Confronting Challenges to Enterotoxigenic Escherichia coli Vaccine Development

The enterotoxigenic Escherichia coli (ETEC) are a diverse and genetically plastic pathologic variant (pathovar) of E. coli defined by their production of heat-labile (LT) and heat-stable (ST) enterotoxins. These pathogens, which came to recognition more than four decades ago in patients presenting with severe cholera-like diarrhea, are now known to cause hundreds of millions of cases of symptomatic infection annually. Children in low-middle income regions of the world lacking access to clean water and basic sanitation are disproportionately affected by ETEC. In addition to acute diarrheal morbidity, these pathogens remain a significant cause of mortality in children under the age of five years and have also been linked repeatedly to sequelae of childhood malnutrition and growth stunting. Vaccines that could prevent ETEC infections therefore remain a high priority. Despite several decades of effort, a licensed vaccine that protects against the breadth of these pathogens remains an aspirational goal, and the underlying genetic plasticity of E. coli has posed a fundamental challenge to development of a vaccine that can encompass the complete antigenic spectrum of ETEC. Nevertheless, novel strategies that include toxoids, a more complete understanding of ETEC molecular pathogenesis, structural details of target immunogens, and the discovery of more highly conserved antigens essential for virulence should accelerate progress and make a broadly protective vaccine feasible.

Factors Associated With Stunting Among Infants and Young Children Aged 7–29 Months in Post-conflict Northern Uganda

Objectives To examine factors associated with stunting in Agago District, Uganda Methods We used cross-sectional data from a quantitative baseline survey of 870 households of the ONCE (One Nutrition in Complex Environments) project currently being conducted in Agago district of Uganda. Survey data used include infant anthropometry, infant feeding practices, 24-hour dietary recall, maternal heights, weights, education and household characteristics. Statistical methods include Pearson correlation coefficients, student T-tests, pair-wise mean comparisons with Bonferroni adjustment, and stepwise multivariable linear and logistic regression analyses controlled for clustering. Dependent variables include length-for-age z-score (LAZ, −6 to 6, continuous) and being stunted (binary). Independent variables include child age, child's birth weight, diarrheal morbidity (past two weeks), maternal education, maternal height, household wealth index, and animal sourced foods consumption (ASF, categorical: no ASF (comparator), 1 ASF, >= 2 ASF). ASF is defined as consumption of dairy, animal flesh, fish of any kind, organ meat, insects, or eggs in previous 24 hours. Results Infants between 7 months and 2.5 years with complete data were included (N = 621), of whom 19.7% were classified as stunted. Mean LAZ was −1.05 (SD: 1.24). Most children did not consume any ASF in the past 24 hours (73.6%). ASF consumption was not associated with LAZ (1 kind of ASF: −0.0699, 95% CI: −0.329, 0.189) or stunting (1 kind of ASF OR: 1.186, 95% CI: 0.614, 2.292). Maternal height was associated with 7.8% decreased odds of being stunted (OR: 0.922, 95% CI: 0.878, 0.969); age was associated with 8.9% increased odds of being stunted (OR: 1.089, 95% CI: 1.011, 1.090); birth weight was associated with 54% decreased odds of being stunted (OR: 0.461, 95% CI: 0.296, 0.717). Infants with diarrhea were 96% more likely to be stunted than those without (OR: 1.956, 95% CI: 1.050, 3.642). Conclusions Factors associated with stunting were maternal height, child age, birth weight and diarrheal morbidity. ASF consumption was not, possibly due to low levels and possibly low frequency of consumption. Mother's nutritional status is likely to be an important predictor in this population. Funding Sources Feed the Future Initiative, U.S. Agency for International Development.

Determinants of Childhood Diarrhea in Households with Improved Water, Sanitation, and Hygiene (WASH) in Ethiopia: Evidence from a Repeated Cross-Sectional Study

Background: Determinants of childhood diarrhea in households with improved WASH (ie, households with improved drinking water sources, improved sanitation facilities, and those who practiced safe child stool disposal) are limited. This study aimed to identify the determinants of diarrhea among under-five children exclusively in households with improved Water, Sanitation, and Hygiene (WASH). Methods: A repeated cross-sectional study design was followed, and data from the Demographic and Health Survey (DHS) conducted between 2005 and 2016 in Ethiopia was used. A total of 1,975 child-mother pairs (257 children with diarrhea and 1718 children without diarrhea) in households with improved WASH were included in this study. Hierarchical conditional logistic regression models were used. Adjusted odds ratios (AOR) with corresponding 95% confidence intervals (CI) were estimated to determine the strength of association. Results: Children aged 13 to 24 months (Adjusted Odds Ratio [AOR] = 2.70, 95%CI: 1.69-4.32), children who did not receive the measles vaccine (AOR = 2.33, 95%CI: 1.60-3.39), and those residing in the agrarian region (AOR = 1.66, 95%CI: 1.10-2.49) were significantly more likely to develop diarrheal morbidity. The size of the child at birth was also found to be significantly associated with diarrheal morbidity. Conclusion: In this study, child factors (age of the child, vaccinated for measles, and the size of a child at birth), and household-related factors (contextual region) had a significant effect on the risk of childhood diarrheal morbidity in households with improved WASH in Ethiopia.

Sanitation and Diarrheal Morbidity: Evidence from Afghanistan

Background: Lack of sanitation facilities and inadequate water is key to many diseases' outcomes, mainly diarrhea. These factors affect the health status of a country and result in increased mortality and morbidity pattern, particularly among the vulnerable population like children and women. Thus, the study assesses the linkages between diarrheal diseases and sanitation in Afghanistan affected since long by political instability, which has derailed the country's health system. Methods: We used the 2015 Afghanistan Demographic and Health Survey to assess the linkages between sanitation and diarrheal diseases among under-five children. Bivariate and multivariate analyses have been used to carry out the study. The logistic model was used to evaluate the risk factors that lead to diarrheal outcomes. Results: Our findings from the results showed that the prevalence of diarrhea among under-five children in Afghanistan was 29%. Pashai is the most affected, with 36% among ethnicities, whereas eastern Afghanistan is the most affected region with a prevalence of (38%). Open defecated Population (OR: 1.17, p<0.001), Tap water (OR: 1.31, p<0.001), Well water (OR: 1.24, p<0.001), and Sharing toilet (OR: 1.15, p<0.001) are significantly associated with childhood diarrhea. Conclusions: A significant impact has been found with inadequate sanitation, shared toilet facility, clean water, and other elements with childhood diarrhea in Afghanistan. The region-wise difference has also been found to be very high across the regions. Thus, it has been found that a lack of such factors has a more significant impact on children's health and needs a particular focus from a policy purpose.

The Association Between Diarrheal Morbidity and ODF Status Among Under Five Children in Southeast, Ethiopia

Background: Diarrheal disease remains one of the leading killers of children around the world. Most cases of diarrhea spread in settings with poor hygiene and lack of access to clean drinking water and sanitation. In Ethiopia, diarrheal disease is more common and kills almost fifteen thousand under-five children in year 2016. Therefore, this study determined diarrheal morbidity among under five children and its association with open defecation free status.Methods: A community-based comparative cross-sectional study was conducted on 732 households that had at least one under-five children. Multistage sampling technique was used to select households. Informed verbal consent was obtained from study participant. Multivariable logistic regression was performed to identify factors associated with diarrheal morbidity among under five children. Odd ratios with 95% confidence interval were reported and p-value of <0.05 was considered as statistical significance. Results: A total of 709 mothers or caregivers of under-five children were interviewed making the response rate 97%. The past two-week diarrhea morbidity in the study area was 20.2%. Multivariable analysis showed that unsanitary disposal of children`s feces (adjusted odds ratio [AOR]= 2.68, 95% confidence interval [CI]: 1.66, 4.30), exclusive breast feeding (AOR=0.43 [0.26, 0.71), mother not attend formal education (AOR=1.93, 95% CI: 1.18, 3.15) and child age (AOR=1.93, 95% CI: 1.04. 3.57) were significantly associated with diarrheal disease. Conversely, there is no association between open defecation free status and childhood diarrhea among under-five children (AOR=0.89, 95% CI: 0.55, 1.44).Conclusions: The prevalence of diarrhea was slightly higher among children from non-open defecation free households when compared to children living in open defecation free households. However, open defecation free status was not significantly associated with diarrhea morbidity during multivariable logistic analysis.

Sanitation and Diarrheal Morbidity: Evidence from Afghanistan

IntroductionLack of sanitation facilities and inadequate water is key to many diseases’ outcomes, mainly diarrhea. These factors not just affect the health status of a country and but also result in increased mortality and morbidity pattern, particularly among the vulnerable population like children and women. Thus, the study assesses the linkages between diarrheal diseases and sanitation in Afghanistan affected since long by political instability which has derailed the health system of the country.Material and MethodsWe used 2015 Afghanistan Demographic and Health Survey to assess the linkages between sanitation and diarrheal diseases among under-five children. Bivariate and multivariate analyses have used to carry out the study. The logistic model was used to evaluate the risk factors that lead to diarrheal outcomes.ResultsOur findings from the results showed that the prevalence of diarrhea among under-five children in Afghanistan was 29%. Pashai is the most affected, with 36% among ethnicities, whereas eastern Afghanistan is the most affected region with the prevalence of (38%). Open defecated Population (OR: 1.17, p<0.001), Tap water (OR: 1.31, p<0.001), Well water (OR: 1.24, p<0.001), and Sharing toilet (OR: 1.15, p<0.001) are significantly associated with childhood diarrhea.ConclusionsA significant impact has found with factors like-inadequate sanitation, shared toilet facility, clean water and other elements with childhood diarrhea in Afghanistan. The region-wise difference has also found to be very high across the regions. Thus, it has found that a lack of such factors has a more significant impact on the health of children and needs a particular focus from a policy purpose.

Evaluation of in vitro and in vivo antibiotic efficacy against a novel bioluminescent Shigella flexneri

Shigella spp., the bacteria responsible for shigellosis, are one of the leading causes of diarrheal morbidity and mortality amongst children. There is a pressing need for the development of novel therapeutics, as resistance of Shigella to many currently used antibiotics is rapidly emerging. This paper describes the development of robust in vitro and in vivo tools to study antibiotic efficacy against Shigella flexneri. A novel bioluminescent S. flexneri strain (S. flexneri lux1) was generated, which can be used in a mammalian epithelial cell co-culture assay to evaluate antibiotic intracellular and extracellular efficacy. In addition, the S. flexneri lux1 strain was used with an intraperitoneal (IP) murine model of shigellosis to test the efficacy of ciprofloxacin and ampicillin. Both antibiotics significantly reduced the observed radiance from the gastrointestinal tissue of infected mice compared to vehicle control. Furthermore, plated gastrointestinal tissue homogenate confirmed antibiotic treatment significantly reduced the S. flexneri infection. However, in contrast to the results generated with tissue homogenate, the radiance data was not able to distinguish between the efficacy of ampicillin and ciprofloxacin. Compared to traditional methods, these models can be utilized for efficient screening of novel antibiotics aiding in the discovery of new treatments against shigellosis.