Clinical Cholera Surveillance Sensitivity in Bangladesh and Implications for Large-Scale Disease Control.

BACKGROUND: A surveillance system that is sensitive to detecting high burden areas is critical for achieving widespread disease control. In 2014, Bangladesh established a nationwide, facility-based cholera surveillance system for Vibrio cholerae infection. We sought to measure the sensitivity of this surveillance system to detect cases to assess whether cholera elimination targets outlined by the Bangladesh national control plan can be adequately measured. METHODS: We overlaid maps of nationally representative annual V cholerae seroincidence onto maps of the catchment areas of facilities where confirmatory laboratory testing for cholera was conducted, and we identified its spatial complement as surveillance greyspots, areas where cases likely occur but go undetected. We assessed surveillance system sensitivity and changes to sensitivity given alternate surveillance site selection strategies. RESULTS: We estimated that 69% of Bangladeshis (111.7 million individuals) live in surveillance greyspots and that 23% (25.5 million) of these individuals live in areas with the highest V cholerae infection rates. CONCLUSIONS: The cholera surveillance system in Bangladesh has the ability to monitor progress towards cholera elimination goals among 31% of the country's population, which may be insufficient for accurately measuring progress. Increasing surveillance coverage, particularly in the highest risk areas, should be considered.

Can Existing Improvements of Water, Sanitation, and Hygiene (WASH) in Urban Slums Reduce the Burden of Typhoid Fever in These Settings?

BACKGROUND: Sustained investments in water, sanitation, and hygiene (WASH) have lagged in resource-poor settings; incremental WASH improvements may, nonetheless, prevent diseases such as typhoid in disease-endemic populations. METHODS: Using prospective data from a large cohort in urban Kolkata, India, we evaluated whether baseline WASH variables predicted typhoid risk in a training subpopulation (n = 28 470). We applied a machine learning algorithm to the training subset to create a composite, dichotomous (good, not good) WASH variable based on 4 variables, and evaluated sensitivity and specificity of this variable in a validation subset (n = 28 470). We evaluated in Cox regression models whether residents of "good" WASH households experienced a lower typhoid risk after controlling for potential confounders. We constructed virtual clusters (radius 50 m) surrounding each household to evaluate whether a prevalence of good WASH practices modified the typhoid risk in central household members. RESULTS: Good WASH practices were associated with protection in analyses of all households (hazard ratio [HR] = 0.57; 95% confidence interval [CI], .37-.90; P = .015). This protection was evident in persons ≥5 years old at baseline (HR = 0.47; 95% CI, .34-.93; P = .005) and was suggestive, though not statistically significant, in younger age groups (HR = 0.61; 95% CI, .27-1.38; P = .235). The level of surrounding household good WASH coverage was also associated with protection (HR = 0.988; 95% CI, .979-.996; P = .004, for each percent coverage increase). However, collinearity between household WASH and WASH coverage prevented an assessment of their independent predictive contributions. CONCLUSIONS: In this typhoid-endemic setting, natural variation in household WASH was associated with typhoid risk. If replicated elsewhere, these findings suggest that WASH improvements may enhance typhoid control, short of major infrastructural investments.

Stunting, recovery from stunting and puberty development in the MINIMat cohort, Bangladesh.

AIM: This paper aimed to analyse the association between small for size at birth, stunting, recovery from stunting and pubertal development in a rural Bangladeshi cohort. METHODS: The participants were 994 girls and 987 boys whose mothers participated in the Maternal and Infant Nutrition Interventions in Matlab trial. The birth cohort was followed from birth to puberty 2001-2017. Pubertal development according to Tanner was self-assessed. Age at menarche was determined and in boys, consecutive height measurements were used to ascertain whether pubertal growth spurt had started. The exposures and outcomes were modelled by Cox's proportional hazards analyses and logistic regression. RESULTS: There was no difference in age at menarche between girls that were small or appropriate for gestational age at birth. Boys born small for gestational age entered their pubertal growth spurt later than those with appropriate weight. Children who were stunted had later pubertal development, age at menarche and onset of growth spurt than non-stunted children. Children who recovered from infant or early childhood stunting had similar pubertal development as non-stunted children. CONCLUSION: Infant and childhood stunting was associated with a later pubertal development. Recovery from stunting was not associated with earlier puberty in comparison with non-stunted children.

Unmasking herd protection by an oral cholera vaccine in a cluster-randomized trial.

BACKGROUND: Several studies have shown that inactivated, whole-cell oral cholera vaccines (OCVs) confer both direct protection on vaccinees and herd protection on populations. Because our earlier cluster-randomized effectiveness trial (CRT) in urban Bangladesh failed to detect OCV herd protection, we reanalysed the trial to assess whether herd effects were masked in our original analysis. METHODS: A total of 267 270 persons were randomized to 90 approximately equal-sized clusters. In 60 clusters persons aged 1 year and older were eligible to receive OCV and in 30 clusters persons received no intervention and served as controls. We analysed OCV protection against severely dehydrating cholera for the entire clusters, as in our original analysis, and for subclusters consisting of residents of innermost households. We hypothesized that if OCV herd protection was attenuated by cholera transmission into the clusters from the outside in this densely populated setting, herd protection would be most evident in the innermost households. RESULTS: During 2 years of follow-up of all residents of the clusters, total protection (protection of OCV recipients relative to control residents) was 58% [95% confidence interval (CI): 43%, 70%; P<0.0001], indirect protection (protection of non-OCV recipients in OCV clusters relative to control participants) was 16% (95% CI: -20%, 41%; P=0.35) and overall OCV protection (protection of all residents in the OCV clusters relative to control residents) was 46% (95% CI: 30%, 59%; P<0.0001). Analyses of the inner 75% and 50% households of the clusters showed similar findings. However, total protection was 75% (95% CI: 50%, 87%, P<0.0001), indirect protection 52% (95% CI: -9%, 79%; P=0.08) and overall protection 72% (95% CI: 49%, 84%; P<0.0001) for the innermost 25% households. CONCLUSION: Consistent with past studies, substantial OCV herd protective effects were identified, but were unmasked only by analysing innermost households of the clusters. Caution is needed in defining clusters for analysis of vaccine herd effects in CRTs of vaccines.

Effects of pre- and postnatal nutrition interventions on child growth and body composition: the MINIMat trial in rural Bangladesh.

BACKGROUND: Nutritional insults and conditions during fetal life and infancy influence subsequent growth and body composition of children. OBJECTIVES: Effects of maternal food and micronutrient supplementation and exclusive breastfeeding counseling on growth of offspring aged 0-54 months and their body composition at 54 months of age were studied. METHODS: In the MINIMat trial (ISRCTN16581394) in Matlab, Bangladesh, pregnant women were randomized to early (around 9 weeks) or usual invitation (around 20 weeks) to food supplementation and to one of the three daily micronutrient supplements: 30-mg Fe and 400-µg folic acid (Fe30F), 60-mg Fe and 400-µg folic acid (Fe60F), and multiple micronutrient supplements (MMS). The supplements were also randomized to exclusive breastfeeding (EBF) counseling or to usual health messages. RESULTS: No differences in background characteristics were observed among the intervention groups. There was also no differential effect of prenatal interventions on birthweight or birthlength. Early food supplementation reduced the level of stunting from early infancy up to 54 months of age among boys (average difference - 6.5% units, 95% confidence interval [CI] 1.7-11.3, p=0.01) but not among girls (average difference - 2.4% units, 95% CI -2.2-7.0, p=0.31). MMS resulted in more stunting compared to standard Fe60F (average difference - 4.8% units, 95% CI 0.8-8.9, p=0.02). Breastfeeding counseling prolonged the duration of EBF (difference - 35 days, 95% CI 30.6-39.5, p<0.001). Neither pregnancy interventions nor breastfeeding counseling influenced the body composition of children at 54 months of age. CONCLUSION: Early food supplementation during pregnancy reduced the occurrence of stunting among boys aged 0-54 months, while prenatal MMS increased the proportion of stunting. Food and micronutrient supplementation or EBF intervention did not affect body composition of offspring at 54 months of age. The effects of prenatal interventions on postnatal growth suggest programming effects in early fetal life.