Moderna COVID-19 vaccine found to be non-inferior in adolescents

Moderna's COVID-19 vaccine was safe in adolescents 12 to 17 years old, with a similar immune response to that in young adults, according to results of an ongoing phase 2-3 trial published in the New England Journal of Medicine yesterday.

The researchers assigned 3,732 participants two doses of either the Moderna vaccine or a placebo in a 2:1 ratio from Dec 9, 2020, to Feb 28, 2021. The average age of the cohort was 14.3 years, 51% were male, and 84% were White. Participants were not excluded if they had experienced anaphylaxis or serious allergic reactions in the past, unless it was to a vaccine.

Geometric mean titer ratio of pseudovirus neutralizing antibody titers in the intervention arm compared with young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24). Serologic response was 98.8% in adolescents, only 0.2 percentage points lower than the 98.6% found in young adults (95% CI, -1.9 to 2.4).

The Moderna vaccine had an acceptable safety profile in adolescents, according to the researchers, but they did note that 6.8% to 8.9% of vaccine recipients had grade 3 local adverse reactions and 4.4% to 13.7% experienced grade 3 systemic adverse reactions. One person even had a grade 4 fever (< 0.1%). As of the report write-up, none had myocarditis or pericarditis, but the researchers say this is expected given the sample size.

No cases of COVID-19 occurred in the intervention group starting 14 days after the second dose, but four occurred in the placebo group. Because of the low cases in either group, the researchers write, "The efficacy analyses were secondary objectives of the trial because of milder Covid-19 disease and a lower disease incidence among adolescents than among adults in the phase 3 trial. However, the effectiveness of the mRNA-1273 vaccine in adolescents between the ages of 12 and 17 years is supported by both the noninferiority of the immunogenicity results for the vaccine and the preliminary estimate of vaccine efficacy."
 Aug 11 N Engl J Med study


Clinical trial shows promise for monoclonal antibody malaria preventive

For the first time, researchers yesterday reported that a monoclonal antibody can prevent malaria in humans. A team based at the National Institute Allergy and Infectious Diseases (NIAID) Vaccine Research Centers published their phase 1 clinical trial results yesterday in the New England Journal of Medicine.

The monoclonal antibody, called CIS43LS, was developed from a neutralizing antibody isolated from the blood of a volunteer who had received an investigational malaria vaccine. Researchers examined whether the monoclonal antibody could safely prompt high-level protection against experimental exposure to infected mosquitoes.

For the phase 1 study, the team enrolled 40 healthy adults ages 18 to 50 who had never had malaria or been vaccinated against the disease. For the first half of the trial, 21 participants got one dose of the monoclonal antibody through intravenous infusion or subcutaneous injection. They followed the group for 6 months, looking at safety, tolerability, and durability of antibody levels.

The second part of the study involved controlled human exposure to the bites of Plasmodium falciparum-infected mosquitos 4 weeks after monoclonal antibody administration. It also evaluated a second IV infusion, included more participants who got a first infusion, and added a control group.

After 3 weeks, none of the patients in the treatment group developed malaria, but five of six in the control group did. Of the treatment group, two had received just one dose 9 months earlier, suggesting that one dose can prevent malaria 1 to 9 months after treatment.

A larger phase 2 trial is underway in Mali during the country's 6-month malaria season.

Robert Seder, MD, part of the study group, said in a National Institutes of Health press release that monoclonal antibodies may be a new approach for preventing malaria in military personnel, travelers, and health workers. "Further research will determine whether monoclonal antibodies can also be used for the seasonal control of malaria in Africa and ultimately for malaria-elimination campaigns."
Aug 11 N Engl J Med study
Aug 11 NIH press release


New Hampshire reports fatal Jamestown Canyon virus case

New Hampshire health officials recently reported the state's first Jamestown Canyon virus (JCV) case of the season, an adult who died from the infection.

The patient is from Dublin, located in the east central part of the state, the New Hampshire Department of Health and Human Services (NHDHHS) said in a statement. The patient was hospitalized with worsening neurological symptoms and died, with JCV as a contributing cause.

 The city's risk level has been raised to high, and the risk level for surrounding cities (Harrisville, Peterborough, Jaffrey, and Marlborough) will increase to moderate. Officials warned that the risk will increase through the summer and into the fall and that residents and visitors should take steps to avoid mosquito bites. New Hampshire has now recorded 15 cases since 2013.

JCV usually circulates between mosquitoes and deer, but can also infect people. Reports in the United States have increased due to enhanced recognition and testing; the United States typically records about 15 cases each year. The virus mainly circulates in the Midwest and Northeast, typically in late spring through the middle of fall. Most infections are asymptomatic or mild, but severe cases can lead to encephalitis, meningitis, or death. There are no vaccines or treatments.
Aug 6 NHDHHS press release


H5N1 avian flu strikes poultry in Ivory Coast

Animal health officials in the Ivory Coast reported a highly pathogenic H5N1 avian influenza outbreak in poultry, the country's first since 2016, according to a notification from the World Organization for Animal Health (OIE).

The outbreak struck a large number of village birds—which included chickens, Guinea fowl, turkeys, ducks, and quail— in Mondoukou in Comoe district, located in the east central part of the country. The events spanned 39 farms. The virus killed 43,410 of 76,613 susceptible birds. Culling, disinfection, and establishing a surveillance zone are part of the response. So far, the source of the virus isn't known.

A few other African nations have reported recent H5N1 outbreak, including Togo, Mali, and South Africa.
Aug 10 OIE report on H5N1 in Ivory Coast

Stewardship / Resistance Scan for Aug 12, 2021

News brief

Study of internet searches finds public AMR awareness lagging

An analysis of Google Trends suggests World Antimicrobial Awareness Week has not improved public awareness of antimicrobial resistance (AMR).

In a study published yesterday in the International Journal of Infectious Diseases, researchers analyzed trends in the search volume of the terms "antimicrobial resistance," "antibiotics," and "antibacterials" in Japan, the United States, the United Kingdom, and worldwide from 2015—when World Antimicrobial Awareness Week was introduced—through 2020. Using relative search volume (RSV) on Google Trends as a surrogate, they performed a joinpoint regression analysis to identify a statistically significant time point of a change in trend.

The results showed that World Antibiotic Awareness Week did not have a significant impact on general public interest in AMR or antibiotics in Japan, the United States, or the United Kingdom, although some increase in RSV was noted worldwide in 2017 and 2020. In addition, the RSV for antibiotics in every country or region significantly declined in 2020 during the COVID-19 pandemic.

"This study implies that we need to develop a more effective method to improve public awareness to fight against AMR," the study authors concluded.
Aug 11 Int J Infect Dis study


Dutch paper: Antibiotics in hospital wastewater a growing problem

A new white paper by Dutch experts is calling for solutions to the problem of antimicrobial residues and resistant bacteria in hospital wastewater.

Citing data from recent research in the Netherlands, the paper from the Dutch Consortium on Antibiotics and Pharmaceutical Residues from Water estimates that 40% of antibiotic residues in the country's wastewater originates from Dutch hospitals, exposing bacteria in the water to concentrations of antibiotics—many of them "last-resort" antibiotics—that are high enough to promote resistance but not high enough to kill the bacteria. The resistant bacteria can then pass on their resistance to other bacteria through the transfer of plasmids that harbor resistance genes.

To address this problem, the consortium calls for a three-pronged approach that removes the antibiotic residues from the water, disinfects the treated water, and removes plasmids containing the resistance genes—both at the source (hospitals) and through "end-of-pipe" solutions at sewage treatment facilities. While many sewage treatment facilities are able to remove antibiotics residues from treated water, additional purification techniques will be needed to remove plasmids, the authors of the paper note.

"In other words: we will not prevent AMR if only the antibiotic residues are removed from wastewater," they write. "We will have to do more."

The authors say the problem demands a targeted joint approach and calls for cooperation between hospitals, water companies, the pharmaceutical sector, and the government.
Aug 10 Dutch white paper

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