News Scan for Jul 13, 2020

News brief

More Ebola cases reported in DRC's latest outbreak

The Democratic Republic of the Congo's Ebola outbreak in Equateur province has risen to 51 cases, 48 confirmed, and 3 probable, reflecting an increase of 5 since Jul 9.

At a World Health Organization (WHO) media briefing today, Mike Ryan, MD, who leads the group's health emergencies program, said as of Jul 12, 20 deaths have been reported, 17 in confirmed cases and 3 in probable ones.

In Equateur province, the cases are spread across 21 health areas in 6 health zones, which means they are broadly distributed and concerning. Ryan said some areas are remote and hard to access, and some are located near the Congo River, posing a risk of spread to Kinshasa and bordering countries. "It's still a very active outbreak," he said.

In an update today, the DRC's multisectoral Ebola technical committee (CMRE) said as of Jul 10, 10,916 people in the outbreak region have been vaccinated with VSV-EBOV.

The DRC's latest outbreak, its 11th, is occurring in the same area where its 9th outbreak unfolded in 2018, which resulted in 54 cases, 33 of them fatal.
Jul 13 CMRE update

Canadian report shows worrisome rise in drug-resistant infections

A new report from the Public Health Agency of Canada (PHAC) indicates antimicrobial resistance (AMR) is worsening in the country, highlighted by dramatic increases in drug-resistant bloodstream infections (BSIs).

The 2020 Canadian Antimicrobial Resistance Surveillance System Report, released late last week, shows that from 2014 through 2018, the rate of healthcare-associated vancomycin-resistant Enterococcus (VRE) BSI more than doubled, while the rate of community-associated methicillin-resistant Staphylococcus aureus (MRSA) BSI rose by 140%. Approximately 30% of VRE-BSI and 20% of MRSA-BSI patients died within 30 days of diagnosis.

The report also showed a nine-fold increase in the number of patients testing positive for carbapenem-resistant organisms without signs of infection, detection of carbapenemase genes in Acinetobacter isolated from hospital patients, a 78% increase in the proportion of multidrug-resistant gonorrhea isolates (including the first Canadian reports of ceftriaxone-resistant gonorrhea), and rising ceftriaxone resistance in Salmonella Typhi (typhoid fever) infections.

The frequency of highly drug-resistant Salmonella enterica isolated from animals, humans, and the food chain reached new highs (132 isolates in 2018).

Antimicrobial use in the country increased as well, with rising prescription rates for Canadians over age 65 and a 30% uptick in antimicrobial purchasing by hospitals. In addition, the use of antibiotics that should be reserved for treating multidrug-resistant infections rose by 10%, and the use of carbapenems increased by more than 120% in the community setting. Kilograms of antimicrobials distributed for use in animals dropped overall by 11% but saw a 6% increase from 2017 to 2018.

The reported also highlighted several new surveillance initiatives, including a pilot project to track AMR in the community sector by looking at patterns of resistance in urinary tract infections, and the implementation of whole-genome sequencing to help identify factors associated with food production and AMR.

"No one country, level of government or single sector can slow the growing problem of AMR on its own," the report said. "Preserving the effectiveness of existing antimicrobial drugs will be achieved through collaboration among governments and partners in healthcare, animal health, agri-food, industry, academia, professional associations and the general public."
Jul 9 PHAC report

International study finds low rate of antibiotic prescribing for kids' bronchiolitis

A large international study of infants evaluated in the emergency department (ED) for bronchiolitis found that the overall rate of antibiotic therapy was low, but the use of laboratory testing was substantial, researchers reported today in Pediatrics.

To address the knowledge gap in the understanding of antibiotic use and laboratory testing in infants with bronchiolitis—both of which are discouraged unless bacterial infections are suspected—researchers with the Pediatric Emergency Research Networks conducted a secondary analysis of a retrospective cohort study of previously healthy infants with bronchiolitis treated at 38 EDs in eight countries (United States, Canada, United Kingdom, Ireland, Spain, Portugal, Australia, and New Zealand).

The primary outcome was administration of at least one antibiotic in the ED or a prescription for an antibiotic at discharge, and the secondary outcome was performance of at least one non-recommended laboratory test.

In total, 180 of 2,359 infants (7.6%) received antibiotics, ranging from 3.5% in the United Kingdom and Ireland to 11.1% in the United States. Chest x-rays (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.6 to 3.2), apnea (aOR, 2.2; 95% CI, 1.1 to 3.5), and fever (aOR, 2.4; 95% confidence interval [CI], 1.7 to 3.4) were associated with antibiotic use.

Antibiotic use did not vary across networks. A total of 768 of 2,359 infants (32.6%) had at least one non-indicated test, with rates of testing ranging from 14.9% in the United Kingdom and Ireland to 50% in Spain and Portugal. Testing was associated with the network, indicators of respiratory distress, fever, and suspected bacterial infection.

The authors said that while the rate of antibiotic use for bronchiolitis is close to the published achievable benchmarks of care, the rate of unnecessary testing observed needs to come down.

"In view of the high global prevalence of bronchiolitis and the cost of bronchiolitis care, our results highlight the need for development of international bronchiolitis benchmarks, guidelines, and quality initiatives to optimize the global management of bronchiolitis," they concluded.
Jul 13 Pediatrics abstract

National stewardship campaign in China tied to fewer primary care antibiotics

A study of community health centers in China found that strict enforcement of a national antimicrobial stewardship campaign had a strong effect on antibiotic prescribing, Chinese researchers reported last week in Clinical Infectious Diseases.

The study used an interrupted time series (ITS) analysis to evaluate the impact of local interventions, based on China's long-term national antimicrobial stewardship campaign, on antibiotic prescribing for primary care in Shenzhen, China, a city of 13 million. Previous studies have shown that the campaign, launched in 2011, has been associated with declines in antibiotic use in Chinese general hospitals, but no studies have assessed the impact on primary care.

The ITS analysis lasted 72 months, including 24 months before the intervention (January 2010 to December 2011) and 48 months after the intervention (January 2012 to December 2015).

Overall, 1,482,223 outpatient prescriptions were obtained from 11 community health centers in Shenzhen. The results of the ITS analysis showed that intervention was associated with an immediate decline of 5.2% and a monthly decline of 3.1% in the percentage of prescriptions with antibiotics, with a cumulative decline of 74% at the end of the study, representing 420,057 antibiotic prescriptions avoided during the 48 post-intervention months.

The percentage of prescriptions for acute upper respiratory infection containing antibiotics fell by 76.2%. In addition, the percentage of prescriptions with broad-spectrum and parenteral antibiotics fell by 36.7% and 77.3%, respectively, immediately after the intervention. But no significant decline in broad-spectrum and parenteral antibiotic use was observed over the course of the study.

The authors of the study said the decline in the percentage of prescriptions with antibiotics was attributed to the multidimensional interventions implemented at the community health centers.

"Additionally, achieving such a good intervention effect was attributed to the strict enforcement of this stewardship campaign," they wrote. "The Chinese government should embed the multidimensional interventions into the routine management of antibiotic prescribing in primary care to optimize antibiotic prescribing and prevent AMR."
Jul 10 Clin Infect Dis abstract

COVID-19 Scan for Jul 13, 2020

News brief

Study finds 11-fold hike in COVID-linked inflammatory syndrome in UK kids

A multicenter observational study published late last week in The Lancet Child & Adolescent Health identified 78 cases of the pediatric inflammatory multisystem syndrome tied to COVID-19 in the United Kingdom from Apr 1 to May 10—at least 11 times more than expected.

Analyzing data from the largest known cohort of patients admitted to pediatric intensive care units (PICUs), researchers compared rates of admissions to PICUs with historical trends for four similar inflammatory diseases: Kawasaki disease, toxic shock syndrome, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome.

Twenty-one of 23 PICUs reported 78 cases total of the multisystem inflammatory syndrome, otherwise known as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, the virus that causes COVID-19 (PIMS-TS).

Data from 2015 to 2019 revealed a mean of one admission per week for all four similar inflammatory diseases, compared with, on average, 14 admissions per week for PIMS-TS and a high of 32 admissions per week during the study period.

Median patient age was 11 years, and boys (52 of 78 [67%]) and ethnic minorities (61/78 [78%] were overrepresented. The most common signs and symptoms were fever (78 [100%]), shock (68 [87%]), stomach pain (48 [62%]), vomiting (49 [63%]), and diarrhea (50 [64%]).

Twenty-eight of 78 children (36%) had coronary artery abnormalities such as aneurysms (weakening and enlargement of an artery wall) and echogenicity (abnormal cardiac ultrasound findings). Sixty-five children (83%) needed medications to regulate their blood pressure, 36 (46%) required invasive mechanical ventilation, 3 (4%) needed oxygen added to their blood outside their body, and 2 (3%) died.

The authors noted that this emerging condition might have a social impact. "Until now, the risk of serious illness resulting from COVID-19 in children has been thought to be negligible: even though the risk is still low, there are implications for health-care resources and balancing the need for adult and paediatric intensive care units," they wrote. "Our data also have important implications for any future peaks of PIMS-TS, especially if the rise in cases coincides with a winter surge of other viral infections."
Jul 9 Lancet Child Adolesc Health study

FDA grants fast track designation to two COVID-19 vaccine candidates

Pfizer and BioNTech announced today that the US Food and Drug Administration (FDA) has granted fast track designation to two of the companies' vaccine candidates for SARS-CoV-2, the virus that causes COVID-19.

The two candidates—BNT162b1 and BNT162b2—are the most promising of the four investigational mRNA vaccines the companies are developing. BNT162b1 encodes an optimized SARS-CoV-2 receptor-binding domain (RBD) antigen, while BNT162b2 encodes an optimized SARS-CoV-2 full-length spike protein antigen.

Recent data from a phase 1/2 trial of BNT162b1 published on the preprint server medRxiv but not yet peer-reviewed showed promising early results. More data from a German trial of BNT162b1 is expected later this month.

The FDA's fast track designation allows for expedited review of investigational drugs that treat a serious or life-threatening condition and fill an unmet medical need.

"We are pleased to have received Fast Track designation from the FDA for two of our vaccine candidates and look forward to working closely with the FDA, along with our partner Pfizer, to expedite the clinical development path forward," BioNTech Chief Medical Officer Ozlem Tureci said in a company press release.

The companies say they that if they receive regulatory approval, they expect to start a phase 2b/3 trial as soon as later this month. They anticipate enrolling as many as 30,000 participants.
Jul 13 BioNTech press release

In other COVID-19 vaccine-related developments, the National Institutes of Health (NIH) announced last week that it has established a new clinical trials network that aims to enroll thousands of volunteers in large-scale trials testing investigational vaccines and monoclonal antibodies.

The COVID-19 Prevention Trials Network (COVPN) is part of Operation Warp Speed, the US Department of Health and Human Services-led effort to develop, manufacture, and distribute COVID-19 vaccines, therapeutics, and diagnostics. The network will operate more than 100 clinical trial sites across the United States and use a harmonized vaccine protocol to enable analyses of correlates of protection across multiple vaccine trials.

The first phase 3 vaccine trial that COVPN is expected to conduct will test the mRNA-1273 vaccine developed by National Institutes of Allergy and Infectious Disease scientists in collaboration with Moderna.
Jul 8 NIH press release

Strokes with COVID more severe, tied to higher rates of death, disability

Ischemic strokes linked to COVID-19 are more severe, lead to worse functional outcomes, and are associated with a higher rate of death, according to a study published late last week in Stroke.

Researchers compared the data of 174 patients with COVID-19 and ischemic stroke treated at 28 healthcare centers in 16 countries from Jan 27 to May 19 with those of 156 matched patients with stroke alone from a Swiss stroke registry from 2003 to 2019.

Patients with the novel coronavirus had more severe strokes, with a median National Institutes of Health Stroke Scale score of 10, versus 6 in those without COVID-19. Coronavirus patients were at higher risk of serious disability after stroke, with a modified Rankin score of 4, versus 2 in non-coronavirus patients. Of 96 surviving COVID-19 patients with disability status data, 49 (51%) had severe disability at hospital release.

COVID-19 patients were also more likely to die; 48 of 174 patients (28%) died, 22 of them due to coronavirus and 26 due to stroke. Median patient age was 71 years, and 38% of the 174 coronavirus patients were women.

The authors said that worse outcomes in COVID-19 patients may be attributed to the more severe strokes in that group and called for further research on the underlying mechanisms of stroke in coronavirus patients and prehospital and in-hospital stroke pathways during this and future pandemics.

"The broad, multi-system complications of COVID-19, including acute respiratory distress syndrome, cardiac arrhythmias, acute cardiac injury, shock, pulmonary embolism, cytokine release syndrome and secondary infection, probably contribute further to the worse outcomes including higher mortality in these patients," they said in a news release from the American Heart Association, which publishes Stroke under its American Stroke Association division.
Jul 9 Stroke abstract
Jul 10 American Heart Association news release

Study: One third of young adults at risk for severe COVID-19 infections

As many as 33% of US men ages 18 to 25 and 30% of women are at risk for serious complications from COVID-19 infections, according to a new study from the University of California- San Francisco (UCSF), published today in the Journal of Adolescent Health. The risk is related to smoking, including the use of e-cigarettes.

To conduct the study, researchers compared and contrasted data from the Centers for Disease Control and Prevention’s list of conditions and associated behaviors linked to COVID-19 disease and death (eg, smoking, heart conditions, diabetes, current asthma, immune conditions) with answers from the National Health Interview Survey (NHIS), a nationally representative data set with pooled data from 2016 to 2018.

Overall, the authors said medical vulnerability for severe COVID-19 outcomes was 32% for the full sample of 8,405 young adults and half that (16%) for the nonsmoking sample. According to the NHIS, over the previous 30 days, 11% of the young adults polled had smoked a cigarette, 5% had smoked a cigar product, and 7% had smoked an e-cigarette.

"The risk of being medically vulnerable to severe disease is halved when smokers are removed from the sample," senior author Charles Irwin, Jr., MD, of the UCSF Division of Adolescent and Young Adult Medicine said in a press release. "Efforts to reduce smoking and e-cigarette use among young adults would likely lower their vulnerability to severe disease."
Jul 13 UCSF press release
Jul 13 J Adolesc Health study