Trichohepatoenteric syndrome type 1: expanding the clinical spectrum of THES type 1 due to a homozygous variant in the SKIC3 gene.

Trichohepatoenteric syndrome (THES), also known as phenotypic diarrhea or syndromic diarrhea, is a rare autosomal recessive genetic disorder caused by mutations in SKIC2 (THES-type 2) or SKIC3 (THES-type 1) and is characterized by early onset diarrhea, woolly brittle hair, facial dysmorphic features and liver disease. We report the case of a 24-month-old girl who presented with chronic diarrhea since the neonatal period along with intrauterine growth restriction (IUGR), developmental delay, dysmorphic features, congenital heart defects, liver disease, and recurrent infections. The diagnosis was made through whole-exome sequencing analysis, which detected a homozygous variant (c.4070del, p.Pro1357Leufs*10) in the SKIC3 gene. The patient required parenteral nutrition and was hospitalized for the first 10 months of life and then discharged on PN after showing improvement. She remained stable on PN after discharge despite a few admissions for central line infections. Recent follow-up at the age of 2 years revealed that she was stable on long-term parenteral nutrition and that she had advanced chronic liver disease.

Importance of genetic sequencing studies in managing chronic neonatal diarrhea: a case report of a novel variant in the glucose-galactose transporter SLC5A1.

Introduction: Congenital glucose-galactose malabsorption (CGGM) is a rare autosomal recessive disorder that primarily causes chronic intractable diarrhea. This study aims to describe the clinical history, laboratory profile, diagnostic workflow, and management of the first patient reported with CGGM in Mexico. Methods: The case involves a Mexican female infant with recurrent admissions to the emergency room since birth due to chronic diarrhea. Results: The infant was born at term by C-section with a birth weight of 3.120 kg and height of 48 cm for consanguineous parents. She had been breastfed until day 5 of her life when she presented lethargy, diarrhea, abdominal discomfort, and jaundice. During the first evaluation at the emergency room, the significant laboratory finding was blood tyrosine elevation; afterward, amino acid and succinylacetone determinations were obtained, discarding tyrosinemia. When admitted to the hospital, an abdominal ultrasound detected a duplex collecting system. At this time, rice formula was introduced to the patient. She was discharged with jaundice improvement, but diarrhea persisted. Several formula changes had been made from rice to extensively hydrolyzed casein protein to whey-based, with no clinical improvement; the patient still had 10-12 excretions daily. In the second hospitalization, the patient presented anemia, severe dehydration, hyperammonemia, and renal tubular acidosis. A next-generation sequencing panel for inborn errors of metabolism and congenital diarrhea was performed, identifying a homozygous variant in SLC5A1 (c.1667T > C). The diagnosis of CGGM was made at 3 months of age. The infant was initially treated with a modular galactose-glucose-free formula with oil, fructose, casein, minerals, and vitamins until a commercial fructose-based formula was introduced. This led to a complete resolution of diarrhea and improved nutritional status. Discussion: Diagnosing CGGM is challenging for clinicians, and next-generation sequencing is a valuable tool for providing appropriate treatment. More detailed information on patients with this condition might lead to possible phenotype-genotype correlations. This case's primary clinical and biochemical findings were chronic diarrhea, anemia, jaundice, renal tubular acidosis, hyperammonemia, and initial hypertyrosinemia. Symptoms were resolved entirely with the fructose-based formula.

Effect of Lactobacillus reuteri NCIMB 30351 drops on symptoms of infantile functional gastrointestinal disorders and gut microbiota in early infants: Results from a randomized, placebo-controlled clinical trial.

Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, representing one of the causes of significant parental anxiety, lead to a significant strain on the healthcare resources. In this study, we aimed to evaluate the effects of Lactobacillus reuteri drops (L. reuteri NCIMB 30351) on the symptoms of infantile colic, constipation, diarrhea, and gastroesophageal reflux, as well as on the levels of intestinal microbiota in full-term newborns during the first months of life. A randomized, placebo-controlled, single-masked (blinded), post-marketing clinical study was conducted in two clinical units-Children's City Clinical Hospital of Moscow and Medical Center "St. Andrew's Hospitals-NEBOLIT" from March 2020 to May 2022 in 90 infants aged from 1 to 4 months (mean age (± SD) 12.3 ± 5.09 weeks; 53.3% females, 46.7% males). Patients with colic, regurgitation (single symptom or combination of several symptoms), and constipation or diarrhea were randomly allocated in two parallel arms to receive either 5 drops (2 × 108 colony forming unit) of L. reuteri NCIMB 30351 (n = 60) or masked placebo (n = 30) for 25 consecutive days. Two treatment arms had equal numbers of patients with constipation and diarrhea (n = 30 each). Daily crying times and their duration, evacuations, and regurgitations were recorded in a structured diary. The levels of gut microbiota were analyzed by deep sequencing of bacterial 16S rRNA gene. Infants with colic receiving supplementary L. reuteri NCIMB 30351 for 25 days had significant reduction in the numbers of colic (change from baseline - 6.3 (7.34) vs - 3.0 (7.29) in placebo, P < 0.05) and numbers of crying cases and mean duration of crying (decrease from baseline - 144 (70.7) minutes, lower in the diarrhea subgroup than in constipation infants, compared with - 80 (58.9) in placebo, P < 0.0001), as well as regurgitation numbers (decreased by - 4.8 (2.49) with L. reuteri vs - 3 (7.74) with placebo). We also observed increased numbers of evacuations in infants with constipation (L. reuteri 2.2 (2.4) vs 0.9 (1.06) in placebo, P < 0.05). There was a remarkable reduction of evacuations in infants with diarrhea, while not statistically significant. The analysis of bacterial 16S rRNA gene in the collected samples showed that L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes. Additional in vitro test for formation of Clostridium colonies in the presence of the probiotic demonstrated that L. reuteri effectively inhibits the growth of pathogenic Clostridium species. No adverse events were reported in this study.   Conclusion: The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. Our results suggest that L. reuteri NCIMB 30351 represents a safe and effective treatment for colic in newborns.  Trial registration: ClinicalTrials.gov : NCT04262648. What is Known: • Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, represent one of the causes of significant parental anxiety. • A number of studies have shown that both the composition and diversity of the intestinal microbiota play important roles in the development and function of the gastrointestinal tract. What is New: • The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. • L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes in gut microbiota.

Potencial do polissacarídeo O26 para ser utilizado como antígeno em formulações vacinais contra a-EPEC e STEC

According to the World Health Organization, diarrheal diseases are the second leading cause of mortality in the world in children under 5 years of age, with diarrheagenic Escherichia coli being the main etiological agent of bacterial origin. This group of E. coli is also responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) in developed countries. Among the main groups of diarrheagenic E. coli are the strains belonging to serogroup O26 that can be categorized as EPEC (enteropathogenic E. coli) and STEC (shiga toxin producing E. coli). Currently, the best way to combat these pathogens is to develop a vaccine that is effective against both categories belonging to serogroup O26. Faced with this problem, this study aimed to determine the potential of the O26 polysaccharide, present in EPEC and STEC strains, to be used as a target antigen in vaccine formulations against these pathogens. For this, we used two different strains of serotype O26:H11, one from the EPEC category and the other from the STEC category. Being EPEC, capsulated bacteria, we determined the ability of anti-O26 antibodies to recognize capsulated and non-encapsulated bacteria. We also verified the ability of these antibodies to recognize bacteria in the presence of biofilm. Finally, we determined the ability of anti-O26 antibodies to increase EPEC phagocytosis by macrophages and inhibit the adhesion of these pathogens to epithelial cells. The results obtained by the ELISA technique showed that the level of recognition of biofilm-forming EPEC by anti-O26 antibodies was equivalent to the recognition of non-biofilm-producing STEC. The results also showed that the antibodies helped macrophages (J774A.1) in the phagocytosis of EPEC and were able to inhibit the adhesion of these bacteria to epithelial cells. In summary, the results indicate that the O26 polysaccharide is a good antigen candidate to be used in vaccine formulations against all E. coli strains belonging to the O26 serogroup, regardless of their virulence mechanism.

Segundo a Organização Mundial da Saúde, as doenças diarreicas são a segunda maior causa de mortalidade no mundo em crianças menores de 5 anos, sendo Escherichia coli diarreiogênicas, o principal agente etiológico de origem bacteriana. Esse grupo de E. coli também é responsável por surtos de diarreia com sangue e síndrome hemolítica urêmica (SHU) em países desenvolvidos. Dentre os principais grupos de E. coli diarreiogênicas encontram-se as linhagens pertencentes ao sorogrupo O26 que podem ser categorizadas como EPEC (E. coli enteropatogênica) e STEC (E. coli produtoras de toxina shiga). Atualmente, a melhor maneira de se combater esses patógenos é o desenvolvimento de uma vacina que seja eficaz contra as duas categorias pertencentes ao sorogrupo O26. Diante dessa problemática, esse estudo visou determinar o potencial do polissacarídeo O26, presente nas cepas de EPEC e STEC de ser utilizado como antígeno alvo em formulações vacinais contra esses patógenos. Para isso utilizamos duas linhagens diferentes do sorotipo O26:H11, sendo uma da categoria EPEC e outra da categoria STEC. Sendo as EPEC bactérias capsuladas, determinamos a capacidade de anticorpos anti-O26 de reconhecer bactérias capsuladas e não capsuladas. Verificamos também, a capacidade desses anticorpos de reconhecer bactérias na presença de biofilme. Finalmente, determinamos a capacidade dos anticorpos anti-O26 de aumentar a fagocitose de EPEC por macrófagos e inibir a adesão desses patógenos a células epiteliais. Os resultados obtidos pela técnica de ELISA mostraram que o nível de reconhecimento de EPEC formadora de biofilme pelos anticorpos anti-O26 foi equivalente ao reconhecimento de STEC não produtoras de biofilme. Os resultados também mostraram que os anticorpos auxiliaram macrófagos (J774A.1) na fagocitose de EPEC e também foram capazes de inibir a adesão dessas bactérias a células epiteliais. Em resumo, os resultados indicam que o polissacarídeo O26 é um bom candidato a antígeno para ser utilizado em formulações vacinais contra todas as linhagens de E. coli pertencentes ao sorogrupo O26 independentemente do mecanismo de virulência das mesmas.

Homozygous Missense Epithelial Cell Adhesion Molecule Variant in a Patient with Congenital Tufting Enteropathy and Literature Review.

Congenital diarrheal disorders (CDDs) with genetic etiology are uncommon hereditary intestinal diseases characterized by chronic, life-threatening, intractable watery diarrhea that starts in infancy. CDDs can be mechanistically divided into osmotic and secretory diarrhea. Congenital tufting enteropathy (CTE), also known as intestinal epithelial dysplasia, is a type of secretory CDD. CTE is a rare autosomal recessive enteropathy that presents with intractable neonatal-onset diarrhea, intestinal failure, severe malnutrition, and parenteral nutrition dependence. Villous atrophy of the intestinal epithelium, crypt hyperplasia, and irregularity of surface enterocytes are the specific pathological findings of CTE. The small intestine and occasionally the colonic mucosa include focal epithelial tufts. In 2008, Sivagnanam et al. discovered that mutations in the epithelial cell adhesion molecule (EpCAM, MIM# 185535) were the genetic cause of CTE (MIM# 613217). More than a hundred mutations have been reported to date. Furthermore, mutations in the serine peptidase inhibitor Kunitz type 2 (SPINT2, MIM# 605124) have been linked to syndromic CTE. In this study, we report the case of a 17-month-old male infant with congenital diarrhea. Despite extensive etiological workup, no etiology could be established before admission to our center. The patient died 15 hours after being admitted to our center in a metabolically decompensated state, probably due to a delay in admission and diagnosis. Molecular autopsy with exome sequencing revealed a previously reported homozygous missense variant, c.757G>A, in EpCAM, which was confirmed by histopathological examination.

Severe congenital diarrhea secondary to tufting enteropathy. case report

ABSTRACT Introduction: Tufting enteropathy is a rare cause of congenital diarrhea in neonates. It is characterized by the abnormal distribution of epithelial adhesion molecules, which causes enterocytes to shed into the lumen, forming the characteristic tufts. Case summary: A 15-day-old female neonate was taken by her parents to the emergency department of a tertiary care hospital due to diarrheal stools she had been experiencing since birth. The patient presented with dehydration, abnormal weight loss, metabolic acidosis, and acute kidney failure. She received treatment with alizapride, loperamide, zinc sulfate, and probiotics, but after 75 days of treatment she was still symptomatic. An upper tract endoscopy and colonoscopy were performed, finding flattening of the villi and lymphoid cells in the lamina propria. However, the symptoms persisted, and she died at the age of ten months. A post-mortem exome sequencing reported tufting enteropathy. Conclusions. When congenital diarrhea is present, tufting enteropathy should be considered. An early molecular study would allow to evaluate the possibility of performing an intestinal transplant or modifying the treatment to meet the patient's palliative care needs.

RESUMEN Introducción. La enteropatía en penacho es una causa rara de diarrea congénita en neonatos; esta se caracteriza por una alteración de la adhesión epitelial que ocasiona desprendimiento de enterocitos hacia el lumen y, en consecuencia, forma los característicos penachos. Se describe el caso de una paciente con esta patología. Presentación del caso. Neonata de 15 días de vida, quien fue llevada por sus padres al servicio de urgencias de un hospital de tercer nivel debido a que desde su nacimiento tuvo deposiciones diarreicas y a causa de esto presentó deshidratación, pérdida de peso, acidosis metabólica e insuficiencia renal aguda. La paciente recibió manejo con alizaprida, loperamida, sulfato de zinc y probióticos, pero a los 75 días de tratamiento continuaba sintomática. Se le practicó una endoscopia de vías digestivas y una colonoscopia que mostraron aplanamiento de las vellosidades e infiltrado de células linfoides en la lámina propia. Los síntomas continuaron y la menor falleció a los 10 meses de nacida. El resultado del exoma post mortem reportó enteropatía en penacho. Conclusiones. Ante la presencia de diarrea congénita, se debe sospechar de una enteropatía en penacho y considerar el estudio molecular temprano, pues este permite evaluar la posibilidad de realizar un trasplante intestinal o modificar el tratamiento según las necesidades de cuidado paliativo del paciente.

Alergia alimentar não IgE mediada: proctocolite induzida por proteínas alimentares ­ Atualização / Non-IgE mediated food allergy: food protein-induced allergic proctocolitis ­ An update

Nas últimas décadas observa-se aumento na prevalência mundial de alergia alimentar, que já acomete aproximadamente 6% das crianças, atribuído à interação entre fatores genéticos, ambientais e alterações na resposta imunológica e pode envolver reações mediadas por IgE, não mediadas e mistas. As formas não IgE mediadas decorrem de reação de hipersensibilidade tardia, mediada por linfócitos T e afetam prioritariamente o trato gastrointestinal, como a Síndrome da enterocolite induzida por proteína alimentar (FPIES), Síndrome da proctocolite alérgica induzida por proteína alimentar (FPIAP), Síndrome da enteropatia induzida por proteína alimentar (FPE) e doença celíaca. As características destas reações podem ser diferenciadas por sua apresentação clínica, gravidade, idade de início e história natural. Entre as reações alérgicas aos alimentos não IgE mediadas, a proctocolite alérgica é a mais frequente. Geralmente ocorre no primeiro ano de vida e apresenta excelente prognóstico. Embora costume ter um curso benigno, traz grande preocupação aos cuidadores por frequentemente cursar com quadro de hematoquezia exigindo diagnóstico diferencial adequado. O conhecimento e manejo da proctocolite alérgica é de suma importância para a prática médica em Alergia e Imunologia. Seu diagnóstico é baseado na história clínica seguindo-se dieta de exclusão, especialmente do leite de vaca, com subsequente provocação oral, que geralmente pode ser realizada no domicílio. O diagnóstico preciso é importante, para se evitar dietas de exclusão desnecessárias. Nesta revisão foram utilizados artigos publicados nos últimos anos, com busca realizada através da base PubMed envolvendo revisões, diagnóstico e tratamento de alergias não IgE mediadas, com foco em proctocolite alérgica.

An increase in the worldwide prevalence of food allergies has been observed in the past decades, currently affecting 6% of children. This increase has been associated with the interaction between genetic, environmental, and immune response factors and can be observed in IgE, non-IgE, and mixed mediated reactions. Non-IgE mediated food allergies result from delayed-type hypersensitivity and mostly affect the gastrointestinal tract, such as food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and celiac disease. These reactions can be differentiated by their clinical presentation, severity, age at onset, and natural history. Among non-IgE-mediated allergic reactions to food, allergic proctocolitis is the most frequent. It usually develops in the first year of life and has excellent prognosis. Although it has a benign course, allergic proctocolitis is challenging for health care professionals because it often presents with hematochezia, requiring an accurate differential diagnosis. Knowledge and management of allergic proctocolitis is of paramount importance for medical practice in allergy and immunology. Its diagnosis is based on clinical history followed by elimination diet, especially cow's milk, with subsequent oral food challenge, which may usually be performed at home. Accurate diagnosis is important to avoid unnecessary elimination diets. For this review, PubMed database was searched for recently published literature reviews and studies on the diagnosis and treatment of non- IgE mediated allergies, with a focus on allergic proctocolitis.

Congenital Glucose-Galactose Malabsorption: A Case With a Novel SLC5A1 Mutation in a Saudi Infant.

While only a few hundred cases have been reported in pediatrics, congenital glucose-galactose malabsorption (GGM) is an extremely rare autosomal-recessive metabolic disorder that is characterized by intractable diarrhea and severe dehydration, which can be life-threatening if not treated appropriately. Due to the rarity of the disease, it is challenging to consider GGM as an initial diagnosis for most clinicians. We report the clinical and diagnostic course of a seven-month-old Saudi infant who presented with severe recurrent episodes of watery diarrhea and failure to thrive in early infancy despite standard treatment. Molecular testing identified that our patient had a compound heterozygous variant in SLC5A1. Fructose-based formulae have been proven to be effective in treating GGM. This case highlights the importance of early diagnosis and timely management to prevent serious complications of undiagnosed GGM.

The laboratory test procedure to confirm rotavirus vaccine infection in severe complex immunodeficiency patients.

The rotavirus vaccine is a live vaccine, and there is a possibility of infection by the virus strain used in the vaccine. We investigated the process of determining whether an infection was caused by the vaccine strain in a severe complex immunodeficiency (SCID) patient with rotavirus infection. The patient was vaccinated with RotaTeq prior to being diagnosed with SCID. The testing process was conducted in the following order: confirming rotavirus infection, determining its genotype, and confirming the vaccine strain. Rotavirus infection was confirmed through enzyme immunoassay and VP6 gene detection. G1 and P[8] were identified by multiplex polymerase chain reaction for the genotype, and G3 was further identified using a single primer. By detecting the fingerprint gene (WC3) of RotaTeq, it was confirmed that the detected virus was the vaccine strain. Genotypes G1 and P[8] were identified, and the infection was suspected of having been caused by rotavirus G1P[8]. G1P[8] is the most commonly detected genotype worldwide and is not included in the recombinant strains used in vaccines. Therefore, the infection was confirmed to have been caused by the vaccine strain by analyzing the genetic relationship between VP4 and VP7. Rotavirus infection by the vaccine strain can be identified through genotyping and fingerprint gene detection. However, genetic linkage analysis will also help to identify vaccine strains.

Efficacy of a Multi-Strain Probiotic Formulation in Pediatric Populations: A Comprehensive Review of Clinical Studies.

A probiotic formulation combining Lactobacillus helveticus Rosell®-52, Bifidobacterium infantis Rosell®-33, and Bifidobacterium bifidum Rosell®-71 with fructooligosaccharides, first commercialized in China, has been sold in over 28 countries since 2002. Clinical studies with this blend of strains were conducted mainly in pediatric populations, and most were published in non-English journals. This comprehensive review summarizes the clinical studies in infants and children to evaluate the efficacy of this probiotic for pediatric indications. Literature searches for pediatric studies on Biostime® or Probiokid® (non-commercial name) in 6 international and Chinese databases identified 28 studies, which were classified by indications. Twelve studies show that the probiotic significantly increases the efficacy of standard diarrhea treatment regardless of etiology, reducing the risk of unresolved diarrhea (RR 0.31 [0.23; 0.42]; p < 0.0001) by 69%. In eight studies, the probiotic enhanced immune defenses, assessed by levels of various immune competence and mucosal immunity markers (six studies), and reduced the incidence of common infections (two studies). The probiotic improved iron deficiency anemia treatment efficacy (three studies), reducing the risk of unresolved anemia by 49% (RR 0.51 [0.28; 0.92]; p = 0.0263) and significantly reducing treatment side effects by 47% (RR 0.53 [0.37; 0.77]; p = 0.0009). Other studies support further investigation into this probiotic for oral candidiasis, eczema, feeding intolerance in premature babies, or hyperbilirubinemia in newborns.

Análisis de la tendencia de la mortalidad por enfermedad diarreica aguda en el Perú y sus regiones, 1986-2015 / Trend analysis of acute diarrheal disease mortality in Peru and regions, 1986-2015

RESUMEN Introducción. La incidencia de las enfermedades diarreicas agudas (EDA) se ha mantenido relativamente constante en las tres últimas décadas; mientras que, la mortalidad ha disminuido principalmente por la terapia de rehidratación oral y a mejora en las condiciones de vida. Sin embargo, la letalidad es mayor en los países más pobres, razón por la cual todavía es considerado un problema de salud pública. Objetivo. Analizar la tendencia de la mortalidad por EDA en menores de 5 años en el Perú y sus regiones, en el periodo 1986-2015. Métodos. Se realizó un estudio observacional, analítico, de tendencias de la mortalidad por EDA en los niños menores de 5 años en el periodo 1986-2015, basado en datos secundarios, a nivel nacional y regional, a través del análisis de regresión segmentada de modelos del tipo Log-Lineal utilizando el programa Joinpoint del Instituto Nacional de Cáncer de Estados Unidos. Resultados. Perú presentó una reducción en la tasa específica de mortalidad por EDA (1986-1990: 243,3 y 2011-2015: 15,3). En el análisis de tendencia si bien todas las regiones mostraron una tendencia descendente, solo en 12 permaneció constante durante todo el periodo, 9 presentaron una tendencia estacionaria, 2 ascendente y en 2 la reducción se desaceleró en el último tramo. Conclusiones. A nivel nacional, la mortalidad por EDA en menores de 5 años tuvo una tendencia descendente, siendo no constante en diferentes momentos del periodo 1986-2015. En todas las regiones la tendencia fue descendente hasta el año 2000, luego se observan comportamientos diferentes.

ABSTRACT Introduction. The incidence of acute diarrheal diseases (ADD) has remained relatively constant in the last three decades, whereas mortality has decreased mainly due to oral rehydration therapy and to improvements in living conditions. However, fatality is higher in poorer countries, which it is still considered a public health problem. Objective. To analyze the ADD mortality trend in children under 5 years old in Peru and its regions, in the period 1986-2015. Methods. An observational, analytical study of trends in ADD mortality in children under 5 years old in the period 1986-2015, based on secondary data, was conducted at national and regional level through segmented regression analysis of Log-Linear models using the Joinpoint program of the National Cancer Institute of the United States. Results. Peru had a reduction in the specific ADD mortality rate (1986-1990: 243.3 and 2011-2015: 15.3). In the trend analysis although all regions showed a downward trend, only in 12 remained constant throughout the period, 9 had a stationary trend, 2 upward and in 2 the reduction slowed in the last stretch. Conclusions. At national level, ADD mortality in children under 5 years old had a downward trend, although it was not constant at different times during the 1986-2015 period. In all regions, the trend was downward until 2000, then different behaviors were observed.

Draft genome sequence of Escherichia coli M51-3: a multidrug-resistant strain assigned as ST131-H30 recovered from infant diarrheal infection in Mexico.

OBJECTIVES: In this study, we report the draft genome sequence of a multidrug-resistant (MDR)Escherichia coli strain recovered from stool sample of an outpatient infant girl with acute diarrheal infection in Mexico. METHODS: Antimicrobial susceptibility testing and PCR-based detection of diarrheagenic E. coli (DEC) were performed. In addition, genomic DNA from E. coli strain M51-3 was sequenced using Ion Torrent PGM platform with 200-bp chemistry and generated reads were de novo assembled using SPAdes v3.11. The draft genome was annotated and analyzed regarding multilocus sequence typing (MLST), serotyping, fimH typing, plasmid replicons, acquired antimicrobial resistance and virulence genes using web tools available at the Center for Genomic Epidemiology. RESULTS: A draft genome comprising 5 088 545 bp in length and 5308 protein-coding sequences was generated. In silico typification revealed that E. coli strain M51-3 belongs to ST131-O25:H4-H30 pandemic subclone. Several genes associated with resistance to ß-lactams [blaTEM-1B], aminoglycosides [aph(3'')-Ib, aadA5, aph(6)-Id and aac(3)-IId], sulfonamides [sul1 and sul2], trimethoprim [dfrA17], and tetracycline [tet(A)] were identified. Besides, point mutations in gyrA, parC, and parE genes were detected. Interestingly, the enterotoxin-coding virulence gene senB was evidenced. CONCLUSIONS: To our knowledge, this is the first draft genome of an E. coli ST131-O25:H4-H30 strain recovered from infant diarrheal stool sample in Mexico. The genome sequence of E. coli M51-3 presented here will be helpful to understand the genomic diversity of this highly virulent and MDR successfully pandemic bacterial pathogen.

Caracterização de Escherichia coli enteroagregativa entre crianças com diarreia na Amazônia ocidental brasileira / Characterization of enteroaggregative escherichia coli among diarrheal childrenin western brazilian amazon

ABSTRACT BACKGROUND: Enteroaggregative Escherichia coli (EAEC) is one of the main acute and chronic diarrhea causes both in children and adults, mainly in developing countries. OBJECTIVE: The aim of the present study is to characterize EAEC strains isolated from faecal samples and to identify genes potentially contributing to virulence, biofilm production and antimicrobial resistance in children admitted to a pediatric hospital in Porto Velho, Rondônia State. METHODS: The total of 1,625 E. coli specimens were isolated from 591 children in the age group 6 years or younger who were hospitalized in Cosme and Damião Children Hospital in Porto Velho, between February 2010 and February 2012, with acute gastroenteritis. Colonies suggestive of E. coli were subjected to polymerase chain reaction testing in order to identify the virulence factors. The in vitro adhesion assays using HEp-2 adherence were tests. Biofilm detection through spectrophotometry and antimicrobial susceptibility tests were conducted in the disk diffusion method. RESULTS: The mentioned study examined 591 stool samples from children with diarrhea. Diarrheogenic E. coli was found in 27.4% (162/591) of the children. EAEC was the diarreagenic E. coli most frequently associated with diarrhea 52.4% (85/162), which was followed by enteropathogenic E. coli 43.8% (71/162), enterotoxigenic E. coli 2.4% (4/162), and enterohemorrhagic E. coli 1.2% (2/162). The aggR gene was detected in 63.5% (54/85) of EAEC isolates; moreover, statistically significant correlation was observed among typical EAEC (aggR) and aatA (P<0.0001), irp2 (P=0.0357) and shf (P=0.0328). It was recorded that 69% (59/85) of the 85 analyzed EAEC strains were biofilm producers; 73% (43/59) of the biofilm producers carried the aggR gene versus 42.3% (11/26) of non-producers (P=0.0135). In addition, there was association between the aatA gene and biofilm production; 61% (36/59) of the samples presented producer strains, versus 19.2% (5/26) of non-producers (P<0.0004). Antibiotic sensitivity test evidenced that most EAEC were ampicillin 70.6% (60/85), sulfamethoxazole 60% (51/85), tetracycline 44.7% (38/85) and cefotaxime 22.4% (19/85) resistant. CONCLUSION: As far as it is known, the present study is pioneer in Northern Brazil to investigate EAEC virulence factors and to show the antimicrobial susceptibility of EAEC strains isolated from children with diarrhea.

RESUMO CONTEXTO: A Escherichia coli enteroagregativa (EAEC) é um dos principais agentes causadores de diarreia aguda e crônica em crianças e adultos, principalmente em países em desenvolvimento. OBJETIVO: Caracterizar cepas de EAEC isoladas de amostras fecais e identificar genes que potencialmente contribuem para a virulência, produção de biofilme e resistência antimicrobiana em crianças internadas em um hospital pediátrico em Porto Velho, Rondônia. MÉTODOS: Um total de 1.625 cepas de E. coli foram isolados de 591 crianças com gastroenterite aguda na faixa etária de 6 anos que foram internadas no Hospital Infantil Cosme e Damião na cidade de Porto Velho, entre fevereiro de 2010 e fevereiro de 2012. Colônias sugestivas de E. coli foram submetidas a reação em cadeia da polimerase para identificação de fatores de virulência. O ensaio de adesão in vitro foi desenvolvido com célula HEp-2. A detecção de biofilme foi realizada através do teste de espectrofotometria e os testes de susceptibilidade aos antimicrobiana foram realizados através do método de difusão em disco. RESULTADOS: A E. coli diarreiogênica foi encontrada em 27,4% (162/591) das crianças e a EAEC foi a E. coli diarreiogênica mais frequentemente associada à diarreia com 52,4% (85/162), seguida pela E. coli enteropatogênica 43,8% (71/162), E. coli enterotoxigênica 2,4% (4/162) e E. coli enterohemorrágica 1,2% (2/162). O gene aggR foi detectado em 63,5% (54/85) dos isolados de EAEC com correlação estatisticamente significante entre esse gene com os genes aatA (P<0,0001), irp2 (P=0,0357) e shf (P=0,0328). Neste estudo 69% (59/85) das cepas de EAEC eram produtoras de biofilme, destas 73% (43/59) possuíam o gene aggR, ao passo que entre as não produtoras 42,3% (11/26) possuíam o gene (P=0,0135). Essa associação também foi observada com o gene aatA, presente em 61% (36/59) das cepas produtoras e em 19,2% (5/26) das não produtoras (P<0,0004). O teste de sensibilidade aos antibimicrobianos evidenciou que a maioria das EAEC eram resistentes a ampicilina 70,6% (60/85), ao sulfametoxazol 60% (51/85), a tetraciclina 44,7% (38/85) e a cefotaxima 22,4% (19/85). CONCLUSÃO: Este é o primeiro estudo no Norte do Brasil sobre a investigação dos fatores de virulência de EAEC mostrando a susceptibilidade antimicrobiana de cepas de EAEC isoladas de crianças com diarreia.

Epidemiología sociocultural de los padecimientos gastrointestinales en niños y niñas del pueblo Nasa, Colombia / Socio-cultural epidemiology of gastrointestinal illness in children of the Nasa people, Colombia

Resumen Introducción: Los padecimientos gastrointestinales son frecuentes en la población indígena, generando diversas interpretaciones y tratamientos. Objetivo: Construir un perfil epidemiológico sociocultural de la enfermedad diarreica en niños Nasas menores de un año. Materiales y métodos: Método mixto e interdisciplinario que trianguló herramientas cuantitativas y cualitativas, y que orientó la caracterización sociocultural de este pueblo, la descripción estadística sobre la presencia y distribución de dicha enfermedad, y el quehacer etnográfico alrededor de su diagnóstico, interpretación y atención. Resultados: El 98.5% de esta población vive en la zona rural y no tiene acceso a saneamiento básico. En los seis meses de investigación se presentaron 349 casos de esta enfermedad en 306 infantes menores de un año, y su incidencia es mayor en las zonas con menor presencia de instituciones estatales. Los diagnósticos los realizan principalmente las madres a partir de elementos específicos: características de las deposiciones, y de situaciones contextuales: incidentes ambientales, sociales y culturales. Las principales causas reconocidas por las cuidadoras son de origen biológico: parásitos (23%) y malnutrición (21%), además de síndromes de filiación cultural: susto (15%), mal viento (8%) y lastimadura (7%). Las estrategias de atención indicaron un pluralismo médico con predominio de la autoatención. La biomedicina es la opción principal cuando las mamás ven comprometida la vida de los infantes. Conclusiones: La enfermedad diarreica entre los Nasas tiene elevada presencia, y es el reflejo de una vida precarizada, dinamizado en un territorio rural excluido y colmado de simbolizaciones.

Abstract Introduction: Gastrointestinal illness are frequent in the indigenous population, generating different interpretations and treatments. Objective: To construct a Socio-cultural epidemiological profile of diarrheal disease in Nasa children under one year of age. Materials and methods: Mixed and interdisciplinary method that triangulated quantitative and qualitative tools, which guide the sociocultural characterization of this people, the statistical description of the presence and distribution of this disease, and the ethnographic work around its diagnosis, interpretation and care. Results: 98.5% of this population live rural areas and do not have access to basic sanitation. During the six months of research, 349 cases of this disease were presented at 306 infants under one year, and its incidence is higher in areas with less presence of State institutions. The diagnoses are mainly made by the mothers based on specific elements: characteristics of the depositions, and contextual situations: environmental, social and cultural incidents. The main causes recognized by the caregivers are of biological origin: parasites (23%) and malnutrition (21%), also syndromes of cultural affiliation: fright (15%), bad wind (8%) and injury (7%). Care strategies indicated a medical pluralism with a predominance of self-care. Biomedicine is the main option when moms see the lives of the infants compromised. Conclusions: Diarrheal disease among the Nasas has a high presence, and it is a reflection of a precarious life, invigorated in a rural territory excluded and filled with symbolizations.

Persistent Enteropathy in a Toddler with a Novel FOXP3 Mutation and Normal FOXP3 Protein Expression.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is caused by mutations in the FOXP3 gene. Patients usually present with a clinical triad of intractable diarrhea, diabetes, and eczema. In this patient, FOXP3 protein expression was normal, but FOXP3 Sanger sequencing confirmed the clinical suspicion of IPEX by detecting a previously unreported missense variant. Early recognition of IPEX is important, because hematopoietic stem cell transplantation can be curative.

Congenital Glucose-Galactose Malabsorption: A Case Report.

Congenital glucose-galactose malabsorption (CGGM) is a rare cause of intractable infantile diarrhea, with only a few hundred cases recognized worldwide. This life-threatening disorder must be considered in the differential diagnosis of an infant who presents with diarrhea and dehydration that fails to respond to standard therapy. The clinical and diagnostic course of an infant with recurrent episodes of watery diarrhea and hypernatremic dehydration found to be homozygous for a rare variant in the SLC5A1 gene, c.187C>T (p.R63X) is described.

Enteropatógenos predominantes en diarreas agudas y variables asociadas en niños atendidos en el Hospital Regional Lambayeque, Perú / Predominant enteropathogens in acute diarrhea and associated variables in children at the Lambayeque Regional Hospital, Peru

Objetivo: Determinar el tipo y frecuencia de enteropatógenos predominantes en diarreas agudas y sus características asociadas en niños atendidos en el Hospital Regional Lambayeque (HRL) - Perú. Materiales y métodos: Se realizó un estudio analítico transversal entre marzo y mayo del 2015 en 70 muestras fecales. Las muestras se estudiaron mediante coprocultivo e inmunocromatografía para la detección de bacterias y virus enteropatógenos respectivamente. Mientras que los enteroparásitos se buscaron mediante examen microscópico directo, tinción de Kinyoun y ELISA para coproantígenos (Entamoeba histolytica, Giardia lamblia y Cryptosporidium spp.). Asimismo se realizó conteo de leucocitos y pruebas químicas (Benedict, Thevenon y Sudan III) para el estudio funcional de la enfermedad diarreica. Resultados: En el 48,6% de muestras se detectó la etiología infecciosa de la diarrea, siendo predominante la causa parasitaria (25,8%), seguida de la bacteriana (17,1%) y viral (5,8%). Los enteropatógenos más frecuentes fueron G. lamblia (18,6%) y Salmonella Enteritidis (10,0%). Se observó asociación entre la cantidad de leucocitos mayor a 100 con la etiología bacteriana (p=0,027), mientras que un número menor de 10 por campo (p=0,002) y el Sudan III positivo (p=0,003) con la etiología parasitaria. Conclusiones: En más de la mitad de muestras (51,4%) no se demostró etiología infecciosa de la diarrea, mientras que Giardia lamblia fue la más frecuente causa de diarrea en la población estudiada. No obstante, es necesaria la implementación de técnicas más sensibles y específicas para la detección de un rango mayor de enteropatógenos con el que se mejore el diagnóstico y tratamiento de la enfermedad

Objective: To determine the type and frequency of predominant enteropathogens in acute diarrhea and their associated characteristics in children treated at Hospital Regional Lambayeque (HRL) - Peru. Materials and methods: A cross-sectional analytical study was carried out in 70 fecal samples between March and May 2015. These samples were studied by coproculture and immunochromatography for the detection of enteropathogenic bacteria and viruses, respectively, while enteroparasites were sought by direct microscopic examination, Kinyoun staining method and ELISA for the detection of coproantigens (Entamoeba histolytica, Giardia lamblia and Cryptosporidium spp). Leukocyte count and chemical tests (Benedict, Thevenon and Sudan III) were also performed for the functional study of the diarrheal disease. Results: In 48.6% of the samples, the infectious etiology of diarrhea was detected, prevailing the parasitic cause (25.8%), followed by the bacterial (17.1%) and viral (5.8%) ones. The most common enteropathogens were G. lamblia (18.6%) and Salmonella enteritidis (10.0%). An association between greater than 100 fecal leukocytes per field and the bacterial etiology (p=0.027) was observed, while less than 10 fecal leukocytes per field (p=0.002) and a positive Sudam III test (p=0.003) were associated with the parasitic etiology. Conclusions: In more than half of the samples (51.4%) the infectious etiology of diarrhea could not be proven, whereas Giardia lamblia was the most frequent cause of diarrhea in the studied population. However, it is necessary to implement more sensitive and specific techniques for the detection of a greater range of enteropathogens with which to improve the diagnosis and treatment of the disease

Diversity of group A rotavirus genes detected in the Triângulo Mineiro region, Minas Gerais, Brazil

ABSTRACT Group A rotaviruses are the main causative agent of infantile gastroenteritis. The segmented nature of the viral genome allows reassortment of genome segments, which can generate genetic variants. In this study, we characterized the diversity of the VP7, VP4 (VP8*), VP6, NSP4, and NSP5 genes of the rotaviruses that circulated from 2005 to 2011 in the Triângulo Mineiro (TM) region of Brazil. Samples with genotypes G2 (sublineages IVa-1 and IVa-3), G1 (sublineage I-A), G9 (lineage III), G12 (lineages II and III), G8 (lineage II), G3 (lineage III), P[4] (sublineages IVa and IVb), P[8] (sublineages P[8]-3.6, P[8]-3.3, and P[8]-3.1), I2 (lineage VII), E2 (lineages VI, XII, and X), and H2 (lineage III) were identified. The associations found in the samples were G1, G9, or G12 with P[8]-I1-E1-H1; G2 or G8 with P[4]-I2-E2-H2; G12 with I3-E3-H6; and G3 with P[4]-I2-E3-H3 (previously unreported combination). Reassortment events in G2P[4] strains and an apparent pattern of temporal segregation within the lineages were observed. Five TM samples contained genes that exhibited high nucleotide and amino acid identities with strains of animal origin. The present study includes a period of pre- and post-introduction of rotavirus vaccination in all Brazilian territories, thereby serving as a basis for monitoring changes in the genetic constitution of rotaviruses. The results also contribute to the understanding of the diversity and evolution of rotaviruses in a global context.

Diversity of group A rotavirus genes detected in the Triângulo Mineiro region, Minas Gerais, Brazil.

Group A rotaviruses are the main causative agent of infantile gastroenteritis. The segmented nature of the viral genome allows reassortment of genome segments, which can generate genetic variants. In this study, we characterized the diversity of the VP7, VP4 (VP8*), VP6, NSP4, and NSP5 genes of the rotaviruses that circulated from 2005 to 2011 in the Triângulo Mineiro (TM) region of Brazil. Samples with genotypes G2 (sublineages IVa-1 and IVa-3), G1 (sublineage I-A), G9 (lineage III), G12 (lineages II and III), G8 (lineage II), G3 (lineage III), P[4] (sublineages IVa and IVb), P[8] (sublineages P[8]-3.6, P[8]-3.3, and P[8]-3.1), I2 (lineage VII), E2 (lineages VI, XII, and X), and H2 (lineage III) were identified. The associations found in the samples were G1, G9, or G12 with P[8]-I1-E1-H1; G2 or G8 with P[4]-I2-E2-H2; G12 with I3-E3-H6; and G3 with P[4]-I2-E3-H3 (previously unreported combination). Reassortment events in G2P[4] strains and an apparent pattern of temporal segregation within the lineages were observed. Five TM samples contained genes that exhibited high nucleotide and amino acid identities with strains of animal origin. The present study includes a period of pre- and post-introduction of rotavirus vaccination in all Brazilian territories, thereby serving as a basis for monitoring changes in the genetic constitution of rotaviruses. The results also contribute to the understanding of the diversity and evolution of rotaviruses in a global context.

Cerebrotendinous xanthomatosis; a genetic condition: Clinical profile of three patients from a rural Indian family and review of literature.

INTRODUCTION: Cerebrotendinous xanthomatosis is a rare lipid storage disease characterized by infantile onset diarrhea, cataract, tendon xanthomas, and progressive neurologic dysfunction. Cerebrotendinous xanthomatosis is exceptionally rare in Indian population with only few case reports till now. CASE REPORT: An 18-year-old male presented to orthopedic outpatients clinic with complaints of insidious onset swelling of both achilles over last 3 years, with history of learning and visual difficulties. On examination, there were firm nontender swellings along the course of both tendoachillis. Plantar response was extensor and Romberg test was positive with eyes closed. Cranial MRI showed diffuse cerebral and cerebellar atrophy. Family history showed history of diarrhea, mental retardation, and visual difficulties in his two younger siblings. They were also called upon and evaluated clinically. All three were diagnosed as having cerebrotendinous xanthomatosis based on clinical and radiological features. CONCLUSION: Cerebrotendinous xanthomatosis is a progressive and preventable disorder and it benefits from therapy, so early diagnosis is mandatory to prevent significant morbidity and mortality associated with this disease.