News Scan for Jul 07, 2022

News brief

Report describes UK outbreak of extensively drug-resistant Shigella

A study yesterday in The Lancet Infectious Diseases describes an ongoing outbreak of sexually transmitted, extensively drug-resistant (XDR) Shigella sonnei in the United Kingdom.

The outbreak began in September 2021 with the identification of an infected patient in England, followed by anecdotal reports of patients hospitalized with severe S sonnei infections in London in November and December, which prompted an investigation led by researchers from the UK Health Security Agency.

Genomic surveillance identified the infections as belonging to S sonnei clade 5. Cases were subsequently reported in Wales, Scotland, and Northern Ireland. Investigators with the Outbreak Control Team conducted whole-genome sequencing on patient isolates and collected demographic, epidemiologic, and clinical data from patients using questionnaires.

A total of 72 confirmed cases (70 of them in men, median age 34 years) were identified in the United Kingdom from Sep 1, 2021, to Feb 9, 2022. All cases were genotypically multidrug-resistant or XDR, exhibiting genotypic antimicrobial resistance determinants for aminoglycosides, sulfonamides, trimethoprim, fluoroquinolones, and macrolides. In addition, 66 of 72 isolates harbored bla_CTX-M-27, a plasmid-mediated gene that confers resistance to ceftriaxone. Of the 33 patients with clinical data, 19 (58%) received antibiotics and 8 (24%) were hospitalized.

Of the 27 patients who filled out an outbreak questionnaire, 25 (93%) were HIV-negative, 21 (78%) were taking HIV pre-exposure prophylaxis (PrEP), and 11 (41%) reported bacterial sexually transmitted infections (STIs) in the past year that required antibiotics. Twenty-two (81%) reported engaging in one or more sequential oral and anal sexual acts in the week before symptom onset. Two of the patients were immunocompromised individuals whose infections were not associated with sexual transmission, which investigators say highlights the threat of wider transmission.

"Previous evidence has shown that sexually transmitted shigellosis can be transmitted sporadically outside sexual networks; enhanced surveillance for this outbreak provided further evidence of this," the investigators wrote. "Sporadic transmission outside sexual networks, leading to severe cases in immunocompromised individuals, highlights the wider public health risk of continued, uncontrolled transmission of XDR shigellosis."

The investigators added that improved surveillance and updated treatment guidelines for drug-resistant Shigella are needed, and suggested that public health messages about the prevention of shigellosis and other enteric STIs should be included in PrEP delivery.
Jul 26 Lancet Infect Dis study

CDC reports 12 more unexplained hepatitis cases in kids, 332 total

In a weekly update, the US Centers for Disease Control and Prevention (CDC) yesterday reported 12 more unexplained pediatric hepatitis cases in children, raising the national total to 332.

The number of affected states held steady, at 42.

In earlier reports, the CDC has said not all recently reported cases reflect new illnesses. Cases under investigation date back to October 2021. Also, an earlier data review from CDC found no increase in pediatric hepatitis above the prepandemic baseline level.

Scientists in multiple countries are investigating several possibilities, with an adenovirus link as the main focus. However, groups are exploring several other possibilities, including prior COVID-19 infection, cofactors, atypical immune response, or exposure to toxin triggers.
Jul 6 CDC unexplained hepatitis update

COVID-19 Scan for Jul 07, 2022

News brief

Novel cancer drug halved deaths in hospitalized COVID-19 patients

The experimental cancer drug sabizabulin slashed all-cause deaths by 55.2% over placebo in high-risk hospitalized COVID-19 patients by 60 days and was tied to fewer adverse events, according to interim results of a randomized, controlled phase 3 trial published yesterday in NEJM Evidence.

Scientists from sabizabulin manufacturer Veru, Inc. led the multicenter trial of the oral drug, which showed both antiviral and anti-inflammatory properties in preclinical models. The drug binds to the microtubules critical for SARS-CoV-2 cell entry and replication and for the outsized inflammatory response leading to acute respiratory distress syndrome (ARDS) and death.

A total of 204 adults with moderate to severe COVID-19 at high risk for poor outcomes were randomly assigned to receive either 9 milligrams of sabizabulin or a placebo daily for up to 21 days. The trial was stopped early owing to demonstrated drug efficacy, resulting in inclusion of 150 patients (98 assigned to sabizabulin and 52 to placebo) in the analysis, 145 of whom completed the study and had a known status at 60 days.

Patients were enrolled at 27 sites in five countries—the United States, Brazil, Bulgaria, Argentina, and Mexico—from May 18, 2021, to Jan 31, 2022.

Sabizabulin led to a 24.9-percentage-point absolute reduction and a 55.2% relative reduction in deaths over placebo (odds ratio, 3.23; 95% confidence interval, 1.45 to 7.22). Nineteen of 94 sabizabulin recipients (20.2%) died, compared with 23 of 51 placebo recipients (45.1%).

Relative to placebo recipients, the sabizabulin group also saw a 43% relative reduction in average days in an intensive care unit (-13.4 days), a 49% relative reduction in days on mechanical ventilation (-14.1), and a 26% relative reduction in days in the hospital (-8.4). Adverse events occurred less often in sabizabulin recipients (61.5%) than in the placebo group (78.3%).

"These data demonstrate that sabizabulin treatment significantly reduced mortality with an acceptable side-effect and safety profile in hospitalized patients with moderate to severe COVID-19 at high risk for ARDS," the researchers concluded.
Jul 6 NEJM Evidence study

Hospitalized immunocompromised people at higher risk of severe COVID

Immunocompromised adults who are hospitalized for COVID-19 are at greater risk of intensive care unit (ICU) admission and death, regardless of vaccination status, according to an analysis led by researchers at the Centers for Disease Control and Prevention (CDC).

They based their findings on data from 10 of the states that participate in the COVID-19-Associated Hospitalization Surveillance Network that was collected from Mar 1, 2020, to Feb 28, 2022. The team published its findings today in Morbidity and Mortality Weekly Report (MMWR).

Of 23,345 adults who were hospitalized for COVID-19, 12.2% were immunocompromised. For comparison, people with immune compromise make up about 2.7% of the US adult population. Of unvaccinated patients, those with immune compromise had higher odds of ICU admission (adjusted odds ratio [aOR] = 1.26; 95% CI = 1.08–1.49) and death (aOR = 1.34; 95% CI = 1.05–1.70). When the researchers looked at vaccinated patients, those who were immunocompromised had higher odds of ICU admission (aOR = 1.40; 95% CI = 1.01–1.92) and death (aOR = 1.87; 95% CI = 1.28–2.75).

Focusing just on the period March 2021 through February 2022 in people who weren't immunocompromised, vaccinated people had lower odds of death than unvaccinated people. However, in those who were immunocompromised, the odds of death didn't vary by vaccination status.

"The generally consistent association of individual immunocompromising conditions with increased odds of death suggests that immunocompromise itself was likely associated with severe outcomes," the group wrote, adding that COVID-19 vaccination in the group is highly protective against hospitalization, but once hospitalized, vaccination status wasn't associated with ICU admission or death.

The higher odds of severe outcomes in immunocompromised people hospitalized with COVID-19 underscores the need for multilayered prevention strategies for this group, such as ensuring that close contacts are up-to-date with vaccinations, encouraging immunocompromised people to use preexposure prophylaxis such as Evusheld, and early testing and treatment.
Jul 8 MMWR report