Search

Background Children frequently travel internationally. Health-related data on such children are limited. We sought to investigate the demographics, health characteristics, and preventive interventions of outbound US international pediatric travelers. Methods We analyzed data from 32 099 travelers presenting for pre-travel healthcare at the Global TravEpiNet (GTEN), a national consortium of 19 travel clinics, from January 1, 2009 to June 6, 2012. Results A total of 3332 (10%) of all GTEN travelers were children (<18 years of age). These children traveled mostly for leisure (36%) or to visit friends or relatives (VFR) (36%). Most popular destination regions were Africa (41%), Southeast Asia (16%), Central America (16%), and the Caribbean (16%). Compared with children traveling for leisure, VFR children were more likely to present <14 days before departure for pre-travel consultation (44% vs 28%), intended to travel for 28 days or longer (70% vs 22%), and to travel to Africa (62% vs 32%). Nearly half of the pediatric travelers (46%) received at least 1 routine vaccine, and most (83%) received at least 1 travel-related vaccine. Parents or guardians of one third of the children (30%) refused at least 1 recommended travel-related vaccine. Most pediatric travelers visiting a malaria-endemic country (72%) received a prescription for malaria chemoprophylaxis. Conclusions Ten percent of travelers seeking pre-travel healthcare at GTEN sites are children. VFR-travel, pre-travel consultation close to time of departure, and refusal of recommended vaccines may place children at risk for travel-associated illness. Strategies to engage pediatric travelers in timely, pre-travel care and improve acceptance of pre-travel healthcare interventions are needed. [ABSTRACT FROM PUBLISHER]

The article discusses that the the World Health Organization (WHO) Global Task Force on Cholera Control announced an initiative titled Ending Cholera; and the objective was a 90% reduction in cholera deaths and the elimination of cholera in 20 countries, including Bangladesh, by 2030. It mentions that the introduction of cholera in Haiti in 2010 spurred new partnerships, investments, and calls to action, prompting the establishment of a global stockpile.

Background. International travel poses a risk of destination-specific illness and may contribute to the global spread of infectious diseases. Despite this, little is known about the health characteristics and pretravel healthcare of US international travelers, particularly those at higher risk of travel-associated illness. Methods. We formed a national consortium (Global TravEpiNet) of 18 US clinics registered to administer yellow fever vaccination. We collected data regarding demographic and health characteristics, destinations, purpose of travel, and pretravel healthcare from 13 235 international travelers who sought pretravel consultation at these sites from January 2009 through January 2011. Results. The destinations and itineraries of Global TravEpiNet travelers differed from those of the overall population of US international travelers. The majority of Global TravEpiNet travelers were visiting low- or lower-middle-income countries, and Africa was the most frequently visited region. Seventy-five percent of travelerswere visitingmalaria-endemic countries, and 38% were visiting countries endemic for yellow fever. Fifty-nine percent of travelers reported ≤1 medical condition. Atovaquone/proguanil was the most commonly prescribed antimalarial drug, and most travelers received an antibiotic for self-treatment of travelers' diarrhea. HepatitisA and typhoid were themost frequently administered vaccines. Conclusions. Data from Global TravEpiNet provide insight into the characteristics and pretravel healthcare of US international travelers who are at increased risk of travel-associated illness due to itinerary, purpose of travel, or existing medical conditions. Improved understanding of this epidemiologically significant population may help target risk-reduction strategies and interventions to limit the spread of infections related to global travel [ABSTRACT FROM AUTHOR]

Globally mobile populations are at higher risk of acquiring geographically restricted infections and may play a role in the international spread of infectious diseases. Despite this, data about sources of health information used by international travelers are limited. We surveyed 1,254 travelers embarking from Boston Logan International Airport regarding sources of health information. We focused our analysis on travelers to low or low-middle income (LLMI) countries, as defined by the World Bank 2009 World Development Report. A total of 476 survey respondents were traveling to LLMI countries. Compared with travelers to upper-middle or high income (UMHI) countries, travelers to LLMI countries were younger, more likely to be foreign-born, and more frequently reported visiting family as the purpose of their trip. Prior to their trips, 46% of these travelers did not pursue health information of any type. In a multivariate analysis, being foreign-born, traveling alone, traveling for less than 14 days, and traveling for vacation each predicted a higher odds of not pursuing health information among travelers to LLMI countries. The most commonly cited reason for not pursuing health information was a lack of concern about health problems related to the trip. Among travelers to LLMI countries who did pursue health information, the internet was the most common source, followed by primary care practitioners. Less than a third of travelers to LLMI countries who sought health information visited a travel medicine specialist. In our study, 46% of travelers to LLMI countries did not seek health advice prior to their trip, largely due to a lack of concern about health issues related to travel. Among travelers who sought medical advice, the internet and primary care providers were the most common sources of information. These results suggest the need for health outreach and education programs targeted at travelers and primary care practitioners. [ABSTRACT FROM AUTHOR]

The serum vibriocidal antibody is the only recognized predictor of protection from cholera, but no seroepidemiological data have been gathered since the emergence of Vibrio cholerae O139. We assessed the association between the vibriocidal antibody titer and protection from cholera in an endemic setting. Although a higher baseline vibriocidal titer correlated with protection from V. cholerae O1, infection still developed in some contacts with very high titers. No association between baseline vibriocidal titer and protection from V. cholerae O139 infection was found. Our findings suggest that the vibriocidal antibody is an incomplete predictor of protection from V. cholerae infection. [ABSTRACT FROM AUTHOR]

Focuses on sputum induction (SI) vis-a-vis Pneumocystis pneumonia in immunocompromised patients without HIV in the U.S. Application of SI among immunocompromised patients; Importance of the application of SI for diagnosis of Pneumocystis pneumonia; Comparison of the clinical study on the outcome of SI between immunocompromised patients with HIV and those without HIV.

Background The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. Methods We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. Results Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2–12.8]; P <.001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2–12.4]; P <.001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. Conclusions These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Background Extended spectrum beta-lactamase producing Enterobacterales (ESBL-PE) present a risk to public health by limiting the efficacy of multiple classes of beta-lactam antibiotics against infection. International travellers may acquire these organisms and identifying individuals at high risk of acquisition could help inform clinical treatment or prevention strategies. Methods We used data collected from a cohort of 528 international travellers enrolled in a multicentre US-based study to derive a clinical prediction rule (CPR) to identify travellers who developed ESBL-PE colonization, defined as those with new ESBL positivity in stool upon return to the United States. To select candidate features, we used data collected from pre-travel and post-travel questionnaires, alongside destination-specific data from external sources. We utilized LASSO regression for feature selection, followed by random forest or logistic regression modelling, to derive a CPR for ESBL acquisition. Results A CPR using machine learning and logistic regression on 10 features has an internally cross-validated area under the receiver operating characteristic curve (cvAUC) of 0.70 (95% confidence interval 0.69–0.71). We also demonstrate that a four-feature model performs similarly to the 10-feature model, with a cvAUC of 0.68 (95% confidence interval 0.67–0.69). This model uses traveller's diarrhoea, and antibiotics as treatment, destination country waste management rankings and destination regional probabilities as predictors. Conclusions We demonstrate that by integrating traveller characteristics with destination-specific data, we could derive a CPR to identify those at highest risk of acquiring ESBL-PE during international travel. [ABSTRACT FROM AUTHOR]

This article discusses the knowledge, attitudes, and practices of US international travelers regarding the use of mobile travel health apps. The study collected data from 261 participants through an electronic survey, which assessed their smartphone usage habits, internet accessibility while traveling, concerns about personal health, and preferences for features in a travel health app. The majority of participants reported always carrying a smartphone during international travel and expressed interest in receiving health information through a travel health app. Preferred features for the app included real-time alerts about local outbreaks, information about nearby medical facilities, and COVID-19 travel-related restrictions. However, some participants had concerns about data security and privacy. The study provides insights into travelers' perspectives on mobile health apps and supports further development in this area. [Extracted from the article]

Rationale for review This review aims to summarize the transmission patterns of influenza, its seasonality in different parts of the globe, air travel- and cruise ship-related influenza infections and interventions to reduce transmission. Key findings The seasonality of influenza varies globally, with peak periods occurring mainly between October and April in the northern hemisphere (NH) and between April and October in the southern hemisphere (SH) in temperate climate zones. However, influenza seasonality is significantly more variable in the tropics. Influenza is one of the most common travel-related, vaccine-preventable diseases and can be contracted during travel, such as during a cruise or through air travel. Additionally, travellers can come into contact with people from regions with ongoing influenza transmission. Current influenza immunization schedules in the NH and SH leave individuals susceptible during their respective spring and summer months if they travel to the other hemisphere during that time. Conclusions/recommendations The differences in influenza seasonality between hemispheres have substantial implications for the effectiveness of influenza vaccination of travellers. Health care providers should be aware of influenza activity when patients report travel plans, and they should provide alerts and advise on prevention, diagnostic and treatment options. To mitigate the risk of travel-related influenza, interventions include antivirals for self-treatment (in combination with the use of rapid self-tests), extending the shelf life of influenza vaccines to enable immunization during the summer months for international travellers and allowing access to the influenza vaccine used in the opposite hemisphere as a travel-related vaccine. With the currently available vaccines, the most important preventive measure involves optimizing the seasonal influenza vaccination. It is also imperative that influenza is recognized as a travel-related illness among both travellers and health care professionals. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments. Methods All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians. Results Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections. Conclusions Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections. [ABSTRACT FROM AUTHOR]

The earth is rapidly warming, driven by increasing atmospheric carbon dioxide and other gases that result primarily from fossil fuel combustion. In addition to causing arctic ice melting and extreme weather events, climatologic factors are linked strongly to the transmission of many infectious diseases. Changes in the prevalence of infectious diseases not only reflect the impacts of temperature, humidity, and other weather-related phenomena on pathogens, vectors, and animal hosts but are also part of a complex of social and environmental factors that will be affected by climate change, including land use, migration, and vector control. Vector- and waterborne diseases and coccidioidomycosis are all likely to be affected by a warming planet; there is also potential for climate-driven impacts on emerging infectious diseases and antimicrobial resistance. Additional resources for surveillance and public health activities are urgently needed, as well as systematic education of clinicians on the health impacts of climate change. [ABSTRACT FROM AUTHOR]

Recent technological and computational advances have made metagenomic assembly a viable approach to achieving high-resolution views of complex microbial communities. In previous benchmarking, short-read (SR) metagenomic assemblers had the highest accuracy, long-read (LR) assemblers generated the most contiguous sequences and hybrid (HY) assemblers balanced length and accuracy. However, no assessments have specifically compared the performance of these assemblers on low-abundance species, which include clinically relevant organisms in the gut. We generated semi-synthetic LR and SR datasets by spiking small and increasing amounts of Escherichia coli isolate reads into fecal metagenomes and, using different assemblers, examined E. coli contigs and the presence of antibiotic resistance genes (ARGs). For ARG assembly, although SR assemblers recovered more ARGs with high accuracy, even at low coverages, LR assemblies allowed for the placement of ARGs within longer, E. coli -specific contigs, thus pinpointing their taxonomic origin. HY assemblies identified resistance genes with high accuracy and had lower contiguity than LR assemblies. Each assembler type's strengths were maintained even when our isolate was spiked in with a competing strain, which fragmented and reduced the accuracy of all assemblies. For strain characterization and determining gene context, LR assembly is optimal, while for base-accurate gene identification, SR assemblers outperform other options. HY assembly offers contiguity and base accuracy, but requires generating data on multiple platforms, and may suffer high misassembly rates when strain diversity exists. Our results highlight the trade-offs associated with each approach for recovering low-abundance taxa, and that the optimal approach is goal-dependent. [ABSTRACT FROM AUTHOR]

Background Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use. Methods Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim–sulfamethoxazole. Results Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade. Conclusions XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology. [ABSTRACT FROM AUTHOR]

Background To assess the implications of coronavirus disease 2019 (COVID-19)–related travel disruptions, we compared demographics and travel-related circumstances of US travelers seeking pretravel consultation regarding international travel at US Global TravEpiNet (GTEN) sites before and after the initiation of COVID-19 travel warnings. Methods We analyzed data in the GTEN database regarding traveler demographics and travel-related circumstances with standard questionnaires in the pre-COVID-19 period (January–December 2019) and the COVID-19 period (April 2020–March 2021), excluding travelers from January to March 2020. We conducted descriptive analyses of differences in demographics, travel-related circumstances, routine and travel-related vaccinations, and medications. Results Compared with 16 903 consultations in the pre-COVID-19 period, only 1564 consultations were recorded at GTEN sites during the COVID-19 period (90% reduction), with a greater proportion of travelers visiting friends and relatives (501/1564 [32%] vs 1525/16 903 [9%]), individuals traveling for >28 days (824/1564 [53%] vs 2522/16 903 [15%]), young children (6 mo–<6 y: 168/1564 [11%] vs 500/16 903 [3%]), and individuals traveling to Africa (1084/1564 [69%] vs 8049/16 903 [48%]). A smaller percentage of vaccine-eligible travelers received vaccines at pretravel consultations during the COVID-19 period than before, except for yellow fever and Japanese encephalitis vaccinations. Conclusions Compared with the pre-COVID-19 period, a greater proportion of travelers during the COVID - 19 period were young children, were planning to visit friends and relatives, were traveling for >28 days, or were traveling to Africa, which are circumstances that contribute to high risk for travel-related infections. Fewer vaccine-eligible travelers were administered travel-related vaccines at pretravel consultations. Counseling and vaccination focused on high-risk international travelers must be prioritized during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background Pediatric international travelers account for nearly half of measles importations in the United States. Over one third of pediatric international travelers depart the United States without the recommended measles-mumps-rubella (MMR) vaccinations: 2 doses for travelers ≥12 months and 1 dose for travelers 6 to <12 months. Methods We developed a model to compare 2 strategies among a simulated cohort of international travelers (6 months to <6 years): (1) No pretravel health encounter (PHE): travelers depart with baseline MMR vaccination status; (2) PHE: MMR-eligible travelers are offered vaccination. All pediatric travelers experience a destination-specific risk of measles exposure (mean, 30 exposures/million travelers). If exposed to measles, travelers' age and MMR vaccination status determine the risk of infection (range, 3%-90%). We included costs of medical care, contact tracing, and lost wages from the societal perspective. We varied inputs in sensitivity analyses. Model outcomes included projected measles cases, costs, and incremental cost-effectiveness ratios ($/quality-adjusted life year [QALY], cost-effectiveness threshold ≤$100 000/QALY). Results Compared with no PHE, PHE would avert 57 measles cases at $9.2 million/QALY among infant travelers and 7 measles cases at $15.0 million/QALY among preschool-aged travelers. Clinical benefits of PHE would be greatest for infants but cost-effective only for travelers to destinations with higher risk for measles exposure (ie, ≥160 exposures/million travelers) or if more US-acquired cases resulted from an infected traveler, such as in communities with limited MMR coverage. Conclusions Pretravel MMR vaccination provides the greatest clinical benefit for infant travelers and can be cost-effective before travel to destinations with high risk for measles exposure or from communities with low MMR vaccination coverage. [ABSTRACT FROM AUTHOR]

Background: Susceptibility to Vibrio cholerae infection is affected by blood group, age, and preexisting immunity, but these factors only partially explain who becomes infected. A recent study used 16S ribosomal RNA amplicon sequencing to quantify the composition of the gut microbiome and identify predictive biomarkers of infection with limited taxonomic resolution.Methods: To achieve increased resolution of gut microbial factors associated with V. cholerae susceptibility and identify predictors of symptomatic disease, we applied deep shotgun metagenomic sequencing to a cohort of household contacts of patients with cholera.Results: Using machine learning, we resolved species, strains, gene families, and cellular pathways in the microbiome at the time of exposure to V. cholerae to identify markers that predict infection and symptoms. Use of metagenomic features improved the precision and accuracy of prediction relative to 16S sequencing. We also predicted disease severity, although with greater uncertainty than our infection prediction. Species within the genera Prevotella and Bifidobacterium predicted protection from infection, and genes involved in iron metabolism were also correlated with protection.Conclusion: Our results highlight the power of metagenomics to predict disease outcomes and suggest specific species and genes for experimental testing to investigate mechanisms of microbiome-related protection from cholera. [ABSTRACT FROM AUTHOR]

We performed prospective screening of stool for multidrug-resistant organisms from 608 US international travelers and identified an acquisition rate of 38% following travel. Carriage rates remained significantly elevated for at least 6 months post-travel. Travel-related diarrhea was a risk factor for acquisition, as well as for long-term carriage upon return. [ABSTRACT FROM AUTHOR]

Background International travelers are often prescribed antibiotics for self-treatment of travelers' diarrhea (TD), but the benefits and risks of antibiotics are debated. We assessed the prescribing patterns of empiric antibiotics for TD in international travelers evaluated at Global TravEpiNet (GTEN) sites (2009–2018). Methods We performed a prospective, multisite cross-sectional study regarding antibiotic prescriptions for the self-treatment of TD at 31 GTEN sites providing pretravel consultations to adult international travelers. We described traveler demographics, itineraries, and antibiotic(s) prescribed. We used multivariable logistic regressions to assess the association of year of consultation with antibiotic prescribing (yes/no) and class (fluoroquinolones vs azithromycin). We performed interrupted time-series analyses to examine differences in prescribing before and after the Food and Drug Administration (FDA) warning on fluoroquinolones (July 2016). Results Antibiotics were not prescribed in 23 096 (22.2%) of 103 843 eligible pretravel GTEN consultations; azithromycin and fluoroquinolones were most frequently prescribed. Antibiotic prescribing declined significantly each year between 2009 and 2018 (odds ratio [OR], 0.84; 95% CI, 0.79–0.89), as did fluoroquinolone prescribing, relative to azithromycin (OR, 0.77; 95% CI, 0.73–0.82). The rate of decline in fluoroquinolone prescribing was significantly greater after the FDA fluoroquinolone warning (15.3%/year) than before (1.1%/year; P <.001). Conclusions Empiric antibiotics for TD were prescribed in >75% of pretravel GTEN consultations, but antibiotic prescribing declined steadily between 2009 and 2018. Fluoroquinolones were less frequently prescribed than azithromycin, especially after the 2016 FDA fluoroquinolone warning. Emphasis on the risks of antibiotics may influence antibiotic prescribing by providers for empiric treatment of TD. [ABSTRACT FROM AUTHOR]

Background Measles importations and the subsequent spread from US travelers returning from abroad are responsible for most measles cases in the United States. Increasing measles-mumps-rubella (MMR) vaccination among departing US travelers could reduce the clinical impact and costs of measles in the United States. Methods We designed a decision tree to evaluate MMR vaccination at a pretravel health encounter (PHE), compared with no encounter. We derived input parameters from Global TravEpiNet data and literature. We quantified Riskexposure to measles while traveling and the average number of US-acquired cases and contacts due to a measles importation. In sensitivity analyses, we examined the impact of destination-specific Riskexposure, including hot spots with active measles outbreaks; the percentage of previously-unvaccinated travelers; and the percentage of travelers returning to US communities with heterogeneous MMR coverage. Results The no-encounter strategy projected 22 imported and 66 US-acquired measles cases, costing $14.8M per 10M travelers. The PHE strategy projected 15 imported and 35 US-acquired cases at $190.3M per 10M travelers. PHE was not cost effective for all international travelers (incremental cost-effectiveness ratio [ICER] $4.6M/measles case averted), but offered better value (ICER <$100 000/measles case averted) or was even cost saving for travelers to hot spots, especially if travelers were previously unvaccinated or returning to US communities with heterogeneous MMR coverage. Conclusions PHEs that improve MMR vaccination among US international travelers could reduce measles cases, but are costly. The best value is for travelers with a high likelihood of measles exposure, especially if the travelers are previously unvaccinated or will return to US communities with heterogeneous MMR coverage. [ABSTRACT FROM AUTHOR]

Background: Cholera is a public health problem worldwide, and the risk factors for infection are only partially understood.Methods: We prospectively studied household contacts of patients with cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro.Results: We found that machine learning models based on gut microbiota, as well as models based on known clinical and epidemiological risk factors, predicted V. cholerae infection. A predictive gut microbiota of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked.Conclusion: These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility. [ABSTRACT FROM AUTHOR]

Background. In modern academic medicine, especially in the fields of infectious diseases and global health, aspiring physician- scientists often wait years before achieving independence as basic, translational, and clinical investigators. This study employed mixed methods to evaluate the success of the Burroughs Wellcome Fund/American Society for Tropical Medicine and Hygiene (BWF/ASTMH) global health postdoctoral fellowship in promoting scientific independence. Methods. We examined quantitative data obtained from the National Institutes of Health (NIH) and qualitative data provided by the ASTMH and program participants to assess BWF/ASTMH trainees’ success in earning NIH grants, publishing manuscripts, and gaining faculty positions. We also calculated the return on investment (ROI) associated with the training program by dividing direct costs of NIH research grants awarded to trainees by the direct costs invested by the BWF/ASTMH fellowship. Results. Forty-one trainees received fellowships between 2001 and 2015. Within 3 years of completing their fellowships, 21 of 35 (60%) had received career development awards, and within 5 years, 12 of 26 (46%) had received independent research awards. Overall, 22 of 35 (63%) received 1 or more research awards. BWF/ASTMH recipients with at least 3 years of follow-up data had coauthored a mean of 36 publications (range, 2–151) and 29 of 35 (82%) held academic positions. The return on investment was 11.9 overall and 31.8 for fellowships awarded between 2001 and 2004. Conclusions. Between 2001 and 2015, the BWF/ASTMH postdoctoral training program successfully facilitated progress to scientific independence. This program model underscores the importance of custom-designed postdoctoral training as a bridge to NIH awards and professional autonomy. [ABSTRACT FROM AUTHOR]

We evaluated immune responses following bivalent oral cholera vaccination (Shanchol [Shantha Biotechnics]; BivWC) in a cohort of 25 human immunodeficiency virus (HIV)-infected adults in Haiti. Compared with adults without HIV infection, vaccination in HIV-infected individuals resulted in lower vibriocidal responses against Vibrio cholerae O1, and there was a positive relationship between the CD4+ T-cell count and vibriocidal responses following vaccination. Nevertheless, seroconversion occurred at a rate of 65% against the Ogawa serotype and 74% against the Inaba serotype in adults with HIV infection. These results suggest that the vaccine retains substantial immunogenicity in adults with HIV infection and may benefit this population by protecting against cholera. [ABSTRACT FROM AUTHOR]

Costs and benefits of malaria prevention are provided during domestic pretravel health consultations. Healthcare payers always, and travelers often, save money when travelers adhere to malaria recommendations and prophylactic regimens in West Africa, especially for longer durations of travel.Background. Pretravel health consultations help international travelers manage travel-related illness risks through education, vaccination, and medication. This study evaluated costs and benefits of that portion of the health consultation associated with malaria prevention provided to US travelers bound for West Africa.Methods. The estimated change in disease risk and associated costs and benefits resulting from traveler adherence to malaria chemoprophylaxis were calculated from 2 perspectives: the healthcare payer's and the traveler's. We used data from the Global TravEpiNet network of US travel clinics that collect de-identified pretravel data for international travelers. Disease risk and chemoprophylaxis effectiveness were estimated from published medical reports. Direct medical costs were obtained from the Nationwide Inpatient Sample and published literature.Results. We analyzed 1029 records from January 2009 to January 2011. Assuming full adherence to chemoprophylaxis regimens, consultations saved healthcare payers a per-traveler average of $14 (9-day trip) to $372 (30-day trip). For travelers, consultations resulted in a range of net cost of $20 (9-day trip) to a net savings of $32 (30-day trip). Differences were mostly driven by risk of malaria in the destination country.Conclusions. Our model suggests that healthcare payers save money for short- and longer-term trips, and that travelers save money for longer trips when travelers adhere to malaria recommendations and prophylactic regimens in West Africa. This is a potential incentive to healthcare payers to offer consistent pretravel preventive care to travelers. This financial benefit complements the medical benefit of reducing the risk of malaria. [ABSTRACT FROM PUBLISHER]

Background. Recent studies demonstrate that long palate, lung, and nasal epithelium clone 1 protein (LPLUNC1) is involved in immune responses to Vibrio cholerae, and that variations in the LPLUNC1 promoter influence susceptibility to severe cholera in humans. However, no functional role for LPLUNC1 has been identified Metods. We investigated the role of LPLUNC1 in immune responses to V. cholerae, assessing its affect on bacterial growth and killing and on innate inflammatory responses to bacterial outer membrane components, including purified lipopolysaccharide (LPS) and outer membrane vesicles. We performed immunostaining for LPLUNC1 in duodenal biopsies from cholera patients and uninfected controls. Results. LPLUNC1 decreased proinflammatory innate immune responses to V. cholerae and Escherichia coli LPS. The effect of LPLUNC1 was dose-dependent and occurred in a TLR4-dependent manner. LPLUNC1 did not affect lipoprotein-mediated TLR2 activation. Immunostaining demonstrated expression of LPLUNC1 in Paneth cells in cholera patients and controls Conclusions. Our results demonstrate that LPLUNC1 is expressed in Paneth cells and likely plays a role in modulating host inflammatory responses to V. cholerae infection. Attenuation of innate immune responses to LPS by LPLUNC1 may have implications for the maintenance of immune homeostasis in the intestine [ABSTRACT FROM AUTHOR]

Background: Globally mobile populations are at higher risk of acquiring geographically restricted infections and may play a role in the international spread of infectious diseases. Despite this, data about sources of health information used by international travelers are limited.Methods: We surveyed 1,254 travelers embarking from Boston Logan International Airport regarding sources of health information. We focused our analysis on travelers to low or low-middle income (LLMI) countries, as defined by the World Bank 2009 World Development Report.Results: A total of 476 survey respondents were traveling to LLMI countries. Compared with travelers to upper-middle or high income (UMHI) countries, travelers to LLMI countries were younger, more likely to be foreign-born, and more frequently reported visiting family as the purpose of their trip. Prior to their trips, 46% of these travelers did not pursue health information of any type. In a multivariate analysis, being foreign-born, traveling alone, traveling for less than 14 days, and traveling for vacation each predicted a higher odds of not pursuing health information among travelers to LLMI countries. The most commonly cited reason for not pursuing health information was a lack of concern about health problems related to the trip. Among travelers to LLMI countries who did pursue health information, the internet was the most common source, followed by primary care practitioners. Less than a third of travelers to LLMI countries who sought health information visited a travel medicine specialist.Conclusions: In our study, 46% of travelers to LLMI countries did not seek health advice prior to their trip, largely due to a lack of concern about health issues related to travel. Among travelers who sought medical advice, the internet and primary care providers were the most common sources of information. These results suggest the need for health outreach and education programs targeted at travelers and primary care practitioners. [ABSTRACT FROM AUTHOR]

Background. Multiple Vibrio cholerae infections in the same household are common. The objective of this study was to examine the incidence of V. cholerae infection and associated clinical symptoms in household contacts of patients with cholera and to identify risk factors for development of severe dehydration in this cohort. Methods. Household contacts of hospitalized patients with cholera were observed with frequent clinical assessments and collection of serum and rectal swab samples for culture for a period of 21 days after presentation of the index case. Results. One-half (460 of 944) of all contacts reported diarrhea during the study period, and symptoms most frequently began 2 days after presentation of the index case. Antibiotics were used by 199 (43%) of 460 contacts with diarrhea. Results of rectal swab cultures for V. cholerae were positive for 202 (21%) of 944 contacts, and 148 (73%) infected contacts experienced diarrhea. Significant dehydration developed in 26 contacts; predictors of dehydration included vomiting, each additional day of diarrhea, and blood group O status. Conclusions. In urban Bangladesh, the burden of diarrheal illness among household contacts of patients with cholera is higher than was previously estimated, and prophylactic intervention is feasible, because the majority of symptomatic cases of V. cholerae infection in contacts begin soon after presentation of the index case. Re-evaluation of targeted chemoprophylaxis for household contacts of patients with cholera may be warranted. [ABSTRACT FROM AUTHOR]

Background. Infection with Vibrio cholerae induces durable immunity against subsequent disease, a process hypothesized to reflect anamnestic immune responses at the intestinal mucosa. The presence of antigen-specific memory B cells may therefore be a more direct measure of protection than serum antibody responses. Methods. We measured immunoglobulin (Ig) G memory B cells specific to cholera toxin B subunit (CTB) in 14 patients up to 90 days after V. cholerae O1 infection, by polyclonal stimulation of peripheral blood mononuclear cells followed by standard enzyme-linked immunospot assay. Results. All patients generated CTB-specific IgG memory B cell responses by day 30 (mean, 0.10% of total circulating IgG memory B cells; range, 0.037%-0.28%), which persisted to day 90 (mean, 0.07%; range, 0.003%- 0.27%). In contrast, circulating CTB-specific IgG antibody-secreting cells and serum vibriocidal and anti-CTB antibody responses peaked on day 7 and declined to undetectable or significantly lower levels by day 90. Conclusions. CTB-specific IgG memory B cell responses are detectable in the circulation at least 3 months after V. cholerae O1 infection and remain measurable even after serum antibody titers have declined to undetectable or considerably lower levels. This suggests that antigen-specific memory B cells may be an important long-term marker of the immune response to cholera. [ABSTRACT FROM AUTHOR]

Background Although pediatric travelers comprise < 10% of US international travelers, they account for almost half of all measles importations among returning travelers. For travelers 1–18 years with no other evidence of measles immunity, the Advisory Committee on Immunization Practices (ACIP) recommends 2 MMR vaccine doses before departure; 1 dose is recommended for infant travelers (6 to <12 months) and does not count toward their primary immunization series. All US travelers (6 months to < 6 years) are at risk for being undervaccinated for measles because MMR is routinely given at 1 years and 4–6 years. Methods We developed a decision tree model to evaluate the clinical impact and cost per case averted of pretravel health encounters (PHE) that vaccinate MMR-eligible pediatric international travelers. We compared 2 strategies for infant (6 to < 12 months) and preschool-aged (1 to <6 years) travelers: (1) no PHE : travelers departed with baseline MMR vaccination status vs. (2) PHE : MMR-eligible travelers were offered vaccination. All simulated travelers experienced a destination-specific risk of measles exposure during travel (mean, 237exposures/10M travelers; range, 19–6,750 exposures/10M travelers); if exposed to measles, travelers were at risk of illness stratified by age and MMR vaccination status (range, 0.03–0.90). Costs include direct medical costs and lost work wages for guardians. Model outcomes included measles cases, costs, and cost per case averted. We varied inputs in sensitivity analyses. Results Compared with no PHE , PHE averted 451 measles cases at $985,000/case averted for infant travelers and 54 measles cases at $1.5 million/case averted for preschool-aged travelers (table, bottom). PHE can be cost-saving for travelers to regions with higher risk of measles exposure and if more MMR-eligible travelers are vaccinated at PHE (Figure 1). At a risk of exposure associated with European travel, PHE had better value when a measles importation led to a higher number of contacts or more US-acquired cases per importation (Figure 2). Conclusion PHE for pediatric travelers (6 months to <6 years) decreased the number of imported measles cases and saved costs, especially if targeted to travelers with higher-risk destinations, if more MMR-eligible travelers are vaccinated at PHE, or if outbreaks are larger. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: Last-minute travellers (LMTs) present challenges for health care providers because they may have insufficient time for recommended vaccinations or pre-travel preparation. Our objective was to obtain a better understanding of LMTs in order to help travel medicine providers develop improved strategies to decrease the number of LMTs and potentially reduce travel-related morbidity.Methods: We defined LMTs as travellers with a departure date of 7 days or fewer from the medical encounter. We analysed the characteristics and health preparation of 12 494 LMTs who presented to a network of US clinical practices for pre-travel health advice between January 2009 and December 2015.Results: LMTs comprised 16% of all travellers. More LMTs than non-LMTs travelled for business or to visit friends and relatives (VFR) (26% vs 16% and 15% vs 8%, respectively; P < 0.0001). More LMTs also travelled for longer than 1 month (27% vs 21%; P < 0.0001) and visited only urban areas (40% vs 29%; P < 0.0001). At least one travel vaccine was deferred by 18% of LMTs because of insufficient time before departure. Vaccines that required multiple vaccinations, such as Japanese encephalitis and rabies, were the most likely to be deferred because of time constraints.Conclusion: Interventions to improve the timing of pre-travel health consultations should be developed, particularly for business and VFR travellers. Recently endorsed accelerated vaccine schedules for Japanese encephalitis and rabies may help some LMTs receive protection against these infections despite late presentation for pre-travel health care. [ABSTRACT FROM AUTHOR]

Travelers seen for pretravel health encounters are frequently prescribed new travel-related medications, which may interact with their previously prescribed medications. In a cohort of 76 324 travelers seen at 23 US clinics, we found that 2650 (3.5%) travelers were prescribed travel-related medications with potential for serious drug interactions. [ABSTRACT FROM AUTHOR]

Background: International travellers are at risk of travel-related, vaccine-preventable diseases. More data are needed on the proportion of travellers who refuse vaccines during a pre-travel health consultation and their reasons for refusing vaccines.Methods: We analyzed data on travellers seen for a pre-travel health consultation from July 2012 through June 2014 in the Global TravEpiNet (GTEN) consortium. Providers were required to indicate one of three reasons for a traveller refusing a recommended vaccine: (1) cost concerns, (2) safety concerns or (3) not concerned with the illness. We calculated refusal rates among travellers eligible for each vaccine based on CDC recommendations current at the time of travel. We used multivariable logistic regression models to examine the effect of individual variables on the likelihood of accepting all recommended vaccines.Results: Of 24 478 travellers, 23 768 (97%) were eligible for at least one vaccine. Travellers were most frequently eligible for typhoid (N = 20 092), hepatitis A (N = 12 990) and influenza vaccines (N = 10 539). Of 23 768 eligible travellers, 6573 (25%) refused one or more recommended vaccine(s). Of those eligible, more than one-third refused the following vaccines: meningococcal: 2232 (44%) of 5029; rabies: 1155 (44%) of 2650; Japanese encephalitis: 761 (41%) of 1846; and influenza: 3527 (33%) of 10 539. The most common reason for declining vaccines was that the traveller was not concerned about the illness. In multivariable analysis, travellers visiting friends and relatives (VFR) in low or medium human development countries were less likely to accept all recommended vaccines, compared with non-VFR travellers (OR = 0.74 (0.59-0.95)).Conclusions: Travellers who sought pre-travel health care refused recommended vaccines at varying rates. A lack of concern about the associated illness was the most commonly cited reason for all refused vaccines. Our data suggest more effective education about disease risk is needed for international travellers, even those who seek pre-travel advice. [ABSTRACT FROM AUTHOR]