News Scan for Feb 21, 2019

News brief

European interim flu vaccine tracking finds moderate effectiveness

An early look at this season's flu vaccine in Europe shows that protection against influenza A has ranged between 32% and 43% across all patients seen at clinics and hospitals and was 59% in groups targeted for vaccination, according to findings from six European studies published today in Eurosurveillance.

Europe's flu season began late in most countries, with little influenza B activity. Both influenza A strains are circulating in some countries, with others reporting dominant 2009 H1N1 or H3N2.

Against the 2009 H1N1 strain, vaccine effectiveness (VE) ranged from 40% to 71%, and three of the studies found lower protection levels in older adults, ranging from 0% to 37%. And, against H3N2—the most challenging strain—three of the four studies of primary care clinics found no protection across all age-groups, though the authors said few H3N2 cases mean VE estimates are less precise than for 2009 H1N1.

When compared with recent interim reports from other countries, the results from three of the studies were similar to estimates from Canada and the United States.

In a UK study that included the inhaled quadrivalent live attenuated influenza vaccine (LAIV), VE against influenza A in children was high, at 80%. And that findings suggest that a 2009 H1N1 vaccine strain switch from A/Bolivia to A/Slovenia after the 2016-17 season may have helped improved performance against circulating strains; however, the authors cautioned that the sample size was very small.

Genetic diversity of flu viruses in the flu season under way in Europe didn't seem to affect VE against 2009 H1N1 in most groups. So far, all H1N1 viruses characterized in Europe are antigenically similar to the vaccine virus, though lower protection in seniors in the Danish primary care clinic study needs further study but might be explained by small sample size.

"End-of-season VE and antigenic studies will provide insight into age- and study-specific variation in VE estimates," the authors wrote.
Feb 21 Eurosurveill study
Jan 24 CIDRAP News scan "Study: Flu vaccine offers 68% protection in Canada, 72% against H1N1"
Feb 14 CIDRAP News story "Early US flu vaccine analysis finds moderate protection"

Three new MERS cases recorded in Saudi Arabia

Saudi Arabia's Ministry of Health (MOH) reported three new MERS-CoV case today in an epidemiologic week 8 notification.

Two male patients from Wadi ad-Dawasir have been diagnosed as having MERS-CoV (Middle East respiratory syndrome coronavirus). The patients are a 26-year-old man who is hospitalized and a 35-year-old man who is in home isolation. Neither patient had camel contact, a known risk factor, and the MOH said it was investigating the source of the patients' infections.

A total of 47 MERS cases have been recorded in Wadi ad-Dawasir since the first of the year, in an apparent hospital outbreak.

A third case was recorded in a 36-year-old man from Buraydah. The man is hospitalized and did not have camel contact. The source of his infection is listed as "primary," meaning it is unlikely he contracted the virus from another person.

Saudi Arabia has now reported 73 MERS-CoV cases this year.
Feb 21 MOH report

Study: Mumps immune response drops off 7 to 17 years after vaccination

In an effort to understand why young adults in the Unites States still contract mumps—despite high vaccination rates—researchers from the Mayo Clinic and Food and Drug Administration followed a cohort of 98 measles, mumps, and rubella (MMR) vaccine recipients for 17 years to measure immune responses to measles and mumps. The results are published in Vaccine.

Each subject was a school-age child from Olmsted County, Minnesota, and received both doses of MMR. The subjects were subjected to two blood draws, one at 7 years after the second MMR dose, and one 10 years later, or 17 years after the second dose.

Mumps immunoglobulin G antibodies (Abs) dropped significantly between the two blood draws.

"The median titer at the first blood draw was 74.8, with an interquartile range of 35.1–170.2. The median titer at the second blood draw (which was between 7.6 and 14.2 years after the first blood draw) was 69.8, with an interquartile range of 25.1–146.2," the authors wrote.

The subjects did not show a significant loss of neutralizing Ab levels to mumps, however. About 42% of the subjects also experienced a more than 20% decrease in measles neutralizing Ab titer.

The authors said their study suggests significant waning in mumps protection in the first 7 to 17 years after vaccination.
Feb 20 Vaccine study

Stewardship / Resistance Scan for Feb 21, 2019

News brief

Genomic analysis shows UK, Australian XDR gonorrhea cases are related

An international team of scientists reported today in Eurosurveillance that the three extensively drug-resistant (XDR) gonorrhea cases identified in Australia and the United Kingdom in 2018 were caused by a single XDR clone.

The three cases, which were identified in February, March, and April 2018, all displayed ceftriaxone resistance and high-level azithromycin resistance, a combination that had not previously been reported. Dual therapy with ceftriaxone and azithromycin is the first-line treatment for gonorrhea.

The UK case involved a man who reported sexual contact with a woman in Thailand; the Australia cases included a man who reported having sex with a woman in Southeast Asia and a woman with no travel history outside of Australia.

Genomic analysis of four isolates (two from the UK case, one each from the Australia cases) revealed that all four shared the same Neisseria gonorrhoeae multi-antigen sequence type (ST 16848), multilocus sequence type (ST 12039) and NG-sequence typing for antimicrobial resistance type (NG-STAR 996), and all harbored the same ceftriaxone resistance–conferring penA allele and copies of the genetic mutation responsible for high-level azithromycin resistance.

Phylogenetic analysis showed that the sequences from the two UK isolates and the isolate from the Australian woman were indistinguishable, and separated from the male Australian case by one single nucleotide polymorphism. These findings suggest the three cases are highly related and of the same gonococcal clone, which the authors of the study named A2543. They warn that the clone could be present elsewhere, but may not have been detected because of a lack of testing and surveillance.

"The isolation of these A2543 clone XDR gonococci within a short time period, with epidemiological links to south-east Asia in two of three cases, suggests that this clone may be circulating in Asia, which is concerning," they write. "Further spread of this A2543 XDR strain would have serious implications for the current first-line NG treatment recommendations."
Feb 21 Eurosurveill rapid communication

Canadian researchers report novel metallo-beta-lactamase gene, CAM-1

Canadian scientists report identifying a novel metallo-beta-lactamase gene, CAM-1, which confers resistance to the antibiotic carbapenem, in clinical Pseudomonas aeruginosa isolates, according to data published yesterday in the Journal of Antimicrobial Chemotherapy.

Using whole-genome sequencing, the researchers analyzed four clinical isolates of P aeruginosa from three patients hospitalized in Alberta in 2008 and 2009 that were negative by polymerase chain reaction for KPC, OXA-48, NDM, VIM, IMP, GES, and NMC/IMI carbapenemase genes. They used bioinformatic analysis; cloning, antimicrobial susceptibility testing, and biochemical and phenotypic characterization; and single-nucleotide variant typing to further assess the isolates.

The group, which included scientists from the Public Health Agency of Canada, called the novel gene Central Alberta Metallo-beta-lactamase, or CAM-1. The gene conferred carbapenem resistance to an Escherichia coli TOP10 strain but could not be transferred by conjugation.

The authors said no additional CAM-1 genes have been identified in the province in more recently hospitalized patients.
Feb 20 J Antimicrob Chemother report

FDA approves New Drug Applications for Nabriva's pneumonia antibiotic

Nabriva Therapeutics of Dublin announced that the US Food and Drug Administration (FDA) has accepted its New Drug Applications (NDAs) and granted priority review for both the oral and intravenous (IV) formulations of lefamulin, a first-in-class, semi-synthetic pleuromutilin antibiotic for treating community-acquired bacterial pneumonia (CABP).

The goal date for the completion of the FDA's review is Aug 19. In addition to authorizing priority review, the FDA has also granted lefamulin Qualified Infectious Disease Product and fast-track designations.

Jennifer Schranz, MD, Nabriva's chief medical officer, said in a company news release. "We believe lefamulin has the potential to provide a much-needed monotherapy treatment option for adults with CABP. As demonstrated in our clinical program, the ability to switch from IV to oral administration and the short-course oral regimen has the potential to position lefamulin, if approved, as a monotherapy option for patients in the hospital, transition of care and ambulatory care settings."

The company said the two NDAs are supported by two phase 3 clinical trials—known as LEAP 1 and LEAP 2—that evaluated the safety and efficacy of IV and oral lefamulin compared with moxifloxacin in adults with CABP, including the option to switch from IV to oral administration and a short course of oral treatment with lefamulin. "In both LEAP 1 and LEAP 2, lefamulin was demonstrated to be non-inferior to moxifloxacin, and met both the FDA and European Medicines Agency (EMA) primary and secondary efficacy endpoints for the treatment of CABP," the company said.

Lefamulin was also generally well tolerated in the trials. Nabriva plans to submit a marketing authorization application for lefamulin in Europe in the first quarter of 2019.
Feb 19 Nabriva news release
Dec 21, 2018, CIDRAP News scan on NDA application