001 and 2003 in a case-control study. Enrollees were over age 18 years from high socioeconomic countries visiting or living in Nepal. Stool samples were assessed by microbiologic, molecular identification, and enzyme immunoassay (EIA) methods, and antimicrobial susceptibility was determined by disk diffusion. Risk factors were assessed by questionnaires.
At least one enteropathogen was identified in 263 of 381 (69%) cases and 47 of 176 (27%) controls (p ≤ 0.001). Pathogens significantly detected among cases were Campylobacter (17%), enterotoxigenic Escherichia coli (ETEC) (15%), Shigella (13%), and Giardia (11%). Cyclospora was detected only in cases (8%) mainly during monsoon season. Although 71% of Campylobacter isolates were resistant to ciprofloxacin, 80% of bacterial isolates overall were sensitive to either ciprofloxacin or azithromycin while 20% were intermediately sensitive or resistant. No bacterial isolates were resistant to both drugs.
The most common pathogens causing TD in Nepal were Campylobacter, ETEC, and Shigella. Because resistance to fluoroquinolone or azithromycin was similar, one of these drugs could be used as empiric therapy for TD with the other reserved for treatment failures.
Summary of Studies in the Current Supplement That Assess Health Impact, Indirect Benefits, or StrainChanges After Rotavirus Vaccination Location (Ref) Vaccine Key Findings InterpretationHealth impactEl Salvador(15)RV1 35%–48% decline in all cause diarrhea events(outpatient and inpatient) and 69%–81%decline in rotavirus hospitalizations amongchildren 5 yearsThe consistency of the findings across regions, predominantlyduring seasons when rotavirus predominates, withincreasing effect among children in ages with the highestvaccination rates strongly supports vaccination as theMexico (17) RV1 11%–40% reduction in all cause diarrhea primary cause of the observed declines in diarrheahospitalizations among children 5Panama (18) RV1 22%–37% reduction in all cause diarrheahospitalizations among children 5The sustained declines in disease for 2–3 year aftervaccination indicates that duration of protection in thesesettings was sufficient to impact the youngest childrenwho bear the greatest burden of severe rotavirus diarrheBelgium (20) RV1 65%–83% reduction in rotavirushospitalizationsAustralia (21) RV1 & RV5 89%–94% vaccine efficacy against rotavirushospitalizations among children 5; 68%–93% reduction in under-1 rotavirus admitsLarge declines in all-cause diarrhea hospitalizations indicatethat rotavirus may be a more important cause of childhooddiarrhea than previously estimatedUnited States(19)RV5* No rotavirus epidemic occurred in January–June 2010, the first time in 19 years of USsurveillance within this systemIndirect benefitsEl Salvador(15)RV1 41%–68% decline during 2008 in childrenolder than 2 yr who were unvaccinatedIndirect benefits of vaccination in the early (1–2) years aftervaccination suggests that young infants may be theprimary drivers of epidemic spread (at least in middle andhigh income settings)United States(23)RV5* 42%–45% reduction among children tooyoung or old to be vaccinatedAustralia (21) RV1 & RV5 50% reduction in rotavirus hospitalizationsamong children older than 2 years who wereunvaccinatedIn poorer countries such as El Salvador, the total protectionat a population level as a result of indirect benefits ofvaccination has the potential to offset the lower efficacydirectly afforded to the vaccineStrain monitoringBrazil (45) RV1 Increase in G2P 4 for 2 year after vaccination Epidemiologic assessments, such as case-control vaccineeffectiveness, and robust longitudinal surveillance areneeded to best assess interaction between rotavirusvaccination and strain ecologyAustralia (47) RV1 & RV5 G1P 8 was the predominant strain nationally,however, some transient increase in G2P 4and G3P 8 prevalence occurred in Rotarixand RotaTeq states, respectivelyExisting strain surveillance data, vaccine effectivenessresults, and the dramatic declines in disease burden incountries with rotavirus vaccination support naturalvariation in strain ecology as the likely explanation for thereported observations in short-term changes in strainsafter vaccinationUnited States(46)RV5* Higher prevalence of G3P 8 in some US citiesafter rotavirus vaccinationOngoing disease and strain surveillance is needed to assesslonger term evolution in stain ecology and potential impacton disease burden
Noroviruses are the leading cause of foodborne disease outbreaks worldwide, and may soon eclipse rotaviruses as the most common cause of severe pediatric gastroenteritis, as the use of rotavirus vaccines becomes more widespread. Genetic mutations and recombinations contribute to the broad heterogeneity of noroviruses and the emergence of new epidemic strains. Although typically a self-limited disease, norovirus gastroenteritis can cause significant morbidity and mortality among children, the elderly, and the immunocompromised. The lack of a cell culture or small animal model has hindered norovirus research and the development of novel therapeutic and preventative interventions. However, vaccines based on norovirus capsid protein virus-like particles are promising and may one day become widely available through transgenic expression in plants.
Because bacterial pathogens are the primary cause of travelers' diarrhea (TD), antibiotic prophylaxis is effective in TD prevention. This study assessed the efficacy and safety of the nonsystemic antibiotic rifaximin in preventing TD in US travelers to Mexico.
Healthy adult students traveling to Mexico received rifaximin 600 mg/d or placebo for 14 days and were followed for 7 days post-treatment. Stool pattern and gastrointestinal symptoms were recorded in daily diary entries. The primary end point was prevention of TD during 14 days of treatment measured by time to first unformed stool.
A total of 210 individuals received rifaximin (n = 106) or placebo (n = 104) and were included in the safety population. Median age was 21 years (range, 18-75 y), and the majority of participants were female (65%). Efficacy analyses were conducted in a modified intent-to-treat population of 201 patients who received rifaximin (n = 99) or placebo (n = 102). Rifaximin prophylaxis reduced risk of developing TD versus placebo (p < 0.0001). A smaller percentage of individuals who received rifaximin versus placebo developed all-cause TD (20% vs 48%, respectively; p < 0.0001) or TD requiring antibiotic therapy (14% vs 32%, respectively; p = 0.003). More individuals in the rifaximin group (76%) completed treatment without developing TD versus those in the placebo group (51%; p = 0.0004). Rifaximin provided a 58% protection rate against TD and was associated with fewer adverse events than placebo.
Prophylactic treatment with rifaximin 600 mg/d for 14 days safely and effectively reduced the risk of developing TD in US travelers to Mexico. Rifaximin chemoprevention should be considered for TD in appropriate individuals traveling to high-risk regions.
Shiga toxin (Verocytotoxin)-producing Escherichia coli (STEC or VTEC) causes serious gastrointestinal infections in humans, including diarrhea and hemorrhagic colitis, and may lead to life-threatening sequelae such as the hemolytic uremic syndrome (HUS). The triennial 'VTEC' meetings provide a multidisciplinary forum for presentation of the latest research on all aspects of STEC, with sessions addressing epidemiology of human disease, animal reservoirs and transmission of STEC via the food chain, mechanisms of pathogenesis and host response, and control and prevention strategies. Management of patients with STEC disease can be challenging, particularly since conventional antibiotic therapy is contraindicated because it is believed to increase the risk of complications by promoting release of Shiga toxin by STEC in the gut. Accordingly, this report will focus on papers presented at the meeting that addressed development of alternative therapeutic strategies.
The most frequent illness among persons traveling from developed to developing countries is travelers' diarrhea. Travelers to high-risk regions traditionally have been educated to exercise care in food and beverage selection. Innovative research is needed to identify ways to motivate people to exercise this care and to determine its value. Chemoprophylaxis can be recommended for certain groups while monitoring for safety, drug resistance, and efficacy against all forms of bacterial diarrhea. Research to evaluate the value of immunoprophylaxis is recommended. In the following document, the authors used an evidence base when available to determine strength and quality of evidence and when data were lacking, the panel experts provided consensus opinion.
A bidirectional cohort study investigates whether pre-travel vaccination with whole cell/recombinant B subunit inactivated, killed oral cholera vaccine reduces the incidence of diarrhoea in young adult travellers to high-risk areas.
Risk of travellers' diarrhoea was assessed according to destination and reason for travel in high-risk travellers of a travel clinic in Barcelona, Spain. Those at high-risk between January and December 2005 were advised on water/food safety and hygiene. High-risk travellers between January and December 2006 were additionally vaccinated with WC/rBS oral cholera vaccine. Data regarding diarrhoea were gathered by structured telephone interview or e-mailed questionnaire following the travellers' return. The incidence of diarrhoea in the group vaccinated with WC/rBS oral cholera vaccine (n=321) was 17.4%, compared with 39.7% in the non-vaccinated group (n=337) (adjusted risk ratio 0.40). The first episode was significantly shorter in the vaccinated group (mean 2.3 days) than in the non-vaccinated group (mean 3.8 days) (p<0.001).
The protective effect of the WC/rBS oral cholera vaccine was 57% in the young, high-risk travellers. Vaccination with the WC/rBS oral cholera vaccine as well as food safety and hygiene advice could offer effective means of reducing the risk of diarrhoea while abroad.
Fifty-one published studies of travelers' diarrhea (TD) were examined to look for regional differences in pathogens identified. Enterotoxigenic E. coli was detected in 1,678/5,518 (30.4%) of TD cases overall, with rates in Latin America/Caribbean (L. America), Africa, south Asia, and Southeast Asia of 1,109/3,302 (33.6%), 389/1,217 (31.2%), 153/499 (30.6%), and 36/500 (7.2%), respectively (P < 0.001). Enteroaggregative E. coli was the second most common agent in L. America, found in 166/689 (24.1%), compared with 3/165 (1.8%) in Africa and 33/206 (16%) in south Asia (P < 0.001). Other significantly regional differences were seen for enteropathogenic E. coli, diffusely adherent E. coli, Campylobacter, Shigella spp., Salmonella, Aeromonas spp., Plesiomonas, Vibrios, rotavirus, noroviruses, Giardia, and Entoamoeba histolytica. The regional differences in pathogen identification identified will serve as a baseline for antimicrobial therapy recommendations and vaccines strategies.
Students attending a Mexican university who developed diarrhea were randomly treated with bismuth subsalicylate or a placebo. One hundred and eleven were given 30 ml each 1/2 hr until eight doses (total dose of active drug 4.2 g) were given and 58 students received twice this dose (8.2 g of active drug) over the 3 1/2-hr treatment period. The number of unformed stools was significantly decreased in both bismuth subsalicylate treatment groups compared to the placebo controls for the period 4 to 24 hr after therapy. A reduction in diarrhea was additionally noted for the duration of the 48-hr surveillance period for the students receiving the higher dose of active drug. Subjective relief within 24 hr of therapy of the symptoms of diarrhea, nausea, and abdominal pain or cramps was reported with a significantly increased frequency in the bismuth subsalicylate group. The most pronounced effect of the treatment occurred in the United States students with diarrhea who had recently arrived in Mexico. This appeared to be related to the favorable effect of bismut subsalicylate on the course of toxigenic Escherichia coli infection. Students with shigellosis did not experience a prolonged illness in either treatment group.
In this double-blind study with 232 patients, 300 mg of ofloxacin given orally twice daily for 5 or 3 days was compared with placebo for the treatment of acute diarrhea in U.S. students visiting Guadalajara, Mexico. The 3-day regimen of ofloxacin was found to be as effective as the 5-day regimen in producing a clinical and microbiologic cure. Clinical cures for patients who received ofloxacin for 5 days occurred in 59 of 66 (89%) subjects, whereas clinical cure occurred in 77 of 81 (95%) of those who received ofloxacin for 3 days and in 56 of 79 (71%) of those who took placebo (P = 0.0001). When the duration of diarrhea after therapy was begun was compared in subgroups, a significant (P less than 0.05) shortening of posttreatment illness occurred in comparison with that in the placebo group for the following groups: for 5 days of ofloxacin, cases of shigellosis (32 versus 98 h); for 3 days of ofloxacin, all cases (28 versus 56 h), cases of enterotoxigenic Escherichia coli diarrhea (26 versus 66 h), cases of shigellosis (24 versus 98 h), all cases of illnesses associated with a bacterial enteropathogen (28 versus 69 h), and cases of illnesses in which numerous leukocytes were found in stool by microscopy (22 versus 49 h). Microbiologic eradication rates were 75 of 78 (96%) for patients who received ofloxacin and 37 of 46 (80%) for patients who received placebo (P = 0.009). There was no significant difference in the number of adverse events reported by patients in either of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
B-subunit/whole-cell cholera vaccine (BS-WC) has been shown to give Bangladeshi mothers and children only 3 months' protection against severe diarrhoea due to enterotoxigenic Escherichia coli (ETEC). Since a long-lasting effect is not necessary for protection against travellers' diarrhoea, a prospective double-blind study was conducted among tourists who went to Morocco from Finland. 307 tourists received two oral doses of BS-WC, whereas 308 controls received a placebo before departure. A research team went out with tourists and a laboratory for enteric pathogens was set up on location. A faecal specimen was taken from 100 randomly selected subjects before departure, from all travellers with diarrhoea, and routinely after return. Enteropathogenic bacteria were not isolated from any of the pre-departure specimens but were present during or after the holiday in 47% of tourists with travellers' diarrhoea, and in 14% of those without diarrhoea. BS-WC induced a 52% protection (p = 0.013) against diarrhoea caused by ETEC. The protection was better for mixed infections (65%, p = 0.016). The protective efficacy against a combination of ETEC and any other pathogen was 71% (p = 0.02), and that against ETEC plus Salmonella enterica even better at 82% (p = 0.01). Partial protection against travellers' diarrhoea is thus obtainable by active immunisation with BS-WC.
To determine the efficacy of ciprofloxacin therapy in eradicating convalescent fecal excretion of salmonellae after acute salmonellosis.
Randomized, placebo-controlled, double-blind trial of ciprofloxacin, with prospective follow-up of nonparticipants.
An acute care community hospital experiencing an outbreak of salmonellosis.
Twenty-eight health care workers developed acute infection with Salmonella java; 15 participated in a placebo-controlled trial of ciprofloxacin, beginning on day 9 after infection.
Eight patients were randomly assigned to receive ciprofloxacin, 750 mg, and 7 patients to receive placebo; both were administered orally twice daily for 14 days. Nonparticipants who received therapy were placed on the same ciprofloxacin regimen.
Study participants had follow-up stool cultures every 3 days initially and then weekly for 3 weeks; nonparticipants were followed until three consecutive cultures were negative. All eight ciprofloxacin recipients showed eradication of S. java from stool cultures within 7 days of beginning therapy (compared with 1 of 7 placebo recipients), and their stool cultures remained negative up to 14 days after discontinuing therapy (P less than 0.01). However, 4 of 8 relapsed; their stool cultures became positive between 14 and 21 days after therapy. In addition, 3 of 3 hospitalized patients treated with ciprofloxacin who did not participate in the controlled trial also relapsed. Thus, the total relapse rate was 7 of 11 (64%; 95% CI, 31% to 89%). In 4 of these 7 patients, relapse was associated with a longer duration of fecal excretion of salmonellae than that of the placebo group. Relapse could not be explained on the basis of noncompliance, development of resistance, or presence of biliary disease.
Despite its excellent antimicrobial activity against salmonellae and its favorable pharmacokinetic profile, ciprofloxacin at a dosage of 750 mg orally twice daily had an unacceptably high failure rate in patients with acute salmonellosis and may have prolonged fecal excretion of salmonellae. The late occurrence of relapses indicates the need to obtain stool cultures up to 21 days after therapy to document fecal eradication in acute salmonellosis.
An open-label, parallel comparison of loperamide hydrochloride (Imodium A-D) and bismuth subsalicylate (Pepto-Bismol) was conducted using nonprescription dosages in adult students with acute diarrhea (three or more unformed stools in the preceding 24 hours plus at least one additional symptom of enteric infection). For the two-day study period, the daily dosage was limited to 8 mg (40 ml) for loperamide-treated subjects and to 4.9 g for bismuth subsalicylate-treated subjects. At these dosages, loperamide significantly reduced the average number of unformed bowel movements relative to bismuth subsalicylate. Following the initial dose of treatment, control of diarrhea was maintained significantly longer with loperamide than with bismuth subsalicylate. Time to last unformed stool was significantly shorter with loperamide than with bismuth subsalicylate. In providing overall subjective relief, subjects rated loperamide significantly better than bismuth subsalicylate at the end of the 24 hours. Both treatments were well tolerated, and none of the minor adverse effects reported resulted in discontinuation of therapy. It was concluded that loperamide is effective at a daily dosage limit of 8 mg (40 ml) for the treatment of acute nonspecific diarrhea and provides faster, more effective relief than bismuth subsalicylate.
So far four randomized studies, three of them double-blind and placebo-controlled, have investigated the role of bismuth subsalicylate
(BSS) in the treatment of travelers' diarrhea. When compared with placebo BSS significantly reduced the number of unformed
stools and increased the proportion of patients free of symptoms at the end of the trial. In the two studies that compared
BSS with loperamide, the latter agent brought significantly faster relief. Diarrhea accompanied by dysenteric symptoms was
influenced most favorably by administration of systemic antimicrobial agents. In all four studies only minor adverse effects
were noted with BSSor the other active agents. One may include loperamide and a systemic antimicrobial agent in one's travel
kit; however, loperamide should not be used for dysentery, and the antimicrobial agent should not be used in uncomplicated
cases. As an alternative, although it is less effective, BSS has the unique advantage of being safe enough to use for all
patients with travelers' diarrhea.
Travellers from temperate climates to the tropics of the Third World face a high risk of acquiring traveller's diarrhea. Epidemiology plays a major role in the exact description of this syndrome. This paper describes the epidemiology of traveller's diarrhea in 3696 Austrian tourists and the influence of various epidemiologic parameters on incidence is evaluated. Destination and season of travel influences attack rates, in particular in the sub-tropics. High (up to app. 60% incidence) and low risk (below 35% incidence) regions can be described, exhibiting risk differences of nearly 100%. Individual parameters, like age and body weight, can influence the risk in an evident manner and, or course, the duration of stay plays a major role. It is pointed out that accommodation and travel characteristics are important factors for risk evaluation, as well as dietary hygiene.
The syndrome "Traveller's Diarrhea" (TD) is important for tourists travelling to warm-climate countries. In this study a worldwide survey on the clinical features of enteritis among 1,455 Austrian tourists is reported. The clinical parameters of TD show that this disease exhibits a very uniform clinical course which is not influenced by different regions with considerable differences in aetiology or by travel-associated parameters such as accommodation, travel style and individual dietary hygiene: TD starts mainly at the end of first week of the stay and the average duration of illness is 3.6 +/- 2.7 days. Watery and mucous stools were reported by 99% of patients with a frequency of 4 bowel movements per day, while bloody diarrhea occurred very rarely. However, 57.2% of patients suffered from abdominal cramps, less than one third of patients reported nausea and/or vomiting and fever accompanied the acute disease in 13%. Symptoms indicate that TD should not be considered a severe disease. The diarrheal illness will show the characteristics of an enteroinvasive disease only in rare cases. Treatment of TD is discussed: symptomatic or other non-antibiotic agents are preferable as antibiotics will only occasionally be necessary for treatment of an illness with a self-limiting character. For prophylaxis of TD, the preferable way to resolve the problem of TD in international travel, very few effective preparations are currently available, emphasizing the need for extensive research in this field.
The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC)oral vaccine
against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field
trial among rural Bangladeshi children and women. The 24 770 persons who ingested two or more doses of BS-WC vaccine were
compared with 24 842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent
fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up
(P < .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against
LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P < .05).
A retrospective survey, which is based on interviews conducted between 1975 and 1984 with 20,000 European tourists returning
from 15 destinations m various climatic zones, demonstrates that travelers' diarrhea is the most frequent health problem encountered
by travelers in the tropics. The incidence varied from 4% to 51%, depending on the destination. High-risk groups were persons
younger than 30 years, adventurous travelers, and travelers with preexisting gastrointestinal illnesses. Illness acquired
at various geographic regions showed only minor differences in chronology and symptomatology. The clinical course of travelers'
diarrhea was usually short and mild. Additionally: by longitudinal and retrospective analyses, the incidence and prognosis
of gastrointestinal infections of greater severity that were acquired after a short stay in a developing country, such as
giardiasis, amebiasis, typhoid fever, and cholera, were evaluated; typhoid fever and cholera, in particular, were found to
be quite rare.
Kozicki M (Institute of Social and Preventive Medicine of the University, Gloriastrasse 30, CH-8006 Zurich, Switzerland), Steffen R and Schär M. ‘Boil it, cook it, peel it or forget it: Does this rule prevent travellers’ diarrhoea? International Journal of Epidemiology 1985. 14: 169‐172.
A total of 688 out of 2240 air charter passengers in flight to Kenya, West Africa or Sri Lanka/Maldives volunteered to participate in a follow-up study investigating the influence of various food and beverage items on the incidence of travellers' diarrhoea. Within the first three days of their stay abroad, 98% accepted food or beverages whose avoidance is traditionally recommended. The incidence of diarrhoea, which was 19.5%, was proportionate to the number of dietary mistakes committed. The most dangerous items were those whose avoidance was traditionally recommended.
Travelers' diarrhea is the most frequent health problem during a stay in developing countries. A recent study basing on interviews with 16,568 charter flight passengers returning to Europe from 13 destinations in various climatic regions provides epidemiological data on a worldwide scale. Significant differences in diarrheal incidence varied not only between individual destinations, but also between hotels in the same area. The highest incidence for a two weeks' stay exceeded 50% in some regions of North and West Africa. Persons under 30 were more often affected than older travelers. Within international groups meeting in developing countries, the risk varied according to the patient's country of origin, with the residents of industrialized nations being most often affected. Even in the tropics, diarrhea usually takes a short and mild course. The various regions show unessential differences in chronology and symptomatology. E. coli is the most frequent causative agent of this ailment.
To investigate diarrhea in tourists on a worldwide scale, 16,568 passengers were interviewed during their flights home from 13 destinations in various climatic regions. Significant differences in diarrheal incidence were observed between individual destinations and also between hotels in the same area. The highest rates exceeded 50%. Younger persons were more often affected. Sex, travel characteristics, and a record of former tropical journeys influenced the incidence to a minor degree. Even in the tropics, diarrhea usually takes a short (average, 3.6 days) and mild (average of 4.6 stools per day) course. Prophylactic or therapeutic medication only slightly influenced these values. The various regions showed minor differences in chronology and symptomatology. This is consistent with quantitative rather than qualitative geographic variations in causative agents. The traditional nutritional recommendations for prophylaxis seemed to be unrealistic and usually unsuccessful.
As no adequate comparison of these widely used drugs has been made, we have performed a double-blind cross-over trial in 30 individuals with chronic diarrhea. Each underwent three randomized treatment periods of 4 wk duration. Patients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable. Stool frequency, consistency, urgency, and incontinence were then compared when a stable dose was reached. Though 2.3 capsules (4.6 mg) of loperamide, 2.3 capsules (103.5 mg) of codeine and 2.5 capsulses (12.5 mg) of diphenoxylate all reduced stool frequency to the same extent, diphenoxylate was significantly less effective in producing a solid stool. Before treatment 95% of patients experienced urgency, sometimes associated with fecal incontinence, often as their major diability. Loperamide and codeine were more effective in relieving this than was diphenoxylate. Side effects, particularly central nervous effects, were greatest with diphenoxylate and least with loperamide. Approximately equal numbers discontinued each preparation; poor control and central-nervous-system side effects were the usual reasons for stopping diphenoxylate and codeine, and abdominal pain and constipation for stopping loperamide. We conclude that both loperamide and codeine phosphate are superior to diphenoxylate in the symptomatic treatment of chronic diarrhea.
Annually, over 75 million international passengers travel to tropical areas, more than 20 million of whom come from industrialized countries. They experience a high rate of traveler's diarrhea (TD), varying from 20 to 56%, which may result in serious limitations to their activities. The cause of TD is considered to be infectious in the overwhelming majority of cases and, apart from differences in relative importance, the list of responsible microbial agents is fairly constant regardless of geographic origin. The ingestion of contaminated food or water is considered to be the principal mode of transmission of the enteric pathogens of TD. Several factors have been proposed as playing a role in the etiogenesis of diarrhea in travelers, including personal (age, socioeconomic status, body weight, preexisting gastrointestinal illnesses), behavioral (mode of travel, standard of accommodation, eating in public places, dietary errors) and travel-related (destination, duration of stay, country of origin, season) factors, which are reviewed in detail.
The therapeutic value of zaldaride maleate (Zm), an intestinal calmodulin inhibitor, was examined in patients with travelers' diarrhea, known to be caused by enterotoxigenic Escherichia coli (ETEC) and other bacterial agents.
One hundred seventy-six American students acquiring diarrhea in Mexico during the summer of 1991 were given Zm in doses of 5 mg, 10 mg, or 20 mg, or a matching placebo, four times a day for 48 hours.
The duration of diarrhea was reduced by 53% in the group given the 20-mg Zm dose (overall P < 0.01). Curative antibiotics were required post-treatment only in the placebo and 5-mg Zm groups (P < 0.01). The number of unformed stools passed during 0-48 hours of therapy with the highest Zm dose was reduced compared with placebo by 36% for all subjects (P < 0.05), by 39% for ETEC diarrhea (NS), by 45% for those with any bacterial agents (NS), and by 38% for those without an identifiable bacterial agent (NS).
The fact that a calmodulin inhibitor decreases the severity and duration of travelers' diarrhea has therapeutic implications and suggests that calmodulin and intracellular calcium may serve as mediators of diarrhea in bacterial enteric infection.