Associations between human milk oligosaccharides and infant growth in a Bangladeshi mother-infant cohort.

BACKGROUND: We aimed to estimate associations between human milk oligosaccharides (HMOs) and infant growth (length-for-age (LAZ) and weight-for-length (WLZ) z-scores) at 12 months postnatal age. METHODS: In this secondary analysis of data from a maternal vitamin D trial in Dhaka, Bangladesh (N = 192), absolute concentrations of HMOs were measured in 13 ± 1 week(s) postpartum milk samples, infant anthropometric measurements were obtained soon after birth and at 12 months postpartum, and infant feeding was classified during 6 months postpartum. Associations between individual HMOs or HMO groups and LAZ or WLZ were estimated by multivariable linear regression adjusting for infant feeding pattern, maternal secretor status, and other potential confounders. RESULTS: The concentrations of 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated HMOs were inversely associated with LAZ at 12 months of age, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months. These associations were robust in analyses restricted to infants who were primarily exclusively/predominantly fed human milk during the first 3 (or 6) months. CONCLUSIONS: Since HMOs are both positively and negatively associated with postnatal growth, there is a need for randomized trials to estimate the causal benefits and risks of exogenously administered HMOs on infant growth and other health outcomes. IMPACT: 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated human milk oligosaccharides (HMOs) were inversely associated with length-for-age z-scores (LAZ) at 12 months, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months among Bangladeshi infants. Associations between individual and grouped HMOs with infant length growth at 12 months were as strong or stronger in analyses restricted to infants who were exclusively or predominantly fed human milk up to 3 (or 6) months. Randomized trials are needed to characterize the effects of specific HMOs on infant growth, particularly in countries where postnatal linear growth faltering is common.

An integrated newborn care kit (iNCK) to save newborn lives and improve health outcomes in Gilgit Baltistan (GB), Pakistan: study protocol for a cluster randomized controlled trial.

BACKGROUND: Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births. Reducing newborn deaths requires sustainable, evidence-based, and cost-effective interventions that can be integrated within existing community healthcare infrastructure across regions with high NMR. METHODS: This pragmatic, community-based, parallel-arm, open-label, cluster randomized controlled trial aims to estimate the effect of Lady Health Workers (LHWs) providing an integrated newborn care kit (iNCK) with educational instructions to pregnant women in their third trimester, compared to the local standard of care in Gilgit-Baltistan, Pakistan, on neonatal mortality and other newborn and maternal health outcomes. The iNCK contains a clean birth kit, 4% chlorhexidine topical gel, sunflower oil emollient, a ThermoSpot™ temperature monitoring sticker, a fleece blanket, a click-to-heat reusable warmer, three 200 µg misoprostol tablets, and a pictorial instruction guide and diary. LHWs are also provided with a handheld scale to weigh the newborn. The primary study outcome is neonatal mortality, defined as a newborn death in the first 28 days of life. DISCUSSION: This study will generate policy-relevant knowledge on the effectiveness of integrating evidence-based maternal and newborn interventions and delivering them directly to pregnant women via existing community health infrastructure, for reducing neonatal mortality and morbidity, in a remote, mountainous area with a high NMR. TRIAL REGISTRATION: NCT04798833, March 15, 2021.

Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh.

BACKGROUND: Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known. METHODS: This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling. RESULTS: Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons). CONCLUSION: Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.

A Bayesian adaptive design for clinical trials of rare efficacy outcomes with multiple definitions.

INTRODUCTION: Bayesian adaptive designs for clinical trials have gained popularity in the recent years due to the flexibility and efficiency that they offer. We consider the scenario where the outcome of interest comprises events with relatively low risk of occurrence and different case definitions resulting in varying control group risk assumptions. This is a scenario that occurs frequently for infectious diseases in global health research. METHODS: We propose a Bayesian adaptive design that incorporates different case definitions of the outcome of interest that vary in stringency. A set of stopping rules are proposed where superiority and futility may be concluded with respect to different outcome definitions and therefore maintain a realistic probability of stopping in trials with low event rates. Through a simulation study, a variety of stopping rules and design configurations are compared. RESULTS: The simulation results are provided in an interactive web application that allows the user to explore and compare the design operating characteristics for a variety of assumptions and design parameters with respect to different outcome definitions. The results for select simulation scenarios are provided in the article. DISCUSSION: Bayesian adaptive designs offer the potential for maximizing the information learned from the data collected through clinical trials. The proposed design enables monitoring and utilizing multiple composite outcomes based on rare events to optimize the trial design operating characteristics.

Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth.

BACKGROUND: It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). RESULTS: Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. CONCLUSIONS: In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).

Genetic characterization of human metapneumovirus identified through community and facility-based surveillance of infants in Dhaka, Bangladesh.

BACKGROUND: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children in low and middle-income countries. Human metapneumovirus (hMPV) is one of the most common viral etiological agents for ARIs in children. OBJECTIVES: In this study, we explored the genotypic diversity and the epidemiology of hMPV among infants in Dhaka, Bangladesh. STUDY DESIGN: Between December 2014 and August 2016, a total of 3810 mid-turbinate nasal swab samples were collected from infants (0 to 6 months of age) who met clinical ARI criteria, as a part of a prospective ARI cohort study. hMPV was detected using polymerase chain reaction, and genotyped by sequencing and phylogenetic analysis. RESULTS: hMPV was identified in 206 (5.4%) nasal swab specimens. One-tenth of the hMPV-positive swabs (n = 19) were also positive for other respiratory viruses. hMPV activity peaked in January and September in 2015; however, no seasonal pattern of hMPV infection was detected. Phylogenetic analyses of the N and F gene-fragments revealed that the hMPV strains circulating in Dhaka, Bangladesh, belonged to three genotypes: A2b, A2c, and B1. Genotype A (57%) was the predominant hMPV genotype circulating in Bangladesh during the study period. CONCLUSION: This study describes both the epidemiology of hMPV infection and its genotypic strain diversity in Dhaka, Bangladesh.

Arguments against routine administration of probiotics for NEC prevention.

PURPOSE OF REVIEW: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among premature neonates. Although randomized trials have shown that probiotics may be efficacious in the prevention of NEC, their use has not been universally adopted in the neonatal intensive care unit (NICU). Caveats regarding routine probiotic supplementation for the prevention of NEC are summarized in this review. RECENT FINDINGS: Accumulating evidence indicates that prophylactic probiotic supplementation in preterm infants can reduce the incidence of NEC. However, substantial knowledge gaps, regulatory issues, and implementation challenges should be addressed before probiotics are introduced as standard of care for all preterm neonates. Limitations of published trial data have made it challenging to define regimens that optimize efficacy and safety in specific patient subgroups. Moreover, the current probiotic market lacks rigorous regulatory oversight, which could raise concerns about the quality and safety of probiotic products. Finally, implementation pitfalls include risks of cross-colonization and resource requirements to monitor and mitigate potential adverse events. SUMMARY: Probiotics have shown promise in the prevention of NEC. However, there is insufficient evidence to guide the selection of optimal regimens. Furthermore, issues related to regulatory and institutional oversight should be addressed before supplementation is routinely implemented in NICUs.

Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial.

BACKGROUND: Early infancy is a high-risk period for severe acute respiratory infection (ARI), particularly in low-income countries with resource-limited health systems. Lower respiratory tract infection (LRTI) is commonly preceded by upper respiratory infection (URTI), and often caused by respiratory syncytial virus (RSV), influenza and other common community-acquired viral pathogens. Vitamin D status is a candidate modifiable early-life determinant of the host antiviral immune response and thus may influence the risk of ARI-associated morbidity in high-risk populations. METHODS/DESIGN: In the Maternal Vitamin D for Infant Growth (MDIG) study in Dhaka, Bangladesh (NCT01924013), 1300 pregnant women are randomized to one of five groups: placebo, 4200 IU/week, 16,800 IU/week, or 28,000 IU/week from 2nd trimester to delivery plus placebo from 0-6 months postpartum; or, 28,000 IU/week prenatal and until 6-months postpartum. In the Maternal Vitamin D for ARI in Infancy (MDARI) sub-study nested within the MDIG trial, trained personnel conduct weekly postnatal home visits to inquire about ARI symptoms and conduct a standardized clinical assessment. Supplementary home visits between surveillance visits are conducted when caregivers make phone notifications of new infant symptoms. Mid-turbinate nasal swab samples are obtained from infants who meet standardized clinical ARI criteria. Specimens are tested by polymerase chain reaction (PCR) for 8 viruses (influenza A/B, parainfluenza 1/2/3, RSV, adenovirus, and human metapneumovirus), and nasal carriage density of Streptococcus pneumoniae. The primary outcome is the incidence rate of microbiologically-positive viral ARI, using incidence rate ratios to estimate between-group differences. We hypothesize that among infants 0-6 months of age, the incidence of microbiologically-confirmed viral ARI will be significantly lower in infants whose mothers received high-dose prenatal/postpartum vitamin D supplements versus placebo. Secondary outcomes include incidence of ARI associated with specific pathogens (influenza A or B, RSV), clinical ARI, and density of pneumococcal carriage. DISCUSSION: If shown to reduce the risk of viral ARI in infancy, integration of maternal prenatal/postpartum vitamin D supplementation into antenatal care programs in South Asia may be a feasible primary preventive strategy to reduce the burden of ARI-associated morbidity and mortality in young infants. TRIAL REGISTRATION: NCT02388516 , registered March 9, 2015.

Effect of provision of an integrated neonatal survival kit and early cognitive stimulation package by community health workers on developmental outcomes of infants in Kwale County, Kenya: study protocol for a cluster randomized trial.

BACKGROUND: Each year, more than 200 million children under the age of 5 years, almost all in low- and middle-income countries (LMICs), fail to achieve their developmental potential. Risk factors for compromised development often coexist and include inadequate cognitive stimulation, poverty, nutritional deficiencies, infection and complications of being born low birthweight and/or premature. Moreover, many of these risk factors are closely associated with newborn morbidity and mortality. As compromised development has significant implications on human capital, inexpensive and scalable interventions are urgently needed to promote neurodevelopment and reduce risk factors for impaired development. METHOD/DESIGN: This cluster randomized trial aims at evaluating the impact of volunteer community health workers delivering either an integrated neonatal survival kit, an early stimulation package, or a combination of both interventions, to pregnant women during their third trimester of pregnancy, compared to the current standard of care in Kwale County, Kenya. The neonatal survival kit comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot(TM), Mylar infant sleeve, and a reusable instant heater. Community health workers are also equipped with a portable hand-held electric scale. The early cognitive stimulation package focuses on enhancing caregiver practices by teaching caregivers three key messages that comprise combining a gentle touch with making eye contact and talking to children, responsive feeding and caregiving, and singing. The primary outcome measure is child development at 12 months of age assessed with the Protocol for Child Monitoring (Infant and Toddler version). The main secondary outcome is newborn mortality. DISCUSSION: This study will provide evidence on effectiveness of delivering an innovative neonatal survival kit and/or early stimulation package to pregnant women in Kwale County, Kenya. Study findings will help inform policy on the most appropriate interventions for promoting healthy brain development and reduction of newborn morbidity and mortality in Kenya and other similar settings. TRIAL REGISTRATION: ClinicalTrial.gov NCT02208960 (August 1, 2014).

Epidemiology and clinical management of tuberculosis in children in Canada.

Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed.

Même si la tuberculose latente et la tuberculose sont souvent considérées comme des maladies étrangères, le dispensateur canadien de soins des enfants les observera souvent dans bien des situations cliniques. Il y a des différences clés entre la tuberculose chez l'enfant et chez l'adulte. Dans le présent article, les auteurs analysent l'évolution de l'épidémiologie de la tuberculose chez les enfants du Canada et de l'étranger, la pathogenèse de l'infection, les tests diagnostiques et la prise en charge de la tuberculose latente et de la tuberculose pendant l'enfance.

The community-based delivery of an innovative neonatal kit to save newborn lives in rural Pakistan: design of a cluster randomized trial.

BACKGROUND: Worldwide, an estimated 2.9 million neonatal deaths occurred in 2012, accounting for 44% of all under-five deaths. In Pakistan, more than 200,000 newborns die annually and neonatal mortality rates are higher than in any other South Asian country and haven't changed over the last three decades. The high number of neonatal deaths highlights the urgent need for effective and sustainable interventions that target newborn mortality in Pakistan. METHOD/DESIGN: This cluster randomized trial aims at evaluating the impact of delivering an integrated neonatal kit to pregnant women during the third trimester of pregnancy and providing education on how to use the contents (intervention arm) compared to the current standard of care (control arm) in the district of Rahimyar Khan, Punjab province, Pakistan. The kit, which will be distributed through the national Lady Health Worker program, comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot™, Mylar infant sleeve, and a reusable instant heat pack. Lady health workers will be provided with a standard portable hand-held electric weighing scale. The primary outcome measure is neonatal mortality (death in the first 28 days of life). DISCUSSION: While many cost-effective, evidence-based interventions to save newborn lives exist, they are not always accessible nor have they been integrated into a portable kit designed for home-based implementation entirely by caregivers. The implementation of cost-effective, portable, and easy-to-use interventions has tremendous potential for sustainably reducing neonatal mortality and long-term improvements in population health. The bundling of interventions and commodities together also has much potential for cost-effective delivery and maximizing gains from points of contact. This study will provide empirical evidence on the feasibility and effectiveness of the delivery of an innovative neonatal kit to pregnant women in Pakistan. Together, these findings will help inform policy on the most appropriate interventions to improve newborn survival. TRIAL REGISTRATION: ClinicalTrial.gov NCT02130856. Registered May 1, 2014.

Detection and absolute quantification of Lactiplantibacillus plantarum ATCC 202195 by quantitative real-time PCR.

IMPORTANCE: When administered for seven consecutive days shortly after birth, the probiotic bacterium Lactiplantibacillus plantarum ATCC 202195 plus fructooligosaccharide (FOS) was reported to reduce sepsis and lower respiratory tract infection events during early infancy in a randomized trial in India. Since probiotic effects are often strain specific, strain-level detection and quantification by routine molecular methods enables the monitoring of safety outcomes, such as probiotic-associated bacteremia, and allows for the quality of probiotic interventions to be assessed and monitored (i.e., verify strain identity and enumerate). Despite the potential clinical applications of L. plantarum ATCC 202195, an assay to detect and quantify this strain has not previously been described. Herein, we report the design of primer and probe sequences to detect L. plantarum ATCC 202195 and the development and optimization of a real-time PCR assay to detect and quantify the strain with high specificity and high sensitivity.

Association of maternal, obstetric, fetal, and neonatal mortality outcomes with Lady Health Worker coverage from a cross-sectional survey of >10,000 households in Gilgit-Baltistan, Pakistan.

Pakistan has among the highest rates of maternal, perinatal, and neonatal mortality globally. Many of these deaths are potentially preventable with low-cost, scalable interventions delivered through community-based health worker programs to the most remote communities. We conducted a cross-sectional survey of 10,264 households during the baseline phase of a cluster randomized controlled trial (cRCT) in Gilgit-Baltistan, Pakistan from June-August 2021. The survey was conducted through a stratified, two-stage sampling design with the objective of estimating the neonatal mortality rate (NMR) within the study catchment area, and informing implementation of the cRCT. Study outcomes were self-reported and included neonatal death, stillbirth, health facility delivery, maternal death, postpartum hemorrhage (PPH), and Lady Health Worker (LHW) coverage. Summary statistics (proportions and rates) were weighted according to the sampling design, and mixed-effects Poisson regression was conducted to explore the relationship between LHW coverage and maternal/newborn outcomes. We identified 7,600 women who gave birth in the past five years, among whom 13% reported experiencing PPH. The maternal mortality ratio was 225 maternal deaths per 100,000 live births (95% confidence interval [CI] 137-369). Among 12,376 total births, the stillbirth rate was 41.4 per 1,000 births (95% CI 36.8-46.7) and the perinatal mortality rate was 53.0 per 1,000 births (95% CI 47.6-59.0). Among 11,863 live births, NMR was 16.2 per 1,000 live births (95% CI 13.6-19.3) and 65% were delivered at a health facility. LHW home visits were associated with declines in PPH (risk ratio [RR] 0.89 per each additional visit, 95% CI 0.83-0.96) and late neonatal mortality (RR 0.80, 95% CI 0.67-0.97). Intracluster correlation coefficients were also estimated to inform the planning of future trials. The high rates of maternal, perinatal, and neonatal death in Gilgit-Baltistan continue to fall behind targets of the 2030 Sustainable Development Goals.

Phages have adapted the same protein fold to fulfill multiple functions in virion assembly.

Evolutionary relationships may exist among very diverse groups of proteins even though they perform different functions and display little sequence similarity. The tailed bacteriophages present a uniquely amenable system for identifying such groups because of their huge diversity yet conserved genome structures. In this work, we used structural, functional, and genomic context comparisons to conclude that the head-tail connector protein and tail tube protein of bacteriophage lambda diverged from a common ancestral protein. Further comparisons of tertiary and quaternary structures indicate that the baseplate hub and tail terminator proteins of bacteriophage may also be part of this same family. We propose that all of these proteins evolved from a single ancestral tail tube protein fold, and that gene duplication followed by differentiation led to the specialized roles of these proteins seen in bacteriophages today. Although this type of evolutionary mechanism has been proposed for other systems, our work provides an evolutionary mechanism for a group of proteins with different functions that bear no sequence similarity. Our data also indicate that the addition of a structural element at the N terminus of the lambda head-tail connector protein endows it with a distinctive protein interaction capability compared with many of its putative homologues.

Long noncontractile tail machines of bacteriophages.

In this chapter, we describe the structure, assembly, function, and evolution of the long, noncontractile tail of the siphophages, which comprise ∼60% of the phages on earth. We place -particular emphasis on features that are conserved among all siphophages, and trace evolutionary connections between these phages and myophages, which possess long contractile tails. The large number of high-resolution structures of tail proteins solved recently coupled to studies of tail-related complexes by electron microscopy have provided many new insights in this area. In addition, the availability of thousands of phage and prophage genome sequences has allowed the delineation of several large families of tail proteins that were previously unrecognized. We also summarize current knowledge pertaining to the mechanisms by which siphophage tails recognize the bacterial cell surface and mediate DNA injection through the cell envelope. We show that phages infecting Gram-positive and Gram-negative bacteria possess distinct families of proteins at their tail tips that are involved in this process. Finally, we speculate on the evolutionary advantages provided by long phage tails.

The phage lambda major tail protein structure reveals a common evolution for long-tailed phages and the type VI bacterial secretion system.

Most bacteriophages possess long tails, which serve as the conduit for genome delivery. We report the solution structure of the N-terminal domain of gpV, the protein comprising the major portion of the noncontractile phage lambda tail tube. This structure is very similar to a previously solved tail tube protein from a contractile-tailed phage, providing the first direct evidence of an evolutionary connection between these 2 distinct types of phage tails. A remarkable structural similarity is also seen to Hcp1, a component of the bacterial type VI secretion system. The hexameric structure of Hcp1 and its ability to form long tubes are strikingly reminiscent of gpV when it is polymerized into a tail tube. These data coupled with other similarities between phage and type VI secretion proteins support an evolutionary relationship between these systems. Using Hcp1 as a model, we propose a polymerization mechanism for gpV involving several disorder-to-order transitions.

Pretravel plans and discrepant trip experiences among travelers attending a tertiary care centre family travel medicine clinic.

BACKGROUND: International travel can expose travelers to a number of health risks. Pretravel consultation (PC) helps mitigate risk and prepare travelers for health concerns that might arise. The assessment of risk, mitigation strategies, and relevance of pretravel advice is dependent on how closely travelers adhere to their planned travel itinerary and activities. We determined the proportion of returned travelers whose completed travel experiences differed from their stated travel itineraries, and identified discrepancies that significantly altered the traveler's health risk and would have required alternative counseling during their PC. METHODS: We conducted a prospective cohort study at the SickKids' Family Travel Clinic between October 2014 and November 2015. Returned travelers who completed a post-travel survey were included. Pretravel consultation assessments and post-trip surveys were compared to identify discrepant trip experiences. RESULTS: A total of 389 travelers presented to the clinic for a PC during the study period and 302 (77.6%) were enrolled. Post-travel surveys were received from 119 (39.4%) participants, representing 101 unique itineraries. The median participant age was 36.3 years (IQR 26.6-47.5) and there were 73 female travelers (61%). Most participants (n = 87,73%) were healthy as well as Canadian born (n = 84, 71%). A quarter of travelers were visiting friends and relatives (VFR) (n = 30, 25.2%). The vast majority of returned travelers (n = 109, 92%) reported discrepant trip experiences involving trip duration, countries visited, accommodations, environmental surroundings and/or activities. Almost two thirds of these individuals (n = 68, 62%) would have required alternative pretravel counseling. We did not identify any demographic or planned trip characteristics that predicted discrepant trip experiences requiring alternative pretravel counseling. CONCLUSIONS: The majority of travelers reported discrepant trip experiences and the discrepancies often affected health risk. Therefore, clinicians should consider providing broader counselling during the PC as discrepancies from planned travel are common.

Underestimation of travel-associated risks by adult and paediatric travellers compared to expert assessment: A cross-sectional study at a hospital-based family pre-travel clinic.

BACKGROUND: Travellers' perception of their risk for acquiring travel-related conditions is an important contributor to decisions and behaviors during travel. In this study, we aimed to assess the differences between traveller-perceived and expert-assessed risk of travel-related conditions in children and adults travelling internationally and describe factors that influence travellers' perception of risk. METHODS: Children and adults were recruited at the Hospital for Sick Children's Family Travel Clinic between October 2014 and July 2015. A questionnaire was administered to participants to assess their perceived risk of acquiring 32 travel-related conditions using a 7-point Likert scale. Conditions were categorized as vector-borne diseases, vaccine-preventable diseases, food and water borne diseases, sexually transmitted infections and other conditions. Two certified travel medicine experts reviewed each patient's chart and assigned a risk score based on the same 7-point Likert scale. Traveller and expert risk scores were compared using paired t-tests. RESULTS: In total, 207 participants were enrolled to participate in this study, 97 children (self-reported, n = 8; parent-reported, n = 89), and 110 adults. Travel-related risk for adults and parents answering for their children were significantly underestimated when compared to expert-assessed risk for 26 of the 32 assessed conditions. The underestimated conditions were the same for both adults and parents answering for children. Travel-related risk was not over-estimated for any condition. CONCLUSIONS: Adults underestimated their children's and their own risk for most travel-related conditions. Strategies to improve the accuracy of risk perception of travel-related conditions by travellers are needed to optimize healthy travel for children and their families.

Micronutrient supplements can promote disruptive protozoan and fungal communities in the developing infant gut.

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, association of gastrointestinal disorders with iron has led to ongoing debate over their administration. To better understand their impact on gut microbiota, we analyse the bacterial, protozoal, fungal and helminth communities of stool samples collected from a subset of 80 children at 12 and 24 months of age, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan (ClinicalTrials.gov identifier NCT00705445). We show that while bacterial diversity is reduced in supplemented children, vitamins and iron (as well as residence in a rural setting) may promote colonization with distinct protozoa and mucormycetes, whereas the addition of zinc appears to ameliorate this effect. We suggest that the risks and benefits of micronutrient interventions may depend on eukaryotic communities, potentially exacerbated by exposure to a rural setting. Larger studies are needed to evaluate the clinical significance of these findings and their impact on health outcomes.

Antimicrobial susceptibilities and comparative whole genome analysis of two isolates of the probiotic bacterium Lactiplantibacillus plantarum, strain ATCC 202195.

A synbiotic containing Lactiplantibacillus plantarum [American Type Culture Collection (ATCC) strain identifier 202195] and fructooligosaccharide was reported to reduce the risk of sepsis in young infants in rural India. Here, the whole genome of two isolates of L. plantarum ATCC 202195, which were deposited to the ATCC approximately 20 years apart, were sequenced and analyzed to verify their taxonomic and strain-level identities, identify potential antimicrobial resistant genes and virulence factors, and identify genetic characteristics that may explain the observed clinical effects of L. plantarum ATCC 202195. Minimum inhibitory concentrations for selected antimicrobial agents were determined using broth dilution and gradient strip diffusion techniques. The two L. plantarum ATCC 202195 isolates were genetically identical with only three high-quality single nucleotides polymorphisms identified, and with an average nucleotide identity of 99.99%. In contrast to previously published reports, this study determined that each isolate contained two putative plasmids. No concerning acquired or transferable antimicrobial resistance genes or virulence factors were identified. Both isolates were sensitive to several clinically important antibiotics including penicillin, ampicillin and gentamicin, but resistant to vancomycin. Genes involved in stress response, cellular adhesion, carbohydrate metabolism and vitamin biosynthesis are consistent with features of probiotic organisms.