Infecciones por Clostridioides difficile en pediatría. La visión del laboratorio a partir del diagnóstico microbiológico / Clostridioides difficile infections in pediatrics. The view of the laboratory based on microbiological diagnosis

La infección por Clostridioides difficile (ICD) es la principal responsable de diarreas nosocomiales en adultos. En los últimos años se registró un aumento en la incidencia de la ICD en la población adulta que, en cambio, no fue bien caracterizado en pediatría. El objetivo de este trabajo es analizar los datos resultantes del diagnóstico microbiológico de ICD en el Hospital de Pediatría "Prof. Dr. Juan P. Garrahan". Materiales y métodos: se realizó un estudio retrospectivo observacional descriptivo que abarcó desde el 01/01/2018 hasta el 31/12/2021. El diagnóstico se realizó mediante enzimoinmunoensayo para glutamato deshidrogenasa (GDH) y toxinas en materia fecal (MF). Cuando sólo se detectó GDH, se realizó un cultivo toxigénico (CT) de la MF para la detección de toxinas in vitro. Se registraron: edad, sexo y procedencia de los pacientes y recurrencias de las ICD. Se efectuaron estudios de sensibilidad de 387 cepas de C. difficile a metronidazol (MTZ) y vancomicina (VAN). Resultados: en 6632 muestras (1764 pacientes) se registraron 649 estudios positivos (9,8%) (139 pacientes), la mayoría correspondieron a pacientes internados en áreas no críticas. Edad promedio: 7 años (7 ± 4,7). Sexo: 55% masculino. Recurrencias: 62 (45%). Positivos detectados mediante CT: 43%. Sensibilidad antibiótica: 100% a MTZ y 99,7% a VAN. Conclusión: Nuestra población presenta un bajo porcentaje de positividad. Se destaca el rendimiento del CT que permitió el diagnóstico de más de un tercio de los casos. MTZ y VANCO tuvieron excelente actividad in vitro frente a C. difficile (AU)

Clostridioides difficile infection (CDI) is the main cause of nosocomial diarrhea in adults. In recent years there has been an increase in the incidence of CDI in the adult population; however, CDI has not been well characterized in pediatrics. The aim of this study was to analyze the data resulting from the microbiological diagnosis of CDI at Hospital de Pediatría Prof. Dr. Juan P. Garrahan. Materials and methods: a retrospective, observational and descriptive study was conducted from 01/01/2018 to 12/31/2021. Diagnosis was made using enzyme immunoassay for glutamate dehydrogenase (GDH) and toxins in stools. When only GDH was detected, toxigenic culture (TC) of stools was performed for in vitro toxin detection. The age, sex and origin of patients and CDI recurrences were recorded. Sensitivity studies of 387 strains of C. difficile to metronidazole (MTZ) and vancomycin (VAN) were performed. Results: In 6,632 samples (1,764 patients), 649 positive results (9.8%) were recorded (139 patients), most of which corresponded to patients hospitalized in noncritical areas. Mean age: 7 years (7 ± 4.7). Sex: 55% male. Recurrences: 62 (45%). TC-positive results: 43%. Antibiotic sensitivity: 100% to MTZ and 99.7% to VAN. Conclusion: A low percentage of positivity was found in our population. The performance of TC was outstanding, allowing for the diagnosis of more than one third of the cases. MTZ and VANCO had excellent in vitro activity against C. difficile (AU)

Diarrea grave en una lactante previamente sana: un reto diagnóstico / Severe diarrhoea in a previously healthy infant: a diagnostic challenge

Aunque la causa más frecuente de los procesos diarreicos infantiles son las infecciones, ante cuadros graves y prolongados en el tiempo en los lactantes hay que descartar causas congénitas como trastornos genéticos o inmunodeficiencias. La colitis por citomegalovirus (CMV) es una causa poco frecuente de diarrea crónica en niños inmunocompetentes. Por lo general, su curso es leve y autolimitado, por lo que debemos pensar la posibilidad de que exista una inmunodeficiencia en los casos con una evolución más grave. Se recomienda realizar un estudio endoscópico en estos pacientes, precisando tratamiento antiviral aquellos con un curso de la enfermedad más grave o en caso de confirmarse situación de inmunodepresión (AU)

Although the most frequent cause of childhood diarrheal processes is infection, in the case of severe and prolonged symptoms in infants, congenital causes such as genetic disorders or immunodeficiencies must be ruled out. Cytomegalovirus (CMV) colitis is a rare cause of chronic diarrhoea in immunocompetent children. In general, it is a mild and self-limiting disease, so the possibility of immunodeficiency should be considered in cases with a more severe course. Performance of an endoscopic examination is recommended in these patients, and antiviral treatment is required in those with more severe forms of disease or with confirmed immunosuppression. (AU)

Principales agentes etiológicos de las enfermedades diarreicas agudas infantiles en Chimborazo, Ecuador / Main etiological agents of childhood acute diarrheal diseases in Chimborazo, Ecuador

Las enfermedades diarreicas constituyen la principal causa de morbimortalidad en niños menores de cinco años, con alrededor de 1.700 millones de casos y 1,5 millones de muertes por año a nivel mundial. Para el año 2010, en la Sierra de Ecuador se registró un alto porcentaje de infantes fallecidos a causa de enfermedades diarreicas agudas (EDA), incluyendo la provincia de Chimborazo; mientras que, para el año 2016, se registraron en Ecuador 590.523 casos de EDA, siendo más afectados los niños de sectores de mayor pobreza. Se realizó un estudio descriptivo en pacientes pediátricos con episodios diarreicos que acudieron a centros de salud de los cantones rurales de la provincia Chimborazo. Se realizó análisis coprológico y coproparasitológico en 258 muestras; se identificaron bacterias enteropatógenas mediante pruebas bioquímicas y de susceptibilidad antimicrobiana, se realizó diagnóstico parasitológico mediante análisis macroscópico y microscópico y para detección de virus se emplearon pruebas inmunológicas. Se observó un mayor número de casos de EDA en los cantones Alausí (50%) y Chunchi (19%). De los pacientes con EDA, los rotavirus son el principal agente etiológico aislado (24,8%), seguido por Shigella (17,8%); mientras que Giardia intestinalis (8,5%) y Salmonella (10,1%) son los microorganismos que se aislaron con menor frecuencia en las muestras. Los resultados del presente estudio, permiten tener un panorama etiológico de las EDA en la provincia de Chimborazo y contribuir en la vigilancia epidemiológica, ejecución de programas sanitarios y de vacunación, para disminuir la vulnerabilidad de la población infantil ante dichas infecciones(AU)

Diarrheal diseases are the main cause of morbidity and mortality in children under five years of age, with around 1.7 billion cases and 1.5 million deaths per year worldwide. For the year 2010, in the Sierra de Ecuador a high percentage of infants died due to acute diarrheal diseases (ADD), including the province of Chimborazo; while, for the year 2016, 590,523 cases of ADD were registered in Ecuador, with children from the poorest sectors being more affected. A descriptive study was carried out in pediatric patients with diarrheal episodes who attended health centers in the rural cantons of Chimborazo province. Coprological and coproparasitological analysis was performed on 258 samples; Enteropathogenic bacteria were identified by biochemical and antimicrobial susceptibility tests, a parasitological diagnosis was made by macroscopic and microscopic analysis, and immunological tests were used to detect viruses. A greater number of ADD cases was observed in the Alausí (50%) and Chunchi (19%) cantons. Of patients with ADD, rotaviruses are the main etiological agent isolated (24.8%), followed by Shigella (17.8%); while Giardia intestinalis (8.5%) and Salmonella (10.1%) are the microorganisms that were isolated less frequently in the samples. The results of this study allow us to have an etiological panorama of EDA in the province of Chimborazo and contribute to epidemiological surveillance, execution of health and vaccination programs, to reduce the vulnerability of the child population to these infections(AU)

Aberrant Epithelial Differentiation Contributes to Pathogenesis in a Murine Model of Congenital Tufting Enteropathy.

BACKGROUND & AIMS: Congenital tufting enteropathy (CTE) is an intractable diarrheal disease of infancy caused by mutations of epithelial cell adhesion molecule (EpCAM). The cellular and molecular basis of CTE pathology has been elusive. We hypothesized that the loss of EpCAM in CTE results in altered lineage differentiation and defects in absorptive enterocytes thereby contributing to CTE pathogenesis. METHODS: Intestine and colon from mice expressing a CTE-associated mutant form of EpCAM (mutant mice) were evaluated for specific markers by quantitative real-time polymerase chain reaction, Western blotting, and immunostaining. Body weight, blood glucose, and intestinal enzyme activity were also investigated. Enteroids derived from mutant mice were used to assess whether the decreased census of major secretory cells could be rescued. RESULTS: Mutant mice exhibited alterations in brush-border ultrastructure, function, disaccharidase activity, and glucose absorption, potentially contributing to nutrient malabsorption and impaired weight gain. Altered cell differentiation in mutant mice led to decreased enteroendocrine cells and increased numbers of nonsecretory cells, though the hypertrophied absorptive enterocytes lacked key features, causing brush border malfunction. Further, treatment with the Notch signaling inhibitor, DAPT, increased the numbers of major secretory cell types in mutant enteroids (graphical abstract 1). CONCLUSIONS: Alterations in intestinal epithelial cell differentiation in mutant mice favor an increase in absorptive cells at the expense of major secretory cells. Although the proportion of absorptive enterocytes is increased, they lack key functional properties. We conclude that these effects underlie pathogenic features of CTE such as malabsorption and diarrhea, and ultimately the failure to thrive seen in patients.

Neonatal late-onset infection with SARS CoV-2 / [Sepsis neonatal tardía por SARS CoV-2].

During the SARS COV-2 pandemic, the vast majority of infected patients are showing symptoms related to lung damage. At pediatric ages, especially newborns, symptoms from other organ systems without respiratory illness could make COVID-19 hard to diagnose. We are reporting three cases of newborns who were attended in the course of the mitigation phase in the emergency service of a maternal hospital in Barranquilla, Colombia, for high temperature and general compromised condition. During their clinical course, they developed gastrointestinal symptoms without showing any respiratory manifestations. They were not epidemiologically linked to a contact suspected to be a COVID-19 case and their mothers had had no respiratory symptoms since the public health emergency in our country was declared 45 days before. The absence of clinical respiratory manifestations in this group of patients with COVID-19 should draw clinicians' attention to the need to suspect SARS CoV-2 infection in febrile newborns.

Durante la pandemia por SARS CoV-2 la gran mayoría de pacientes ha presentado afectación pulmonar como síntoma cardinal. En los niños, especialmente en recién nacidos, la sintomatología debida al efecto en otros sistemas diferentes al respiratorio puede dificultar el diagnóstico. Se reportan tres casos de recién nacidos atendidos durante la fase de mitigación de la pandemia por SARS CoV-2 en el servicio de urgencias de un hospital materno-infantil en Barranquilla, Colombia, por presentar cuadros febriles que afectaban su estado general. En su evolución clínica predominó la sintomatología gastrointestinal sin que desarrollaran nunca manifestaciones respiratorias. La investigación epidemiológica no evidenció contacto con casos sospechosos o positivos para COVID-19. Sus madres no habían tenido síntomas respiratorios en los 45 días transcurridos desde la declaración de la emergencia en salud pública en el país. La ausencia de manifestaciones clínicas respiratorias en este grupo de pacientes con COVID-19 debe llamar la atención de los clínicos sobre la necesidad de sospechar la infección por SARS CoV-2 en recién nacidos con estados febriles.

Maternal Diarrhea and Antibiotic Use are Associated with Increased Risk of Diarrhea among HIV-Exposed, Uninfected Infants in Kenya.

HIV-exposed, uninfected (HEU) children are a growing population at particularly high risk of infection-related death in whom preventing diarrhea may significantly reduce under-5 morbidity and mortality in sub-Saharan Africa. A historic cohort (1999-2002) of Kenyan HEU infants followed from birth to 12 months was used. Maternal and infant morbidity were ascertained at monthly clinic visits and unscheduled sick visits. The Andersen-Gill Cox model was used to assess maternal, environmental, and infant correlates of diarrhea, moderate-to-severe diarrhea (MSD; diarrhea with dehydration, dysentery, or related hospital admission), and prolonged/persistent diarrhea (> 7 days) in infants. HIV-exposed, uninfected infants (n = 373) experienced a mean 2.09 (95% CI: 1.93, 2.25) episodes of diarrhea, 0.47 (95% CI: 0.40, 0.55) episodes of MSD, and 0.34 (95% CI: 0.29, 0.42) episodes of prolonged/persistent diarrhea in their first year. Postpartum maternal diarrhea was associated with increased risk of infant diarrhea (Hazard ratio [HR]: 2.09; 95% CI: 1.43, 3.06) and MSD (HR: 2.89; 95% CI: 1.10, 7.59). Maternal antibiotic use was a risk factor for prolonged/persistent diarrhea (HR: 1.63; 95% CI: 1.04, 2.55). Infants living in households with a pit latrine were 1.44 (95% CI: 1.19, 1.74) and 1.49 (95% CI: 1.04, 2.14) times more likely to experience diarrhea and MSD, respectively, relative to those with a flush toilet. Current exclusive breastfeeding was protective against MSD (HR: 0.30; 95% CI: 0.15, 0.58) relative to infants receiving no breast milk. Reductions in maternal diarrhea may result in substantial reductions in diarrhea morbidity among HEU children, in addition to standard diarrhea prevention interventions.

Disease burden and risk factors of diarrhoea in children under five years: Evidence from Kenya's demographic health survey 2014.

OBJECTIVE: This study aimed at examining the socio-demographic, environmental and behavioural determinants of diarrhoea in children under five years in Kenya. METHODS: The study entailed an analysis of secondary data from the Kenya Demographic Health Survey (DHS) 2014 using STATA Corp 2010. A total of 19,889 children <5 years were in the study, out of whom 2,906 had diarrhoea in the last two weeks prior to the survey. Descriptive analysis of independent variables and logistic regression model was used to analyse risk factors associated with diarrhoea in children <5 years. RESULTS: The most significant risk factors (p < 0.05) associated with diarrhoea morbidity in children <5 years were child age (AOR 2.26 95% CI 1.64, 3.11), low level of caregiver's education (AOR 1.45 95% CI 1.11, 1.90) and unsafe disposal of children's faeces (AOR 1.29 95% CI 1.03, 1.61). Wealthier households (AOR 0.83 95% CI 0.68, 1) were protective for diarrhoea in children <5 years. CONCLUSION: Increasing caregiver education, wealthier households and promoting hygienic behaviours in poor households were associated with reducing diarrhoea. Programmes aimed at reducing diarrhoea may achieve better results in targeting caregivers with children in high risk age cohorts of 6-23 months.

Prelacteal and early formula feeding increase risk of infant hospitalisation: a prospective cohort study.

OBJECTIVE: To ascertain the relationship between prelacteal feeding, early formula feeding and adverse health outcomes, especially hospitalisation during the first year of life. DESIGN: Multicentre prospective cohort study. SETTING: Six hospitals across three cities in Vietnam. PATIENTS: A total of 2030 pregnant women were recruited at 24-28 weeks of gestation and followed up at hospital discharge, 1, 3, 6 and 12 months post partum. MAIN OUTCOME MEASURES: Rates of infant hospitalisation, diarrhoea and lower respiratory tract infection during the first 12 months. RESULTS: For the final complete sample (n=1709, 84%), about one-quarter of the infants experienced diarrhoea (25.5%) or were admitted to hospital with at least one episode (24.8%), and almost half (47.6%) the cohort contracted lower respiratory tract infection by 12 months. The prevalence of prelacteal feeding was high (56.5%) while formula feeding was common (79.5%) before hospital discharge, both of which increased the risks of adverse health outcomes particularly hospitalisation by approximately 1.5-fold, with adjusted OR (95% CI) 1.43 (1.09 to 1.88) and 1.48 (1.07 to 2.05), respectively for these infants by 12 months, when compared with others who were exclusively breast fed. CONCLUSIONS: Prelacteal feeding and early formula feeding before hospital discharge are associated with higher risks of infection and hospital admission in Vietnamese infants. Support for exclusive breast feeding should be provided to mothers to avoid the adverse consequences of giving formula milk and prelateal foods.

¿La patata es culpable? / Is the potato guilty?

El síndrome de enterocolitis inducida por proteínas alimentarias (FPIES o food protein-induced enterocolytis syndrome) es una patología alérgica no mediada por IgE inducida por proteínas alimentarias. Cursa con vómitos de repetición asociados a diarrea, palidez, letargia o hipotensión 1-4 horas tras la ingesta del alimento desencadenante. Los desencadenantes más habituales son la leche de vaca y la soja; sin embargo, también se han descrito asociada a alimentos sólidos, como la patata

Food protein-induced enterocolitis syndrome (FPIES) is a non IgE mediated allergic disorder induced by food protein that presents in young infants. It is characterized by persistent vomiting associated to diarrhea, lethargy, pallor or hypotension presenting 1-4 hours after the ingestion of the triggering food. The most frequent triggers are cows's milk and soy, but solid foods have also been described as triggers, including potato

Geographical Variations and Factors Associated with Childhood Diarrhea in Tanzania: A National Population Based Survey 2015-16.

BACKGROUND: Diarrhea remains the leading cause of morbidity and mortality among under 5 children in low- and middle-income countries. In Tanzania, diarrhea remains one of the major public health problems. This study aimed to investigate spatial variations and the factors correlated with diarrhea in under five children. METHODS: This is a secondary data analysis using data from the population-based cross section Tanzanian Demographic and Health Survey 2015-16 data. Spatial analysis was done using the Bernoulli model from SaTScan™ software, and a generalized linear mixed model was used to identify the factors associated with childhood diarrhea. RESULTS: The overall reported prevalence of childhood diarrhea for the under five children in Tanzania was 12.1% (95%CI 11.3%-12.9%). The SaTScan spatial statics analysis revealed that diarrhea in children was not random. The odds of diarrhea were 7.35 times higher (AOR= 7.35; 95%CI: 5.29, 10.22) among children in the 6-11 months age group compared to children within the 48-59 months of age. As mother's age increased, the risk of diarrhea for the under five children decreased whereas the highest risk of diarrhea was observed in the two rich income brackets richer (AOR=1.70, 95%CI=1.30, 2.22), and richest (AOR= 1.05, 95%CI=1, 1.09). The odds of diarrhea were 1.25 times higher (AOR=1.25, 95%CI=1.06, 1.46) among children with unsafe stool disposal compared to those with safe disposal. CONCLUSION: The socio-demographic factors associated with diarrhea among children were mother's age in years, current age of the child, wealth index and child stool disposal.

Oral Rehydration in Children with Acute Diarrhoea and Moderate Dehydration-Effectiveness of an ORS Tolerance Test.

Oral rehydration solution (ORS) is the mainstay of treatment of acute watery diarrhoea, but it is underutilized in many hospitals, resulting in children with moderate degrees of dehydration being unnecessarily hospitalized and receiving intravenous fluids. We aimed to assess the utility of an ORS tolerance test on initial presentation to an emergency department, and determine the volume of ORS a child with diarrhoea and moderate dehydration needed to tolerate to be successfully managed at home. One hundred and twenty-nine children with acute watery diarrhoea and moderate dehydration were given ORS and observed in a Children's Emergency Department (CED) over a period of 2-4 h. Patients were admitted, kept in the CED for further management or discharged, based on the assessment of oral intake and the clinical judgement of the treating health workers. Seventy-nine (61.2%) patients tolerated ORS well. They drank a median [interquartile range (IQR)] of 24.4 ml (IQR 12.5-28.8) ml/kg, were judged to have passed the ORS test and were discharged to continue oral rehydration treatment at home. At follow-up on days 2 and 5, 63/79 (79.7%) children had improved, were adequately hydrated and the diarrhoea had reduced. Sixteen of the 79 (20.3%) failed oral home treatment, with persisting diarrhoea, vomiting, hypokalaemia and/or weakness. The 63 who succeeded had tolerated a median of 25.8 (IQR 18.4-30.0) ml/kg of ORS in the CED, whilst the 16 who failed oral home treatment had tolerated 11.1 (IQR 9.1-23.0) ml/kg ORS (p < 0.001).

A Rare Cause of Intractable Diarrhea of Infancy.

Intractable watery diarrhea presenting in the neonatal period is a relatively uncommon condition. Congenital disorders of malabsorption are among the major causes of prolonged watery diarrhea. This is the case report of a 3-month male infant born to consanguineous parents, who presented with intractable diarrhea since birth. He was failing to thrive and wasted. Persistent diarrhea lead to prolonged hospitalisation and recurrent hypernatremic dehydration. Relevant investigations clinched the diagnosis of ''congenital glucose galactose malabsorption (CGGM)''. The astute clinician should have a high index of suspicion regarding such rare causes of diarrhea in early infancy, as an appropriate rational diagnosis can lead to life-saving treatment as depicted in this case report.

Malabsorción congénita de glucosa y galactosa: una causa rara de diarrea grave en el lactante / Congenital glucose-galactose malabsorption: A rare and severe cause of infant diarrhea

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The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: a 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS).

BACKGROUND: Diarrheal diseases remain a leading cause of illness and death among children younger than 5 years in low-income and middle-income countries. The Global Enteric Multicenter Study (GEMS) has described the incidence, aetiology, and sequelae of medically attended moderate-to-severe diarrhoea (MSD) among children aged 0-59 months residing in censused populations in sub-Saharan Africa and south Asia, where most child deaths occur. To further characterise this disease burden and guide interventions, we extended this study to include children with episodes of less-severe diarrhoea (LSD) seeking care at health centres serving six GEMS sites. METHODS: We report a 1-year, multisite, age-stratified, matched case-control study following on to the GEMS study. Six sites (Bamako, Mali; Manhiça, Mozambique; Basse, The Gambia; Mirzapur, Bangladesh; Kolkata, India; and Bin Qasim Town, Karachi, Pakistan) participated in this study. Children aged 0-59 months at each site who sought care at a sentinel hospital or health centre during a 12-month period were screened for diarrhoea. New (onset after ≥7 diarrhoea-free days) and acute (onset within the previous 7 days) episodes of diarrhoea in children who had sunken eyes, whose skin lost turgor, who received intravenous hydration, who had dysentery, or who were hospitalised were eligible for inclusion as MSD. The remaining new and acute diarrhoea episodes among children who sought care at the same health centres were considered LSD. We aimed to enrol the first eight or nine eligible children with MSD and LSD at each site during each fortnight in three age strata: infants (aged 0-11 months), toddlers (aged 12-23 months), and young children (aged 24-59 months). For each included case of MSD or LSD, we enrolled one to three community control children without diarrhoea during the previous 7 days. From patients and controls we collected clinical and epidemiological data, anthropometric measurements, and faecal samples to identify enteropathogens at enrolment, and we performed a follow-up home visit about 60 days later to ascertain vital status, clinical outcome, and interval growth. Primary outcomes were to characterise, for MSD and LSD, the pathogen-specific attributable risk and population-based incidence values, and to assess the frequency of adverse clinical consequences associated with these two diarrhoeal syndromes. FINDINGS: From Oct 31, 2011, to Nov 14, 2012, we recruited 2368 children with MSD, 3174 with LSD, and one to three randomly selected community control children without diarrhoea matched to cases with MSD (n=3597) or LSD (n=4236). Weighted adjusted population attributable fractions showed that most attributable cases of MSD and LSD were due to rotavirus, Cryptosporidium spp, enterotoxigenic Escherichia coli encoding heat-stable toxin (with or without genes encoding heat-labile enterotoxin), and Shigella spp. The attributable incidence per 100 child-years for LSD versus MSD, by age stratum, for rotavirus was 22·3 versus 5·5 (0-11 months), 9·8 versus 2·9 (12-23 months), and 0·5 versus 0·2 (24-59 months); for Cryptosporidium spp was 3·6 versus 2·3 (0-11 months), 4·3 versus 0·6 (12-23 months), and 0·3 versus 0·1 (24-59 months); for enterotoxigenic E coli encoding heat-stable toxin was 4·2 versus 0·1 (0-11 months), 5·2 versus 0·0 (12-23 months), and 1·1 versus 0·2 (24-59 months); and for Shigella spp was 1·0 versus 1·3 (0-11 months), 3·1 versus 2·4 (12-23 months), and 0·8 versus 0·7 (24-59 months). Participants with both MSD and LSD had significantly more linear growth faltering than controls at follow-up. INTERPRETATION: Inclusion of participants with LSD markedly expands the population of children who experience adverse clinical and nutritional outcomes from acute diarrhoeal diseases. Since MSD and LSD have similar aetiologies, interventions targeting rotavirus, Shigella spp, enterotoxigenic E coli producing heat-stable toxin, and Cryptosporidium spp might substantially reduce the diarrhoeal disease burden and its associated nutritional faltering. FUNDING: Bill & Melinda Gates Foundation.

Protective Effect of Low Molecular Weight Seleno-Aminopolysaccharide on the Intestinal Mucosal Oxidative Damage.

Low molecular weight seleno-aminopolysaccharide (LSA) is an organic selenium compound comprising selenium and low molecular weight aminopolysaccharide (LA), a low molecular weight natural linear polysaccharide derived from chitosan. LSA has been found to exert strong pharmacological activity. In this study, we aimed to investigate the protective effect of LSA on intestinal mucosal oxidative stress in a weaning piglet model by detecting the growth performance, intestinal mucosal structure, antioxidant indices, and expression level of intracellular transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its related factors. Our results indicated that LSA significantly increased the average daily gain and feed/gain (p < 0.05), suggesting that LSA can effectively promote the growth of weaning piglets. The results of scanning electron microscope (SEM) microscopy showed that LSA effectively reduced intestinal damage, indicating that LSA improved the intestinal stress response and protected the intestinal structure integrity. In addition, diamine oxidase (DAO) and d-lactic acid (d-LA) levels remarkably decreased in LSA group compared with control group (p < 0.05), suggesting that LSA alleviated the damage and permeability of weaning piglets. LSA significantly increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) levels, but decreased malondialdehyde (MDA) level, indicating that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress in weaning piglets. RT-PCR results showed that LSA significantly increased GSH-Px1, GSH-Px2, SOD-1, SOD-2, CAT, Nrf2, HO-1, and NQO1 gene expression (p < 0.05). Western blot analysis revealed that LSA activated the Nrf2 signaling pathway by downregulating the expression of Keap1 and upregulating the expression of Nrf2 to protect intestinal mucosa against oxidative stress. Collectively, LSA reduced intestinal mucosal damage induced by oxidative stress via Nrf2-Keap1 pathway in weaning stress of infants.

Socio-environmental factors and diarrheal diseases in under five-year old children in the state of Tocantins, Brazil.

BACKGROUND: Diarrhea is a waterborne disease that affects children, especially those under 5 years of age. The objective of this study was to identify the spatial patterns of distribution of diarrheal disease in under 5-year-old children in the State of Tocantins, Brazil, from 2008 to 2013. METHODS: Geoprocessing tools were used to carry out an epidemiological study, to prepare thematic maps in the TerraView 4.2.2 software based on secondary data. General indicators of the disease, presence of spatial dependence through the Global Moran's Index (I) and the Spatial Association Index (LISA) were described. RESULTS: There were 3,015 cases of under 5-year-old children hospitalized for diarrhea, with an average annual rate (AAR) of 4.10/1,000 inhabitants (inhab.). Among the main characteristics were: increasing rates in under 1-year-old children (6.16 to 9.66/1,000 inhabitants); children aged 1 to 4 full years (63%); males (55%); 8 deaths of under one-year-old children (75%); county of Araguaína (67%); incidence in the county of Nazaré (63.97/1,000 inhab.); prevalence and incidence in the Araguaína microregion (45%, AAR 9.38/1,000 inhab.). The presence of a cluster with spatial autocorrelation was found in the Araguaína microregion, which was statistically significant (I = 0.11, p-value < 0.03), with priority of intervention (Moran Map). CONCLUSIONS: There was an increase in the number of hospitalizations for diarrhea in under 5-year-old children in the state of Tocantins. The spatial analysis identified clusters of priority areas for measures of maintenance and control of diarrheal diseases.

Advances in Evaluation of Chronic Diarrhea in Infants.

Diarrhea is common in infants (children less than 2 years of age), usually acute, and, if chronic, commonly caused by allergies and occasionally by infectious agents. Congenital diarrheas and enteropathies (CODEs) are rare causes of devastating chronic diarrhea in infants. Evaluation of CODEs is a lengthy process and infrequently leads to a clear diagnosis. However, genomic analyses and the development of model systems have increased our understanding of CODE pathogenesis. With these advances, a new diagnostic approach is needed. We propose a revised approach to determine causes of diarrhea in infants, including CODEs, based on stool analysis, histologic features, responses to dietary modifications, and genetic tests. After exclusion of common causes of diarrhea in infants, the evaluation proceeds through analyses of stool characteristics (watery, fatty, or bloody) and histologic features, such as the villus to crypt ratio in intestinal biopsies. Infants with CODEs resulting from defects in digestion, absorption, transport of nutrients and electrolytes, or enteroendocrine cell development or function have normal villi to crypt ratios; defects in enterocyte structure or immune-mediated conditions result in an abnormal villus to crypt ratios and morphology. Whole-exome and genome sequencing in the early stages of evaluation can reduce the time required for a definitive diagnosis of CODEs, or lead to identification of new variants associated with these enteropathies. The functional effects of gene mutations can be analyzed in model systems such as enteroids or induced pluripotent stem cells and are facilitated by recent advances in gene editing procedures. Characterization and investigation of new CODE disorders will improve management of patients and advance our understanding of epithelial cells and other cells in the intestinal mucosa.