Gastrointestinal parasite infections in Nepalese Gurkha recruits arriving in the United Kingdom from 2012-2020.

BACKGROUND: Gastrointestinal parasite (GIP) infections are a major cause of global morbidity, infecting hundreds of millions of people each year and potentially leading to lifelong infection and serious complications. Few data exist on screening for GIP infections in migrants entering the UK or on the current performance of different traditional diagnostic approaches. This study aimed to describe the prevalence of GIP infections in Nepalese Gurkha recruits screened on arrival in the UK. METHODOLOGY/PRINCIPAL FINDINGS: We present a retrospective analysis of data from screening male adults (18-21 years) who arrived in the UK from Nepal between 2012 and 2020. Three separate faecal samples were obtained from participants at weekly intervals and processed for formalin-ethyl acetate (FEA) concentration/light microscopy and charcoal culture. Serum samples were analysed for IgG antibodies to Strongyloides stercoralis by ELISA. Results were available from 2,263 participants, of whom 463 (20.5%, 95% CI 18.8%-22.2%) had a positive diagnostic test for at least one GIP infection. A total of 525 potential infections were identified. Giardia duodenalis was most common (231/2263, 10.2%), followed by S. stercoralis (102/2263, 4.5%), and hookworm species (86/2263, 3.8%). Analysis (microscopy and culture) of the initial stool sample diagnosed only 244/427 (57.1%) faecally identified pathogens, including 41/86 (47.7%) hookworm infections. The proportion of participants infected with any GIP showed a downward trend over the study period. Log-binomial regression showed risk of infection decreasing by 6.1% year-on-year (95% CI 3.2% - 9.0%). This was driven predominantly by a fall in hookworm, S. stercoralis and Trichuris trichiura prevalence. CONCLUSIONS/SIGNIFICANCE: The level of potentially pathogenic GIP infection in young Nepalese men migrating to the UK is high (20.5%) and requires a combined diagnostic approach including serology and analysis of multiple stool samples incorporating specialised parasitological methods. Advances in molecular approaches may optimise and simplify the intensive screening strategy required.

Outbreak of Diarrhea Caused by a Novel Cryptosporidium hominis Subtype During British Military Training in Kenya.

Background: We report clinical, epidemiological, and laboratory features of a large diarrhea outbreak caused by a novel Cryptosporidium hominis subtype during British military training in Kenya between February and April 2022. Methods: Data were collated from diarrhea cases, and fecal samples were analyzed on site using the multiplex polymerase chain reaction (PCR) BioFire FilmArray. Water was tested using Colilert kits (IDEXX, UK). DNA was extracted from feces for molecular characterization of Cryptosporidium A135, Lib13, ssu rRNA, and gp60 genes. Results: One hundred seventy-two of 1200 (14.3%) personnel at risk developed diarrhea over 69 days. One hundred six primary fecal samples were tested, and 63/106 (59.4%; 95% CI, 0.49%-0.69%) were positive for Cryptosporidium spp. Thirty-eight had Cryptosporidium spp. alone, and 25 had Cryptosporidium spp. with ≥1 other pathogen. A further 27/106 (25.5%; 95% CI, 0.18%-0.35%) had non-Cryptosporidium pathogens only, and 16/106 (15.1%; 95% CI, 0.09%-0.23%) were negative. C. hominis was detected in 58/63 (92.1%) Cryptosporidium spp.-positive primary samples, but the others were not genotypable. Twenty-seven C. hominis specimens were subtypable; 1 was gp60 subtype IeA11G3T3, and 26 were an unusual subtype, ImA13G1 (GenBank accession OP699729), supporting epidemiological evidence suggesting a point source outbreak from contaminated swimming water. Diarrhea persisted for a mean (SD) of 7.6 (4.6) days in Cryptosporidium spp. cases compared with 2.3 (0.9) days in non-Cryptosporidium cases (P = .001). Conclusions: Real-time multiplex PCR fecal testing was vital in managing this large cryptosporidiosis outbreak. The etiology of a rare C. hominis gp60 subtype emphasizes the need for more genotypic surveillance to identify widening host and geographic ranges of novel C. hominis subtypes.

Clinical predictors of encephalitis in UK adults-A multi-centre prospective observational cohort study.

OBJECTIVES: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body's immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment. METHODS: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals. We evaluated clinical features and investigated for infectious and autoimmune causes. RESULTS: 341 patients were enrolled between December 2012 and December 2015 and followed up for 12 months. 233 had encephalitis, of whom 65 (28%) had HSV, 38 (16%) had confirmed or probable autoimmune encephalitis, and 87 (37%) had no cause found. The median time from admission to 1st dose of aciclovir for those with HSV was 14 hours (IQR 5-50); time to 1st dose of immunosuppressant for the autoimmune group was 125 hours (IQR 45-250). Compared to non-HSV encephalitis, patients with HSV more often had fever, lower serum sodium and lacked a rash. Those with probable or confirmed autoimmune encephalitis were more likely to be female, have abnormal movements, normal serum sodium levels and a cerebrospinal fluid white cell count < 20 cells x106/L, but they were less likely to have a febrile illness. CONCLUSIONS: Initiation of treatment for autoimmune encephalitis is delayed considerably compared with HSV encephalitis. Clinical features can help identify patients with autoimmune disease and could be used to initiate earlier presumptive therapy.

Viral capture sequencing detects unexpected viruses in the cerebrospinal fluid of adults with meningitis.

OBJECTIVES: Many patients with meningitis have no aetiology identified leading to unnecessary antimicrobials and prolonged hospitalisation. We used viral capture sequencing to identify possible pathogenic viruses in adults with community-acquired meningitis. METHODS: Cerebrospinal fluid (CSF) from 73 patients was tested by VirCapSeq-VERT, a probe set designed to capture viral targets using high throughput sequencing. Patients were categorised as suspected viral meningitis - CSF pleocytosis, no pathogen identified (n = 38), proven viral meningitis - CSF pleocytosis with a pathogen identified (n = 15) or not meningitis - no CSF pleocytosis (n = 20). RESULTS: VirCapSeq-VERT detected virus in the CSF of 16/38 (42%) of those with suspected viral meningitis, including twelve individual viruses. A potentially clinically relevant virus was detected in 9/16 (56%). Unexpectedly Toscana virus, rotavirus and Saffold virus were detected and assessed to be potential causative agents. CONCLUSION: VirCapSeq-VERT increases the probability of detecting a virus. Using this agnostic approach we identified Toscana virus and, for the first time in adults, rotavirus and Saffold virus, as potential causative agents in adult meningitis. Further work is needed to determine the prevalence of atypical viral candidates as well as the clinical impact of using sequencing methods in real time. This knowledge can help to reduce antimicrobial use and hospitalisations leading to both patient and health system benefits.

An evaluation of 1 year of advice calls to a tropical and infectious disease referral Centre.

OBJECTIVES: Many secondary care departments receive external advice calls. However, systematic advice-call documentation is uncommon and evidence on call nature and burden infrequent. The Liverpool tropical and infectious disease unit (TIDU) provides specialist advice locally, regionally and nationally. We created and evaluated a recording system to document advice calls received by TIDU. METHODS: An electronic advice-call recording system was created for TIDU specialist trainees to document complex, predominantly external calls. Fourteen months of advice calls were summarised, analysed and recommendations for other departments wishing to replicate this system made. RESULTS: Five-hundred and ninety calls regarding 362 patients were documented. Median patient age was 44 years (interquartile range 29-56 years) and 56% were male. Sixty-nine per cent of patients discussed were referred from secondary healthcare, half from emergency or acute medicine departments; 43% of patients were returning travellers; 59% of returning travellers had undifferentiated fever, one-third of whom returned from sub-Saharan Africa; 32% of patients discussed were further reviewed at TIDU. Interim 6-month review showed good user acceptability of the system. CONCLUSIONS: Implementing an advice-call recording system was feasible within TIDU. Call and follow-up burden was high with advice regarding fever in returned travellers predominating. Similar systems could improve clinical governance, patient care and service delivery in other secondary care departments.

Genital secretion HIV RNA shedding in HIV-positive patients on ritonavir-boosted protease inhibitor monotherapy or standard combination ART: a cross-sectional sub-study from the PIVOT Trial.

BACKGROUND: Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PI-mono). METHODS: We measured HIV RNA and PI drug concentrations in samples of semen, cervico-vaginal and rectal mucosa secretions, and plasma in patients after 48-96 weeks on PI-mono or standard triple therapy. RESULTS: A total of 85 participants were recruited. Of the 43 participants on PI-mono (70% on darunavir [DRV]/ritonavir [r]), 3 had detectable virus in semen or vaginal secretions (all below quantification limit), and none in rectal mucosa or plasma. Among those taking triple therapy, five had detectable virus in semen or vaginal secretions (HIV RNA >50 copies/ml in one), none in rectal mucosa and one in plasma. The median (IQR) concentration of DRV and atazanavir in semen (659.7 [339-1,089] and 128.8 [63-368] ng/ml, respectively) and cervico-vaginal samples (2,768 [312-7,879] and 1,836 [359-3,314] ng/ml, respectively) exceeded their protein adjusted median inhibition concentration (MIC50). DRV concentration in rectal secretions showed higher variability compared with concentration in the other sites, with particularly high rectal secretion/blood ratios (median 8.4, IQR 2.6-68.7:1). CONCLUSIONS: We found no substantive evidence of HIV shedding in patients taking PI-mono, suggesting that PIs provide adequate control of virus in the genital compartment and are unlikely to lead to ongoing sexual transmission.

Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: epidemiological results.

OBJECTIVES: To estimate the incidence of gastroenteritis in individuals in care homes. DESIGN: Prospective cohort study. SETTING: Five participating care homes in North West England, UK. PARTICIPANTS: Residents and staff present at the five study care homes between 15 August 2017 and 30 May 2019 (n=268). OUTCOME MEASURES: We calculated incidence rates for all gastroenteritis cases per 1000 person-years at risk and per 1000 bed-days at risk. We also calculated the incidence rate of gastroenteritis outbreaks per 100 care homes per year. RESULTS: In total 45 cases were reported during the surveillance period, equating to 133.7 cases per 1000 person-years at risk. In residents the incidence rate was 0.62 cases per 1000 bed-days. We observed seven outbreaks in all care homes included in surveillance, a rate of 76.4 outbreaks per 100 care homes per year. 15 stool samples were tested; three were positive for norovirus, no other pathogens were detected. CONCLUSIONS: We found that surveillance of infectious gastroenteritis disease in care homes based on outbreaks, the current general approach, detected a majority of cases of gastroenteritis. However, if policymakers are to estimate the burden of infectious gastroenteritis in this setting using only routine outbreak surveillance data and not accounting for non-outbreak cases, this study implies that the total burden will be underestimated.

Detection of Crimean-Congo Haemorrhagic Fever cases in a severe undifferentiated febrile illness outbreak in the Federal Republic of Sudan: A retrospective epidemiological and diagnostic cohort study.

BACKGROUND: Undifferentiated febrile illness (UFI) is one of the most common reasons for people seeking healthcare in low-income countries. While illness and death due to specific infections such as malaria are often well-quantified, others are frequently uncounted and their impact underappreciated. A number of high consequence infectious diseases, including Ebola virus, are endemic or epidemic in the Federal Republic of Sudan which has experienced at least 12 UFI outbreaks, frequently associated with haemorrhage and high case fatality rates (CFR), since 2012. One of these occurred in Darfur in 2015/2016 with 594 cases and 108 deaths (CFR 18.2%). The aetiology of these outbreaks remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We report a retrospective cohort study of the 2015/2016 Darfur outbreak, using a subset of 65 of 263 outbreak samples received by the National Public Health Laboratory which met selection criteria of sufficient sample volume and epidemiological data. Clinical features included fever (95.8%), bleeding (95.7%), headache (51.6%) and arthralgia (42.2%). No epidemiological patterns indicative of person-to-person transmission or health-worker cases were reported. Samples were tested at the Public Health England Rare and Imported Pathogens Laboratory using a bespoke panel of likely pathogens including haemorrhagic fever viruses, arboviruses and Rickettsia, Leptospira and Borrelia spp. Seven (11%) were positive for Crimean-Congo haemorrhagic fever virus (CCHFV) by real-time reverse transcription PCR. The remaining samples tested negative on all assays. CONCLUSIONS/SIGNIFICANCE: CCHFV is an important cause of fever and haemorrhage in Darfur, but not the sole major source of UFI outbreaks in Sudan. Prospective studies are needed to explore other aetiologies, including novel pathogens. The presence of CCHFV has critical infection, prevention and control as well as clinical implications for future response. Our study reinforces the need to boost surveillance, lab and investigative capacity to underpin effective response, and for local and international health security.

Brucellosis in pregnancy: results of multicenter ID-IRI study.

Brucellosis in pregnant women is reported to be associated with obstetric complications (OCs), and adequate data for human brucellosis during pregnancy are largely lacking. We performed this multicenter retrospective cross-sectional study to evaluate the epidemiology, clinical course, treatment responses, and outcomes of brucellosis among pregnant women. The study period comprised a 14-year period from January 2002 to December 2015. All consecutive pregnant women diagnosed with brucellosis in 23 participating hospitals were included. Epidemiological, clinical, laboratory, therapeutic, and outcome data along with the assessment data of the neonate were collected using a standardized questionnaire. Data of 242 patients were analyzed. The OC rate was 14.0% (34/242) in the cohort. Of the 242 women, 219 (90.5%) delivered at term, 3 (1.2%) had preterm delivery, 15 (6.2%) aborted, and 5 (2.1%) had intrauterine fetal demise. Seventeen (7.0%) of the newborns were considered as low birth weight. Spontaneous abortion (6.1%) was the commonest complication. There were no maternal or neonatal deaths and pertinent sequelae or complications were not detected in the newborns. Splenomegaly (p = 0.019), nausea and/or vomiting (p < 0.001), vaginal bleeding (p < 0.001), anemia (blood hemoglobin < 11 g/dL; p < 0.001), high level of serum aspartate aminotransferase (> 41 IU/L; p = 0.025), oligohydramnios on ultrasonography (p = 0.0002), history of taking medication other than Brucella treatment during pregnancy (p = 0.027), and Brucella bacteremia (p = 0.029) were the significant factors associated with OCs. We recommend that pregnant women with OC or with fever should be investigated for brucellosis if they live in or have traveled to an endemic area.

Clinical and molecular epidemiology of Crimean-Congo hemorrhagic fever in Oman.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a serious disease with a high fatality rate reported in many countries. The first case of CCHF in Oman was detected in 1995 and serosurveys have suggested widespread infection of humans and livestock throughout the country. METHODOLOGY: Cases of CCHF reported to the Ministry of Health (MoH) of Oman between 1995 and 2017 were retrospectively reviewed. Diagnosis was confirmed by serology and/or molecular tests in Oman. Stored RNA from recent cases was studied by sequencing the complete open reading frame (ORF) of the viral S segment at Public Health England, enabling phylogenetic comparisons to be made with other S segments of strains obtained from the region. FINDINGS: Of 88 cases of CCHF, 4 were sporadic in 1995 and 1996, then none were detected until 2011. From 2011-2017, incidence has steadily increased and 19 (23.8%) of 80 cases clustered around Eid Al Adha. The median (range) age was 33 (15-68) years and 79 (90%) were male. The major risk for infection was contact with animals and/or butchering in 73/88 (83%) and only one case was related to tick bites alone. Severe cases were over-represented: 64 (72.7%) had a platelet count < 50 x 109/L and 32 (36.4%) died. There was no intrafamilial spread or healthcare-associated infection. The viral S segments from 11 patients presenting in 2013 and 2014 were all grouped in Asia 1 (IV) lineage. CONCLUSIONS: CCHF is well-established throughout Oman, with a single strain of virus present for at least 20 years. Most patients are men involved in animal husbandry and butchery. The high mortality suggests that there is substantial under-diagnosis of milder cases. Preventive measures have been introduced to reduce risks of transmission to animal handlers and butchers and to maintain safety in healthcare settings.

Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study.

BACKGROUND: Viral meningitis is increasingly recognised, but little is known about the frequency with which it occurs, or the causes and outcomes in the UK. We aimed to determine the incidence, causes, and sequelae in UK adults to improve the management of patients and assist in health service planning. METHODS: We did a multicentre prospective observational cohort study of adults with suspected meningitis at 42 hospitals across England. Nested within this study, in the National Health Service (NHS) northwest region (now part of NHS England North), was an epidemiological study. Patients were eligible if they were aged 16 years or older, had clinically suspected meningitis, and either underwent a lumbar puncture or, if lumbar puncture was contraindicated, had clinically suspected meningitis and an appropriate pathogen identified either in blood culture or on blood PCR. Individuals with ventricular devices were excluded. We calculated the incidence of viral meningitis using data from patients from the northwest region only and used these data to estimate the population-standardised number of cases in the UK. Patients self-reported quality-of-life and neuropsychological outcomes, using the EuroQol EQ-5D-3L, the 36-Item Short Form Health Survey (SF-36), and the Aldenkamp and Baker neuropsychological assessment schedule, for 1 year after admission. FINDINGS: 1126 patients were enrolled between Sept 30, 2011, and Sept 30, 2014. 638 (57%) patients had meningitis: 231 (36%) cases were viral, 99 (16%) were bacterial, and 267 (42%) had an unknown cause. 41 (6%) cases had other causes. The estimated annual incidence of viral meningitis was 2·73 per 100 000 and that of bacterial meningitis was 1·24 per 100 000. The median length of hospital stay for patients with viral meningitis was 4 days (IQR 3-7), increasing to 9 days (6-12) in those treated with antivirals. Earlier lumbar puncture resulted in more patients having a specific cause identified than did those who had a delayed lumbar puncture. Compared with the age-matched UK population, patients with viral meningitis had a mean loss of 0·2 quality-adjusted life-years (SD 0·04) in that first year. INTERPRETATION: Viruses are the most commonly identified cause of meningitis in UK adults, and lead to substantial long-term morbidity. Delays in getting a lumbar puncture and unnecessary treatment with antivirals were associated with longer hospital stays. Rapid diagnostics and rationalising treatments might reduce the burden of meningitis on health services. FUNDING: Meningitis Research Foundation and UK National Institute for Health Research.

Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America.

The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.

Human Hookworm Infection Enhances Mycobacterial Growth Inhibition and Associates With Reduced Risk of Tuberculosis Infection.

Soil-transmitted helminths and Mycobacterium tuberculosis frequently coincide geographically and it is hypothesized that gastrointestinal helminth infection may exacerbate tuberculosis (TB) disease by suppression of Th1 and Th17 responses. However, few studies have focused on latent TB infection (LTBI), which predominates globally. We performed a large observational study of healthy adults migrating from Nepal to the UK (n = 645). Individuals were screened for LTBI and gastrointestinal parasite infections. A significant negative association between hookworm and LTBI-positivity was seen (OR = 0.221; p = 0.039). Hookworm infection treatment did not affect LTBI conversions. Blood from individuals with hookworm had a significantly greater ability to control virulent mycobacterial growth in vitro than from those without, which was lost following hookworm treatment. There was a significant negative relationship between mycobacterial growth and eosinophil counts. Eosinophil-associated differential gene expression characterized the whole blood transcriptome of hookworm infection and correlated with improved mycobacterial control. These data provide a potential alternative explanation for the reduced prevalence of LTBI among individuals with hookworm infection, and possibly an anti-mycobacterial role for helminth-induced eosinophils.

Identifying volatile metabolite signatures for the diagnosis of bacterial respiratory tract infection using electronic nose technology: A pilot study.

OBJECTIVES: New point of care diagnostics are urgently needed to reduce the over-prescription of antimicrobials for bacterial respiratory tract infection (RTI). We performed a pilot cross sectional study to assess the feasibility of gas-capillary column ion mobility spectrometer (GC-IMS), for the analysis of volatile organic compounds (VOC) in exhaled breath to diagnose bacterial RTI in hospital inpatients. METHODS: 71 patients were prospectively recruited from the Acute Medical Unit of the Royal Liverpool University Hospital between March and May 2016 and classified as confirmed or probable bacterial or viral RTI on the basis of microbiologic, biochemical and radiologic testing. Breath samples were collected at the patient's bedside directly into the electronic nose device, which recorded a VOC spectrum for each sample. Sparse principal component analysis and sparse logistic regression were used to develop a diagnostic model to classify VOC spectra as being caused by bacterial or non-bacterial RTI. RESULTS: Summary area under the receiver operator characteristic curve was 0.73 (95% CI 0.61-0.86), summary sensitivity and specificity were 62% (95% CI 41-80%) and 80% (95% CI 64-91%) respectively (p = 0.00147). CONCLUSIONS: GC-IMS analysis of exhaled VOC for the diagnosis of bacterial RTI shows promise in this pilot study and further trials are warranted to assess this technique.

Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: a study protocol.

INTRODUCTION: Noroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes. METHODS AND ANALYSIS: We will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes. ETHICS AND DISSEMINATION: The study has been approved by the North West-Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination.

Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report.

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