Outbreak of sexually transmitted, extensively drug-resistant Shigella sonnei in the UK, 2021-22: a descriptive epidemiological study.

BACKGROUND: Shigellosis, traditionally a foodborne and waterborne infection, causes substantial morbidity globally. It is now a leading cause of sexually transmitted gastroenteritis among gay, bisexual, and other men who have sex with men (MSM). We describe an ongoing outbreak of extensively drug-resistant (XDR) Shigella sonnei in the UK. METHODS: Routine laboratory surveillance (Second Generation Surveillance System, Gastrointestinal Data Warehouse) identified an exceedance of S sonnei clade 5 in England, first detected in September, 2021. Cases within this clade were subsequently reported from Scotland, Wales, and Northern Ireland. Confirmed cases in this outbreak were defined as individuals diagnosed with S sonnei clade 5 in the UK, with a specimen date between Sept 1, 2021, and Feb 9, 2022, who were genomically confirmed as part of a ten-single nucleotide polymorphism (SNP) linkage cluster. We used whole-genome sequencing with SNP typing to identify genomic clusters and antimicrobial-resistance determinants, analysing cases across the UK. We collected demographic, epidemiological, and clinical data from people infected with S sonnei clade 5 in England using questionnaires (standard and bespoke outbreak questionnaires). We used descriptive summary statistics to characterise cases. FINDINGS: 72 cases (70 [97%] male, median age 34 years [IQR 27-39]) belonging to the ten-SNP single linkage cluster of S sonnei clade 5 were identified between Sept 4, 2021, and Feb 9, 2022. Isolates were predominantly XDR, with 66 (92%) of 72 harbouring bla_CTX-M-27, a plasmid-mediated gene for production of extended-spectrum ß-lactamases (ESBLs). Of 33 cases with clinical data, 19 (58%) received antibiotics and eight (24%) were hospitalised. 21 (78%) of 27 cases with completed bespoke outbreak questionnaires were HIV-negative MSM taking HIV pre-exposure prophylaxis (PrEP) who reported sexual contacts in the UK and Europe within the incubation period. INTERPRETATION: We highlight the rapid dissemination of XDR ESBL-producing S sonnei in sexual networks of MSM. We recommend strengthening shigella testing where clinically indicated, antimicrobial-resistance surveillance, and integrated health promotion messaging among all MSM, including PrEP users, to reduce the burden of shigellosis. FUNDING: National Institute for Health Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool in partnership with the UK Health Security Agency.

A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis.

Shigella species account for the second-leading cause of deaths due to diarrheal diseases among children of less than 5 years of age. The emergence of multi-drug-resistant Shigella isolates and the lack of availability of Shigella vaccines have led to the pertinence in the efforts made for the development of new therapeutic strategies against shigellosis. Consequently, designing small-interfering RNA (siRNA) candidates against such infectious agents represents a novel approach to propose new therapeutic candidates to curb the rampant rise of anti-microbial resistance in such pathogens. In this study, we analyzed 264 conserved sequences from 15 different conserved virulence genes of Shigella sp., through extensive rational validation using a plethora of first-generation and second-generation computational algorithms for siRNA designing. Fifty-eight siRNA candidates were obtained by using the first-generation algorithms, out of which only 38 siRNA candidates complied with the second-generation rules of siRNA designing. Further computational validation showed that 16 siRNA candidates were found to have a substantial functional efficiency, out of which 11 siRNA candidates were found to be non-immunogenic. Finally, three siRNA candidates exhibited a sterically feasible three-dimensional structure as exhibited by parameters of nucleic acid geometry such as: the probability of wrong sugar puckers, bad backbone confirmations, bad bonds, and bad angles being within the accepted threshold for stable tertiary structure. Although the findings of our study require further wet-lab validation and optimization for therapeutic use in the treatment of shigellosis, the computationally validated siRNA candidates are expected to suppress the expression of the virulence genes, namely: IpgD (siRNA 9) and OspB (siRNA 15 and siRNA 17) and thus act as a prospective tool in the RNA interference (RNAi) pathway. However, the findings of our study require further wet-lab validation and optimization for regular therapeutic use for treatment of shigellosis.

A Significant Decrease in the Incidence of Shigellosis in Israel during COVID-19 Pandemic.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19 and is mostly person-to-person transmitted through respiratory droplets. The implications of the strategies implemented to prevent COVID-19 transmission on other infectious diseases are unclear. We aimed to appraise trends in the incidence of salmonellosis, shigellosis and campylobacteriosis in Israel during COVID-19 pandemic. Positive stool samples for Salmonella, Shigella and Campylobacter are reported on a monthly basis to the Israel Center for Disease Control from sentinel laboratories, within the framework of a surveillance network of bacterial culture-proven enteric diseases. Age-adjusted incidence rates per 100,000 of shigellosis, salmonellosis and campylobacteriosis were calculated. Mean rates before and after the local onset of COVID-19 pandemic in Israel were compared and Relative Risk Reduction (RRR) was calculated. Joinpoint was used to evaluate secular trends. The mean age-adjusted incidence rate of shigellosis in March-July 2020 was lower than the rate observed in March-July 2018-2019 (RRR = 86.6%), but also decreased for salmonellosis (RRR = 33.0%) and campylobacteriosis (RRR = 30.0%). Using Joinpoint we have shown that the decrease observed for shigellosis was significantly sharper (Annual Percent Change (APC) = -77.7) between February 2020 and May 2020 than for salmonellosis (APC = -14.0) between July 2019 and April 2020 and for campylobacteriosis (APC = -1.1) between January 2018 and July 2020. The preventive measures applied to reduce transmission of COVID-19, including social distancing and hand washing, were ecologically associated with a decreased risk of bacterial enteric diseases in Israel. The association was strongest for shigellosis, a disease that is mostly person-to-person transmitted, as compared to salmonellosis and campylobacteriosis which are mostly foodborne transmitted.

Antiviral activity of the high-molecular-weight plant polysaccharides (Panavir®).

This short report is dedicated to the description of the wide antiviral and antibacterial activity of the immune-modulating agent Panavir®. Panavir® is a high-molecular-weight fraction of the polysaccharides extracted from the shoots of the Solanum tuberosum. It demonstrates activity against many types of viruses, including animal coronavirus and also against bacterial infections. These properties look very promising considering the COVID-19 epidemy and allow propose that Panavir® would be effective in the therapy of the SARS-CoV-2 infection.