Flu Scan for Nov 12, 2021

News brief

US flu shows another small rise, with 90% of cases in young people

Though the nation's flu activity is still at low levels, the number of detections has increased in recent weeks, mostly due to the H3N2 strain and with 90% of cases in people ages 5 to 24, the US Centers for Disease Control and Prevention (CDC) said today in an update that covers last week.

Most flu markers remained below baselines, and the CDC notes that public health labs over the past 3 weeks have reported H3N2 in 7 of 10 of US regions. Flu seasons dominated by H3N2 are concerning, because the subtype causes more severe illness in older people and vaccines don't typically protect as well against it.

A spurt of cases in Michigan is linked to a single outbreak among young adults, the CDC said.

New Mexico reported a high level of flu activity, as measured by doctor's visits for flulike illness. Very few nursing homes reported flu positives among residents.

Last week, 295 people with lab-confirmed flu were admitted to the hospital, the CDC said. So far, no pediatric flu deaths have been reported for the current flu season.
Nov 12 CDC FluView report


Europe and South Korea report more H5 avian flu outbreaks

As avian flu outbreak activity picks up steam in Europe and Asia, South Korea and the United Kingdom reported more H5N1 events in poultry, and European countries reported more highly pathogenic H5N1 and H5N8 outbreaks in wild birds.

South Korea reported its second H5N1 outbreak of the season, which occurred at a duck farm in North Chungcheong province, not far from the initial event reported earlier this week, according to an agriculture ministry statement translated and posted by Avian Flu Diary (AFD), an infectious disease news blog.

Elsewhere, the UK's Department of Environment, Food, and Rural Affairs (DEFRA) yesterday reported an H5N1 outbreak, with the pathogenicity still to be determined, at a facility in Essex. According to the BBC, the facility is a wildlife sanctuary, and the affected birds included guinea fowl, chickens, and geese.

In related developments, a number of European countries reported more highly pathogenic H5 detections in wild birds, according to the latest notifications from the World Organization for Animal Health (OIE). Countries reporting H5N1 were Hungary (wild goose, Baranya County), Poland (mute swans, Wielkopolska province), and Bosnia and Herzegovina (mute swan, Republika Srpska). Meanwhile, two reported H5N8: Sweden (Canada goose, Ostergotland County) and Luxembourg (backyard birds, Grevenmacher commune).
Nov 12 AFD post
Nov 11 DEFRA report
Nov 12 BBC report
OIE reports on wild bird outbreaks in Hungary, Poland, Bosnia and Herzegovina, Sweden, and Luxembourg

ASP Scan (Weekly) for Nov 12, 2021

News brief

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Study highlights non-medical factors behind irresponsible antibiotic use

Originally published by CIDRAP News Nov 11

Non-prescription and irresponsible antibiotic use are prevalent across the world and are largely influenced by non-biomedical factors, an international team of researchers reported this week in Clinical Microbiology and Infection.

The review and meta-analysis of 71 studies covering 52 countries, many of them low- and middle-income countries (LMICS), explored the non-biomedical factors that influence healthcare consumers' antibiotic use globally. The aim was to develop a better understanding of what drives community antibiotic use in different parts of the world, and how future mitigation policies could help improve antibiotic use practices.

The analysis revealed a wide range of irresponsible antibiotic use in all regions. Self-medication with antibiotics for therapeutic purposes was reported in 48 studies from 40 countries, with a prevalence ranging from 3.1% (in 19 European countries) to 82% (Qatar) among adults, and from 3.3% (the United States) to 62% (China) among children.

The prevalence of prophylactic self-medication with antibiotics ranged from 6.0% (Serbia) to 33.4% (China). Over-the-counter purchasing of antibiotics was reported in 34 studies from 35 countries and ranged from 5.2% (Lebanon) to 88.8% (Tanzania). The prevalence of household storage of antibiotics ranged from 6.5% (Hong Kong) to 80.5% (Pakistan).

Antibiotic use was found to be heavily influenced by individuals' sociodemographic variables, perceptions of vulnerability and susceptibility to infections, and access to drugs. In addition, social-contextual factors such as barriers to healthcare resulted in avoiding medical interactions, purchasing antibiotics over-the-counter, and self-medicating. The meta-analysis further identified older age, living in rural areas, storing antibiotics at home, having relatives with medical backgrounds, and bearing a positive attitude towards self-medication with antibiotics to be risk factors for self-medication with antibiotics.

"This study identified the non-biomedical factors that drive antibiotic use in the community within different cultural contexts, highlighting the complexity of the challenge," the study authors wrote. "Future AMR [antimicrobial resistance] strategies that aim to reduce antibiotic use without clinical indication should incorporate a multifaceted community-based design that addresses non-biomedical drivers tailored to local contexts." 
Nov 9 Clin Microbiol Infect study


Beta-lactam plus doxycycline tied to better pneumonia outcomes in elderly

Originally published by CIDRAP News Nov 11

A retrospective study of elderly pneumonia patients treated at Department of Veterans Affairs (VA) hospitals found that use of doxycycline as part of guideline-concordant therapy was associated with lower mortality than regimens without doxycycline, researchers reported this week in Clinical Infectious Diseases.

Of the 70,533 patients 65 and older who were hospitalized with community-acquired pneumonia (CAP) at VA hospitals from 2002 through 2012, 5,282 (7.5%) received empiric therapy with a beta-lactam antibiotic plus doxycycline. That combination is an alternative regimen recommended for CAP under 2019 American Thoracic Society/Infectious Diseases Society of America guidelines, but prior to this study, there was limited evidence supporting its use.

To evaluate its efficacy, researchers compared 30- and 90-day mortality in patients who received a beta-lactam plus doxycycline with those who received other guideline-concordant regimens, using propensity score matching to balanced measured confounders between groups.

The unadjusted 30- and 90-day mortality rates were 6.4% and 13.8% for those who received a beta-lactam plus doxycycline, respectively, versus 9.1% and 16.8% in those who did not. In the propensity-score matched models, both 30-day (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.63 to 0.84) and 90-day (OR, 0.83; 95% CI, 0.74 to 0.92) mortality were significantly lower for those who receive doxycycline.

"With growing antibiotic resistance to frontline agents, there is an urgent need for exploring and promoting newer antibacterial regimens to address the escalating burden of CAP," the study authors wrote.

"Our study suggests that an empiric regimen of beta-lactam and doxycycline is associated with similar, or better, outcomes compared to other guideline concordant empiric therapies. Randomized control trials are needed to confirm this finding and to identify the best therapies for patients hospitalized with CAP." 
Nov 9 Clin Infect Dis abstract


AMR Industry Alliance report highlights progress, challenges

Originally published by CIDRAP News Nov 10

A new report from the AMR Industry Alliance (AMRIA) highlights some of the efforts that life sciences companies are pursuing to deliver on commitments to tackle antimicrobial resistance.

The 2021 AMRIA Progress Report draws on a survey completed by 53 alliance members and looks at efforts across four strategic pillars—research and science, access, appropriate use, and manufacturing and the environment.

The survey showed that AMRIA members invested $1.8 to $1.9 billion in antimicrobial resistance (AMR)-relevant research and development (R&D) in financial years 2019 and 2020 and contributed to R&D on 93 products, including 54 antibiotics, 12 vaccines, 13 diagnostic platforms, and 14 non-traditional products. Eighty-one percent of surveyed companies actively supported access to AMR-relevant products and technologies.

Support for appropriate use and appropriate manufacturing was strong as well. Overall, 92% of pharmaceutical companies, 89% of generics companies, and 80% of diagnostics companies have implemented appropriate use and stewardship activities, while 76% of manufacturing sites owned by alliance members have fully met all requirements for the Common Antibiotic Manufacturing Framework, and 98% have partially met the requirements.

The report also highlights the continuing challenges, however. Overall, 80% of AMRIA members said they were actively engaged in efforts to strengthen financial incentives to stimulate antibiotic development. But those efforts in are in the early stages of implementation, and 32% percent of alliance members said they expected to reduce their investments in AMR-related R&D if market conditions don't improve for antibiotic development. And only 51% of members reported collecting and/or sharing surveillance data to generate evidence to support appropriate use and stewardship.

AMRIA, formed in 2017, represents a coalition of 93 biotechnology, diagnostics, generics, and large research-based biopharmaceutical companies and associations. The survey was conducted by RAND Europe.
Nov 9 AMRIA 2021 Progress Report executive summary


Project focuses on vaccines, monoclonal antibodies to fight AMR

Originally published by CIDRAP News Nov 10

A coalition of academic researchers and industry partners yesterday announced a new public-private partnership to use artificial intelligence and big data to unlock the potential of vaccines and monoclonal antibodies to fight AMR.

The primary goal of PrIMAVeRa (Predicting the Impact of Monoclonal Antibodies & Vaccines on Antimicrobial Resistance) is to develop an open-sourced, web-based platform that combines mathematical models with health and economic data to predict how much vaccines and monoclonal antibodies could reduce AMR and help policymakers determine which specific vaccines and monoclonal antibodies should be prioritized. The initiative involves 19 partners in the European Union, United Kingdom, and Russia.

Leaders of the initiative say the lack of such data-driven tools has discouraged investment in the development of vaccines and monoclonal antibodies against drug-resistant pathogens.

"This is a highly innovative project that will highlight the important, but often forgotten role that vaccines can play in combatting AMR," Ole F. Olesen, executive director of the European Vaccine Initiative, said in a press release.

PrIMAVeRa is being backed by €9 million (US $10.3 million) from the Innovative Medicines Initiative 2.
Nov 9 European Vaccine Initiative press release


UK report shows veterinary antibiotics have been cut in half since 2014

Originally published by CIDRAP News Nov 9

New data released today by the United Kingdom's Veterinary Medicines Directorate (VMD) show that the use of antibiotics in UK livestock continues to fall.

The 2020 UK Veterinary Antibiotic Resistance and Sales Surveillance Report (UK-VARSS) shows sales of antibiotics for use in food-producing animals fell by 1% from 2019 and have declined by 52% since 2014. In addition, sales of highest-priority critically important antibiotics (HP-CIAs) have declined by 79% since 2014.

HP-CIAs, which are considered the most vital antibiotics in human medicine, now only account for 0.5% of antibiotics sold for use in UK livestock. The report also shows that the amount of antibiotics prescribed in pigs, chickens, turkeys, and gamebirds declined in 2020.

Data collected on zoonotic and commensal bacteria from healthy animals at slaughter indicated that antibiotic resistance in Escherichia coli from broilers has declined since 2014, while resistance to HP-CIAs in broilers and turkeys remains very low. Since 2016, there's also been a decline in E coli from broilers and turkeys carrying resistance genes. The report suggests the reductions in veterinary antibiotic sales and use may be responsible for the declines in resistance.

"This year's VARSS report shows how the UK continues to make important reductions in antibiotic use in livestock across the board," Christine Middlemiss, the UK's Chief Veterinary Officer, said in a VMD press release. "It is encouraging to see farmers and vets continuing to work together to tackle antibiotic resistance through the responsible use of antibiotics, which in turn protects human health as well as reducing the burden of disease in animals."
Nov 9 UK-VARSS report
Nov 9 VMD press release


UK livestock sector making progress toward 2024 antibiotic targets

Originally published by CIDRAP News Nov 9

In another UK report today, the Responsible Use of Medicines in Agriculture Alliance (RUMA) reported that the UK's livestock sector is making progress on its next set of targets for reducing antibiotic use, despite some setbacks during the pandemic.

The summary report, which covers 10 sectors across aquaculture, pigs, poultry, and ruminants, indicates many sectors are making progress toward hitting their 2024 targets on data collection, use of antibiotics, uptake of preventive measures such as vaccines and training, and development of industry initiatives. Some sectors, including the poultry, pig, and salmon industries, are ahead of schedule or have already achieved their goals.

But some sectors, like the beef and dairy industry, have not had enough time to collect accurate data on antibiotic use. And the pandemic delayed the launch of key initiatives in other sectors.

"Events of the past year have undoubtedly affected the industry in many ways, but producers, vets, and wider industry have continued to manage with the utmost professionalism and commitment to the responsible use of antibiotics through this challenging time," RUMA chair Cat McLaughlin said in a press release.

RUMA's 2017 targets for antibiotic use in UK livestock are widely credited for helping achieve the antibiotic sales and use reductions documented in the 2020 UK-VARSS report. The goals for 2021 through 2024, set last year by a RUMA task force, include a 30% reduction in antibiotic use in pigs, reductions of 15% in dairy herds and 25% in calf rearing units, and a 40% reduction in game birds.
Nov 9 RUMA report
Nov 9 RUMA press release


Mandated sepsis bundle tied to increased antibiotic use, fewer deaths

Originally published by CIDRAP News Nov 8

A series of measures mandated by the Centers for Medicare and Medicaid Services (CMS) to improve sepsis care in US hospitals was associated with increased sepsis diagnosis and antibiotic use, but also with reduced mortality, researchers reported late last week in Clinical Infectious Diseases.

In their analysis of the Severe Sepsis and Septic Shock: Management Bundle (SEP-1) Core Measure, required at all US hospitals that receive CMS compensation as of October 2015, the researchers looked at antibiotic use among adult patients at 26 hospitals during the year before and the year after implementation (October 2014 through October 2016).

The SEP-1 bundle promotes early administration of effective antibiotic therapy in sepsis patients, but its impact on antibiotic use wasn't known. Sepsis diagnosis rates and all-cause mortality were also analyzed.

A total of 701,055 patient were included in the study, and more than 1.9 million antibiotic days of therapy (DOT) were administered during the study period. Antibiotic use and sepsis diagnosis increased 2% each month during the SEP-1 preparation period (October 2014 through September 2015) and remained elevated. Cumulatively, the rate of sepsis diagnosis increased 32.9% during the entire study period, and the mean monthly antibiotic DOT per 1,000 patient-days increased 24.4%.

The rate of all-cause mortality fell 5% each month during the SEP-1 preparation period, then declined by 2% each month during the SEP-1 implementation period (November 2015 through October 2016). Cumulatively, the monthly mean all-cause mortality per 1,000 patients declined 38.5% over the entire study period.

The study authors note that while it's plausible the decline in mortality was related to improved antibiotic therapy for sepsis patients, they did not observe changes in mortality in a subset of patients with suspected sepsis. Furthermore, the decline in mortality was out of proportion to the increased number of patients diagnosed as having sepsis and to the increase in antibiotic use.

"Our analysis does not demonstrate a causal association between implementation of SEP-1 and changes in antibacterial use or mortality, but strongly suggests that additional investigation into the value and potential adverse events of mandated antibiotic therapy is required," the authors wrote. "Any benefits provided by the prompt and broad application of antibacterial therapy for patients with suspected sepsis may be quickly outweighed by adverse events."
Nov 5 Clin Infect Dis abstract

News Scan for Nov 12, 2021

News brief

COVID-19, flu vaccines safe to give at the same time, study shows

A UK study yesterday in The Lancet finds that flu and COVID-19 vaccines can be safely co-administered.

Led by researchers from the Weston NHS Foundation Trust and the University of Bristol, the multicenter phase 4 clinical trial involved 679 adults at 12 UK sites. Participants were randomly assigned to receive one of three inactivated age-appropriate seasonal flu vaccines and either the second dose of a Pfizer/BioNTech (BNT162b2) or AstraZeneca/Oxford (ChAdOx1) COVID-19 vaccine or a placebo from Apr 1 to Jun 26, 2021.

The goal was to determine whether co-administration of the vaccines, which would free up healthcare provider time to vaccinate more people, is safe and will provoke an immune response at least as robust as is produced when the two vaccines are given 3 weeks apart.

Of the 679 participants, 340 were assigned to receive simultaneous administration of flu vaccine and a second dose of COVID-19 vaccine followed by a placebo 3 weeks later, and 339 were given a placebo and a second COVID-19 vaccine dose followed by a flu vaccine 3 weeks later. The researchers followed participants for up to 6 weeks.

Four combinations of co-administered vaccines produced a similar antibody response as those given 3 weeks apart: AstraZeneca plus quadrivalent (four-strain) flu vaccine (risk difference for flu vaccine minus placebo, -1.29%), Pfizer plus cellular quadrivalent flu vaccine (6.27%), Pfizer plus MF59C-adjuvanted flu vaccine (-12.9%), and AstraZeneca plus recombinant quadrivalent flu vaccine (2.53%). Likewise, the combination of AstraZeneca plus MF59C and Pfizer plus recombinant quadrivalent flu vaccine surpassed the 0.25 noninferiority margin (10.3% and 6.75%, respectively).

Most systemic adverse reactions were mild to moderate, and rates of local and unsolicited systemic reactions were similar among all-groups. One serious adverse event—hospitalization with severe headache)—was considered related to the intervention. Immune responses weren't dampened.

"Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines," the study authors concluded.
Nov 11 Lancet study


Ivory Coast, Niger report new polio cases

Ivory Coast and Niger reported new polio cases this week, according to the weekly update from the Global Polio Eradication Initiative (GPEI). Both involve circulating vaccine-derived poliovirus type 2.

The Ivory Coast case was reported in Marahoue, bringing the country's total cases recorded 2020 to 63.

Niger had 10 cases in 2020, and with 3 new cases recorded in the previous week, the 2021 total stands at 5. The 3 cases were in Agadez, Diffa, and Zinder regions.
Nov 12 GPEI update

This week's top reads