Cause Of Persistent Diarrhea Research Articles

Insoliti sospetti: una diarrea intrattabile da citomegalovirus

Intractable diarrhoea in infancy is defined as diarrhoea persisting for more than 2 weeks in infants up to 3 months of age and requiring parenteral nutrition. It is often a diagnostic and therapeutic challenge for paediatricians. The following case report suggests that, once the most common diagnoses for this age group have been excluded, a cause of persistent diarrhoea that is usually overlooked and neglected such as cytomegalovirus enterocolitis should be always kept in mind.

POS-774 Role of Noro virus infection in post renal transplant persistent diarrhea

Diarrhea is common gastrointestinal problem in kidney transplant recipients. Numerous cases of post-transplant diarrhea in the past have been ascribed solely to the toxicity of immunosuppressive drugs, leading to diagnostic misconceptions. Noro Virus, one of the common cause of acute diarrhea in adult is emerging as important cause of persistent diarrhea in solid organ transplant recipients.Here, we are presenting our experience with chronic Noro virus infection in renal transplant recipients.

A COMPARISON OF RAPID DIAGNOSTIC TEST AND MODIFIED ZIEHL-NEELSEN METHOD IN THE DIAGNOSIS OF CRYPTOSPORIDIOSIS.

Background: Cryptosporidium parvum as a leading cause of persistent diarrhoea in developing countries causes a more severe illness in patients infected with human immunodeficiency virus (HIV). The intermittent shedding of Cryptosporidium parvum oocysts in stool, even in patients with massive diarrhoea, makes diagnosis difficult. This study evaluated the validity of Crypto-Strip test in comparison to the modified Ziehl-Neelsen for the diagnosis of Cryptosporidium infection using polymerase chain reaction (PCR) as gold standard. Methods: This was a hospital based cross-sectional study of 100 HIV positive patients with diarrhoea at a tertiary health facility in Jos, Nigeria. We collected 15mls of stool sample and relevant information from patients who gave informed consent. The oocytes of Cryptosporidium parvum were identified in the stool samples using modified Ziehl-Neelsen stain and Rapid diagnostic test (Crypto-Strip). We also ran all samples using polymerase chain reaction (PCR). Statistical analysis was with statistical package for Social Sciences (SPSS) version 21. Result: Out of the 100 stool samples analysed, 13 (13%) were positive for cryptosporidiosis by PCR. Crypto- Strips recorded 12 (12%) positive with one (1) being false negative as compared to PCR. Conversely, eight (8%) of the 100 samples collected were positive for Cryptosporidium oocysts using modified Ziehl Neelsen (mZN) stain. Out of the eight positives by mZN stain, two were false positive as both tested negative by the PCR. The Crypto-Strip test kit had a sensitivity of 92.3% and a specificity of 100.0% and also positive and negative predictive values of 100.0% and 98.9%, respectively. Whereas, the modified Ziehl Neelsen stain had a sensitivity of 46.2% and a specificity of 97.7% with a positive and negative predictive value of 75.0% and 92.4%, respectively. Conclusion: In this study, we have shown that Crypto-Strip test was a better diagnostic method for the diagnosis of crypto

Microsporidiosis after liver transplantation: A French nationwide retrospective study.

Microsporidiosis has been largely reported in patients with acquired immunodeficiency syndrome, but emerged as a cause of persistent diarrhea in solid organ transplant patients. Through the French Microsporidiosis Network and the Groupe français de recherche en greffe de foie, we collected all microsporidiosis cases identified in liver transplant patients between 1995 and 2020 in France. We identified 24 liver transplant recipients with microsporidiosis. Sex ratio was balanced and median age was 58.8 (3.5-83.5) years (there were 4 children). Microsporidiosis occurred at a median time of 3.9 (0.1-18.9) years post-transplant. Median duration of diarrhea before diagnosis was 22days (12-45). Therapeutic care included immunosuppressive therapy changes in 20 patients, as follows: stop cyclosporine or tacrolimus (n=2), dose reduction of cyclosporine or tacrolimus (n=12), stop MMF (n=5), and dose reduction of corticosteroids (n=1). In addition, 15 patients received specific therapy against microsporidiosis: fumagillin (n=11) or albendazole (n=4). Median duration of treatment was 14days (8-45days). Finally, 7 patients had immunosuppressive treatment tapering only. Microsporidiosis was complicated by renal failure in 15 patients, requiring dialysis in one case. Two patients had infection relapse. No patient presented proven rejection within the 3months after microsporidiosis. None of the patients died within the 3months after microsporidiosis. Microsporidiosis is a very rare infection after liver transplantation but can induce severe dehydration and renal failure. Therefore, it must be systematically sought in any case of persistent diarrhea after first line screening of frequent infectious causes.

Typical and atypical enteropathogenic Escherichia coli in children with acute diarrhoea: Changing trend in East Delhi

BackgroundWorldwide around 2 million deaths occur every year due to diarrhoeal illnesses among children less than 5 years of age. Among diarrhoeagenic Escherichia coli, Enteropathogenic E. coli (EPEC) is highly prevalent in both community and hospital settings and is one of the main causes of persistent diarrhea in children in developing countries. EPEC remains underdiagnosed in India due to lack of conventional tools for identification. MethodsWe in this study investigated the prevalence and regional variation of EPEC in paediatric population suffering from diarrhoea in East Delhi, India. Two hundred stool samples were collected from children, aged between 0.5 and 5 years, with acute diarrhoea. E. coli were identified by conventional tests and PCR. ResultsWe observed 7% atypical EPEC (aEPEC) and 2.5% typical EPEC (tEPEC), with an overall 9.5% EPEC prevalence amongst total samples. E. coli phylogenetic group A was the predominant. The most common age group affected was 6–23 months with common symptoms being vomiting, watery diarrhoea and severe dehydration. High drug resistance pattern was observed in EPEC isolates. ConclusionThe study depicts a changing trend of aEPEC over tEPEC in children less than 5 years with diarrhoea, an emerging drug resistant enteropathogen and a public health concern demanding monitoring and surveillance.

Coincidental CMV Colitis Post-hemorrhoidopexy in an Immunocompetent patient

This is a case of a 74 years old immunocompetent female who developed severe diarrhea after haemorrhoidopexy for 2 months duration. Investigations to find the cause of persistent diarrhea were done, including colonoscopy showed ulcers from which biopsy was taken and the presence of CMV-DNA was identified. She got treated with IV and oral Ganciclovir and repeated colonoscopy showed improvement of the ulcers with gradually improvement of diarrhea.

Comparative evaluation of Cryptosporidium infection in malnourished and well-nourished children: Parasitic infections are affected by the interaction of nutritional status and socio-demographic characteristics

Cryptosporidium, as a small protozoan parasite, is a leading cause of persistent diarrhea in children in developing countries and has both a short and long-term impact on the growth of children. In the present study, Cryptosporidium infection was compared in malnourished and well-nourished children by modified acid-fast staining, nested-polymerase chain reaction (nested-PCR) and loop-mediated isothermal amplification (LAMP) methods. As a case-control study, Cryptosporidium infection in 94 malnourished children was evaluated and compared with those of 188 age and gender-matched well-nourished children. Oocysts of Cryptosporidium were detected by modified acid-fast staining method. The extracted DNA was amplified by nested-PCR and LAMP techniques. In addition, positive amplicons were directly sequenced for phylogenetic analysis. Cryptosporidium oocysts were found in the stools of two (2.12 %) children who were hospitalized and had diarrhea by nested-PCR while three isolates (3.2 %) were found by LAMP. Cryptosporidium-positive children were more malnourished compared to those who were negative for Cryptosporidium infection but this important finding was not statistically significant. C. parvum was the main species of Cryptosporidium detected in malnourished children in northwest Iran. LAMP can be considered as a sensitive field monitoring assay in patients with low parasite burden. Nutritional status and socio-demographic factors may have interactive effects on the incidence and severity of parasitic diseases.

TLR4 Participates in the Inflammatory Response Induced by the AAF/II Fimbriae From Enteroaggregative Escherichia coli on Intestinal Epithelial Cells.

Enteroaggregative Escherichia coli (EAEC) infections are one of the most frequent causes of persistent diarrhea in children, immunocompromised patients and travelers worldwide. The most prominent colonization factors of EAEC are aggregative adherence fimbriae (AAF). EAEC prototypical strain 042 harbors the AAF/II fimbriae variant, which mediates adhesion to intestinal epithelial cells and participates in the induction of an inflammatory response against this pathogen. However, the mechanism and the cell receptors implicated in eliciting this response have not been fully characterized. Since previous reports have shown that TLR4 recognize fimbriae from different pathogens, we evaluated the role of this receptor in the response elicited against EAEC by intestinal cells. Using a mutual antagonist against TLR2 and TLR4 (OxPAPC), we observed that blocking of these receptors significantly reduces the secretion of the inflammatory marker IL-8 in response to EAEC and AAF/II fimbrial extract in HT-29 cells. Using a TLR4-specific antagonist (TAK-242), we observed that the secretion of this cytokine was significantly reduced in HT-29 cells infected with EAEC or incubated with AAF/II fimbrial extract. We evaluated the participation of AAF/II fimbriae in the TLR4-mediated secretion of 38 cytokines, chemokines, and growth factors involved in inflammation. A reduction in the secretion of IL-8, GRO, and IL-4 was observed. Our results suggest that TLR4 participates in the secretion of several inflammation biomarkers in response to AAF/II fimbriae.

Variation in co-morbidities does not have an impact on the outcome of acute pancreatitis – a comparison between a northern and a southern European cohort

Cryptosporidium parvum is the second leading cause of persistent diarrhea among children in low-resource settings. This study examined the effect of oregano essential oil (OEO) and carvacrol (CV) on inhibition of C. parvum infectivity in vitro. HCT-8 cells were seeded (1 × 106) in 96-well microtiter plates until confluency. Cell viability and infectivity were assessed by seeding HCT-8 cell monolayers with C. parvum oocysts (1 × 104) in two modalities: 1) 4 h co-culture with bioactive (0–250 μg/mL) followed by washing and incubation (48 h, 37 °C, 5% CO2) in bioactive-free media; and 2) 4 h co-culture of C. parvum oocysts followed by washing and treatment with bioactive (0–250 μg/mL) during 48-h incubation. Cell viability was tested using Live/Dead™ assay whereas infectivity was measured using C. parvum-specific antibody staining via immunofluorescence detection. Loss of cell viability was observed starting at 125 μg/mL and 60 μg/mL for OEO and CV, respectively. Neither OEO nor CV modulated the invasion of C. parvum sporozoites in HCT-8 cells. Treatment with bioactive after invasion reduced relative C. parvum infectivity in a dose-dependent manner to 55.6 ± 10.4% and 45.8 ± 4.1% at 60 and 30 μg/mL of OEO and CV, respectively. OEO and CV are potential bioactives to counteract C. parvum infection in children.

Effect of oregano essential oil and carvacrol on Cryptosporidium parvum infectivity in HCT-8 cells

Cryptosporidium parvum is the second leading cause of persistent diarrhea among children in low-resource settings. This study examined the effect of oregano essential oil (OEO) and carvacrol (CV) on inhibition of C. parvum infectivity in vitro. HCT-8 cells were seeded (1×106) in 96-well microtiter plates until confluency. Cell viability and infectivity were assessed by seeding HCT-8 cell monolayers with C. parvum oocysts (1×104) in two modalities: 1) 4h co-culture with bioactive (0–250μg/mL) followed by washing and incubation (48h, 37°C, 5% CO2) in bioactive-free media; and 2) 4h co-culture of C. parvum oocysts followed by washing and treatment with bioactive (0–250μg/mL) during 48-h incubation. Cell viability was tested using Live/Dead™ assay whereas infectivity was measured using C. parvum-specific antibody staining via immunofluorescence detection. Loss of cell viability was observed starting at 125μg/mL and 60μg/mL for OEO and CV, respectively. Neither OEO nor CV modulated the invasion of C. parvum sporozoites in HCT-8 cells. Treatment with bioactive after invasion reduced relative C. parvum infectivity in a dose-dependent manner to 55.6±10.4% and 45.8±4.1% at 60 and 30μg/mL of OEO and CV, respectively. OEO and CV are potential bioactives to counteract C. parvum infection in children.

Cryptosporidium spp. Infection in Solid Organ Transplantation

Diarrhea is a frequent complication of solid organ transplantation. Cryptosporidiosis is classically reported in patients with acquired immunodeficiency syndrome and emerged as a cause of persistent diarrhea in solid organ transplant patients. Through the ANOFEL Cryptosporidium National Network and the French Transplantation Society, we collected all cryptosporidiosis cases identified in solid organ transplanted patients between 2006 and 2010 in France. We reported 47 solid organ transplant recipients (41 kidneys) with cryptosporidiosis, mostly men (68%), with a median age of 52 (6-70) years old. Five patients had additional immunodepression favoring cryptosporidiosis (CD40 ligand deficiency [n = 1], human immunodeficiency virus infection [n = 4]). Cryptosporidiosis occurred at a median time of 3.4 (0-19.8) years posttransplant. Exposure to environmental risk factors was found before infection onset in 18 patients. Time between first symptoms and diagnosis was 10 (2-110) days. Four patients had associated extraintestinal location (biliary tract [n = 3] and lung [n = 1]). Thirty-five patients received specific therapy against cryptosporidiosis ie nitozoxanide, 25 in monotherapy, and 10 in association with azithromycin, 13 in association with immunosuppression (IS) reduction. Four patients were cured with IS treatment tapering only. The others patients had neither IS reduction nor specific therapy against cryptosporidiosis. Cryptosporidiosis was complicated by renal failure in 15 patients. Symptoms resolved after a median of 10 days of treatment. Six patients relapsed and 3 died, 1 with evolutive infection. Cryptosporidiosis is a late posttransplant infection that disseminated to biliar duct or lung in 9% of patients. When limited to digestive tract, infection may resolve without IS reduction.

Primary Lactase Deficiency among Malnourished Children with Persistent Diarrhea in Tbilisi, Georgia

AbstractPersistent diarrhea became the major cause for diarrheal mortality in children from developing countries. This study was therefore designed to establish the prevalence of primary lactase deficiency and associated factors among mild malnourished children with persistent diarrhea. This was a prospective cohort study. The study population consisted of mild malnourished children with persistent diarrhea aged 3–24 months admitted between October 2014 and September 2015. The Gomez classification of malnutrition was used. A mild malnourished child was whose weight-for-height was less than 75%–90% of the median National Centre for Health Statistics (NCHS)/WHO reference median. The study included 78 malnourished children with persistent diarrhea 3–24 months of age. The prevalence of primary lactase deficiency among the study children was 41.0%. The reasons of persistent diarrhea in lactose tolerant group were: Rotavirus infection – 33.3%, Bacterial gastroenteritis –20.5% (Enteropathogenic E.coli (EPEC) – 7.7%, Shigella – 6.4%, Yersinia enterocolitica – 3.8%, Salmonella – 2.6 %) and Gastroenteritis of unknown etiology – 5.1%. Only 4 children had Rotavirus infection in lactose intolerant group. The relationship between diarrhea and malnutrition is bidirectional: diarrhea leads to malnutrition while malnutrition aggravates the course of diarrhea. Lactose intolerance is a relatively common cause of persistent diarrhea. The most common cause of primary lactase deficiency is lactase enzyme non-persistence.

Distribution and Molecular Characterization of Enteroaggregative Escherichia coli Isolated from Children in A Case-control Study of Acute Diarrhea in Thailand

Background: Enteroaggregative Escherichia coli (EAEC) is a major cause of acute diarrhea in children, adults, and travelers as well as an important cause of persistent diarrhea. Due to the limited information on EAEC virulence genes, EAEC isolates isolated from children with diarrhea and asymptomatic controls in Thailand were characterized for the presence of virulence factors. Method: A study of diarrhea etiology in children from Thailand was conducted during 2008-2009 and 301 EAEC isolates were identified by pCVD432 probe/hybridization assays from diarrhea cases and controls. A total of 200 EAEC isolates were further characterized by PCR for EAEC genotypes, aggregative adherence fimbria (AAF/I-AAF/ IV), serine protease autotransporters of Enterobacteriaceae (SPATEs) class I & II, and enterotoxin genes. Results: The prevalence of EAEC isolates in this study were 7.7% and 9.1% among cases (n=1803) and controls (n=1790). Of 200 EAEC isolates, 69% of case and 58% of control isolates were classified as typical EAEC genotype. AAF/I (aggA) was the major fimbria type for cases (37%) and controls (23%), followed by AAF/III (9%, 13%), AAF/II (11%, 17%) and AAF/IV (5%, 3%). In confirmed cases, class II SPATE-sepA (19%, 7%) and pic (75%, 60%) and enterotoxin-set (75%, 61%) genes were detected in significantly more strains when compared to the controls. Additionally, typical EAEC isolates containing genes for AAF/I, Class II SPATEs (sepA, pic), and enterotoxin (set) were detected more frequently in cases than controls (P value<0.05). Conclusion: This study suggests virulence gene heterogeneity of EAEC isolated from children with diarrhea as compared to asymptomatic controls, and that specific virulence genes are associated with diarrhea.

IDENTIFIKASI KRIPTOSPORIDIOSIS DI PASIEN ANAK HIV DENGAN DIARE KRONIS DI RUANG GASTRO ANAK

Based on the results of overseas researchers, Cryptosporidiosis occurs in immunosuppressive cases with chronic diarrhoea. In this study the researchers would like to know exactly whether that Cryptosporidiosis occurs also in paediatric HIV patients. The latest data show that the incidence of opportunistic infection is characterized by persistent diarrhoea and severe malnutrition as a complication of the paediatric HIV-infected patients is increasing. The objects of the research were fifteen paediatric HIV-infected patients which treated at the Paediatric Gastro Ward of Dr. Soetomo Hospital Surabaya due to persistent diarrhoea. Paediatric patients were less than five years old, suffered persistent diarrhoea more than two weeks with severe malnutrition. Stool specimens were transported using 10% formalin. The stool suspension was filtered, and distilled water was added followed by centrifugation (sedimentation method). The precipitate material was placed on a glass object and dried, and then fixed by methanol and stained with Acid Fast Staining and trichrome staining. The protozoa Cryptosporidium spp. was observed under a binocular microscope with 100í— magnification (immersion oil) objective. The result was confirmed as positive if a red spherical or oval formation of oocyste of 4–6 micron appeared. Sixty percent of the 15 paediatric HIV-infected patients with chronic diarrhoea showed positive cryptosporidiosis. Cryptosporidiosis is one of the opportunistic infections resulting in chronic diarrhoea in paediatric HIV-infected patients. The results of the present research indicate that the enteric parasite Cryptosporidium spp. was the main cause of persistent diarrhoea in paediatric HIV-infected patients

Prevalence and Characteristics of Duodenal Villous Atrophy in Renal Transplant Patients Presenting With Persistent Diarrhea in a Developing Country.

Persistent diarrhea is a common complication after solid-organ transplant, including kidney transplant. Data on duodenal villous atrophy as a cause of persistent diarrhea in renal transplant recipients are scarce. We conducted a prospective analysis of 207 patients who received renal transplants from 2009 to 2012 with persistent diarrhea and who underwent upper gastrointestinal endoscopy and duodenal biopsies. Duodenal biopsies were examined for duodenal villous atrophy. Age, sex, transplant duration, and drugs were compared between patients with and without duodenal villous atrophy. After exclusion of known causes of duodenal villous atrophy, a 3-month course of antibiotics was given and outcomes were analyzed. Of 207 renal transplant recipients, 104 patients (49.8%) displayed duodenal villous atrophy. Of these, 92 (88.5%) were male patients. The mean age of patients with duodenal villous atrophy was 34.9 ± 10.3 years. The mean onset of persistent diarrhea in DVA-positive patients posttransplant was 2.16 ± 0.8 years. Celiac disease serology was positive in 18 (17.3) patients. Giardiasis was demonstrated in 11 patients (10.7%), whereas immunoproliferative small intestinal disease was shown in 7 patients (6.8%). The remaining 68 patients (65.38%) received antibiotics, with 50 recipients (74.6%) showing complete response, although 13 of these patients (26%) relapsed. Among the remaining 18 patients (26.47%), 9 (50%) had other causes and 9 (50%) had no cause found. Isoniazid prophylaxis showed statistically significant negative association with duodenal villous atrophy. Duodenal villous atrophy is highly prevalent in renal transplant recipients irrespective of age, sex, and posttransplant duration. We found tropical sprue, giardiasis, immunoproliferative small intestinal disease, and celiac disease to be important causes of duodenal villous atrophy. Therefore, duodenal biopsy is recommended in renal transplant recipients with persistent diarrhea.

Whole Genome Sequencing of an Unusual Serotype of Shiga Toxin–producingEscherichia coli

Shiga toxin–producing Escherichia coli serotype O117:K1:H7 is a cause of persistent diarrhea in travelers to tropical locations. Whole genome sequencing identified genetic mechanisms involved in the pathoadaptive phenotype. Sequencing also identified toxin and putative adherence genes flanked by sequences indicating horizontal gene transfer from Shigella dysenteriae and Salmonella spp., respectively.

The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infection

BackgroundEnteroaggregative Escherichia coli (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the modulation of host responses to EAEC in nourished and malnourished mice.Methods/Principal FindingsWild-type and T cell-specific PPARγ null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5×109cfu EAEC strain JM221 to measure colonic gene expression and immune responses to EAEC. Antigen-specific responses to E. coli antigens were measured in nourished and malnourished mice following infection and demonstrated the immunosuppressive effects of malnutrition at the cellular level. At the molecular level, both pharmacological blockade and deletion of PPARγ in T cells resulted in upregulation of TGF-β, IL-6, IL-17 and anti-microbial peptides, enhanced Th17 responses, fewer colonic lesions, faster clearance of EAEC, and improved recovery. The beneficial effects of PPARγ blockade on weight loss and EAEC clearance were abrogated by neutralizing IL-17 in vivo.ConclusionsOur studies provide in vivo evidence supporting the beneficial role of mucosal innate and effector T cell responses on EAEC burden and suggest pharmacological blockade of PPARγ as a novel therapeutic intervention for EAEC infection.

Enzootic Enteropathogenic Escherichia coli Infection in Laboratory Rabbits

Enteropathogenic Escherichia coli (EPEC) is the most important cause of persistent diarrhea in children, particularly in developing countries. Animals serve as pathogenic E. coli reservoirs, and compelling evidence for cross-species EPEC transmission exists. In this report, enzootic EPEC infection associated with up to 10.5% diarrhea-associated morbidity in a large laboratory Dutch Belted rabbit colony was investigated. These rabbits were obtained from a commercial vendor and had acute diarrhea following shipment. Fecal culture of 20 rabbits yielded 48 E. coli isolates, 83% of which were eae positive. Repetitive sequence-based PCR (REP-PCR) and serologic analysis identified a single disease-associated EPEC O145:H2 strain. In sampled rabbits, EPEC-positive culture and the presence of diarrhea were significantly associated. This strain displayed a localized adherence-like HEp-2 cell adherence pattern, as seen in diarrheic human infant EPEC isolates. Treatment was instituted with the fluoroquinolone antibiotic enrofloxacin, to which all isolates were susceptible. Preshipment parenteral enrofloxacin administration reduced diarrhea-associated morbidity 22-fold and mortality 12-fold in subsequent deliveries. This report emphasizes the zoonotic potential of animal EPEC strains and the need for virulence determinant-based screening of E. coli isolates from diarrheic animals.

Cochrane Review: Probiotics for treating persistent diarrhoea in children

AbstractBackgroundPersistent diarrhoea (diarrhoea lasting more than 14 days) accounts for one third of all diarrhoea related deaths in developing countries in some studies. Probiotics may help treatment.ObjectivesTo evaluate probiotics for treating persistent diarrhoea in children.Search strategyIn August 2010, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, and LILACS. We also contacted authors of included trials and organizations working in the field, and checked reference lists.Selection criteriaRandomized controlled trials comparing a specified probiotic agent with placebo or no probiotic in children with persistent diarrhoea.Data collection and analysisTwo review authors assessed the eligibility, risk of bias, extracted and analysed data. Differences were resolved by discussion. Statistical analysis were performed using the fixed‐effect model and the results were expressed as mean difference (MD) for continuous outcomes with 95% confidence intervals (CI).Main resultsFour trials were included, with a total number of 464 participants; one trial had a low risk of bias. Meta‐analysis showed that probiotics reduced the duration of persistent diarrhoea (mean difference 4.02 days, 95% CI 4.61 to 3.43 days, n=324, 2 trials). Stool frequency was reduced with probiotics in two trials. One trial reported a shorter hospital stay, which was significant, but numbers were small. No adverse events were reported.Authors' conclusionsThere is limited evidence suggesting probiotics may be effective in treating persistent diarrhoea in children.Plain Language SummaryProbiotics for persistent diarrhoea in childrenPersistent diarrhoea is defined as a diarrhoeal episode that starts acutely but then lasts for 14 days or more, and it is an important cause of morbidity and mortality in children under five years old in developing countries throughout the world. The cause of persistent diarrhoea is not completely understood but is likely to be complex; this in turn makes management of the condition difficult. Probiotics are bacteria and yeasts that are similar to the normal bacteria found in a healthy gut. These so called friendly bacteria have been used in several studies to treat acute infectious diarrhoea with encouraging results. This review found four trials involving children with persistent diarrhoea. Two studies with a combined total of 324, showed that probiotics shorten the duration of diarrhoea and reduce the stool frequency on day 5. One study (235 children) suggested that probiotics reduce the hospital stay. Three out of four trials reported that no adverse events occurred. However, this review is limited by few trials with small number of participants, and therefore may not represent a reliable estimate of probiotics' effect.

Cryptosporidium-Malnutrition Interactions: Mucosal Disruption, Cytokines, and TLR Signaling In A Weaned Murine Model

Cryptosporidiosis is a leading cause of persistent diarrhea in children in impoverished and developing countries and has both a short- and long-term impact on the growth and development of affected children. An animal model of cryptosporidial infection that mirrors closely the complex interaction between nutritional status and infection in children, particularly in vulnerable settings such as post-weaning and malnourishment, is needed to permit exploration of the pathogenic mechanisms involved. Weaned C57BL/6 mice received a protein-deficient (2%) diet for 3-12 days, then were infected with 5 × 10(7) excysted C. parvum oocyts, and followed for rate of growth, parasite stool shedding, and intestinal invasion/morphometry. Mice had about 20% reduction in weight gain over 12 days of malnutrition and an additional 20% weight loss after C. parvum challenge. Further, a significantly higher fecal C. parvum shedding was detected in malnourished infected mice compared to the nourished infected mice. Also, higher oocyst counts were found in ileum and colon tissue samples from malnourished infected mice, as well as a significant reduction in the villous height-crypt depth ratio in the ileum. Tissue Th1 cytokine concentrations in the ileum were significantly diminished by malnutrition and infection. mRNA for toll-like receptors 2 and 4 were diminished in malnourished infected mice. Treatment with nitazoxanide did not prevent weight loss or parasite stool shedding. These findings indicate that, in the weaned animal, malnutrition intensifies cryptosporidial infection, while cryptosporidial infection further impairs normal growth. Depressed TLR2 and 4 signaling and Th1 cytokine response may be important in the mechanisms underlying the vicious cycle of malnutrition and enteric infection.