The Centers for Disease Control and Prevention (CDC) today shared new sequencing findings on samples from two people with H5N1 avian flu infections, one a patient from Wyoming who was hospitalized after contact with backyard poultry and the other a dairy worker from Nevada. It also fleshed out clinical findings for the two patients, plus another from Ohio.

The CDC said the patient from Wyoming, who had underlying health conditions, had respiratory symptoms and had tested negative for the virus from an upper respiratory sample but was positive on a lower respiratory sample. Meanwhile, the patient from Nevada was a dairy worker whose only symptom was conjunctivitis.

Similarly, the CDC added that a recent patient from Ohio, who had prolonged contact with sick and dead poultry, initially tested negative on upper-respiratory samples but was positive on lower respiratory tract sampling. It noted that both of the patients with poultry exposure had severe illness and were hospitalized but are both home and recovering.

Both had D1.1 genotype, notable mutations

Sequencing of viruses from both patients revealed the D1.1 genotype, which is circulating widely in wild birds and poultry, with known jumps to dairy cows in Nevada and Arizona. 

The tests also identified some notable mutations. The Wyoming patient’s virus had the E627K mutation in the polymerase basic 2 (PB2) protein that has been linked to efficient replication in people and mammals and was also seen in a human case from Texas in 2024. 

The CDC said the Nevada patent’s virus had the D701N mutation in PB2 that has been linked to more efficient virus replication in mammalian cells and was seen in a patient from Chile in 2023. It added that the nucleotide sequence was almost identical to viruses from the dairy cows the patient worked with.

For both patients, the CDC didn’t identify any genetic changes in the virus that would impact the effectiveness of antiviral medications or H5 candidate vaccine viruses.

CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) today announced a new round of funding targeting therapeutics for gram-negative bacterial infections and rapid diagnostics for typhoid fever.

Awards for gram-negative therapeutics will be restricted to direct-acting small-molecule therapeutics that demonstrate activity against both susceptible and multidrug-resistant organisms, with a preference for products with both intravenous and oral step-down options. New antibiotics for gram-negative pathogens, which are a leading cause of deaths from antimicrobial resistance (AMR), have been a focus for CARB-X since its inception in 2016. 

For typhoid fever diagnostics, CARB-X is interested in affordable, easy-to-use tests for diagnosing acute infections caused by Salmonella enterica serovar Typhi in low-resource settings. An estimated 11 million to 21 million cases of typhoid fever occur each year, primarily among people in low- and middle-income countries in South and Southeast Asia and sub-Saharan Africa.

New antibiotics needed for gram-negative pathogens

"Although progress has been made in the discovery and early development of therapeutics addressing various AMR challenges, there is broad agreement that we still need a new antibiotic, particularly an orally available one, with broad-spectrum activity against Gram-negative pathogens," Erin Duffy, PhD, CARB-X's chief of research and development, said in a press release. "At the same time, fast, affordable, and accessible diagnostics for S. typhi are essential to improve early detection and treatment."

CARB-X says applicants from around the world, particularly countries in which the AMR burden is high, are encouraged to apply. Proposals can be submitted from April 16 through April 30.

Since 2016, CARB-X has supported 113 early-stage projects designed to prevent, treat, and diagnose antibiotic-resistant infections. Of those projects, 19 have advanced into or completed clinical trials, 12 remain active in clinical development, and 2 products have reached the market.