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PURPOSE OF REVIEW: Viruses are the most common etiological agents of diarrhea in children. Despite rotavirus vaccine introduction, rotavirus remains as the leading cause of death globally, followed by norovirus, which represents a diagnostic challenge. Here, we describe new advances in the diagnosis and management of viral diarrheas. RECENT FINDINGS: Although immunoassays are widely used for their fast turnaround time and low cost, molecular techniques have become the most reliable diagnostic method due to their high sensitivity and capacity to analyze multiple pathogens in gastrointestinal panels. Isothermal nucleic acid amplification assays (LAMP and RPA) are promising techniques since they do not require sophisticated equipment and can be used as point-of-care testing. CRISPR/Cas nucleic acid detection systems are new diagnostic methods with great potential. Several recent published articles describe the role of human intestinal enteroids to characterize norovirus infection, to test new drugs, and for vaccine development. The interaction between the human gut microbiota and gastrointestinal viral infections has been extensively reviewed and offers some innovative mechanisms for therapeutic and preventive measures. SUMMARY: Although important advances have been made, more research is needed to address remaining challenges and further improve diagnostic capabilities and better management strategies for this critical infectious disease.
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Diarrea , Humanos , Diarrea/diagnóstico , Diarrea/virología , Diarrea/terapia , Técnicas de Diagnóstico Molecular/métodos , Virosis/diagnóstico , Virosis/terapia , Norovirus/genética , Norovirus/aislamiento & purificación , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/terapia , Técnicas de Amplificación de Ácido Nucleico/métodos , Microbioma GastrointestinalRESUMEN
Cryptosporidiosis has previously been reported in animals, humans, and water sources in the United Arab Emirates (UAE). However, most reports were only to the genus level, or generically identified as cryptosporidiosis. We aimed to investigate the genetic diversity of Cryptosporidium species occurring in diarrhetic ungulates which were brought to the Central Veterinary Research Laboratory (CVRL) in Dubai. Using a combination of microscopic and molecular methods, we identified five species of Cryptosporidium occurring among ungulates in the UAE, namely C. parvum, C. hominis, C. xiaoi, C. meleagridis, and C. equi. Cryptosporidium parvum was the most prevalent species in our samples. Furthermore, we identified subtypes of C. parvum and C. hominis, which are involved in both human and animal cryptosporidiosis. This is also the first reported occurrence of Cryptosporidium spp. in the Arabian Tahr, to our knowledge. Since the animals examined were all in contact with humans, the possibility of zoonotic spread is possible. Our study correlates with previous reports in the region, building upon the identification of Cryptosporidium sp. However, there is a need to further investigate the endemic populations of Cryptosporidium, including more hosts, sampling asymptomatic animals, and location data.
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Criptosporidiosis , Cryptosporidium , Diarrea , Variación Genética , Emiratos Árabes Unidos/epidemiología , Animales , Criptosporidiosis/parasitología , Criptosporidiosis/epidemiología , Cryptosporidium/genética , Cryptosporidium/clasificación , Cryptosporidium/aislamiento & purificación , Diarrea/veterinaria , Diarrea/parasitología , Diarrea/epidemiología , Heces/parasitología , Bovinos , Filogenia , Cabras/parasitología , ADN Protozoario/genéticaRESUMEN
BACKGROUND: Low-osmolarity oral rehydration salt (ORS) and zinc therapy effectively manage diarrhea in children under five years of age, offering both short- and long-term benefits. Despite this, caregivers' adherence to ORS and zinc is often unsatisfactory due to factors such as forgetfulness, resolution of symptoms, and underestimation of the disease's severity. This study assessed the effect of mobile call reminders on ORS and zinc tablet adherence among children with acute diarrhea in a secondary-level health facility in Kwara State, Nigeria. METHODS: Using an open-label, randomized controlled trial design, this study compared caregiver-child pairs with acute diarrhea aged 6-59 months who received standard instructions (SI) alone (control group) and an intervention group (IG) who received SI plus phone call reminders on days three and seven of zinc sulfate therapy. All participants used a pictorial diary to track loose/watery stools and ORS and zinc tablet treatments for ten days. The primary outcome measures were independent and combined adherence to ORS and zinc therapy. The secondary outcomes were independent and combined adherence scores, defined as the percentage of times the ORS was given post-diarrhea and the percentage of prescribed zinc tablets administered out of ten. RESULTS: A total of 364/400 mother-child pairs completed the study. The percentage of mothers with full adherence in the intervention group was 82.5% for ORS, 72.1% for zinc, and 58.5% for combined use, compared to 78.8%, 60.8%, and 43.6%, respectively, in the control group. The odds of full adherence to ORS and zinc were 1.6 and 1.7 times higher among intervention mothers [ORS: OR = 1.561, 95% CI = 0.939-2.598, P = 0.085; zinc: OR = 1.671, 95% CI = 1.076-2.593, P = 0.022], and 1.8 times higher for combined use according to WHO guidelines [OR = 1.818, 95% CI = 1.200-2.754, P = 0.005]. The mean adherence scores for the intervention group were higher than those for the control group by 4.1% (95% CI = 0.60-7.60) for ORS, 7.3% (95% CI = 3.74-10.86) for zinc, and 5.7% (95% CI = 3.23-8.17) for the combined treatment. CONCLUSION: Phone reminders can effectively improve consistency of home treatment administered by caregivers for children under five years old. TRIAL REGISTRATION: The study was registered retrospectively (17/3/2023) with the Pan African Clinical Trial Registry (PACTR202301560735856).
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Teléfono Celular , Diarrea , Fluidoterapia , Sistemas Recordatorios , Humanos , Lactante , Femenino , Preescolar , Masculino , Fluidoterapia/métodos , Diarrea/tratamiento farmacológico , Diarrea/terapia , Nigeria , Zinc/uso terapéutico , Zinc/administración & dosificación , Enfermedad Aguda , Cumplimiento de la Medicación/estadística & datos numéricos , Sulfato de Zinc/uso terapéutico , Sulfato de Zinc/administración & dosificación , AdultoRESUMEN
BACKGROUND: In sub-Saharan African countries, preventable and manageable diseases such as diarrhea and acute respiratory infections still claim the lives of children. Hence, this study aims to estimate the rate of change in the log expected number of days a child suffers from Diarrhea (NOD) and flu/common cold (NOF) among children aged 6 to 11 months at the baseline of the study. METHODOLOGY: This study used secondary data which exhibit a longitudinal and multilevel structure. Based on the results of exploratory analysis, a multilevel zero-inflated Poisson regression model with a rate of change in the log expected NOD and NOF described by a quadratic trend was proposed to efficiently analyze both outcomes accounting for correlation between observations and individuals through random effects. Furthermore, residual plots were used to assess the goodness of fit of the model. RESULTS: Considering subject and cluster-specific random effects, the results revealed a quadratic trend in the rate of change of the log expected NOD. Initially, low dose iron Micronutrient Powder (MNP) users exhibited a higher rate of change compared to non-users, but this trend reversed over time. Similarly, the log expected NOF decreased for children who used MNP and exclusively breastfed for six months, in comparison to their counterparts. In addition, the odds of not having flu decreased with each two-week increment for MNP users, as compared to non-MNP users. Furthermore, an increase in NOD resulted in an increase in the log expected NOF. Region and exclusive breastfeeding also have a significant relationships with both NOD and NOF. CONCLUSION: The findings of this study underscore the importance of commencing analysis of data generated from a study with exploratory analysis. The study highlights the critical role of promoting EBF for the first six months and supporting children with additional food after six months to reduce the burden of infectious diseases.
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Diarrea , Humanos , Etiopía/epidemiología , Lactante , Estudios Longitudinales , Masculino , Femenino , Diarrea/epidemiología , Distribución de Poisson , Resfriado Común/epidemiología , Gripe Humana/epidemiología , Modelos Estadísticos , Enfermedades Transmisibles/epidemiologíaRESUMEN
BACKGROUND: School-based water, sanitation and hygiene (WASH) may improve the health and attendance of schoolchildren, particularly post-menarcheal girls, but existing evidence is mixed. We examined the impact of an urban school-based WASH programme (Project WISE) on child health and attendance. METHODS: The WISE cluster-randomised trial, conducted in 60 public primary schools in Addis Ababa, Ethiopia over one academic year, enrolled 2-4 randomly selected classes per school (~ 100 pupils) from grades 2 to 8 (aged 7-16) in an 'open cohort'. Schools were assigned 1:1 by stratified randomisation to receive the intervention during the 2021/2022 or the 2022/2023 academic year (waitlist control). The intervention included improvements to drinking water storage, filtration and access, handwashing stations and behaviour change promotion. Planned sanitation improvements were not realised. At four unannounced classroom visits post-intervention (March-June 2022), enumerators recorded primary outcomes of roll-call absence, and pupil-reported respiratory illness and diarrhoea in the past 7 days among pupils present. Analysis was by intention-to-treat. RESULTS: Of 83 eligible schools, 60 were randomly selected and assigned. In total, 6229 eligible pupils were enrolled (median per school 101.5; IQR 94-112), 5987 enrolled at study initiation (23rd November-22nd December 2021) and the remaining 242 during follow-up. Data were available on roll-call absence for 6166 pupils (99.0%), and pupil-reported illness for 6145 pupils (98.6%). We observed a 16% relative reduction in odds of pupil-reported respiratory illness in the past 7 days during follow-up in intervention vs. control schools (aOR 0.84; 95% CI 0.71-1.00; p = 0.046). There was no evidence of effect on pupil-reported diarrhoea in the past 7 days (aOR 1.15; 95% CI 0.84-1.59; p = 0.39) nor roll-call absence (aOR 1.07; 95% 0.83-1.38; p = 0.59). There was a small increase in menstrual care self-efficacy (aMD 3.32 on 0-100 scale; 95% CI 0.05-6.59), and no evidence of effects on other secondary outcomes. CONCLUSIONS: This large-scale intervention to improve school WASH conditions city-wide had a borderline impact on pupil-reported respiratory illness but no effect on diarrhoeal disease nor pupil absence. Future research should establish relationships between WASH-related illness, absence and other educational outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT05024890.
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Salud Infantil , Higiene , Instituciones Académicas , Humanos , Etiopía , Niño , Femenino , Masculino , Adolescente , Saneamiento/métodos , Saneamiento/normas , Servicios de Salud Escolar , Diarrea/prevención & control , Diarrea/epidemiología , Abastecimiento de Agua/normasRESUMEN
Porcine epidemic diarrhea virus (PEDV) causes diarrhea and vomiting in piglets, leading to a mortality rate of 100%. Due to the high frequency of mutation, it is important to monitor the evolution of PEDV and develop potential vaccine candidates. In this study, two PEDV strains (ZJ2022 and ZQ2022) were identified by PCR. These strains were subsequently isolated, and their genome sequences, growth characteristics, and pathogenicity were compared. Phylogenetic and recombination analyses revealed that both strains belonged to GIIa-subgroup, and ZQ2022 was identified as a recombinant strain derived from ZJ2022. Further sequence analysis showed that the ZJ2022 strain had a modified top region of the S1 protein due to a three amino acid insertion (T380_Y380insGGE) in the S1 gene. According to the virus growth curve, ZJ2022 exhibited better cellular adaptation than ZQ2022, with higher viral titers from 8 hpi to 24 hpi. Additionally, ZQ2022 exhibited a high level of pathogenicity, causing severe diarrhea in piglets at 36 hpi and a 100% mortality rate by 96 hpi. In contrast, ZJ2022 showed lower pathogenicity, inducing severe diarrhea in piglets at 60 hpi, with a mortality rate of 60% at 96 hpi and 100% at 120 hpi. In summary, our findings provided evidence of the undergoing mutations in Chinese PEDV strains. Furthermore, the S gene insertion strain ZJ2022 exhibited strong cellular adaptability and low pathogenicity, making it a potential candidate strain for vaccine development.
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Animales Recién Nacidos , Infecciones por Coronavirus , Diarrea , Filogenia , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Virus de la Diarrea Epidémica Porcina/genética , Virus de la Diarrea Epidémica Porcina/patogenicidad , Virus de la Diarrea Epidémica Porcina/aislamiento & purificación , Virus de la Diarrea Epidémica Porcina/clasificación , Porcinos , Enfermedades de los Porcinos/virología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Virulencia , Diarrea/virología , Diarrea/veterinaria , Glicoproteína de la Espiga del Coronavirus/genética , Genoma Viral , Mutagénesis Insercional , China , Células VeroRESUMEN
PURPOSE: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease. METHODS: Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cTFH) cells, and T-cell proliferation were analyzed. RESULTS: Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the TH2-like skewing accompanied by reduced TH17-like responses was observed in cTFH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs. CONCLUSIONS: The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.
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Factores de Transcripción Forkhead , Enfermedades Genéticas Ligadas al Cromosoma X , Linfocitos T Reguladores , Humanos , Turquía , Masculino , Preescolar , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Linfocitos T Reguladores/inmunología , Lactante , Femenino , Niño , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/congénito , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/terapia , Enfermedades del Sistema Inmune/congénito , Autoinmunidad , Adolescente , DiarreaRESUMEN
In this paper, we have provided more insights on the relationship between under five morbidity in Nigeria and some background characteristics using a Poisson regression model and the most recent 2018 NDHS data on Acute Respiratory Infection (ARI), diarrhoea and fever. Some of our results are that children 36-47 months old have the highest risk of ARI [OR = 1.45; CI (1.31,1.60)] while children less than 6 months old have the lowest risk of ARI [OR = 0.14; CI (0.11,0.17)]. The prevalence of diarrhoea is generally high among children under 48-59 months old but highest among children 6-11 months old [OR = 4.34; CI (3.69,5.09)]. Compared to children 48-59 months old, children in all other age categories except 24-34 months old have a high risk of fever [OR = 0.95; CI (0.73,1.24)]. ARI is more prevalent among female children [OR = 8.88; CI (8.02,9.82)] while diarrhoea [OR = 21.75; (19.10,24.76)] and fever [OR = 4.78; CI (4.31,5.32)] are more prevalent among male children. Children in urban areas are more likely to suffer ARI [OR = 9.49; CI (8.31,10.85)] while children in rural areas are more likely to suffer both diarrhoea [OR = 21.75; CI (19.10,24.76)] and fever [OR = 4.90; CI (4.26,5.63)]. Children in the South-South have the highest risk of ARI [OR = 4.03; CI (3.65,4.454)] while children in the North Central have the lowest risk of ARI [OR = 1.55; CI (1.38,1.74)] and highest risk of diarrhoea [OR = 3.34; CI (2.30,5.11)]. Children in the Northeast have the highest risk of fever [OR = 1.30; CI (1.14,1.48)]. In the Northcentral region, Kogi state has the highest prevalence of fever [OR = 2.27; CI (1.62,3.17)], while Benue state has the lowest [OR = 0.35; CI (0.20,0.60)]. Children in Abuja state face similar risks of fever and diarrhoea [OR = 0.84; CI (0.55,1.27)], with the risk of diarrhoea in Abuja being comparable to that in Plateau state [OR = 1.57; CI (0.92,2.70)]. Nasarawa state records the highest incidence of diarrhoea in the Northcentral [OR = 5.12; CI (3.03,8.65)], whereas Kogi state reports the lowest [OR = 0.29; CI (0.16,0.53)]. In the Northeast, Borno state has the highest rate of fever [OR = 3.28; CI (2.80,3.84)], and Bauchi state the lowest [OR = 0.38; CI (0.29,0.50)]. In Adamawa state, the risks of fever and diarrhoea are nearly equivalent [OR = 1.17; CI (0.97,1.41)], and the risk of fever there is similar to that in Taraba state [OR = 0.92; CI (0.75,1.12)]. Diarrhoea is most prevalent in Yobe state [OR = 3.17; CI (2.37,4.23)] and least prevalent in Borno state [OR = 0.26; CI (0.20,0.33)]. In the Northwest, the risk of fever is similarly high in Zamfara and Kebbi states [OR = 1.04; CI (0.93,1.17)], with Kastina state showing the lowest risk [OR = 0.39; CI (0.34,0.46)]. Children in Zamfara state experience notably different risks of fever and diarrhoea [OR = 0.07; CI (0.05,0.10)]. Kaduna state reports the highest incidence of diarrhoea [OR = 21.88; CI (15.54,30.82)], while Kano state has the lowest [OR = 2.50; CI (1.73,3.63)]. In the Southeast, Imo state leads in fever incidence [OR = 8.20; CI (5.61,11.98)], while Anambra state has the lowest [OR = 0.40; CI (0.21,0.78)]. In Abia state, the risk of fever is comparable to that in Enugu state [OR = 1.03; CI (0.63,1.71)], but the risks of fever and diarrhoea in Abia differ significantly [OR = 2.67; CI (1.75,4.06)]. Abia state also has the highest diarrhoea rate in the Southeast [OR = 2.67; CI (1.75,4.06)], with Ebonyi state having the lowest [OR = 0.05; CI (0.03,0.09)]. In the South-South region, Bayelsa and Edo states have similar risks of fever [OR = 1.28; CI (0.84,1.95)], with Akwa Ibom state reporting the highest fever rate [OR = 4.62; CI (3.27,6.52)] and Delta state the lowest [OR = 0.08; CI (0.02,0.25)]. Children in Bayelsa state face distinctly different risks of fever and diarrhoea [OR = 0.56; CI (0.34,0.95)]. Rivers state shows the highest incidence of diarrhoea in the South-South [OR = 10.50; CI (4.78,23.06)], while Akwa Ibom state has the lowest [OR = 0.30; CI (0.15,0.57)]. In the Southwest, Lagos and Osun states have similar risks of fever [OR = 1.00; CI (0.59,1.69)], with Ogun state experiencing the highest incidence [OR = 3.47; CI (2.28,5.28)] and Oyo state the lowest [OR = 0.18; CI (0.07,0.46)]. In Lagos state, the risks of fever and diarrhoea are comparable [OR = 0.96; CI (0.57,1.64)], and the risk of diarrhoea is similar to those in Ekiti, Ogun, and Ondo states. Oyo state has the highest diarrhoea rate in the Southwest [OR = 10.99; CI (3.81,31.67)], with Ogun state reporting the lowest [OR = 0.77; CI (0.42,1.42)]. Children of mothers with more than secondary education are significantly less likely to suffer ARI [OR = 0.35; CI (0.29,0.42)], whereas children of mothers without any education run a higher risk of diarrhoea [OR = 2.12; CI (1.89,2.38)] and fever [OR = 2.61; CI (2.34,2.91)]. Our analysis also indicated that household wealth quintile is a significant determinant of morbidity. The results in this paper could help the government and non-governmental agencies to focus and target intervention programs for ARI, diarrhoea and fever on the most vulnerable and risky under five groups and populations in Nigeria.
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Diarrea , Fiebre , Infecciones del Sistema Respiratorio , Humanos , Nigeria/epidemiología , Preescolar , Masculino , Lactante , Femenino , Diarrea/epidemiología , Fiebre/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Distribución de Poisson , Morbilidad , Factores de Riesgo , Prevalencia , Recién Nacido , Medición de RiesgoRESUMEN
Background: Diarrhea is a major cause of mortality and morbidity in under-5 children globally, especially in developing countries like Ethiopia. Limited research has used machine learning to predict childhood diarrhea. This study aimed to compare the predictive performance of ML algorithms for diarrhea in under-5 children in Ethiopia. Methods: The study utilized a dataset of 9501 under-5 children from the Ethiopia Demographic and Health Survey 2016. Five ML algorithms were used to build and compare predictive models. The model performance was evaluated using various metrics in Python. Boruta feature selection was employed, and data balancing techniques such as under-sampling, over-sampling, adaptive synthetic sampling, and synthetic minority oversampling as well as hyper parameter tuning methods were explored. Association rule mining was conducted using the Apriori algorithm in R to determine relationships between independent and target variables. Results: 10.2% of children had diarrhea. The Random Forest model had the best performance with 93.2% accuracy, 98.4% sensitivity, 85.5% specificity, and 0.916 AUC. The top predictors were residence, wealth index, and child age, number of living children, deworming, wasting, mother's occupation, and education. Association rule mining identified the top 7 rules most associated with under-5 diarrhea in Ethiopia. Conclusion: The RF achieved the highest performance for predicting childhood diarrhea. Policymakers and healthcare providers can use these findings to develop targeted interventions to reduce diarrhea. Customizing strategies based on the identified association rules has the potential to improve child health and decrease the impact of diarrhea in Ethiopia.
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Algoritmos , Diarrea , Aprendizaje Automático , Humanos , Etiopía/epidemiología , Diarrea/epidemiología , Diarrea/diagnóstico , Preescolar , Lactante , Femenino , Masculino , Recién Nacido , Encuestas Epidemiológicas/métodosRESUMEN
The gut microbiota of infants in low- to middle-income countries is underrepresented in microbiome research. This study explored the faecal microbiota composition and faecal cytokine profiles in a cohort of infants in a rural province of Cambodia and investigated the impact of sample storage conditions and infant environment on microbiota composition. Faecal samples collected at three time points from 32 infants were analysed for microbiota composition using 16S rRNA amplicon sequencing and concentrations of faecal cytokines. Faecal bacterial isolates were subjected to whole genome sequencing and genomic analysis. We compared the effects of two sample collection methods due to the challenges of faecal sample collection in a rural location. Storage of faecal samples in a DNA preservation solution preserved Bacteroides abundance. Microbiota analysis of preserved samples showed that Bifidobacterium was the most abundant genus with Bifidobacterium longum the most abundant species, with higher abundance in breast-fed infants. Most infants had detectable pathogenic taxa, with Shigella and Klebsiella more abundant in infants with recent diarrhoeal illness. Neither antibiotics nor infant growth were associated with gut microbiota composition. Genomic analysis of isolates showed gene clusters encoding the ability to digest human milk oligosaccharides in B. longum and B. breve isolates. Antibiotic-resistant genes were present in both potentially pathogenic species and in Bifidobacterium. Faecal concentrations of Interlukin-1alpha and vascular endothelial growth factor were higher in breast-fed infants. This study provides insights into an underrepresented population of rural Cambodian infants, showing pathogen exposure and breastfeeding impact gut microbiota composition and faecal immune profiles.
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Bifidobacterium , Citocinas , Diarrea , Heces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Población Rural , Humanos , Heces/microbiología , Lactante , Cambodia , Citocinas/metabolismo , ARN Ribosómico 16S/genética , Femenino , Masculino , Diarrea/microbiología , Bifidobacterium/genética , Bifidobacterium/aislamiento & purificación , Dieta , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Shigella/genética , Shigella/aislamiento & purificación , Bacteroides/genética , Bacteroides/aislamiento & purificación , Klebsiella/genética , Klebsiella/aislamiento & purificación , Lactancia Materna , ADN Bacteriano/genética , Secuenciación Completa del Genoma , Leche Humana/microbiología , Leche Humana/químicaRESUMEN
Diarrhea claims >500,000 lives annually among children under five years of age in low- and middle-income countries. Mortality due to acute diarrhea (<7 days' duration) is decreasing, but prolonged (7-13 days) and persistent (≥14 days of duration) diarrhea remains a massive challenge. Here, we use a case-control study to decipher if fecal gut microbiota compositional differences between Ethiopian children with acute (n=554) or prolonged/persistent (n=95) diarrhea and frequency-matched non-diarrheal controls (n=663) are linked to diarrheal etiology. We show that diarrhea cases are associated with lower bacterial diversity and enriched in Escherichia spp., Campylobacter spp., and Streptococcus spp. Further, diarrhea cases are depleted in gut commensals such as Prevotella copri, Faecalibacterium prausnitzii, and Dialister succinatiphilus, with depletion being most pronounced in prolonged/persistent cases, suggesting that prolonged duration of diarrhea is accompanied by depletion of gut commensals and that re-establishing these via e.g., microbiota-directed food supplements offer a potential treatment strategy.
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Diarrea , Heces , Microbioma Gastrointestinal , Humanos , Etiopía/epidemiología , Diarrea/microbiología , Diarrea/epidemiología , Preescolar , Lactante , Estudios de Casos y Controles , Masculino , Femenino , Heces/microbiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genéticaRESUMEN
BACKGROUND: Calf diarrhea is a major cause of morbidity and mortality in the livestock sector worldwide and it can be caused by multiple infectious agents. In Ethiopia, cattle are the most economically important species within the livestock sector, but at the same time the young animals suffer from high rates of morbidity and mortality due to calf diarrhea. However, studies including both screening and molecular characterization of bovine enteric pathogens are lacking. Therefore, we aimed to both detect and molecularly characterize four of the major enteric pathogens in calf diarrhea, Enterotoxigenic Escherichia coli (E. coli K99 +), Cryptosporidium spp., rotavirus A (RVA), and bovine coronavirus (BCoV) in calves from central Ethiopia. Diarrheic and non-diarrheic calves were included in the study and fecal samples were analyzed with antigen-ELISA and quantitative real-time PCR (qPCR). Positive samples were further characterized by genotyping PCRs. RESULTS: All four pathogens were detected in both diarrheic and non-diarrheic calves using qPCR and further characterization showed the presence of three Cryptosporidium species, C. andersoni, C. bovis and C. ryanae. Furthermore, genotyping of RVA-positive samples found a common bovine genotype G10P[11], as well as a more unusual G-type, G24. To our knowledge this is the first detection of the G24 RVA genotype in Ethiopia as well as in Africa. Lastly, investigation of the spike gene revealed two distinct BCoV strains, one classical BCoV strain and one bovine-like CoV strain. CONCLUSIONS: Our results show that Cryptosporidium spp., E. coli K99 + , RVA and BCoV circulate in calves from central Ethiopia. Furthermore, our findings of the rare RVA G-type G24 and a bovine-like CoV demonstrates the importance of genetic characterization.
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Enfermedades de los Bovinos , Coronavirus Bovino , Cryptosporidium , Diarrea , Heces , Rotavirus , Animales , Bovinos , Etiopía/epidemiología , Diarrea/veterinaria , Diarrea/virología , Diarrea/microbiología , Diarrea/parasitología , Enfermedades de los Bovinos/virología , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/parasitología , Heces/virología , Heces/parasitología , Heces/microbiología , Rotavirus/genética , Rotavirus/aislamiento & purificación , Rotavirus/clasificación , Cryptosporidium/aislamiento & purificación , Cryptosporidium/genética , Cryptosporidium/clasificación , Coronavirus Bovino/genética , Coronavirus Bovino/aislamiento & purificación , Escherichia coli Enterotoxigénica/aislamiento & purificación , Escherichia coli Enterotoxigénica/genética , Genotipo , Criptosporidiosis/epidemiología , Infecciones por Rotavirus/veterinaria , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/epidemiología , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiologíaRESUMEN
Congenital diarrhoeas and enteropathies (CODE) are a heterogeneous group of disorders. Many affected infants present with catastrophic dehydration in the first few days of life, although the clinical phenotype is variable. Advances in the understanding of underlying pathomechanisms and genetic testing, as well as improved management, in particular intravenous nutrition support, have allowed affected patients to survive well beyond childhood. Awareness and understanding of these rare diseases are hence needed, both amongst paediatricians and adult physicians. In this review, we discuss the different groups of disorders based on a review of the current literature and provide a diagnostic and therapeutic approach. Many of the subtypes of CODE result in the need for prolonged or indefinite parenteral nutrition. Further research is needed to identify new CODE to improve the recognition and management of these children, which can assist in developing new targeted therapies and potentially a long-term cure.
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Diarrea , Nutrición Parenteral , Humanos , Recién Nacido , Diarrea/terapia , Diarrea/congénito , Diarrea/etiología , Enfermedades Intestinales/terapia , Enfermedades Intestinales/genética , Deshidratación/terapia , LactanteRESUMEN
Chemotherapy-induced diarrhea (CID) is a potentially serious side effect that often occurs during anticancer therapy and is caused by the toxic effects of chemotherapeutic drugs on the gastrointestinal tract, resulting in increased frequency of bowel movements and fluid contents. Among these agents, irinotecan (CPT-11) is most commonly associated with CID. Hesperidin (HPD), a flavonoid glycoside found predominantly in citrus fruits, has anti-oxidation properties and anti-inflammation properties that may benefit CID management. Nevertheless, its potential mechanism is still uncertain. In this study, we firstly evaluated the pharmacodynamics of HPD for the treatment of CID in a mouse model, then used network pharmacology and molecular docking methods to excavate the mechanism of HPD in relieving CID, and finally further proved the predicted mechanism through molecular biology experiments. The results demonstrate that HPD significantly alleviated diarrhea, weight loss, colonic pathological damage, oxidative stress, and inflammation in CID mice. In addition, 74 potential targets for HPD intervention in CID were verified by network pharmacology, with the top 10 key targets being AKT1, CASP3, ALB, EGFR, HSP90AA1, MMP9, ESR1, ANXA5, PPARG, and IGF1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the PI3K-Akt pathway, FoxO pathway, MAPK pathway, TNF pathway, and Ras pathway were most relevant to the HPD potential treatment of CID genes. The molecular docking results showed that HPD had good binding to seven apoptosis-related targets, including AKT1, ANXA5, CASP3, HSP90AA1, IGF1, MMP9, and PPARG. Moreover, we verified apoptosis by TdT-mediated dUTP nick-end labeling (TUNEL) staining and immunohistochemistry, and the hypothesis about the proteins above was further verified by Western blotting in vivo experiments. Overall, this study elucidates the potential and underlying mechanisms of HPD in alleviating CID.
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Diarrea , Hesperidina , Irinotecán , Simulación del Acoplamiento Molecular , Farmacología en Red , Hesperidina/farmacología , Hesperidina/química , Hesperidina/uso terapéutico , Animales , Diarrea/tratamiento farmacológico , Diarrea/inducido químicamente , Ratones , Irinotecán/efectos adversos , Irinotecán/farmacología , Modelos Animales de Enfermedad , Masculino , Estrés Oxidativo/efectos de los fármacosRESUMEN
Irritable bowel syndrome with diarrhea (IBS-D) is the most prevalent subtype of IBS, characterized by chronic gastrointestinal symptoms in the absence of identifiable pathological findings. This study aims to investigate the molecular mechanisms underlying IBS-D using transcriptomic data. By employing causal network inference methods, we identify key transcriptomic modules associated with IBS-D. Utilizing data from public databases and applying advanced computational techniques, we uncover potential biomarkers and therapeutic targets. Our analysis reveals significant molecular alterations that affect cellular functions, offering new insights into the complex pathophysiology of IBS-D. These findings enhance our understanding of the disease and may foster the development of more effective treatments.
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Diarrea , Redes Reguladoras de Genes , Síndrome del Colon Irritable , Transcriptoma , Síndrome del Colon Irritable/genética , Síndrome del Colon Irritable/metabolismo , Humanos , Diarrea/genética , Perfilación de la Expresión Génica/métodos , Biología Computacional/métodos , BiomarcadoresRESUMEN
INTRODUCTION: Zinc with oral re-hydration salt supplementation provides much improved outcomes for managing childhood diarrhea. There is scarcity of evidence in the study area regarding zinc supplementation adherence and factors associated with. Thus, the aim of this study was to assess zinc supplementation adherence and associated factors among caregivers of under five children with diarrhea attending health centers in Gondar City. METHODS: An institutional based cross-sectional study was conducted with 405 caregivers of under-five children with diarrhea who received zinc supplementation in Gondar City health centers. Bivariable and multivariable logistic regression analysis were computed. RESULTS: 35% (95% CI: 29.91, 39.21) of caregivers of under five children adhered for zinc supplementation. Adherence was observed among caregivers with good knowledge about zinc supplementation (AOR = 3.01 95%CI = 1.73, 5.24), and who received counseling (AOR = 8.4, 95%CI = 4.66, 15.13), presence of side effects (AOR = 0.35, 95% CI 0.20, 0.65) was negatively associated with zinc supplementation adherence. CONCLUSION: In the study area, more than one third of children with diarrhea were adhered to zinc supplementation. Thus, improving the knowledge of caregivers and enhancing counseling services on benefits, dosage, duration and side effects of zinc supplementation are vital to improve adherence in the area.
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Cuidadores , Diarrea , Suplementos Dietéticos , Cumplimiento de la Medicación , Zinc , Humanos , Cuidadores/psicología , Femenino , Masculino , Zinc/uso terapéutico , Zinc/administración & dosificación , Diarrea/tratamiento farmacológico , Etiopía , Estudios Transversales , Preescolar , Lactante , Adulto , Cumplimiento de la Medicación/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Adulto Joven , Adolescente , Persona de Mediana EdadRESUMEN
Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of diarrheal illnesses annually ranging from mildly symptomatic cases to severe, life-threatening cholera-like diarrhea. Although ETEC are associated with long-term sequelae including malnutrition, the acute diarrheal illness is largely self-limited. Recent studies indicate that in addition to causing diarrhea, the ETEC heat-labile toxin (LT) modulates the expression of many genes in intestinal epithelia, including carcinoembryonic cell adhesion molecules (CEACAMs) which ETEC exploit as receptors, enabling toxin delivery. Here, however, we demonstrate that LT also enhances the expression of CEACAMs on extracellular vesicles (EV) shed by intestinal epithelia and that CEACAM-laden EV increase in abundance during human infections, mitigate pathogen-host interactions, scavenge free ETEC toxins, and accelerate ETEC clearance from the gastrointestinal tract. Collectively, these findings indicate that CEACAMs play a multifaceted role in ETEC pathogen-host interactions, transiently favoring the pathogen, but ultimately contributing to innate responses that extinguish these common infections.
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Toxinas Bacterianas , Escherichia coli Enterotoxigénica , Enterotoxinas , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Interacciones Huésped-Patógeno , Escherichia coli Enterotoxigénica/metabolismo , Humanos , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Enterotoxinas/metabolismo , Toxinas Bacterianas/metabolismo , Vesículas Extracelulares/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Animales , Ratones , Antígenos CD/metabolismo , Antígenos CD/genética , Antígeno Carcinoembrionario/metabolismo , Antígeno Carcinoembrionario/genética , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Diarrea/microbiología , Diarrea/metabolismoRESUMEN
Bongkrekic acid (BKA), a rarely happened foodborne toxin by Burkholderia gladioli pathovar cocovenenans (Burkholderia cocovenenans) might leads to devastating life-threatening condition after eating meal contaminated BKA. Unbelievable event from March 19, 2024, to March 24, 2024, there was an outbreak of BAP in a luxury shopping area of eastern Taipei, Taiwan. Most of the victims are young to middle-aged people who made a tour over there and ate the cooked wet rice noodles. Of them, 13 males and 20 females, aged 40.9 ± 14.7 years old visited or were sent by ambulances to the emergency department presenting with watery diarrhea, and vomiting. Some progressed to severe hepatic and renal failure, altered mental status, disseminated intravascular coagulation, and fatalities within several hours within 2 days. The primary health workers especially emergency physicians need to keep in mind of BKA poisoning is quite different in presentations from other infectious colitis commonly seen before. Knowing the toxic-kinetic and toxic-dynamic mechanisms is important to farseeing the presentation of these BAP patients. Throughout this outbreak, we gathered abundant experiences in mitigating and managing these debilitated patients. Aggressively supportive care and early liver transplantation if there is no concurrent inflammatory process and the patient's condition is tolerable to surgical intervention saves lives. For food safety education, it is crucial to enhance our understanding of inhibiting BKA production and promote proper food preservation methods and a suitable environment to ensure food safety.
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Enfermedades Transmitidas por los Alimentos , Humanos , Taiwán/epidemiología , Femenino , Masculino , Adulto , Enfermedades Transmitidas por los Alimentos/etiología , Enfermedades Transmitidas por los Alimentos/epidemiología , Brotes de Enfermedades , Burkholderia gladioli , Persona de Mediana Edad , Diarrea/inducido químicamenteAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunodeficiencia Combinada Grave , Humanos , Inmunodeficiencia Combinada Grave/terapia , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/genética , Masculino , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Lactante , Diabetes Mellitus Tipo 1/congénito , Diarrea , Enfermedades del Sistema Inmune/congénitoRESUMEN
INTRODUCTION: Diarrhoea is a major public health concern in developing countries, usually exacerbated by poor water, sanitation and hygiene but its aetiology is under-studied, particularly away from capital cities. We identified diarrhoeagenic Escherichia coli (DEC) from stools collected in Ile-Ife and Ilesa, Osun state, Nigeria and determined their antibiotic resistance profiles. METHODS: Stool samples from 167 children with diarrhoea and 334 controls under the age of 5 years were cultured for Escherichia coli and Salmonella. Bacterial isolates were identified biochemically and DEC were identified by PCR. Antimicrobial susceptibility testing was by modified Kirby-Bauer disc diffusion method in accordance with the CLSI guidelines. Data were analyzed using Chi-square and Fisher's exact tests. RESULT: Diarrhoea infection is significantly high among children under 12 months (p = 0.002), caregivers without at least primary school education (p = 0.006), breastfeeding for under 6 months (pË0.001), and caregivers who were siblings (p = 0.004). DEC was detected in 69(41.3%) cases but only 86(25.7%) controls (p < 0.001) and more commonly recovered during the wet season (p < 0.001). Enterotoxigenic E. coli (p = 0.031), enteropathogenic E. coli (p = 0.031) and Shiga-toxin-producing E. coli (p = 0.044) were recovered more commonly from cases than controls. DEC from patients with diarrhoea were commonly resistant to sulphonamides (91.3%), trimethoprim (82.6%), and ampicillin (78.3%) but were largely susceptible to quinolones and carbapenems (97.1%). CONCLUSION: Enteropathogenic, enterotoxigenic and Shiga toxin-producing E. coli are associated with diarrhoea in our setting, and show considerable resistance to first-line antimicrobials. Risk factors for DEC diarrhoea include infancy, inadequate breastfeeding and caregivers with education below primary school.