Nina Cosdon

This article first appeared in our sister brand, 

For the first time in 2 decades, the United States has locally acquired malaria infections. Six cases were 

 in Florida and 1 in Texas, none related to international travel.

Additionally, the CDC reported that the 2 states’ cases did not appear to be related. In Florida, all 6 cases were reported in Sarasota County, and active surveillance for additional infections is ongoing. Mosquito and infection surveillance and control are also underway in Texas, where 1 case was identified in a man working for the National Guard.

) is transmitted via the bite of an infected female anopheline mosquito. Malaria can be deadly, with nonspecific flu-like presentations including fever, chills, headache, myalgias, fever, nausea, vomiting, and diarrhea.

The initial 5 malaria patients have been treated and are clinically improving, the 

 on June 26 in response to the first confirmed infections.

The risk of malaria is very low, but with these 5 outlier infections, the CDC emphasized that clinicians should consider malaria as a possible diagnosis for patients with a fever of unknown origin. The risk is higher in areas where climactic conditions enable the 

 mosquito to survive most of the year. Clinicians should order a rapid diagnostic test and microscopic examination of thick and thin blood smears for suspected malaria patients.

In the US, an average of 5 people a year die of malaria, Healthline 

. Comparatively, in Africa, there were 594,240 malaria mortalities in 2021. The World Health Organization (WHO) estimates that 619,000 people died of malaria in 2021, meaning Africa accounts for 96% of worldwide mortalities.

 by WHO, but it is designated for children aged 36 months to 5 years in sub-Saharan Africa, who are at the highest risk for malaria-related death.

The last time locally acquired malaria occurred in the US was in 2003 when 8 cases of 

 malaria were confirmed in Palm Beach County, Florida. Malaria was once endemic in the US, but implementing insecticides, drainage ditches, and window screens enabled it to be declared eliminated in 1951. Approximately 1500–2000 malaria cases are still reported in the US each year, but this is the first time in 20 years that malaria was confirmed to be locally acquired rather than contracted during international travel.

Articles

Six confirmed cases of malaria in Florida and 1 in Texas have not been linked to international travel.


7 US Cases of Malaria Contracted Locally for First Time in 20 Years

Today, the US Food and Drug Administration’s (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) met in an open session to discuss and recommend the strains included in updated COVID-19 vaccines for the 2023-2024 vaccination campaign.

Just after 4 pm, VRBPAC voted on the following question: “For the 2023-2024 Formula of COVID-19 vaccines in the US, does the committee recommend an update of the current vaccine composition to a monovalent 

After all 21 VRBPAC members voted “Yes,” the committee moved on to their primary discussion topic: “Based on the evidence and other considerations presented, please discuss a selection of a specific XBB lineage (eg XBB.1.5 or XBB.1.16 or XBB.2.3) for inclusion in the 2023-2024 Formula of COVID-19 vaccines in the US.”

Over the course of a day-long meeting, CBER viewed and responded to presentations from the FDA, CDC, World Health Organization (WHO), Moderna, Pfizer, and Novavax, as well as hearing opinions from speakers during an open public forum.

 to move toward a unified strain composition for COVID-19 primary and booster vaccines on January 26, 2023. The committee aimed to provide more transparent information to the public and health care providers by simplifying strain composition. Additionally, the COVID-19 virus has evolved so significantly that there is no longer a need to include the original, wild-type Wuhan strain in the next generation of vaccines.

By the spring of 2023, virus surveillance revealed that the XBB sublineages were the predominant COVID-19 strains in the US and the world. The XBB parent lineage is a recombinant of BA.2.10.1 and BA.2.75 sublineages, indicating that we may expect more recombination variants in the future. Recombination occurs during virus replication when a cell is infected by more than 1 variant.

By June 2023, XBB sublineages accounted for over 95% of the world’s circulating COVID-19 variants. “The current trajectory of virus evolution indicates that XBB will likely be the progenitor of SARS-CoV-2 variants in the near future,” the FDA wrote in a 

. “XBB descendent lineages are highly immune evasive. To improve protection, particularly against symptomatic disease, COVID-19 vaccines should induce antibodies that neutralize XBB descendent lineage viruses.”

The director of the FDA Office of Vaccines Research and Review, David Kaslow, MD, reiterated this during the meeting. “First, we need a periodic update. Second, it’s time to move from the current bivalent to a monovalent.” He noted that we might shift to a bivalent strain composition in the future, but that current evidence suggests the need for a monovalent COVID-19 vaccine of the XBB lineage.

The FDA will seriously consider VRBPAC’s recommendation before relaying their official 2023-2024 COVID-19 vaccine composition guidelines to vaccine manufacturers.

The FDA committee, known as VRBPAC, in charge of evaluating vaccines and related biological products recently voted unanimously that the upcoming 2023-2024 COVID-19 vaccines should be updated with a monovalent XBB strain.

FDA Committee Recommends COVID-19 Vaccines Should Be Monovalent, Contain the XBB Strain

The Antimicrobial Drugs Advisory Committee (AMDAC) to the US Food and Drug Administration (FDA) has voted to recommend the approval of nirsevimab (Beyfortus) for the prevention of respiratory syncytial virus (RSV) disease in infants.

Nirsevimab is a long-acting antibody, in development by Sanofi and AstraZeneca, to protect all infants against RSV disease. “Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid, and direct protection against the disease,” Sanofi previously explained in a 

Though we now have 2 RSV vaccines approved for adults 60 years and older, 

; no vaccine nor antiviral options are available for infants and young children.

The proposed indication of nirsevimab is to prevent RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season. Additionally, the treatment was recommended for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.

After hearing presentations from AstraZeneca and the FDA, and reviewing all available clinical trial data, AMDAC voted on the following questions:

Is the overall benefit-risk assessment favorable for the use of nirsevimab for the prevention of RSV lower respiratory disease in neonates and infants born during or entering their first RSV season?

Is the overall benefit-risk assessment favorable for the use of nirsevimab for the prevention of RSV lower respiratory tract disease in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season?

All 21 AMDAC members voted in favor of the first question, and 19 voted in favor of the second, with 2 voting “no.”

Explaining her affirmative vote, Dr. Mary Anne Jackson said, “This is one of the most important infectious diseases affecting the pediatric population.” She also noted her recommendation was informed by good safety and efficacy data for nirsevimab. Several other AMDAC voting members voiced their support for how well the study was designed, with clear endpoints.

Some of the most promising trial data came from the 

, which recruited more than 8000 infants under 12 months of age across Germany, France, and the United Kingdom. The investigators compared a single intramuscular dose of nirsevimab (<5 kg 50 mg; ≥5 kg 100 mg) to no intervention and found nirsevimab reduced hospitalizations due to severe RSV-related LRTD by 83.21%.

Additional data from the HARMONIE trial suggest nirsevimab reduced the incidence of hospitalizations due to severe RSV-related LRTD, defined by requiring oxygen supplementation, by 75.71%. Nirsevimab also reduced all-cause LRTD hospitalization by 58.04% compared to infants who received no intervention. Throughout the HARMONIE trial, and into the 12-month follow-up period, nirsevimab maintained a favorable safety profile.

RSV is the leading cause of hospitalizations in infants in the US.

 “RSV causes a lot of fluid buildup in the lungs,” Iona Munjal, MD, a senior director of vaccine research and development at Pfizer, 

. “When babies breathe, they breathe through lung tubes that are many times smaller than ours. So fluid buildup can almost completely occlude their breathing airways and really fill up their lungs with a lot of inflammation and fluid.”

The FDA will seriously consider AMDAC’s recommendation before deciding to approve nirsevimab. Nirsevimab's Prescription Drug User Fee Act (PDUFA) date, the FDA target action date for their decision, is in the third quarter of 2023. The CDC will make a separate authorization decision if approved.

Although older adults have 2 vaccines, this would be the first vaccine or antiviral option for infants. 

FDA Advisory Committee AMDAC Recommends Nirsevimab to Protect Infants Against RSV 

A version of this article first appeared in our sister publication, 

Yesterday, Pfizer Inc. declared that the US Food and Drug Administration (FDA) gave approval for their respiratory syncytial virus (RSV) vaccine, Abrysvo, to be used by older adults. This endorsement permits the use of Abrysvo in people aged 60 years and older to prevent lower respiratory tract disease caused by RSV.

Pfizer’s Abrysvo vaccine targets both RSV A and B strains with its 2 preF proteins. The FDA has approved Abrysvo based on comprehensive trial data that confirms its safety and efficacy.

“A vaccine to help prevent RSV had been an elusive public health goal for more than half a century," stated Annaliesa Anderson, PhD, senior vice president and chief scientific officer of vaccine research and development at Pfizer. “Abrysvo will address a need to help protect older adults against the potentially serious consequences of RSV disease. We are extremely grateful to the clinical trial participants, study investigator teams and our dedicated Pfizer colleagues for their roles in making this vaccine available.”

With Abrysvo being granted approval, it becomes the second RSV vaccine to be approved after GSK's 

 after more than 50 years of working to develop an RSV vaccine. The approval was based on data obtained from a Phase 3 clinical trial (NCT05035212) called RENOIR (RSV vaccine Efficacy study iNOlder adults Immunized against RSV disease). This study is designed to evaluate the efficacy, safety, and immunogenicity of a single dose of the vaccine in adults aged 60 and above. The trial enrolled around 37,000 randomly assigned participants to receive either RSVpreF 120 μg or a placebo in a 1:1 ratio. The study is ongoing, and efficacy data is being collected during the second RSV season.

Edward E. Walsh, MD, Professor of Medicine at the University of Rochester Medical Center and principal investigator of the RENOIR trial, commented, "This 

 demonstrated the serious consequences and potential health risks this virus poses for older adults. Today’s FDA approval of Abrysvo recognizes significant scientific progress, and importantly helps provide older adults potential protection against RSV and an opportunity to improve community health by helping prevent the disease.”

RSV is a virus that spreads easily and causes respiratory illnesses worldwide. It mainly affects the lungs and airways, which can lead to serious health problems and even death. Older adults in the US are especially at risk from RSV, with the severity of the illness increasing with age and the presence of other health issues like asthma, congestive heart failure, or chronic obstructive pulmonary disease (COPD).

For most people who are generally healthy, RSV causes mild symptoms similar to a cold. They usually recover within 2 weeks without realizing they had the virus. Infants and young children, however, are more vulnerable to severe RSV infections. Pfizer is therefore seeking approval to give RSVpreF to pregnant people, to prevent medically attended lower respiratory tract disease (MA-LRTD) and serious MA-LRTD caused by RSV in babies from birth to 6 months old. The maternal vaccine was 

 by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), and a decision is expected by August 21, 2023.

The CDC Advisory Committee on Immunization Practices (ACIP) will have a meeting on June 21, 2023, to discuss the use of RSV vaccines in older adults. Pending the outcome of this meeting, Pfizer expects Abrysvo to be available in the third quarter of 2023, just in time for the anticipated RSV season this fall. Pfizer also reported positive top-line results earlier this month from a Phase 3 study on the safety and effectiveness of Abrysvo when coadministered with seasonal inactivated influenza vaccine (SIIV) in adults aged 65 and older. Additionally, Pfizer plans to conduct multiple clinical trials to evaluate RSVpreF in healthy children aged 2 to 5 years, children aged 5 to18 years with comorbidities, adults aged 18-60 years with comorbidities, and adults aged 18 years and older who are immunocompromised and at high risk for adverse RSV outcomes.

The FDA's decision to approve Abrysvo was based on data from a Phase 3 clinical trial, RENOIR, demonstrating the RSV vaccine's efficacy, immunogenicity, and safety in adults 60 and older.


FDA Approves Pfizer's Abrysvo Vaccine for Older Adults

This article first appeared on our sister brand, 


Following the US Food and Drug Administration 

 on April 18, 2023, the US Centers for Disease Control and Prevention (CDC) has significantly changed its COVID-19 vaccine recommendations.

The most significant update is that the FDA and CDC now recommend that the Moderna and Pfizer-BioNTech mRNA 

 (original and Omicron BA.4/BA.5 strains) be used for all future vaccinations in the US. This means both agencies are officially moving away from the initial, monovalent COVID-19 vaccines.

Adults 65 years and older receive an additional dose of the Moderna or Pfizer-BioNTech COVID-19 

Everyone 6 years and older receive an updated bivalent mRNA vaccine (unless they have already).

Individuals unvaccinated against COVID-19 receive a single dose of an authorized bivalent vaccine rather than multiple doses of original monovalent mRNA vaccines to complete a primary series.

Immunocompromised individuals may be eligible to receive additional doses of a bivalent vaccine, even if they have already. Individuals with comorbidities or otherwise immunocompromised should consult a health care provider to determine their needs and ensure they can mount an adequate immune response to vaccination.

The new regulations were announced tonight, April 19, after the CDC’s Advisory Committee on Immunization Practices (ACIP) met to discuss these changes to their COVID-19 vaccine recommendation.

Most individuals who have already received a single dose of the bivalent Pfizer-BioNTech or Moderna booster are only eligible for another dose if they are immunocompromised or 65 years and older. The FDA will likely announce future vaccination recommendations after determining fall’s vaccine strain composition in their June advisory meeting.

Alternative options are still available for individuals unable to receive an updated bivalent COVID-19 vaccine. Today's decision did not affect the CDC’s recommendation of the (monovalent) Novavax or Johnson & Johnson’s Janssen COVID-19 vaccines.

The CDC updated and simplified its vaccine recommendations on April 19, 2023, and the Moderna and Pfizer-BioNTech mRNA bivalent COVID-19 vaccines should be used for all vaccinations in the US.


FDA and CDC Update COVID-19 Vaccine Recommendations

H. Nina Kim, MD, MSc, a professor and hepatologist at the University of Washington, Seattle, gave a presentation titled “HBV Prevention: Newer Vaccines and the Boundaries of HBV Protection” at the Conference on Retroviruses and Opportunistic Infections 2023 (CROI2023) held in February.

Kim focused on 2 hepatitis B virus (HBV) vaccines––the CpG-adjuvanted hepatitis B vaccine and the 3-antigen hepatitis B vaccine. Both are licensed in multiple countries but are still relatively new hepatitis B prevention modalities.

As the first protein-based hepatitis B vaccine has been licensed for 40 years, it may lead some people to disregard the severity and urgency of hepatitis B erroneously. “Hepatitis B…remains a major public health issue today,” said Kim. “People living with HIV are particularly vulnerable.”

“The fact that we have a number of available vaccines doesn’t necessarily mean that everybody is getting them the way that they’re supposed to,” Kim said. Social determinants of health, such as race, socioeconomic status, or geographic location, often inhibit patients most at risk of contracting hepatitis B from obtaining the treatment and protection they need. “It’s not for the lack of available tools,” she emphasized.

Kim said she hopes the future of hepatitis B virus vaccines will include more real-world studies. “You want to look at how these drugs or vaccines perform in settings where you’re not going to see that uniformity in patient characteristics.”

In addition to raising public awareness, Kim wants to see better hepatitis B representation at CROI. She noted that there were relatively few posters and abstracts on hepatitis B at CROI 2023 and said, “I’m hoping in years to come in CROI that that will change, that there are just a lot more people excited about looking at hepatitis B prevention and treatments.”  

Hepatitis B prevention needs more real-world studies, according to an expert who gave a presentation at CROI.