Risk Assessment of the Tropism and Pathogenesis of the Highly Pathogenic Avian Influenza A/H7N9 Virus Using Ex Vivo and In Vitro Cultures of Human Respiratory Tract.

BACKGROUND: Highly pathogenic avian influenza (HPAI)-H7N9 virus arising from low pathogenic avian influenza (LPAI)-H7N9 virus with polybasic amino acid substitutions in the hemagglutinin was detected in 2017. METHODS: We compared the tropism, replication competence, and cytokine induction of HPAI-H7N9, LPAI-H7N9, and HPAI-H5N1 in ex vivo human respiratory tract explants, in vitro culture of human alveolar epithelial cells (AECs) and pulmonary microvascular endothelial cells (HMVEC-L). RESULTS: Replication competence of HPAI- and LPAI-H7N9 were comparable in ex vivo cultures of bronchus and lung. HPAI-H7N9 predominantly infected AECs, whereas limited infection was observed in bronchus. The reduced tropism of HPAI-H7N9 in bronchial epithelium may explain the lack of human-to-human transmission despite a number of mammalian adaptation markers. Apical and basolateral release of virus was observed only in HPAI-H7N9- and H5N1-infected AECs regardless of infection route. HPAI-H7N9, but not LPAI-H7N9 efficiently replicated in HMVEC-L. CONCLUSIONS: Our findings demonstrate that a HPAI-H7N9 virus efficiently replicating in ex vivo cultures of human bronchus and lung. The HPAI-H7N9 was more efficient at replicating in human AECs and HMVEC-L than LPAI-H7N9 implying that endothelial tropism may involve in pathogenesis of HPAI-H7N9 disease.

Needs Assessment for a Targeted Health Promotion Campaign.

ABSTRACTSince the first human A/H7N9 infection in Hong Kong, there has been an ongoing threat of human-to-human transmission, potentially causing a pandemic. Because there is no vaccine for A/H7N9, the individual preventive measures become all the more important for reducing transmission. However, due to the ongoing threat of numerous avian influenza viruses, the public may suffer from pandemic-media-fatigue. This study was done to assess the need for a targeted A/H7N9 health promotion campaign. Steven and Gillam's framework using epidemiological, comparative, and corporate approaches was used to assess the need for a targeted A/H7N9 health promotion campaign.Local surveillance data showed that Hong Kong faces a double burden of increasing seasonal influenza activity and threat of an avian influenza pandemic. Experts warned of potential severity and difficulties in A/H7N9 control. In contrast, surveys showed that the Hong Kong public were suffering from pandemic-media-fatigue, lacked anxiety, had misconceptions, and were not vigilant in preventive practices. This was more evident in certain demographics. Content analysis showed that health promotion materials were not targeted or tailored in countries with human A/H7N9 cases. Targeted health promotion campaigns and framing the issue to increase public and media awareness are crucial in preventing the current pandemic-media-fatigue. (Disaster Med Public Health Preparedness. 2019;13:596-604).

Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models.

The fifth wave of the H7N9 influenza epidemic in China was distinguished by a sudden increase in human infections, an extended geographic distribution, and the emergence of highly pathogenic avian influenza (HPAI) viruses. Genetically, some H7N9 viruses from the fifth wave have acquired novel amino acid changes at positions involved in mammalian adaptation, antigenicity, and hemagglutinin cleavability. Here, several human low-pathogenic avian influenza (LPAI) and HPAI H7N9 virus isolates from the fifth epidemic wave were assessed for their pathogenicity and transmissibility in mammalian models, as well as their ability to replicate in human airway epithelial cells. We found that an LPAI virus exhibited a similar capacity to replicate and cause disease in two animal species as viruses from previous waves. In contrast, HPAI H7N9 viruses possessed enhanced virulence, causing greater lethargy and mortality, with an extended tropism for brain tissues in both ferret and mouse models. These HPAI viruses also showed signs of adaptation to mammalian hosts by acquiring the ability to fuse at a lower pH threshold than other H7N9 viruses. All of the fifth-wave H7N9 viruses were able to transmit among cohoused ferrets but exhibited a limited capacity to transmit by respiratory droplets, and deep sequencing analysis revealed that the H7N9 viruses sampled after transmission showed a reduced amount of minor variants. Taken together, we conclude that the fifth-wave HPAI H7N9 viruses have gained the ability to cause enhanced disease in mammalian models and with further adaptation may acquire the ability to cause an H7N9 pandemic.IMPORTANCE The potential pandemic risk posed by avian influenza H7N9 viruses was heightened during the fifth epidemic wave in China due to the sudden increase in the number of human infections and the emergence of antigenically distinct LPAI and HPAI H7N9 viruses. In this study, a group of fifth-wave HPAI and LPAI viruses was evaluated for its ability to infect, cause disease, and transmit in small-animal models. The ability of HPAI H7N9 viruses to cause more severe disease and to replicate in brain tissues in animal models as well as their ability to fuse at a lower pH threshold than LPAI H7N9 viruses suggests that the fifth-wave H7N9 viruses have evolved to acquire novel traits with the potential to pose a higher risk to humans. Although the fifth-wave H7N9 viruses have not yet gained the ability to transmit efficiently by air, continuous surveillance and risk assessment remain essential parts of our pandemic preparedness efforts.

A Comparison of China's Risk Communication in Response to SARS and H7N9 Using Principles Drawn From International Practice.

BACKGROUND: China's emergency management of severe acute respiratory syndrome (SARS) was heavily criticized, whereas the H7N9 response was praised by the international community.AimsThe aims of this study were to examine and compare the strengths and weaknesses of risk communication conducted in response to SARS and H7N9 and their associated social impacts on affected communities in China. METHOD: A qualitative comparative case study approach was employed in the present study, using a set of 8 risk communication principles selected from international literature to suit the Chinese context for the comparative analysis of emergency responses of SARS and H7N9. RESULTS: The study found significant differences in the risk communication conducted in the 2 cases. The SARS outbreak fully exposed China's lack of experience in public health risk communication. By contrast, the Chinese government's risk communication strategies had improved significantly during the H7N9 outbreak.DiscussionTrust is the basis for communication. Maintaining an open and honest attitude and actively engaging stakeholders to address their risk information needs will serve to build trust and facilitate multi-sector collaborations in dealing with a public health crisis. CONCLUSIONS: From SARS to H7N9, risk communication practices in China greatly improved, which, in turn, lessened adverse social impacts and improved outcomes in emergency management of public health crises. (Disaster Med Public Health Preparedness. 2018;12:587-598).

Assessment of the internal genes of influenza A (H7N9) virus contributing to high pathogenicity in mice.

UNLABELLED: The recently identified H7N9 influenza A virus has caused severe economic losses and worldwide public concern. Genetic analysis indicates that its six internal genes all originated from H9N2 viruses. However, the H7N9 virus is more highly pathogenic in humans than H9N2, which suggests that the internal genes of H7N9 have mutated. To analyze which H7N9 virus internal genes contribute to its high pathogenicity, a series of reassortants was generated by reverse genetics, with each virus containing a single internal gene of the typical A/Anhui/1/2013 (H7N9) (AH-H7N9) virus in the genetic background of the A/chicken/Shandong/lx1023/2007 (H9N2) virus. The replication ability, polymerase activity, and pathogenicity of these viruses were then evaluated in vitro and in vivo. These recombinants displayed high genetic compatibility, and the H7N9-derived PB2, M, and NP genes were identified as the virulence genes for the reassortants in mice. Further investigation confirmed that the PB2 K627 residue is critical for the high pathogenicity of the H7N9 virus and the reassortant containing the H7N9-derived PB2 segment (H9N2-AH/PB2). Notably, the H7N9-derived PB2 gene displayed greater compatibility with the H9N2 genome than that of H7N9, endowing the H9N2-AH/PB2 reassortant with greater viability and virulence than the parental H7N9 virus. In addition, the H7N9 virus, with the exception of the H9N2 reassortants, could effectively replicate in human A549 cells. Our results indicate that PB2, M, and NP are the key virulence genes, together with the surface hemagglutinin (HA) and neuraminidase (NA) proteins, contributing to the high infectivity of the H7N9 virus in humans. IMPORTANCE: To date, the novel H7N9 influenza A virus has caused 437 human infections, with approximately 30% mortality. Previous work has primarily focused on the two viral surface proteins, HA and NA, but the contribution of the six internal genes to the high pathogenicity of H7N9 has not been systematically studied. Here, the H9N2 virus was used as a genetic backbone to evaluate the virulence genes of H7N9 virus in vitro and in vivo. Our data indicate that the PB2, M, and NP genes play important roles in viral infection in mice and, together with HA and NA, contribute to the high infectivity of the H7N9 virus in humans.

Viral lung infections: epidemiology, virology, clinical features, and management of avian influenza A(H7N9).

PURPOSE OF REVIEW: The avian influenza A(H7N9) virus has jumped species barrier and caused severe human infections. Here, we present the virological features relevant to clinical practice, and summarize the epidemiology, clinical findings, diagnosis, treatment, and preventive strategies of A(H7N9) infection. RECENT FINDINGS: As of 18 February 2014, A(H7N9) virus has caused 354 infections in mainland China, Taiwan, and Hong Kong with a case-fatality rate of 32%. Elderly men were most affected. Most patients acquired the infection from direct contact with poultry or from a contaminated environment, although person-to-person transmission has likely occurred. A(H7N9) infection has usually presented with severe pneumonia, often complicated by acute respiratory distress syndrome and multiorgan failure. Mild infections have been reported in children and young adults. Nasopharyngeal aspirate and sputum samples should be collected for diagnosis, preferably using reverse transcriptase-PCR. Early treatment with neuraminidase inhibitors improved survival, but the efficacy of antivirals was hampered by resistant mutants. The closure of live poultry markets in affected areas has significantly contributed to the decline in the incidence of human cases. SUMMARY: The emergence of A(H7N9) virus represents a significant health threat. High vigilance is necessary so that appropriate treatment can be instituted for the patient and preventive measures can be implemented.