Extensively drug-resistant Shigella sonnei infections - Europe

24 March 2022

Outbreak at a glance
The World Health Organisation (WHO) was notified on 4 February 2022 of an unusually high number of cases of extensively drug-resistant (XDR) Shigella sonnei which have been reported in the United Kingdom of Great Britain and Northern Ireland and several other countries in the WHO European Region since late 2021. Although most infections with S. sonnei result in a short duration of disease and low case fatality, multi-drug resistant (MDR) and XDR shigellosis is a public health concern since treatment options are very limited for moderate to severe cases.
Situation in the United Kingdom
The United Kingdom is currently investigating a cluster of 84 cases of XDR S. sonnei, with the dates of sample collection between 4 September 2021 and 1 March 2022. This compares to 16 cases, none of which were XDR, in a 17-month period between 1 April 2020 and 31 August 2021, although case notification rates during this time may have been underestimated due to the COVID-19 pandemic control measures. Cases from the investigated cluster are distributed across all regions of England, Scotland and Northern Ireland.

Figure 1. Epidemic curve of extensively drug-resistant Shigella sonnei cases reported in England, the United Kingdom between 4 September 2021 and 1 March 2022, by date of sample collection
*This epidemic curve excludes eight cases which were reported from areas in the United Kingdom outside of England. The data should be interpreted with due consideration for care-seeking, testing and reporting practices.
During investigations, 37 cases were interviewed, of which 46% (17/37) attended emergency services and 24% (9/37) were hospitalized. Direct, person-to-person transmission including sexual transmission between men who have sex with men (MSM) was identified as the most frequently reported route of transmission among the interviewed cases. All 37 cases were reported to be non-susceptible to various types of antibiotics (penicillin, third generation cephalosporins, aminoglycosides, tetracycline, sulphonamides, quinolones and azithromycin), leaving very limited treatment options for severe cases.
Situation in other countries in the WHO European Region
As of 17 March 2022, at least nine additional countries in the European Region have reported cases of S. sonnei, including some cases infected with XDR S. sonnei. These cases show a resistance profile similar to that reported in the United Kingdom (Figure 2, Table 1).

Figure 2. Countries in the WHO European Region which have reported extensively drug-resistant Shigella sonnei in 2020-2022 as of 17 March 2022
Table 1. Reports of extensively drug-resistant Shigella sonnei from countries in WHO European Region in 2020-2022, excluding the United Kingdom, as of 7 March 2022
Austria 9 cases 10 February 2022 28 June - 16 November 2021 All strains detected from these cases show resistance to ciprofloxacin and azithromycin. Based on sequencing and genomic analyses, all samples were related to the cluster in the United Kingdom.
Belgium 20 cases (randomly selected samples of drug-resistant S. sonnei) 9 February 2022 19 July - 2 September 2021 Whole genome sequencing (WGS) analyses identified four strains related to the cluster in the United Kingdom
Denmark 2 cases of XDR shigellosis 23 March 2022 29 November 2021 - 11 February 2022 Samples from the cases showed the same resistance profile reported from the United Kingdom cluster.
France Over 100 isolates 9 February 2022 September 2020 - February 2022 Isolates displayed a similar resistance profile to that reported in the United Kingdom.
Germany 14 cases 10 February 2022 10 February 2022 Isolates of the cases had sequences similar to that reported in the United Kingdom with two having the same resistance profile
Ireland 8 cases of XDRshigellosis; 2 additional cases under investigation 24 February 2022 Date of sample collection is unknown. Dates of onset were October -December 2021 Isolates of the cases had the same gene and resistance profiles as those reported in the United Kingdom. Three of seven cases with available information had recent travel history to the United Kingdom, Italy and Spain.
Italy 6 cases 10 February 2022 July - September 2021 Two strains, isolated from the same region in September 2021, showed resistance to ampicillin, sulphonamides, fluoroquinolones, third generation cephalosporins, azithromycin, trimethoprim and trimethoprim/sulfamethoxazole.
Norway 6 cases 4 February 2022 21 September 2021 - 16 January 2022 Isolates of cases were similar to each other and closely related to representative sequences from the United Kingdom
Spain 30 cases 23 March 2022 February 2021 - March 2022 Sequencing and genomic analysis of isolates showed that 19 were part of the same cluster related to the United Kingdom. Three cases have been excluded and eight are pending. These 19 isolates were all resistant to ampicillin, third generation cephalosporins, fluoroquinolones, sulphonamides, trimethoprim, azithromycin and streptomycin.
Epidemiology of Shigellosis
Shigellosis isa gastrointestinal infection caused by one of four species of Shigella bacteria, including S. sonnei. It is a virulent pathogen with a very low infective dose, which means that only a small number of bacteria, approximately 10 to 100 organisms, is sufficient to cause disease. Humans are the only known reservoir and can excrete bacteria in stool for weeks after bloody diarrhoea.
Shigella is found in the intestinal tract of infected people and can be transmitted through the faecal-oral route by person-to-person contact, contact with faeces from an infected person, or indirect contact such as by flies, fomites, consumption of contaminated food or water. Asymptomatic carriers can also transmit the disease. Sustained sexual transmission has become an important transmission route for shigellosis.
Themost common symptoms associated with S. sonnei infections include: watery or bloody diarrhoea, abdominal pain and cramps, fever, nausea, vomiting, loss of appetite, headache and malaise. While most infections with S. sonnei result in a short duration of disease, with recovery within a week and low case fatality rate, this is not always the prognosis for immunocompromised cases and complications can occur. Moderate to severe infection is typically treated with antibiotics, however with the growing incidence of MDR and XDR Shigella globally, treatment options become increasingly limited. Cases of XDR S. sonnei have been reported previously in Australia and the United States of America.
Shigellosis is endemic in most low- or middle-income countries (LMICs) and is a major cause of bloody diarrhoea worldwide. Each year, it is estimated to cause at least 80 million cases of bloody diarrhoea and 700 000 deaths. Almost all (99%) Shigella infections occur in LMICs, and the majority of cases (~70%), and of deaths (~60%), occur among children less than five years of age. It is estimated that <1% of cases are treated in the hospital.

Public health response

National health authorities are conducting epidemiological and genomic investigations in their respective countries to determine the route of transmission and the genomic linkage of the cases with the representative strain of the cluster detected in the United Kingdom.
WHO has communicated to national authorities to report cases or clusters of drug-resistant S. sonnei using Global Antimicrobial Resistance Emerging Antimicrobial Resistance Reporting component (GLASS EAR), and to share this information with relevant services and clinics dealing with sexual transmitted infections.

WHO risk assessment

Based on the limited information available at this stage, the likelihood of spread from the United Kingdom to other countries and the prevalence of XDR S. sonnei is high. Some findings from case interviews suggest possible exposure in other countries. Authorities in the United Kingdom are investigating cases in other countries that may be linked to the same cluster. The risk of spread of this particular strain of S. sonnei among the general population and the proportion of secondary cases among non-high-risk groups is unknown.
The recent increase in S. sonnei infections in the United Kingdom may represent an increase in reporting activities following the COVID-19 pandemic and resumption of social contact, especially in MSM exposed to high-risk sexual practices and in immunocompromised adults. This outbreak may represent a serious public health impact because the pathogen is XDR and the number of cases is unusually above previously reported numbers in the United Kingdom in 2020-2021. In addition, the mechanism of antimicrobial resistance by which this S. sonnei strain has gained XDR characteristics is unusual and bacteria with this type of resistance mechanism have not been frequently reported in the United Kingdom recently. Currently, phenotypic data and Whole Genomic Sequencing (WGS) data from isolates is limited, which challenges the characterization and tracking of the event.
Thus far, cases have only been reported in countries with high surveillance capacity and high water, sanitation and hygiene (WASH) standards. However, the long carriage of Shigella bacteria post-infection, the potential role of asymptomatic carriers, and the very low infective dose are factors that could enable spread of the XDR strains globally. If XDR S. sonnei is introduced to resource limited countries where WASH conditions are suboptimal, there is a risk for a major diarrhoeal disease outbreak with potentially a high case fatality rate, including among children.

WHO advice

Prevention: General hygiene measures including handwashing with soap and water are important for reducing transmission of Shigella. Prevention of bloody diarrhoea caused by Shigella relies primarily on measures that prevents spread of the bacteria within the community, including person-to-person transmission. These include hand washing with soap, ensuring the availability of safe drinking water, safely disposing of human waste, breastfeeding of infants and young children, safe handling and processing of food, and controlling houseflies.
Symptomatic individuals are recommended to avoid sexual contact to reduce transmission.
Treatment: For moderate to severe cases of non-resistant shigellosis, antibiotic therapy is recommended. Clinical improvement can be expected within 48 hours of antibiotic therapy for non-drug resistant shigella, which results in a decreased risk of serious complications and death, shorter duration of symptoms, the elimination of Shigella from the stool, lowering the probability of onward transmission.
Enhanced surveillance: The geographical spread of XDR S. sonnei is under reported. WHO advises national authorities to reinforce Shigella surveillance including testing for antimicrobial resistance to detect potential introductions to new areas and to prevent the establishment of local cycles of transmission in communities. This outbreak highlights the importance of public health measures to detect, prevent and control the spread of drug-resistant pathogens within and across countries.

Further information
Acknowledgement: We would like to acknowledge the National Authorities for the information provided to enable the publication of this Disease Outbreak News.
Citable reference: World Health Organization (24 March 2022). Disease Outbreak News; Extensively drug-resistant Shigella sonnei infections - Europe.Available at: