Increase in resistant Shigella infections among men who have sex with men

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Feb 7 2023

Shigellosis, which arises due to Shigella species transmission through the fecal-oral route, was initially identified among individuals with recent travel history to England. Notably, Shigella sonnei and Shigella flexneri reportedly transmit through sexual contact among gay, bisexual, and other men who have sexual intercourse with men (MSM).

In a recent study published in The Lancet Infectious Diseases, researchers report a rise in Shigella flexneri type 2a infections in men who have sexual intercourse with men (MSM) in England from September 2021 onward.

Study: Emergence of extensively drug-resistant and multidrug-resistant Shigella flexneri serotype 2a associated with sexual transmission among gay, bisexual, and other men who have sex with men, in England: a descriptive epidemiological study. Image Credit: AnaLysiSStudiO / Shutterstock.com

About the study

In September of 2021, the emergence of the extensively drug-resistant (XDR) Shigella sonnei that consists of the plasmid-encoded extended-spectrum beta-lactamase-producing -producing (ESBL) bla_CTX-M-27 gene was reported.

Specimens obtained between September 1, 2015, and 1June 23, 2022, containing Shigella flexneri encoding the bla_CTX-M-27 gene, as well as those verified by phylogenetic analysis as belonging to any of the t10 clusters with approximately 10 single nucleotide polymorphisms (SNP), were identified as cases.

Genomic deoxyribonucleic acid (DNA) was extracted and subsequently subjected to long-read Nanopore sequencing to determine the genetic location of the bla_CTX-M-27 gene. Patients completed questionnaires on their clinical and demographic information, which was also analyzed in conjunction with the laboratory findings.

MEDLINE and PubMed databases were also searched from the inception of the study until July 2022, with search terms including ‘sexually transmitted,’ ‘MSM,’ ‘Shigellosis,’ ‘Shigella,’ ‘CTX-M,’ ‘Shigella flexneri,’ ‘CTX-M-27,’ and ‘antimicrobial resistance.’ Regional healthcare protection teams administered Shigella surveillance questionnaires through telephonic interviews.

Study findings

A persistent elevation in infections by Shigella flexneri encoding the bla_CTX-M-27 gene, which amounted to a total of 26 cases, was observed from September 2021 onward. Acquisition of the bla_CTX-M-27 gene by Shigella flexneri serotype 2a led to the generation of an XDR paraphyletic cluster in eight cases, as well as 18 cases with monophyletic cluster of Shigella flexneri resistance to multiple antimicrobials.

All 26 Shigella flexneri serotype 2a cases were identified in adult males with a median age of 37 years and no prior travel to endemic nations. Of the 13 males who completed the surveillance questionnaires, 77% were MSM and 54% were engaged in sexual activities during the week before the onset of symptoms.

Antimicrobials were administered in 54% of cases, the most commonly administered including ciprofloxacin and azithromycin. Among the patients, 31% were hospitalized for a median of five days.

IncFII-type plasmids comprising the bla_CTX-M-27 gene were identical to XDR Shigella sonnei plasmids, with 82.0% nucleotide (nt) similarity and 99.0% nt resemblance between the Shigella flexneri and Shigella sonnei plasmid clusters.

Shigella flexneri serotype 2a cases reduced considerably in mid-2020, during which coronavirus disease 2019 (COVID-19) preventive measures were widely implemented. However, cases resurged later that year and onward.

Shigella flexneri serotype 2a was identified as the predominant serotype until late 2019. However, serotypes 1b and 3a have since been identified as key contributors to the burden of S. flexneri 2a cases, with few S. flexneri serotypes 1c and 6 reported.

Between September 1, 2015, and June 12, 2022, 1.3% of the 2,779 Shigella flexneri infection cases were caused by organisms harboring the bla_CTX-M-27m gene, with 70% of the bla_CTX-M-27-encoding Shigella flexneri pathogenic isolates documented from September 2021 onward. Prior to September 2021, 30% of cases were documented sporadically, including four cases caused by serotype 2a, three cases caused by serotype 1c, two cases caused by serotype 1a, and two cases caused by serotype 3a.

Conclusions

The study findings highlight the sustained increase in XDR and multidrug-resistant Shigella flexneri serotype 2a infections due to pathogens harboring the plasmid-encoded bla_CTX-M-27 gene among MSM individuals in England from September 2021 onward. Plasmid and epidemiological similarities were observed with XDR Shigella sonnei infections, thus indicative of horizontal-type acquisitional events in community settings.