Explore the vast range of titles available.

During 2023-2024, highly pathogenic avian influenza A(H5N1) viruses from clade 2.3.2.1c caused human infections in Cambodia and from clade 2.3.4.4b caused human infections in the Americas. We assessed the susceptibility of those viruses to approved and investigational antiviral drugs. Except for 2 viruses isolated from Cambodia, all viruses were susceptible to M2 ion channel-blockers in cell culture-based assays. In the neuraminidase inhibition assay, all viruses displayed susceptibility to neuraminidase inhibitor antiviral drugs oseltamivir, zanamivir, peramivir, laninamivir, and AV5080. Oseltamivir was ≈4-fold less potent at inhibiting the neuraminidase activity of clade 2.3.4.4b than clade 2.3.2.1c viruses. All viruses were susceptible to polymerase inhibitors baloxavir and tivoxavir and to polymerase basic 2 inhibitor pimodivir with 50% effective concentrations in low nanomolar ranges. Because drug-resistant viruses can emerge spontaneously or by reassortment, close monitoring of antiviral susceptibility of H5N1 viruses collected from animals and humans by using sequence-based analysis supplemented with phenotypic testing is essential.

Highly pathogenic avian influenza A virus (HPAIV) H5N1, clade 2.3.4.4b, has emerged as a significant zoonotic threat. H5N1 is widely circulating in wild birds, and an increasing number of spillover events have been observed in a wide range of mammalian species. These cases are primarily reported in countries on the European and American continents. This review describes the likely transmission routes, lesions, and clinical manifestations of HPAIV H5N1 clade 2.3.4.4b in naturally infected mammals, with a focus on the involvement of the central nervous system (CNS). In the analysis, pathological findings were categorized by organ system and host species, which were further divided into terrestrial mammals, marine mammals, and dairy cattle. The most frequently reported clinical manifestations were neurological and respiratory signs in marine mammals and neurological signs and lethargy in terrestrial mammals. Macroscopic and histological lesions were commonly found in the CNS and lungs of terrestrial and marine mammals, while dairy cattle showed mainly gastrointestinal and mammary gland involvement. Immunohistochemistry and reverse transcriptase real-time PCR analyses confirmed high viral loads in brain tissues, indicating a neurological tropism of H5N1 clade 2.3.4.4b. Routes of CNS invasion remain uncertain, though both hematogenous and olfactory nerve pathways are discussed. Recent evidence suggests mammal-to-mammal and vertical transmission, raising concerns for the zoonotic and pandemic potential of this virus. In conclusion, the findings emphasize an urgent need for enhanced surveillance to effectively disclose changes in viral pathogenicity and transmissibility among mammalian hosts.

Ocular inoculation of a clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) virus caused severe and fatal infection in ferrets. Virus was transmitted to ferrets in direct contact. The results highlight the potential capacity of these viruses to cause human disease after either respiratory or ocular exposure.

Background. Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections. Methods. We compared individual-level data from patients hospitalized with infection by H7N9 (n = 123), H5N1 (n = 119; 43 China, 76 Vietnam), and pH1N1 (n = 3486) viruses. We assessed risk factors for hospitalization after adjustment for age- and sex-specific prevalence of risk factors in the general Chinese population. Results. The median age of patients with H7N9 virus infection was older than other patient groups (63 years; P < .001) and a higher proportion was male (71%; P < .02). After adjustment for age and sex, chronic heart disease was associated with an increased risk of hospitalization with H7N9 (relative risk, 9.68; 95% confidence interval, 5.24–17.9). H7N9 patients had similar patterns of leukopenia, thrombocytopenia, and elevated alanine aminotransferase, creatinine kinase, C-reactive protein, and lactate dehydrogenase to those seen in H5N1 patients, which were all significantly different from pH1N1 patients (P < .005). H7N9 patients had a longer duration of hospitalization than either H5N1 or pH1N1 patients (P < .001), and the median time from onset to death was 18 days for H7N9 (P = .002) vs 11 days for H5N1 and 15 days for pH1N1 (P = .154). Conclusions. The identification of known risk factors for severe seasonal influenza and the more protracted clinical course compared with that of H5N1 suggests that host factors are an important contributor to H7N9 severity.

We detected Eurasian-origin highly pathogenic avian influenza A(H5N1) virus belonging to the Gs/GD lineage, clade 2.3.4.4b, in wild waterfowl in 2 Atlantic coastal states in the United States. Bird banding data showed widespread movement of waterfowl within the Atlantic Flyway and between neighboring flyways and northern breeding grounds.

We show that human myxovirus resistance protein 1 (MxA) suppresses replication of highly pathogenic avian influenza A(H5N1) viruses isolated from mammals in vitro and in MxA-transgenic mice. However, H5N1 can evade MxA restriction through replacement of individual viral polymerase complex components from a human-adapted MxA-resistant strain in vitro.

We describe the pathology of natural infection with highly pathogenic avian influenza A(H5N1) virus of Eurasian lineage Goose/Guangdong clade 2.3.4.4b in 67 wild terrestrial mammals throughout the United States during April 1‒July 21, 2022. Affected mammals include 50 red foxes (Vulpes vulpes), 6 striped skunks (Mephitis mephitis), 4 raccoons (Procyon lotor), 2 bobcats (Lynx rufus), 2 Virginia opossums (Didelphis virginiana), 1 coyote (Canis latrans), 1 fisher (Pekania pennanti), and 1 gray fox (Urocyon cinereoargenteus). Infected mammals showed primarily neurologic signs. Necrotizing meningoencephalitis, interstitial pneumonia, and myocardial necrosis were the most common lesions; however, species variations in lesion distribution were observed. Genotype analysis of sequences from 48 animals indicates that these cases represent spillover infections from wild birds.

Introduction During the 2021 COVID‐19 pandemic, Ghana experienced outbreaks of high pathogenic avian influenza virus (HPAIV) H5N1 among poultry. Objectives Here, we describe the distribution and genetic characterisation of clade 2.3.4.4b HPAIV H5N1 isolated among poultry. Methods We conducted active surveillance for influenza viruses among animals (poultry and swine) and environmental samples across Ghana from 2021 to 2022. Tracheal/cloacal swabs were collected from poultry while nasal/anal swabs were collected from swine. Environmental samples (bird droppings, feathers, and water) were collected from Ramsar sites. We detected the presence of influenza viruses using specific primers and probes and reverse transcription polymerase chain reactions previously described by the US‐CDC. We sequenced and detected viruses using Oxford Nanopore Technologies. Results A total of 2847 samples were collected: 2640 from birds, 207 from swine, and 186 from the environment. Out of 2847, 2.2% (63/2847) were positive for HPAIV H5N1. All the H5N1 viruses were detected in poultry populations and none in swine. Again, environmental samples tested negative for influenza. Greater Accra (35), Central (10), and Upper East (7) regions recorded the highest number of H5N1 infections. Phylogenetic analysis of H5N1 showed that these viruses belonged to the clade 2.3.4.4b, which is currently circulating worldwide. Genetic analysis of the HA revealed some mammalian adaptive motifs. Conclusion These findings highlight the importance of continuous genomic surveillance for these zoonotic pathogens in‐country and further analyses to determine their zoonotic potential. Early detection and local containment are critical for mitigating the threat posed by zoonotic influenza. Ghana experienced outbreaks of highly pathogenic avian influenza A H5N1 among poultry from 2021 to 2022. Analysing poultry, pigs, and environmental samples showed H5N1 prevalence of 2.36% (63/2640) among poultry only. The clade 2.3.4.4b virus showed mammalian adaptive motifs in haemagglutinin, emphasising the need for ongoing genomic surveillance among poultry.

Highly pathogenic avian influenza (HPAI) H5 clade 2.3.4.4b viruses are widespread in wild and domestic birds, causing severe economic damage to the global poultry industry. Moreover, viruses of this clade are known to cause infections in mammals, posing a potential pandemic threat. Due to the ongoing evolution and change in the dominant strains of H5 clade 2.3.4.4b, it is important to investigate the cross-reactivity of vaccines in use and under development against clade 2.3.4.4b viruses. In this study, the immunogenicity of the previously developed DNA vaccine encoding a modified hemagglutinin of the influenza A/turkey/Stavropol/320-01/2020 (H5N8) virus, administered by jet injection at doses of 1, 10, 50, 100, and 200 μg, was investigated. The highest titer of specific to recombinant hemagglutinin antibodies was detected in the group of animals injected with 100 µg of DNA vaccine. The cross-reactivity study of sera of animals immunized with 100 µg of DNA vaccine in a microneutralization assay against the strains A/chicken/Astrakhan/321-05/2020 (H5N8), A/chicken/Komi/24-4V/2023 (H5N1), and A/chicken/Khabarovsk/24-1V/2022 (H5N1) showed the formation of cross-neutralizing antibodies. Moreover, the study of protective properties showed that the DNA vaccine protected animals from mortality after infection with A/chicken/Khabarovsk/24-1V/2022 (H5N1) virus.

We detected high titers of cross-reactive neuraminidase inhibition antibodies to influenza A(H5N1) virus clade 2.3.4.4b in 96.8% (61/63) of serum samples from healthy adults in Hong Kong in 2020. In contrast, antibodies at low titers were detected in 42% (21/50) of serum samples collected in 2009. Influenza A(H1N1)pdm09 and A(H5N1) titers were correlated.