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HIV | Drug-resistant Shigella is becoming a global public health challenge

The results of two recent studies warn that these outbreaks require coordinated strategies and highlight the existing weaknesses in public health responses to the increase in inequality

In two studies published in The Lancet Infectious Diseases separate outbreaks of Shigella resistant to drugs in two world areas far from each other, which demonstrates the permeability of cases among different vulnerable populations and requires a coordinated response to this challenge for global public health. The areas described in the studies were the state of Washington (USA) – where the appearance of various strains of Shigella con endurance to several drugs (MDR) – and England – where extremely drug resistant (XDR) strains were detected.

Shigellosis is an acute infection that affects the intestine and is caused by a family of bacteria known as Shigella (being the bacterium Shigella sonnei responsible for most cases). Symptoms can range from mild diarrhea to severe cases and are often confused with episodes of food contamination. Most cases are self-limiting, but antibiotics are often used to treat symptoms and reduce shedding, which may help limit transmission. Transmission occurs when the feces of an infected person get into the mouth of another person.

Gay, bisexual, and other men who have sex with men (GBHSM) men are at particularly high risk of acquiring an infection from Shigella and, in fact, in recent years the number of reports on strains of Shigella MDR and XDR spreading between male GBHSH networks.

The first study described an outbreak of shigellosis that began in the city of Seattle (USA) in 2017, initially among the GBHSM male population. However, starting in 2020, a large increase in drug-resistant shigellosis cases was observed in the homeless population, which the authors blamed on reduced hygiene options after the closure of public toilets in the city (due to the pandemic of COVID-19) that these people used to use.

Over the course of the outbreak, there was also evidence that different patterns of endurance antibiotics, making treatment more difficult. The strains that affected homeless people were largely sensitive to standard treatments while the strains seen in GBHSM men were drug resistant. Examining data from 171 patients seen at Harbor View Medical Center and UW Medical Center between May 2017 and February 2022, it was found that 46% were GBHSM men and 51% were homeless (11 of these people belonged to both population groups at the same time). Up to 56 people were hospitalized and 8 cases ended up in an intensive care unit. 51% of the isolated samples contained Shigella multidrug resistant (MDR).

The sequencing of the genome Complete analysis of the samples revealed that the outbreak was mainly due to the parallel appearance of many different variants of S flexneri y S sonneiwhich were first observed in the GBHSM male population before spreading to the homeless population, which the authors say reflects the fluidity and interaction between these populations.

The study also revealed the efficacy of using rapid diagnostic tests and using susceptibility results to direct intervention while the patient was still in the ED. Data from 143 patients who received antibiotics showed that despite high levels of multidrug resistance, 70% received adequate antibiotic therapy. This was especially important in the case of the homeless, who are often lost to follow-up.

In addition, genome analysis made it possible to link outbreaks of Shigella MDR in Seattle with others detected in other parts of the world. Thus, one of the samples of S flexneri of the Seattle outbreak was linked to a cepa MDR from China, while isolates from S sonnei showed similarities with a strain causing an outbreak of Shigella MDR in England.

Precisely the second study mentioned focused on the outbreak in England which, since 2009, has been the scene of successive outbreaks of Shigella by sexual transmission between men GBHSH (see The News of the Day 02/01/2019) where both strains of S flexneri y S sonnei multidrug resistant.

In January 2022, UK health authorities reported an increase in infections by S sonnei extremely drug resistant (XDR) that were resistant to all but two classes of antibiotics. Subsequently, similar increases have been reported in other parts of Europe (see The News of the Day 03/28/2022).

The appearance and spread of S sonnei XDR among the GBHSM male population in England led to an analysis of national epidemiological surveillance data to see if an XDR strain of GBHSM was also present. S flexneri. Between September 2015 and June 2022, 37 samples of S flexneri harboring the blaCTX-M-27 gene (which confers multidrug resistance), 26 of which were identified as of September 2021. Of those 26 samples, 8 had Shigella XDR y 18, Shigella MDR. In all cases, the samples came from adult men, and of the 13 people who completed a questionnaire, 10 (77%) identified themselves as GBHSM men and 7 (54%) reported having had sexual contact in the weeks prior to the onset of the symptoms. In the case of 2 people possible treatment failures were reported.

When analyzing the plasmids – the mobile fragments of ADN carriers of antibiotic resistance genes – of the isolates of S flexnerifound a “high similarity” with the plasmids detected during the outbreak of S sonnei XDR. The team of researchers points out that their findings demonstrate the existence of links between the increase of the two strains of Shigella XDR during the same period, suggesting that transmission of both strains of Shigella within overlapping sexual networks.

Taken together, the findings of the two aforementioned studies highlight the risk posed by the spread of drug-resistant strains of Shigella both for individual health and for public health in general. The UK study (among others) reflects the rapid spread of strains of Shigella highly drug-resistant (and therefore difficult to treat) among networks of GBHSM men who engage in risky sexual behavior.

Therefore, to curb these outbreaks of Shigella drug resistant a globally coordinated strategy is needed to implement effective public health interventions to limit the spread of this bacterium. In addition, the outbreak detected in the US shows that Rising inequality and homelessness in cities are creating another population, with a different set of risk factors, that is vulnerable to this highly infectious pathogen. These are public health problems that will require different approaches from health authorities.

Fuente:Cidrap/Own elaboration (gTt-HIV)
References:Tansarli GS, Long DR, Waalkes A, et al. Genomic reconstruction and directed interventions in a multidrug-resistant Shigellosis outbreak in Seattle, WA, USA: a genomic surveillance study. The Lancet:January 30, 2023DOI:https://doi.org/10.1016/S1473-3099(22)00879-9

Thorley K, Charles H, Greig DR, et al. 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. The Lancet:January 30, 2023DOI:https://doi.org/10.1016/S1473-3099(22)00807-6

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