Shigella sonnei Outbreak Investigation During a Municipal Water Crisis-Genesee and Saginaw Counties, Michigan, 2016.

Objectives. To investigate a shigellosis outbreak in Genesee County, Michigan (including the City of Flint), and Saginaw County, Michigan, in 2016 and address community concerns about the role of the Flint water system.Methods. We met frequently with community members to understand concerns and develop the investigation. We surveyed households affected by the outbreak, analyzed Shigella isolate data, examined the geospatial distribution of cases, and reviewed available water quality data.Results. We surveyed 83 households containing 158 cases; median age was 10 years. Index case-patients from 55 of 83 households (66%) reported contact with a person outside their household who wore diapers or who had diarrhea in the week before becoming ill; results were similar regardless of household drinking water source. Genomic diversity was not consistent with a point source. In Flint, no space-time clustering was identified, and average free chlorine residual values remained above recommended levels throughout the outbreak period.Conclusions. The outbreak was most likely caused by person-to-person contact and not by the Flint water system. Consistent community engagement was essential to the design and implementation of the investigation.

Feasibility of containing shigellosis in Hubei Province, China: a modelling study.

BACKGROUND: The transmission features and the feasibility of containing shigellosis remain unclear among a population-based study in China. METHODS: A population-based Susceptible - Exposed - Infectious / Asymptomatic - Recovered (SEIAR) model was built including decreasing the infectious period (DIP) or isolation of shigellosis cases. We analyzed the distribution of the reported shigellosis cases in Hubei Province, China from January 2005 to December 2017, and divided the time series into several stages according to the heterogeneity of reported incidence during the period. In each stage, an epidemic season was selected for the modelling and assessing the effectiveness of DIP and case isolation. RESULTS: A total of 130,770 shigellosis cases were reported in Hubei Province. The median of Reff was 1.13 (range: 0.86-1.21), 1.10 (range: 0.91-1.13), 1.09 (range: 0.92-1.92), and 1.03 (range: 0.94-1.22) in 2005-2006 season, 2010-2011 season, 2013-2014 season, and 2016-2017 season, respectively. The reported incidence decreased significantly (trend χ2 = 8260.41, P <  0.001) among four stages. The incidence of shigellosis decreased sharply when DIP implemented in three scenarios (γ = 0.1, 0.1429, 0.3333) and when proportion of case isolation increased. CONCLUSIONS: Year heterogeneity of reported shigellosis incidence exists in Hubei Province. It is feasible to contain the transmission by implementing DIP and case isolation.

Epidemiological characteristics and transmissibility of shigellosis in Hubei Province, China, 2005 - 2017.

BACKGROUND: Shigellosis is one of the main diarrhea diseases in developing countries. However, the transmissibility of shigellosis remains unclear. METHODS: We used the dataset of shigellosis cases reported between January 2005 and December 2017, from Hubei Province, China. A mathematical model was developed based on the natural history and the transmission mechanism of the disease. By fitting the data using the model, transmission relative rate from person to person (b) and from reservoir to person (bw), and the effective reproduction number (Reff) were estimated. To simulate the contribution of b and bw during the transmission, we performed a "knock-out" simulation in four scenarios: A) b = 0 and bw = 0; B) b = 0; C) bw = 0; D) control (no intervention). RESULTS: A total of 130,770 shigellosis cases were reported in Hubei province, among which 13 cases were dead. The median annual incidence was 19.96 per 100,000 persons (range: 5.99 per 100,000 persons - 29.47 per 100,000 persons) with a decreased trend (trend χ2 = 25,470.27, P < 0.001). The mean values of b and bw were 0.0898 (95% confidence interval [CI]: 0.0851-0.0946) and 1.1264 × 10- 9 (95% CI: 4.1123 × 10- 10-1.8416 × 10- 9), respectively. The "knock-out" simulation showed that the number of cases simulated by scenario A was almost the same as scenario B, and scenario C was almost the same as scenario D. The mean value of Reff of shigellosis was 1.19 (95% CI: 1.13-1.25) and decreased slightly with a Linear model until it decreased to an epidemic threshold of 0.99 (95% CI: 0.65-1.34) in 2029. CONCLUSIONS: The incidence of shigellosis is still in high level. The transmissibility of the disease is low in Hubei Province. The transmission would be interrupted in the year of 2029.

Evaluation of the impact of shigellosis exclusion policies in childcare settings upon detection of a shigellosis outbreak.

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 < 1%, with up to 17 childcare-days lost for children receiving effective treatment, and 53 days lost for those receiving ineffective treatment. CONCLUSIONS: Of the policies analyzed, requiring negative PCR testing before returning to childcare was the most effective to reduce the risk of shigellosis transmission, with one PCR test being the most effective for the least childcare-days lost.

Microevolution and Patterns of Transmission of Shigella sonnei within Cyclic Outbreaks Shigellosis, Israel.

Whole-genome sequencing unveiled host and environment-related insights to Shigella sonnei transmission within cyclic epidemics during 2000-2012 in Israel. The Israeli reservoir contains isolates belonging to S. sonnei lineage III but of different origin, shows loss of tetracycline resistance genes, and little genetic variation within the O antigen: highly relevant for Shigella vaccine development.

Recent epidemiology of sexually transmissible enteric infections in men who have sex with men.

PURPOSE OF REVIEW: Sexual transmission of enteric pathogens in men who have sex with men (MSM) has been described since the 1970s. Recently, an increasing number of enteric infection outbreaks have been reported in MSM. This article summarizes recent outbreaks and discusses the key issues for prevention and control. RECENT FINDINGS: Sexually transmissible enteric infections (STEIs) can spread rapidly and internationally within highly connected MSM populations and are often associated with antimicrobial resistance (AMR). The infections often cluster in high-risk groups of HIV-positive MSM who are more likely to engage in diverse sexual practices and chemsex, and to have multiple other sexually transmitted infections (STIs). SUMMARY: The roles of asymptomatic and/or persistent infection and other contextual factors in STEI transmission are not well described. STEI-associated AMR is increasing and has potential to spread rapidly in MSM, warranting further public health attention. A better understanding of the factors associated with sexual transmission will enable the development of more effective control measures. A holistic approach that promotes health and wellbeing as well as infection prevention and management is needed.

What is the overlap between HIV and shigellosis epidemics in England: further evidence of MSM transmission?

BACKGROUND: Evidence suggests that sexual transmission between men has replaced foreign travel as the predominant mode of Shigella transmission in England. However, sexuality and HIV status are not routinely recorded for laboratory-reported Shigella, and the role of HIV in the Shigella epidemic is not well understood. METHODS: The Modular Open Laboratory Information System containing all Shigella cases reported to Public Health England (PHE) and the PHE HIV and AIDS Reporting System holding all adults living with diagnosed HIV in England were matched using a combination of Soundex code, date of birth and gender. RESULTS: From 2004 to 2015, 88 664 patients were living with HIV, and 10 269 Shigella cases were reported in England; 9% (873/10 269) of Shigella cases were diagnosed with HIV, of which 93% (815/873) were in men. Shigella cases without reported travel history were more likely to be living with HIV than those who had travelled (14% (751/5427) vs 3% (134/4854); p<0.01). From 2004 to 2015, the incidence of Shigella in men with HIV rose from 47/100 000 to 226/100 000 (p<0.01) peaking in 2014 at 265/100 000, but remained low in women throughout the study period (0-24/100 000). Among Shigella cases without travel and with HIV, 91% (657/720) were men who have sex with men (MSM). HIV preceded Shigella diagnosis in 86% (610/720), and 65% (237/362) had an undetectable viral load (<50 copies/mL). DISCUSSION: We observed a sustained increase in the national rate of shigellosis in MSM with HIV, who may experience more serious clinical disease. Sexual history, HIV status and STI risk might require sensitive investigation in men presenting with gastroenteritis.

Use of gender distribution in routine surveillance data to detect potential transmission of gastrointestinal infections among men who have sex with men in England.

Detecting gastrointestinal (GI) infection transmission among men who have sex with men (MSM) in England is complicated by a lack of routine sexual behavioural data. We investigated whether gender distributions might generate signals for increased transmission of GI pathogens among MSM. We examined the percentage male of laboratory-confirmed patient-episodes for patients with no known travel history for 10 GI infections of public health interest in England between 2003 and 2013, stratified by age and region. An adult male excess was observed for Shigella spp. (annual maximum 71% male); most pronounced for those aged 25-49 years and living in London, Brighton and Manchester. An adult male excess was observed every year for Entamoeba histolytica (range 59.8-76.1% male), Giardia (53.1-57.6%) and Campylobacter (52.1-53.5%) and for a minority of years for hepatitis A (max. 69.8%) and typhoidal salmonella (max. 65.7%). This approach generated a signal for excess male episodes for six GI pathogens, including a characterised outbreak of Shigella among MSM. Stratified analyses by geography and age group were consistent with MSM transmission for Shigella. Optimisation and routine application of this technique by public health authorities elsewhere might help identify potential GI infection outbreaks due to sexual transmission among MSM, for further investigation.

Enteric Infections Circulating during Hajj Seasons, 2011-2013.

Hajj, the annual Muslim pilgrimage to Mecca, Saudi Arabia, is a unique mass gathering event that raises public health concerns in the host country and globally. Although gastroenteritis and diarrhea are common among Hajj pilgrims, the microbial etiologies of these infections are unknown. We collected 544 fecal samples from pilgrims with medically attended diarrheal illness from 40 countries during the 2011-2013 Hajj seasons and screened the samples for 16 pathogens commonly associated with diarrheal infections. Bacteria were the main agents detected, in 82.9% of the 228 positive samples, followed by viral (6.1%) and parasitic (5.3%) agents. Salmonella spp., Shigella/enteroinvasive Escherichia coli, and enterotoxigenic E. coli were the main pathogens associated with severe symptoms. We identified genes associated with resistance to third-generation cephalosporins ≈40% of Salmonella- and E. coli-positive samples. Hajj-associated foodborne infections pose a major public health risk through the emergence and transmission of antimicrobial drug-resistant bacteria.

Update on: Shigella new serogroups/serotypes and their antimicrobial resistance.

Shigellosis represents a major burden of disease in developing countries. A low infectious dose allows the disease to be spread effectively. Although shigellosis is mostly a self-limiting disease, antibiotics are recommended to reduce deaths, disease symptoms and organism-shedding time. However, in India, antimicrobial resistance among the genus Shigella is more common than among any other enteric bacteria. Notably, new serotypes or subserotypes in Shigella are reported from various parts of the world. Identification of new subserotypes of Shigella spp. is becoming a major issue as these strains are nontypeable by conventional serotyping. The commercially available antisera may not cover all possible epitopes of the O lipopolysaccharide antigen of Shigella serotypes. Therefore, molecular methods which most closely approach the resolution of full serotyping are necessary to identify such strains. In addition, the knowledge of a prevalent serotype in various geographic regions may assist in formulating strategies such as the development of a vaccine to prevent infection especially when the immunity to disease is serotype specific, and to understand the disease burden caused by new Shigella serotypes.

Travel- and Community-Based Transmission of Multidrug-Resistant Shigella sonnei Lineage among International Orthodox Jewish Communities.

Shigellae are sensitive indicator species for studying trends in the international transmission of antimicrobial-resistant Enterobacteriaceae. Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in OJCs in Israel, and sporadic outbreaks occur in OJCs elsewhere. We generated whole-genome sequences for 437 isolates of S. sonnei from OJCs and non-OJCs collected over 22 years in Europe (the United Kingdom, France, and Belgium), the United States, Canada, and Israel and analyzed these within a known global genomic context. Through phylogenetic and genomic analysis, we showed that strains from outbreaks in OJCs outside of Israel are distinct from strains in the general population and relate to a single multidrug-resistant sublineage of S. sonnei that prevails in Israel. Further Bayesian phylogenetic analysis showed that this strain emerged approximately 30 years ago, demonstrating the speed at which antimicrobial drug-resistant pathogens can spread widely through geographically dispersed, but internationally connected, communities.

Elevated Risk for Antimicrobial Drug-Resistant Shigella Infection among Men Who Have Sex with Men, United States, 2011-2015.

Shigella spp. cause ≈500,000 illnesses in the United States annually, and resistance to ciprofloxacin, ceftriaxone, and azithromycin is emerging. We investigated associations between transmission route and antimicrobial resistance among US shigellosis clusters reported during 2011-2015. Of 32 clusters, 9 were caused by shigellae resistant to ciprofloxacin (3 clusters), ceftriaxone (2 clusters), or azithromycin (7 clusters); 3 clusters were resistant to >1 of these drugs. We observed resistance to any of these drugs in all 7 clusters among men who have sex with men (MSM) but in only 2 of the other 25 clusters (p<0.001). Azithromycin resistance was more common among MSM-associated clusters than other clusters (86% vs. 4% of clusters; p<0.001). For adults with suspected shigellosis, clinicians should culture feces; obtain sex histories; discuss shigellosis prevention; and choose treatment, when needed, according to antimicrobial drug susceptibility. Public health interviews for enteric illnesses should encompass sex practices; health messaging for MSM must include shigellosis prevention.

The class II phosphatidylinositol 3-phosphate kinase PIK3C2A promotes Shigella flexneri dissemination through formation of vacuole-like protrusions.

Intracellular pathogens such as Shigella flexneri and Listeria monocytogenes achieve dissemination in the intestinal epithelium by displaying actin-based motility in the cytosol of infected cells. As they reach the cell periphery, motile bacteria form plasma membrane protrusions that resolve into vacuoles in adjacent cells, through a poorly understood mechanism. Here, we report on the role of the class II phosphatidylinositol 3-phosphate kinase PIK3C2A in S. flexneri dissemination. Time-lapse microscopy revealed that PIK3C2A was required for the resolution of protrusions into vacuoles through the formation of an intermediate membrane-bound compartment that we refer to as a vacuole-like protrusion (VLP). Genetic rescue of PIK3C2A depletion with RNA interference (RNAi)-resistant cDNA constructs demonstrated that VLP formation required the activity of PIK3C2A in primary infected cells. PIK3C2A expression was required for production of phosphatidylinositol 3-phosphate [PtdIns(3)P] at the plasma membrane surrounding protrusions. PtdIns(3)P production was not observed in the protrusions formed by L. monocytogenes, whose dissemination did not rely on PIK3C2A. PIK3C2A-mediated PtdIns(3)P production in S. flexneri protrusions was regulated by host cell tyrosine kinase signaling and relied on the integrity of the S. flexneri type 3 secretion system (T3SS). We suggest a model of S. flexneri dissemination in which the formation of VLPs is mediated by the PIK3C2A-dependent production of the signaling lipid PtdIns(3)P in the protrusion membrane, which relies on the T3SS-dependent activation of tyrosine kinase signaling in protrusions.

Shigella Infections in Household Contacts of Pediatric Shigellosis Patients in Rural Bangladesh.

To examine rates of Shigella infections in household contacts of pediatric shigellosis patients, we followed contacts and controls prospectively for 1 week after the index patient obtained care. Household contacts of patients were 44 times more likely to develop a Shigella infection than were control contacts (odds ratio 44.7, 95% CI 5.5-361.6); 29 (94%) household contacts of shigellosis patients were infected with the same species and serotype as the index patient's. Pulsed-field gel electrophoresis showed that 14 (88%) of 16 with infected contacts had strains that were indistinguishable from or closely related to the index patient's strain. Latrine area fly counts were higher in patient households compared with control households, and 2 patient household water samples were positive for Shigella. We show high susceptibility of household contacts of shigellosis patients to Shigella infections and found environmental risk factors to be targeted in future interventions.

Shigella flexneri serotype 1 infections in men who have sex with men in Vancouver, Canada.

OBJECTIVES: Outbreaks of shigellosis have been documented in men who have sex with men (MSM), associated with interpersonal transmission and underlying HIV infection. We observed a rise in Shigella flexneri isolates identified in a downtown tertiary-care hospital laboratory located within the city centre community health area (CHA-1) of Vancouver, Canada. The objectives of this study were to evaluate clinical outcomes of shigellosis cases among MSM admitted to hospital and to evaluate trends in Shigella cases within Vancouver, Canada. METHODS: Adult rates of shigellosis were analysed by gender and health region, from 2005 to 2011, followed by retrospective chart review of all hospital laboratory-identified S. flexneri cases from 2008 to 2012. Serotyping and pulsed-field gel electrophoresis (PFGE) were performed on these isolates. RESULTS: Although shigellosis rates in men within CHA-1 did not change from 2005 to 2011 (range 33.4-68.5 per 100 000; P = 0.74), they were significantly higher than in other regions within the city of Vancouver (P ≤ 0.001) and the province of British Columbia (P ≤ 0.001). Shigella flexneri rates in men within CHA-1 increased significantly (range 2.3-51.4 per 100 000; P < 0.001), starting in 2008, and were higher than in other regions within Vancouver (P ≤ 0.01). Seventy-nine isolates of S. flexneri from 72 patients were identified by a single hospital laboratory. All patients were male and predominantly MSM (91.7%) and HIV-infected (86.1%), with most (92.6%) demonstrating CD4 counts ≥ 200 cells/µL. In total, 38.0% required hospitalization. Most (87.3%) had S. flexneri serotype 1 infection, with 72.9% of these representing a single PFGE pattern. CONCLUSIONS: We identified high levels of transmission of a primarily clonal strain of S. flexneri serotype 1 in our local MSM population, resulting in a substantial burden of illness and health care resource use secondary to hospital admissions.

Importation and domestic transmission of Shigella sonnei resistant to ciprofloxacin - United States, May 2014-February 2015.

In December 2014, PulseNet, the national molecular subtyping network for foodborne disease, detected a multistate cluster of Shigella sonnei infections with an uncommon pulsed-field gel electrophoresis (PFGE) pattern. CDC's National Antimicrobial Resistance Monitoring System (NARMS) laboratory determined that isolates from this cluster were resistant to ciprofloxacin, the antimicrobial medication recommended to treat adults with shigellosis. To understand the scope of the outbreak and to try to identify its source, CDC and state and local health departments conducted epidemiologic and laboratory investigations. During May 2014-February 2015, PulseNet identified 157 cases in 32 states and Puerto Rico; approximately half were associated with international travel. Nine of the cases identified by PulseNet, and another 86 cases without PFGE data, were part of a related outbreak of ciprofloxacin-resistant shigellosis in San Francisco, California. Of 126 total isolates with antimicrobial susceptibility information, 109 (87%) were nonsusceptible to ciprofloxacin (108 were resistant, and one had intermediate susceptibility). Travelers need to be aware of the risks of acquiring multidrug-resistant pathogens, carefully wash their hands, and adhere to food and water precautions during international travel. Clinicians should request stool cultures and antimicrobial susceptibilities when they suspect shigellosis, and counsel shigellosis patients to follow meticulous hygiene regimens while ill.

Intensified shigellosis epidemic associated with sexual transmission in men who have sex with men--Shigella flexneri and S. sonnei in England, 2004 to end of February 2015.

Surveillance data suggest an intensification of the shigellosis epidemic associated with sexual transmissionin men who have sex with men (MSM) in England with separate introductions into the population. In 2014, sexual transmission between MSM might have accounted for 97%, 89%, and 43% of non-travel associated Shigella flexneri 3a and S. flexneri 2a, andS. sonnei diagnoses. Clinicians should sensitively ascertain sexual history for men with enteric infections to facilitate prompt diagnosis and appropriate management.

[Analysis of the epidemiological pattern of Shigellosis in Barcelona between 1988 and 2012: Is it an emerging sexually transmitted infection?]. / Análisis del patrón epidemiológico de la shigelosis en Barcelona entre 1988 y 2012: ¿es una infección de transmisión sexual emergente?

INTRODUCTION: The aim of this study was to describe the evolution and epidemiologic characteristics of shigellosis patients over a 25 year period in a large city. METHODS: Shigellosis is a notifiable disease in Spain since 1988. Cases are analyzed in Barcelona residents included in the registry between 1988-2012. A descriptive analysis by sex, age, mode of transmission and Shigella species is presented. Trend analysis and time series were performed. RESULTS: Of the 559 cases analyzed, 60.15% were males. A sustained increase was observed in the trend since 2008 in males (p<0,05), especially at the expense of males who had no history of food poisoning or travel to endemic areas. The increasing tendency was greater in males from 21 to 60 years, both for S. flexneri (since 2009), and for S. sonnei (since 2004). In 2012 it was noted that in the men with S. flexneri, the 63% were men who have sex with men. CONCLUSIONS: An increased trend was detected in men who had no history of food poisoning or travel to endemic areas. This increase points to a change in the pattern of shigellosis, becoming predominantly male and its main mechanism probably by sexual transmission.