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.

Nucleótidos y carotenoides naturales / Nucleotides and carotenoids

El concepto de los nucleótidos no es nuevo; máxime que son elementos que hacen parte de los componentes naturales de la leche materna. Casi todos los estudios señalan que el consumo de carotenoides, previenen el desarrollo de enfermedades crónicas en la edad adulta, posiblemente por su efecto antioxidante que disminuye el estrés oxidativo, mejorando enfermedades degenerativas y malignas.

The concept of nucleotides is not new, especially since they are elements that are part of the natural components of human milk. Most studies indicate that the consumption of carotenoids, prevent the development of chronic diseases in adulthood, possibly by its antioxidant effect that reduces oxidative stress, improving degenerative diseases and malignancies.

Zinc en la infancia: rompiendo paradigmas / Zinc in childhood: breaking paradigms

El zinc es un ejemplo de un micronutriente esencial, cuya deficiencia juega un papelimportante en la comprensión de las altas tasas de mortalidad y morbilidad infantil en países en desarrollo. Tanto la deficiencia intermedia de zinc como de vitamina A, pueden pasar inadvertidas clínicamente. Con respecto a la inmunidad, el zinc es fundamental para las funciones de tejidos de alto recambio, especialmente en el sistema inmunitario, y su deficiencia se asocia a alteraciones de la inmunidad innata, la inmunidad humoral y la inmunidad celular. Existe evidencia que avala la s u p l eme n t a c i o n d e z i n c d u r a n t e e inmediatamente después de un episodio de diarrea aguda, con lo que se disminuye su tiempo de duración y la gravedad, con reducción en la incidencia de diarrea en los dos o tres meses siguientes.Aun no se conoce exactamente cuál es el mecanismo que explique por qué se encuentra limitada la proliferación celular ante la deficiencia de zinc.

Zinc is an example of an essential micronutrient whose deficiency plays an important role in understanding the high rates of infant mortality and morbidity in developing countries. Both intermediate zinc deficiency and vitamin A, may go unnoticed clinically.With respect to immunity, zinc is essential for the functions of tissues of high turnover, especially in the immune system, and its deficiency is associated with alterations of innate immunity, humoral immunity and cellular immunity. There is evidence supporting zinc supplementation during and immediately after an episode of acute diarrhea, which shortens their duration and severity, with a reduction in the incidence of diarrhea in the two or three months. Still not known exactly what the mechanism that explains why it is limited to cell proliferation in zinc deficiency.

Bacterial aetiology of diarrhoea in young children: high prevalence of enteropathogenic Escherichia coli (EPEC) not belonging to the classical EPEC serogroups.

Diarrhoeal disease continues to be one of the most common causes of admittance in Children hospital emergency. The aim of the present study was to investigate the relative contribution of enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively) as a cause of infectious bacterial diarrhoea in children from the region of Toulouse. We analysed 280 samples of stools from 280 children (<2 years) with diarrhoea admitted in the "Hopital des Enfants" from January to August 2005. Classic pathogens (Salmonella, Campylobacter, Yersinia, Shigella, Aeromonas and Vibrio) were detected by standard culture methods. Enterotoxigenic Clostridium difficile were identified after culture by immuno-enzyme assay (IEA). Virulence genes of EPEC and EHEC were detected by using PCR. Shiga-toxin production of EHEC strains was confirmed with an IEA test. Potential enteric pathogens were identified in 55 patients. EPEC was the most frequently identified agent (30 patients), followed by Campylobacter (9 cases: 7 C. jejuni and 2 C. coli) and C. difficile (8 patients), then EHEC (5 patients) and Salmonella (3 patients). No Shigella, Yersinia, Aeromonas or other pathogenic bacteria were detected during this period in that class of children. EPEC not belonging to the classical EPEC serogroups were highly prevalent (24 versus 6). EHEC possessed different genotypes and serogroups: O26 (2 strains), O157 (2 strains) and one un-typable strain. This study demonstrates the importance of EPEC (55 % of positive cases) and of EHEC (more frequent than Salmonella) in the aetiology of diarrhoeal diseases of young children. We confirm the usefulness of the PCR methodology: it allows the detection of virulent E. coli and thus increases by two fold the diagnosis of bacterial diarrhoea.

Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants.

OBJECTIVE: To determine the association between maternal milk levels of 2-linked fucosylated oligosaccharide and prevention of diarrhea as a result of Campylobacter, caliciviruses, and diarrhea of all causes in breast-fed infants. STUDY DESIGN: Data and banked samples were analyzed from 93 breast-feeding mother-infant pairs who were prospectively studied during 1988-1991 from birth to 2 years with infant feeding and diarrhea data collected weekly; diarrhea was diagnosed by a study physician. Milk samples obtained 1 to 5 weeks postpartum were analyzed for oligosaccharide content. Data were analyzed by Poisson regression. RESULTS: Total 2-linked fucosyloligosaccharide in maternal milk ranged from 0.8 to 20.8 mmol/L (50%-92% of milk oligosaccharide). Moderate-to-severe diarrhea of all causes (n=77 cases) occurred less often (P=.001) in infants whose milk contained high levels of total 2-linked fucosyloligosaccharide as a percent of milk oligosaccharide. Campylobacter diarrhea (n=31 cases) occurred less often (P=.004) in infants whose mother's milk contained high levels of 2'-FL, a specific 2-linked fucosyloligosaccharide, and calicivirus diarrhea (n=16 cases) occurred less often (P=.012) in infants whose mother's milk contained high levels of lacto-N-difucohexaose (LDFH-I), another 2-linked fucosyloligosaccharide. CONCLUSION: This study provides novel evidence suggesting that human milk oligosaccharides are clinically relevant to protection against infant diarrhea.

Local beliefs about childhood diarrhoea: importance for healthcare and research.

The aim of this study was to describe perceptions and beliefs about childhood diarrhoea in a rural South African area. A further aim was to describe mismatches with medical concepts that may influence quality of diarrhoea care and validity of population-based diarrhoea research. This was a descriptive study carried out in a rural district of KwaZulu/Natal, South Africa. Using a validated ethnographic method information was compiled from semi-structured interviews, card sorting exercises, case histories, and focus group discussions with 29 caregivers in total. Description of locally perceived diarrhoea types, signs, symptoms, causes and actions taken were recorded. Eleven 'local types of diarrhoea' were identified, which were classified into three categories: (A) natural causation, (B) supernatural causation, and (C) caused by 'germs' or change in diet. Conceptual mismatches included: (1) not all conditions with frequent or watery stools were perceived as diarrhoea; (2) hygiene was considered irrelevant in the causation of A and B; (3) signs of dehydration were not always attributed to loss of fluid; (4) medical care and oral rehydration therapy were considered useless in B; (5) potentially harmful treatments, such as herbal enemas, are always preferred in B, sometimes in A. These mismatches carry the potential to hamper health promotion, predispose to delayed and poor care and may lead to selection bias, under- and misreporting and poor compliance in research. This study highlights the discrepancies in concepts between medically trained and local people regarding the nature of childhood diarrhoea, the rationale behind care-seeking behaviour, and what can be expected from proposed interventions. Taking these discrepancies into account is not only essential to programmatic success and continued support but also for epidemiological surveys.

Factors affecting decisions to seek treatment for sick children in Kerala, India.

The purpose of this study was to measure the effects of social and economic variables, disease-related variables, and child gender on the decisions of parents in Kerala, India, to seek care for their children and on their choice of providers in the allopathic vs. the alternative system. A case-control analysis was done using data from the Kerala section of the 1996 Indian National Family Health Survey, a cross-sectional survey of a probability sample of households conducted by trained interviewers with a close-ended questionnaire. Of the 469 children who were eligible for this study because they had at least one common symptom suggestive of acute respiratory illness or diarrhea during the 2 weeks before the interview, 78 (17%) did not receive medical care, while the remaining 391 (83%) received medical care. Of the 391 children who received medical care, 342 (88%) received allopathic medical care, and 48 (12%) received alternative medical care. In multivariable analyses, parents chose not to seek medical care for their children significantly more often when the illness was mild, the child had a specific diagnosis, the mother had previously made fewer antenatal visits, and the family had a higher economic status. When parents sought medical care for their children, care was sought significantly more often in the alternative provider system when the child was a boy, the family lived in a rural area, and the family had a lower social class. We conclude that, in Kerala, disease severity and economic status predict whether children with acute respiratory infection or diarrhea are taken to medical providers. In contrast, most studies of this issue carried out in other populations have identified economic status as the primary predictor of medical system utilization. Also in Kerala, the gender of the child did not influence whether or not the child was taken for treatment but did influence whether care was sought in the alternative or the allopathic system.

Haga su diagnóstico: Datos Clínicos / Do his i diagnosis: clinician data

Niño de 3 años de edad que consultó por desnutrición grave, retraso del crecimiento, distención abdominal desde los 6 meses de vida y deposiciones diarreicas intermitentes

A seven-year audit of a diarrhoea training unit (DTU) in Port Harcourt, Nigeria.

The Diarrhoea Training Unit [DTU] of the University of Port Harcourt Teaching Hospital in Nigeria was established in 1991 and has, in addition to treating cases, been involved in training medical students, paediatric residents, health workers and mothers caregivers on correct case management of diarrhoeal disease. The accomplishment of the Unit over a defined time frame, January 1993 to December 1999, was evaluated by employing predetermined indicators and the data were analyzed by using the Statistical Package PEPI [Computer Programs for Epidemiologic Analysis Version 2.07a]. Eight thousand, four hundred and eighty-six cases (4557 males and 3929 females) of acute diarrhoea were treated. Those with severe dehydration were eleven times fewer in 1998 and eight times fewer in 1999 than in 1993. The number of Oral Rehydration Salts (ORS) sachets used in the Unit increased from 3064 in 1993/94 to 17,549 in 1998/99. There was no reduction in the number of cases treated, but the case-fatality rates dropped from 6 per 1000 in 1993 to 0.6 per 1000 in 1999 [likelihood ratio chi2 = 9.874, p = 0.02]. There was a significant reduction in the proportion of patients with bloody stools towards the end of the observation period [chi2(trend) = 82.60, 1 df, p = 0.000 (1.00E-19)]. These results indicate some positive impact on the severity of diarrhoea in the area, but preventive measures should now constitute the main thrust.

Association between clinical type of diarrhoea and growth of children under 5 years in rural Bangladesh.

BACKGROUND: The role of diarrhoea in the aetiology of growth retardation in young children remains controversial. To evaluate this, a population-based, longitudinal study of young children aged 6-48 months was conducted in Matlab, a rural area of Bangladesh, between May 1988 and April 1989. METHODS: Data obtained from 584 children were examined by one-year (n = 412) and 3-month (n = 1220) growth periods. Each growth period was analysed based on clinical types of diarrhoea, namely, non-diarrhoea, non-dysentery diarrhoea (diarrhoea without blood), and dysentery (diarrhoea with blood). Weight and height gains were compared among the study groups initially by one-way analysis of variance followed by multivariate analysis adjusting for potential confounding variables. RESULTS: Compared to non-diarrhoea and non-dysentery diarrhoea, dysentery was associated with significantly lower annual weight gain (1866 g [P < 0.01] and 1550 g [P < 0.05] versus 1350 g, respectively) and height gain (6.51 cm and 5.87 cm versus 5.27 cm [P < 0.01], respectively). Both 3-month dysentery and non-dysentery intervals were significantly associated with less weight gain compared to non-diarrhoea intervals (490 g and 522 g versus 637 g [P: < 0.05], respectively). Dysentery intervals were also associated with significantly poorer height gain compared to other intervals (2.19 cm versus 2.42 cm [P < 0.05] and 2.46 cm [P < 0.01], respectively). CONCLUSIONS: The growth of young children is strongly influenced by the clinical type of diarrhoea and the impact is dependent on the proportion of dysentery episodes in the total diarrhoeal burden.

Diarrea y nutrición: experiencias en niños y ratas / Nutrition and diarrhea: experiences with childrens and rats

La diarrea infantil es un problema de salud pública en Venezuela y el proceso diarreico es un problema clínico que acompaña numerosas patologías. Independientemente de la causa, la diarrea deteriora el estado nutricional del paciente. El déficit nutricional ocurre por el bajo consumo de alimentos, una menor absorción y retención de nutrientes y el incremento en los requerimientos nutricionales. A su vez, el déficit nutricional limita la capacidad inmunitaria y altera la morfología de la mucosa intestinal facilitando el ciclo diarrea-desnutrición. Nuestro interés se ha enfocado en los aspectos nutricionales del manejo del niño con diarrea y en la utilización de los nutrientes durante el proceso diarreico. Realizamos estudios de balance en 165 niños con diarrea aguda y en 15 niños con diarrea aguda y en 15 niños con diarrea prolongada. Encontramos que los niños con diarrea aguda consumen solo un 50-75 por ciento de su requerimiento energético y que la absorción de macronutrientes provenientes de diferentes fuentes alimentarias fue de 55-78 por ciento; siendo la grasa, el nutriente menos afectado por la severidad de la diarrea. Cuantitativamente la reducción en el consumo es el elememto mas importante en el deterioro nutricional. Adicionalmente, hemos realizado estudios de balance en ratas con diarrea inducida por lactosa o bisoxatin acetato encontrando tendencias similares a lo observado en niños. Por tanto, aparte de la rehidratación oral, lo mas importante en el tratamiento del niño con diarrea es lograr un adecuado consumo energético

Differentiation of osmotic and secretory diarrhoea by stool carbohydrate and osmolar gap measurements.

Clinical features and laboratory tests that determine carbohydrate in faeces were evaluated to determine which was best able to distinguish between osmotic and secretory diarrhoea in infants and children. For this purpose 80 boys aged 3 to 24 months, with acute watery diarrhoea, were studied prospectively. The faecal osmolar gap (FOG) was calculated as: serum osmolarity-[2 x (faecal sodium + potassium concentration)]. Fifty eight patients were classified as having predominantly osmotic diarrhoea (FOG > 100 mosmol/l), and 22 as having predominantly secretory diarrhoea (FOG < or = 100 mosmol/l). The two groups were comparable in their clinical features on admission, in the results of blood and urine tests, and in the evolution of their diarrhoeal illness. Evidence of steatorrhoea (by positive Sudan III test) and of acid faecal pH on admission were significantly more frequent in patients with osmotic diarrhoea. Mean (SD) faecal osmolarity was not significantly different between the two groups (319 (80) mosmol/l in secretory diarrhoea v 361 (123) mosmol/l in osmotic diarrhoea). Tests for reducing substances in faeces such as Benedict's test--with and without hydrolysis--and glucose strip, all showed a positive and significant association with osmotic diarrhoea (p < 0.05, < 0.025, < 0.05, respectively). The presence of excess reducing substances (Benedict's test with hydrolysis > 2+) on admission was the most sensitive and specific test with the best predictive value for differentiating between the two types of watery diarrhoea.

The associations between feeding modes and diarrhoea among urban children in a newly developed country.

The protective effect of breastfeeding against infantile diarrhoea may be less pronounced in areas with modern water supply and sanitation facilities. This finding raises the question whether protection by breastfeeding against infantile diarrhoea in developing countries will decline with improvement in water supply and sanitation. To address this question a historical cohort study of the associations between feeding modes and diarrhoea incidence and severity in children aged 0-14 months at baseline was done in Al Ain city, United Arab Emirates. In this city in a newly developed country, modern water supply and sanitation facilities have become available to everyone during the last two decades. During three months of follow-up of 249 children, the nonbreastfed had more diarrhoea than did the partly breastfed, who in turn had more diarrhoea than did the fully breastfed. After multivariate adjustment, this dose-response effect was consistent for three measures of diarrhoeal morbidity in each child: occurrence or non-occurrence of incidence episodes, number of episodes, and total severity score. However, significant differences were seen only between the nonbreastfed and fully breastfed subgroups. These results indicate that in Al Ain, despite the universal access to modern water supply and sanitation facilities, breastfeeding plays an important role in reducing the incidence and severity of infantile diarrhoea. This observation is particularly important given the growing concern that, as an unwanted effect of 'modernisation', breastfeeding is on the decline in Al Ain and comparable populations elsewhere.

PIP: Since the protective effect of breast feeding against infantile diarrhea may be less pronounced in areas with modern water supply and sanitation facilities, this effect may decline as developing countries make improvements in these areas. This possibility was addressed in a historical cohort study of the association between feeding modes and diarrhea incidence and severity in 249 children from Al Ain city, United Arab Emirates, who were 0-14 months of age at baseline. During the past two decades, a modern water supply and sanitation facilities have become universally available in this newly developed country. During 3 months of follow-up, 69 (28%) of the 249 children had at least 1 diarrhea episode. The 61 non-breast-fed infants had more diarrhea than the 45 partially breast-fed infants, who in turn had more diarrhea than the 143 fully breast fed ones. After multivariate adjustment, this dose-response effect was consistent for three measures of diarrheal morbidity in each child: occurrence or nonoccurrence of incidence episodes, number of episodes, and total severity score. However, significant differences were seen only between the non-breast-fed and fully breast-fed infants. These findings indicate that breast feeding remains a critical child health intervention, even in areas with universal access to modern water supply and sanitation facilities.

Novedoso expansor de volumen con doble disponibilidad en el tratamiento de niños con deshidratación moderada y grave producida por diarrea aguda / Expansor new of volume with availability double in the childrens of treatment with grave and moderate dehydratation cause by acute diarrhea

Evaluar la efectividad e inocuidad de la Solución Electrolítica "Q" con doble disponibilidad. Estudio prospectivo; descriptivo y observacional. 45 pacientes divididos en dos grupos: 1) Veinte y tres pacientes (edad promedio 5.5 a 45.5 meses de edad) con deshidratación severa (choque hipovolémico), debida a diarrea aguda; II) veintidós pacientes con deshidratación moderada por diarrea. I) La terapia de Rehidratación Intravenosa (TRIV) fue indicada por choque hipovolémico, fue realizada con una Solución Electrolítica "Quisber" (Q) con doble disponibilidad, inducida a 50 ml/kg durante la primera hora y 25 ml/kg la segunda y tercera hora II) La terapia de Rehidratación Oral (TRO), fue indicada por deshidratación sin choque hipovolémico. Fue realizada a 100 ml/kg/4 horas, con la misma Solución Electrolítica "Quisber" (Q). I) Primera hora 43.2 por ciento (10/23) corregidos los parámetros hemodinámicos, siete con choque leve, seis con choque moderado y diez con choque grave. Segunda hora corregidos 52.1 por ciento (12/23), tres choque grave, con choque moderado y cuatro con choque grave. Tercera hora 4.3 por ciento (1/23), constituido por choque leve. II) Corregidos los parámetros el 91.6 por ciento (21/22), a las cuatro horas y el 8.3 por ciento (1/22) a las seis horas no existiendo diferencias significativas estadísticas en ambos grupos. Igual que otras soluciones sirve para contrarrestar los efectos de una deshidratación por diarrea aguda y para revertir el choque hipovolémico. Sin embargo, a diferencia de los demás expansores de volumen intravascular

Rotavirus infection in infants as protection against subsequent infections.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in infants. To provide a base line for assessing the efficacy of rotavirus vaccines, we evaluated the protection that is conferred by natural rotavirus infection. METHODS: We monitored 200 Mexican infants from birth to two years of age by weekly home visits and stool collections. A physician assessed the severity of any episodes of diarrhea and collected additional stool specimens for testing by enzyme immunoassay and typing of strains. Serum collected during the first week of life and every four months thereafter was tested for antirotavirus IgA and IgG. RESULTS: A total of 316 rotavirus infections were detected on the basis of the fecal excretion of virus (56 percent) or a serologic response (77 percent), of which 52 percent were first and 48 percent repeated infections. Children with one, two, or three previous infections had progressively lower risks of both subsequent rotavirus infection (adjusted relative risk, 0.62, 0.40, and 0.34, respectively) and diarrhea (adjusted relative risk, 0.23, 0.17, and 0.08) than children who had no previous infections. No child had moderate-to-severe diarrhea after two infections, whether symptomatic or asymptomatic. Subsequent infections were significantly less severe than first infections (P=0.024), and second infections were more likely to be caused by another G type (P=0.054). CONCLUSION: In infants, natural rotavirus infection confers protection against subsequent infection. This protection increases with each new infection and reduces the severity of the diarrhea.

Maternal education and family income as determinants of severe disease following acute diarrhoea in children: a case control study.

In a case-control study among the urban poor of Dhaka, Bangladesh, the association of maternal education and family income with severity of disease due to diarrhoea in children was examined. After adjusting for family income, 7 or more years of school education was associated with 54% reduced risk of severe disease as indicated by the presence of dehydration. Income in the uppermost quartile of this population, independently of maternal education, was associated with 41% reduced risk of severe disease compared to the lowest quartile. In the logistic regression model the effect of maternal education remained high after adjustment for several confounders. Based on the concept that socioeconomic variables operate through a set of proximate variables it is contended that maternal education, independently of economic power, through its impact on disease from acute diarrhoea, favourably influences child survival.

Doce mil trescientos niños con diarrea

Se presentan los datos de 12.300 pacientes atendidos en la consulta de diarreas de la Unidad de Capacitación para el Tratamiento de la Diarrea del Hospital Universitario San Vicente de Paúl de Medellín, durante un período de cinco años. De los pacientes, 56.8 por ciento fueron hombres, 78 por ciento fueron menores de dos años y 43 por ciento menores de un año, 69 por ciento de los niños fueron eutróficos, 24 por ciento presentaron desnutrición leve y 7 por ciento desnutrición avanzada; 90.8 por ciento de los niños tuvieron diarrea aguda, el resto diarrea persistente; 84.3 por ciento tuvieron diarrea acuosa, 10.4 por ciento diarrea disentérica, y 5.2 por ciento consultaba sólo por vómito; 58 por ciento de los niños habían sido atendidos previamente en forma ambulatoria por lo menos una vez por médico; 60 por ciento de los niños recibían suero para rehidratación oral (SRO) con 90 mmol de sodio por litro. Casi 40 por ciento de los niños, cuando consultaron recibían antibióticos, 16 por ciento recibían antidiarreicos e igual proporción antiparasitarios, 18 por ciento habían recibido antieméticos, 53.9 por ciento se encontraron hidratos, 44.4 por ciento presentaron algún grado deshidratación y 1.8 por ciento tuvo deshidratación grave.