Diarrhoea, enteric pathogen detection and nutritional indicators among controls in the Global Enteric Multicenter Study, Kenya site: an opportunity to understand reference populations in case-control studies of diarrhoea.
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SUBMITTER: Berendes DM
PROVIDER: S-EPMC6518569 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRotavirus is the most common cause of fatal diarrhoeal disease among children under the age of five globally and is responsible for millions of hospitalizations each year. Although nutritional status and environmental enteric dysfunction (EED) are recognized as important predictors of susceptibility to diarrhoeal disease, no research to date has examined the mechanisms by which undernutrition and EED may protect against prevalence of rotavirus infection.MethodsWe utilized data collected from a study evaluating the effectiveness of Rotarix™ vaccine against severe gastroenteritis among children under the age of 5 in Zambia. The prevalence of malnutrition, wasting, and stunting at the time of study enrollment was calculated using WHO child growth standards. Commercial ELISA kits were used to assess levels of faecal biomarkers for EED: alpha-1-antitrypsin and myeloperoxidase, and calprotectin. Separate multivariate logistic regression models were used to examine each measure of nutritional status and rotavirus diarrhoea including and excluding adjustment for EED.ResultsIn models that did not include adjustment for EED, malnourished children had 0.66 times the odds of having rotavirus diarrhoea compared to children with normal nutritional status (95% CI: 0.42, 1.0; p = 0.07). EED severity score was significantly higher among controls asymptomatic for diarrhoeal disease compared to cases with rotavirus diarrhoea (p = 0.02).ConclusionThe morphological changes associated with EED may confer protection against rotavirus infection and subsequent diarrhoeal disease among children. Further research is critically needed to better understand the complex mechanisms by which nutritional status and EED may impact susceptibility to rotavirus in early life.
| S-EPMC7531814 | biostudies-literature
Project description:Pediatric diarrheal disease remains the second most common cause of preventable illness and death among children under the age of five, especially in low and middle-income countries (LMICs). However, there is limited information regarding the role of food in pathogen transmission in LMICs. For this study, we examined the frequency of enteric pathogen occurrence and co-occurrence in 127 infant weaning foods in Kisumu, Kenya, using a multi-pathogen PCR diagnostic tool, and assessed household food hygiene risk factors for contamination. Bacterial, viral, and protozoan enteric pathogen DNA and RNA were detected in 62% of the infant weaning food samples collected, with 37% of foods containing more than one pathogen type. Multivariable generalized linear mixed model analysis indicated type of infant food best explained the presence and diversity of enteric pathogens in infant food, while most household food hygiene risk factors considered in this study were not significantly associated with pathogen contamination. Specifically, cow's milk was significantly more likely to contain a pathogen (adjusted risk ratio = 14.4; 95% confidence interval (CI) 1.78⁻116.1) and more likely to have higher number of enteric pathogen species (adjusted risk ratio = 2.35; 95% CI 1.67⁻3.29) than porridge. Our study demonstrates that infants in this low-income urban setting are frequently exposed to diarrhoeagenic pathogens in food and suggests that interventions are needed to prevent foodborne transmission of pathogens to infants.
| S-EPMC6388216 | biostudies-literature
Project description:Tricho-hepatic-enteric syndrome (THES) is a genetically heterogeneous rare syndrome (OMIM: 222470 (THES1) and 614602 (THES2)) that typically presents in the neonatal period with intractable diarrhoea, intra-uterine growth retardation (IUGR), facial dysmorphism, and hair and skin changes. THES is associated with pathogenic variants in either TTC37 or SKIV2L; both are components of the human SKI complex, an RNA exosome cofactor. We report an 8?year old girl who was diagnosed with THES by the Undiagnosed Disease Program-WA with compound heterozygous pathogenic variants in SKIV2L. While THES was considered in the differential diagnosis, the absence of protracted diarrhoea delayed definitive diagnosis. We therefore suggest that SKIV2L testing should be considered in cases otherwise suggestive of THES, but without the characteristic diarrhoea. We expand the phenotypic spectrum while reviewing the current knowledge on SKIV2L.
| S-EPMC7872052 | biostudies-literature
Project description:BackgroundHost vulnerabilities associated with acute malnutrition could facilitate the ability of specific enteric pathogens to cause diarrhoea and associated mortality. Using data from the Global Enteric Multicenter Study, we assessed whether acute malnutrition modifies the association between common enteric pathogens and moderate-to-severe diarrhoea, and whether associations between enteric pathogens and death were modified by acute malnutrition.MethodsChildren with moderate-to-severe diarrhoea and age-matched and community-matched controls were included in this post-hoc analysis if their mid-upper arm circumference had been measured and if they were older than 6 months of age. Acute malnutrition was defined as mid-upper arm circumference below 12·5 cm, capturing both severe acute malnutrition (<11·5 cm) and moderate acute malnutrition (≥11·5 cm and <12·5 cm). We tested whether acute malnutrition modified associations between enteric pathogens and moderate-to-severe diarrhoea in conditional logistic regression models. Among children with moderate-to-severe diarrhoea, Cox proportional hazards regression evaluated the modifying effect of acute malnutrition on the relationship between pathogens and 60-day fatality rate.FindingsThe age, site, and co-infection adjusted odds ratios (aORs) for moderate-to-severe diarrhoea associated with typical enteropathogenic Escherichia coli among children aged 6-11 months was 2·08 (95% CI 1·14-3·79) in children with acute malnutrition, and 0·97 (0·77-1·23) in children with better nutritional status, compared with healthy controls. Enterotoxigenic E coli producing heat-stable toxin among children aged 12-23 months also had a stronger association with moderate-to-severe diarrhoea in children with acute malnutrition (aOR 7·60 [2·63-21·95]) than among similarly aged children with better nutritional status (aOR 2·39 [1·76-3·25]). Results for Shigella spp, norovirus, and sapovirus suggested they had a stronger association with moderate-to-severe diarrhoea than other pathogens among children with better nutritional status, although Shigella spp remained associated with moderate-to-severe diarrhoea in both nutritional groups. 92 (64%) of 144 children with moderate-to-severe diarrhoea who died had acute malnutrition. Pathogen-specific 60-day fatality rates for all pathogens were higher among children with acute malnutrition, but no individual pathogen had a significantly larger increase in its relative association with mortality.InterpretationAcute malnutrition might strengthen associations between specific pathogens and moderate-to-severe diarrhoea. However, the strong link between acute malnutrition and mortality during moderate-to-severe diarrhoea in children is not limited to specific infections, and affects a broad spectrum of enteric pathogens. Interventions addressing acute malnutrition could be an effective way to lower the mortality of both childhood malnutrition and diarrhoea.FundingThe Bill & Melinda Gates Foundation.
| S-EPMC7025322 | biostudies-literature
Project description:Hypertension (HTN) is quantitatively the major cardiovascular risk factor and responsible for ∼50% of cardiovascular morbidity and mortality. Blood pressure (BP) is also a classical complex genetic trait with heritability estimates of 30-50%. Although much is known about BP regulation, the intrinsic origin of essential HTN remains obscure although many environmental factors are known. Analyses of rare monogenic syndromes of HTN have focused attention on pathways that involve renal sodium handling, and steroid hormone metabolism including the mineralocorticoid receptor activity. The genetic basis of common essential HTN on the other hand is only just becoming accessible through high-throughput approaches. Unbiased genome-wide analyses of BP genomics have identified 43 genetic variants associated with systolic, diastolic BP, and HTN. It is highly likely based on current findings that there are hundreds of such loci with small effects on BP, opening a perspective on the genetic architecture of BP that was unknown before. It is our hope that the knowledge of these and further loci will lead to improved understanding of BP pathophysiology and to the identification of new targets for drug therapy.
| S-EPMC3612776 | biostudies-literature
Project description:BackgroundPoor nutrition and exposure to faecal contamination are associated with diarrhoea and growth faltering, both of which have long-term consequences for child health. We aimed to assess whether water, sanitation, handwashing, and nutrition interventions reduced diarrhoea or growth faltering.MethodsThe WASH Benefits cluster-randomised trial enrolled pregnant women from villages in rural Kenya and evaluated outcomes at 1 year and 2 years of follow-up. Geographically-adjacent clusters were block-randomised to active control (household visits to measure mid-upper-arm circumference), passive control (data collection only), or compound-level interventions including household visits to promote target behaviours: drinking chlorinated water (water); safe sanitation consisting of disposing faeces in an improved latrine (sanitation); handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate maternal, infant, and young child feeding plus small-quantity lipid-based nutrient supplements from 6-24 months (nutrition); and combined water, sanitation, handwashing, and nutrition. Primary outcomes were caregiver-reported diarrhoea in the past 7 days and length-for-age Z score at year 2 in index children born to the enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105.FindingsBetween Nov 27, 2012, and May 21, 2014, 8246 women in 702 clusters were enrolled and randomly assigned an intervention or control group. 1919 women were assigned to the active control group; 938 to passive control; 904 to water; 892 to sanitation; 917 to handwashing; 912 to combined water, sanitation, and handwashing; 843 to nutrition; and 921 to combined water, sanitation, handwashing, and nutrition. Data on diarrhoea at year 1 or year 2 were available for 6494 children and data on length-for-age Z score in year 2 were available for 6583 children (86% of living children were measured at year 2). Adherence indicators for sanitation, handwashing, and nutrition were more than 70% at year 1, handwashing fell to less than 25% at year 2, and for water was less than 45% at year 1 and less than 25% at year 2; combined groups were comparable to single groups. None of the interventions reduced diarrhoea prevalence compared with the active control. Compared with active control (length-for-age Z score -1·54) children in nutrition and combined water, sanitation, handwashing, and nutrition were taller by year 2 (mean difference 0·13 [95% CI 0·01-0·25] in the nutrition group; 0·16 [0·05-0·27] in the combined water, sanitation, handwashing, and nutrition group). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth.InterpretationBehaviour change messaging combined with technologically simple interventions such as water treatment, household sanitation upgrades from unimproved to improved latrines, and handwashing stations did not reduce childhood diarrhoea or improve growth, even when adherence was at least as high as has been achieved by other programmes. Counselling and supplementation in the nutrition group and combined water, sanitation, handwashing, and nutrition interventions led to small growth benefits, but there was no advantage to integrating water, sanitation, and handwashing with nutrition. The interventions might have been more efficacious with higher adherence or in an environment with lower baseline sanitation coverage, especially in this context of high diarrhoea prevalence.FundingBill & Melinda Gates Foundation, United States Agency for International Development.
| S-EPMC5809717 | biostudies-literature
Project description:ObjectivesThe aim of this study was to test whether household environmental hygiene and behavioural conditions moderated associations between diarrhoea and enteric pathogen detection in infants 5 months of age in Kenya and pathogen sources, including latrine access, domestic animal co-habitation and public food sources.DesignCross-sectional study utilising enrolment survey data of households participating in the Safe Start cluster-randomised controlled trial .SettingKisumu, Kenya.ParticipantsA total of 898 caregivers with 5-month (22 week ± 1 week) aged infants were enrolled in the study and completed the enrolment survey.Primary and secondary outcome measuresOutcomes were (1) caregiver-reported 7-day diarrhoea prevalence and (2) count of types of enteric viruses, bacteria and parasites in infant stool. Exposures and effect modifiers included water access and treatment, cohabitation with domestic animals, sanitation access, handwashing practices, supplemental feeding, access to refrigeration and flooring.ResultsReported handwashing after handling animals (adjusted odds ratio (aOR)=0.20; 95% CI=0.06 to 0.50) and before eating (aOR=0.44; 95% CI=0.26 to 0.73) were strongly associated with lower risk of caregiver-reported diarrhoea, while cohabitation with animals (aOR=1.54; 95% CI=1.01 to 2.34) living in a household with vinyl-covered dirt floors (aOR=0.60; 95% CI=0.45 to 0.87) were strongly associated with pathogen codetection in infants. Caregiver handwashing after child (p=0.02) or self-defecation (p=0.03) moderated the relationship between shared sanitation access and infant exposure to pathogens, specifically private latrine access was protective against pathogen exposure of infants in households, where caregivers washed hands after defecation. In the absence of handwashing, access to private sanitation posed no benefits over shared latrines for protecting infants from exposure.ConclusionOur evidence highlights eliminating animal cohabitation and improving flooring, postdefecation and food-related handwashing, and safety and use of cow milk sources as interventions to prevent enteric pathogen exposure of young infants in Kenya.Trial registration numberNCT03468114.
| S-EPMC9628658 | biostudies-literature
Project description:The enteric pathogen Salmonella enterica is one of the leading causes of foodborne illness in the world. The species is extremely diverse, containing more than 2,500 named serovars that are designated for their unique antigen characters and pathogenicity profiles-some are known to be virulent pathogens, while others are not. Questions regarding the evolution of pathogenicity, significance of antigen characters, diversity of clustered regularly interspaced short palindromic repeat (CRISPR) loci, among others, will remain elusive until a strong evolutionary framework is established. We present the first large-scale S. enterica subsp. enterica phylogeny inferred from a new reference-free k-mer approach of gathering single nucleotide polymorphisms (SNPs) from whole genomes. The phylogeny of 156 isolates representing 78 serovars (102 were newly sequenced) reveals two major lineages, each with many strongly supported sublineages. One of these lineages is the S. Typhi group; well nested within the phylogeny. Lineage-through-time analyses suggest there have been two instances of accelerated rates of diversification within the subspecies. We also found that antigen characters and CRISPR loci reveal different evolutionary patterns than that of the phylogeny, suggesting that a horizontal gene transfer or possibly a shared environmental acquisition might have influenced the present character distribution. Our study also shows the ability to extract reference-free SNPs from a large set of genomes and then to use these SNPs for phylogenetic reconstruction. This automated, annotation-free approach is an important step forward for bacterial disease tracking and in efficiently elucidating the evolutionary history of highly clonal organisms.
| S-EPMC3845640 | biostudies-literature
Project description:Young children are infected by a diverse range of enteric pathogens in high disease burden settings, suggesting pathogen contamination of the environment is equally diverse. This study aimed to characterize across- and within-neighborhood diversity in enteric pathogen contamination of public domains in urban informal settlements of Kisumu, Kenya, and to assess the relationship between pathogen detection patterns and human and domestic animal sanitation conditions. Microbial contamination of soil and surface water from 166 public sites in three Kisumu neighborhoods was measured by enterococcal assays and quantitative reverse transcription polymerase chain reaction (qRT-PCR) for 19 enteric pathogens. Regression was used to assess the association between observed sanitary indicators of contamination with enterococci and pathogen presence and concentration, and pathogen diversity. Seventeen types of pathogens were detected in Kisumu public domains. Enteric pathogens were codetected in 33% of soil and 65% of surface water samples. Greater pathogen diversity was associated with the presence of domestic animal feces but not with human open defecation, deteriorating latrines, flies, or disposal of human feces. Sanitary conditions were not associated with enterococcal bacteria, specific pathogen concentrations, or "any pathogen". Young children played at 40% of observed sites. Managing domestic animal feces may be required to reduce enteric pathogen environmental contamination in high-burden settings.
| S-EPMC6557411 | biostudies-literature
Project description:UnlabelledBovine parvovirus (BPV), the causative agent of respiratory and gastrointestinal disease in cows, is the type member of the Bocaparvovirus genus of the Parvoviridae family. Toward efforts to obtain a template for the development of vaccines and small-molecule inhibitors for this pathogen, the structure of the BPV capsid, assembled from the major capsid viral protein 2 (VP2), was determined using X-ray crystallography as well as cryo-electron microscopy and three-dimensional image reconstruction (cryo-reconstruction) to 3.2- and 8.8-Å resolutions, respectively. The VP2 region ordered in the crystal structure, from residues 39 to 536, conserves the parvoviral eight-stranded jellyroll motif and an αA helix. The BPV capsid displays common parvovirus features: a channel at and depressions surrounding the 5-fold axes and protrusions surrounding the 3-fold axes. However, rather than a depression centered at the 2-fold axes, a raised surface loop divides this feature in BPV. Additional observed density in the capsid interior in the cryo-reconstructed map, compared to the crystal structure, is interpreted as 10 additional N-terminal residues, residues 29 to 38, that radially extend the channel under the 5-fold axis, as observed for human bocavirus 1 (HBoV1). Surface loops of various lengths and conformations extend from the core jellyroll motif of VP2. These loops confer the unique surface topology of the BPV capsid, making it strikingly different from HBoV1 as well as the type members of other Parvovirinae genera for which structures have been determined. For the type members, regions structurally analogous to those decorating the BPV capsid surface serve as determinants of receptor recognition, tissue and host tropism, pathogenicity, and antigenicity.ImportanceBovine parvovirus (BPV), identified in the 1960s in diarrheic calves, is the type member of the Bocaparvovirus genus of the nonenveloped, single-stranded DNA (ssDNA) Parvoviridae family. The recent isolation of human bocaparvoviruses from children with severe respiratory and gastrointestinal infections has generated interest in understanding the life cycle and pathogenesis of these emerging viruses. We have determined the high-resolution structure of the BPV capsid assembled from its predominant capsid protein VP2, known to be involved in a myriad of functions during host cell entry, pathogenesis, and antigenicity for other members of the Parvovirinae. Our results show the conservation of the core secondary structural elements and the location of the N-terminal residues for the known bocaparvovirus capsid structures. However, surface loops with high variability in sequence and conformation give BPV a unique capsid surface topology. Similar analogous regions in other Parvovirinae type members are important as determinants of receptor recognition, tissue and host tropism, pathogenicity, and antigenicity.
| S-EPMC4325758 | biostudies-literature