Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics.

BACKGROUND: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. METHODS: AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies. RESULTS: Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, -11.6 [95% confidence interval {CI}, -15.6 to -7.6]) and possible bacterial etiology (RDpossible, -8.7 [95% CI, -13.0 to -4.4]) but not in other children (RDunlikely, -0.3% [95% CI, -2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, -3.1 [95% CI, -5.3 to -1.0]; RDpossible, -2.3 [95% CI, -4.5 to -.01]; RDunlikely, -0.6 [95% CI, -1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. CONCLUSIONS: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment. CLINICAL TRIALS REGISTRATION: NCT03130114.

Metagenomic analysis for exploring the potential of Lactobacillus yoelii FYL1 to mitigate bacterial diarrhea and changes in the gut microbiota of juvenile yaks.

Diarrhea in calves is a common disease that results in poor nutrient absorption, poor growth and early death which leads to productivity and economic losses. Therefore, it is important to explore the methods to reduce diarrhea in yak's calves. Efficacy of lactic acid bacteria (LAB) for improvement of bacterial diarrhea is well recognized. For this purpose, two different doses (107 CFU, 1011 CFU) of Lactobacillus yoelii FYL1 isolated from yaks were fed to juvenile yaks exposed to E. coli O78. After a trial period of ten days fresh feces and intestinal contents of the experimental yaks were collected and metagenomics sequencing was performed. It was found that feeding a high dose of Lactobacillus yoelii FYL1 decreased abundance of phylum Firmicutes in the E. coli O78 infected group whereas, it was high in animals fed low dose of Lactobacillu yoelii FYL1. Results also revealed that counts of bacteria from the family Oscillospiraceae, genus Synergistes and Megasphaera were higher in control group whereas, order Bifidobacteriales and family Bifidobacteriaceae were higher in infected group. It was observed that bacterial counts for Pseudoruminococcus were significantly (P < 0.05) higher in animals of group that were given high dose of Lactobacillus yoelii FYL1 (HLAB). Compared to infected group multiple beneficial bacterial genera such as Deinococus and Clostridium were found higher in the animals that were given a low dose of Lactobacillus yoelii FYL1 (LLAB). The abundance of pathogenic bacterial genera that included Parascardovia, Bacteroides and Methanobrevibacter was decreased (P < 0.05) in the lower dose treated group. The results of functional analysis revealed that animals of LLAB had a higher metabolism of terpenoids and polyketides compared to animals of infected group. Virus annotation also presented a significant inhibitory effect of LLAB on some viruses (P < 0.05). It was concluded that L. yoelii FYL1 had an improved effect on gut microbiota of young yaks infected with E. coli O78. This experiment contributes to establish the positive effects of LAB supplementation while treating diarrhea.

Molecular characterization and phylogenetic analysis of porcine epidemic diarrhea virus in Xinjiang, China, from 2020 to 2022.

In recent years, the pig industry in Xinjiang, China, has been severely impacted by outbreaks of porcine epidemic diarrhea (PED), despite vaccination efforts. In this study, we investigated the genetic characteristics of currently prevalent porcine epidemic diarrhea virus (PEDV) strains in the region. We collected 548 samples from animals with suspected PED on large-scale pig farms in Xinjiang. Of these, 258 tested positive for PEDV by RT-PCR, yielding an overall positivity rate of 47.08%. S1 gene sequencing and phylogenetic analysis were conducted on 23 randomly selected RT-PCR-positive samples. Three endemic strains of PEDV (PEDV/CH/XU/2020, PEDV/CH/XK/2020, and PEDV/CH/XA/2020) were isolated, and their complete genome sequences were analyzed for evidence of genetic recombination. Sequence comparison of the S gene indicated significant variations in the S1 gene of the Xinjiang strains compared to the vaccine strains CV777, AJ1102, and LWL, with 90.2%-98.5% nucleotide sequence identity. Notably, both the N-terminal and C-terminal domains of the S protein showed significant variation. Genetic evolutionary analysis identified the GIIa subtype as the dominant genotype among the epidemic strains in Xinjiang. Recombination analysis revealed inter-subtype recombination events in the PEDV/CH/XK/2020 and XJ1904-34 strains. These findings highlight the extensive genetic variation in the predominant GIIa genotype of PEDV in Xinjiang, which does not match the genotype of the currently used vaccine strains. These data may guide further efforts toward the development of effective vaccines for the control of PED.

Spatiotemporal distribution of climate-sensitive disease incidences in ethiopia: a longitudinal retrospective analysis of Malaria, Meningitis, Cholera, Dysentery, Leishmaniasis and Dengue fever between 2010 and 2022/2023.

BACKGROUND: Understanding the temporal and geographic distribution of disease incidences is crucial for effective public health planning and intervention strategies. This study presents a comprehensive analysis of the spatiotemporal distribution of disease incidences in Ethiopia, focusing on six major diseases: Malaria, Meningitis, Cholera and Dysentery, over the period from 2010 to 2022, whereas Dengue Fever and Leishmaniasis from 2018 to 2023. METHODS: Using data from Ethiopian public health institute: public health emergency management (PHEM), and Ministry of Health, we examined the occurrence and spread of each disease across different regions of Ethiopia. Spatial mapping and time series analysis were employed to identify hotspots, trends, and seasonal variations in disease incidence. RESULTS: The findings reveal distinct patterns for each disease, with varying cases and temporal dynamics. Monthly wise, Malaria exhibits a cyclical pattern with a peak during the rainy and humid season, while Dysentery, Meningitis and Cholera displays intermittent incidences. Dysentery cases show a consistent presence throughout the years, while Meningitis remains relatively low in frequency but poses a potential threat due to its severity. Dengue fever predominantly occurs in the eastern parts of Ethiopia. A significant surge in reported incident cases occurred during the years 2010 to 2013, primarily concentrated in the Amhara, Sidama, Oromia, Dire Dawa, and Benishangul-Gumuz regions. CONCLUSIONS: This study helps to a better understanding of disease epidemiology in Ethiopia and can serve as a foundation for evidence-based decision-making in disease prevention and control. By recognizing the patterns and seasonal changes associated with each disease, health authorities can implement proactive measures to mitigate the impact of outbreaks and safeguard public health in the region.

[Pathological profile of S.P. Botkin infectious hospital during the siege of Leningrad (1941-1944)]. / Patologo-anatomicheskii profil' infektsionnoi bol'nitsy im. S.P. Botkina v gody blokady Leningrada (1941­1944 gg.).

The results of autopsies performed in the pathological department of the Infectious Diseases Hospital named after. S.P. Botkin during the siege of Leningrad (from September 8, 1941 to January 27, 1944). The structure of diseases of the deceased varied during different periods of the siege of Leningrad. In the first period (September-December 1941), diphtheria, dysentery, measles, typhoid fever, and scarlet fever prevailed among the diseases. The most common causes of death in the second period (April-December 1942) were typhus, dysentery, tuberculosis, lobar pneumonia, and typhoid fever. Nosological structure in the third period of the blockade (January 1943 - January 1944): tuberculosis, dysentery, cachexia, lobar pneumonia, infectious jaundice. The discrepancy between clinical and morphological diagnoses is most often noted for the following nosology: pulmonary tuberculosis, typhoid fever, pneumonia, stomach and hepatopancreatobiliary cancer, measles, influenza. The first period of the blockade was distinguished by a high specific proportion of examination of children's bodies - 51.2% of all autopsies; in subsequent periods, the specific share of autopsies of deceased adults (20-59 years) increased to 76.2%. The difference in the nosological structure and age groups of those who died during different periods of the siege of Leningrad was determined by the epidemiological situation in the city, social and living conditions and medical and organizational factors. Conducted in the pathological-anatomical department of the hospital named after. S.P. Botkin during the siege of Leningrad, pathological studies made it possible to timely establish the causes of deaths and identify the peculiarities of the course of infectious diseases against the background of cachexia. Regularly held clinical and anatomical conferences contributed to the reduction of defects in the diagnosis and treatment of infectious diseases.

Etiology, Presentation, and Risk Factors for Diarrheal Syndromes in 3 Sub-Saharan African Countries After the Introduction of Rotavirus Vaccines From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: Diarrheal disease is heterogeneous, including watery diarrhea (WD) and dysentery, some cases of which become persistent diarrhea (PD). Changes in risk over time necessitate updated knowledge of these syndromes in sub-Saharan Africa. METHODS: The Vaccine Impact on Diarrhea in Africa (VIDA) study was an age-stratified, case-control study of moderate-to-severe diarrhea among children <5 years old in The Gambia, Mali, and Kenya (2015-2018). We analyzed cases with follow-up of about 60 days after enrollment to detect PD (lasting ≥14 days), examined the features of WD and dysentery, and examined determinants for progression to and sequelae from PD. Data were compared with those from the Global Enteric Multicenter Study (GEMS) to detect temporal changes. Etiology was assessed from stool samples using pathogen attributable fractions (AFs), and predictors were assessed using χ2 tests or multivariate regression, where appropriate. RESULTS: Among 4606 children with moderate-to-severe diarrhea, 3895 (84.6%) had WD and 711 (15.4%) had dysentery. PD was more frequent among infants (11.3%) than in children 12-23 months (9.9%) or 24-59 months (7.3%), P = .001 and higher in Kenya (15.5%) than in The Gambia (9.3%) or Mali (4.3%), P < .001; the frequencies were similar among children with WD (9.7%) and those with dysentery (9.4%). Compared to children not treated with antibiotics, those who received antibiotics had a lower frequency of PD overall (7.4% vs 10.1%, P = .01), and particularly among those with WD (6.3% vs 10.0%; P = .01) but not among children with dysentery (8.5% vs 11.0%; P = .27). For those with watery PD, Cryptosporidium and norovirus had the highest AFs among infants (0.16 and 0.12, respectively), while Shigella had the highest AF (0.25) in older children. The odds of PD decreased significantly over time in Mali and Kenya while increasing significantly in The Gambia. CONCLUSIONS: The burden of PD endures in sub-Saharan Africa, with nearly 10% of episodes of WD and dysentery becoming persistent.

Burden of diarrhea and antibiotic use among children in low-resource settings preventable by Shigella vaccination: A simulation study.

BACKGROUND: Shigella is a leading cause of diarrhea and dysentery in children in low-resource settings, which is frequently treated with antibiotics. The primary goal of a Shigella vaccine would be to reduce mortality and morbidity associated with Shigella diarrhea. However, ancillary benefits could include reducing antibiotic use and antibiotic exposures for bystander pathogens carried at the time of treatment, specifically for fluoroquinolones and macrolides (F/M), which are the recommended drug classes to treat dysentery. The aim of the study was to quantify the reduction in Shigella attributable diarrhea, all diarrhea, and antibiotic use in the first 2 years of life that could be prevented by a Shigella vaccine. METHODS AND FINDINGS: We used data from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, a birth cohort study that followed 1,715 children with twice weekly surveillance for enteric infections, illnesses, and antibiotic use for the first 2 years of life from November 2009 to February 2014 at 8 sites. We estimated the impact of 2 one-dose (6 or 9 months) and 3 two-dose (6 and 9 months, 9 and 12 months, and 12 and 15 months) Shigella vaccines on diarrheal episodes, overall antibiotic use, and F/M use. Further, we considered additional protection through indirect and boosting effects. We used Monte Carlo simulations to estimate the absolute and relative reductions in the incidence of diarrhea and antibiotic use comparing each vaccination scenario to no vaccination. We analyzed 9,392 diarrhea episodes and 15,697 antibiotic courses among 1,715 children in the MAL-ED birth cohort study. There were 273.8 diarrhea episodes, 30.6 shigellosis episodes, and 457.6 antibiotic courses per 100 child-years. A Shigella vaccine with a mean vaccine efficacy of 60% against severe disease given at 9 and 12 months prevented 10.6 (95% CI [9.5, 11.5]) Shigella diarrhea episodes of any severity per 100 child-years (relative 34.5% reduction), 3.0 (95% CI [2.5, 3.5]) F/M courses for Shigella treatment per 100 child-years (relative 35.8% reduction), and 5.6 (95% CI [5.0, 6.3]) antibiotic courses of any drug class for Shigella treatment per 100 child-years (relative 34.5% reduction). This translated to a relative 3.8% reduction in all diarrhea, a relative 2.8% reduction in all F/M courses, a relative 3.1% reduction in F/M exposures to bystander pathogens, and a relative 0.9% reduction in all antibiotic courses. These results reflect Shigella incidence and antibiotic use patterns at the 8 MAL-ED sites and may not be generalizable to all low-resource settings. CONCLUSIONS: Our simulation results suggest that a Shigella vaccine meeting WHO targets for efficacy could prevent about a third of Shigella diarrhea episodes, antibiotic use to treat shigellosis, and bystander exposures due to shigellosis treatment. However, the reductions in overall diarrhea episodes and antibiotic use are expected to be modest (<5%).

Porcine intestinal glycosphingolipids recognized by Brachyspira hyodysenteriae.

Swine dysentery caused by Brachyspira hyodysenteriae is a disease present worldwide with an important economic impact on the farming business, resulting in an increased use of antibiotics. In the present study, we investigated the binding of B. hyodysenteriae to glycosphingolipids from porcine small intestinal epithelium in order to determine the glycosphingolipids involved in B. hyodysenteriae adhesion. Specific interactions between B. hyodysenteriae and two non-acid glycosphingolipids were obtained. These binding-active glycosphingolipids, were characterized by mass spectrometry as lactotetraosylceramide (Galß3GlcNAcß3Galß4Glcß1Cer) and the B5 glycosphingolipid (Galα3Galß4GlcNAcß3Galß4Glcß1Cer). Comparative binding studies using structurally related reference glycosphingolipids showed that B. hyodysenteriae binding to lactotetraosylceramide required an unsubstituted terminal Galß3GlcNAc sequence, while for binding to the B5 pentaosylceramide the terminal Galα3Galß4GlcNAc sequence is the minimum element recognized by the bacteria. Binding of Griffonia simplicifolia IB4 lectin to pig colon tissue sections from healthy control pig and B. hyodysenteriae infected pigs showed that in the healthy pigs the Galα3Gal epitope was mainly present in the lamina propria. In contrast, in four out of five pigs with swine dysentery there was an increased expression of Galα3Gal in the goblet cells and in the colonic crypts, where B. hyodysenteriae also was present. The one pig that had recovered by the time of necropsy had the Galα3Gal epitope only in the lamina propria. These data are consistent with a model where a transient increase in the carbohydrate sequence recognized by the bacteria occur in colonic mucins during B. hyodysenteriae infection, suggesting that the mucins may act as decoys contributing to clearance of the infection. These findings may lead to novel strategies for treatment of B. hyodysenteriae induced swine dysentery.

Prevalence of bovine coronavirus in cattle in China: A systematic review and meta-analysis.

Bovine coronavirus (BCoV) is one of the important pathogens that cause calf diarrhea (CD), winter dysentery (WD), and the bovine respiratory disease complex (BRDC), and spreads worldwide. An infection of BCoV in cattle can lead to death of young animals, stunted growth, reduced milk production, and milk quality, thus bringing serious economic losses to the bovine industry. Therefore, it is necessary to prevent and control the spread of BCoV. Here, a systematic review and meta-analysis was conducted to assess the prevalence of BCoV in cattle in China before 2022. A total of 57 articles regarding the prevalence of BCoV in cattle in China were collected from five databases (PubMed, ScienceDirect, CNKI, VIP, and Wan Fang). Based on the inclusion criteria, a total of 15,838 samples were included, and 6,136 were positive cases. The overall prevalence of BCoV was 30.8%, with the highest prevalence rate (60.5%) identified in South China and the lowest prevalence (15.6%) identified in Central China. We also analyzed other subgroup information, included sampling years, sample sources, detection methods, breeding methods, age, type of cattle, presence of diarrhea, and geographic and climatic factors. The results indicated that BCoV was widely prevalent in China. Among all subgroups, the sample sources, detection methods, breeding methods, and presence or absence of diarrheal might be potential risk factors responsible for BCoV prevalence. It is recommended to strengthen the detection of BCoV in cattle, in order to effectively control the spread of BCoV.

Insights and progress on epidemic characteristics, genotyping, and preventive measures of PEDV in China: A review.

Porcine Epidemic Diarrhoea (PED) is an acute, extremely infectious intestinal disease of pigs caused by the Porcine Epidemic Diarrhoea Virus (PEDV). The virus can affect pigs of all breeds and age groups and shows varying degrees of symptoms, with piglets, in particular, being infected with mortality rates of up to 100%. PEDV was first identified in China in the 1980s and in October 2010 a large-scale PED outbreak caused by a variant of PEDV occurred in China, resulting in huge economic losses. Initially, vaccination can effectively prevent the classical strain, but since December 2010, the PEDV variant has caused "persistent diarrhoea" with severe vomiting, watery diarrhoea, and high morbidity and mortality in newborn piglets as the dominant clinical features, with a significant increase in morbidity and mortality. This indicates that PEDV strains have mutated during evolution and that traditional vaccines no longer provide effective cross-immune protection, so it is necessary to optimize immunization programs and find effective treatments through epidemiological surveys of PEDV to reduce the economic losses caused by infections with mutated strains. This article reviews the progress of research on the aetiology, epidemiological characteristics, genotyping, pathogenesis, transmission routes, and comprehensive control of PEDV infection in China.

Improving the consistency of experimental swine dysentery inoculation strategies.

Swine dysentery (SD) caused by pathogenic Brachyspira spp. is an economic challenge for the swine industry. In research settings, experimental reproduction of swine dysentery typically relies on intragastric inoculation which has shown variable success. This project aimed to improve the consistency of the experimental inoculation protocol used for swine dysentery in our laboratory. Over six experiments, we evaluated the influence of group housing in inoculated pigs using a frozen-thawed broth culture of strongly hemolytic B. hyodysenteriae strain D19 (Trial A), compared the relative virulence of B. hyodysenteriae strains D19 and G44 (Trial B), compared inoculum volumes (50 mL vs 100 mL) for G44 and B. hampsonii 30446 (Trial C), and performed three independent trials evaluating intragastric inoculation using different oral inoculation methods: oral feed balls (Trial D), and oral syringe bolus of 100 mL (Trial E) or 300 mL (Trial F). Intragastric inoculation with a fresh broth culture of B. hyodysenteriae strain G44 resulted in a shorter incubation period and a higher proportionate duration of mucohemorrhagic diarrhea (MMHD) compared to D19. Intragastric inoculation with either 50 or 100 mL of B. hampsonii 30446 or B. hyodysenteriae (G44) were statistically equivalent. Oral inoculation with 100 mL or 300 mL also yielded similar results to intragastric inoculation but was more expensive due to the additional work and supplies associated with syringe training. Our future research will use intragastric inoculation with 100 mL of a fresh broth culture containing B. hyodysenteriae strain G44 as it yields a high incidence of mucohaemorrhagic diarrhea with a reasonable cost.

Vitamin D3 supplementation as an adjunct in the management of childhood infectious diarrhea: a systematic review.

BACKGROUND: Some studies have reported the possible role of vitamin D3 in ameliorating disease outcomes in childhood infectious diarrhea. However, findings about its effectiveness and the association of serum vitamin D levels with diarrhea risk appear inconsistent. We aimed to determine the efficacy of oral vitamin D3 as an adjunct in managing childhood infectious diarrhea and the relationship between vitamin D status and the disease. METHODS: We searched the PubMed and Google Scholar electronic databases for relevant articles without limiting their year of publication. We selected primary studies that met the review's inclusion criteria, screened their titles and abstracts, and removed duplicates. We extracted data items from selected studies using a structured data-extraction form. We conducted a quality assessment of randomized controlled trials (RCTs) and non-randomized studies with the Cochrane collaboration tool and the Newcastle Ottawa Scale, respectively. We assessed the strength of the relationship between serum vitamin D levels and diarrhea using the correlation model. We estimated the I2 and tau2 values to assess between-study heterogeneity. RESULTS: Nine full-text articles were selected, consisting of one RCT, three cross-sectional studies, two cohort studies, two longitudinal/prospective studies, and one case-control study. A total of 5,545 participants were evaluated in the nine studies. Six non-randomized studies provided weak evidence of the relationship between vitamin D levels and diarrhea risk as there was no correlation between the two variables. The only RCT failed to demonstrate any beneficial role of vitamin D3 in reducing the risk of recurrent diarrhea. The calculated I2 and tau2 values of 86.5% and 0.03, respectively suggested a high between-study heterogeneity which precluded a meta-analysis of study results. CONCLUSION: Oral vitamin D3 may not be an effective adjunct in managing childhood infectious diarrhea. Additionally, the relationship between vitamin D status and infectious diarrhea appears weak. We recommend more adequately-powered RCTs to determine the effectiveness of vitamin D3 as an adjunct therapy in infectious diarrhea.

Giardia duodenalis and dysentery in Iron Age Jerusalem (7th-6th century BCE).

The aim of this study was to determine if the protozoa that cause dysentery might have been present in Jerusalem, the capital of the Kingdom of Judah, during the Iron Age. Sediments from 2 latrines pertaining to this time period were obtained, 1 dating from the 7th century BCE and another from the 7th to early 6th century BCE. Microscopic investigations have previously shown that the users were infected by whipworm (Trichuris trichiura), roundworm (Ascaris lumbricoides), Taenia sp. tapeworm and pinworm (Enterobius vermicularis). However, the protozoa that cause dysentery are fragile and do not survive well in ancient samples in a form recognizable using light microscopy. Enzyme-linked immunosorbent assay kits designed to detect the antigens of Entamoeba histolytica, Cryptosporidium sp. and Giardia duodenalis were used. Results for Entamoeba and Cryptosporidium were negative, while Giardia was positive for both latrine sediments when the analysis was repeated three times. This provides our first microbiological evidence for infective diarrhoeal illnesses that would have affected the populations of the ancient near east. When we integrate descriptions from 2nd and 1st millennium BCE Mesopotamian medical texts, it seems likely that outbreaks of dysentery due to giardiasis may have caused ill health throughout early towns across the region.

Interventions to improve sanitation for preventing diarrhoea.

BACKGROUND: Diarrhoea is a major contributor to the global disease burden, particularly amongst children under five years in low- and middle-income countries (LMICs). As many of the infectious agents associated with diarrhoea are transmitted through faeces, sanitation interventions to safely contain and manage human faeces have the potential to reduce exposure and diarrhoeal disease. OBJECTIVES: To assess the effectiveness of sanitation interventions for preventing diarrhoeal disease, alone or in combination with other WASH interventions. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and Chinese language databases available under the China National Knowledge Infrastructure (CNKI-CAJ). We also searched the metaRegister of Controlled Trials (mRCT) and conference proceedings, contacted researchers, and searched references of included studies. The last search date was 16 February 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-RCTs, non-randomized controlled trials (NRCTs), controlled before-and-after studies (CBAs), and matched cohort studies of interventions aimed at introducing or expanding the coverage and/or use of sanitation facilities in children and adults in any country or population. Our primary outcome of interest was diarrhoea and secondary outcomes included dysentery (bloody diarrhoea), persistent diarrhoea, hospital or clinical visits for diarrhoea, mortality, and adverse events. We included sanitation interventions whether they were conducted independently or in combination with other interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligible studies, extracted relevant data, assessed risk of bias, and assessed the certainty of evidence using the GRADE approach. We used meta-analyses to estimate pooled measures of effect, described results narratively, and investigated potential sources of heterogeneity using subgroup analyses. MAIN RESULTS: Fifty-one studies met our inclusion criteria, with a total of 238,535 participants. Of these, 50 studies had sufficient information to be included in quantitative meta-analysis, including 17 cluster-RCTs and 33 studies with non-randomized study designs (20 NRCTs, one CBA, and 12 matched cohort studies). Most were conducted in LMICs and 86% were conducted in whole or part in rural areas. Studies covered three broad types of interventions: (1) providing access to any sanitation facility to participants without existing access practising open defecation, (2) improving participants' existing sanitation facility, or (3) behaviour change messaging to improve sanitation access or practices without providing hardware or subsidy, although many studies overlapped multiple categories. There was substantial heterogeneity amongst individual study results for all types of interventions. Providing access to any sanitation facility Providing access to sanitation facilities was evaluated in seven cluster-RCTs, and may reduce diarrhoea prevalence in all age groups (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.73 to 1.08; 7 trials, 40,129 participants, low-certainty evidence). In children under five years, access may have little or no effect on diarrhoea prevalence (RR 0.98, 95% CI 0.83 to 1.16, 4 trials, 16,215 participants, low-certainty evidence). Additional analysis in non-randomized studies was generally consistent with these findings. Pooled estimates across randomized and non-randomized studies provided similar protective estimates (all ages: RR 0.79, 95% CI 0.66 to 0.94; 15 studies, 73,511 participants; children < 5 years: RR 0.83, 95% CI 0.68 to 1.02; 11 studies, 25,614 participants).  Sanitation facility improvement Interventions designed to improve existing sanitation facilities were evaluated in three cluster-RCTs in children under five and may reduce diarrhoea prevalence (RR 0.85, 95% CI 0.69 to 1.06; 3 trials, 14,900 participants, low-certainty evidence). However, some of these interventions, such as sewerage connection, are not easily randomized. Non-randomized studies across participants of all ages provided estimates that improving sanitation facilities may reduce diarrhoea, but may be subject to confounding (RR 0.61, 95% CI 0.50 to 0.74; 23 studies, 117,639 participants, low-certainty evidence). Pooled estimates across randomized and non-randomized studies provided similar protective estimates (all ages: RR 0.65, 95% CI 0.55 to 0.78; 26 studies, 132,539 participants; children < 5 years: RR 0.70, 95% CI 0.54 to 0.91, 12 studies, 23,353 participants).  Behaviour change messaging only (no hardware or subsidy provided) Strategies to promote behaviour change to construct, upgrade, or use sanitation facilities were evaluated in seven cluster-RCTs in children under five, and probably reduce diarrhoea prevalence (RR 0.82, 95% CI 0.69 to 0.98; 7 studies, 28,909 participants, moderate-certainty evidence). Additional analysis from two non-randomized studies found no effect, though with very high uncertainty. Pooled estimates across randomized and non-randomized studies provided similar protective estimates (RR 0.85, 95% CI 0.73 to 1.01; 9 studies, 31,080 participants). No studies measured the effects of this type of intervention in older populations.  Any sanitation intervention A pooled analysis of cluster-RCTs across all sanitation interventions demonstrated that the interventions may reduce diarrhoea prevalence in all ages (RR 0.85, 95% CI 0.76 to 0.95, 17 trials, 83,938 participants, low-certainty evidence) and children under five (RR 0.87, 95% CI 0.77 to 0.97; 14 trials, 60,024 participants, low-certainty evidence). Non-randomized comparisons also demonstrated a protective effect, but may be subject to confounding. Pooled estimates across randomized and non-randomized studies provided similar protective estimates (all ages: RR 0.74, 95% CI 0.67 to 0.82; 50 studies, 237,130 participants; children < 5 years: RR 0.80, 95% CI 0.71 to 0.89; 32 studies, 80,047 participants). In subgroup analysis, there was some evidence of larger effects in studies with increased coverage amongst all participants (75% or higher coverage levels) and also some evidence that the effect decreased over longer follow-up times for children under five years. There was limited evidence on other outcomes. However, there was some evidence that any sanitation intervention was protective against dysentery (RR 0.74, 95% CI 0.54 to 1.00; 5 studies, 34,025 participants) and persistent diarrhoea (RR 0.57, 95% CI 0.43 to 0.75; 2 studies, 2665 participants), but not against clinic visits for diarrhoea (RR 0.86, 95% CI 0.44 to 1.67; 2 studies, 3720 participants) or all-cause mortality (RR 0.99, 95% CI 0.89 to1.09; 7 studies, 46,123 participants). AUTHORS' CONCLUSIONS: There is evidence that sanitation interventions are effective at preventing diarrhoea, both for young children and all age populations. The actual level of effectiveness, however, varies by type of intervention and setting. There is a need for research to better understand the factors that influence effectiveness.

Spatio-temporal pattern and associate factors of intestinal infectious diseases in Zhejiang Province, China, 2008-2021: a Bayesian modeling study.

BACKGROUND: Despite significant progress in sanitation status and public health awareness, intestinal infectious diseases (IID) have caused a serious disease burden in China. Little was known about the spatio-temporal pattern of IID at the county level in Zhejiang. Therefore, a spatio-temporal modelling study to identify high-risk regions of IID incidence and potential risk factors was conducted. METHODS: Reported cases of notifiable IID from 2008 to 2021 were obtained from the China Information System for Disease Control and Prevention. Moran's I index and the local indicators of spatial association (LISA) were calculated using Geoda software to identify the spatial autocorrelation and high-risk areas of IID incidence. Bayesian hierarchical model was used to explore socioeconomic and climate factors affecting IID incidence inequities from spatial and temporal perspectives. RESULTS: From 2008 to 2021, a total of 101 cholera, 55,298 bacterial dysentery, 131 amoebic dysentery, 5297 typhoid, 2102 paratyphoid, 27,947 HEV, 1,695,925 hand, foot and mouth disease (HFMD), and 1,505,797 other infectious diarrhea (OID) cases were reported in Zhejiang Province. The hot spots for bacterial dysentery, OID, and HEV incidence were found mainly in Hangzhou, while high-high cluster regions for incidence of enteric fever and HFMD were mainly located in Ningbo. The Bayesian model showed that Areas with a high proportion of males had a lower risk of BD and enteric fever. People under the age of 18 may have a higher risk of IID. High urbanization rate was a protective factor against HFMD (RR = 0.91, 95% CI: 0.88, 0.94), but was a risk factor for HEV (RR = 1.06, 95% CI: 1.01-1.10). BD risk (RR = 1.14, 95% CI: 1.10-1.18) and enteric fever risk (RR = 1.18, 95% CI:1.10-1.27) seemed higher in areas with high GDP per capita. The greater the population density, the higher the risk of BD (RR = 1.29, 95% CI: 1.23-1.36), enteric fever (RR = 1.12, 95% CI: 1.00-1.25), and HEV (RR = 1.15, 95% CI: 1.09-1.21). Among climate variables, higher temperature was associated with a higher risk of BD (RR = 1.32, 95% CI: 1.23-1.41), enteric fever (RR = 1.41, 95% CI: 1.33-1.50), and HFMD (RR = 1.22, 95% CI: 1.08-1.38), and with lower risk of HEV (RR = 0.83, 95% CI: 0.78-0.89). Precipitation was positively correlated with enteric fever (RR = 1.04, 95% CI: 1.00-1.08), HFMD (RR = 1.03, 95% CI: 1.00-1.06), and HEV (RR = 1.05, 95% CI: 1.03-1.08). Higher HFMD risk was also associated with increasing relative humidity (RR = 1.20, 95% CI: 1.16-1.24) and lower wind velocity (RR = 0.88, 95% CI: 0.84-0.92). CONCLUSIONS: There was significant spatial clustering of IID incidence in Zhejiang Province from 2008 to 2021. Spatio-temporal patterns of IID risk could be largely explained by socioeconomic and meteorological factors. Preventive measures and enhanced monitoring should be taken in some high-risk counties in Hangzhou city and Ningbo city.

Bacterial resistance to commonly prescribed antibiotics was rare among children hospitalised for clinical dysentery.

AIM: Temporal changes in common pathogens that cause clinical dysentery have been described in Europe. We aimed to describe the distribution of pathogens and their antibiotic resistance in hospitalised Israeli children. METHODS: This study retrospectively studied children hospitalised for clinical dysentery, with or without a positive stool culture, from 1 January 2016 to 31 December 2019. RESULTS: We diagnosed 137 patients (65% males), with clinical dysentery at a median age of 3.7 (interquartile range 1.5-8.2) years. Stools were cultured in 135 patients (99%), and the results were positive in 101 (76%). These comprised Campylobacter (44%), Shigella sonnei (27%), non-typhoid Salmonella (18%) and enteropathogenic Escherichia coli (12%). Only one of the 44 Campylobacter cultures was resistant to erythromycin and one of the 12 enteropathogenic Escherichia coli cultures was resistant to ceftriaxone. None of the Salmonella and Shigella cultures were resistant to ceftriaxone or erythromycin. We did not find any pathogens that were associated with a typical clinical presentation or laboratory results on admission. CONCLUSION: The most common pathogen was Campylobacter, in line with recent European trends. Bacterial resistance for commonly prescribed antibiotics was rare, and these findings support the current European recommendations.

Impact of insertion sequences on convergent evolution of Shigella species.

Shigella species are specialised lineages of Escherichia coli that have converged to become human-adapted and cause dysentery by invading human gut epithelial cells. Most studies of Shigella evolution have been restricted to comparisons of single representatives of each species; and population genomic studies of individual Shigella species have focused on genomic variation caused by single nucleotide variants and ignored the contribution of insertion sequences (IS) which are highly prevalent in Shigella genomes. Here, we investigate the distribution and evolutionary dynamics of IS within populations of Shigella dysenteriae Sd1, Shigella sonnei and Shigella flexneri. We find that five IS (IS1, IS2, IS4, IS600 and IS911) have undergone expansion in all Shigella species, creating substantial strain-to-strain variation within each population and contributing to convergent patterns of functional gene loss within and between species. We find that IS expansion and genome degradation are most advanced in S. dysenteriae and least advanced in S. sonnei; and using genome-scale models of metabolism we show that Shigella species display convergent loss of core E. coli metabolic capabilities, with S. sonnei and S. flexneri following a similar trajectory of metabolic streamlining to that of S. dysenteriae. This study highlights the importance of IS to the evolution of Shigella and provides a framework for the investigation of IS dynamics and metabolic reduction in other bacterial species.

Antibiotics for Clinical Dysentery in the Pediatric Emergency Department.

BACKGROUND: Clinical dysentery causes hundreds of thousands of deaths annually worldwide. However, current recommendations reserve antibiotics for those either clinically sick or with highly suspected cases of shigellosis. This treatment stems from rising antibiotic resistance. Children diagnosed with clinical dysentery in the pediatric emergency department (PED) are regarded more cautiously. OBJECTIVES: To explore the use of antibiotics in children diagnosed with clinical dysentery in the PED. METHODS: A retrospective case study of children with clinical dysentery at a single PED during the years 2015 and 2018. Demographics as well as clinical findings were compared to culture results and antibiotic treatment. RESULTS: The study included 281 children who were diagnosed with clinical dysentery during the study period; 234 (83%) were treated with antibiotics. However, cultures were positive in only 162 cases (58%). Only 32% were Shigella spp. Younger age, fever, and leukocytosis were related to antibiotic treatment. CONCLUSIONS: The diagnosis of clinical dysentery is misgiven commonly in the PED leading to widespread use of antibiotics when not indicated. This treatment may impact antibiotic resistance patterns. Further studies and interventions are necessary to create clear guidelines in the PED setting.

[Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021].

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

Colonic innate immune defenses and microbiota alterations in acute swine dysentery.

Brachyspira hyodysenteriae, an etiologic agent of swine dysentery (SD), is known for causing colitis. Although some aspects of colonic defenses during infection have been described previously, a more comprehensive picture of the host and microbiota interaction in clinically affected animals is required. This study aimed to characterize multiple aspects of colonic innate defenses and microbiome factors in B. hyodysenteriae-infected pigs that accompany clinical presentation of hemorrhagic diarrhea. We examined colonic mucus barrier modifications, leukocyte infiltration, cathelicidin expression, as well as microbiome composition. We showed that B. hyodysenteriae infection caused microscopic hemorrhagic colitis with abundant neutrophil infiltration in the colonic lamina propria and lumen, with minor macrophage infiltration. Mucus hypersecretion with abundant sialylated mucus in the colon, as well as mucosal colonization by [Acetivibrio] ethanolgignens, Lachnospiraceae, and Campylobacter were pathognomonic of B. hyodysenteriae infection. These findings demonstrate that B. hyodysenteriae produces clinical disease through multiple effects on host defenses, involving alterations of mucosal innate immunity and microbiota. Given that B. hyodysenteriae is increasingly resistant to antimicrobials, this understanding of SD pathogenesis may lead to future development of non-antibiotic and anti-inflammatory alternative therapeutics.