Traveler's Diarrhea Research Articles

What Do Travelers Know about Traveler's Diarrhea? Impact of a Pre-Travel Consultation in the Lisbon Area, Portugal.

Traveler's diarrhea (TD) is one of the most common travel-related health problems, largely interfering with planned activities and potentially contributing to antimicrobial resistance. This study aimed to characterize the knowledge about TD among pre-travel consultation users of one Portuguese travel clinic and determine the impact of the consultation on knowledge levels. Using a quasi-experimental, separate-sample pretest-posttest design, participants were randomly assigned to two groups: control/pre-consultation group (CG) or experimental/post-consultation group (EG). An anonymous self-administered questionnaire was used. A total of 470 participants were analyzed (227 CG; 243 EG). The EG/post-consultation group showed significant improvement in knowledge, with correct answers increasing from 63% to 75% (p < 0.001). However, knowledge gaps persisted: over 50% were unaware of TD's self-limited nature, 30% did not recognize loperamide as a symptom reliever, and 36% believed all travelers should take antibiotics to prevent TD. The educational level and previous travel outside Europe influenced baseline knowledge; previous travel medicine consultations and information on TD improved knowledge in both groups and made it easier to acquire knowledge on the subject. Thus, a pre-travel consultation effectively increased travelers' TD knowledge. However, post-consultation knowledge levels remained suboptimal, indicating the need for targeted interventions to increase travelers' literacy and optimize pre-travel consultations.

Challenges and Considerations in Selecting Animal Models for Evaluating a Live, Cold-Chain-Free, Dual-Use Vaccine (MyChol) for Diarrhoeal Diseases: A Comprehensive Review.

Diarrhoeal diseases are the second leading cause of death for children under 5 years old in 69 low- and middle-income countries, with an annual economic burden of US$ 4 billion and over 525,000 lives lost. Cholera and enterotoxigenic Escherichia coli (ETEC) traveller's diarrhoea are major diarrhoeal diseases caused by Vibrio cholerae (O1 and O139 serogroups) and ETEC, which have similar pathogeneses and can co-infect. There is no exclusive vaccine for ETEC, but cholera vaccines containing the cholera toxin B (CT-B) component offer short-term cross-protection. However, licensed oral cholera vaccines are expensive due to cold-chain supplies and the need for multiple doses. A cost-effective, dual-protection, live, cold-chain-free vaccine is, therefore, required for vaccination campaigns in low-resource settings, and MyChol - a prototype cold-chain-free live attenuated cholera vaccine, targeting V. cholerae O139 and ETEC H10407 - was developed in this context. The vaccine was evaluated in three animal models (Sprague Dawley [SD] rats, BALB/c mice and New Zealand white rabbits) for safety, colonisation capacity, reactogenicity and immunogenicity against challenge strains. In suckling mice, MyChol displayed high colonisation potential compared to unformulated VCUSM14P (the vaccine candidate) and wild-type O139. In the acute toxicity assessment, the SD rats with the highest MyChol dose (1 × 107 colony-forming unit [CFU]/kg) demonstrated no adverse effects or mortality. Mice vaccinated with MyChol exhibited elevated antibody levels, including anti-CT, anti-heat-labile enterotoxin (LT), anti-CT-B and anti-LT-B. Anti-CT antibodies neutralised LT toxin in ETEC H10407 in challenge studies and cross-protected against ETEC H10407 in both mice and rabbits, preventing weight loss and diarrhoea. Ileal loop experiments in rabbits and BALB/c mice showed no reactogenicity. This review, based on our previous research, therefore provides valuable insights into improving the selection of animal models to advance preclinical evaluations of diarrhoeal vaccines.

The role of pharmaceutical care in the use of rifaximin for the treatment of diarrhea

the management of diarrhea represents a prevalent issue within the realm of healthcare. Rifaximin is recommended to treat traveler's diarrhea and irritable bowel syndrome. At the same time, it is important to rationally use an antimicrobial drug to prevent the development of antimicrobial resistance. Aim: to evaluate the role of pharmaceutical care in using rifaximin to treat diarrhea, based on a questionnaire. A questionnaire survey was done among 55 pharmacy professionals and 42 pharmacy visitors regarding the dispensing and use of rifaximin for diarrhea treatment. The survey of pharmacy visitors revealed that rifaximin was used for the treatment of small intestinal bacterial overgrowth syndrome (32 cases), traveler's diarrhea (7 cases), and irritable bowel syndrome with diarrhea (3 cases). Patients did not undergo stool culture before rifaximin prescription, which could have prevented antimicrobial resistance and ruled out other causes of diarrhea. It was found that 14% of respondents reported improvement the next day, while 83.3% reported improvement within three days. Pharmacists can educate visitors about the importance of completing the treatment course. Five percent of respondents reported nausea as an adverse reaction. Pharmacists dispensed rifaximin for the treatment of diarrhea in adults almost three times more often than in children. The tablet form of the drug was used in 94.5% of cases, while the oral suspension was used in 5.5% of cases. The majority of pharmacy visitors (89.0%) received rifaximin with a doctor's prescription, and 10.9% without a prescription, which emphasizes the importance of pharmaceutical care to prevent irrational use of the drug. The results of the study show that 92.7% of pharmacists provide recommendations on the safety of rifaximin use, and 78.2% recommend abstaining from alcohol during treatment. Only 21.8% of pharmacists warn about the possible staining of urine, which can cause concern for patients. The majority of pharmacists (89.1%) systematically ask women about possible pregnancy, which indicates their awareness of safe pharmacotherapy. Pharmacists also clarify the simultaneous use of rifaximin with other drugs: 32.7% ask about taking oral contraceptives, 7.3% – antiarrhythmic drugs, and 3.6% – warfarin. mailto:https://meshb.nlm.nih.gov/record/ui?ui=D002648Pharmacists can enhance the effectiveness of rifaximin treatment by preventing its uncontrolled use, emphasizing the importance of completing the treatment course and informing about possible adverse reactions. When providing pharmaceutical care to visitors taking rifaximin, pharmacists should educate them about potential changes in urine color. Additionally, pharmaceutical workers advise women taking oral contraceptives to use additional contraceptive methods while taking rifaximin.

A Longitudinal Study of Escherichia coli Clinical Isolates from the Tracheal Aspirates of a Paediatric Patient-Strain Type Similar to Pandemic ST131.

Escherichia coli is a Gram-negative bacterium and part of the intestinal microbiota. However, it can cause various diarrhoeal illnesses, i.e., traveller's diarrhoea, dysentery, and extraintestinal infections when the bacteria are translocated from the intestine to other organs, such as urinary tract infections, abdominal and pelvic infections, pneumonia, bacteraemia, and meningitis. It is also an important pathogen in intensive care units where cross-infection may cause intrahospital spread with serious consequences. Within this study, four E. coli isolates from the tracheal aspirates of a tracheotomised paediatric patient on chronic respiratory support were analysed and compared for antibiotic resistance and virulence potential. Genomes of all four isolates (5381a, 5381b, 5681, 5848) were sequenced using Oxford Nanopore Technology. According to PFGE analysis, the clones of isolates 5681 and 5848 were highly similar, and differ from 5381a and 5381b which were isolated first chronologically. All four E. coli isolates belonged to an unknown sequence type, related to the E. coli ST131, a pandemic clone that is evolving rapidly with increasing levels of antimicrobial resistance. All four E. coli isolates in this study exhibited a multidrug-resistant phenotype as, according to MIC data, they were resistant to ceftriaxone, ciprofloxacin, doxycycline, minocycline, and tetracycline. In addition, principal component analyses revealed that isolates 5681 and 5848, which were recovered later than 5381a and 5381b (two weeks and three weeks, respectively) possessed more complex antibiotic resistance genes and virulence profiles, which is concerning considering the short time period during which the strains were isolated.

A Comprehensive Narrative Review of Drug Interactions Between Traveler's Diarrhea Medications and Chronic Therapies: Implications for Clinical Practice.

Diarrhea is a common illness for travelers. Traveler's diarrhea is typically defined as experiencing at least three unformed stools per day during a stay abroad or within 10 days of returning from the destination. In this review, we consulted five databases, namely, Medicine Complete, Medscape, Drugs.com, Epocrates, and DDInter, to conduct a comprehensive drug interaction analysis. We selected commonly prescribed medications used for the treatment of traveler's diarrhea, including ciprofloxacin, levofloxacin, norfloxacin, ofloxacin, azithromycin, rifaximin, bismuth salicylate, and loperamide. The antidiabetic medications chosen included metformin, glipizide, glimepiride, sitagliptin, linagliptin, dapagliflozin, empagliflozin, and acarbose. The chosen antihypertensive drugs were telmisartan, olmesartan, amlodipine, nifedipine, enalapril, ramipril, metoprolol, and propranolol. Aspirin, clopidogrel, ticagrelor, rivaroxaban, warfarin, atorvastatin, and rosuvastatin were also chosen as they play an essential role in cardiovascular treatment. We performed comprehensive interaction checks across all five databases for each combination of a traveler's diarrhea medication and medication from one of the three comorbid conditions (antidiabetic, antihypertensive, or cardioprotective). We categorized the severity of interactions as mild, moderate, or severe. Similarly, we used colors to highlight the number of databases reporting drug interactions, providing insights into the reliability of these interactions across sources. Interactions with antidiabetic drugs revealed that fluoroquinolones and sulfonylureas produce severe interaction effects. Comparatively, rifaximin can be safer as it exhibited mild interaction only with metformin, whereas the other antidiabetic drugs showed no interaction effect. Levofloxacin was found to be the safest drug among hypertensive individuals as it exerted no interaction effects with any of the antihypertensive medications. Levofloxacin and rifaximin were considered to be safe as these drugs interacted with only two cardioprotective drugs. This review features the importance of a precise approach in prescribing medications for traveler's diarrhea, especially for patients with chronic comorbidities. These findings play a pivotal role in improving awareness and providing tailored treatment for the interaction to ensure patient well-being.

Host-derived CEACAM-laden vesicles engage enterotoxigenic E. coli for elimination and toxin neutralization.

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of diarrheal illnesses annually ranging from mildly symptomatic cases to severe, life-threatening cholera-like diarrhea. Although ETEC are associated with long-term sequelae including malnutrition, the acute diarrheal illness is largely self-limited. Recent studies indicate that in addition to causing diarrhea, the ETEC heat-labile toxin (LT) modulates the expression of many genes in intestinal epithelia, including carcinoembryonic cell adhesion molecules (CEACAMs) which ETEC exploit as receptors, enabling toxin delivery. Here however, we demonstrate that LT also enhances the expression of CEACAMs on extracellular vesicles (EV) shed by intestinal epithelia and that CEACAM-laden EV increase in abundance during human infections, mitigate pathogen-host interactions, scavenge free ETEC toxins, and accelerate ETEC clearance from the gastrointestinal tract. Collectively, these findings indicate that CEACAMs play a multifaceted role in ETEC pathogen-host interactions, transiently favoring the pathogen, but ultimately contributing to innate responses that extinguish these common infections.

Rifaximin: A Comprehensive Review of Structure, Uses, Mechanisms of Action, and Assay Methods

Rifaximin, a derivative of rifamycin, has emerged as a promising therapeutic tool in gastroenterology. This review explores rifaximin's intricate molecular structure and pharmacokinetic properties, highlighting its minimal systemic absorption and targeted action within the gut. The multifaceted mechanisms of action, including direct antibacterial effects and modulation of gut microbiota, are discussed. The review then examines the efficacy of rifaximin in treating various gastrointestinal disorders like traveler's diarrhea, Irritable Bowel Syndrome with Diarrhea (IBS-D), and Small Intestinal Bacterial Overgrowth (SIBO). Dosage recommendations and the well-tolerated safety profile of rifaximin are presented. Finally, the importance of quality control measures using techniques like HPLC and spectroscopy is emphasized to ensure the drug's effectiveness and safety.

Travel medicine updates for the NP.

This article provides an overview of the approach to preparing patients for travel, including travel counseling and risk mitigation through vaccination and chemoprophylaxis. Although some patients require referral for consultation with a travel medicine specialist, others can be managed by their primary care provider. In this article, traveler's diarrhea, updated travel-related immunizations, and malaria prophylaxis are discussed.

Gut microbiota composition in travellers is associated with faecal lipocalin-2, a mediator of gut inflammation.

We examined the gut microbiota of travellers returning from tropical areas with and without traveller's diarrhoea (TD) and its association with faecal lipocalin-2 (LCN2) levels. Participants were recruited at the Hospital Clinic of Barcelona, Spain, and a single stool sample was collected from each individual to perform the diagnostic of the etiological agent causing gastrointestinal symptoms as well as to measure levels of faecal LCN2 as a biomarker of gut inflammation. We also characterised the composition of the gut microbiota by sequencing the region V3-V4 from the 16S rRNA gene, and assessed its relation with the clinical presentation of TD and LCN2 levels using a combination of conventional statistical tests and unsupervised machine learning approaches. Among 61 participants, 45 had TD, with 40% having identifiable etiological agents. Surprisingly, LCN2 levels were similar across groups, suggesting gut inflammation occurs without clinical TD symptoms. Differential abundance (DA) testing highlighted a microbial profile tied to high LCN2 levels, marked by increased Proteobacteria and Escherichia-Shigella, and decreased Firmicutes, notably Oscillospiraceae. UMAP analysis confirmed this profile's association, revealing distinct clusters based on LCN2 levels. The study underscores the discriminatory power of UMAP in capturing meaningful microbial patterns related to clinical variables. No relevant differences in the gut microbiota composition were found between travellers with or without TD. The findings suggest a correlation between gut microbiome and LCN2 levels during travel, emphasising the need for further research to discern the nature of this relationship.

The colonization factor CS6 of enterotoxigenic Escherichia coli contributes to host cell invasion

Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of diarrhea in children and travelers in low-income regions. The virulence of ETEC is attributed to its heat-labile and heat-stable enterotoxins, as well as its colonization factors (CFs). CFs are essential for ETEC adherence to the intestinal epithelium. However, its invasive capability remains unelucidated. In this study, we demonstrated that the CS6-positive ETEC strain 4266 can invade mammalian epithelial cells. The invasive capability was reduced in the 4266 ΔCS6 mutant but reintroduction of CS6 into this mutant restored the invasiveness. Additionally, the laboratory E. coli strain Top 10, which lacks the invasive capability, was able to invade Caco-2 cells after gaining the CS6-expressing plasmid pCS6. Cytochalasin D inhibited cell invasion in both 4266 and Top10 pCS6 cells, and F-actin accumulation was observed near the bacteria on the cell membrane, indicating that CS6-positive bacteria were internalized via actin polymerization. Other cell signal transduction inhibitors, such as genistein, wortmannin, LY294002, PP1, and Ro 32–0432, inhibited the CS6-mediated invasion of Caco-2 cells. The internalized bacteria of both 4266 and Top10 pCS6 strains were able to survive for up to 48 h, and 4266 cells were able to replicate within Caco-2 cells. Immunofluorescence microscopy revealed that the internalized 4266 cells were present in bacteria-containing vacuoles, which underwent a maturation process indicated by the recruitment of the early endosomal marker EEA-1 and late endosomal marker LAMP-1 throughout the infection process. The autophagy marker LC3 was also observed near these vacuoles, indicating the initiation of LC-3-associated phagocytosis (LAP). However, intracellular bacteria continued to replicate, even after the initiation of LAP. Moreover, intracellular filamentation was observed in 4266 cells at 24 h after infection. Overall, this study shows that CS6, in addition to being a major CF, mediates cell invasion. This demonstrates that once internalized, CS6-positive ETEC is capable of surviving and replicating within host cells. This capability may be a key factor in the extended and recurrent nature of ETEC infections in humans, thus highlighting the critical role of CS6.

Inflammation, the kynurenines, and mucosal injury during human experimental enterotoxigenic Escherichia coli infection

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children and travelers, especially in low- and middle-income countries. ETEC is a non-invasive gut pathogen colonizing the small intestinal wall before secreting diarrhea-inducing enterotoxins. We sought to investigate the impact of ETEC infection on local and systemic host defenses by examining plasma markers of inflammation and mucosal injury as well as kynurenine pathway metabolites. Plasma samples from 21 volunteers experimentally infected with ETEC were collected before and 1, 2, 3, and 7 days after ingesting the ETEC dose, and grouped based on the level of intestinal ETEC proliferation: 14 volunteers experienced substantial proliferation (SP) and 7 had low proliferation (LP). Plasma markers of inflammation, kynurenine pathway metabolites, and related cofactors (vitamins B2 and B6) were quantified using targeted mass spectrometry, whereas ELISA was used to quantify the mucosal injury markers, regenerating islet-derived protein 3A (Reg3a), and intestinal fatty acid-binding protein 2 (iFABP). We observed increased concentrations of plasma C-reactive protein (CRP), serum amyloid A (SAA), neopterin, kynurenine/tryptophan ratio (KTR), and Reg3a in the SP group following dose ingestion. Vitamin B6 forms, pyridoxal 5'-phosphate and pyridoxal, decreased over time in the SP group. CRP, SAA, and pyridoxic acid ratio correlated with ETEC proliferation levels. The changes following experimental ETEC infection indicate that ETEC, despite causing a non-invasive infection, induces systemic inflammation and mucosal injury when proliferating substantially, even in cases without diarrhea. It is conceivable that ETEC infections, especially when repeated, contribute to negative health impacts on children in ETEC endemic areas.

Construction of an aerolysin-based multi-epitope vaccine against Aeromonas hydrophila: an in silico machine learning and artificial intelligence-supported approach.

Aeromonas hydrophila, a gram-negative coccobacillus bacterium, can cause various infections in humans, including septic arthritis, diarrhea (traveler's diarrhea), gastroenteritis, skin and wound infections, meningitis, fulminating septicemia, enterocolitis, peritonitis, and endocarditis. It frequently occurs in aquatic environments and readily contacts humans, leading to high infection rates. This bacterium has exhibited resistance to numerous commercial antibiotics, and no vaccine has yet been developed. Aiming to combat the alarmingly high infection rate, this study utilizes in silico techniques to design a multi-epitope vaccine (MEV) candidate against this bacterium based on its aerolysin toxin, which is the most toxic and highly conserved virulence factor among the Aeromonas species. After retrieval, aerolysin was processed for B-cell and T-cell epitope mapping. Once filtered for toxicity, antigenicity, allergenicity, and solubility, the chosen epitopes were combined with an adjuvant and specific linkers to create a vaccine construct. These linkers and the adjuvant enhance the MEV's ability to elicit robust immune responses. Analyses of the predicted and improved vaccine structure revealed that 75.5%, 19.8%, and 1.3% of its amino acids occupy the most favored, additional allowed, and generously allowed regions, respectively, while its ERRAT score reached nearly 70%. Docking simulations showed the MEV exhibiting the highest interaction and binding energies (-1,023.4 kcal/mol, -923.2 kcal/mol, and -988.3 kcal/mol) with TLR-4, MHC-I, and MHC-II receptors. Further molecular dynamics simulations demonstrated the docked complexes' remarkable stability and maximum interactions, i.e., uniform RMSD, fluctuated RMSF, and lowest binding net energy. In silico models also predict the vaccine will stimulate a variety of immunological pathways following administration. These analyses suggest the vaccine's efficacy in inducing robust immune responses against A. hydrophila. With high solubility and no predicted allergic responses or toxicity, it appears safe for administration in both healthy and A. hydrophila-infected individuals.

Characteristics of Traveler’s Diarrhea in Foreign Traveler’s Visiting Beaches in Badung Regency, Bali

Traveler’s Diarrhea (TD) is a common infectious disease impacting travelers from developed countries who visit developing countries, such as Indonesia. Reporting of Traveler’s Diarrhea (TD) cases in Indonesia is still low, especially in Bali. This study aimed to describe the characteristics of Traveler’s Diarrhea (TD) in foreign travelers visiting beaches in Badung Regency, Bali. This study used cross sectional descriptive method in collecting data. The population was all foreign travelers visiting eight beaches in Badung Regency, Bali. In this study 61 respondents were selected using a purposive sampling technique. Data collection involved a questionnaire and analyzed using univariate statistics. The majority of respondents were European females (70,5%), aged 26-35 (41%), from Germany (11,5%), visiting Bali for tourism (80,3%), their first time in Southeast Asia (47,5%) and Bali (45,9%). Predominant diarrhea characteristics included 3-4 bowel movements per day (75,4%), loose stool consintency (59%) accompanied by abdominal cramps (41%), lasting 1-7 days (96,7%), a single episode (73,8%). Most managed Traveler’s Diarrhea (TD) with medication (63,2%) and continued their travels (80,3%), consumed vegetable salad (50,8%), consumed overnight food (91,8%), consumed raw meat (80,3%) and drank tap water (95,1%). This study suggest that Traveler’s Diarrhea (TD) is prevalent among foreign travelers visiting beaches in Badung Regency, Bali with key factors being the absence of pre-travel consultations, consumption of drinks with ice and vegetables salad. Keywords: Traveler’s Diarrhea, TD, Foreign Traveler, Characteristic

Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.

The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.

Incidence and risk factors for travellers' diarrhoea among short-term international adult travellers from high-income countries: a systematic review with meta-analysis of cohort studies.

Travellers' Diarrhoea (TD) continues to be the most common travel-related medical event in international travellers. Updated incidence and risk factor data will improve pre-travel medical advice for travellers from high-income countries (HIC), providing an opportunity for disease prevention, and appropriate disease management. A systematic search for cohort studies of TD incidence published between 1 January 1997 and 2 March 2023 was performed using Ovid Medline, SCOPUS, and Google Scholar databases. Study quality was assessed with a modified Newcastle-Ottawa scale (NOS). We extracted incidence data for adults travelling less than 100days from HIC and available risk factor data. The overall random-effects pooled incidence and the corresponding 95% confidence intervals (95% CI) were estimated. Heterogeneity was assessed using the I2 statistic, tau and the 95% prediction intervals. Subgroup analyses were conducted to identify sources of heterogeneity. Risk factor studies were reviewed qualitatively and described. Ten studies were included in the meta-analysis, containing 8478 participants. Two of the studies measured as high quality and eight as good quality as assessed by the modified NOS. The TD incidence was 36.1% (95% CI 24-41%; I2 94%), with a prediction interval ranging from 20.3% to 55.8%. The pooled incidence of mild, moderate, and severe TD was 23.6%, 8.1% and 2.9%, respectively. Subgroup analysis showed that the incidence increased with increasing average data collection period. Risk factors for TD in travellers from HIC identified include younger age, longer travel periods, low and middle-income destinations, travelling for tourism, backpacking travel styles and pre-travel health status. It is estimated that between 20 to 56% of international travellers can expect to develop TD in travel of under 100days. While most cases are mild, approximately 3% of all travellers will experience a disease that prevents usual activities or requires medical attention.

Epidemiological trends of traveler's diarrhea in Japan: An analysis of imported infectious disease registry data from 2017-2022.

Traveler's diarrhea (TD) is a global problem, and identifying the causative organisms of TD is important for adequate treatment. Therefore, this study retrospectively analyzed TD cases in patients who returned to Japan after traveling abroad to determine the causative organisms by travel region. We included patients with a final diagnosis of TD registered in the Japan Registry for Infectious Diseases from Abroad database from September 25, 2017, to September 1, 2022, from 14 medical institutions. A total of 919 patients were analyzed; the causative TD pathogen was identified in 188 cases (20%), of which 154 were caused by diarrheagenic bacteria, the most common being Campylobacter spp. (64%). A 2.2 mg/dL C-reactive protein concentration cutoff value had some predictive ability for bacterial TD (negative predictive value, 89%). Therefore, the C-reactive protein level may help rule out bacterial diarrhea and prevent unnecessary antimicrobial administration when patients cannot provide a stool specimen.

Differences in the gut microbiota between Gurkhas and soldiers of British origin.

Previous work indicated that the incidence of travellers' diarrhoea (TD) is higher in soldiers of British origin, when compared to soldiers of Nepalese descent (Gurkhas). We hypothesise that the composition of the gut microbiota may be a contributing factor in the risk of developing TD in soldiers of British origin. This study aimed to characterise the gut microbial composition of Gurkha and non-Gurkha soldiers of the British Army. Recruitment of 38 soldiers (n = 22 Gurkhas, n = 16 non-Gurkhas) and subsequent stool collection, enabled shotgun metagenomic sequencing-based analysis of the gut microbiota. The microbiota of Gurkhas had significantly (P < 0.05) lower diversity, for both Shannon and Simpson diversity indices, using species level markers than the gut microbiota of non-Gurkha soldiers. Non-metric Multidimensional Scaling (NMDS) of the Bray-Curtis distance matrix revealed a significant difference in the composition of the gut microbiota between Gurkhas and non-Gurkha soldiers, at both the species level (P = 0.0178) and the genus level (P = 0.0483). We found three genera and eight species that were significantly enriched in the non-Gurkha group and one genus (Haemophilus) and one species (Haemophilus parainfluenzae) which were enriched in the Gurkha group. The difference in the microbiota composition between Gurkha soldiers and soldiers of British origin may contribute to higher colonization resistance against diarrhoeal pathogens in the former group. Our findings may enable further studies into interventions that modulate the gut microbiota of soldiers to prevent TD during deployment.

The potential for development of clinically relevant microbial resistance to rifaximin-α: a narrative review.

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. Its important biologic effects are largely at sub-inhibitory concentration. Although in vitro testing of clinical isolates from rifaximin recipients has revealed rifaximin-resistant strains in some studies, the risk of emergent rifaximin-α resistance appears to be lower than for many other antibiotics. Rifaximin-α has been used for many years for traveler's diarrhea with no apparent increase in resistance levels in causative pathogens. Further, rifaximin-α retains its efficacy after long-term and recurrent usage in chronic gastrointestinal disorders. There are numerous reasons why the risk of microbial resistance to rifaximin-α may be lower than that for other agents, including low intestinal bioavailability in the aqueous colon, the mechanisms of action of rifaximin-α not requiring inhibitory concentrations of drug, and the low risk of cross transmission of rifaximin-α resistance between bacterial species. Reported emergence of vancomycin-resistant Enterococcus in liver-disease patients maintained on rifaximin needs to be actively studied. Further studies are required to assess the possible correlation between in vitro resistance and rifaximin-α efficacy.

A First in Human Clinical Trial Assessing the Safety and Immunogenicity of Two Intradermally Delivered Enterotoxigenic Escherichia coli CFA/I Fimbrial Tip Adhesin Antigens with and without Heat-Labile Enterotoxin with Mutation LT(R192G).

Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model.

Traveler's diarrhea.

Traveler's diarrhea (TD) is one of the most common illnesses afflicting the modern traveler. TD refers to a watery diarrhea that varies in severity from tolerable to incapacitating and that develops in individuals during or within 10 days of returning from travel to developing or low-/middle-income countries. Most cases of TD are self-limiting, but in consideration of the ease of international travel, it is important for providers to diagnose and manage TD with the best available evidence.