Use of TaqMan Array Cards to investigate the aetiological agents of diarrhoea among young infants with severe acute malnutrition.

OBJECTIVE: Studies involving less sensitive conventional microscopy and culture-based approaches have identified distinct differences in diarrhoeal aetiology in childhood malnutrition. Our study involved the use of an advanced molecular biology technique, the TaqMan Array Cards (TAC), to elucidate the diarrhoeal aetiology among young infants with severe acute malnutrition (SAM). METHOD: A total of 113 faecal samples was collected from SAM infants, aged 2-6 months, upon admission to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) with complications of diarrhoea and related comorbidities. We used TAC for the detection of 29 different diarrhoeal enteropathogens from a single faecal sample. For comparison, we also analysed 25 diarrhoeal samples from well-nourished infants of similar age. RESULTS: Higher odds of detection of all bacterial enteropathogens were associated with diarrhoea among SAM infants. In particular, the detection of Aeromonas sp (aOR: 25.7, p = 0.011), Campylobacter sp (aOR: 9.6, p < 0.01) and ETEC (aOR: 5.2, p = 0.022) was significantly associated with diarrhoea among SAM infants in comparison to well-nourished infants. 80% higher odds of detection of rotavirus and norovirus GII were associated with diarrhoea among well-nourished infants in comparison to SAM infants (aOR: 0.2, p < 0.05). CONCLUSION: Our study findings demonstrate a difference in diarrhoeal aetiology among SAM and well-nourished young infants, which may be useful in providing an evidence-based logic for possible revision of treatment guidelines for treatment of young diarrhoeal infants with SAM in the early management of the menace of antimicrobial resistance.

Plasmid-borne colistin resistance gene mcr-1 in a multidrug resistant Salmonella enterica serovar Typhimurium isolate from an infant with acute diarrhea in China.

BACKGROUND: Antimicrobial resistance of Salmonella enterica is a major global concern. Recent findings suggest that colistin as a last resort treatment for multidrug-resistant gram-negative bacteria is seriously threatened by the report of plasmid-mediated colistin resistance gene mcr-1 in China. METHODS: A total of 827 S. Typhimurium isolates were recovered from 4 cities of China, including Henan, Shanghai, Zhejiang, and Hubei provinces. Subsequently, mcr-1 presence was identified by PCR screening. Antimicrobial susceptibility testing was performed by broth microdilution using a 96-well microtiter plate. Plasmid conjugation transfer experiments were conducted using Escherichia coli J53 as the recipient. RESULTS: Only one mcr-1 positive strain from the stool sample of an infant with acute diarrhea was isolated. Apart from colistin, the mcr-1-positive isolate showed co-resistance to the third-generation cephalosporins, ampicillin, nalidixic acid, tetracycline, chloramphenicol, sulfisoxazole, gentamicin, and cefotaxime revealing a multidrug-resistant phenotype. This strain harbored mcr-1 on a 227 kb IncHI2 plasmid, termed pJZ26, which could be transferred to E. coli J53. In addition to mcr-1, pJZ26 coharbored other resistance genes, including aph(4)-Ia, aac(3)-IVa, fosA, floR, sul2, and blaCTX-M-14. Compared with p2474-MCR1 and pHYEC7-IncHI2, pJZ26 contains an additional 4.6 kb fragment harboring the resistance gene tet(A) and its regulator tetR located on TnAs1 transposable element, which could mediate resistance to tetracycline. CONCLUSIONS: These findings highlight that the fact the mcr-1-harboring plasmid pJZ26 has a high potential to disseminate the mcr-1 gene and further challenge the clinical treatment.

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.

A Prospective Study on Child Morbidity and Gut Microbiota in Rural Malawi.

OBJECTIVES: The determinants of gut microbiota composition and its effects on common childhood illnesses are only partly understood, especially in low-income settings. The aim of the present study was to investigate whether morbidity predicts gut microbiota composition in Malawian children and whether microbiota predicts subsequent morbidity. We tested the hypothesis that common infectious disease symptoms would be predictive of lower microbiota maturity and diversity. METHODS: We used data from 631 participants in a randomized-controlled nutrition intervention trial, in which a small-quantity lipid-based nutrient supplement was provided to pregnant and lactating mothers and their children at 6 to 18 months of age. Fecal samples were collected from the children at 6, 12, 18, and 30 months of age and analyzed using 16S rRNA sequencing. Microbiota variables consisted of measures of microbiota diversity (Shannon Index), microbiota maturity (microbiota-for-age z score), and the relative abundances of taxa. Morbidity variables included gastrointestinal and respiratory symptoms and fever. RESULTS: Diarrhea and respiratory symptoms from 11 to 12 months were predictive of lower microbiota-for-age z score and higher Shannon Index, respectively (P = 0.035 and P = 0.023). Morbidity preceding sample collection was predictive of the relative abundances of several bacterial taxa at all time points. Higher microbiota maturity and diversity at 6 months were predictive of a lower incidence rate of fever in the subsequent 6 months (P = 0.007 and P = 0.031). CONCLUSIONS: Our findings generally do not support the hypothesis that morbidity prevalence predicts a subsequent decrease in gut microbiota maturity or diversity in rural Malawian children. Certain morbidity symptoms may be predictive of microbiota maturity and diversity and relative abundances of several bacterial taxa. Furthermore, microbiota diversity and maturity may be associated with the subsequent incidence of fever.

The seasonality of diarrheal pathogens: A retrospective study of seven sites over three years.

BACKGROUND: Pediatric diarrhea can be caused by a wide variety of pathogens, from bacteria to viruses to protozoa. Pathogen prevalence is often described as seasonal, peaking annually and associated with specific weather conditions. Although many studies have described the seasonality of diarrheal disease, these studies have occurred predominantly in temperate regions. In tropical and resource-constrained settings, where nearly all diarrhea-associated mortality occurs, the seasonality of many diarrheal pathogens has not been well characterized. As a retrospective study, we analyze the seasonal prevalence of diarrheal pathogens among children with moderate-to-severe diarrhea (MSD) over three years from the seven sites of the Global Enteric Multicenter Study (GEMS), a case-control study. Using data from this expansive study on diarrheal disease, we characterize the seasonality of different pathogens, their association with site-specific weather patterns, and consistency across study sites. METHODOLOGY/PRINCIPAL FINDINGS: Using traditional methodologies from signal processing, we found that certain pathogens peaked at the same time every year, but not at all sites. We also found associations between pathogen prevalence and weather or "seasons," which are defined by applying modern machine-learning methodologies to site-specific weather data. In general, rotavirus was most prevalent during the drier "winter" months and out of phase with bacterial pathogens, which peaked during hotter and rainier times of year corresponding to "monsoon," "rainy," or "summer" seasons. CONCLUSIONS/SIGNIFICANCE: Identifying the seasonally-dependent prevalence for diarrheal pathogens helps characterize the local epidemiology and inform the clinical diagnosis of symptomatic children. Our multi-site, multi-continent study indicates a complex epidemiology of pathogens that does not reveal an easy generalization that is consistent across all sites. Instead, our study indicates the necessity of local data to characterizing the epidemiology of diarrheal disease. Recognition of the local associations between weather conditions and pathogen prevalence suggests transmission pathways and could inform control strategies in these settings.

Salmonella Typhimurium and Salmonella Enteritidis Infections in Sporadic Diarrhea in Children: Source Tracing and Resistance to Third-Generation Cephalosporins and Ciprofloxacin.

OBJECTIVES: This study aimed to trace the transmission source of Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis strains associated with enteric infections in Shanghainese children, and understand the molecular mechanism of resistance to third-generation cephalosporins and ciprofloxacin. MATERIALS AND METHODS: The profiles of pulsed-field gel electrophoresis (PFGE) were compared among the isolates from children, animal, and environment. Antimicrobial susceptibility was determined using the minimal inhibitory concentrations and Kirby-Bauer disk diffusion method. Extended-spectrum ß-lactamase (ESBL) producing isolates mediated by resistance genes were identified using polymerase chain reaction and sequencing. RESULTS: Based on PFGE patterns, 49 (33.1%) of 148 human Salmonella Typhimurium isolates located in the dominant PFGE clusters were genetically related to the isolates from poultry source, environment water, aquatic products, and reptiles, whereas 97 (97.0%) of 100 human Salmonella Enteritidis isolates were genetically related to isolates from poultry and water. The rates of resistance to ceftriaxone among clinical Salmonella Typhimurium and Salmonella Enteritidis isolates were 42.0% and 14.2%, respectively. Besides, 35.1% of Salmonella Typhimurium isolates displayed resistance to ciprofloxacin; 64.9% of Salmonella Typhimurium isolates and 97.0% of Salmonella Enteritidis isolates displayed reduced susceptibility to ciprofloxacin. Of 64 ESBL/AmpC-producing strains, CTX-M, TEM, DHA, and CMY were detected at frequencies of 86.0%, 62.5%, 7.8%, 3.1%, and 3.1%, respectively. CONCLUSIONS: The transmission sources of Salmonella Typhimurium and Salmonella Enteritidis infections in Shanghainese children were diverse. The high prevalence of resistance to third-generation cephalosporins and ciprofloxacin mediated by multiple molecular mechanisms needs continuous monitoring and intervention.

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.

Hydrometeorology and flood pulse dynamics drive diarrheal disease outbreaks and increase vulnerability to climate change in surface-water-dependent populations: A retrospective analysis.

BACKGROUND: The impacts of climate change on surface water, waterborne disease, and human health remain a growing area of concern, particularly in Africa, where diarrheal disease is one of the most important health threats to children under 5 years of age. Little is known about the role of surface water and annual flood dynamics (flood pulse) on waterborne disease and human health nor about the expected impact of climate change on surface-water-dependent populations. METHODS AND FINDINGS: Using the Chobe River in northern Botswana, a flood pulse river-floodplain system, we applied multimodel inference approaches assessing the influence of river height, water quality (bimonthly counts of Escherichia coli and total suspended solids [TSS], 2011-2017), and meteorological variability on weekly diarrheal case reports among children under 5 presenting to health facilities (n = 10 health facilities, January 2007-June 2017). We assessed diarrheal cases by clinical characteristics and season across age groups using monthly outpatient data (January 1998-June 2017). A strong seasonal pattern was identified, with 2 outbreaks occurring regularly in the wet and dry seasons. The timing of outbreaks diverged from that at the level of the country, where surface water is largely absent. Across age groups, the number of diarrheal cases was greater, on average, during the dry season. Demographic and clinical characteristics varied by season, underscoring the importance of environmental drivers. In the wet season, rainfall (8-week lag) had a significant influence on under-5 diarrhea, with a 10-mm increase in rainfall associated with an estimated 6.5% rise in the number of cases. Rainfall, minimum temperature, and river height were predictive of E. coli concentration, and increases in E. coli in the river were positively associated with diarrheal cases. In the dry season, river height (1-week lag) and maximum temperature (1- and 4-week lag) were significantly associated with diarrheal cases. During this period, a 1-meter drop in river height corresponded to an estimated 16.7% and 16.1% increase in reported diarrhea with a 1- and 4-week lag, respectively. In this region, as floodwaters receded from the surrounding floodplains, TSS levels increased and were positively associated with diarrheal cases (0- and 3-week lag). Populations living in this region utilized improved water sources, suggesting that hydrological variability and rapid water quality shifts in surface waters may compromise water treatment processes. Limitations include the potential influence of health beliefs and health seeking behaviors on data obtained through passive surveillance. CONCLUSIONS: In flood pulse river-floodplain systems, hydrology and water quality dynamics can be highly variable, potentially impacting conventional water treatment facilities and the production of safe drinking water. In Southern Africa, climate change is predicted to intensify hydrological variability and the frequency of extreme weather events, amplifying the public health threat of waterborne disease in surface-water-dependent populations. Water sector development should be prioritized with urgency, incorporating technologies that are robust to local environmental conditions and expected climate-driven impacts. In populations with high HIV burdens, expansion of diarrheal disease surveillance and intervention strategies may also be needed. As annual flood pulse processes are predominantly influenced by climate controls in distant regions, country-level data may be inadequate to refine predictions of climate-health interactions in these systems.

INTRACELLULAR PERSISTENCE OF ENTEROAGGREGATIVE ESCHERICHIA COLI INDUCES A PROINFLAMMATORY CYTOKINES SECRETION IN INTESTINAL EPITHELIAL T84 CELLS.

BACKGROUND: The competence of enteroaggregative Escherichia coli (EAEC) to adhere to the intestinal epithelium of the host is a key role to the colonization and disease development. The virulence genes are crucial for EAEC pathogenicity during adherence, internalization and persistence in the host. The overwhelming majority of antigen encounters in a host occurs on the intestine surface, which is considered a part of innate mucosal immunity. Intestinal epithelial cells (IECs) can be activated by microorganisms and induce an immune response. OBJECTIVE: The present study investigated the interaction of invasive EAEC strains with T84 intestinal epithelial cell line in respect to bacterial invasiveness, persistence and cytokines production. METHODS: We evaluated intracellular persistence of invasive EAEC strains (H92/3, I49/3 and the prototype 042) and production of cytokines by sandwich ELISA in T84 cells upon 24 hours of infection. RESULTS: The survival rates of the prototype 042 was 0.5x103 CFU/mL while survival of I49/3 and H92/3 reached 3.2x103 CFU/mL and 1.4x103 CFU/mL, respectively. Infection with all EAEC strains tested induced significant amounts of IL-8, IL-6 and TNF-α compared to uninfected T84 cells. CONCLUSION: These data showed that infection by invasive EAEC induce a proinflammatory immune response in intestinal epithelial T84 cells.

A persistência intracelular de Escherichia coli enteroagregativa induz a secreção de citocinas pró-inflamatórias em células epiteliais intestinais T84 / Intracellular persistence of enteroaggregative escherichia coli induces a proinflammatory cytokines secretion in intestinal epithelial t84 cells

ABSTRACT BACKGROUND: The competence of enteroaggregative Escherichia coli (EAEC) to adhere to the intestinal epithelium of the host is a key role to the colonization and disease development. The virulence genes are crucial for EAEC pathogenicity during adherence, internalization and persistence in the host. The overwhelming majority of antigen encounters in a host occurs on the intestine surface, which is considered a part of innate mucosal immunity. Intestinal epithelial cells (IECs) can be activated by microorganisms and induce an immune response. OBJECTIVE: The present study investigated the interaction of invasive EAEC strains with T84 intestinal epithelial cell line in respect to bacterial invasiveness, persistence and cytokines production. METHODS: We evaluated intracellular persistence of invasive EAEC strains (H92/3, I49/3 and the prototype 042) and production of cytokines by sandwich ELISA in T84 cells upon 24 hours of infection. RESULTS: The survival rates of the prototype 042 was 0.5x103 CFU/mL while survival of I49/3 and H92/3 reached 3.2x103 CFU/mL and 1.4x103 CFU/mL, respectively. Infection with all EAEC strains tested induced significant amounts of IL-8, IL-6 and TNF-α compared to uninfected T84 cells. CONCLUSION: These data showed that infection by invasive EAEC induce a proinflammatory immune response in intestinal epithelial T84 cells.

RESUMO CONTEXTO: A competência de Escherichia coli enteroagregativa (EAEC) para aderir ao epitélio intestinal do hospedeiro é um papel fundamental para a colonização e o desenvolvimento da doença. Os genes de virulência são cruciais para a patogenicidade de EAEC durante a aderência, a internalização e a persistência no hospedeiro. A grande maioria dos encontros de antígenos em um hospedeiro ocorre na superfície do intestino, que é considerada parte da imunidade inata da mucosa. As células epiteliais intestinais (IECs) podem ser ativadas por micro-organismos e induzir uma resposta imune. OBJETIVO: O presente estudo investigou a interação de cepas invasoras de EAEC com a linhagem celular epitelial intestinal T84 em relação a invasão bacteriana, a persistência e a produção de citocinas. MÉTODOS: Avaliamos a persistência intracelular de cepas invasoras de EAEC (H92/3, I49/3 e o protótipo 042) e a produção de citocinas por ELISA "sanduíche" em células T84 após 24 horas de infecção. RESULTADOS: As taxas de sobrevivência da cepa protótipo 042 foi de 0,5x103 UFC/mL, enquanto a sobrevivência de I49/3 e H92/3 atingiu 3,2x103 UFC/mL e 1,4x103 UFC/mL, respectivamente. A infecção com todas as cepas EAEC testadas induziu quantidades significativas de IL-8, IL-6 e TNF-α em comparação com células T84 não infectadas. CONCLUSÃO: Estes dados mostraram que a infecção por EAEC invasoras induzem uma resposta imune pró-inflamatória em células epiteliais intestinais T84.

Birth weight and postnatal microbial exposures predict the distribution of peripheral blood leukocyte subsets in young adults in the Philippines.

The immune system not only provides protection against infectious disease but also contributes to the etiology of neoplastic, atopic, and cardiovascular and metabolic diseases. Prenatal and postnatal nutritional and microbial environments have lasting effects on multiple aspects of immunity, indicating that immune processes may play important roles in the developmental origins of disease. The objective of this study is to evaluate the association between birth weight and the distribution of leukocyte (white blood cell) subsets in peripheral blood in young adulthood. Postnatal microbial exposures were also considered as predictors of leukocyte distribution. Participants (n=486; mean age=20.9 years) were drawn from a prospective birth cohort study in the Philippines, and analyses focused on the following cell types: CD4 T lymphocytes, CD8 T lymphocytes, B lymphocytes, natural killer cells, monocytes, granulocytes. Higher birth weight was a strong predictor of higher proportion of CD4 T lymphocytes (B=0.12, s.e.=0.041, P=0.003), lower proportion of CD8 T lymphocytes (B=-0.874, s.e.=0.364, P=0.016), higher CD4:CD8 ratio (B=1.964, s.e.=0.658, P=0.003), and higher B lymphocytes (B=0.062, s.e.=0.031, P=0.047). Measures of microbial exposure in infancy were negatively associated with proportions of B lymphocytes and granulocytes, and lower CD4:CD8 ratio. Leukocytes are the key regulators and effectors of innate and specific immunity, but the origins of variation in the distribution of cell type across individuals are not known. Our findings point toward nutritional and microbial exposures in infancy as potentially important determinants of immune-phenotypes in adulthood, and they suggest that leukocyte distribution is a plausible mechanism through which developmental environments have lasting effects on disease risk in adulthood.

Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children.

Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions.

An untypeable enterotoxigenic Escherichia coli represents one of the dominant types causing human disease.

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhoea in children below 5 years of age in endemic areas, and is a primary cause of diarrhoea in travellers visiting developing countries. Epidemiological analysis of E. coli pathovars is traditionally carried out based on the results of serotyping. However, genomic analysis of a global ETEC collection of 362 isolates taken from patients revealed nine novel O-antigen biosynthesis gene clusters that were previously unrecognized, and have collectively been called unclassified. When put in the context of all isolates sequenced, one of the novel O-genotypes, OgN5, was found to be the second most common ETEC O-genotype causing disease, after O6, in a globally representative ETEC collection. It's also clear that ETEC OgN5 isolates have spread globally. These novel O-genotypes have now been included in our comprehensive O-genotyping scheme, and can be detected using a PCR-based and an in silico typing method. This will assist in epidemiological studies, as well as in ETEC vaccine development.

Typical & atypical enteropathogenic Escherichia coli in diarrhoea & their role as carrier in children under five.

BACKGROUND & OBJECTIVES: Multidrug-resistant enteropathogenic Escherichia coli (EPEC) is responsible for a large number of cases of infantile diarrhoea in developing countries, causing failure in treatment with consequent health burden and resulting in a large number of deaths every year. This study was undertaken to determine the proportion of typical and atypical EPEC in under five children with diarrhoea and controls, their function as a carriage and to identify virulent genes associated with them. METHODS: During the study period, 120 stool samples including 80 from controls children were collected and analyzed for the presence of EPEC using standard bacteriological methods. Isolates were subjected to antimicrobial testing by disc diffusion method. Isolates confirmed as E. coli by phenotypic method were further tested for the presence of attaching and effacing (eae) and bundle-forming pilus (bfpA) genes by real-time SYBR Green-based polymerase chain reaction. RESULTS: All isolates were tested for the presence of EPEC. The frequency of typical EPEC was 20 and 16.25 per cent whereas the frequency of atypical EPEC strains was 5 and 23.75 per cent in patients and controls, respectively (PbfpA was seen in 45 and 18.75 per cent isolates of diarrhoeal patients and controls, respectively. INTERPRETATION & CONCLUSIONS: Our results showed that typical EPEC was a common cause of diarrhoea, but at the same time, atypical EPEC was emerging as colonizers in the intestine of children with and without diarrhoea in and around Delhi. Children can be considered asymptomatic carriers of these pathogens and can transmit them to other susceptible children. Adequate steps need to be taken to stop these strains from developing and spreading further.

Campylobacter jejuni and associated immune mechanisms: short-term effects and long-term implications for infants in low-income countries.

PURPOSE OF REVIEW: Campylobacter jejuni is recognized as one of the most common causes of food-borne gastrointestinal illness worldwide, resulting in a self-limiting dysentery in developed countries. However, it is increasingly gaining attention due to its association with postinfectious complications such as Guillain-Barré Syndrome and recently recognized importance in early childhood diarrhea in developing countries. We hypothesize that the inflammation mediated by C. jejuni infection causes environmental enteric dysfunction, and with contribution from diet and the host, microbiome may be responsible for growth faltering in children and developmental disability. RECENT FINDINGS: Diet plays a major role in the impact of C. jejuni infection, both by availability of micronutrients for the bacteria and host as well as shaping the microbiome that affords resistance. Early childhood repeated exposure to the bacterium results in inflammation that affords long-term immunity but, in the short term, can lead to malabsorption, oral vaccine failure, cognitive delay and increased under-5 mortality. SUMMARY: As interest in C. jejuni increases, our understanding of its virulence mechanisms has improved. However, much work remains to be done to fully understand the implications of immune-mediated inflammation and its potential role in diseases such as environmental enteric dysfunction.

The aetiology of diarrhoea, pneumonia and respiratory colonization of HIV-exposed infants randomized to breast- or formula-feeding.

BACKGROUND: Diarrhoea and pneumonia are common causes of childhood death in sub-Saharan Africa but there are few studies describing specific pathogens. OBJECTIVES: The study aimed to describe the pathogens associated with diarrhoea, pneumonia and oropharyngeal colonization in children born to HIV-infected women (HIV-exposed infants). METHODS: The Mashi Study randomized 1200 HIV-infected women and their infants to breastfeed for 6 months with ZDV prophylaxis or formula-feed with 4 weeks of ZDV. Children were tested for HIV by PCR at 1, 4, 7, 9 and 12 months and by ELISA at 18 months. Pre-defined subsets of children were sampled during episodes of diarrhoea (n = 300) and pneumonia (n = 85). Stool was tested for bacterial pathogens, rotavirus and parasites. Children with pneumonia underwent bacterial blood culture, and testing of nasopharyngeal aspirates for viral pathogens by PCR. Oropharyngeal swabs were collected from a consecutive subset of 561 infants at the routine 3-month visit for bacterial culture. RESULTS: The median age (range) at sampling was 181 days for diarrhoea (0-730) and 140 days for pneumonia (2-551). Pathogens were identified in 55 (18%) children with diarrhoea and 32 (38%) with pneumonia. No differences in pathogens by child HIV status (HIV-infected vs HIV-uninfected) or feeding strategy were identified. Campylobacter was the most common diarrhoeal pathogen (7%). Adenovirus (22%) and other viruses (19%) were the primary pathogens isolated during pneumonias. More formula-fed infants had oropharyngeal colonization by pathogenic Gram-negative bacteria (16.8% vs 6.2%, P = 0.003), which was associated with a non-significant increased risk of pneumonia (OR 2.2, 95% CI 0.8-5.7). CONCLUSION: A trend toward oropharyngeal bacterial colonization was observed in formula-fed infants. Although viruses were most commonly detected during pneumonia, respiratory colonization by Gram-negative bacteria may have contributed to pneumonia in formula-fed infants.

Identification of Infantile Diarrhea Caused by Breast Milk-Transmitted Staphylococcus aureus Infection.

Staphylococcus aureus is a well-known organism which is responsible for a variety of human infectious diseases including skin infections, pneumonia, bacteremia, and endocarditis. Few of the microorganisms can be transmitted from mother to the newborn or infant by milk breastfeeding. This study aims to identify transmission of S. aureus from healthy, lactating mothers to their infants by breastfeeding. Stool specimens of diarrheal infants and breast milk of their mother (totally three pairs) were collected and six Staphylococcus aureus isolates were cultured positively. Homology and molecular characters of isolated strains were tested using pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing. Furthermore, toxin genes detection was also performed. Each pair of isolates has the same PFGE type and spa type. Four Sequence types (STs) were found among all the isolates; they are ST15, ST188, and ST59, respectively. Among the strains, seb, sec, and tst genes were found, and all were negative for pvl gene. The homology of the S. aureus strains isolated from the infants' stool and the mothers' milk was genetically demonstrated, which indicated that breastfeeding may be important in the transmission of S. aureus infection, and the character of S. aureus needed to be further evaluated.

Probiotics and prebiotics in infectious gastroenteritis.

Acute gastroenteritis (AGE) is worldwide a common problem in infants and children. While AGE is still an important cause of morbidity and mortality in developing countries, it is mainly a problem with high socioeconomic impact in the rest of the world. Oral rehydration solutions (ORS) and rapid refeeding remain the cornerstone of the management. However, ORS does not decrease the duration of diarrhea. There is evidence that selected strains of probiotics decrease the duration of AGE with 24 h, both in ambulatory care and in hospitalized children, resulting also in a decrease of the duration of hospitalization. Synbiotics are equally effective as probiotics alone, but prebiotics are not effective. Both pro- and prebiotics have limited to no efficacy in the prevention of AGE. The administration of pre- and probiotics is considered to be safe, even in newborns. Only these pre-, pro and synbiotics that have been clinically tested can be recommended.

Environmental Enteric Dysfunction in Children.

Diarrheal diseases are a major cause of childhood death in resource-poor countries, killing approximately 760,000 children younger than 5 years each year. Although deaths due to diarrhea have declined dramatically, high rates of stunting and malnutrition have persisted. Environmental enteric dysfunction (EED) is a subclinical condition caused by constant fecal-oral contamination with resultant intestinal inflammation and villous blunting. These histological changes were first described in the 1960s, but the clinical effect of EED is only just being recognized in the context of failure of nutritional interventions and oral vaccines in resource-poor countries. We review the existing literature regarding the underlying causes of and potential interventions for EED in children, highlighting the epidemiology, clinical and histologic classification of the entity, and discussing novel biomarkers and possible therapies. Future research priorities are also discussed.

Cryptosporidium ubiquitum in Venezuela: First report in a paediatric patient with acute diarrhea / Cryptosporidium ubiquitum en Venezuela: primer informe en un paciente pediátrico con diarrea aguda

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