Associations between household-level exposures and all-cause diarrhea and pathogen-specific enteric infections in children enrolled in five sentinel surveillance studies

Diarrheal disease remains a major cause of childhood mortality and morbidity causing poor health and economic outcomes. In low-resource settings, young children are exposed to numerous risk factors for enteric pathogen transmission within their dwellings, though the relative importance of different transmission pathways varies by pathogen species. The objective of this analysis was to model associations between five household-level risk factors-water, sanitation, flooring, caregiver education, and crowding-and infection status for endemic enteric pathogens in children in five surveillance studies. Data were combined from 22 sites in which a total of 58,000 stool samples were tested for 16 specific enteropathogens using qPCR. Risk ratios for pathogen- and taxon-specific infection status were modeled using generalized linear models along with hazard ratios for all-cause diarrhea in proportional hazard models, with the five household-level variables as primary exposures adjusting for covariates. Improved drinking water sources conferred a 17% reduction in diarrhea risk; however, the direction of its association with particular pathogens was inconsistent. Improved sanitation was associated with a 9% reduction in diarrhea risk with protective effects across pathogen species and taxa of around 10-20% risk reduction. A 9% reduction in diarrhea risk was observed in subjects with covered floors, which were also associated with decreases in risk for zoonotic enteropathogens. Caregiver education and household crowding showed more modest, inconclusive results. Combining data from diverse sites, this analysis quantified associations between five household-level exposures on risk of specific enteric infections, effects which differed by pathogen species but were broadly consistent with hypothesized transmission mechanisms. Such estimates may be used within expanded water, sanitation, and hygiene (WASH) programs to target interventions to the particular pathogen profiles of individual communities and prioritize resources

Associations between eight earth observation-derived climate variables and enteropathogen infection: An independent participant data meta-analysis of surveillance studies with broad spectrum nucleic acid diagnostics

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen‐specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens—adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia—was matched by date with hydrometeorological variables from a global Earth observation dataset—precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non‐linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7‐day average temperatures—a relative risk of 0.76 (95% confidence interval: 0.69–0.85) above 28°C—while ETEC risk increased by almost half, 1.43 (1.36–1.50), in the 20–35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species\u27 risk increased following lower‐than‐average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea‐causing agents as the global climate changes

A longitudinal study of household water, sanitation, and hygiene characteristics and environmental enteropathy markers in children less than 24 months in Iquitos, Peru

Funding Information: Financial support: The MAL-ED is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, and the National Institutes of Health, Fogarty International Center. While conducting this work, Natalie Exum was supported by The NSF IGERT Grant 1069213, The Osprey Foundation of Maryland Grant 1602030014, the Johns Hopkins Water Institute, Johns Hopkins Fisher Center Discovery Program Grant 010 KOS2015, The Kazuyoshi Kawata fund in Sanitary Engineering and Science, and the Dr. C. W. Kruse Memorial Fund Scholarship. Publisher Copyright: © 2018 by The American Society of Tropical Medicine and Hygiene.Peer reviewedPublisher PD

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

Funding Information: Financial support. This work was funded by the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project funded by the Bill & Melinda Gates Foundation (BMGF) (BMGF-47075), the Foundation for the National Institutes of Health, and the National Institutes of Health, Fogarty International Center, whereas additional support was obtained from BMGF for the examination of host innate factors on enteric disease risk and enteropathy (Grants OPP1066146 and OPP1152146; to M. N. K.). Additional funding was obtained from teh Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins School of Medicine (to M. N. K) and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institues of health 1UL1TR001079. Acknowledgments. We thank the participants, their families, and the study community for their dedicated time and effort to better the understanding the transmission and more enduring impact of enteric infections in early childhood. We also thank the following: Jan Vinje (Centers for Disease Control and Prevention) for critical input and manuscript review; Dr. Leah Jager for consultation regarding the statistical analysis; Dr. Ben Jann (University of Bern, Switzerland) for guidance in generating the figures; Christine Szymanski for insight and encouragement, particularly regarding Campylobacter infection and disease patency; Chris Damman and Anita Zaidi for input on early iterations of the analysis; and Dick Guerrant for final reflections.Peer reviewe

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

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.publishedVersionPeer reviewe

Spatial variation in housing construction material in low- and middle-income countries: A Bayesian spatial prediction model of a key infectious diseases risk factor and social determinant of health.

Housing infrastructure and quality is a major determinant of infectious disease risk and other health outcomes in regions where vector borne, waterborne and neglected tropical diseases are endemic. It is important to quantify the geographical distribution of improvements to dwelling components to identify and target resources towards populations at risk. This study aimed to model the sub-national spatial variation in housing materials using covariates with quasi-global coverage and use the resulting estimates to map predicted coverage across the world's low- and middle-income countries. Data on materials used in dwelling construction were sourced from nationally representative household surveys conducted since 2005. Materials used for construction of flooring, walls, and roofs were reclassified as improved or unimproved. Households lacking location information were georeferenced using a novel methodology. Environmental and demographic spatial covariates were extracted at those locations for use as model predictors. Integrated nested Laplace approximation models were fitted to obtain, and map predicted probabilities for each dwelling component. The dataset compiled included information from households in 283,000 clusters from 350 surveys. Low coverage of improved housing was predicted across the Sahel and southern Sahara regions of Africa, much of inland Amazonia, and areas of the Tibetan plateau. Coverage of improved roofs and walls was high in the Central Asia, East Asia and Pacific and Latin America and the Caribbean regions. Improvements in all three components, but most notably floors, was low in Sub-Saharan Africa. The strongest determinants of dwelling component quality related to urbanization and economic development, suggesting that programs should focus on supply-side interventions, providing resources for housing improvements directly to the populations that need them. These findings are made available to researchers as files that can be imported into a GIS for integration into relevant analyses to derive improved estimates of preventable health burdens attributed to housing

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

Abstract 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 (Rt) 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 Rt. 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 Rt 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

The Planetary Child Health and 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 Low- and Middle-Income Countries

Abstract Background: Diarrhea remains a leading cause of childhood illness throughout the world 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: To date Plan-EO has compiled data from 23 studies comprising almost 80,000 stool samples from 35,000 children aged 0 – 59 months at 80 sites in 24 countries and georeferenced to over 9,000 unique locations, with DUAs for two further studies under negotiation. An initial analysis of Shigella has been published and has yielded detailed prediction maps.Results like these can be used to identify and target priority populations living in transmission hotspots and to provide an urgently needed evidence base for decision-making, scenario-planning. Study registration: PROSPERO protocol #CRD42023384709</jats:p