Stewardship / Resistance Scan for Jan 06, 2022

News brief

Trial finds three rounds of azithromycin better than one for yaws reduction

The results of a randomized trial in Papua New Guinea suggest three rounds of mass administration of azithromycin led to a greater reduction in the prevalence of yaws than a single round, researchers reported today in the New England Journal of Medicine.

In the community-based, open-label trial, conducted in an area of Papua New Guinea where yaws—an infection of the skin, bone, and cartilage caused by the bacterium Treponema pallidum subspecies pertenue—is endemic, an international team of investigators randomly assigned more than 56,000 villagers in 38 wards to receive one round of mass administration of azithromycin (the control group) or three rounds at 6-month intervals (the experimental group). The current World Health Organization strategy for eradicating yaws by 2030 involves one round of azithromycin followed by active case detection surveys and targeted treatment every 6 months, but previous studies in Papua New Guinea, the Solomon Islands, and Ghana have found that this strategy has not been enough to stop transmission.

The coprimary endpoints of the trial, conducted from April 2018 through October 2019, were the prevalence of active yaws cases in the two groups at 18 months, and the prevalence of latent yaws in a subgroup of asymptomatic children.

At 18 months, the prevalence of active yaws had decreased from 0.46% (102 of 22,033 people) to 0.16% (47 of 29,954) in the control group, and 0.43% (87 of 20,331) to 0.04% (10 of 25,987) in the experimental group (relative risk adjusted for clustering, 4.08; 95% confidence interval [CI], 1.90 to 8.76). The prevalence of latent yaws at 18 months was 6.54% among 994 children in the control group and 3.28% in the experimental group (relative risk adjusted for clustering of age, 2.03; 95% CI, 1.12 to 3.70). Molecular analysis of three cases of yaws found mutations associated with macrolide resistance.

"Our data suggest more than one round of mass drug administration should be considered as part of the strategy for yaws eradication," the authors write. But they caution that the failure to completely eliminate yaws, and the finding of resistance mutations, highlight the need for further clinical and molecular surveillance for the emergence of antimicrobial resistance.
Jan 6 N Engl J Med study

High mortality persists for Candida bloodstream infections

Bloodstream infections (BSIs) caused by Candida species were associated with a more than two-fold increased risk of mortality, researchers reported yesterday in Clinical Infectious Diseases.

The single-center study by researchers with Washington University in St. Louis School of Medicine, frequency-matched 626 adult patients with Candida BSIs with 6,269 control patients who had at least one risk factor for Candida BSI but did not develop one. They calculated 90-day all-cause mortality attributable to Candida BSI using propensity score matching, matching by inverse-weighting of propensity score, and stratified analysis by quintile.

The 90-day crude all-cause mortality for patients with Candida BSI was 42.4%, compared with 17.1% for the frequency-matched controls, with a crude mortality rate difference of 25.3%. In the propensity-scored matched pairs analysis, the hazard ratio (HR) for 90-day all-cause mortality associated with Candida BSI was 2.1 (95% CI, 2.0 to 2.3), with an attributable risk difference of 28.4%. In the analysis using inverse-weighting by the propensity score, the HR for 90-day all-cause mortality associated with Candida BSI was 2.1 (95%, 2.0 to 2.3).

In the stratified analysis, the risk for mortality at 90 days was highest in patients in the lowest risk quintile to develop Candida BSI (HR, 3.13; 95% CI, 2.33 to 4.19), a finding the researchers attribute to a higher proportion of these low-risk patients going untreated.

"Overall, Candida BSI was associated with 2.3-fold increased risk of 90-day all-cause mortality," the study authors wrote. "High mortality observed has persisted over decades despite treatment advances, though mortality attributable to Candida BSI has decreased compared to most historical studies. It is imperative that clinicians maximize efforts to adhere to guideline recommendations and seek Infectious Disease consultation to assist in timely, efficacious treatment of Candida BSI."
Jan 5 Clin Infect Dis abstract

News Scan for Jan 06, 2022

News brief

Preprint study shows significant vaccine efficacy waning in adolescents

Yesterday a new preprint study out of Israel showed the efficacy of the Pfizer-BioNTech vaccine waned in 12- to 17-year-olds in a similar pattern seen in adult recipients. Within 5 month after completing the initial two-dose vaccinations series, protection against infection with SARS-CoV-2 dropped to 58%. The study was published on the preprint server medRxiv.

The study took place between Jun 15 and Dec 8, 2021, when the Delta variant became the dominant strain in Israel. Cases were patients ages 12 to 16 who had a positive PCR test. The study participants included 129,909 patients served by Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel.

Overall, vaccinated adolescents had a notably lower percent of tests that were positive for COVID-19, the authors said, with 6.6% of tests among unvaccinated individuals coming back positive, compared with less than 1.4% for those who received their second dose 14 to149 days before the test, and 3.6% for those who received their second dose more than 150 days before the test.

The peak protection provided by the vaccine was between 2 weeks and 3 months after the second dose, and the effectiveness of the vaccine against infection was subsequently reduced to 75% (95% confidence interval [CI]: 71% to 79%) and 58% (95% CI: 52% to 64%) 90 to149 days and 150 to180 days following receipt of the second dose, respectively.

"Long-term protection conferred by the vaccine was reduced to 75-78% against infection and symptomatic infection, respectively, 3 to 5 months after the second dose, and waned to 58% against infection and 65% against COVID-19 after 5 months," the authors said.
Jan 5 medRxiv study

UK detects human H5 avian flu case

The United Kingdom's Health Security Agency (HSA) today reported a human H5 avian flu infection, which involves a person who had very close and regular contact with sick birds. The infection was detected during routine monitoring of people who have been around sick birds.

In a statement, the HSA said the patient is well and is self-isolating. Contact tracing has found no evidence of further spread.

Laboratory tests revealed the virus is the H5 type found in birds. The UK's Animal and Plant Health Agency (APHA) had identified an H5N1 outbreak in the individual's flock of birds, which have all been culled. The United Kingdom is among the several countries in Europe to report several recent H5N1 detections in poultry and wild birds.

So far, tests on the human isolate haven't confirmed H5N1. The HSA added that though the H5 case is the first involving the strain in Britain, similar cases have been reported from other parts of the world.

Isabel Oliver, MD, the HSA's chief scientific officer, said in the statement, "Currently there is no evidence that this strain detected in the UK can spread from person to person, but we know that viruses evolve all the time and we continue to monitor the situation closely. We have followed up all of this individual’s contacts and have not identified any onward spread."

In early 2021, Russia reported the first known human H5N8 infections in humans, which involved seven people who worked at a poultry plant.
Jan 6 HSA statement
Feb 22, 2021, CIDRAP News story