COVID-19 Scan for Jan 29, 2021

News brief

COVID inflammatory syndrome in kids ranges from mild to life-threatening

An international survey of 183 pediatric patients with the rare but serious COVID-19–related multisystem inflammatory syndrome in children (MIS-C) shows broad clinical presentations, from mild illness featuring fever and inflammation to life-threatening shock similar to that of Kawasaki disease (KD).

The study, led by researchers at Royal Brompton Hospital in London and published today in Pediatrics, was a retrospective case series of children younger than 18 years diagnosed as having MIS-C who were released from the hospital or died from Mar 1 to Jun 15, 2020, from 33 hospitals in American, Asian, and European countries.

Of the 183 patients, 114 (62.3%) had evidence of severe COVID-19. All had fever, 117 (63.9%) had gastrointestinal symptoms, and 79 (43.2%) had shock. Shock was linked to black race, higher levels of inflammation, and abnormal imaging findings.

Twenty-seven of 183 children (14.7%) met the criteria for KD. They were younger, did not experience shock, and had fewer cardiorespiratory, gastrointestinal, and neurologic symptoms. The remaining patients primarily had fever and inflammation.

The 78 patients (42.6%) with shock were older than their counterparts and significantly more likely to have positive antibody test results. Black children had substantially higher rates of cardiorespiratory, gastrointestinal, and neurologic symptoms.

Children hospitalized sooner rather than later after they developed symptoms were linked to worse outcomes and were more likely to need extracorporeal membrane oxygenation (ECMO, or oxygen added to the blood outside the body) (72.3% higher risk per day reduction) and to die (63.3% higher risk per day reduction).

Seventy-two patients (39.3%) required drugs to strengthen their heartbeats, 43 (23.5%) received mechanical ventilation, and 4 (2.2%) needed ECMO. Three children (1.6%) died. Mean patient age was 7.0 years, 30.6% were black, and 26.2% were obese.

"MIS-C has emerged with a wide clinical spectrum at presentation, including KD-like, life-threatening shock and milder forms with mainly fever and inflammation," the authors concluded. "The risk for worse outcome (ECMO and/or death) is associated with a short time interval between the onset of symptoms and admission. More studies encompassing larger numbers of patients are needed to better describe this new disease, its optimal treatment, and long-term monitoring."
Jan 29 Pediatrics study

Rates of screening for cervical cancer drop during COVID

During California's 3-month stay-at-home order, cervical screening rates dropped 80% per 100 person-months compared with the 2019 baseline, according to a study today in Morbidity and Mortality Weekly Report. The researchers write that rates returned almost to baseline by Sep 30, 2020.

The study pulled from 2019 and 2020 health records from the Kaiser Permanente Southern California network, which recommends Pap tests every 3 years for women 21 to 29 years of age and human papillomavirus (HPV) tests every 5 years for women 30 to 65. More than 1,455,200 women were included per year in the study after the researchers excluded women who had complete hysterectomies or who had histories of precancer or cervical cancer.

Before the stay-at-home order started on Mar 19, 2020, younger women had 8% less screenings per 100 person-months, 82% less during the order, and then 24% less after it was lifted Jun 12, 2020, in comparison to 2019. Older women had a 3% decrease, 89% decrease, and then 29% decrease, respectively, when compared with the 2019 baseline.

The researchers note that it is unknown whether women who missed screenings during the stay-at-home-order came back after it was lifted.

"During a pandemic, bringing populations at higher risk back to screening first, such as those with abnormal results or increased risk for precancers and cancers, is important," they write. The researchers recommend enhanced outreach with prioritized targets as well as additional resources such as telemedicine or the development of tests involving HPV self-collected samples.
Jan 29 MMWR study

News Scan for Jan 29, 2021

News brief

Study: Vaccinating against 10 diseases will prevent 69 million deaths

A modeling study published yesterday in The Lancet estimates that vaccination against 10 diseases from 2000 to 2030 will prevent 69 million vaccine-preventable deaths (VPDs) in low- and middle-income countries (LMICs).

The study suggests that a baby born in 2019 in 98 LMICs countries will experience 72% lower mortality from the 10 diseases, including measles, rotavirus, human papillomavirus, and hepatitis, over their lifetime than if there were no immunizations.

"Our modelling has provided robust evidence on the effectiveness of vaccination programmes in LMICs and indicated what might be lost if current vaccination programmes are not sustained,” said Caroline Trotter, PhD, from the University of Cambridge, a co-author of the study in a Lancet press release.

The study combined data from 20 models following immunization trends, and compared outcomes to scenarios where there were no vaccinations. The authors found vaccinations against measles were the most impactful—projected to prevent 56 million deaths from 2000 to 2030.

In a commentary on the study, experts from the US Centers for Disease Control and Prevention (CDC) and the World Health Organization suggest the models underestimate the true number of deaths the vaccines prevent in the 30-year period because they take into account LMICs only. They warn that the COVID-19 pandemic could hinder the progress made in tackling VPDs.

"This decline in coverage together with vaccine scepticism, which is being increasingly reported in low-income and middle-income countries, threatens to reverse the gains that have been achieved," the commentary authors said.
Jan 28 Lancet study
Jan 28 Lancet commentary
Jan 28 Lancet press release

H3N2v flu case reported in Wisconsin child

The CDC today reported the first variant H3N2 (H3N2v) case of the year, which involves a child from Wisconsin who lives on a farm that has pigs, according the CDC's weekly FluView report.

The patient wasn't hospitalized and has completely recovered.

Only one H3N2v case was reported to the CDC last year, which involved a child from Hawaii. Since the 2010-11 flu season, 431 cases have been reported to the agency. Earlier H3N2v cases were linked to swine exposure in settings such as agricultural fairs in the summer.
Jan 29 CDC FluView report
CDC variant flu totals

H9N2 avian flu infects 1 more in China

China reported a new H9N2 avian flu case, this time in an adult from Fujian province, marking its first such infection of the new year, the European Centre for Disease Prevention and Control (ECDC) said in its weekly communicable disease threat report.

The patient is a 52-year-old woman from the city of Xiamen in Fujian province in the southeast. Her symptoms began on Jan 2. The investigation found that she didn't have any history of exposure to poultry or birds. No other infections were found in her contacts.

China reported 16 H9N2 cases in 2020, and globally since 1998, 78 confirmed cases have been reported, mostly from China, which continues to report sporadic infections. H9N2 infections have been more common in children and are typically mild, and so far, the infections haven't been linked to sustained transmission.
Jan 29 ECDC communicable disease update

Four countries report more vaccine-derived polio cases

Four countries in the Middle East and Africa reported more polio cases last week, all involving vaccine-derived strains, according to the latest update from the Global Polio Eradication Initiative (GPEI).

In the Middle East, Pakistan reported 6 more vaccine-derived poliovirus type 2 (cVDPV2) cases, 2 each in Sindh, Punjab, and Balochistan provinces, raising the total for 2020 to 128 cases. Also, Yemen reported 1 circulating vaccine-derived poliovirus type 1 (cVDPV1) case, putting its overall total at 29.

Meanwhile, in Africa, Burkina Faso reported 3 more cVDPV2 cases, all in Dori, bringing its total to 59 from two different outbreaks, 1 linked to circulation in Nigeria and the other due to activity in Togo. Also, Mali reported 7 cVDPV2 cases from four different regions, raising its total for 2020 to 35.
Jan 28 GPEI update

ASP Scan (Weekly) for Jan 29, 2021

News brief

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

Study finds most outpatient antibiotics in China are inappropriate

Originally published by CIDRAP News Jan 28

More than half of outpatient antibiotic prescriptions at Chinese hospitals over a 3.5-year period were inappropriate, Chinese researchers reported yesterday in The Lancet Infectious Diseases.

Using data from the Beijing Data Center for Rational Use of Drugs, a national database that collects prescription data from hospitals from all provincial-level regions in mainland China, the researchers analyzed antibiotic prescriptions linked to visits to outpatient clinics and emergency departments from Oct 1, 2014, through April 30, 2018.

A total of nearly 173 million outpatient visits to 139 secondary and tertiary hospitals were evaluated in the study. ICD-10 diagnostic codes were used to classify outpatient antibiotic prescriptions issued on the same day as diagnosis as appropriate, potentially appropriate, inappropriate, or not linked to any diagnosis for antibiotic use.

Over the study period, 18,848,864 outpatient visits (10.9%) ended with an antibiotic prescription, with prescribing rates of 9.3% for outpatient clinics and 26.9% for emergency departments. Of the antibiotic prescriptions, 51.4% were classified as inappropriate, 28.4% as potentially appropriate, and 15.3% as appropriate, and 4.8% could not be linked to any diagnosis.

Children younger than 6 years had the highest proportion of inappropriate prescriptions, at 71.1%. A substantial amount of antibiotic overuse was driven by respiratory conditions, mainly viral upper respiratory tract infections and bronchitis.

Of the more than 23 million individual antibiotics prescribed, 80% were broad-spectrum. The top four most prescribed antibiotics were third-generation cephalosporins (21.7%), second-generation cephalosporins (16.4%), macrolides (15.3%), and fluoroquinolones (14.1%).

The authors say the findings of the study—the first of its kind conducted in China—suggest China's efforts to curb antibiotic overuse over the past decade have had little effect. Promoting appropriate use of antibiotics and establishing antibiotic stewardship programs in secondary and tertiary hospitals are two of the targets of China's 5-year national action plan (NAP) to contain antimicrobial resistance, which was launched in 2016.

"In conclusion, our findings indicate that inappropriate antibiotic prescribing was highly prevalent nationwide in China," the authors wrote. "More in-depth antibiotic stewardship programmes focusing on optimising antibiotic prescribing need to be implemented in China to achieve the goals set in the NAP."
Jan 27 Lancet Infect Dis abstract

European biotech firms urge support for antibiotic development measures

Originally published by CIDRAP News Jan 28

A coalition of European biotech companies is voicing its support for the European Commission's efforts to boost antibiotic development.

In a statement posted on its website, the BEAM (Biotech companies from Europe innovating in Anti-Microbial resistance research) Alliance said it welcomes the European Commission's Pharmaceutical Strategy, which aims to ensure that Europe has the supply of safe, effective, and affordable medicines to meet its needs. Adopted on Nov 25, 2020, the strategy recognizes the development of novel antibiotics as a prime example of addressing unmet medical needs—one of the strategy's four pillars—and calls for new economic incentives and reimbursement models to boost antibiotic development.

The Alliance also said that while new incentives and reimbursement reforms are needed to maintain a sustainable pipeline of new antibiotics over the long-term, faster solutions are needed. And it argues that innovative approaches to boost antibiotic research and development should embrace a broad definition of antibiotics, including nontraditional approaches, and take into account the needs of small- to medium-sized companies, which are struggling to advance their antibiotic-development programs because of the financial challenges.

"The BEAM Alliance stands ready to provide all necessary input to support the Commission in finding innovative solutions that can be deployed in the short term, and to contribute to the debates on systemic, long-term reforms," the group wrote.
Jan 26 BEAM Alliance statement

Groups criticize One Health Certified food label over antibiotic use standards

Originally published by CIDRAP News Jan 27

A coalition of animal welfare, public health, environmental, and consumer organizations is speaking out against use of the One Health Certified (OHC) label on chicken and turkey products, claiming the standards behind the label don't protect against overuse of medically important antibiotics in food-producing animals.

The OHC program is open to food producers who want to demonstrate to consumers a commitment to responsible, sustainable, and transparent animal care practices. Responsible antibiotic use in livestock is listed as one of the core principles of the OHC program, which links itself to the concept that human, animal, and environmental health are inextricably linked.

But in a press release yesterday, the coalition of 13 organizations said the OHC standards are weaker than and out of line with the responsible antibiotic use practices recommended by the World Health Organization (WHO) in 2017, and are less stringent than those already adopted by the US poultry industry.

In particular, the groups note that OHC standards allow the use of medically important antibiotics for disease prevention in animals, rather than reserving them for treating sick animals or controlling disease outbreaks on farms. The WHO guidelines recommend against using medically important antibiotics for disease prevention in food-producing animals, and many public health and antibiotic-resistance experts believe the practice contributes to the emergence and spread of resistant bacteria.

"Antibiotic resistance is one of the greatest threats to public health today and overuse of antibiotics in animal agriculture is one of the driving forces behind this crisis," said Laura Rogers, deputy director for the Antibiotic Resistance Action Center at George Washington University's Milken Institute School of Public Health. "Genuinely responsible use of antibiotics needs to be addressed in conjunction with improved animal health and welfare practices to decrease disease risks and minimize the need for antibiotics in the first place."

The groups also say the OHC standards on animal welfare and environmental protection are lacking.

The OHC label was approved in early 2020 and is currently being used by a handful of grocery chains.
Jan 26 Coalition press release

CARB-X to fund development of low-cost diarrheal disease treatment

Originally published by CIDRAP News Jan 27

CARB-X announced today that it is awarding up to $5.35 million to Lumen Bioscience of Seattle to develop a new immunotherapy to prevent diarrheal diseases caused by Campylobacter jejuni and enterotoxigenic Escherichia coli.

The money will help fund development of LMN-GI-EEC-401, an oral antibiotic-alternative biologic designed to bind to and neutralize C jejuni and enterotoxigenic E coli, the two primary causes of what is commonly known as traveler's diarrhea. In low- and middle-income countries, diarrheal diseases are a leading cause of death and disease among infants and children.

Lumen says the goal is to develop a cheap, edible, immuno-prophylactic drug that could be distributed in areas of the world where healthcare temperature control is not available.

"Preventatives are urgently needed for deadly infections," CARB-X research and development chief Erin Duffy, PhD, said in a press release. "The Lumen project is an extremely innovative immunotherapy in the early phases of development, and if successful, could potentially transform the way we prevent deadly infections in infants and children, and save precious lives."

The project could be eligible for up to $8.26 million more in non-dilutive funding from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) if certain project milestones are met.
Jan 27 CARB-X press release

French study finds high antibiotic use in COVID-19 patients

Originally published by CIDRAP News Jan 25

Antibiotics were widely prescribed to hospitalized COVID-19 patients at Dijon University Hospital in France during the first wave of the pandemic but did not have any impact on outcome, French researchers reported yesterday in the International Journal of Infectious Diseases.

To assess the potential usefulness of empiric antibiotic therapy in patients hospitalized with COVID-19, hospital researchers conducted a retrospective study of all patients hospitalized for a confirmed COVID-19 infection from Feb 27 through Apr 30, 2020. They collected clinical, biologic, treatment, and outcome data, then compared the characteristics and outcomes of patients treated with and without antibiotics using propensity score matching.

Of the 220 patients included in the study, 174 (78%) were treated with antibiotics, most frequently amoxicillin-clavulanic acid (95 patients, 55%) and third-generation cephalosporins with or without macrolides (25, 14% and 27, 16%, respectively). No bacterial co-infections were documented.

Univariate analysis found that patients treated with antibiotics were significantly older, frailer, and had more severe disease on admission, and an unfavorable event (death or transfer to the intensive care unit) was more frequent in patients with antibiotic therapy than those without (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.07 to 8.11). In the multivariate analysis, however, antibiotic therapy was not significantly associated with outcome (HR, 1.612; 95% CI, 0.562 to 4.629), and no significant association between antibiotic use and outcome was observed on the propensity score matching (HR, 1.238; 95% CI, 0.77 to 2.00).

The study is the latest to document high antibiotic use in COVID-19 patients in the early months of the pandemic. The authors say the findings indicate that antibiotics should not be prescribed systematically for COVID-19 unless there is strong suspicion or proof of bacterial co-infection.
Jan 24 Int J Infect Dis study

Poor sanitation promotes antibiotic resistance, study reveals

Originally published by CIDRAP News Jan 25

Poor sanitation may play a significant role in selecting for antibiotic-resistant bacteria among residents, according to a study conducted in one of Africa's largest slums.

In the 5-month longitudinal study, published late last week in Antimicrobial Resistance and Infection Control, researchers with Washington State University, Kenya Medical Research Institute, and the US Centers for Disease Control and Prevention (CDC) selected 200 households from two villages in Kibera, an informal settlement in Nairobi, Kenya, for biweekly interviews that included questions on water, sanitation, hygiene, and antibiotic use practices. They also collected stool, hand swab, and drinking water samples to analyze for the presence of antibiotic-resistant bacteria. E coli isolated from the samples were tested against nine antibiotics from seven classes.

The analysis of E coli isolates found that 87.4% of stool, 83% of hand swab, and 79.7% of water sample isolates were resistant to at least one antibiotic, and 80% of all presumptive E coli isolates were resistant to at least three antibiotics. Stool isolates were resistant to trimethoprim (81%), sulfamethoxazole (80%), ampicillin (68%), streptomycin (60%), and tetracycline (55%).

Interviews found that 97 households (48.5%) reported using an antibiotic in at least one visit over the study period, for a total of 144 antibiotic episodes and 190 doses. Children in the households had 5 times the number of antibiotic episodes reported by adults (96 vs 19).

Multivariable regression models indicated antibiotic use within the household was not a significant risk factor for resistance to any of the nine antibiotics tested in adults and was only associated with resistance to two antibiotics in children. Enrolled children eating soil from the household compound and the presence of a common hand-washing station were both associated with an increased load of antibiotic-resistant E coli at the household and individual levels.

The authors concluded that while the presence of resistant bacteria appeared to be more affected by poor sanitation and environmental contamination, antibiotic use in the community could still play a role in promoting antibiotic resistance.

"Kibera experiences sanitation challenges that promote disease transmission and demand for antibiotics within a highly dense population," they wrote. "Under these conditions it is likely that selection of antibiotic-resistant bacteria within the gut, their disposal and enrichment within the environment, and recurrent transmission to humans occurs continuously."
Jan 22 Antimicrob Resist Infect Control study