The study involved five ferrets from one household in Poland, comprising three sick 9-week-old juveniles, their healthy mother, and another clinically normal adult, admitted to the veterinary clinic in June 2023. The juvenile ferrets displayed significant lethargy and a pronounced unwillingness to move with accompanying pulmonary distress. Prompted by concurrent outbreaks of A/H5N1 influenza virus infections in Polish cats, point-of-care tests were conducted that revealed type A influenza antigens in the throat swabs of all five ferrets. Despite treatment, one juvenile ferret exhibited dyspnea and neurological symptoms and eventually died. The two remaining ferrets recovered fully, including one severely affected showing persistent dyspnea and incoordination without fever that recovered after 11 days of treatment. In the RT-qPCR, the throat swabs collected from all surviving ferrets as well as the samples of lungs, trachea, heart, brain, pancreas, liver, and intestine of the succumbed ferret were found positive for A/H5N1 virus RNA. To our best knowledge, this is the first documented natural A/H5N1 avian influenza in domestic ferrets kept as pets. In addition, this outbreak suggests the possibility of asymptomatic A/H5N1 virus shedding by ferrets, highlighting their zoonotic potential and the advisability of excluding fresh or frozen poultry from their diet to reduce the A/H5N1 virus transmission risks.

In summer 2023, during an outbreak of highly pathogenic avian influenza (HPAI) in cats in Poland, a 16-year-old dog was presented to the veterinary clinic with persistent, debilitating, dry cough, submandibular lymphadenomegaly, mild serous nasal discharge, and left apical heart murmur. A preliminary diagnosis of kennel cough was made and the treatment with amoxicillin/clavulanic acid and dexamethasone was initiated. Due to the lack of improvement within 2 days, a blood check-up, thoracic radiography and ultrasonography, and echocardiography were performed. Moreover, a rapid test for orthomyxovirus type A antigen in a throat swab was carried out and proved positive. The result was verified using RT-qPCR, which yielded a positive result for A/H5N1 influenza virus and negative results for A/H1N1, A/H3N2, type B influenza, and SARS-CoV-2. This case indicates that HPAI should be considered as a differential diagnosis not only in cats, but also in dogs with upper respiratory tract disease, particularly in regions experiencing A/H5N1 avian influenza outbreaks.

Avian influenza causes substantial economic loss in the poultry industry and potentially threatens human health. Over recent years, the highly pathogenic avian influenza A/H5N1 virus has led to devastating losses in poultry flocks and wild birds. At the same time, the number of mammalian species identified to be infected with A/H5N1 is increasing, with recent outbreaks in domestic cats, including household individuals, evidenced in July 2023 in Poland, ultimately creating opportunities for the virus to adapt better to mammalian hosts, including humans. Overall, between 2003 and 2023, over 10 outbreaks in felids have been documented globally, and in six of them, feed based on raw chicken was suspected as a potential source of A/H5N1, fuelling a debate on threats posed by A/H5N1 and methods to decrease the associated risks. This article debates that technology allowing the production of slaughter-free meat, including poultry, from cell and tissue cultures could be considered as a part of a mitigation strategy to decrease the overall burden and threat of adaptation of avian influenza viruses to human hosts. By shifting poultry production to the cultured meat industry, the frequency of A/H5N1 outbreaks in farmed birds may be decreased, leading to a reduced risk of virus acquisition by wild and domesticated mammals that have direct contact with birds or eat raw poultry and have close contact with human (including domestic cats), ultimately minimizing the potential of A/H5N1 to adapt better to mammalian host, including humans. This adds to the list of other benefits of cultured meat that are also reviewed in this paper, including decreased antibiotic use, risk of microbial contamination and parasite transmission, and environmental and ethical advantages over conventional slaughtered meat. In conclusion, further development and implementation of this technology, also in the context of poultry production, is strongly advocated. Although cultured poultry is unlikely to replace the conventional process in the near future due to challenges with scaling up the production and meeting the continuously increased demand for poultry meat, it may still decrease the pressures and threats related to the transmission of highly pathogenic avian influenza in selected world regions.

Live bird markets (LBMs) have been identified as key factors in the spread, persistence and evolution of avian influenza viruses (AIVs). In addition, these settings have been associated with human infections with AIVs of pandemic concern. Exposure to aerosolised AIVs by workers in a Cambodian LBM was assessed using aerosol impact samplers. LBM vendors were asked to wear an air sampler for 30 min per day for 1 week while continuing their usual activities in the LBM during a period of high AIV circulation (February) and a period of low circulation (May). During the period of high circulation, AIV RNA was detected from 100% of the air samplers using molecular methods and viable AIV (A/H5N1 and/or A/H9N2) was isolated from 50% of air samplers following inoculation into embryonated chicken eggs. In contrast, AIV was not detected by molecular methods or successfully isolated during the period of low circulation. This study demonstrates the increased risk of aerosol exposure of LBM workers to AIVs during periods of high circulation and highlights the need for interventions during these high-risk periods. Novel approaches, such as environmental sampling, should be further explored at key high-risk interfaces as a potentially cost-effective alternative for monitoring pandemic threats.

In May 2021, Lesotho reported its first outbreak of highly pathogenic avian influenza (HPAI) to the OIE. Samples were collected from infected poultry and the virus was confirmed by molecular tests to be of the H5N1 subtype. Full genome sequencing and phylogenetic analysis revealed that the viruses belonged to clade 2.3.4.4b and showed high identity with A/H5N1 viruses identified in Nigeria and Senegal in early 2021. The identification of A/H5N1 HPAI in Lesotho has important implications for disease management and food security in the region.

The highly pathogenic avian influenza H5N1 virus continues to spread globally in domestic poultry with sporadic transmission to humans. The possibility for its rapid transmission to humans raised global fears for the virus to gain capacity for human-to-human transmission to start a future pandemic. Through direct contact with infected poultry, it caused the largest number of reported cases of severe disease and death in humans of any avian influenza strains. For pandemic preparedness, use of safe and effective vaccine adjuvants and delivery systems to improve vaccine efficacy are considered imperative. We previously demonstrated CaPtivate\'s proprietary CaP nanoparticles (CaPNP) as a potent vaccine adjuvant/delivery system with ability to induce both humoral and cell-mediated immune responses against many viral or bacterial infections. In this study, we investigated the delivery of insect cell culture-derived recombinant hemagglutinin protein (HA) of A/H5N1/Vietnam/1203/2004 virus using CaPNP. We evaluated the vaccine immunogenicity in mice following two intramuscular doses of 3 μg antigen combined with escalating doses of CaPNP. Our data showed CaPNP-adjuvanted HA(H5N1) vaccines eliciting significantly higher IgG, hemagglutination inhibition, and virus neutralization titers compared to non-adjuvanted vaccine. Among the four adjuvant doses that were tested, CaPNP at 0.24% final concentration elicited the highest IgG and neutralizing antibody titers. We also evaluated the inflammatory response to CaPNP following a single intramuscular injection in guinea pigs and showed that CaPNP does not induce any systemic reaction or adverse effects. Current data further support our earlier studies demonstrating CaPNP as a safe and an effective adjuvant for influenza vaccines.

Current therapies against avian influenza (H5N1) provide limited clinical benefit. FBF-001 is a highly purified equine polyclonal immunoglobulin fragment against H5N1.
Using a ferret model of severe acute H5N1 infection, we assessed FBF-001 when administered on the same day or 1 day after viral challenge, in comparison with oseltamivir therapy.
Untreated animals died 2-3 days after challenge. FBF-001 prevented most severe illness and reduced nasal viral load, with best efficacy when administered on the day of viral challenge. Oseltamivir and FBF-001 had synergistic impact on survival.
FBF-001 prevented severe consequences of lethal H5N1 challenge in ferrets by controlling viral replication, an effect synergistic to oseltamivir. FBF-001 has recently been granted EMA orphan drug status.