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To: STI Network

Cc: National Coordinators

Dear Colleagues,

In recent years, 2022 to 2024, cases have been reported in EpiPulse of Shigella infection with MDR/XDR strains that predominantly affect gay, bisexual and other men who have sex with men (MSM) in several Member States. Most often these alerts were initiated by the FWD Network. Considering the relevance for the STI Network of being aware of the ongoing transmission clusters, access has been given by ECDC to the STI Network to the EpiPulse items reporting on Shigella cases among MSM.

Considering the need to collaborate across networks to adequately understand transmission dynamics and to identify, report and respond to the continued transmission of MDR/XDR Shigella, on 7 June 2024 ECDC organised a joint virtual meeting of the Coordination Committees of the two networks. The aim was to obtain guidance on what the networks expect from ECDC and where collaboration across countries and networks would be of EU-added value.

We are sharing attached for your information the minutes of the meeting and are available for any further clarifications.

Many thanks to the STI Network Coordination Committee and FWD Network Coordination Committee members who contributed to this discussion.

With best regards,

Otilia Mardh and Therese Westrell, on behalf of ECDC STI and FWD team, respectively

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Joint STI-FWD DNCC_7 June 2024_Report.pdf

Joint STI-FWC DNCC MEETING 2024

Meeting report

7 June 2024 Online meeting, 12:30-14:00

Opening and meeting objectives A joint meeting of the ECDC Disease Network Coordinating Committees for sexually transmitted infections (STI) and food- and waterborne diseases (FWD) was held on 7 June 2024, 12:30-14:00.

Otilia Mardh and Therese Westrell (ECDC) welcomed the participants and outlined the agenda (Annex 1). Participants from the two networks introduced themselves (Annex 2).

The overall aim of the meeting was to obtain guidance on what the networks expect from ECDC in the area of sexually transmitted enteric pathogens, in particular MDR/XRD Shigella and where collaboration across countries and networks would be of EU-added value.

The specific objective was to discuss and collect opinions of the following topics:

• How concerned are we about the MDR/XDR aspect and risk for spread into the general community? The severity of these infections? The sexual health aspects of these diseases?

• How do we want to react/communicate across the networks about these MDR/XDR Shigella clusters/cases? Is the information provided in EpiPulse adequate for you to take action?

• Any additional actions from ECDC to facilitate collaboration across networks/countries on the MDR/XDR Shigella issue and other “enteric” STIs?

Background

Over the course of 2022, 2023 and 2024, cases have been reported in EpiPulse of Shigella infection with MDR/XDR strains that predominantly affect gay, bisexual and other men who have sex with men (MSM) in several Member States. The events were periodically reflected in ECDC’s weekly Communicable Disease Threats Reports (CDTR) and epidemiological updates that we hope were useful for guiding national responses.

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The FWD Network had a pivotal role in contributing to the reporting of these cases in EpiPulse by providing epidemiological and microbiology updates, and outbreak strain sequencing details that helped defining the multi-country geographical spread, the role of mass gathering events attended by MSM as transmission hot- spots, and the MDR/XDR characteristics of the strains. There have also been cases alerted and reported by STI, Antimicrobial resistance, and Epidemic Intelligence networks.

Considering the relevance for the STI Network of being aware of the ongoing transmission clusters, access has been given by ECDC to the STI Network to the EpiPulse items reporting on Shigella cases among MSM. This is especially important in relation to the Pride season and other festivals attended by MSM, and the involvement of the STI Network experts in tailoring national public health measures.

More details on the events can be found in the ECDC presentation shared together with this report.

Discussion

How concerned are we about the MDR/XDR and sexual health aspects of these diseases?

Germany mentioned that it may be worth noting notification aspects - it is not clear how many countries are collecting and reporting information on transmission category or sexual orientation of the individual.

It was noted that, in Belgium, Shigella is notifiable only in part of the country. In 2022, the risk assessment and risk management groups from STI and FWD, including the regional health authorities, did a joint risk assessment on this topic, including actions for response.

Denmark has noted a large increase in gonorrhoea in MSM as well as in young heterosexuals, but sequencing of these clusters indicated insignificant overlap in the two populations (Pedersen et al. 2024). There is a higher resistance pattern in gonorrhoea cases in the MSM population than among the young heterosexuals.

In the Netherlands, about 60% of the Shigella patients are men, but 40% are women. The strains corresponding to these cases are mixed and not completely distinct. In 2023, the Netherlands had the highest incidence of shigellosis in 10 years’ time. There is an increasing trend towards only doing molecular diagnostics and only culturing the most severe hospitalised cases. The lack of Shigella isolates for characterisation puts a threat on the possibility to receive and analyse trends for surveillance.

Regarding the latter: it is the same in Germany, i.e. surveillance concerns following the introduction and application of PCR panel diagnostics.

In France, shigellosis is not a reportable disease and the reported data come from laboratories. In the Shigella isolates received, 94% are from men, mostly young men. France attempted an ad hoc study on previous sexual exposure, but it was complicated due to cross-disciplinary nature of the work. This trend has been observed for some time but spillover to other populations has not yet been observed. Most physicians see Shigella as a travel- associated infection. There may be a need to educate physicians that Shigella in men that do not have a recent travel history should be an indication for screened for other STI and counselling on sexual transmission.

It may be relevant to consider how treatment guidelines for other STIs (e.g. gonorrhoea) may be impacting the MDR/XDR Shigella situation.

In France, the ANRS Doxyvac open-label trial was conducted in MSM on PrEP to receive either doxycycline or non-doxycycline (2:1) post-exposure prophylaxis (PEP); all patients were screened for ESBL-producing E. coli on selective agar and, in some cases, ESBL-producing Shigella were detected. Which arm of the study the patients

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were in has not yet been looked at. Many of the Shigella infections detected were not accompanied by symptoms, but shigellosis with or without ESBL production has been described in some participants.

In Belgium there has been increased azithromycin resistance in gonorrhoea, from 0 to 36%, starting with MSM and now spreading to other populations. Azithromycin has been removed as first-line treatment option for both chlamydia and gonorrhoea in Belgium in 2023 and in France in 2022.

In Germany, the current difference between travel-associated infections with Shigella and the sexually transmitted infections are the AMR profiles, so one important public health measure would be to sensitize treating physicians for a higher probability of AMR in STI-related Shigella cases and to inform about smart therapeutic approaches, as well as to initiate necessary partner notification and treatment to avoid further clinically serious infections.

In summary, there appears to be substantial antimicrobial resistance in gonorrhoea cases and substantial use of antimicrobials in some populations of MSM. The latter may increase the selection of multiresistant bacteria in this particular population, and thus have an influence on a potential resistance exchange and rise of MDR/XDR Shigella cases. Data on severity and treatment outcomes of MDR/XDR Shigella cases are not very complete. Several countries indicated that the threshold for diagnostics for diarrhoeal disease is quite high, so there is likely a large under-estimate of the number of shigellosis cases in general with diagnosis primarily of more severe cases. The same can be assumed for MDR/XDR Shigella cases. Studies in the US have shown that 30% of adult male shigellosis cases suffered from severe disease (hospitalisation, septicaemia or death) compared to 25% of adult female cases (McKrickard et al, 2018).

ECDC asked the DNCCs to provide input on how much to focus on this issue, given that source control does not seem to be possible such as in the classical approach to Shigella for FWD outbreaks.

With information provided via EpiPulse, Germany liaises with FWD counterparts, but also with specialised clinicians to sensitize on treatment options to allow quicker and more appropriate treatment. There is no possibility to do full source control for sexually acquired cases, but advice can be given if it is clear that sexual transmission is increasing. For example, patients and the MSM community could be sensitized and this could impact the most appropriate treatment.

Spain indicated that notifications were helpful, but that determining the nature of transmission is difficult (sexual versus food or other items). As many individuals are treated without confirmation of the bacteria, it is difficult to know the true burden of disease. Spain indicated that continued alerts are important as they increase awareness of the problem.

In Portugal, notification of shigellosis is mandatory. Clinical and laboratory notifications are collected in SINAVE (national portal for reporting), however the level of completeness of reporting is uncertain. Epidemiological criteria include “transmission between humans” without further information on sexual transmission being available. The DGS is however aware of the risk of sexually transmitted outbreaks. A study with a EUPHEM fellow involving the Portuguese National Institute for Health and a Spanish laboratory, found similarity between Shigella strains in both countries.

The Netherlands noted that most cases are responded to by municipal health services and they are responding locally. It is not possible to do source control, but the Netherlands does surveillance to understand whether international links are there but not otherwise.

Croatia also mentioned that reports are helpful in raising awareness, although there are mostly sporadic cases thus far, with some increases in recent years. In Croatia, shigellosis is a mandatory notifiable disease. According

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to reports, there have been only few cases i.e. less than five (1-3), in 2020, 2021, 2022, but an increased number of reports in 2023 and 2024 compared to the previous few years, i.e. more than 50 cases with 10 so far in 2024, mostly men. The route of transmission is not collected routinely in the reports, but Croatia tries to find out the route of transmission through surveys administered to the cases (it is routine part of epidemiological investigation and contact tracing). Information from ECDC about the occurrence of cases is helpful; Croatia follows EWRS and Epipulse data as well as reports from ECDC about events and, on this basis, strengthens the monitoring of shigellosis in the country and informs epidemiologists and clinicians to pay attention to the sexual route of transmission when surveying. Also, the NGOs that work with the MSM population are informed about the occurrence of shigellosis in the EU related to MSM and certain events.

Discussion on sexual health aspects concluded that screening for Shigella in high-risk groups of MSM may be beneficial.

Any additional actions from ECDC to facilitate collaboration across networks/countries on the MDR/XDR Shigella issue and other “enteric” STIs?

Information on Shigella clusters and outbreaks is relevant in conjunction with Pride events when the attendees and/or sexual health services should become aware of XDR Shigella strains circulation and sensitised about prevention measures. The importance of working with Civil Society representatives on XDR Shigella was noted. If the community does not consider MDR/XDR Shigella in MSM as a serious issue, then we cannot expect significant progress/impact on epidemiology. Mpox is a good example of a fruitful collaboration with Civil Society.

ECDC has produced several outputs which mention this issue including a rapid risk assessment (2022), epidemiological update (2023), and in communicable disease threat reports in 2023 and 2024, as well as in news items.

ECDC’s FWD team also has a sequencing contract available and if needed, support is available from ECDC to assist countries with whole-genome sequencing. The outbreak strains sequencing data shared by countries are also analysed and the clusters are monitored in EpiPulse Molecular Typing Tool where the AMR determinants are also recorded.

ECDC’s ARHAI team indicated that carbapenems are often the only option when treatment of infection by MDR/XDR Shigella is clearly indicated (e.g. in severely ill or immunocompromised patients). Use of carbapenems in cases without a clear indication for treatment should be weighed with the risk of selection of resistance against these last-resort antibiotics. It was also suggested that more information should be collected on severity. It should also be explored whether a prospective study for Shigella cases could be conducted, in liaison with Civil Society, where clinicians could take a history on antibiotic use (including, but not limited to, DoxyPEP) and sexual practices. This could help provide additional information on the cases and more information on how to address this issue.

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Annex 1. Agenda Time Agenda item Facilitator(s) 12:30 – 12:45 Welcome and introductions Otilia Mardh

Therese Westrell 12:45 – 13:00 Brief overview of the events (ECDC)

Cecilia Jernberg Lina Nerlander Therese Westrell

13:00 – 13:50 Discussion

o How concerned are we about the MDR/XDR and sexual health aspects of these diseases?

o How do we want to react/communicate across the networks about these MDR/XDR Shigella clusters/cases?

o Any additional actions from ECDC to facilitate collaboration across networks/countries on the MDR/XDR Shigella issue and other “enteric” STIs?

All

13:50 – 14:00 Conclusions, further actions (ECDC)

Otilia Mardh Therese Westrell

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Annex 2. List of participants Name Country or Affiliation E-mail

FWD Coordination Committee Members

Eelco Franz Netherlands [email protected]

Eva Grilc Slovenia [email protected]

Silvia Herrera León Spain [email protected]

Stefano Morabito (apologies) Italy [email protected]

Maria Pavlova (apologies) Bulgaria [email protected]

Ruska Rimhanen-Finne (apologies) Finland [email protected]

Mathieu Tourdjman (apologies) France [email protected]

Dieter van Cauteren Belgium [email protected]

Oliver Vandenberg (apologies) Belgium [email protected]

Hendrik Wilking Germany [email protected]

STI Coordination Committee Members

Béatrice Berçot France [email protected]

Irith De Baetselier Belgium [email protected]

Maria José Borrego Portugal [email protected]

Steen Hoffmann (apologies) Denmark [email protected]

Javier Gómez Castellá (apologies) Spain [email protected]

Klaus Jansen Germany [email protected]

Maartje Visser Netherlands [email protected]

Erna M Kojic Iceland [email protected]

Maria Wessman Denmark [email protected]

Tatjana Nemeth-Blažić Croatia [email protected]

ECDC Staff

Therese Westrell ECDC [email protected]

Otilia Mardh ECDC [email protected]

Cecilia Jernberg ECDC [email protected]

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Lina Nerlander ECDC [email protected]

Celine Gossner ECDC [email protected]

Diamantis Plachouras ECDC [email protected]

Dominque Monnet ECDC [email protected]

Anastasia Pharris ECDC [email protected]

Taina Niskainen ECDC [email protected]

STI&FWD DNCCslides.pdf

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Joint virtual meeting of STI and FWD Networks Coordination Committees 7 June 2024

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Agenda

12:30 – 12:45 Welcome and introductions

12:45 – 13:00 Brief overview of the events (ECDC)

13:00 – 13:50 Discussion

• How concerned are we about the MDR/XDR and sexual health aspects of

these diseases?

• How do we want to react/communicate across the networks about these

MDR/XDR Shigella clusters/cases?

• Any additional actions from ECDC to facilitate collaboration across

networks/countries on the MDR/XDR Shigella issue and other “enteric” STIs?

13:50 – 14:00 Conclusions, further actions (ECDC)

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Introductions

FWD ECDC team

FWD DNCC Eelco Franz

Silvia Herrera León

Stefano Morabito

Maria Pavlova

Ruska Rimhanen-Finne

Mathieu Tourdjman

Dieter Van Cauteren

Hendrik Wilking

Eva Grilc

STI ECDC team

STI DNCC Béatrice Berçot

Irith De Baetselier

Maria José Borrego

Steen Hoffmann

Javier Gómez Castellá

Klaus Jansen

Maartje Visser

Erna M. Kojic

Maria Wessman

Tatjana Nemeth-Blažić

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Overview of the events

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Outbreaks of Shigella within the EU/EEA have previously mainly been associated with schools, other institutional settings, restaurants, imported fresh vegetables. Large proportion of infections associated with travel.

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Increase of events reported in EpiPulse associated with men who have sex with men (MSM)

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In June 2023, the Netherlands launches an event in EpiPulse, FWD domain…

“Cluster of cases with a new strain not seen before, mainly among men who have sex with men.”

Outbreak strain sequence file shared

In December 2023 the UK launches an event in the STI domain. “Detection of a new cluster of extremely antibiotic-resistant Shigella sonnei in men who have sex with men.“ Outbreak strain sequence file shared and compared. ->Strain matches the Netherlands outbreak strain.

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Sequences added to EpiPulse Molecular Typing Tool

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April 2024 Belgium launches an event in the FWD domain

“Shigella cases linked to Darklands festival Belgium”

Same outbreak strain again, events are merged.

Persistent multi drug (extensively drug) resistant Shigella strains within the MSM population.

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Context

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‘Traditional’ STIs are increasing in MSM

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Source: Country reports from Czechia, Germany, Greece, Latvia, the Netherlands, Norway, Romania, Slovakia, Slovenia, and Sweden.

ECDC (2024). Syphilis - Annual Epidemiological Report for 2022 (europa.eu)

Syphilis

Source: Country reports from Czechia, Denmark, Finland, Greece, the Netherlands, Norway, Romania, Slovenia, and Sweden.

Gonorrhoea

ECDC (2024). Gonorrhoea - Annual Epidemiological Report for 2022 (europa.eu)

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Non-traditional STIs

Enteric

- Shigella

- Hepatitis A

- Mpox

- Meningitis

https://www.ecdc.europa.eu/en/publications-data/rapid-risk-assessment-increase-extensively-drug-resistant-shigella-sonnei 13

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Hepatitis A

Spread of genotype IB hepatitis A virus strains in several EU/EEA countries and UK

• 300 cases

• Majority young males-many MSM

• Q1-Q2 of 2022

Outbreak also in 2016-2018

2024: Portugal and a few cases in NL, DE

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https://www.ecdc.europa.eu/sites/default/files/documents/RRA%20hep%20A%20outbreak%20EU%20EE A%20in%20MSM%20third%20update%2028%20June%202017_0.pdf https://www.ecdc.europa.eu/en/news-events/spread-hepatitis-virus-strains-genotype-ib-several-eu- countries-and-united-kingdom

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0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022

Year

Proportion males among shigellosis cases 20-64 years, EU/EEA, 2007-2022

Proportion males among hepatitis A cases 20-64 years, EU/EEA, 2007-2022

Changing epidemiology

Confirmed shigellosis cases per 100 000 population, by age and gender, EU/EEA, 2022

Confirmed hepatitis A cases per 100 000 population, by age and gender, EU/EEA, 2022

0%

10%

20%

30%

40%

50%

60%

70%

80%

2007 2008200920102011201220132014201520162017201820192020 20212022

Year

Multi-country outbreak in MSM, 4 500 confirmed cases

in 22 EU/EEA countries

Reported transmission mode, EU/EEA

2018-2022

Animal

Food

Lab

Other

PTP

Recreational water Sex

Sexual transmission: 100% males

Sexual transmission: 98% males

Reported transmission mode, EU/EEA

2018-2022

Food

HAI

IDU

Other

PTP

Recreational water Sex

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Antimicrobial resistance in gbMSM strains

ECDC contacted by Irish FWD expert, April 2023

In June 2023, Ireland published ”Recommendation on aspects of management of shigellosis in Ireland in the context of current antimicrobial resistant Shigella species associated with gay, bisexual and men who have sex with men (gbMSM)”

1. For severe cases, IE recommends last resort intravenous antimicrobial treatment until known whether susceptible to normal first line antimicrobials

2. For less severe cases, recommends macrolide (azithromycin), second line oral antimicrobial

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Sexual practices associated with transmission of enteric pathogens in MSM

- Faecal-oral contact

- Anal => oral

- Fisting, fingering

- Rimming

- Use of sex toys

- Douching (contaminated equipment)

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Sexual partnership frequency distribution

https://www.ecdc.europa.eu/sites/default/files/documents/European-MSM-internet-survey-2017-findings.pdf 18

More likely to be on apps / HIV+: May not be representative of all MSM

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Sexual networks / international spread

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Shigella

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Civil society

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Who takes care of it?

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FWD STI Shigella outbreak

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We need both skillsets

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FWD STI

The pathogen

Nomenclature

Routes of transmission

Incubation

Duration of infectiousness

Persistence in the environment

Treatment

Species / serotypes

AMR issues

The population

MSM population

Sexual risk behaviours

Venues

Terminology

Stigma

Connections with civil society

How to communicate

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Outputs so far

Feb 2022 – rapid risk assessment

https://www.ecdc.europa.eu/en/publ ications-data/rapid-risk-assessment- increase-extensively-drug-resistant- shigella-sonnei

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July 2023 – Epi update

Spread of multidrug-resistant Shigella in EU/EEA among gay, bisexual and other men who have sex with men (europa.eu)

December 2023 – CDTR

Communicable disease threats report, 17- 23 December 2023, week 51

April 2024 – CDTR

ECDC weekly CDTR Week 15, 7–13 April 2024

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Discussion

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Discussion

How concerned are we about

- the MDR/XDR aspect and risk for spread into general community?

- the severity of these infections?

- the sexual health aspects of these diseases?

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Discussion

How do we want to react/communicate across the networks about these MDR/XDR Shigella clusters/cases? Is the information provided in EpiPulse adequate for you to take action?

Any additional actions from ECDC to facilitate collaboration across networks/countries on the MDR/XDR Shigella issue and other “enteric” STIs?

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Thank you for today!

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Our recommendations (if we have time)

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What we advise - prevention

- Disposable gloves for fingering or fisting

- Dental dams during oral-anal sex

- Changing condoms between anal and oral sex

- Not share sex toys

- Ensure proper cleaning and disinfection after use of sex toys and between partners

- Wash hands, genital and anal areas before and after sexual contact

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What we advise – if symptoms

If a person develops gastrointestinal symptoms:

- Refrain from sexual activity, pay extra attention to personal hygiene and seek healthcare

- Inform the physician that the infection may have been acquired through sexual activity.

- Not handle or prepare food in catering establishments, avoid using public pools, spas and hot tubs

If diagnosed:

- Avoid sexual activity for at least seven days after symptoms have completely disappeared

- Avoid oral-anal contact during sex for four to six weeks

- Sexual partners of patients diagnosed with shigellosis should be notified

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What we advise – for clinicians

- Increase awareness among clinicians and microbiology laboratories

- Ensure antimicrobial susceptibility testing of Shigella for cases of gastroenteritis in gbMSM

- Physicians should be aware that among young adult males the route of acquisition can be sexual (especially among those without travel history to a country with known increased risk of shigellosis).

- Report shigellosis cases to public health authorities and send Shigella isolates to national reference laboratories