Rotavirus infections and climate variability in Dhaka, Bangladesh: a time-series analysis.

Attempts to explain the clear seasonality of rotavirus infections have been made by relating disease incidence to climate factors; however, few studies have disentangled the effects of weather from other factors that might cause seasonality. We investigated the relationships between hospital visits for rotavirus diarrhoea and temperature, humidity and river level, in Dhaka, Bangladesh, using time-series analysis adjusting for other confounding seasonal factors. There was strong evidence for an increase in rotavirus diarrhoea at high temperatures, by 40.2% for each 1 degrees C increase above a threshold (29 degrees C). Relative humidity had a linear inverse relationship with the number of cases of rotavirus diarrhoea. River level, above a threshold (4.8 m), was associated with an increase in cases of rotavirus diarrhoea, by 5.5% per 10-cm river-level rise. Our findings provide evidence that factors associated with high temperature, low humidity and high river-level increase the incidence of rotavirus diarrhoea in Dhaka

Developing a forecasting model for cholera incidence in Dhaka megacity through time series climate data.

Cholera, an acute diarrheal disease spread by lack of hygiene and contaminated water, is a major public health risk in many countries. As cholera is triggered by environmental conditions influenced by climatic variables, establishing a correlation between cholera incidence and climatic variables would provide an opportunity to develop a cholera forecasting model. Considering the auto-regressive nature and the seasonal behavioral patterns of cholera, a seasonal-auto-regressive-integrated-moving-average (SARIMA) model was used for time-series analysis during 2000-2013. As both rainfall (r = 0.43) and maximum temperature (r = 0.56) have the strongest influence on the occurrence of cholera incidence, single-variable (SVMs) and multi-variable SARIMA models (MVMs) were developed, compared and tested for evaluating their relationship with cholera incidence. A low relationship was found with relative humidity (r = 0.28), ENSO (r = 0.21) and SOI (r = -0.23). Using SVM for a 1 °C increase in maximum temperature at one-month lead time showed a 7% increase of cholera incidence (p < 0.001). However, MVM (AIC = 15, BIC = 36) showed better performance than SVM (AIC = 21, BIC = 39). An MVM using rainfall and monthly mean daily maximum temperature with a one-month lead time showed a better fit (RMSE = 14.7, MAE = 11) than the MVM with no lead time (RMSE = 16.2, MAE = 13.2) in forecasting. This result will assist in predicting cholera risks and better preparedness for public health management in the future

Genome-Wide Association Study of Cryptosporidiosis in Infants Implicates PRKCA.

Diarrhea is a major cause of both morbidity and mortality worldwide, especially among young children. Cryptosporidiosis is a leading cause of diarrhea in children, particularly in South Asia and sub-Saharan Africa, where it is responsible for over 200,000 deaths per year. Beyond the initial clinical presentation of diarrhea, it is associated with long-term sequelae such as malnutrition and neurocognitive developmental deficits. Risk factors include poverty and overcrowding, and yet not all children with these risk factors and exposure are infected, nor do all infected children develop symptomatic disease. One potential risk factor to explain these differences is their human genome. To identify genetic variants associated with symptomatic cryptosporidiosis, we conducted a genome-wide association study (GWAS) examining 6.5 million single nucleotide polymorphisms (SNPs) in 873 children from three independent cohorts in Dhaka, Bangladesh, namely, the Dhaka Birth Cohort (DBC), the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) study, and the Cryptosporidiosis Birth Cohort (CBC). Associations were estimated separately for each cohort under an additive model, adjusting for length-for-age Z-score at 12 months of age, the first two principal components to account for population substructure, and genotyping batch. The strongest meta-analytic association was with rs58296998 (P = 3.73 × 10-8), an intronic SNP and expression quantitative trait locus (eQTL) of protein kinase C alpha (PRKCA). Each additional risk allele conferred 2.4 times the odds of Cryptosporidium-associated diarrhea in the first year of life. This genetic association suggests a role for protein kinase C alpha in pediatric cryptosporidiosis and warrants further investigation.IMPORTANCE Globally, diarrhea remains one of the major causes of pediatric morbidity and mortality. The initial symptoms of diarrhea can often lead to long-term consequences for the health of young children, such as malnutrition and neurocognitive developmental deficits. Despite many children having similar exposures to infectious causes of diarrhea, not all develop symptomatic disease, indicating a possible role for human genetic variation. Here, we conducted a genetic study of susceptibility to symptomatic disease associated with Cryptosporidium infection (a leading cause of diarrhea) in three independent cohorts of infants from Dhaka, Bangladesh. We identified a genetic variant within protein kinase C alpha (PRKCA) associated with higher risk of cryptosporidiosis in the first year of life. These results indicate a role for human genetics in susceptibility to cryptosporidiosis and warrant further research to elucidate the mechanism

Enteric viral pathogens and child growth among under-five children: findings from South Asia and sub-Saharan Africa.

Enteric viral pathogens are associated with a significant burden of childhood morbidity and mortality. We investigated the relationship between viral pathogens and child growth among under-5 children. We analyzed data from 5572/22,567 children enrolled in the Global Enteric Multicenter Study across seven study sites (2007-2011). Multiple linear regression was used to examine the association between the viral pathogens and changes of length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-scores, stratified by diarrheal symptoms and adjusted for potential covariates. Rotavirus (18.51%) and norovirus (7.33%) were the most prevalent enteric viral pathogens among symptomatic and asymptomatic under-5 children, respectively. Infection with individual enteric viral pathogens hurts child growth in asymptomatic children. However, the relationship with HAZ was less clear and statistically non-significant. On the other hand, the combined viral pathogens demonstrated a strong negative influence on child growth [WAZ: β coef.: - 0.10 (95%, CI - 0.15, - 0.05); P < 0.001 and WHZ: β: - 0.12 (95% CI - 0.17, - 0.07); P < 0.001] among asymptomatic children. Infection with any viral pathogen was associated with growth shortfalls [HAZ: β: - 0.05 (95% CI - 0.09, 0.00); P = 0.03 and WAZ: β: - 0.11 (95% CI - 0.16, - 0.07); P < 0.001 and WHZ: β: - 0.13 (95% CI - 0.18, - 0.09); P < 0.001], though the relationship with HAZ was less evident and became statistically non-significant in older children. Notably, among symptomatic children with moderate-to-severe diarrhea, individual enteric viral pathogens, as well as the combined effects of these pathogens [WHZ: β: 0.07; (95% CI 0.01, 0.14); P = 0.03] and the presence of any virus [HAZ: β: 0.09 (95% CI 0.05, 0.13) & WAZ: β: 0.08 (95% CI 0.03, 0.12); P < 0.001], exhibited positive effects on child growth. While previous studies hypothesized that several viral pathogens had a conflicting controversial role in child growth, we find clear indications that enteric viral pathogens are associated with growth shortfalls, specifically among asymptomatic children. These findings highlight the need for preventive strategies targeting children with enteric viral pathogens, which could address the consequences of growth faltering

Health Education Through a Campaign and mHealth to Enhance Knowledge and Quality of Life Among Patients With Chronic Kidney Disease in Bangladesh: Protocol for a Randomized Controlled Trial

BACKGROUND: Despite the growing burden of chronic kidney disease (CKD), disease knowledge and understanding are still lacking, especially in Bangladesh. OBJECTIVE: The aim of this study was to evaluate the outcome of a health education intervention in order to enhance knowledge, health-related quality of life (QOL), and motivation regarding healthy lifestyles among rural and periurban adults suffering from CKD. METHODS: A parallel-group (1:1) randomized controlled trial is ongoing in the Mirzapur subdistrict, Bangladesh, where two groups of patients with CKD are being compared. Patients aged 18 years and over with CKD (stages 1-3) were enrolled in November 2020. Patients were randomly allocated into either the intervention group (n=63) or the control group (n=63). The control group received usual treatment, while the intervention group received health education through a CKD campaign facilitated by a nephrologist and via mHealth (ie, periodic mobile phone calls) from community health workers. Both groups were followed up for a period of 6 months. The primary endpoint is patients' increased knowledge measured using the Chronic Kidney Disease Knowledge Questionnaire. The secondary endpoints are improved QOL measured using the standardized EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire as well as improvements in the levels of blood pressure, BMI, serum creatinine, fasting blood sugar, hemoglobin, cholesterol, high-density lipoprotein cholesterol, triglyceride, serum uric acid, blood urea nitrogen, and albumin to creatinine ratio. RESULTS: Enrollment of participants began in November 2020; the intervention and follow-up were completed in May 2021. We enrolled 126 patients in the study. Patients' mean ages were 57.97 (SD 15.03) years in the control group and 57.32 (SD 14.37) years in the intervention group. There were 45 out of 63 (71%) females in the control group and 38 out of 63 (60%) females in the intervention group. In addition, there were 38 out of 63 (60%) literate patients in the control group and 33 out of 63 (52%) literate patients in the intervention group. CONCLUSIONS: It is expected that a combined approach, incorporating both a CKD campaign and mHealth, for health education may be an effective tool for increasing knowledge and improving QOL among patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094831; https://clinicaltrials.gov/ct2/show/NCT04094831. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30191

Anthropometric Indices of Giardia-Infected Under-Five Children Presenting with Moderate-to-Severe Diarrhea and Their Healthy Community Controls: Data from the Global Enteric Multicenter Study

Among all intestinal parasitosis, giardiasis has been reported to be associated with delayed growth in malnourished children under 5 living in low- and middle-income countries. Relevant data on the nutritional status of children aged 0-59 months presenting with moderate-to-severe diarrhea (MSD) and giardia infection were collected from sentinel health facilities of the Global Enteric Multicenter Study's (GEMS) seven field settings, placed in diverse countries of Sub-Saharan Africa and South Asia between, December 2007 and February 2011. Then, this study analyzed a robust dataset of study participants (n = 22,569). Children having giardiasis with MSD constituted as cases (n = 1786), and those without MSD constituted as controls (n = 3470). Among the seven field sites, symptomatic giardiasis was 15% and 22% in Asian and African sites, respectively, whereas asymptomatic giardia infection (healthy without MSD) in Asian and African sites was 21.7% and 30.7%, respectively. Wasting and underweight were more frequently associated and stunting less often associated with symptomatic giardiasis (for all, p < 0.001). Symptomatic giardiasis had a significant association with worsening of nutritional status in under-five children. Improved socio-economic profile along with proper sanitation and hygienic practices are imperative to enhance child nutritional status, particularly in resource limited settings

A comparison of traditional diarrhoea measurement methods with microbiological and biochemical indicators : a cross-sectional observational study in the Cox's Bazar displaced persons camp

Background Water, Sanitation, and Hygiene (WASH) systems aim to reduce the spread of enteric pathogens, particularly amongst children under five years old. The most common primary outcome of WASH trials is carer-reported diarrhoea. We evaluate different diarrhoea survey instruments as proxy markers of enteric pathogen presence in stool. Methods We recruited 800 community-based participants from the Cox's Bazar Displaced Person's Camp in Bangladesh, split evenly between the rainy (July/August 2020) and dry (November/December 2020) periods. Participants were randomized evenly into either a standard survey asking carers if their child under five years old has had diarrhoea in the past fortnight, or a pictorial survey asking carers to pick from a pictorial chart which stools their child under five years old has had in the past fortnight. We collected stools from a random sub-sample of 120. Stools were examined visually, and tested for proteins associated with enteric infection and 16 enteric pathogens. We calculated sensitivities and specificities for each survey type, visual examination, and proteins with respect to enteric pathogen presence. Findings The sensitivity of the standard survey for enteric pathogen presence was 0.49[95%CI:0.32,0.66] and the specificity was 0.65[0.41,0.85]. Similar sensitivities and specificities were observed for pictorial survey, visual inspection, and proteins. Interpretation While diarrhoea is an important sign in clinical practice it appears that it is a poor proxy for enteric pathogen presence in stool in epidemiological surveys. When enteric infection is of interest, this should be measured directly

The clinical presentation of culture-positive and culture-negative, qPCR-attributable shigellosis in the Global Enteric Multicenter Study and derivation of a Shigella severity score: implications for pediatric Shigella vaccine trials

BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, qPCR-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (n=745), culture-negative/qPCR-attributable Shigella cases (n=852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age < 12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity