Diarrheal Pathogens Research Articles

Variation of Secondary Metabolite Contents and Activities against Bovine Diarrheal Pathogens among Zygophyllaceae Species in Benin and Implications for Conservation.

Balanites aegyptiaca is a wild plant species largely used in folk medicine and a priority fruit tree in West Africa. In Benin, its overexploitation for ethnoveterinary uses could lead to its rarity or extinction in the long term. In this study, we evaluate the possibilities of its substitution by other Zygophyllaceae species. This study was based on optimal defense theory, which distinguished 2 categories of plants: K-strategist species and r-strategist species. Phytochemical screening was carried out based on aqueous extracts of the leafy stems of B. aegyptiaca and Guaiacum officinale (K-strategist species) and Tribulus terrestris and Kallstroemia pubescens (r-strategist species) for the identification of chemical compounds. The phenolic compounds were quantified by quercetin and vanillin methods. The extracts were tested against 5 bacterial strains responsible for severe diarrhea in bovines. Our results indicated the presence of many phytochemicals, such as alkaloids, flavonoids, saponosides, and tannins. The diversity in secondary metabolites is higher for r-strategist than K-strategist species. The contents of total polyphenols ranged from 4.82 ± 0.05 to 41.84 mg GAE/g of extract. The flavonoid contents varied from 30.64 ± 0.35 to 57.11 ± 0.13 mg QE/g of extract and those of the tannins from 0.04 ± 0.00 to 0.06 ± 0.01 mg PE/mL. The sensitivity of the bacterial strains showed a significant dependence on the extracts. Of the species, K.pubescens showed a bactericidal activity on the majority of strains tested and thus could be a potential substitute for B.aegyptiaca in the treatment of infectious diarrhea.

Milk Product Safety and Household Food Hygiene Influence Bacterial Contamination of Infant Food in Peri-Urban Kenya.

BackgroundMilk is a common infant food in peri-urban Kenya that can transmit diarrhea-causing enteric pathogens. Little is known about how contamination of milk at point of purchase and household handling of milk-based infant foods contribute to infant exposure to enteric pathogens.ObjectiveTo compare the prevalence and concentrations of bacterial indicator organisms and enteric pathogens in unpackaged, fresh pasteurized, and ultra-high temperature (UHT) treated milk at purchase and assess the influence of the type of milk used to prepare infant food on contamination of this food.MethodsPaired samples of purchased milk and infant food prepared with this milk were obtained from 188 households in low-income neighborhoods in Kisumu, Kenya. Samples were cultured on selective media to isolate Salmonella enterica, Shigella spp., Klebsiella aerogenes, Proteus spp., and Escherichia coli, with pathogens validated by PCR. Probability of detection of these bacteria was compared by milk product treatment and packaging method, and between milk at point of purchase vs. food at point of infant consumption.ResultsUnpackaged milk was most contaminated at point of purchase, but bacterial contamination was also present in pasteurized and UHT milk at purchase. Presence of bacteria in UHT and fresh pasteurized milk at purchase predicted presence of the same bacteria type in infant food. Prevalence of bacterial contamination and concentration level for bacterial indicators generally increased between point of purchase and consumption in UHT and fresh pasteurized milk-based food but decreased in unpackaged milk-based food. Prevalence of the four fecal bacteria were similar in infant foods prepared with each type of milk.ConclusionBoth pre-market contamination and post-purchase handling influence the likelihood of infants ingesting foods contaminated by diarrheal pathogens.

Diarrheal disease and gut microbiome.

Diarrheal disease remains a great public health problem in many countries. Enteric infections caused by several viral, bacterial and parasitic species not only affect the host, but also alter the gut microbiome. The host physiology dictates the intestinal milieu and decides the composition and richness of gut microbiota, which forms a homeostatic ecosystem with numerous functions and provide protection against invading pathogens. During diarrheal infection, patients are affected by gut microbial dysbiosis, which benefits the pathogenic and pro-inflammatory bacteria by enhancing their colonization and proliferation. Gut microbes are associated with several pathophysiological mechanisms, including distorted motility, intestinal barrier dysfunction, malabsorption, immunity disorder, systemic inflammation and changes in the gut-organ axis. Several abiotic factors and childhood malnutrition have negative influences on the gut microbiota, including antibiotics that lead to antibiotic-associated diarrhea and persistent infection. DNA sequencing and bioinformatic analyses enhanced our perception of the gut microbiota, network of metabolic interdependence and their role in health and disease. However, the precise functions of microbiota in gut homeostasis are not well defined. In this chapter, we recapitulate the impact of gut microbiota on diarrheal pathogens, their importance in the immune system and how reshaping the gut microbiota can help during the recovery phase. Additionally, we discuss about impediments and influences beyond diarrhea, particularly on the nutritional status of children.

Simultaneous Detection of 20 Key Infectious Diarrhoeal Pathogens and Pathogen Subtypes by Combination of Multiplex Asymmetric-PCR and Electrochemical DNA Sensor Assay

Simultaneous Detection of 20 Key Infectious Diarrhoeal Pathogens and Pathogen Subtypes by Combination of Multiplex Asymmetric-PCR and Electrochemical DNA Sensor Assay

Biodigester Cookstove Interventions and Child Diarrhea in Semirural Nepal: A Causal Analysis of Daily Observations.

Background:Hundreds of thousands of biodigesters have been constructed in Nepal. These household-level systems use human and animal waste to produce clean-burning biogas used for cooking, which can reduce household air pollution from woodburning cookstoves and prevent respiratory illnesses. The biodigesters, typically operated by female caregivers, require the handling of animal waste, which may increase domestic fecal contamination, exposure to diarrheal pathogens, and the risk of enteric infections, especially among young children.Objective:We estimated the effect of daily reported biogas cookstove use on incident diarrhea among children old in the Kavrepalanchok District of Nepal. Secondarily, we assessed effect measure modification and statistical interaction of individual- and household-level covariates (child sex, child age, birth order, exclusive breastfeeding, proof of vaccination, roof type, sanitation, drinking water treatment, food insecurity) as well as recent 14-d acute lower respiratory infection (ALRI) and season.Methods:We analyzed 300,133 person-days for 539 children in an observational prospective cohort study to estimate the average effect of biogas stove use on incident diarrhea using cross-validated targeted maximum likelihood estimation (CV-TMLE).Results:Households reported using biogas cookstoves in the past 3 d for 23% of observed person-days. The adjusted relative risk of diarrhea for children exposed to biogas cookstove use was 1.31 (95% confidence interval (CI): 1.00, 1.71) compared to unexposed children. The estimated effect of biogas stove use on diarrhea was stronger among breastfed children (2.09; 95% CI: 1.35, 3.25) than for nonbreastfed children and stronger during the dry season (2.03; 95% CI: 1.17, 3.53) than in the wet season. Among children exposed to biogas cookstove use, those with a recent ALRI had the highest mean risk of diarrhea, estimated at 4.53 events (95% CI: 1.03, 8.04) per 1,000 person-days.Discussion:This analysis provides new evidence that child diarrhea may be an unintended health risk of biogas cookstove use. Additional studies are needed to identify exposure pathways of fecal pathogen contamination associated with biodigesters to improve the safety of these widely distributed public health interventions. https://doi.org/10.1289/EHP9468

Evaluation of the BioFire Gastrointestinal Panel to Detect Diarrheal Pathogens in Pediatric Patients.

Infectious diarrhea is a global pediatric health concern; therefore, rapid and accurate detection of enteropathogens is vital. We evaluated the BioFire® FilmArray® Gastrointestinal (GI) Panel with that of comparator laboratory tests. Stool samples of pediatric patients with diarrhea were prospectively collected and tested. As a comparator method for bacteria, culture, conventional PCR for diarrheagenic E. coli, and Allplex GI-Bacteria(I) Assay were tested. For discrepancy analysis, BD MAX Enteric Bacterial Panel was used. As a comparator method for virus, BD MAX Enteric Virus Panel and immunochromatography was used and Allplex GI-Virus Assay was used for discrepancy analysis. The “true positive” was defined as culture-positive and/or positive results from more than two molecular tests. Of the 184 stool samples tested, 93 (50.5%) were true positive for 128 pathogens, and 31 (16.9%) were positive for multiple pathogens. The BioFire GI Panel detected 123 pathogens in 90 of samples. The BioFire GI Panel demonstrated a sensitivity of 100% for 12 targets and a specificity of >95% for 16 targets. The overall positive rate and multiple pathogen rate among patients in the group without underlying diseases were significantly higher than those in the group with hematologic disease (57.0% vs. 28.6% (p = 0.001) and 20.4% vs. 4.8% (p = 0.02), respectively). The BioFire GI Panel provides comprehensive results within 2 h and may be useful for the rapid identification of enteropathogens.

698. Contemporary Clinical Epidemiology of Pediatric Shigella and Campylobacter Infections in Houston, TX, 2019 and 2020

BackgroundInfections due to Gram-negative, diarrheal pathogens are a significant cause of morbidity in children. Clinical features of pediatric Shigella and Campylobacter infections in urban cities in the United States are not well described.MethodsWe used a retrospective chart review of records (0-18 years of age) from a network of hospitals in Houston, TX. Only patients with Shigella spp. or Campylobacter spp. isolated from clinical samples in 2019 and 2020 were included. Demographic, clinical, and microbiological data were extracted from the medical record. ResultsWe identified a total of 59 and 16 pediatric patients with Shigella spp. and Campylobacter spp. infections, respectively. Hospital admission occurred in 27.1% (16/59) of Shigella and 25% (4/16) of Campylobacter. Length of stay ranged between 1 and 2 days for both pathogens (Table 1). Of cases with available clinical data, Shigella infections were more likely to report fever during their illness compared to Campylobacter (80% versus 45.4%) (Table 2). Seizures were observed in 4 Shigella infected patients. No episodes of Shigella or Campylobacter bacteremia were identified. Among patients with an identified exposure, daycare attendance and contact with individuals experiencing similar symptoms were most common (Table 2). The vast majority of Shigella species were S. sonnei (96.6%) and all Campylobacter were C. jejuni (Table 3). Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) was common (40/55, 72.7%) among Shigella isolates tested. No resistance to fluoroquinolones or third generation cephalosporins in any of the Shigella spp. isolates was observed. Susceptibility testing was not performed in Campylobacter due to lack of isolates. The most frequent antibiotic used was azithromycin (in 73.3% and 75% of patients with Shigella and Campylobacter, respectively). Major complications included urinary tract infection (n=1), rectal prolapse (n=1) and splenomegaly (n=1). ConclusionInfections due to Shigella and Campylobacter were a significant burden among pediatric patients between 2019 and 2020 in Houston, TX. The observed high frequency of resistance to TMP-SMX and emergence of multi-drug resistant Shigella in other countries warrants continued surveillance. Disclosures Anthony R. Flores, MD, MPH, PhD, Nothing to disclose Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Grant/Research Support)MeMed Diagnostics (Grant/Research Support)Merk (Grant/Research Support)

16S rRNA-based metagenomic profiling of microbes on contact surfaces within shared sanitation facilities

Contact surfaces within shared sanitation facilities could lead to disease transmission due to contamination. In this study, we applied metagenomics, by targeting the 16S rRNA gene region using illumina sequencing to determine the common bacterial communities on key contact surfaces in shared sanitation facilities within a metropolitan area. The common bacterial phyla identified on these surfaces were Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes, with average counts up to 12 Log 10 and a prevalence of 100% for each of these phyla. Known diarrhoeal pathogens like , Salmonella enterica, Bacillus cereus, Campylobacter jejuni, Campylobacter coli, Yersinia pestis, Yersinia pseudotuberculosis, Vibrio cholerae, Vibrio parahaemolyticus and Vibrio vulnificus were detected on almost all surfaces. Cistern handles, tap handles and toilet seats had the highest number of potentially pathogenic bacteria, such as S. enterica . Additionally, uncommon and very rarely pathogenic bacteria such as Cedecea neteri, Enterobacter hormaechei, Klebsiella michiganensis, Pluralibacter gergoviae, Kosakonia cowanii and Raou l tella ornithinoly t i ca were also detected. Many of these can be considered as environmental commensals. These results show that contact surfaces within shared sanitation facilities could have been contaminated with faecal matter as well as soil. In conclusion, being the first study to apply metagenomics in profiling bacterial communities on contact surfaces in shared sanitation facilities in South Africa, it shows the potential of disease transmission via the use of these shared facilities. Additionally, the results also show the application of 16S rRNA-based metagenomics in determining the potential role of shared sanitation in disease transmission.

Antibody in Lymphocyte Supernatant (ALS) responses after oral vaccination with live Shigella sonnei vaccine candidates WRSs2 and WRSs3 and correlation with serum antibodies, ASCs, fecal IgA and shedding.

The levels of antigen-specific Antibodies in Lymphocyte Supernatant (ALS) using an ELISA are being used to evaluate mucosal immune responses as an alternate to measuring the number of Antibody Secreting Cells (ASCs) using an ELISpot assay. A recently completed trial of two novel S. sonnei live oral vaccine candidates WRSs2 and WRSs3 established that both candidates were safe, well tolerated and immunogenic in a vaccine dose-dependent manner. Previously, mucosal immune responses were measured by assaying IgA- and IgG-ASC in peripheral blood mononuclear cells (PBMCs). In this report, the magnitude of the S. sonnei antigen-specific IgA- and IgG-ALS responses was measured and correlated with previously described ASCs, serum antibodies, fecal IgA and vaccine shedding. Overall, the magnitude of S. sonnei anti-Invaplex50 ALS was higher than that of LPS or IpaB, and both vaccines demonstrated a more robust IgA-ALS response than IgG; however, compared to WRSs3, the magnitude and percentage of responders were higher among WRSs2 recipients for IgA- or IgG-ALS. All WRSs2 vaccinees at the two highest doses responded for LPS and Invaplex50-specific IgA-ALS and 63–100% for WRSs3 vaccinees responded. Regardless of the vaccine candidate, vaccine dose or detecting antigen, the kinetics of ALS responses were similar peaking on days 7 to 9 and returning to baseline by day 14. The ALS responses were vaccine-specific since no responses were detected among placebo recipients at any time. A strong correlation and agreement between responders/non-responders were noted between ALS and other mucosal (ASC and fecal IgA) and systemic (serum antibody) immune responses. These data indicate that the ALS assay can be a useful tool to evaluate mucosal responses to oral vaccination, an observation noted with trials of other bacterial diarrheal pathogens. Furthermore, this data will guide the list of immunological assays to be conducted for efficacy trials in different populations. It is hoped that an antigen-specific-ALS titer may be a key mucosal correlate of protection, a feature not currently available for any Shigella vaccines candidates. https://clinicaltrials.gov/show/NCT01336699.

Combating Childhood Infections in LMICs: evaluating the contribution of Big Data Big data, biomarkers and proteomics: informing childhood diarrhoeal disease management in Low- and Middle-Income Countries

<h2>Abstract</h2> Despite efforts to reduce the global burden of childhood diarrhoea, 50% of all cases globally occur in children under five years in Low–Income and Middle- Income Countries (LMICs) and knowledge gaps remain regarding the aetiological diagnosis, introduction of diarrhoeal vaccines, and the role of environmental enteric dysfunction and severe acute malnutrition. Biomarkers may assist in understanding disease processes, from diagnostics, to management of childhood diarrhoea and the sequelae to vaccine development. Proteomics has the potential to assist in the identification of new biomarkers to understand the processes in the development of childhood diarrhoea and to aid in developing new vaccines. Centralised repositories that enable mining of large data sets to better characterise risk factors, the proteome of both the patient and the different diarrhoeal pathogens, and the environment, could inform patient management and vaccine development, providing a systems biological approach to address the burden of childhood diarrhoea in LMICs.

Molecular diversity survey on diarrheagenic Escherichia coli isolates among children with gastroenteritis inFars, Iran.

Aim: To differentiate Escherichia coli isolates from diarrheal pediatric patients in clinical laboratories. Materials & methods: Patients with watery diarrhea were selected for sampling and tested for diarrheagenic E. coli(DEC)by APIkit. DEC isolates were tested for phylotyping, pathotyping and presence of determined virulence-encoding genes by specific molecular methods. Results: About 50% of isolates were detected as DECs (>55and >31% were categorized B2 and D phylotypes respectively). Enterotoxigenic E. coli was the most and enteroinvasive E. coli was the lowest prevalent pathotypes. csgand fim genes were the most present virulence factors. Conclusion: Typing of E. coli isolates from stool specimens will help to determine the diversity of diarrheal pathogens and take proper decisions to reduce the health burden of diarrheal diseases.

A short chain fatty acid-centric view of Clostridioides difficile pathogenesis.

Clostridioides difficile is an opportunistic diarrheal pathogen responsible for significant morbidity and mortality worldwide. A disrupted (dysbiotic) gut microbiome, commonly engendered by antibiotic treatment, is the primary risk factor for C. difficile infection, highlighting that C. difficile–microbiome interactions are critical for determining the fitness of this pathogen. Here, we review short chain fatty acids (SCFAs): a major class of metabolites present in the gut, their production by the gut microbiome, and their impacts on the biology of the host and of C. difficile. We use these observations to illustrate a conceptual model whereby C. difficile senses and responds to SCFAs as a marker of a healthy gut and tunes its virulence accordingly in order to maintain dysbiosis. Future work to learn the molecular mechanisms and genetic circuitry underlying the relationships between C. difficile and SCFAs will help to identify precision approaches, distinct from antibiotics and fecal transplant, for mitigating disease caused by C. difficile and will inform similar investigations into other gastrointestinal pathogens.

Is It Human or Animal? The Origin of Pathogenic E. coli in the Drinking Water of a Low-Income Urban Community in Bangladesh.

This study aimed to investigate the origin of diverse pathotypes of E. coli, isolated from communal water sources and from the actual drinking water vessel at the point-of-drinking inside households in a low-income urban community in Arichpur, Dhaka, Bangladesh, using a polymerase chain reaction (PCR). Forty-six percent (57/125, CI 95%: 41−58) of the isolates in the point-of-drinking water and 53% (55/103, CI 95%: 45−64) of the isolates in the source water were diarrheagenic E. coli. Among the pathotypes, enterotoxigenic E. coli (ETEC) was the most common, 81% (46/57) of ETEC was found in the point-of-drinking water and 87% (48/55) was found in the communal source water. Phylogenetic group B1, which is predominant in animals, was the most frequently found isolate in both the point-of-drinking water (50%, 91/181) and in the source (50%, 89/180) water. The phylogenetic subgroup B23, usually of human origin, was more common in the point-of-drinking water (65%, 13/20) than in the source water (35%, 7/20). Our findings suggest that non-human mammals and birds played a vital role in fecal contamination for both the source and point-of-drinking water. Addressing human sanitation without a consideration of fecal contamination from livestock sources will not be enough to prevent drinking-water contamination and thus will persist as a greater contributor to diarrheal pathogens.

Prevalence of diarrhoeal pathogens among children under five years of age with and without diarrhoea in Guinea-Bissau.

BackgroundChildhood diarrhoea, a major cause of morbidity and mortality in low-income regions, remains scarcely studied in many countries, such as Guinea-Bissau. Stool sample drying enables later qPCR analyses of pathogens without concern about electricity shortages.MethodsDried stool samples of children under five years treated at the Bandim Health Centre in Bissau, Guinea-Bissau were screened by qPCR for nine enteric bacteria, five viruses, and four parasites. The findings of children having and not having diarrhoea were compared in age groups 0–11 and 12–59 months.ResultsOf the 429 children– 228 with and 201 without diarrhoea– 96.9% and 93.5% had bacterial, 62.7% and 44.3% viral, and 52.6% and 48.3% parasitic pathogen findings, respectively. Enteroaggregarive Escherichia coli (EAEC; 60.5% versus 66.7%), enteropathogenic E. coli (EPEC; 61.4% versus 62.7%), Campylobacter (53.2% versus 51.8%), and enterotoxigenic E. coli (ETEC; 54.4% versus 44.3%) were the most common bacterial pathogens. Diarrhoea was associated with enteroinvasive E. coli (EIEC)/Shigella (63.3%), ETEC (54.4%), astrovirus (75.0%), norovirus GII (72.6%) and Cryptosporidium (71.2%). The only pathogen associated with severe diarrhoea was EIEC/Shigella (p<0.001). EAEC was found more frequent among the infants, and EIEC/Shigella, Giardia duodenalis and Dientamoeba fragilis among the older children.ConclusionsStool pathogens proved common among all the children regardless of them having diarrhoea or not.

Detailed analysis of enteric pathogen incidence associated with COVID-19 mitigation behaviors informs upcoming clinical and policy decision making.

There is a growing body of literature on the impact of COVID-19 nonpharmaceutical interventions (NPI) on other infectious diseases. [1-7] In their article published in The Lancet Regional Health – Western Pacific, Li-Ping Wang and colleagues [8] analyzed data from 134 hospitals across 27 provinces in China to evaluate the incidence of common acute diarrheal pathogens through four phases of COVID-19 NPI in 2020 compared to historical data. Their data was obtained from the Chinese Center for Disease Control and Prevention's nationwide surveillance program for acute diarrhoea, offering a lengthy (the program began in 2009) and detailed historical record of geographic and seasonal variations for comparison.

Acute Watery Diarrhea Surveillance During the Rohingya Crisis 2017-2019 in Cox's Bazar, Bangladesh.

BackgroundForcibly Displaced Myanmar Nationals (FDMNs) fled into Cox’s Bazar, Bangladesh due to internal conflict. Considering the public health situation, a surveillance network was established to identify the enteric pathogens and early detection of cholera epidemics. The purpose of this manuscript is to report the clinical, epidemiological determinants of cholera and other enteric pathogens among hospitalized diarrheal patients from FDMNs and host community.MethodsA total of 11 sentinel surveillance sites were established around the camps in Ukhia and Teknaf Upazila, Cox’s Bazar. Rapid diagnostic testing was conducted for immediate detection of cholera cases. Stool samples were transferred to the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) laboratory for culture.ResultsA total of 8134 participants with diarrhea were enrolled from 2017 to 2019: 4881 were FDMNs and 3253 were from the Bangladeshi host community. Among the FDMNs, the proportion of Vibrio cholerae was 0.7%, the proportion of enterotoxigenic Escherichia coli (ETEC) was 4.9%, and the proportion of Shigella was 1.5%. The distributions from host community were 1.2% V cholerae, 1.8% ETEC, and 1.1% Shigella. Similar risk factors have been identified for the diarrheal pathogens for both communities.ConclusionsThis surveillance helped to monitor the situation of diarrheal diseases including cholera in refugee camps as well as in the neighboring host community. These findings lead policymakers to take immediate preventive measures.

Estimating the disease burden ascribed to specific enteropathogens

Julia Baker and colleagues1 report a systematic review and meta-analysis (SRMA) in The Lancet Global Health, which informs the estimation of disease burden ascribed to individual diarrhoeal pathogens. When accurate, such estimates provide evidence to prioritise the development and deployment of rapid diagnostic tests, targeted treatment, and vaccines.

A Descriptive Cross-Sectional Assessment of Caregivers' Knowledge and Practices Regarding the Prevention and Management of Diarrhea among Children under the Age of Five in Thulamela B Clinics, South Africa.

Diarrhea is a common cause of child-related hospitalization and mortality among children under the age of five in South Africa. This study was conducted to assess the knowledge and practices of caregivers regarding prevention and management of diarrhea among children under the age of five in the Thulamela Municipality of South Africa. A quantitative approach using a descriptive cross-sectional survey was used. A questionnaire was adopted to collect data from caregivers at thirty primary health-care facilities using convenient sampling. Statistical Package for Social Sciences (SPSS) version 24.0 was used to analyze data. Most of the respondents have fair knowledge about diarrhea, oral rehydration therapy/salt sugar solution and its usage during diarrheal episodes. However, most of them (81.7%) do not use the salt sugar solution when their children have diarrhea. Almost all the respondents practice a hand washing hygiene for themselves and their children; 97.2% do not reheat cooked food before feeding their children; 95.5% do not drink untreated water as their source of drinking water is the municipal supply. The practices of these respondents do not reflect their knowledge in terms of the use of oral rehydration solution/salt and sugar solution. Further efforts should be made to educate caregivers on the mode of transmission of diarrheal pathogens.

Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger

High-resolution data on the etiology of childhood diarrhea in countries with the highest burden and mortality remain sparse and are needed to inform burden estimates and prioritize interventions. We tested stool specimens collected between October 2014 and December 2017 from children under 2 years of age from the per-protocol population of a placebo-controlled clinical trial of a bovine rotavirus pentavalent vaccine (Rotasiil) in Niger. We tested 1729 episodes of moderate-to-severe diarrhea (Vesikari score ≥ 7) using quantitative PCR and estimated pathogen-specific burdens by age, season, severity, and trial intervention arm. The 4 pathogens with the highest attributable incidence of diarrhea were Shigella (7.2 attributable episodes per 100 child-years; 95% confidence interval: 5.2, 9.7), Cryptosporidium (6.5; 5.8, 7.2), rotavirus (6.4; 5.9, 6.7), and heat-stabile toxin-producing enterotoxigenic Escherichia coli (ST-ETEC) (6.2; 3.1, 7.7). Cryptosporidium was the leading etiology of severe diarrhea (Vesikari score ≥ 11) and diarrhea requiring hospitalization. Shigella was the leading etiology of diarrhea in children 12-23 months of age but also had a substantial burden in the first year of life, with 60.5% of episodes of severe shigellosis occurring in infants. Shigella, Cryptosporidium, and ST-ETEC incidence peaked during the warmer and wetter period and coincided with peak all-cause diarrhea incidence. In this high-burden setting, the leading diarrheal pathogens were Shigella, Cryptosporidium, rotavirus, and ST-ETEC, and each was disproportionately seen in infants. Vaccine development should target these pathogens, and the impact of vaccine schedule on diarrhea burden in the youngest children will need to be considered.

Correlation Between Prevalence of Selected Enteropathogens and Diarrhea in Children: A Case-Control Study in China.

BackgroundThe application of nucleic acid detection methods improves the ability of laboratories to detect diarrheal pathogens, but it also poses new challenges for the interpretation of results. It is often difficult to attribute a diarrhea episode to the detected pathogens. Here we investigated the prevalence of 19 enteropathogens among diarrheal and nondiarrheal children and provided support for understanding the clinical significance of the pathogens.MethodsA total of 710 fecal samples were collected from children under 5 years old in 2 different regions of China from May 2017 to March 2018, comprising 383 mild to moderate diarrheal cases and 327 nondiarrheal controls. The enteropathogens were detected using real-time polymerase chain reaction (PCR) or real-time reverse transcription PCR (RT-PCR).ResultsEnteropathogens were detected in 68.9% of cases and 41.3% of controls. Rotavirus A (adjusted OR [aOR], 9.91; 95% CI, 4.99–19.67), norovirus GI and GII (aOR, 3.82; 95% CI, 2.12–6.89), and Campylobacter jejuni (aOR, 20.12; 95% CI, 2.57–157.38) were significantly associated with diarrhea (P < .05). Adenovirus, norovirus GII, rotavirus A, and enteroaggregative Escherichia coli (pCVD432) gave lower cycle threshold (Ct) values in cases than in controls (P < .05). Rotavirus A and norovirus GII were associated with diarrhea when the Ct values were ≤30 and ≤25, respectively.ConclusionsThe types and loads of enteropathogens are likely to influence the interpretation of the clinical significance of positive results.