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Background: Sphingomonas paucimobilis is a gram-negative pathogen that causes urinary tract infections, diarrhea, septicemia, and wound infections. Due to the spread of patients with high mortality but low mortality in Sphingomonas paucimobilis, it has been isolated from Sphingomonas paucimobilis in different clinical samples and is increasing antibiotic resistance all over the world. Objectives: The aim of our research was to look at the epidemiology, antibiotic susceptibility series, and pathogenic potential in different clinical samples from Erbil's Rizgary and Raparin hospitals. Materials and Methods: A total of 2582 samples were reviewed from different clinical samples from Rizgary Hospital and Raparin Hospital from male and female, we found 24 Sphingomonas paucimobilis isolates, identified by using microscopical, morphological, biochemical tests and Vitek2 compact system according to the standard protocol against Ampicillin/Sulbactam, Cefazolin, Ceftazidime, Ceftriaxone, Cefepime, Imipenem, Tobramycin, Ciprofloxacin, Levofloxacin, Trimethoprim. using Vitek 2 compact system. Results: 24 total positive results of Sphingomonas paucimobilis isolated from 2582 different clinical samples the highest percentage of Sphingomonas paucimobilis was isolated from female samples (65%) while from male (35%) wen performing antibiotic susceptibility the highest resistance rate was Trimethoprim (66.66%), followed by To bramycin (50%), Ciprofloxacin (50%) and Levofloxacin (41.66%), respectively in contrast the highest effective antibiotic against Sphingomonas paucimobilis was Cefepime (75%), Imipenem (75%), followed by Ceftriaxone (66.66%), Ceftazidime (66.66%), Cefazolin (66.66%), Ampicillin/Sulbactam (66.66%) Conclusion: Morbidity attribute to antibiotic resistance to third generation cephalosporin resistant, Sphingomonas paucimobilis resistant is significant, if prevailing resistance trends continue, high societal and economic costs can be expected. Better management of antibiotic use, and infection control is needed to avoid infections that caused by drug resistant pathogens like Sphingomonas paucimobilis. [ABSTRACT FROM AUTHOR]

Background Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. Methods We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. Results Compared to culture-positive Shigella MSD cases (n = 745), culture-negative/qPCR-attributable Shigella cases (n = 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. Conclusions A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity. [ABSTRACT FROM AUTHOR]

Multiple factors contribute to variation in disease burden, including the type and quality of data, and inherent properties of the models used. Understanding how these factors affect mortality estimates is crucial, especially in the context of public health decision making. We examine how the quality of the studies selected to provide mortality data, influence estimates of burden and provide recommendations about the inclusion of studies and datasets to calculate mortality estimates. To determine how mortality estimates are affected by the data used to generate model outputs, we compared the studies used by The Institute of Health Metrics and Evaluation (IHME) and Maternal and Child Epidemiology Estimation (MCEE) modelling groups to generate enterotoxigenic Escherichia coli (ETEC) and Shigella -associated mortality estimates for 2016. Guided by an expert WHO Working Group, we applied a modified Newcastle-Ottawa Scale (NOS) to evaluate the quality of studies used by both modelling groups. IHME and MCEE used different sets of ETEC and Shigella studies in their models and the majority of studies were high quality. The distribution of the NOS scores was similar between the two modelling groups. We observed an overrepresentation of studies from some countries in SEAR, AFR and WPR compared to other WHO regions. We identified key differences in study inclusion and exclusion criteria used by IHME and MCEE and discuss their impact on datasets used to generate diarrhoea-associated mortality estimates. Based on these observations, we provide a set of recommendations for future estimates of mortality associated with enteric diseases. [ABSTRACT FROM AUTHOR]

Background: The natural hosts of Shigella are typically humans and other primates, but it has been shown that the host range of Shigella has expanded to many animals. Although Shigella is becoming a major threat to animals, there is limited information on the genetic background of local strains. The purpose of this study was to assess the presence of virulence factors and the molecular characteristics of S. flexneri isolated from calves with diarrhea. Results: Fifty-four S. flexneri isolates from Gansun, Shanxi, Qinghai, Xinjiang and Tibet obtained during 2014 to 2016 possessed four typical biochemical characteristics of Shigella. The prevalences of ipaH, virA, ipaBCD, ial, sen, set1A, set1B and stx were 100 %, 100 %, 77.78 %, 79.63 %, 48.15 %, 48.15 and 0 %, respectively. Multilocus variable number tandem repeat analysis (MLVA) based on 8 variable number of tandem repeat (VNTR) loci discriminated the isolates into 39 different MLVA types (MTs), pulsed field gel electrophoresis (PFGE) based on NotI digestion divided the 54 isolates into 31 PFGE types (PTs), and multilocus sequence typing (MLST) based on 15 housekeeping genes differentiated the isolates into 7 MLST sequence types (STs). Conclusions: The findings from this study enrich our knowledge of the molecular characteristics of S. flexneri collected from calves with diarrhea, which will be important for addressing clinical and epidemiological issues regarding shigellosis. [ABSTRACT FROM AUTHOR]

Background This study aimed to identify enteric and sexually acquired rectal pathogens, other than chlamydia and gonorrhea, associated with symptomatic proctitis in men who have sex with men (MSM). Methods Anorectal swab samples were obtained from MSM presenting with rectal symptoms and a clinical diagnosis of proctitis at the Melbourne Sexual Health Centre between January 2017 and March 2019. Samples that tested positive for Neisseria gonorrhoeae and Chlamydia trachomatis were excluded. As a comparison group, anorectal samples were also obtained from MSM not reporting symptoms of proctitis between November 2018 and February 2019. Samples from both groups were tested for 15 viral, bacterial, and protozoal enteric pathogens using polymerase chain reaction. Results Anorectal samples from 499 men with symptomatic proctitis and 506 asymptomatic men were analyzed. Age, HIV status, and pre-exposure prophylaxis (PrEP) use did not differ between men with proctitis and asymptomatic men. Treponema pallidum was more common in men with proctitis (risk difference [RD], 3.6%; 95% CI, 2.0%–5.2%). Most men with anorectal T. pallidum presented with painful anal primary infections. Shigella spp. was more common among men with proctitis compared with asymptomatic men (RD, 1.8%; 95% CI, 0.1%–3.5%). Most men with Shigella did not report diarrhea. Mycoplasma genitalium was more common in men with proctitis (RD, 4.3%; 95% CI, 1.1%–7.5%). Herpes simplex virus (HSV)–1 (RD, 10.1%; 95% CI, 6.8%–13.3%) and HSV-2 (RD, 7.2%; 95% CI, 4.5%–10.0%) were more common with proctitis. Conclusions Testing for T. pallidum , Shigella , and HSV should be considered in MSM presenting with symptomatic proctitis. These data provide support for M. genitalium as a significant cause of proctitis. A comprehensive diagnostic evaluation is required for MSM with proctitis. [ABSTRACT FROM AUTHOR]

The association between floods and the risk of dysentery remain controversial. Therefore, we performed a meta-analysis to clarify this relationship. A literature search was performed in PubMed, Web of science, and Embase for relevant articles published up to November 2019. Random-effects model was used to pool relative risks with 95% confidence intervals. The sensitivity analysis was carried out to evaluate the stability of the results. Publication bias was estimated using Egger's test. Eleven studies from 10 articles evaluated the association between floods and the risk of dysentery in China. The pooled RR (95% CI) of dysentery for the flooded time versus non-flooded period was 1.48 (95% CI: 1.14–1.91). Significant association was found in subgroup analysis stratified by dysentery styles [dysentery: 1.61 (95% CI: 1.34–1.93) and bacillary dysentery: 1.46 (95% CI: 1.06–2.01)]. The pooled RR (95%CI) of sensitivity analysis for dysentery was 1.26 (95% CI: 1.05–1.52). No significant publication bias was found in our meta-analysis. This meta-analysis confirms that floods have significantly increased the risk of dysentery in China. Our findings will provide more evidence to reduce negative health outcomes of floods in China. [ABSTRACT FROM AUTHOR]

Shigellosis, a diarrheal disorder caused by an entero-invasive bacterium Shigella , is a major concern among children often leading to mortality. As most of these strains have developed universal antibiotic resistance, the development of a vaccine is crucial in combating the infection. The O-specific polysaccharide (O-PSs) from S. flexneri type 2a is considered to be the major disease-causing antigen in shigellosis. Therefore, the O-PSs conjugated with carrier proteins, can serve as a potential high molecular weight vaccine candidate. Accordingly, in the present study, O-PS extracted from S. flexneri 2a is conjugated with Cross-Reactive Material (CRM 197), a non-toxic mutant of diphtheria toxin. We derivatized CRM 197 and O-PS separately with adipic acid dihydrazide (ADH) and reacted with their counterparts to probe the conjugation efficacy. Among the two strategies, the CRM 197 -ADH treated with O-PS has yielded a stable glycoconjugate of 311 kDa. The conjugation efficiency has been probed by estimating the free protein, free O-PS and O-PS:CRM 197 ratio using slot-blot, size exclusion and high-performance anion exchange chromatography techniques. The conjugate exhibited enhanced shelf-life of three months. The cytotoxicity studies with Vero/MRC-5 cells have confirmed the non-toxicity of the conjugate, which makes the glycoconjugate a potential vaccine candidate for shigellosis. • CRM 197 - S. flexneri O-PS conjugate as a potential vaccine candidate for shigellosis. • ADH was used to separately activate CRM 197 and O-PS for efficient conjugation. • ADH-CRM 197 + O-PS conjugate yielded a high molecular weight immunogen (>300 kDa). • The glycoconjugate exhibited sustained shelf-life of over three months. [ABSTRACT FROM AUTHOR]

Background Shigella infections are an important cause of diarrhea in young children and can result in severe complications. Disparities in Shigella infections are well documented among US adults. Our objective was to characterize disparities in incidence and severity of Shigella infections among US children. Methods We analyzed laboratory-diagnosed Shigella infections reported to FoodNet, an active, population-based surveillance system in 10 US sites, among children during 2009-2018. We calculated the incidence rate stratified by sex, age, race/ethnicity, Shigella species, and disease severity. Criteria for severe classification were hospitalization, bacteremia, or death. The odds of severe infection were calculated using logistic regression. Results During 2009-2018, 10 537 Shigella infections were reported in children and 1472 (14.0%) were severe. The incidence rate was 9.5 infections per 100 000 child-years and the incidence rate of severe infections was 1.3 per 100 000 child-years. Incidence was highest among children aged 1-4 years (19.5) and lowest among children aged 13-17 years (2.3); however, children aged 13-17 years had the greatest proportion of severe infections (21.2%). Incidence was highest among Black (16.2 total; 2.3 severe), Hispanic (13.1 total; 2.3 severe), and American Indian/Alaska Native (15.2 total; 2.5 severe) children. Infections caused by non- sonnei species had higher odds of severity than infections caused by Shigella sonnei (adjusted odds ratio 2.58; 95% confidence interval 2.12-3.14). Conclusions The incidence and severity of Shigella infections among US children vary by age, race/ethnicity, and Shigella species, warranting investigation of unique risk factors among pediatric subpopulations. [ABSTRACT FROM AUTHOR]

Background: Shigellosis is a significant public health challenge particularly in developing countries, and the spread of antibiotic resistance genes through integron structures has become an important problem in the treatment of Shigellosis. The aim of this study was to investigate the genetic association of Shigella flexneri antibiotic resistant clones collected from Ahvaz between 2013 and 2015 by pulse field gel electrophoresis (PFGE) method. Methods: A total of 45 S. flexneri isolates, which were resistant to ampicillin and cotrimoxazole, were obtained from patients with Shigellosis referred to Ahvaz hospitals during 2013 - 2015. PCR was performed to evaluate the frequency of Sul1, int1, blaQX4, and int2 genes. In addition, pulse field gel electrophoresis method was used to investigate the genetic relationship between 40 S. flexneri isolates. Results: PCR results showed that the highest frequency was related to the sul1 gene with 80% (36 isolates) and the lowest frequency was related to class 2 integron with 15.5% (7 isolates); 31.11% (14 isolates) of the isolates were sul1 and int1. Also, 13.33% (6 isolates) had blaOXA and int1 genes, simultaneously. But none of the isolates had class 1 integrons and class 2 integrons at the same time. PFGE results showed 25 different pulsotype patterns, of which 16 isolates had their own unique pattern and were divided into 16 pulsotypes, and 27 isolates were divided into 9 pulsotypes. Conclusions: int2 and sul1 resistance genes had an upward trend from 2013 to 2015 and the results of PFGE indicated a different origin of S. flexneri clones. [ABSTRACT FROM AUTHOR]

This study focuses on speciation of air borne microbes in an office building and health impacts of these microbes in terms of Quantitative Microbial Risk Assessment (QMRA), Hazard Quotient (HQ) and Hazard Index (HI). This is important in the wake of Sustainability Development Goal 3 (Public Health and well-being) specially when there is a lack of standards in terms of microbial air quality in office buildings where people spend 8–10 h indoors. Air borne bacterial and fungal species in different floors of the office building with varying occupancy and work profile were identified. The load of bacterial count on an average for the entire building was found to be 1917 CFU/m3. Overall, Gram-positive bacteria were predominant (>53%). Based on V3–V4 sequencing Staphylococcus scuiri (causing UTIs) was the most abundant (93.7%) and other bacterial species found were Lactobacillus hamsteri, Prevotella copri, Bacteroides plebeius Faecalibacterium prausnitzii, Bacillus coagulans (gut commensals), Shigella boydii (causes bacillary dysentery), and Propionibacterium acnes (acne producing). Fungal load was 4000 CFU/m3. Based on ITS sequencing Aspergillus (45.6%) was the dominant fungus and other fungi found were Cunninghamella , Lichtheimia, Fusarium, and Circinella Grammothele , Chondrostereum , and Pseudolagarobasidium , Candida sp., Chondrostereum, Sarocladium. The QMRA of gram-negative air borne bacteria showed a high disease burden, well over the WHO benchmark values even though Hazard Quotient (HQ) and Hazard Index (HI) was found to be negligible. These findings can contribute to the development of guidelines for seemingly safe workplaces that may harbour disease-causing microbes and calls for an immediate attention from policy makers as it is a major cause of concern for public health. [Display omitted] • The quantification and speciation of air-borne bacteria and fungi were done in an office building. • Staphylococcus scuiri and Aspergillus species were found to be dominant. • QMRA of Gram-Negative air-borne bacteria showed a high disease burden. • The Hazard Index (HI) were found to negligible for the building under study. • There is immediate requirement of defining benchmarks on indoor air-borne microorganism. [ABSTRACT FROM AUTHOR]

We compared the Allplex Gastrointestinal V/B1/B2 Assays and Seeplex Diarrhea V/B1/B2 ACE Detection Assays in patients with acute gastroenteritis (AGE). Of the total 432 specimens, 48.8% and 54.9% samples were positive for any bacterial or viral target using Seeplex and Allplex, respectively (P = 0.002). The overall percent agreement (OPA) between the two panels was >95% and the lowest OPA was 95.4% for CdB. Allplex identified 40 samples positive for Salmonella spp. , while Seeplex and OBC identified only 27 (67.5%) and 8 (20%), respectively. Shigella spp. were detected by assays in six samples, but none were identified using culture. Clostridium perfringens with Seeplex was detected in 70 (16.2%). It remained an informative species in identifying AGE although cpe gene showed only 9.8% positivity. Pathogenic Escherichia coli with Allplex could be detected in 40 (9.3%) samples, which could provide valuable information for the diagnosis of AGE. [ABSTRACT FROM AUTHOR]

Abstract Background Shigella spp. and entero-invasive E. coli (EIEC) use the same invasive mechanism to cause diarrheal diseases. Public health regulations apply only to Shigella spp. infections, but are hampered by the lack of simple methods to distinguish them from EIEC. In the last decades, molecular methods for detecting Shigella spp. and EIEC were implemented in medical microbiological laboratories (MMLs). However, shigellosis cases identified with molecular techniques alone are not notifiable in most countries. Our study investigates the impact of EIEC versus Shigella spp. infections and molecular diagnosed shigellosis versus culture confirmed shigellosis for re-examination of the rationale for the current public health regulations. Methods In this multicenter cross-sectional study, fecal samples of patients suspected for gastro-enteritis, referred to 15 MMLs in the Netherlands, were screened by PCR for Shigella spp. or EIEC. Samples were cultured to discriminate between the two pathogens. We compared risk factors, symptoms, severity of disease, secondary infections and socio-economic consequences for (i) culture-confirmed Shigella spp. versus culture-confirmed EIEC cases (ii) culture positive versus PCR positive only shigellosis cases. Results In 2016–2017, 777 PCR positive fecal samples with patient data were included, 254 of these were culture-confirmed shigellosis cases and 32 were culture-confirmed EIEC cases. EIEC cases were more likely to report ingestion of contaminated food and were less likely to be men who have sex with men (MSM). Both pathogens were shown to cause serious disease although differences in specific symptoms were observed. Culture-negative but PCR positive cases were more likely report travel or ingestion of contaminated food and were less likely to be MSM than culture-positive cases. Culture-negative cases were more likely to suffer from multiple symptoms. No differences in degree of secondary infections were observed between Shigella spp. and EIEC, and culture-negative and culture-positive cases. Conclusions No convincing evidence was found to support the current guidelines that employs different measures based on species or detection method. Therefore, culture and molecular detection methods for Shigella spp. and EIEC should be considered equivalent for case definition and public health regulations regarding shigellosis. Differences were found regarding risks factors, indicating that different prevention strategies may be required.

Objective: to study the clinical and laboratory manifestations of acute intestinal infections of bacterial etiology in hospitalized children, depending on the etiology, age, topic of the lesion, and complications.A cohort clinical study of 570 children hospitalized from January to October 2019 in the infectious wards of Children's Clinical Hospital No.9 in Moscow was conducted. Studies included routine laboratory methods, bacteriological analysis of feces, Latex test, ELISA, PCR to detect pathogens, serological reactions to detect specific antibodies in blood serum. Two groups of patients were specially formed to compare the features of the course of bacterial diarrhea without hemorrhagic colitis (n = 111) and with hemorrhagic colitis (n = 125).Among 33.2% of cases of deciphered etiology of bacterial diarrhea, Salmonella was isolated in 14.6%, Campylobacter — in 4.7%, Shigella — in 3%, in other cases — conditionally pathogenic flora. Salmonellosis and Сampylobacteriosis with the same frequency are recorded in children in the age groups of 1—3 and 3—7 years, in half of the patients proceed as enterocolitis (58 and 52%, respectively). Shigellosis is diagnosed in children older than 1 year of life with the same frequency in age groups 1—3, 3—7 and older than 7 years, a third of patients (35%) develop severe forms.In most cases (83.2%), a complicated course of bacterial diarrhea was detected, more often dehydration 1 and 2 degrees (36.5%), acute respiratory viral infections (19.6%), mesadenitis (11.2%), community-acquired pneumonia (4.6%).Enterocolitis is the topic of lesion in half of the children, and every 5th patient develops hemorrhagic colitis (21.9%). In 44% of cases of established etiology of hemorrhagic colitis, Salmonella was confirmed. Hemocolitis also develops more often with shigellosis, campylobacteriosis and clostridiosis. In the group of bacterial diarrhea with hemorrhagic colitis, significant differences were revealed compared with the group without hemocolitis: by the frequency of development in children under 3 years of age; by the duration of treatment in a hospital; by the frequency of mesadenitis; by the content of stab neutrophils in the hemogram, reflecting a more pronounced inflammation in hemorrhagic colitis.Thus, bacterial diarrhea in children remains relevant due to the severity of inflammation, the incidence of complicated course and hemorrhagic colitis, which requires hospitalization.

Background: Shigella flexneri is a pathogen responsible for shigellosis around the world, especially in developing countries. Many immunogenic antigens have been introduced as candidate vaccines against Shigella, including N-terminal region of IpaD antigen (NIpaD). Objective: To evaluate the efficiency of O-metylated free trimethyl chitosan nanoparticles (TMC NPs) in the oral delivery of NIpaD. Methods: TMC was synthesized by a two-step method from high molecular weight chitosan. The recombinant NIpaD protein was used as the immunogen. The protein was overexpressed in E. coli BL21 (DE3) and characterized by gel electrophoresis. The NIpaD-loaded TMC NPs were synthesized by ionic gelation method and were characterized by electron microscopy. NPs were orally administered to guinea pigs and specific humoral and mucosal immune responses were assessed by serum IgG and secretory IgA, respectively. The protectivity of the formulation was assessed by keratoconjunctivitis (Sereny) test. Results: The immunized guinea pigs showed a significant raise in rNIpaD-specific serum IgG and faecal IgA titers. Specific secretory IgA was detected in eye-washes. Sereny test results showed that immunized animals vaccinated with IpaD-loaded TMC NPS tolerated the wild type of Shigella flexneri 2a in Sereny test. However, in the group immunized with NIpaD antigen and non-immunized group, no increase was observed in antibody titer against NIpaD. These animals were infected following the challenge with Shigella flexneri 2a (pConclusion: The recombinant rNIpaD formulated with TMC obtained from high molecular weight chitosan, can be considered as a mucosal vaccine against Shigella flexneri through oral route.

Abstract Background Diarrheal disease still remains a major public health threat and is often associated with fatal outcome especially in children with shigellosis mostly in developing countries. This study aimed to determine the presence of any associations between drinking shallow tube well (STW) water and childhood shigellosis. A total of 1394 children aged 0–59 months who presented with moderate-to-severe diarrhea (MSD) in Kumudini Women’s Medical College and Hospital, Bangladesh, from December 2007 to March 2011 were enrolled into the study. Results Among the study children, STW users often represented poor families (44% vs. 37%, p = 0.010); less often had household electricity (60% vs. 68%, p = 0.001) and cemented floor material (12% vs. 21%, p

The aim of the current study is to investigate the efficacy of a probiotic beverage prepared from underutilized resources in preventing Shigella-induced pathogenicity in mice model. Probiotic beverage having high counts (1011–1012, cfu/ml) was prepared from whey-skim milk (60:40, v/v), germinated pearl millet flour (4.73%, w/v) and liquid barley malt extract (3.27%, w/v) with Lactobacillus acidophilus NCDC 13. Albino mice were challenged using pathogenic Shigella dysenteriae orally. Mice were sacrificed on the 2nd, 5th and 8th days post-challenge and colonization of pathogen and IgA concentration in intestine fluids was estimated. Long term (7 days) feeding of probiotic beverage stimulated immune system by enhanced secretion of IgA. Further inhibition of pathogen was clearly observed in all organs and feaces. However, short term (2 days) feeding was not much effective as there was non-significant increase in IgA level in intestine fluids, whereas control sample was unable to inhibit the infection.

Background. Acute intestinal infections remain actual diseases for many countries of the world now, especially with middle and low income, in spite of improving sanitary and hygienic conditions of living, drinking water quality. Therefore, the system of epidemiological surveillance of acute intestinal infections needs to be improved. Based on the study of the dynamics of morbidity, risk factors, new ways to improve the epidemiological surveillance of acute intestinal infections were offered. Materials and methods. The paper presents the results of studies on the dynamics of the incidence of schigellosis, salmonellosis, diarrheal escherichiosis, demographic statistics and indicators of sanitary-hygienic monitoring for 2001–2017 in the Sumy region. Epidemiological and statistical methods of research, multivariate analysis were applied. Results. It was found that in the studied period, the incidence rates for shigellosis decreased from 42.3 per 100,000 population to 0.5, salmonellosis — increased from 13.0 to 17.7, diarrheal escherichiosis — varied at 3.70–2.20. At the same time, the population of the region has decreased from 1,317.8 thousand people in 2001 to 1,104.5 in 2017, the population density — from 55.3 (persons per 1 km2) to 46.3, the natural population movement — from –11.1 to –8.6 %, migratory movement — from – 5.2 to –0.7 %, the prevalence of digestive diseases has increased — from 13,004.0 per 100,000 people to 17,124.89. It has been found that in those examined for prophylactic purposes, the frequency of shigella and salmonella isolation decreased from 146.5 and 20.7 per 100,000 population to 0, enteropathogenic colibacilli — from 671.4 to 24.9. Results of sanitary-hygienic monitoring of food and drinking water showed that the frequency of detection of “substandard” water samples was 8.1 %, meat and meat products — 5.2 %, milk and dairy products — 4.3 %, sugar and confectionery products — 5.6 %, eggs — 4.2 %. The frequency of isolation of sanitary and indicative microflora from equipment, the hands of workers in public catering facilities was 4.7 %, food enterprises and enterprises for the production of confectionery with cream — 3.4 and 1.03 %, respectively, dairies — 1.6 %. Statistical analysis conducted with the help of Statistica software package showed the dependence of the morbidity on the influence of risk factors, which can be presented as a linear multivariate regression equation. Using predictive values of risk factors, as well as regression equations, predictive values of morbidity were obtained for the most significant forms of acute intestinal infections. In 2018–2020, an increase in the incidence rate of shigellosis, salmonella, diarrheal escherichiosis is expected. Among the risk factors, the greatest impact will be the increase in population density, the prevalence of digestive diseases, migration of the population, “substandard” microbiological indicators of meat and meat products. Conclusions. Thus, identifying risk factors for unfavorable epidemiological situation and using a mathematical model to predict the development of the epidemic process of acute intestinal infections, taking into account demographic indicators and socio-hygienic monitoring data, can be an important part of the system for improving epidemiological surveillance.

Abstract Background In the event of a shigellosis outbreak in a childcare setting, exclusion policies are typically applied to afflicted children to limit shigellosis transmission. However, there is scarce evidence of their impact. Methods We evaluated five exclusion policies: Children return to childcare after: i) two consecutive laboratory tests (either PCR or culture) do not detect Shigella, ii) a single negative laboratory test (PCR or culture) does not detect Shigella, iii) seven days after beginning antimicrobial treatment, iv) after being symptom-free for 24 h, or v) 14 days after symptom onset. We also included four treatments to assess the policy options: i) immediate, effective treatment; ii) effective treatment after laboratory diagnosis; iii) no treatment; iv) ineffective treatment. Relying on published data, we calculated the likelihood that a child reentering childcare would be infectious, and the number of childcare-days lost per policy. Results Requiring two consecutive negative PCR tests yielded a probability of onward transmission of

Shigella is the leading cause of global diarrheal deaths that currently lacks a licensed vaccine. Shigellosis drives antimicrobial resistance and leads to economic impact through linear growth faltering. Today, there is a robust pipeline of vaccines in clinical development which are broadly divided into parenteral glycoconjugate vaccines, consisting of O-antigen conjugated to carrier proteins, and oral live attenuated vaccines, which incorporate targeted genetic mutations seeking to optimize the balance between reactogenicity, immunogenicity and ultimately protection. Proof of efficacy has previously been shown with both approaches but for various reasons no vaccine has been licensed to date. In this report, we outline the requirements for a Shigella vaccine and describe the current pipeline in the context of the many candidates that have previously failed or been abandoned. The report refers to papers from individual vaccine developers in this special supplement of Vaccines which is focused on Shigella vaccines. Once readouts of safety and immunogenicity from current trials of lead candidate vaccines among the target population of young children in low- and middle-income countries are available, the likely time to licensure of a first Shigella vaccine will become clearer.

Background: Despite the global roll-out of rotavirus vaccines (RotaTeq/Rotarix / ROTAVAC/Rotasiil), mortality and morbidity due to group A rotavirus (RVA) remains high in sub-Saharan Africa, causing 104,000 deaths and 600,000 hospitalizations yearly. In Cameroon, Rotarix™ was introduced in March 2014, but, routine laboratory diagnosis of rotavirus infection is not yet a common practice, and vaccine effectiveness studies to determine the impact of vaccine introduction have not been done. Thus, studies examining RVA prevalence post vaccine introduction are needed. The study aim was to determine RVA prevalence in severe diarrhoea cases in Littoral region, Cameroon and investigate the role of other diarrheagenic pathogens in RVA-positive cases.Methods: We carried out a study among hospitalized children < 5 years of age, presenting with acute gastroenteritis in selected hospitals of the Littoral region of Cameroon, from May 2015 to April 2016. Diarrheic stool samples and socio-demographic data including immunization and breastfeeding status were collected from these participating children. Samples were screened by ELISA (ProSpecT™ Rotavirus) for detection of RVA antigen and by gel-based RT-PCR for detection of the VP6 gene. Co-infection was assessed by multiplexed molecular detection of diarrheal pathogens using the Luminex xTAG GPP assay.Results: The ELISA assay detected RVA antigen in 54.6% (71/130) of specimens, with 45, positive by VP6 RT-PCR and 54, positive using Luminex xTAG GPP. Luminex GPP was able to detect all 45 VP6 RT-PCR positive samples. Co-infections were found in 63.0% (34/54) of Luminex positive RVA infections, with Shigella (35.3%; 12/34) and ETEC (29.4%; 10/34) detected frequently. Of the 71 ELISA positive RVA cases, 57.8% (41/71) were fully vaccinated, receiving two doses of Rotarix.Conclusion: This study provides insight on RVA prevalence in Cameroon, which could be useful for post-vaccine epidemiological studies, highlights higher than expected RVA prevalence in vaccinated children hospitalized for diarrhoea and provides the trend of RVA co-infection with other enteric pathogens. RVA genotyping is needed to determine circulating rotavirus genotypes in Cameroon, including those causing disease in vaccinated children. [ABSTRACT FROM AUTHOR]

Both Campylobacter- and Shigella-induced invasive enteritis are common in under-5 Bangladeshi children. Our study aimed to determine the factors associated with Campylobacter and Shigella enteritis among under-5 children, the post-infection worsening growth, and the household cost of invasive enteritis. Data of children having Shigella (591/803) and Campylobacter (246/1148) isolated from the fecal specimen in Bangladesh were extracted from the Global Enteric Multicenter Study (GEMS) for the period December 2007 to March 2011. In multiple logistic regression analysis, fever was observed more frequently among shigellosis cases [adjusted OR 2.21; (95% CI 1.58, 3.09)]. Breastfeeding [aOR 0.55; (95% CI 0.37, 0.81)] was found to be protective against Shigella. The generalized estimating equations multivariable model identified a negative association between Shigella and weight-for-height z score [aOR − 0.11; (95% CI − 0.21, − 0.001)]; a positive association between symptomatic Campylobacter and weight-for-age z score [aOR 0.22; (95% CI 0.06, 0.37)] and weight-for-height z score [aOR 0.22; (95% CI 0.08, 0.37)]. Total costs incurred by households were more in shigellosis children than Campylobacter-induced enteritis ($4.27 vs. $3.49). Households with low-level maternal education tended to incur less cost in case of their shigellosis children. Our findings underscore the need for preventive strategies targeting Shigella infection, which could potentially reduce the disease burden, associated household costs, and child growth faltering. [ABSTRACT FROM AUTHOR]

Shigellosis is a heavy disease burden in China especially in children aged under 5 years. However, the age-related factors involved in transmission of shigellosis are unclear. An age-specific Susceptible–Exposed–Infectious/Asymptomatic–Recovered (SEIAR) model was applied to shigellosis surveillance data maintained by Hubei Province Centers for Disease Control and Prevention from 2005 to 2017. The individuals were divided into four age groups (≤ 5 years, 6–24 years, 25–59 years, and ≥ 60 years). The effective reproduction number (Reff), including infectivity (RI) and susceptibility (RS) was calculated to assess the transmissibility of different age groups. From 2005 to 2017, 130,768 shigellosis cases were reported in Hubei Province. The SEIAR model fitted well with the reported data (P < 0.001). The highest transmissibility (Reff) was from ≤ 5 years to the 25–59 years (mean: 0.76, 95% confidence interval [CI]: 0.34–1.17), followed by from the 6–24 years to the 25–59 years (mean: 0.69, 95% CI: 0.35–1.02), from the ≥ 60 years to the 25–59 years (mean: 0.58, 95% CI: 0.29–0.86), and from the 25–59 years to 25–59 years (mean: 0.50, 95% CI: 0.21–0.78). The highest infectivity was in ≤ 5 years (RI = 1.71), and was most commonly transmitted to the 25–59 years (45.11%). The highest susceptibility was in the 25–59 years (RS = 2.51), and their most common source was the ≤ 5 years (30.15%). Furthermore, "knock out" simulation predicted the greatest reduction in the number of cases occurred by when cutting off transmission routes among ≤ 5 years and from 25–59 years to ≤ 5 years. Transmission in ≤ 5 years occurred mainly within the group, but infections were most commonly introduced by individuals in the 25–59 years. Infectivity was highest in the ≤ 5 years and susceptibility was highest in the 25–59 years. Interventions to stop transmission should be directed at these age groups. Author summary: Shigellosis has a heavy disease burden in developing countries. The incidence of shigellosis is highest in children aged under 5 years. The transmission characteristics of shigellosis are unclear in different groups, such as age and occupation groups. In this study, we applied an age-specific mathematical model to analyze data on shigellosis built in Hubei Province from 2005 to 2017. The study found that: 1) Shigellosis transmission in children aged 5 years and under occurred among themselves, but was most commonly transmitted by adults aged 25–59 years; 2) The transmission interaction was greatest between children aged 5 years and under, and adults aged 25–59 years; 3) Infectivity was highest in children aged 5 years and under, and susceptibility was highest in adults aged 25–59 years. [ABSTRACT FROM AUTHOR]

Globally, shigellosis remains the second leading cause of diarrhea-associated deaths among children under five years of age, and the infections are disproportionately higher in resource-limited settings due to overcrowding, poor sanitation, and inadequate safe drinking water. The emergence and global spread of multidrug-resistant (MDR) Shigella are exacerbating the shigellosis burden. We adopted a cross-sectional study design to determine the distribution and antimicrobial susceptibility (AST) patterns of Shigella serogroups among children aged below five years presenting with diarrhea at Banadir Hospital in Mogadishu, Somalia, from August to October 2019. Stool and rectal swab samples were collected from 180 children consecutively enrolled using a convenient sampling technique and processed following standard bacteriological methods. AST was determined using the Kirby–Bauer disc diffusion method and interpreted as per the Clinical Laboratory Standard Institute (2018) guidelines. Shigellosis prevalence was 20.6% (37/180), and S. flexneri (26/37 (70.3%)) was the predominant serogroup. All the serogroups were 100% resistant to ampicillin (AMP), trimethoprim-sulfamethoxazole (SXT), and tetracycline (TE). Ceftriaxone (CRO) resistance was the highest among S. sonnei (66.7%) isolates. 19.2% of S. flexneri and S. sonnei (50%) serogroups were resistant to ciprofloxacin (CIP), but all S. dysenteriae type 1 isolates remained (100%) susceptible. Forty percent of CIP-susceptible S. dysenteriae type 1 were resistant to CRO. Seven MDR Shigella phenotypes were identified, dominated by those involving resistance to AMP, SXT, and TE (100%). Our findings showed a high prevalence of shigellosis with S. flexneri as the most predominant serogroup among children under five years of age in Banadir Hospital, Somalia. AMP and SXT are no longer appropriate treatments for shigellosis in children under five years in Banadir Hospital. MDR Shigella strains, including those resistant to CIP and CRO, have emerged in Somalia, posing a public health challenge. Therefore, there is an urgent need for AMR surveillance and continuous monitoring to mitigate the further spread of the MDR Shigella strains in Banadir Hospital and beyond. [ABSTRACT FROM AUTHOR]

Cells infected with pathogens can contribute to clearing infections by releasing signals that instruct neighbouring cells to mount a pro-inflammatory cytokine response, or by other mechanisms that reduce bystander cells' susceptibility to infection. Here, we show the opposite effect: epithelial cells infected with Salmonella Typhimurium secrete host factors that facilitate the infection of bystander cells. We find that the endoplasmic reticulum stress response is activated in both infected and bystander cells, and this leads to activation of JNK pathway, downregulation of transcription factor E2F1, and consequent reprogramming of microRNA expression in a time-dependent manner. These changes are not elicited by infection with other bacterial pathogens, such as Shigella flexneri or Listeria monocytogenes. Remarkably, the protein HMGB1 present in the secretome of Salmonella-infected cells is responsible for the activation of the IRE1 branch of the endoplasmic reticulum stress response in non-infected, neighbouring cells. Furthermore, E2F1 downregulation and the associated microRNA alterations promote Salmonella replication within infected cells and prime bystander cells for more efficient infection. Cells infected with pathogens can release signals that instruct neighbouring cells to mount an immune response or that reduce these cells' susceptibility to infection. Here, Aguilar et al. show the opposite effect: cells infected with Salmonella Typhimurium secrete host factors that facilitate the infection of bystander cells by activating their ER-stress response. [ABSTRACT FROM AUTHOR]

Shigella flexneri , causative agent of bacillary dysentery (shigellosis), uses a type III secretion system (T3SS) as its primary virulence factor. The T3SS injectisome delivers effector proteins into host cells to promote entry and create an important intracellular niche. The injectisome's cytoplasmic sorting platform (SP) is a critical assembly that contributes to substrate selection and energizing secretion. The SP consists of oligomeric Spa33 "pods" that associate with the basal body via MxiK and connect to the Spa47 ATPase via MxiN. The pods contain heterotrimers of Spa33 with one full-length copy associated with two copies of a C-terminal domain (Spa33C). The structure of Spa33C is known, but the precise makeup and structure of the pods in situ remains elusive. We show here that recombinant wild-type Spa33 can be prepared as a heterotrimer that forms distinct stable complexes with MxiK and MxiN. In two-hybrid analyses, association of the Spa33 complex with these proteins occurs via the full-length Spa33 component. Furthermore, these complexes each have distinct biophysical properties. Based on these properties, new high-resolution cryo-electron tomography data and architectural similarities between the Spa33 and flagellar FliM-FliN complexes, we provide a preliminary model of the Spa33 heterotrimers within the SP pods. From these findings and evolving models of SP interfaces and dynamics in the Yersinia and Salmonella T3SS, we suggest a model for SP function in which two distinct complexes come together within the context of the SP to contribute to form the complete pod structures during the recruitment of T3SS secretion substrates. [ABSTRACT FROM AUTHOR]

Multidrug resistant Shigella is one of the leading causes of mortality in children and infants. Availability of vaccine could prevent the Shigella infection and reduce the mortality. Conventional approaches of vaccine development against shigellosis have not resulted in desirable vaccine. As shigellosis may be caused by multiple strains and serotypes, there is a need to develop a multivalent vaccine, capable of providing protection against multiple Shigella strains. To develop broad spectrum vaccine, we had previously derived a pool of conserved epitopes against Shigella by using multiple immunoinformatic tools. In this study, the identified conserved epitopes derived from the Outer Membrane Proteins A and C of Shigella were chemically synthesized, and the EpiMix made up of 5 epitopes coupled to a carrier protein, ovalbumin was developed and validated for its immunogenicity. The intramuscular immunization with EpiMix in Balb/c mice led to increase in EpiMix specific serum IgG, and significant increase in fecal IgA as well as in IL-4, IL-2and IFN-γ levels. Further, the EpiMix immunized mice showed protection when challenged against S. flexneri ATCC 12022 using the intraperitoneal route. Moreover, the analysis of cytokine profile and IFN-γ/IL4 ratio in post Shigella challenge immunized mice suggested the high levels of IFN-γ levels and possible dominance of Th1 response, playing pivotal role in the elimination of Shigella. Collectively, the results demonstrate the immunogenic potential and protective efficacy of the EpiMix in the murine shigellosis model. However, the detailed study and further optimisation of epitopes would substantiate the prospective use of EpiMix as a prophylactic candidate for vaccination. [ABSTRACT FROM AUTHOR]

In a cohort of infants, we found that lack of the Lewis histo-blood group antigen was associated with increased susceptibility to shigellosis. Broadly inhibiting fucosylation in epithelial cells in vitro decreased invasion by Shigella flexneri. These results support a role for fucosylated glycans in susceptibility to shigellosis. [ABSTRACT FROM AUTHOR]

To explore the impact of site, and macaque age, sex, and body mass, on bacterial infection, we ran a multivariate logistic general linear model (GLM) on an "effective" sample size of 140 macaques (details in the ESM). Among the most widely distributed, socioecologically flexible primates, long-tailed macaques ( I Macaca fascicularis i ) are found throughout Southeast Asia, where frequent occurrence of human-macaque interactions have led to calls for macaque population control (Malaivijitnond I et al. i [4]). 10.1002/ajp.20844 3 Malaivijitnond S, Sae-low W, Hamada Y. The human-ABO blood groups of free-ranging long-tailed macaques (Macaca fascicularis) and parapatric rhesus macaques (M. mulatta) in Thailand. [Extracted from the article]

The genus Swertia (Family: Gentianaceae) has cosmopolitan distribution which is present in almost all the continents except South America and Australia. Swertia genus has been renowned as one of the potent herbal drugs in the British, American, and Chinese Pharmacopeias as well as well-documented in the Indian traditional medicinal systems, viz. Ayurveda, Siddha, and Unani. Many species of this genus have therapeutic properties and have been used traditionally in the treatment of a number of health ailments viz. hepatitis, diabetes, inflammation, bacillary dysentery, cancer, malaria, fever etc. This genus is industrially important medicinal plant that has been used as a principal component in numerous marketed herbal/ polyherbal formulations. Medicinal usage of Swertia is endorsed to the miscellaneous compounds viz. xanthones, irridoids, seco-irridoids, and triterpenoids. A chain of systematic isolation of bio-active compounds and their diverse range of pharmacological effects during last 15–20 years proved this genus as industrially important plant. Due to the various practices of the Swertia species, annual demand is more than 100 tons per year for this important herb which is continuously increasing 10% annually. The market value rises 10% by the year as there is increased demand in national and international market resulted in adulteration of many Swertia spp. due to paucity of agricultural practices, exomorphological, phytochemical, and molecular characterization. Thus, efficient biotechnology methods are prerequisite for the mass production of authentic species, sustainable production of bio-active compounds and ex situ conservation. A chain of systematic biotechnological interventions in Swertia herb during last 20 years cover the assessment of genetic diversity, in vitro sustainable production of bio-active compounds and mass propagation of elite genotypes via direct and indirect organogenesis. This review attempts to present the comprehensive assessment on biotechnological process made in Swertia over the past few years. Key points: • Critical and updated assessment on biotechnological aspects of Swertia spp. • In vitro propagation and genetic diversity assessment in Swertia spp. • Biosynthesis and sustainable production of secondary metabolites in Swertia spp. [ABSTRACT FROM AUTHOR]

Introduction: Shigellosis, is a leading cause of moderate-to-severe diarrhoea and related mortality in young children in low and middle income countries (LMICs). Knowledge on naturally acquired immunity can support the development of Shigella candidate vaccines mostly needed in LMICs. We aimed to quantify Shigella-specific antibodies of maternal origin and those naturally acquired in Zambian infants. Methods: Plasma samples collected from infants at age 6, 14 and 52-weeks were tested for Shigella (S. sonnei and S. flexneri 2a) lipopolysaccharide (LPS) antigen specific immunoglobulin G (IgG) and A (IgA) by enzyme-linked immunosorbent assay. Results: At 6 weeks infant age, the IgG geometric mean titres (GMT) against S. sonnei (N = 159) and S. flexneri 2a (N = 135) LPS were 311 (95% CI 259–372) and 446 (95% CI 343–580) respectively. By 14 weeks, a decline in IgG GMT was observed for both S. sonnei to 104 (95% CI 88–124), and S. flexneri 2a to 183 (95% CI 147–230). Both S. sonnei and S. flexneri 2a specific IgG GMT continued to decrease by 52 weeks infant age when compared to 6 weeks. In 27% and 8% of infants a significant rise in titre (4 fold and greater) against S. flexneri 2a and S. sonnei LPS, respectively, was detected between the ages of 14 and 52 weeks. IgA levels against both species LPS were very low at 6 and 14 weeks and raised significantly against S. flexneri 2a and S. sonnei LPS in 29% and 10% of the infants, respectively. Conclusion: In our setting, transplacental IgG anti-Shigella LPS is present at high levels in early infancy, and begins to decrease by age 14 weeks. Our results are consistent with early exposure to Shigella and indicate naturally acquired IgG and IgA antibodies to S. flexneri 2a and S. sonnei LPS in part of infants between 14 and 52 weeks of age. These results suggest that a potential timing of vaccination would be after 14 and before 52 weeks of age to ensure early infant protection against shigellosis. [ABSTRACT FROM AUTHOR]

The article examines data on outbreaks associated with treated recreational water in the U.S. from 2015 to 2019. Topics discussed include the illness, hospitalizations and deaths resulting from outbreaks associated with public pools, hot tubs or water playgrounds, attribution of the outbreaks to Cryptosporidium and Legionella, and the guidelines for hyperchlorination to inactivate oocysts recommended in the 2018 Model Aquatic Health Code (MAHC) of the Centers for Disease Control and Prevention.

We conducted a controlled before-and-after trial to evaluate the impact of an onsite urban sanitation intervention on the prevalence of enteric infection, soil transmitted helminth reinfection, and diarrhea among children in Maputo, Mozambique. A non-governmental organization replaced existing poor-quality latrines with pour-flush toilets with septic tanks serving household clusters. We enrolled children aged 1-48 months at baseline and measured outcomes before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. Despite nearly exclusive use, we found no evidence that intervention affected the prevalence of any measured outcome after 12 or 24 months of exposure. Among children born into study sites after intervention, we observed a reduced prevalence of Trichuris and Shigella infection relative to the same age group at baseline (<2 years old). Protection from birth may be important to reduce exposure to and infection with enteric pathogens in this setting. [ABSTRACT FROM AUTHOR]

Background Azithromycin is frequently used to treat shigellosis; however, clinical outcomes are uncertain. Methods We performed an observational cohort study in Bangladesh of patients with invasive diarrhea treated empirically with azithromycin. Susceptibility testing was performed by broth microdilution and disk diffusion post hoc on all Shigella isolates and clinical response was correlated with in vitro susceptibility. Results There were 149 Shigella culture-positive patients in the primary analysis. Infection with Shigella with decreased susceptibility to azithromycin was significantly associated with persistence of diarrhea at day 5 (31% vs 12%; relative risk [RR], 2.66; 95% confidence interval [CI], 1.34–5.28), culture positivity at day 5 or 6 (35% vs 5%; RR, 5.26; 95% CI, 1.84–14.85), and a higher rate of overnight hospitalization (58% vs 39%; RR, 1.49; 95% CI, 1.06–2.09). Shigella flexneri was more common than Shigella sonnei (58% vs 36%); however, S. sonnei constituted most of the isolates with decreased susceptibility to azithromycin (67%) and most of the multidrug-resistant strains (54%); thus, poor clinical outcomes were associated with S. sonnei. The current epidemiological cutoff for S. flexneri of ≥16 µg/mL to define decreased susceptibility to azithromycin was clinically predictive of poor outcome. Patients with S. sonnei and a low MIC (4 µg/mL) still had elevated rates of persistent diarrhea and culture positivity. Conclusions This study documents worse clinical outcomes for S. flexneri with decreased susceptibility to azithromycin, as well as S. sonnei , and supports the utility of susceptibility testing and clinical breakpoints for azithromycin. S. sonnei is an emerging drug-resistant threat. Clinical Trials Registration NCT03778125. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is a global public health threat and is increasingly prevalent among enteric pathogens in low- and middle-income countries (LMICs). However, the burden of multidrug-resistant organisms (MDROs) in older children, adults, and elderly patients with acute diarrhea in LMICs is poorly understood. This study's aim was to characterize the prevalence of MDR enteric pathogens isolated from patients with acute diarrhea in Dhaka, Bangladesh, and assess a wide range of risk factors associated with MDR. Methods: This study was a secondary analysis of data collected from children over 5 years, adults, and elderly patients with acute diarrhea at the International Centre for Diarrhoeal Disease Research, Bangladesh Dhaka Hospital between March 2019 and March 2020. Clinical, historical, socio-environmental information, and a stool sample for culture and antimicrobial susceptibility testing were collected from each patient. Univariate statistics and multiple logistic regression were used to assess the prevalence of MDR among enteric pathogens and the association between independent variables and presence of MRDOs among culture-positive patients. Results: A total of 1198 patients had pathogens isolated by stool culture with antimicrobial susceptibility results. Among culture-positive patients, the prevalence of MDR was 54.3%. The prevalence of MDR was highest in Aeromonas spp. (81.5%), followed by Campylobacter spp. (72.1%), Vibrio cholerae (28.1%), Shigella spp. (26.2%), and Salmonella spp. (5.2%). Factors associated with having MDRO in multiple logistic regression included longer transport time to hospital (>90 min), greater stool frequency, prior antibiotic use prior to hospital presentation, and non-flush toilet use. However, pseudo-R2 was low 0.086, indicating that other unmeasured variables need to be considered to build a more robust predictive model of MDR. Conclusions: MDR enteric pathogens were common in this study population with clinical, historical, and socioenvironmental risk factors associated with MDROs. These findings may help guide clinical decision-making regarding antibiotic use and selection in patients at greatest risk of complications due to MDROs. Further prospective research is urgently needed to determine what additional factors place patients at greatest risk of MDRO, and the best strategies to mitigate the spread of MDR in enteric pathogens. [ABSTRACT FROM AUTHOR]

Shigella is the second most deadly diarrheal disease among children under five years of age, after rotavirus, with high morbidity and mortality in developing countries. Currently, no vaccine is widely available, and the increasing levels of multidrug resistance make Shigella a high priority for vaccine development. The single-component candidate vaccine against Shigella sonnei (1790GAHB), developed using the GMMA technology, contains the O antigen (OAg) portion of lipopolysaccharide (LPS) as active moiety. The vaccine was well tolerated and immunogenic in early-phase clinical trials. In a phase 1 placebo-controlled dose escalation trial in France (NCT02017899), three doses of five different vaccine formulations (0.06/1, 0.3/5, 1.5/25, 3/50, 6/100 µg of OAg/protein) were administered to healthy adults. In the phase 1 extension trial (NCT03089879), conducted 2–3 years following the parent study, primed individuals who had undetectable antibody levels before the primary series received a 1790GAHB booster dose (1.5/25 µg OAg/protein). Controls were unprimed participants immunized with one 1790GAHB dose. The current analysis assessed the functionality of sera collected from both studies using a high-throughput luminescence-based serum bactericidal activity (SBA) assay optimized for testing human sera. Antibodies with complement-mediated bactericidal activity were detected in vaccinees but not in placebo recipients. SBA titers increased with OAg dose, with a persistent response up to six months after the primary vaccination with at least 1.5/25 µg of OAg/protein. The booster dose induced a strong increase of SBA titers in most primed participants. Correlation between SBA titers and anti- S. sonnei LPS serum immunoglobulin G levels was observed. Results suggest that GMMA is a promising OAg delivery system for the generation of functional antibody responses and persistent immunological memory. [ABSTRACT FROM AUTHOR]

Macrophages provide the first line of defense against Shigella flexneri infection in the gastrointestinal tract by inducing a variety of inflammatory and antimicrobial responses. Secondary metabolites of plants are used as drugs against infections that are resistant to common antibiotics. In this study, the innate effects of asiaticoside on the proinflammatory activity of mouse macrophages infected with S. flexneri were investigated. The viability of the infected mouse macrophages were examined using viability assay, while the pro-inflammatory cytokines productions were determined using the enzyme-linked immunosorbent assay (ELISA) for determination of IL-1ß, IL-12 p40 and TNF-a levels. The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) protein were determined using the Griess assay and western blot, respectively. Statistical analyses were performed using the Statistical Package of Social Sciences (SPSS) software, version 20. The data obtained from independent experiments (n = 3) were presented as the mean ± standard error of mean (SEM). The results showed that, asiaticoside stimulated the infected macrophages by stimulating increased production of TNF-a, IL-12 p40 and NO as well as increased expression of iNOS in a dose-dependent manner. In contrast the viability of the cells and the production of IL-1ß and were reduced also in a dose-dependent manner when compared to untreated cells. These results indicate that asiaticoside has immunomodulatory effects on the innate immune function of infected macrophages, showing the potential use of this compound to reduce the clinical symptoms of the infections. [ABSTRACT FROM AUTHOR]

Bacterial Type III Secretion Systems (T3SSs) are specialized multicomponent nanomachines that mediate the transport of proteins either to extracellular locations or deliver Type III Secretion effectors directly into eukaryotic host cell cytoplasm. Shigella , the causing agent of bacillary dysentery or shigellosis, bears a set of T3SS proteins termed translocators that form a pore in the host cell membrane. IpaB, the major translocator of the system, is a key factor in promoting Shigella pathogenicity. Prior to secretion, IpaB is maintained inside the bacterial cytoplasm in a secretion competent folding state thanks to its cognate chaperone IpgC. IpgC couples T3SS activation to transcription of effector genes through its binding to MxiE, probably after the delivery of IpaB to the secretion export gate. Small Angle X-ray Scattering experiments and modeling reveal that IpgC is found in different oligomeric states in solution, as it forms a stable heterodimer with full-length IpaB in contrast to an aggregation-prone homodimer in the absence of the translocator. These results support a stoichiometry of interaction 1:1 in the IpgC/IpaB complex and the multi-functional nature of IpgC under different T3SS states. [ABSTRACT FROM AUTHOR]

Shigellosis caused by Shigella dysenteriae is a major public health concern worldwide, particularly in developing countries. The bacterial genome is known, but there are many hypothetical proteins whose functions are yet to be discovered. A hypothetical protein (accession no. WP_128879999.1, 161 residues) of S. dysenteriae ATCC 12039 strain was selected in this study for comprehensive structural and functional analysis. Subcellular localization and different physicochemical properties of this hypothetical protein were estimated indicating it as a stable, soluble, and extracellular protein. Functional annotation tools, such as NCBI-CD Search, Pfam, and InterProScan, predicted our target protein to be an amidase effector protein 4 (Tae4) of type-VI secretion system (T6SS). Multiple sequence alignment of the homologous sequences coincided with previous findings. Random coil was found to be predominant in secondary structure. Three-dimensional (3D) structure of the protein was obtained using homology modeling method by SWISS-MODEL server using a template protein (PDB ID: 4J30) of 80.12% sequence identity. The 3D structure became more stable after YASARA energy minimization and was validated by several quality assessment tools like PROCHECK, QMEAN, Verify3D, and ERRAT. Superimposition of the target with the template protein by UCSF Chimera generated RMSD value of 0.115 Å, suggesting a reliable 3D structure. The active site of the modeled structure was predicted and visualized by CASTp server and PyMOL. Interestingly, similar binding affinity and key interacting residues were found for the target protein and a Salmonella enterica Tae4 protein with the ligand L-Ala D-Glu-mDAP by molecular docking analysis. Protein-protein docking was also performed between the target protein and hemolysin coregulated protein 1 of T6SS. Finally, the protein was found to be a unique protein of S. dysenteriae nonhomologous to human by comparative genomics approach indicating a potential therapeutic target. Most pathogens harboring T6SS in their system pose a significant threat to the human health. Many T6SSs and their effectors are associated with interbacterial competition, pathogenesis, and virulency; however, relationships between these effectors and pathogenicity of S. dysenteriae are yet to be determined. The study findings provide a lucrative platform for future antibacterial treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the genetic relatedness and antimicrobial resistance among Shigella species isolated from food and stool samples. Using cross sectional study method, Shigella spp. were isolated from food and clinical samples using culture-based, biochemical and serological methods. Antimicrobial susceptibility and genetic relatedness among the isolates were evaluated using disk diffusion and RAPD-PCR methods respectively. Results: The prevalence of Shigella spp. were 4.84 and 7.7% in food and stool samples respectively. All food isolates were Sh. sonnei. 91.42% of the Shigella stool isolates were Sh. sonnei. 62.5% of food isolates were resistant to tetracycline. 46.8, 50 and 65.8% of clinical isolates were resistant to imipenem, amikacin and azithromycin respectively. 50 and 85.7% of the food and clinical isolates respectively were MDR. Dendrogram generated by RAPD-PCR showed that the isolates from food and stool samples were categorized in a same group. Close genetic relatedness between MDR Shigella isolates from food and clinical samples indicate that foods can be considered as one of the main vehicles for transmission of MDR Shigella to human causing acute diseases. Survey of MDR Shigella among food and clinical samples is strongly suggested to be implemented. [ABSTRACT FROM AUTHOR]

Background: Shigella remains in the top four pathogens responsible for moderate to severe diarrhoea in children below 5 years of age. The shigella O-specific polysaccharide (O-SP) is a promising vaccine target. We developed a conjugate vaccine prototype incorporating a unique well defined synthetic oligosaccharide hapten, chemically designed for optimal antigenic, conformational, structural, and functional mimicry of the O-SP from Shigella flexneri 2a (SF2a). We aimed to assess the safety, tolerability, and immunogenicity of this original synthetic oligosaccharide-based vaccine candidate, SF2a-TT15, conceived to drive the antibody response towards the key protective determinants of the native lipopolysaccharide antigen, in a first-in-human phase 1 study.Methods: We did a first-in-human, dose-escalating, single-blind, observer-masked, randomised, placebo-controlled study at the Clinical Research Center of Tel Aviv Sourasky Medical Center (Israel). Participants were healthy adults aged 18-45 years with low titres of serum SF2a-specific IgG antibodies. 64 eligible participants were assigned to one of two cohorts. 32 participants in each of the two cohorts were randomly assigned via computer-generated algorithm in a stepwise manner to receive the 2 μg (cohort 1) and 10 μg oligosaccharide dose (cohort 2) of the SF2a-TT15 vaccine candidate non-adjuvanted or adjuvanted with aluminium hydroxide (alum) or matching placebos. The vaccine was administered as three single intramuscular injections into the arm, 28 days apart. The primary outcome was the incidence and severity of adverse events, which were assessed in the intention-to-treat safety population analysis including all participants who were randomly assigned and received at least one vaccine or placebo injection. The immunogenicity endpoints were secondary outcomes and were analysed in all participants who were randomly assigned, received all of the assigned injections before the time of the immunogenicity assessment, and provided blood samples for immunological follow-up (per-protocol immunogenicity analysis). The study is registered with ClinicalStudies.gov, NCT02797236 and is completed.Findings: Of 203 volunteers initially screened, 64 participants were enrolled between Sept 20, 2016, and Sept 26, 2017. In each of the two cohorts, 12 participants received the adjuvanted vaccine, 12 received the non-adjuvanted vaccine and eight received the matching placebo (four each). The SF2a-TT15 glycoconjugate was well tolerated at both doses. No serious or severe adverse events occurred. Overall, seven (88%) of eight to 12 (100%) of 12 in each group of volunteers had one adverse event or more after receiving the study agents with the majority of adverse events, 300 (98%) of 307, considered mild in intensity. Of the seven adverse events defined as moderate in severity, one (nausea) was suspected to be related to the vaccine candidate. At all post-immunisation days and for both oligosaccharide doses, whether adjuvanted or not, SF2a-TT15 induced significantly higher serum IgG anti-SF2a lipopolysaccharide geometric mean titres (GMTs) as compared with baseline or with the corresponding GMTs in placebo recipients (p<0·01). After one injection, the non-adjuvanted 10 μg oligosaccharide dose induced a 27-times increase in IgG GMT (5080 vs 189) and the non-adjuvanted 2 μg oligosaccharide dose induced a five-times increase (1411 vs 283), compared with baseline. Alum enhanced the specific IgG response at 2 μg oligosaccharide dose after the third injection (GMTs 3200 vs 1176, p=0.045).Interpretation: SF2a-TT15 was safe and well tolerated and induced high titres of anti-SF2a LPS IgG antibodies. These results support further evaluation of this original synthetic oligosaccharide-protein conjugate vaccine candidate for safety, immunogenicity, and protective efficacy in target populations.Funding: The European Union Seventh Framework Programme. [ABSTRACT FROM AUTHOR]

Background: As antimicrobials increase the risk of acquiring multidrug-resistant (MDR) bacteria, unnecessary antibiotics should be avoided for travellers' diarrhoea (TD). Antibiotics are recommended in TD accompanied by fever or incapacitation (TD justifying use of antibiotics, TDjuAB). Seeking tools for reducing antibiotic use, we explored factors predisposing to TDjuAB and scrutinized antibiotic treatment among those with TDjuAB [TDjuAB(+) subgroup] and those with diarrhoea not justifying antibiotics [TDjuAB(-) subgroup].Methods: We conducted a study among 370 prospectively recruited visitors to the tropics. Stool samples and questionnaires were collected before and after travel. Enteric pathogens were analysed by qPCR for enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC) and enteroinvasive (EIEC) E. coli/Shigella, Campylobacter, Salmonella, Yersinia and Vibrio cholerae, and for ETEC's toxins LT (heat-labile), STh (human heat-stable) and STp (porcine heat-stable). TD was defined by the WHO criteria and TDjuAB as diarrhoea accompanied by fever, and/or disrupting or preventing daily activities. Multivariable analysis was applied-separately for travel-related factors and pathogens-to identify risk factors for TDjuAB(+).Results: Among the 370 travellers, TD was contracted by 253 (68%), categorized as TDjuAB(+) in 93/253 (37%) and TDjuAB(-) in 160/253 (63%) of the cases. Antibiotics were used for TD by 41% in TDjuAB(+) and by 7% in the TDjuAB(-) group. Relative risk ratios (RRR)s are presented for both the TDjuAB(+) and the TDjuAB(-) groups. TDjuAB(+) was associated with long travel duration and young age. Among the 298 subjects not having taken antibiotics, increased RRRs were found e.g. for findings of Campylobacter coli/jejuni and ETEC's STh toxin.Conclusions: The first to analyse risk factors for TDjuAB, our study presents RRRs for demographic and behavioural factors and for various pathogens. Only less than half of those in the TDjuAB(+) group took antibiotics, which demonstrates that most cases meeting the current criteria recover without antimicrobial treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine the etiological factors in adult cases with acute gastroenteritis (AGE). Materials and Methods: In this study, bacteriological, parasitological and virological examinations were performed on the stool samples of 110 patients, admitted in a 7-month period with a diagnosis of acute gastroenteritis with a daily stool frequency of more than three and symptoms of less than 14 days, were evaluated. Toxin A of Clostridium difficile was investigated in the stools of patients who have taken antibiotics in the last 10 days. Results: Of the 110 patients with acute gastroenteritis, 59 (53.6%) were male, and the mean age was 36 (± 14). At least one pathogen was detected as an acute gastroenteritis agent in 44.5% of the patients (n = 49), but no pathogen was identified in 55.5% of them. The detected pathogens were as follows: Entamoeba histolytica (11.8%), Shigella spp. (10.9%), rotavirus (10,9%), Giardia intestinalis (5.4%), Salmonella spp. (2.7%), Candida spp. (2.7%), enteropathogenic Escherichia coli (0.9%), Blastocystis hominis (0.9%), and Clostridium difficile (0.9%). More than one pathogen was detected in three patients (2.7%). Among Shigella spp. (n=12), Shigella sonnei (n = 6), Shigella flexneri (n = 4) and Shigella boydii (n = 2); and among Salmonella spp. (n=3) Salmonella enteritidis (n = 2) and Salmonella arizonae (n = 1) were identified. Conclusion: In this study, pathogens were identified in 44.5% of stool samples of the patients with AGE. The most common pathogens identified in etiology are protozoa (18.1%), bacteria (15.5%), mainly Shigella spp., and rotavirus (10.9%). It is concluded that no antibiotic is needed for more than 65% of adult patients with AGE. [ABSTRACT FROM AUTHOR]

Campylobacteriosis is a disease of worldwide importance, but aspects of its transmission dynamics, particularly risk factors, are still poorly understood. We used data from a matched case-control study of 4,269 men who have sex with men (MSM) and 26,215 controls, combined with national surveillance data on Campylobacter spp., Salmonella spp., and Shigella spp., to calculate matched odds ratios (mORs) for infection among MSM and controls. MSM had higher odds of Campylobacter (mOR 14, 95% CI 10-21) and Shigella (mOR 74, 95% CI 27-203) infections, but not Salmonella (mOR 0.2, 95% CI 0-13), and were less likely than controls to have acquired Campylobacter infection abroad (χ2 = 21; p<0.001). Our results confirm that sexual contact is a risk factor for campylobacteriosis and also suggest explanations for unique features of Campylobacter epidemiology. These findings provide a baseline for updating infection risk guidelines to the general population. [ABSTRACT FROM AUTHOR]