Antibiotic Use and Stewardship Practices in a Pediatric Community-based Cohort Study in Peru: Shorter Would be Sweeter.

BACKGROUND: There is a need to evaluate antibiotic use, duration of therapy, and stewardship in low- and middle-income countries to guide the development of appropriate stewardship programs that are global in scope and effectively decrease unnecessary antibiotic use. METHODS: We prospectively collected information on illness occurrence and antibiotic use from a cohort of 303 children. We evaluated the incidence, duration of therapy, and appropriateness of antibiotic prescriptions by 5 main antibiotic prescribers (physicians and nurses, pharmacists, nursing assistants, self-prescriptions, and neighbors or family members). RESULTS: Ninety percent of children received an antibiotic during follow-up, and on average, by the end of follow-up a child had spent 4.3% of their first 5 years of life on antibiotics. The most frequent prescribers were physicians/nurses (79.4%), followed by pharmacists (8.1%), self-prescriptions (6.8%), nursing assistants (3.7%), and family or neighbors (1.9%). Of the 3702 courses of antibiotics prescribed, 30.9% were done so for the occurrence of fever, 25.3% for diarrhea, 2.8% for acute lower respiratory disease, 2.7% for dysentery, and 38.2% for an undetermined illness. Courses exceeding the recommended duration were common for the principal diseases for which treatment was initiated, with 27.3% of courses exceeding the recommended length duration, representing a potential reduction in 13.2% of days on which this cohort spent on antibiotics. CONCLUSIONS: Stewardship programs should target medical personnel for a primary care stewardship program even in a context in which antibiotics are available to the public with little or no restrictions and appropriate duration should be emphasized in this training.

Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study.

BACKGROUND: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. METHODS: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. DISCUSSION: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. STUDY REGISTRATION: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020-2021.

Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020-October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.

Effects of Child and Maternal Histo-Blood Group Antigen Status on Symptomatic and Asymptomatic Enteric Infections in Early Childhood.

BACKGROUND: Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections. METHODS: In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 diarrheal and 18 148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n = 520) and mothers' (n = 519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens. RESULTS: Children of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15-1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71-0.93) and 27% (HR = 0.83; 95% CI, 0.74-0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli, and Campylobacter jejuni/coli. CONCLUSIONS: Histo-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers' HBGA status.

Antibiotic Resistance of Campylobacter Species in a Pediatric Cohort Study.

The objective of this study was to determine the phenotypic patterns of antibiotic resistance and the epidemiology of drug-resistant Campylobacter spp. from a low-resource setting. A birth cohort of 303 patients was followed until 5 years of age. Stool samples from asymptomatic children (n = 10,008) and those with diarrhea (n = 3,175) were cultured for Campylobacter Disk diffusion for ciprofloxacin (CIP), nalidixic acid (NAL), erythromycin (ERY), azithromycin (AZM), tetracycline (TE), gentamicin (GM), ampicillin (AMP), amoxicillin and clavulanic acid (AMC), ceftriaxone (CRO), chloramphenicol (C), and trimethoprim-sulfamethoxazole (TMS) was determined. Antibiotic resistances in Campylobacter jejuni and non-C. jejuni isolates from surveillance and diarrhea samples were compared, and the association between personal macrolide exposure and subsequent occurrence of a macrolide-resistant Campylobacter spp. was assessed. Of 917 Campylobacter isolates, 77.4% of C. jejuni isolates and 79.8% of non-C. jejuni isolates were resistant to ciprofloxacin, while 4.9% of C. jejuni isolates and 24.8% of non-C. jejuni isolates were not susceptible to azithromycin. Of the 303 children, 33.1% had been diagnosed with a Campylobacter strain nonsusceptible to both azithromycin and ciprofloxacin. Personal macrolide exposure did not affect the risk of macrolide-resistant Campylobacter Amoxicillin and clavulanic acid (94.0%) was one of the antibiotics with the highest rates of susceptibility. There is a high incidence of quinolone- and macrolide-resistant Campylobacter infections in infants under 24 months of age. Given the lack of association between personal exposure to macrolides and a subsequent Campylobacter infection resistant to macrolides, there is a need to evaluate the source of multidrug-resistant (MDR) Campylobacter This study provides compelling evidence to propose amoxicillin/clavulanic acid as a treatment for campylobacteriosis.

Evaluating meteorological data from weather stations, and from satellites and global models for a multi-site epidemiological study.

BACKGROUND: Longitudinal and time series analyses are needed to characterize the associations between hydrometeorological parameters and health outcomes. Earth Observation (EO) climate data products derived from satellites and global model-based reanalysis have the potential to be used as surrogates in situations and locations where weather-station based observations are inadequate or incomplete. However, these products often lack direct evaluation at specific sites of epidemiological interest. METHODS: Standard evaluation metrics of correlation, agreement, bias and error were applied to a set of ten hydrometeorological variables extracted from two quasi-global, commonly used climate data products - the Global Land Data Assimilation System (GLDAS) and Climate Hazards Group InfraRed Precipitation with Stations (CHIRPS) - to evaluate their performance relative to weather-station derived estimates at the specific geographic locations of the eight sites in a multi-site cohort study. These metrics were calculated for both daily estimates and 7-day averages and for a rotavirus-peak-season subset. Then the variables from the two sources were each used as predictors in longitudinal regression models to test their association with rotavirus infection in the cohort after adjusting for covariates. RESULTS: The availability and completeness of station-based validation data varied depending on the variable and study site. The performance of the two gridded climate models varied considerably within the same location and for the same variable across locations, according to different evaluation criteria and for the peak-season compared to the full dataset in ways that showed no obvious pattern. They also differed in the statistical significance of their association with the rotavirus outcome. For some variables, the station-based records showed a strong association while the EO-derived estimates showed none, while for others, the opposite was true. CONCLUSION: Researchers wishing to utilize publicly available climate data - whether EO-derived or station based - are advised to recognize their specific limitations both in the analysis and the interpretation of the results. Epidemiologists engaged in prospective research into environmentally driven diseases should install their own weather monitoring stations at their study sites whenever possible, in order to circumvent the constraints of choosing between distant or incomplete station data or unverified EO estimates.

The Planetary Child Health & Enterics Observatory (Plan-EO): a protocol for an interdisciplinary research initiative and web-based dashboard for mapping enteric infectious diseases and their risk factors and interventions in LMICs.

Background: Diarrhea remains a leading cause of childhood illness throughout the world that is increasing due to climate change and is caused by various species of ecologically sensitive pathogens. The emerging Planetary Health movement emphasizes the interdependence of human health with natural systems, and much of its focus has been on infectious diseases and their interactions with environmental and human processes. Meanwhile, the era of big data has engendered a public appetite for interactive web-based dashboards for infectious diseases. However, enteric infectious diseases have been largely overlooked by these developments. Methods: The Planetary Child Health and Enterics Observatory (Plan-EO) is a new initiative that builds on existing partnerships between epidemiologists, climatologists, bioinformaticians, and hydrologists as well as investigators in numerous low- and middle-income countries. Its objective is to provide the research and stakeholder community with an evidence base for the geographical targeting of enteropathogen-specific child health interventions such as novel vaccines. The initiative will produce, curate, and disseminate spatial data products relating to the distribution of enteric pathogens and their environmental and sociodemographic determinants. Discussion: As climate change accelerates there is an urgent need for etiology-specific estimates of diarrheal disease burden at high spatiotemporal resolution. Plan-EO aims to address key challenges and knowledge gaps by making rigorously obtained, generalizable disease burden estimates freely available and accessible to the research and stakeholder communities. Pre-processed environmental and EO-derived spatial data products will be housed, continually updated, and made publicly available to the research and stakeholder communities both within the webpage itself and for download. These inputs can then be used to identify and target priority populations living in transmission hotspots and for decision-making, scenario-planning, and disease burden projection. Study registration: PROSPERO protocol #CRD42023384709.

The Planetary Child Health & Enterics Observatory (Plan-EO): A protocol for an interdisciplinary research initiative and web-based dashboard for mapping enteric infectious diseases and their risk factors and interventions in LMICs.

BACKGROUND: Diarrhea remains a leading cause of childhood illness throughout the world that is increasing due to climate change and is caused by various species of ecologically sensitive pathogens. The emerging Planetary Health movement emphasizes the interdependence of human health with natural systems, and much of its focus has been on infectious diseases and their interactions with environmental and human processes. Meanwhile, the era of big data has engendered a public appetite for interactive web-based dashboards for infectious diseases. However, enteric infectious diseases have been largely overlooked by these developments. METHODS: The Planetary Child Health & Enterics Observatory (Plan-EO) is a new initiative that builds on existing partnerships between epidemiologists, climatologists, bioinformaticians, and hydrologists as well as investigators in numerous low- and middle-income countries. Its objective is to provide the research and stakeholder community with an evidence base for the geographical targeting of enteropathogen-specific child health interventions such as novel vaccines. The initiative will produce, curate, and disseminate spatial data products relating to the distribution of enteric pathogens and their environmental and sociodemographic determinants. DISCUSSION: As climate change accelerates there is an urgent need for etiology-specific estimates of diarrheal disease burden at high spatiotemporal resolution. Plan-EO aims to address key challenges and knowledge gaps by making and disseminating rigorously obtained, generalizable disease burden estimates. Pre-processed environmental and EO-derived spatial data products will be housed, continually updated, and made publicly available for download to the research and stakeholder communities. These can then be used as inputs to identify and target priority populations living in transmission hotspots and for decision-making, scenario-planning, and disease burden projection. STUDY REGISTRATION: PROSPERO protocol #CRD42023384709.

Efficacy of Single-Dose Albendazole and Albendazole Plus Ivermectin for Soil-Transmitted Helminth Infection in Children in the Peruvian Amazon.

In countries where soil-transmitted helminth (STH) infections are endemic, deworming programs are recommended to reduce morbidity; however, increasing levels of resistance to benzimidazoles are of concern. In an observational study in Peru, we studied the clinical efficacy of 400 mg of albendazole 20 days after treatment among children aged 2-11 years. Of 426 participants who provided samples, 52.3% were infected with a STH, 144 (33.8%) were positive for Ascaris (41.8% light, 50.8% moderate, and 7.4% heavy infections), 147 (34.5%) were positive for Trichuris (75.2% light, 22.5% moderate, and 2.3% heavy infections), and 1.1% were positive for hookworm species (100% light infections). Additional stool samples were examined at 20, 90, and 130 days after the initial treatment. At 20 days post-administration of albendazole, the cure rate (CR) of Ascaris infection was 80.1% (95% CI: 73.5-86.7), and the egg reduction rate (ERR) was 70.8% (95% CI: 57.8-88.7); the CR for Trichuris infection was 27.1% (95% CI: 20.0-34.3), and the ERR was 29.8% (95% CI: -1.40 to 57.5). Among participants with persistent or recurrent infections with Trichuris, the combined therapy of albendazole (400 mg) and ivermectin at 600 µg/dose increased overall CR for Trichuris infection to 75.2% (95% CI: 67.3-83.2%) with an ERR of 84.2% (95% CI: 61.3-93.8%). Albendazole administration alone for the control of STH was associated with high rates of treatment failure, especially for Trichuris. Combined single doses of albendazole and ivermectin was observed to have improved efficacy.

The Enterics for Global Health (EFGH) Shigella Surveillance Study in Peru.

Background: The Enterics for Global Health (EFGH) Peru site will enroll subjects in a periurban area of the low Amazon rainforest. The political department of Loreto lags behind most of Peru in access to improved sources of water and sanitation, per capita income, children born <2.5 kg, and infant and child mortality. Chronic undernutrition as manifested by linear growth shortfalls is common, but wasting and acute malnutrition are not. Methods: The recruitment of children seeking care for acute diarrheal disease takes place at a geographic cluster of government-based primary care centers in an area where most residents are beneficiaries of free primary healthcare. Results: Rates of diarrheal disease, dysentery, and Shigella are known to be high in the region, with some of the highest rates of disease documented in the literature and little evidence in improvement over the last 2 decades. This study will update estimates of shigellosis by measuring the prevalence of Shigella by polymerase chain reaction and culture in children seeking care and deriving population-based estimates by measuring healthcare seeking at the community level. Conclusions: Immunization has been offered universally against rotavirus in the region since 2009, and in a context where adequate water and sanitation are unlikely to obtain high standards in the near future, control of principal enteropathogens through immunization may be the most feasible way to decrease the high burden of disease in the area in the near future.

Population Enumeration and Household Utilization Survey Methods in the Enterics for Global Health (EFGH): Shigella Surveillance Study.

Background: Accurate estimation of diarrhea incidence from facility-based surveillance requires estimating the population at risk and accounting for case patients who do not seek care. The Enterics for Global Health (EFGH) Shigella surveillance study will characterize population denominators and healthcare-seeking behavior proportions to calculate incidence rates of Shigella diarrhea in children aged 6-35 months across 7 sites in Africa, Asia, and Latin America. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will use a hybrid surveillance design, supplementing facility-based surveillance with population-based surveys to estimate population size and the proportion of children with diarrhea brought for care at EFGH health facilities. Continuous data collection over a 24 month period captures seasonality and ensures representative sampling of the population at risk during the period of facility-based enrollments. Study catchment areas are broken into randomized clusters, each sized to be feasibly enumerated by individual field teams. Conclusions: The methods presented herein aim to minimize the challenges associated with hybrid surveillance, such as poor parity between survey area coverage and facility coverage, population fluctuations, seasonal variability, and adjustments to care-seeking behavior.

Evolving Drivers of Brazilian SARS-CoV-2 Transmission: A Spatiotemporally Disaggregated Time Series Analysis of Meteorology, Policy, and Human Mobility.

Brazil has been severely affected by the COVID-19 pandemic. Temperature and humidity have been purported as drivers of SARS-CoV-2 transmission, but no consensus has been reached in the literature regarding the relative roles of meteorology, governmental policy, and mobility on transmission in Brazil. We compiled data on meteorology, governmental policy, and mobility in Brazil's 26 states and one federal district from June 2020 to August 2021. Associations between these variables and the time-varying reproductive number (R t ) of SARS-CoV-2 were examined using generalized additive models fit to data from the entire 15-month period and several shorter, 3-month periods. Accumulated local effects and variable importance metrics were calculated to analyze the relationship between input variables and R t . We found that transmission is strongly influenced by unmeasured sources of between-state heterogeneity and the near-recent trajectory of the pandemic. Increased temperature generally was associated with decreased transmission and increased specific humidity with increased transmission. However, the impacts of meteorology, policy, and mobility on R t varied in direction, magnitude, and significance across our study period. This time variance could explain inconsistencies in the published literature to date. While meteorology weakly modulates SARS-CoV-2 transmission, daily or seasonal weather variations alone will not stave off future surges in COVID-19 cases in Brazil. Investigating how the roles of environmental factors and disease control interventions may vary with time should be a deliberate consideration of future research on the drivers of SARS-CoV-2 transmission.

Assessment of Model Estimated and Directly Observed Weather Data for Etiological Prediction of Diarrhea.

Recent advances in clinical prediction for diarrheal etiology in low- and middle-income countries have revealed that addition of weather data improves predictive performance. However, the optimal source of weather data remains unclear. We aim to compare model estimated satellite- and ground-based observational data with weather station directly-observed data for diarrheal prediction. We used clinical and etiological data from a large multi-center study of children with diarrhea to compare these methods. We show that the two sources of weather conditions perform similarly in most locations. We conclude that while model estimated data is a viable, scalable tool for public health interventions and disease prediction, directly observed weather station data approximates the modeled data, and given its ease of access, is likely adequate for prediction of diarrheal etiology in children in low- and middle-income countries.

Effects of hydrometeorological and other factors on SARS-CoV-2 reproduction number in three contiguous countries of tropical Andean South America: a spatiotemporally disaggregated time series analysis.

Background: The COVID-19 pandemic has caused societal disruption globally, and South America has been hit harder than other lower-income regions. This study modeled the effects of six weather variables on district-level SARS-CoV-2 reproduction numbers (Rt ) in three contiguous countries of tropical Andean South America (Colombia, Ecuador, and Peru), adjusting for environmental, policy, healthcare infrastructural and other factors. Methods: Daily time-series data on SARS-CoV-2 infections were sourced from the health authorities of the three countries at the smallest available administrative level. Rt values were calculated and merged by date and unit ID with variables from a unified COVID-19 dataset and other publicly available sources for May-December, 2020. Generalized additive models were fitted. Findings: Relative humidity and solar radiation were inversely associated with SARS-CoV-2 Rt . Days with radiation above 1000 kJ/m2 saw a 1.3% reduction in Rt , and those with humidity above 50% recorded a 0.9% reduction in Rt . Transmission was highest in densely populated districts, and lowest in districts with poor healthcare access and on days with lowest population mobility. Wind speed, temperature, region, aggregate government policy response, and population age structure had little impact. The fully adjusted model explained 4.3% of Rt variance. Interpretation: Dry atmospheric conditions of low humidity increase district-level SARS-CoV-2 reproduction numbers, while higher levels of solar radiation decrease district-level SARS-CoV-2 reproduction numbers - effects that are comparable in magnitude to population factors like lockdown compliance. Weather monitoring could be incorporated into disease surveillance and early warning systems in conjunction with more established risk indicators and surveillance measures. Funding: NASA's Group on Earth Observations Work Programme (16-GEO16-0047).

Unified real-time environmental-epidemiological data for multiscale modeling of the COVID-19 pandemic.

An impressive number of COVID-19 data catalogs exist. However, none are fully optimized for data science applications. Inconsistent naming and data conventions, uneven quality control, and lack of alignment between disease data and potential predictors pose barriers to robust modeling and analysis. To address this gap, we generated a unified dataset that integrates and implements quality checks of the data from numerous leading sources of COVID-19 epidemiological and environmental data. We use a globally consistent hierarchy of administrative units to facilitate analysis within and across countries. The dataset applies this unified hierarchy to align COVID-19 epidemiological data with a number of other data types relevant to understanding and predicting COVID-19 risk, including hydrometeorological data, air quality, information on COVID-19 control policies, vaccine data, and key demographic characteristics.

Etiology of Acute Febrile Illness in the Peruvian Amazon as determined by modular formatted quantitative PCR: A Protocol for RIVERA, a Health Facility-Based Case-Control Study.

Background: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. Methods: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. Discussion: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 hours and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific, prevalent pathogens as a cause of acute illness. Study Registration: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Intestinal Colonization With Bifidobacterium longum Subspecies Is Associated With Length at Birth, Exclusive Breastfeeding, and Decreased Risk of Enteric Virus Infections, but Not With Histo-Blood Group Antigens, Oral Vaccine Response or Later Growth in Three Birth Cohorts.

Bifidobacterium longum subspecies detected in infant stool have been associated with numerous subsequent health outcomes and are potential early markers of deviation from healthy developmental trajectories. This analysis derived indicators of carriage and early colonization with B. infantis and B. longum and quantified their associations with a panel of early-life exposures and outcomes. In a sub-study nested within a multi-site birth cohort, extant stool samples from infants in Bangladesh, Pakistan and Tanzania were tested for presence and quantity of two Bifidobacterium longum subspecies. The results were matched to indicators of nutritional status, enteropathogen infection, histo-blood group antigens, vaccine response and feeding status and regression models were fitted to test for associations while adjusting for covariates. B. infantis was associated with lower quantity of and decreased odds of colonization with B. longum, and vice versa. Length at birth was associated with a 0.36 increase in log10 B. infantis and a 0.28 decrease in B. longum quantity at 1 month of age. B. infantis colonization was associated with fewer viral infections and small reductions in the risk of rotavirus and sapovirus infections, but not reduced overall diarrheal disease risk. No associations with vaccine responses, HBGAs or later nutritional status were identified. Suboptimal intrauterine growth and a shorter duration of exclusive breastfeeding may predispose infants to early intestinal colonization with the B. longum subspecies at the expense of B. infantis, thus denying them potential benefits of reduced enteric virus episodes.

Enteropathy Markers in Early Life Were Associated with Adipokine, Apolipoprotein, and Cytokine Profiles Consistent with an Adverse Cardiometabolic Disease Risk Profile Later in Childhood in a Peruvian Birth Cohort.

Metabolic syndrome is a cluster of risk factors for cardiovascular disease afflicting more than 1 billion people worldwide and is increasingly being identified in younger age groups and in socioeconomically disadvantaged settings in the global south. Enteropathogen exposure and environmental enteropathy in infancy may contribute to metabolic syndrome by disrupting the metabolic profile in a way that is detectable in cardiometabolic markers later in childhood. A total of 217 subjects previously enrolled in a birth cohort in Amazonian Peru were monitored annually from ages 2 to 5 years. A total of 197 blood samples collected in later childhood were analyzed for 37 cardiometabolic biomarkers, including adipokines, apolipoproteins, cytokines, which were matched to extant early-life markers of enteropathy ascertained between birth and 2 years. Multivariate and multivariable regression models were fitted to test for associations, adjusting for confounders. Fecal and urinary markers of intestinal permeability and inflammation (myeloperoxidase, lactulose, and mannitol) measured in infancy were associated with later serum concentrations of soluble CD40-ligand, a proinflammatory cytokine correlated with adverse metabolic outcomes. Fecal myeloperoxidase was also associated with later levels of omentin-1. Enteric protozoa exposure showed stronger associations with later cardiometabolic markers than viruses, bacteria, and overall diarrheal episodes. Early-life enteropathy markers were associated with altered adipokine, apolipoprotein, and cytokine profiles later in childhood consistent with an adverse cardiometabolic disease risk profile in this cohort. Markers of intestinal permeability and inflammation measured in urine (lactulose, mannitol) and stool (myeloperoxidase, protozoal infections) during infancy may predict metabolic syndrome in adulthood.