H9N2 avian flu infects children in India, China

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India has reported an H9N2 avian flu case involving a child in West Bengal state who was exposed to poultry, marking the country's second such case since 2019, the World Health Organization (WHO) said today in a statement, and China confirmed another pediatric H9N2 infection.

backyard poultry
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The 4-year-old child, who had a history of upper-airway disease, was first hospitalized in February for complications from respiratory virus infections, which included influenza B and adenovirus. In early March, the child was hospitalized again with severe respiratory symptoms, which were positive for unsubtyped influenza A and rhinovirus.

Further testing of the flu virus sample revealed H9N2. The child was discharged from the hospital on oxygen support on May 1. The follow-up investigation found that the patient had been exposed to poultry at home. No similar symptoms were reported in the patient's family, community, or healthcare contacts.

The WHO said most H9N2 infections are typically mild, though a few hospitalizations and deaths have been reported. It added that sporadic infections will likely continue, though the overall risk is low, given that H9N2 hasn't shown a capacity to transmit easily among people.

China reports another H9N2 case

China's H9N2 case is in Guangxi province, according to a weekly avian influenza update from Hong Kong's Centre for Health Protection. The 3-year-old boy's symptoms began on May 2. No other details were available about his condition or how he likely contracted the virus.

H9N2 circulates as a low-pathogenic virus in poultry in many parts of the world. China's mainland has reported five infections involving the virus this year.

Moderna reports promising findings for flu-COVID combo vaccine

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Moderna yesterday reported promising phase 3 clinical trial findings for its candidate combination mRNA vaccine (mRNA-1083) against influenza and COVID-19. The vaccine contains components of Moderna's candidate seasonal flu vaccine and its next-generation COVID-19 vaccine.

vaccine supplies
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The company tested the vaccine in two adult cohorts, one adults ages 65 and older—some who were coadministered Fluzone high-dose flu vaccine and Moderna's current COVID vaccine and some who got Moderna's combination vaccine. The other group comprised adults ages 50 to 64 years old, some of whom were co-administered Fluarix, a standard-dose flu vaccine, and Moderna's current COVID vaccine and some who got Moderna's combo vaccine.

In both groups, the combo vaccine prompted higher immune response against seasonal flu strains and SARS-CoV-2. Safety and tolerability measures were similar to that of licensed vaccines used in the trial.

Moderna said it will present the findings at an upcoming conference and will submit them for publication in a medical journal. The company said it would engage with regulators on the next steps.

Combo vaccine could help fill vaccination gaps

In a blog post, Francesca Ceddia, MD, Moderna's chief medical affairs officer, said other combinations such as tetanus, diphtheria, and pertussis (TDaP) and measles, mumps, and rubella (MMR) have been shown to protect against multiple disease and have been tied to improved vaccine coverage and adherence to immunization schedules.

She said that, as of May, flu vaccine uptake for the 2023-24 season was more than double that of COVID for US adults. Ceddia added, however, that COVID hospitalizations were higher than for flu, especially in older adults. "The convenience that a combination vaccine could offer patients may help fill this gap while simplifying and routinizing vaccination against both diseases, which could help improve compliance with public health recommendations."

RSV hospitalizations for kids doubled in 2022-23

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rsvp
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A new study today in JAMA Network Open shows that pediatric hospitalizations for respiratory syncytial virus (RSV) doubled during the 2022-2023 season compared to the prior year. 

The population-based cohort study of children aged 5 years and younger in Ontario, Canada, looked at hospitalization and intensive care unit (ICU) admissions for RSV from July 1, 2017,  through March 31, 2023.

On average, 700,000 children per study year were included. Though the 2021-2022 season peaked a bit earlier than prepandemic seasons, the number of hospitalizations was similar, at 289.1 per 100,000 children in 2021-2022, compared to 281.4 to 334.6 per 100,000 in 2017 through 2020.

In 2022-2023, however, RSV season peaked a month earlier and resulted in more than twice as many hospitalizations (770.0 per 100 000).

ICU admissions tripled

The RSV hospitalizations also led to more ICU admissions.

”The proportion of children admitted to an ICU in 2022-2023 (13.9%) was slightly higher than prepandemic (9.6%-11.4%); however, the population-based rate was triple the prepandemic levels (106.9 vs 27.6-36.6 per 100 000 children in Ontario)," the authors said. 

The rate of mechanical ventilation use was also two- to three-fold higher in 2022-2023 compared with prepandemic years, the authors said. 

During 2020 and 2021, cases of RSV dropped as COVID-19 mitigation measures, including masking and school closures, halted transmission of RSV. In Ontario, only 11 RSV hospitalizations and seven ICU admissions occurred during the 2020-2021 season. But in 2022-2023, a resurgence was seen as RSV, flu, and COVID-19 all co-circulated with most mitigation efforts removed. 

The unexpected and widespread influences on seasonal respiratory viruses that followed the COVID-19 pandemic underscore the need for ongoing research.

"The unexpected and widespread influences on seasonal respiratory viruses that followed the COVID-19 pandemic underscore the need for ongoing research to understand the impact of pandemic mitigation measures and the unique factors of transmission for common pathogens to ensure societies are better prepared to respond to future pandemics," the authors concluded. 


 

GARDP, Bugworks to collaborate on broad-spectrum antibiotic

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The Global Antibiotic Research & Development Partnership (GARDP) today announced an agreement with Indian pharmaceutical company Bugworks Research Inc. to co-develop a new broad-spectrum antibiotic that targets some of the most difficult-to-treat bacterial pathogens

Under the agreement, GARDP will provide Bugworks up to $20 million in financial and technical support to develop BWC0977, a compound that has demonstrated in vitro activity against World Health Organization critical priority pathogens, including carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae. In return, GARDP will acquire the manufacturing and commercialization rights for BWC0977 in 146 primarily low- and middle-income countries (LMICs).

Addressing unmet public health needs

"We are excited to work with Bugworks to make key investments at this critical stage in the development of compound BWC0977," GARDP Executive Director Manica Balasegaram, MRCP, MSc, said in a press release. "Many compounds in the antibiotic pipeline lack innovative characteristics and fail to target priority pathogens. In contrast, BWC0977 stands out for its novelty and potential to address unmet public health needs."

The agreement makes official an alliance that was first announced in July 2023, when GARDP and Bugworks signed a non-binding term sheet to define the framework of a potential collaboration. GARDP says its support of BWC0977 depends on successful completion of key research and development milestones that align with its public health objectives.

Many compounds in the antibiotic pipeline lack innovative characteristics and fail to target priority pathogens. In contrast, BWC0977 stands out for its novelty and potential to address unmet public health needs.

Bugworks has received more than $12 million from CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) for pre-clinical development and a phase 1 study of BWC0977. The collaboration with GARDP aims to take the compound through approval and commercialization.

"An overarching goal of this partnership is to enable access to this compound simultaneously in Western countries and in LMICs with high AMR [antimicrobial resistance] burden," said Bugworks co-founder and CEO Anand Anandkumar, PhD. "We are grateful to CARB-X for their continued support for BWC0977 from lead optimization to human clinical trials, thus enabling the asset to enter the GARDP collaborative orbit."

Emergency department data show shift in antibiotics used for pediatric UTIs

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An analysis of US emergency department (ED) visits for pediatric urinary tract infections (UTIs) provides some new insight into antibiotic prescribing practices, researchers reported today in Pediatrics.

Led by researchers from Boston Children's Hospital, the analysis aimed to evaluate changes in antibiotic prescribing at US ED visits for pediatric UTIs from 2011 to 2020 using nationally representative data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). A previous analysis of NHAMCS data found that, from 1998 to 2007, there was a decline in use of trimethoprim-sulfamethoxazole (TMP-SMX) for pediatric UTIs amid rising resistance rates and a significant increase in the use of enteral third-generation cephalosporins (e3GC). 

That finding raised concerns because e3GC are broad-spectrum antibiotics that can select for antibiotic resistance. In 2014, updated cephalosporin susceptibility criteria for Enterobacterales species made enteral first-generation cephalosporins (e1GC), which target fewer bacterial species, a potential empiric option for uncomplicated UTIs.

Increased use of first-generation cephaloporins

A total of 1,083 UTI visits by non-pregnant patients ages 18 and younger were included in the analysis. Over the study period, TMP-SMX prescriptions declined from 20.6% to 9.9% of visits, while use of e1GC increased from 15.2% to 32.6% of visits and use of e3CG remained unchanged. The findings persisted despite adjustments for age, sex, region, fever on presentation, payment type, and hospitalization.

"Although e3GC use had increased previously, their prescription rate did not significantly change, perhaps reflecting appropriate use in areas with higher resistance," the study authors wrote. "Given their association with development of resistance, ongoing monitoring and quality improvement will be important."

The authors add that the increased use of e1CG for pediatric UTIs is encouraging, because they're appropriate for empiric treatment but less likely to drive antibiotic resistance than other agents.

Having symptoms after getting a COVID vaccine may indicate robust immune response

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Immunization against COVID-19
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Headache, fatigue, malaise, and chills after COVID-19 vaccination are signs the immune system is marshalling a strong response against future infection, suggests a study posted today in the Annals of Internal Medicine.

University of California at San Francisco (UCSF) investigators analyzed serum neutralizing antibody (nAB) levels against the wild-type SARS-CoV-2 strain and daily symptom surveys in 363 unvaccinated, never-infected adults given two doses of an mRNA COVID-19 vaccine in 2021.

About 40% of the participants also wore a biometric device to measure their skin temperature and heart and breathing rate. Most participants were in their 40s to 60s.

Higher antibody levels after second dose

One and 6 months after receipt of the second vaccine dose, fatigue, malaise, chills, and headache were each tied to 1.4- to 1.6-fold higher nAB concentrations. nAB levels in participants who experienced at least seven symptoms were nearly double the levels of those who reported no symptoms. 

In participants who wore a biometric device, each 1°C (1.8°F) increase in skin temperature after the second dose was associated with 1.8-fold and 3.1-fold higher nAB levels 1 and 6 months later.

"Generally, we found that the higher the number of side effects, the higher the level of antibodies," first author Ethan Dutcher, MD, PhD, said in a UCSF news release. "But this wasn't a hard rule: some people without side effects had better antibodies than some people with side effects."

The team noted that concerns about vaccine side effects often contribute to vaccine hesitancy. "The toll of COVID is still high for some—sickness, lost work, lasting fatigue and the dreaded long COVID," co–senior author Elissa Epel, PhD, said in the release. "While the symptoms from vaccination can be very unpleasant, it's important to remember that they don't come close to the disease's potential complications," she said.

While the symptoms from vaccination can be very unpleasant, it's important to remember that they don't come close to the disease's potential complications.

Elissa Epel, PhD

The Centers for Disease Control and Prevention recommends that everyone 6 months and older receive the updated COVID-19 vaccine and those 65 years and older receive an additional dose.

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