Diet management in congenital diarrheas and enteropathies - general concepts and disease-specific approach, a narrative review.

Congenital diarrheas and enteropathies (CODE) are a group of rare, heterogenous, monogenic disorders that lead to chronic diarrhea in infancy. Definitive treatment is rarely available, and supportive treatment is the mainstay. Nutritional management in the form of either specialized formulas, restrictive diet, or parenteral nutrition support in CODE with poor enteral tolerance is the cornerstone of CODE treatment and long-term growth. The evidence to support the use of specific diet regimens and nutritional approaches in most CODE disorders is limited due to the rarity of these diseases and the scant published clinical experience. The goal of this review was to create a comprehensive guide for nutritional management in CODE, based on the currently available literature, disease mechanism, and the PediCODE group experience. Enteral diet management in CODE can be divided into 3 distinct conceptual frameworks: nutrient elimination, nutrient supplementation, and generalized nutrient restriction. Response to nutrient elimination or supplementation can lead to resolution or significant improvement in the chronic diarrhea of CODE and resumption of normal growth. This pattern can be seen in CODE due to carbohydrate malabsorption, defects in fat absorption, and occasionally in electrolyte transport defects. In contrast, general diet restriction is mainly supportive. However, occasionally it allows parenteral nutrition weaning or reduction over time, mainly in enteroendocrine defects and rarely in epithelial trafficking and polarity defects. Further research is required to better elucidate the role of diet in the treatment of CODE and the appropriate diet management for each disease.

Duración de la diarrea aguda infecciosa con el uso de leche deslactosada vs leche con lactosa en la población pediátrica: Revisión sistemática / Duration of acute infectious diarrhea with the use of lactose-free milk vs. lactose-containing milk in the pediatric population: A systematic review

Introducción: La diarrea aguda es una entidad frecuente en pediatría, constituyendo una de las principales causas de mortalidad en países en desarrollo y en niños menores de cinco años. Si bien la alimentación representa uno de los pilares fundamentales en el tratamiento de la misma, no existe consenso entre los profesionales en cuanto a la indicación de leche deslactosada durante el curso del cuadro. Objetivos: Realizar una revisión sistemática para estudiar el impacto del consumo de leche deslactosada vs leche regular en la duración de la diarrea aguda infecciosa en niños. Materiales y métodos: Se realizó una revisión sistemática incluyendo artículos publicados desde el año 2008 al 2023, utilizando para la búsqueda las bases de datos PubMed, Lillacs, Cochrane Library y literatura gris. Se incluyeron estudios experimentales, observacionales, revisiones, guías de atención y metaanálisis, realizados en pacientes pediátricos sin patologías de base, cursando cuadro de diarrea aguda infecciosa, que compararan el uso de leche deslactosada frente a leche regular. Resultados: Se seleccionaron doce artículos. En 9 de ellos se constató una disminución en la duración de la diarrea en los pacientes que recibieron leche deslactosada con una diferencia de medias de 18 horas (en un rango entre 4 y 32.6 horas). No se reportaron diferencias estadísticamente significativas en la mortalidad entre el uso de una u otra fórmula láctea. En relación al uso de una u otra fórmula no se objetivaron variaciones en el peso estadísticamente significativas. La necesidad de hospitalización fue similar entre ambos grupos. Solo un artículo analizó la frecuencia o volumen de deposiciones sin encontrar diferencias significativas (AU)

Introduction:Acute diarrhea is frequent in pediatrics, and constitutes one of the main causes of mortality in developing countries and in children under five years of age. Although feeding is one of the fundamental pillars in the treatment of diarrhea, there is no consensus among professionals regarding the indication of lactose-free milk during the course of the symptoms. Objectives: To conduct a systematic review to study the impact of lactose-free milk vs. regular milk consumption on the duration of acute infectious diarrhea in children. Materials and methods: A systematic review was conducted including articles published between 2008 and 2023, using PubMed, Lillacs, Cochrane Library databases, and gray literature for the search. Experimental and observational studies, reviews, care guidelines and meta-analysis were included, conducted in pediatric patients without underlying diseases, with acute infectious diarrhea, comparing the use of lactose-free milk versus regular milk. Results: Twelve articles were selected. Nine of them showed a decrease in the duration of diarrhea in patients who received lactose-free milk with a mean difference of 18 hours (ranging from 4 to 32.6 hours). No statistically significant differences in mortality were reported between the use of one or the other milk formula. Regarding the use of one or the other formula, there were no statistically significant variations in weight. The need for hospital admission was similar between the two groups. Only one article analyzed stool frequency or volume with no significant differences (AU)

Chronic diarrhoea due to trichohepatoenteric syndrome (THES) in an infant.

An infant was admitted with suspected postinfectious malabsorption with watery diarrhoea, fever and failure to thrive. She had dehydration, acute kidney injury and metabolic acidosis, which were corrected with intravenous fluids and managed with empiric antibiotics and prophylactic antifungals. She also developed Escherichia coli sepsis, meningitis and Candida skin infections during hospitalisation, which were treated according to the culture reports. Intrauterine growth restriction, woolly hair and a broad nasal bridge with chronic refractory diarrhoea prompted genetic testing to rule out syndromic diarrhoea. Whole-exome sequencing revealed a pathogenic compound heterozygous mutation causing trichohepatoenteric syndrome. She succumbed to severe infections at 80 days of life. The condition is rare, and no established guidelines or specific treatments exist; the focus is to promote optimal growth through parenteral nutrition, elemental formula and infection control. Early suspicion and molecular genetic testing can help reduce the time to diagnosis, treatment and genetic counselling.

Long term outcomes in children with trichohepatoenteric syndrome.

Trichohepatoenteric syndrome (THES) is a rare autosomal recessive disorder caused by mutations in either TTC37 or SKIV2L, usually leading to congenital diarrhea as part of a multisystem disease. Here, we report on the natural history of the disease for the largest UK cohort of patients with THES from 1996 to 2020. We systematically reviewed the clinical records and pathological specimens of patients diagnosed with THES managed in a single tertiary pediatric gastroenterology unit. Between 1996 and 2020, 13 patients (7 female and 6 male) were diagnosed with THES either by mutation analysis or by clinical phenotype. Two patients died from complications of infection. All patients received parenteral nutrition (PN) of which six patients were weaned off PN. All patients had gastrointestinal tract inflammation on endoscopy. Almost half of the cohort were diagnosed with monogenic inflammatory bowel disease (IBD) by the age of 11 years, confirmed by endoscopic and histological findings. Protracted diarrhea causing intestinal failure improves with time in all patients with THES, but monogenic IBD develops in later childhood that is refractory to conventional IBD treatments. Respiratory issues contribute to significant morbidity and mortality, and good respiratory care is crucial to prevent comorbidity.

A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: "VS002A" trial protocol.

BACKGROUND: Diarrhea is the second deadliest disease for under-five children globally and the situation is more serious in developing countries. Oral rehydration solution (ORS) is being used as a standard treatment for acute watery diarrhea for a long time. Our objective is to compare the efficacy of amino acid-based ORS "VS002A" compared to standard glucose-based WHO-ORS in infants and young children suffering from acute non-cholera watery diarrhea. METHODS: It is a randomized, double-blind, two-cell clinical trial at Dhaka Hospital of icddr,b. A total of 312 male children aged 6-36 months old with acute non-bloody watery diarrhea are included in this study. Intervention arm participants get amino acid-based ORS (VS002A) and the control arm gets standard glucose-based WHO-ORS. The primary efficacy endpoint is the duration of diarrhea in the hospital. DISCUSSION: Oral rehydration therapy (ORT) with the present ORS formulation has certain limitations - it does not reduce the volume, frequency, or duration of diarrhea. Additionally, the failure of present standard ORS to significantly reduce stool output likely contributes to the relatively limited use of ORS by mothers as they do not feel that ORS is helping their child recover from the episode of diarrhea. Certain neutral amino acids (e.g., glycine, L-alanine, L-glutamine) can enhance the absorption of sodium ions and water from the gut. By using this concept, a shelf-stable, sugar-free amino acid-based hydration medicinal food named 'VS002A' that effectively rehydrates, and improves the barrier function of the bowel following infections targeting the gastrointestinal tract has been developed. If the trial shows significant benefits of VS002A use, this may provide evidence to support consideration of the use of VS002A in the present WHO diarrhea management guidelines. Conversely, if there is no evidence of benefit, these results will reaffirm the current guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT04677296 . Registered on December 21, 2020.

Traditional Chinese Medicine Moxibustion in the Treatment of Infantile Diarrhea.

The main contribution of this research paper is to summarize the results of Meta-analysis of moxibustion in the treatment of infantile diarrhea which is one the common disease and requires considerable attention from the research community and funding organizations. In order to verify that the proposed scheme has merits, a comprehensive searching methodology was adopted by considering various databases such as China Biomedical Literature Database (CBM), China National Knowledge Network Infrastructure (CNKI), Wanfang Database, Pub Med Database, Google Academic, and Cochrane Library. It is important to note that a powerful computer has been utilized to carry out this searching. Finally, only those literature contents are selected which meet the inclusion criteria. Likewise, exclusion criteria was used to exclude irrelevant contents of the literature. RevMan 5.3 was used to analyze the collected data and after reading the titles and abstracts, 29 well-designed studies were selected. Through searching the full text, reading literature, and quality evaluation, 17 papers were finally included. Response rates were reported in all 17 studies, and subgroup analysis was performed based on whether or not other therapies were combined. 7 studies compared the effectiveness of simple moxibustion and conventional therapy in the treatment of infantile diarrhea, and the results showed statistically significant differences [OR = 4.01, 95% CI (2.03, 7.84), P < 0.0001]; 10 studies compared the effectiveness of moxibustion combined with other therapies and conventional therapies in the treatment of diarrhea in children, and the results showed that the difference had general meaning [OR = 4.45, 95% CI (2.83, 7.10), P < 0.00001]. The funnel plot (in Figure) showed that the distribution of included studies was asymmetrical on both sides of the baseline, which could be considered as publication bias. Traditional Chinese medicine moxibustion could effectively relieve the symptoms of infantile diarrhea, and the effect was significant.

Moxibustion for diarrhea in children: A protocol for systematic review and meta-analysis.

BACKGROUND: Infantile Diarrhea is a common and frequent digestive tract disease in children. The causes of this disease are relatively complex and the onset time is relatively long. At present, there is no specific treatment method in Western medicine. Moxibustion is a simple and painless external treatment. However, due to the lack of high-quality evidence to support the effectiveness and safety of moxibustion therapy for pediatric diarrhea. Therefore, the purpose of this study is to verify the effectiveness and safety of moxibustion in the treatment of pediatric diarrhea. METHODS: We will use PubMed, Cochrane Library, Wan Fang Database, Web of Science, China National Knowledge Infrastructure Database, Chinese Science Journal Database, China Biomedical Literature Database to carry out a progressive search of diseases. The study will be screened according to eligibility criteria, and quality of the study will be assessed by using the Cochrane Risk of Bias Tool. RESULTS: Through this study, we will systematically evaluate the effectiveness and safety of moxibustion in the treatment of pediatric diarrhea. CONCLUSION: The results of this study will provide reliable evidence of the safety and effectiveness of moxibustion in the treatment of infantile diarrhea, and provide a therapeutic basis for the future clinical application. ETHICS AND DISSEMINATION: Since this paper does not involve ethical issues, it does not need to pass the review of the ethics committee. It can only collect relevant literature and study. INPLASY REGISTRATION NUMBER: INPLASY202130091.

Chinese pediatric Tuina on children with acute diarrhea: a randomized sham-controlled trial.

BACKGROUND: Pediatric Tuina has been widely used in children with acute diarrhea in China. However, due to the lack of high-quality clinical evidence, the benefit of Tuina as a therapy is not clear. We aimed to assess the effect of pediatric Tuina compared with sham Tuina as an add-on therapy in addition to usual care for 0-6-year-old children with acute diarrhea. METHODS: Eighty-six participants aged 0-6 years with acute diarrhea were randomized to receive pediatric Tuina plus usual care (n = 43) or sham Tuina plus usual care (n = 43). The primary outcomes were days of diarrhea from baseline and times of diarrhea on day 3. Secondary outcomes included a global change rating (GCR) and the number of days when the stool characteristics returned to normal. Adverse events were assessed. RESULTS: Pediatric Tuina was associated with a reduction in times of diarrhea on day 3 compared with sham Tuina in both ITT (crude RR, 0.73 [95% CI, 0.59-0.91]) and PP analyses (crude RR, 0.66 [95% CI, 0.53-0.83]). However, the results were not significant when we adjusted for social demographic and clinical characteristics. No significant difference was found between groups in days of diarrhea, global change rating, or number of days when the stool characteristics returned to normal. CONCLUSIONS: In children aged 0-6 years with acute diarrhea, pediatric Tuina showed significant effects in terms of reducing times of diarrhea compared with sham Tuina. Studies with larger sample sizes and adjusted trial designs are warranted to further evaluate the effect of pediatric Tuina therapy. TRIAL REGISTRATION: Clinicaltrials.gov, Identifier: NCT03005821 , Data of registration: 2016-12-29.

Congenital Diarrheal Diseases.

Early diagnosis of diarrhea is critical to prevent disease progression. Diarrhea in newborns can be congenital or acquired; acquired diarrheas are the major cause in infants. Congenital diarrheal diseases are rare and include defects in digestion, absorption, and transport of nutrients, and electrolytes; disorders of enterocyte differentiation and polarization; defects of enteroendocrine cell differentiation; dysregulation of the intestinal immune response; and dysfunction of the immune system. This review discusses the clinical approach that may help in early identification and management of different congenital diarrheal diseases.

Intestinal Failure: A Description of the Problem and Recent Therapeutic Advances.

Pediatric intestinal failure occurs when gut function is insufficient to meet the nutrient and hydration needs of the growing child. The commonest cause is short bowel syndrome with maldigestion and malabsorption following massive bowel loss. The remnant bowel adapts during the process of intestinal rehabilitation. Management promotes the achievement of enteral autonomy while mitigating the risk of comorbid disease. The future of care is likely to see expansion of pharmacologic methods for augmenting bowel adaptation, tissue engineering techniques enabling immune suppression-free autologous bowel transplant, and the development of electronic health record tools for efficient, collaborative study and care improvement.

Congenital Diarrheal Syndromes.

Congenital diarrheal disorders are heterogeneous conditions characterized by diarrhea with onset in the first years of life. They range from simple temporary conditions, such as cow's milk protein intolerance to irreversible complications, such as microvillous inclusion disease with significant morbidity and mortality. Advances in genomic medicine have improved our understanding of these disorders, leading to an ever-increasing list of identified causative genes. The diagnostic approach to these conditions consists of establishing the presence of diarrhea by detailed review of the history, followed by characterizing the composition of the diarrhea, the response to fasting, and with further specialized testing.

A comparative study of the prevalence of zinc deficiency among children with acute diarrhoea in SouthWestern Nigeria.

BACKGROUND: Zinc deficiency has been associated with increased incidence, severity and duration of childhood diarrhoea. OBJECTIVE: The objective of the study was to determine the prevalence of zinc deficiency among under-five children with acute diarrhoea. METHODS: The study was a comparative cross-sectional study in which serum zinc levels were determined using atomic absorption spectrometry in under-five children with acute diarrhoea and in apparently healthy contols. Two hundred and fifty children with acute diarrhoea and 250 controls were studied at the Wesley Guild Hospital, Ilesa, Nigeria. RESULTS: The diarrhoea patients had a mean ± SD serum zinc level of 78.8 ± 35.6 µg/dl, while the controls had a mean of 107.3 ± 46.8 µg/dl. The mean serum zinc level was significantly lower in the patients than the controls (t = -7.66; p < 0.001). Furthermore, the prevalence of zinc deficiency was significantly higher among the patients (30.4% versus 12.4% in the controls; OR = 3.09; 95% CI = 1.94 - 4.90; χ2 = 24.08; p < 0.001). Low social class was associated with a significantly higher prevalence of zinc deficiency among the patients (p = 0.013). CONCLUSION: Zinc deficiency is significantly associated with diarrhoea among under-five children in the study community. Hence, routine zinc supplementation should be encouraged for the treatment of diarrhoea, and availability should be ensured.

Bovine Colostrum in the Treatment of Acute Diarrhea in Children: A Double-Blinded Randomized Controlled Trial.

OBJECTIVES: To evaluate the effect of bovine colostrum (BC) on the treatment of children with acute diarrhea attending the outpatient clinic. METHODS: This double-blind randomized controlled trial was conducted on 160 children with diarrhea; 80 cases were randomly treated with BC group and 80 cases randomly received placebo (placebo group). All cases were investigated for bacterial causes of diarrhea (Salmonella spp, Shigella spp, diarrheagenic E. coli (DEC), Campylobacter spp., and Vibrio cholerae) as well as for Rotavirus antigen in stool. RESULTS: After 48 h, the BC group had a significantly lower frequency of vomiting, diarrhea and Vesikari scoring compared with the placebo group (p = 0.000, p = 0.000, p = 0.000, respectively), whether it was due to Rotavirus or E. coli infection. CONCLUSIONS: BC is effective in the treatment of acute diarrhea and can be considered as adjuvant therapy in both viral and bacterial diarrhea to prevent diarrhea-related complications.

'Know-Can' gap: gap between knowledge and skills related to childhood diarrhoea and pneumonia among frontline workers in rural Uttar Pradesh, India.

OBJECTIVES: In India, frontline workers (FLWs) - public accredited social health activists (ASHAs) and private rural medical providers (RMPs) - are important for early detection and treatment of childhood diarrhoea and pneumonia. This cross-sectional study aims to measure knowledge and skills, and the gap between the two ('know-can' gap), regarding assessment of childhood diarrhoea with dehydration and pneumonia among FLWs, and to explore factors associated with them. METHODS: We surveyed 473 ASHAs and 447 RMPs in six districts of Uttar Pradesh. We assessed knowledge and skills using face-to-face interviews and video vignettes, respectively, about key signs of both conditions. The 'know-can' gap corresponds to absent skills among FLWs with correct knowledge. We used logistic regression to identify the correlates of knowledge and skills. RESULTS: FLWs' correct knowledge ranged from 23% to 48% for dehydration signs and 27% to 37% for pneumonia signs. Their skills ranged from 3% to 42% for dehydration and 3% to 18% for pneumonia. There was a significant 'know-can' gap in all the signs, except 'sunken eyes'. Training and supervisory support was associated with better knowledge and skills for diarrhoea with dehydration, but only better knowledge for pneumonia. CONCLUSIONS: FLWs are crucial to the Indian health system, and high-quality FLW services are necessary for continued progress against under-five deaths. The gap between FLWs' knowledge and skills warrants immediate attention. In particular, our results suggest that knowledge-focused trainings are insufficient for FLWs to convert knowledge into appropriate assessment skills.

OBJECTIFS: En Inde, les travailleurs de première ligne (TPL) - activistes de la santé sociale accrédités par le public (ASSAP) et prestataires médicaux ruraux privés (PMRP) - sont importants pour la détection et le traitement précoces de la diarrhée et de la pneumonie infantiles. Cette étude transversale vise à mesurer les connaissances et les compétences, et l'écart entre les deux (écart ''savoir-pouvoir''), en ce qui concerne l'évaluation de la diarrhée infantile avec déshydratation et la pneumonie chez les TPL et à explorer les facteurs qui leur sont associés. MÉTHODES: Nous avons mené une enquête sur 473 ASSAP et 447 PMRP dans six districts de l'Uttar Pradesh. Nous avons évalué les connaissances et les compétences à l'aide d'entretiens de face à face et de vignettes vidéo, respectivement, sur les signes clés des deux conditions. L'écart «savoir-pouvoir¼ correspond à des compétences absentes parmi les TPL ayant des connaissances correctes. Nous avons utilisé la régression logistique pour identifier les corrélats des connaissances et des compétences. RÉSULTATS: Les connaissances correctes des TPL variaient de 23% à 48% pour les signes de déshydratation, 27% à 37% pour les signes de pneumonie. Leurs compétences variaient de 3% à 42% pour la déshydratation et de 3% à 18% pour la pneumonie. Il y avait un écart important dans le «savoir-pouvoir¼ pour tous les signes, à l'exception des «yeux enfoncés¼. La formation et le soutien à la supervision étaient associés à de meilleures connaissances et compétences pour la diarrhée avec déshydratation, mais seulement à de meilleures connaissances pour la pneumonie. CONCLUSIONS: Les TPL sont cruciaux pour le système de santé indien, et des services de TPL de haute qualité sont nécessaires pour continuer à lutter contre les décès d'enfants de moins de cinq ans. L'écart entre les connaissances et les compétences des TPL mérite une attention immédiate. En particulier, nos résultats suggèrent que les formations axées sur les connaissances sont insuffisantes pour que les TPL convertissent les connaissances en compétences d'évaluation appropriées.

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).

The role of price and convenience in use of oral rehydration salts to treat child diarrhea: A cluster randomized trial in Uganda.

BACKGROUND: Over half a million children die each year of diarrheal illness, although nearly all deaths could be prevented with oral rehydration salts (ORS). The literature on ORS documents both impressive health benefits and persistent underuse. At the same time, little is known about why ORS is underused and what can be done to increase use. We hypothesized that price and inconvenience are important barriers to ORS use and tested whether eliminating financial and access constraints increases ORS coverage. METHODS AND FINDINGS: In July of 2016, we recruited 118 community health workers (CHWs; representing 10,384 households) in Central and Eastern Uganda to participate in the study. Study villages were predominantly peri-urban, and most caretakers had no more than primary school education. In March of 2017, we randomized CHWs to one of four methods of ORS distribution: (1) free delivery of ORS prior to illness (free and convenient); (2) home sales of ORS prior to illness (convenient only); (3) free ORS upon retrieval using voucher (free only); and (4) status quo CHW distribution, where ORS is sold and not delivered (control). CHWs offered zinc supplements in addition to ORS in all treatment arms (free in groups 1 and 3 and for sale in group 2), following international treatment guidelines. We used household surveys to measure ORS (primary outcome) and ORS + zinc use 4 weeks after the interventions began (between April and May 2017). We assessed impact using an intention-to-treat (ITT) framework. During follow-up, we identified 2,363 child cases of diarrhea within 4 weeks of the survey (584 in free and convenient [25.6% of households], 527 in convenient only [26.1% of households], 648 in free only [26.8% of households], and 597 in control [28.5% of households]). The share of cases treated with ORS was 77% (448/584) in the free and convenient group, 64% (340/527) in the convenient only group, 74% (447/648) in the free only group, and 56% (335/597) in the control group. After adjusting for potential confounders, instructing CHWs to provide free and convenient distribution increased ORS coverage by 19 percentage points relative to the control group (95% CI 13-26; P < 0.001), 12 percentage points relative to convenient only (95% CI 6-18; P < 0.001), and 2 percentage points (not significant) relative to free only (95% CI -4 to 8; P = 0.38). Effect sizes were similar, but more pronounced, for the use of both ORS and zinc. Limitations include short follow-up period, self-reported outcomes, and limited generalizability. CONCLUSIONS: Most caretakers of children with diarrhea in low-income countries seek care in the private sector where they are required to pay for ORS. However, our results suggest that price is an important barrier to ORS use and that switching to free distribution by CHWs substantially increases ORS coverage. Switching to free distribution is low-cost, easily scalable, and could substantially reduce child mortality. Convenience was not important in this context. TRIAL REGISTRATION: Trial registry number AEARCTR-0001288.

Bacteriophage Therapy Testing Against Shigella flexneri in a Novel Human Intestinal Organoid-Derived Infection Model.

OBJECTIVE: Enteric bacterial pathogens cause diarrheal disease and mortality at significant rates throughout the world, particularly in children younger than 5 years. Our ability to combat bacterial pathogens has been hindered by antibiotic resistance, a lack of effective vaccines, and accurate models of infection. With the renewed interest in bacteriophage therapy, we sought to use a novel human intestinal model to investigate the efficacy of a newly isolated bacteriophage against Shigella flexneri. METHODS: An S. flexneri 2457T-specific bacteriophage was isolated and assessed through kill curve experiments and infection assays with colorectal adenocarcinoma HT-29 cells and a novel human intestinal organoid-derived epithelial monolayer model. In our treatment protocol, organoids were generated from intestinal crypt stem cells, expanded in culture, and seeded onto transwells to establish 2-dimensional monolayers that differentiate into intestinal cells. RESULTS: The isolated bacteriophage efficiently killed S. flexneri 2457T, other S. flexneri strains, and a strain of 2457T harboring an antibiotic resistance cassette. Analyses with laboratory and commensal Escherichia coli strains demonstrated that the bacteriophage was specific to S. flexneri, as observed under co-culture conditions. Importantly, the bacteriophage prevented both S. flexneri 2457T epithelial cell adherence and invasion in both infection models. CONCLUSIONS: Bacteriophages offer feasible alternatives to antibiotics for eliminating enteric pathogens, confirmed here by the bacteriophage-targeted killing of S. flexneri. Furthermore, application of the organoid model has provided important insight into Shigella pathogenesis and bacteriophage-dependent intervention strategies. The screening platform described herein provides proof-of-concept analysis for the development of novel bacteriophage therapies to target antibiotic-resistant pathogens.

Mothers' knowledge, attitude and practice towards the prevention and home-based management of diarrheal disease among under-five children in Diredawa, Eastern Ethiopia, 2016: a cross-sectional study.

BACKGROUND: Diarrhea remains the 2nd leading cause of death among children under 5 globally. It kills more young children than AIDS. It would have been prevented by simple home management using oral rehydration therapy. Mothers play a central role in its management and prevention. So, the main objective of this study was to assess mothers' knowledge, attitude & practice in prevention & home-based management of diarrheal disease among under-five children in Dire Dawa, Eastern Ethiopia. METHODS: Institutional based cross-sectional study was conducted from March 15-April 14, 2016, in Diredawa among 295 Mothers who had under-five child with diarrhea in the last 2 weeks using simple random sampling method. Mothers were interviewed face to face by using pretested, standard and structured questionnaire. The data quality was assured by translation, retranslation and pretesting the questionnaire. Data were checked for completeness, consistency and then entered into Epi Info v3.1 and analyzed using SPSS v20. The descriptive statistical analysis was used to compute frequency, percentages, and mean of the findings of this study. The results were presented using tables, charts, and graphs. RESULTS: In this study, 295 participants were included with 100% response rate. From total 295 mothers, around two-thirds (65.2%) of them had good knowledge, but more than half of mothers (54.9%) had a negative attitude towards home-based management and prevention of diarrhea among under-five children. Regarding the attitude of the mothers, 58% had poor practice towards home-based management and prevention of diarrhea among under-five children. CONCLUSION: The finding of this study showed that the attitude and practice of mothers were unsatisfactory about the prevention and home-based management of under-five diarrheal diseases. Therefore, Health education, dissemination of information, and community conversation should plan and implement to create a positive attitude and practice towards the better prevention and management of under 5 diarrheal diseases.