Cholera forecast for Dhaka, Bangladesh, with the 2015-2016 El Nino: Lessons learned

A substantial body of work supports a teleconnection between the El Nino-Southern Oscillation (ENSO) and cholera incidence in Bangladesh. In particular, high positive anomalies during the winter (Dec-Feb) in sea surface temperatures (SST) in the tropical Pacific have been shown to exacerbate the seasonal outbreak of cholera following the monsoons from August to November. Climate studies have indicated a role of regional precipitation over Bangladesh in mediating this long-distance effect. Motivated by this previous evidence, we took advantage of the strong 2015-2016 El Nino event to evaluate the predictability of cholera dynamics for the city in recent times based on two transmission models that incorporate SST anomalies and are fitted to the earlier surveillance records starting in 1995. We implemented a mechanistic temporal model that incorporates both epidemiological processes and the effect of ENSO, as well as a previously published statistical model that resolves space at the level of districts (thanas). Prediction accuracy was evaluated with "out-of-fit" data from the same surveillance efforts (post 2008 and 2010 for the two models respectively), by comparing the total number of cholera cases observed for the season to those predicted by model simulations eight to twelve months ahead, starting in January each year. Although forecasts were accurate for the low cholera risk observed for the years preceding the 2015-2016 El Nino, the models also predicted a high probability of observing a large outbreak in fall 2016. Observed cholera cases up to Oct 2016 did not show evidence of an anomalous season. We discuss these predictions in the context of regional and local climate conditions, which show that despite positive regional rainfall anomalies, rainfall and inundation in Dhaka remained low. Possible explanations for these patterns are given together with future implications for cholera dynamics and directions to improve their prediction for the city

Health care seeking for Childhood Diarrhea in Developing Countries: Evidence from Seven Sites in Africa and Asia

We performed serial Health Care Utilization and Attitudes Surveys (HUASs) among caretakers of children ages 0–59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case-control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0–11 months of age), from 0.4% to 4.7% for toddlers (12–23 months of age), and from 0.3% to 2.4% for preschoolers (24–59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15–56%, 17–64%, and 7–33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial HUASs as a tool for optimizing operational and methodological issues related to the performance of a large case-control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings

Cholera in Bangladesh: Climatic Components of Seasonal Variation

Background: The mechanisms underlying the seasonality of cholera are still not fully understood, despite long-standing recognition of clear bimodal seasonality in Bangladesh. We aimed to quantify the contribution of climatic factors to seasonal variations in cholera incidence. Methods: We investigated the association of seasonal and weather factors with the weekly number of cholera patients in Dhaka, Bangladesh, using Poisson regression models. The contribution of each weather factor (temperature and high and low rainfall) to seasonal variation was estimated as the mean over the study period (1983-2008) for each week of the year of each weather term. Fractions of the number of cholera patients attributed to each weather factor, assuming all values were constant at their minimum risk levels throughout the year, were estimated for spring and monsoon seasons separately. Results: Lower temperature predicted a lower incidence of cholera in the first 15 weeks of the year. Low rainfall predicted a peak in spring, and high rainfall predicted a peak at the end of the monsoon. The risk predicted from all the weather factors combined showed a broadly bi-modal pattern, as observed in the raw data. Low rainfall explained 18% of the spring peak, and high rainfall explained 25% of the peak at the end of the monsoon. Conclusions: Seasonal variation in temperature and rainfall contribute to cholera incidence in complex ways, presumably in interaction with unmeasured environmental or behavioral factors

In ricordo di Paolo Sylos Labini

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved

Is heat wave a predictor of diarrhoea in Dhaka, Bangladesh? A time-series analysis in a South Asian tropical monsoon climate

While numerous studies have assessed the association between temperature and diarrhoea in various locations, evidence of relationship between heat wave and diarrhoea is scarce. We defined elevated daily mean and maximum temperature over the 95th and 99th percentiles lasting for at least one day between March to October 1981–2010 as TAV95 and TAV99 and D95 and D99 heat wave, respectively. We investigated the association between heat wave and daily counts of hospitalisations for all-cause diarrhoea in Dhaka, Bangladesh using time series regression analysis employing constrained distributed lag-linear models. Effects were assessed for all ages and children aged under 5 years of age. Diarrhoea hospitalisation increased by 6.7% (95% CI: 4.6%– 8.9%), 8.3% (3.7–13.1), 7.0 (4.8–9.3) and 7.4 (3.1–11.9) in all ages on a TAV95, TAV99, D95 and D99 heat wave day, respectively. These effects were more pronounced for under-5 children with an increase of 13.9% (95% CI: 8.3–19.9), 24.2% (11.3–38.7), 17.0 (11.0–23.5) and 19.5 (7.7–32.6) in diarrhoea hospitalisations on a TAV95, TAV99, D95 and D99 heat wave day, respectively. At lags of 3 days, we noticed a negative association indicating a ‘harvesting’ effect. Our findings suggest that heat wave was a significant risk factor for diarrhoea hospitalisation in Dhaka. Further research is needed to elucidate the causal pathways and identify the preventive measures necessary to mitigate the impacts of heat waves on diarrhoea. Given that no heat wave definitions exist for Dhaka, these results may help to define heat waves for Dhaka and trigger public health interventions including heat alerts to prevent heat-related morbidity in Dhaka, Bangladesh.publishedVersio

Sanitation and Hygiene-Specific Risk Factors for Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study, 2007-2011: Case-Control Study.

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved

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

Determinants of linear growth faltering among children with moderate-to-severe diarrhea in the global enteric multicenter study

Background: Moderate-to-severe diarrhea (MSD) in the first 2 years of life can impair linear growth. We sought to determine risk factors for linear growth faltering and to build a clinical prediction tool to identify children most likely to experience growth faltering following an episode of MSD.Methods: Using data from the Global Enteric Multicenter Study of children 0-23 months old presenting with MSD in Africa and Asia, we performed log-binomial regression to determine clinical and sociodemographic factors associated with severe linear growth faltering (loss of ≥ 0.5 length-for-age z-score [LAZ]). Linear regression was used to estimate associations with ΔLAZ. A clinical prediction tool was developed using backward elimination of potential variables, and Akaike Information Criterion to select the best fit model.Results: Of the 5902 included children, mean age was 10 months and 43.2% were female. Over the 50-90-day follow-up period, 24.2% of children had severe linear growth faltering and the mean ΔLAZ over follow-up was - 0.17 (standard deviation [SD] 0.54). After adjustment for age, baseline LAZ, and site, several factors were associated with decline in LAZ: young age, acute malnutrition, hospitalization at presentation, non-dysenteric diarrhea, unimproved sanitation, lower wealth, fever, co-morbidity, or an IMCI danger sign. Compared to children 12-23 months old, those 0-6 months were more likely to experience severe linear growth faltering (adjusted prevalence ratio [aPR] 1.97 [95% CI 1.70, 2.28]), as were children 6-12 months of age (aPR 1.72 [95% CI 1.51, 1.95]). A prediction model that included age, wasting, stunting, presentation with fever, and presentation with an IMCI danger sign had an area under the ROC (AUC) of 0.67 (95% CI 0.64, 0.69). Risk scores ranged from 0 to 37, and a cut-off of 21 maximized sensitivity (60.7%) and specificity (63.5%).Conclusion: Younger age, acute malnutrition, MSD severity, and sociodemographic factors were associated with short-term linear growth deterioration following MSD. Data routinely obtained at MSD may be useful to predict children at risk for growth deterioration who would benefit from interventions

Immunologic Responses to Vibrio cholerae in Patients Co-Infected with Intestinal Parasites in Bangladesh

Vibrio cholerae causes cholera, a severe diarrhea that may lead to fatal dehydration if not treated. Cholera occurs mostly in impoverished areas where there is poor sanitation and intestinal parasites are also common. However, little is known about the relationship between intestinal parasites and cholera. To learn about how parasites affect the immune response to Vibrio cholerae, this article describes 361 patients with cholera, including 53 who had intestinal parasitic infection. We found that cholera patients with parasitic worms had decreased antibody response to cholera toxin. The decrease was greatest in IgA antibodies, which are secreted in the intestine. However, patients with worm infection did not have a difference in their immune response to lipopolysaccharide, a sugar-based molecule that is important for immunity. These different effects on the immune response to cholera toxin and lipopolysaccharide could be explained by the effect of parasitic infection on CD4+ T cells, a type of cell that influences the development of the antibody response to proteins such as cholera toxin but may not always influence the response to sugar-based molecules. The finding that worm infection is associated with decreased immune responses to cholera provides an additional reason for deworming in cholera-endemic areas

The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).

Background: The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Methods: Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Findings: Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27–4.67) and 3.18 (95% CI, 1.85–4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73–2.08) and 1.36 (95% CI, 0.66–2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33–5.01) and 4.88 (95% CI, 0.82–8.92) in infants and 4.04 (95% CI, 0.56–7.51) and 4.71 (95% CI, 0.24–9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. Conclusions: The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies