Human Infections with Influenza A(H5N6), China

Background Understanding the transmission source, pattern, and mechanism of infectious diseases is essential for targeted prevention and control. Though it has been studied for many years, the detailed transmission patterns and drivers for the seasonal influenza epidemics in China remain elusive. Methods In this study, utilizing a suite of epidemiological and genetic approaches, we analyzed the updated province-level weekly influenza surveillance, sequence, climate, and demographic data between 1 April 2010 and 31 March 2018 from continental China, to characterize detailed transmission patterns and explore the potential initiating region and drivers of the seasonal influenza epidemics in China. Results An annual cycle for influenza A(H1N1)pdm09 and B and a semi-annual cycle for influenza A(H3N2) were confirmed. Overall, the seasonal influenza A(H3N2) virus caused more infection in China and dominated the summer season in the south. The summer season epidemics in southern China were likely initiated in the “Lingnan” region, which includes the three most southern provinces of Hainan, Guangxi, and Guangdong. Additionally, the regions in the south play more important seeding roles in maintaining the circulation of seasonal influenza in China. Though intense human mobility plays a role in the province-level transmission of influenza epidemics on a temporal scale, climate factors drive the spread of influenza epidemics on both the spatial and temporal scales. Conclusion The surveillance of seasonal influenza in the south, especially the “Lingnan” region in the summer, should be strengthened. More broadly, both the socioeconomic and climate factors contribute to the transmission of seasonal influenza in China. The patterns and mechanisms revealed in this study shed light on the precise forecasting, prevention, and control of seasonal influenza in China and worldwide.

H9N2 avian influenza viruses (AIVs) have become panzootic and caused sporadic human cases since 1998. Based on the poultry-related environmental surveillance data in mainland China from 2013 to 2016, a total of 68 representative environment isolates were selected and further investigated systematically. Phylogenetic analysis indicated that Y280-like H9N2 viruses have been predominant during 2013-2016 and acquired multiple specific amino acid substitutions that might favor viral transmission from avian to mammalians. Additionally, the viruses have undergone dramatic evolution and reassortment, resulting in an increased genetic diversity or acting as the gene contributors to new avian viruses. Receptor-binding tests indicated that most of the H9N2 isolates bound to human-type receptor, making them easily cross the species barrier and infect human efficiently. Our results suggested that the H9N2 AIVs prevalent in poultry may pose severe public health threat.

Wild waterfowl are recognized as the natural reservoir for influenza A viruses. Two distinct lineages, the American and Eurasian lineages, have been identified in wild birds. Gene flow between the two lineages is limited. The H9N2 virus has become prevalent in poultry throughout Eurasia, and mainly circulates in wild ducks and shorebirds in North America. In this study, 22 H9N2 avian influenza viruses were isolated from wild waterfowl feces in East Dongting Lake Nature Reserve in November 2011 and March 2012. The phylogenetic, molecular, and antigenic characteristics of these viruses were analyzed based on analyses of the whole genome sequence of each isolate. Phylogenetic analyses indicated that these H9N2 viruses were generated by reassortment events. The HA, NA, PA, and NS genes were derived from the American gene pool, and the other four genes were derived from the Eurasian gene pool. Antigenic analyses indicated that these viruses were significantly different from the Eurasian lineage viruses. This study presents the isolation of novel intercontinental recombinant H9N2 viruses from wild waterfowl in the East Dongting Lake wetland. The novel genotype H9N2 virus has not been detected in poultry in the region yet, and may be transmitted to naïve birds in poultry farms. Therefore, our results highlight the need for ongoing surveillance of wild birds and poultry in this region.

The H3 subtype avian influenza virus (AIV) has been widely spread in birds and is known as a natural source of mammalian influenza viruses. Based on data from public databases and our surveillance data, we analyzed the ecology, evolution, and spread of H3 AIVs. Sublineages of H3 AIVs have been detected worldwide, infecting various birds, at least 90 species in wild birds and poultry. Important areas for large-scale and local dissemination of H3 AIVs were identified, such as Alaska, Central Asia, and Chinese provinces. The H3 viruses have elevated the HA gene substitution rate after introduction from wild birds to domestic poultry, and even faster in domestic chickens. Our results implied an evolutionary mechanism of H3 AIV cross-species transmission, that viruses from wild birds to domestic poultry have accelerated substitution rate by shorter generation time and host selection. Novel chicken H3 viruses, especially H3N8 G25 viruses that have spilled over to humans, require high attention.

Human infection with avian influenza A (H7N9) virus was first reported on March, 2013 in the Yangtze River Delta region of China. The majority of human cases were detected in mainland China; other regions out of mainland China reported imported human cases, including Hong Kong SAR, Taiwan (the Republic of China) and Malaysia, due to human transportation. Here, we report the first human case of H7N9 infection imported into Guizhou Province during the Spring Festival travel season in January 2014. In early January 2014, a 38-year-old healthy Chinese man, a migrant worker returning from previously H7N9-affected Zhejiang Province, was identified as the first human case of infection with avian influenza A(H7N9) virus in Guizhou Province. He developed fever in Zhejiang at the beginning of January 2014, and returned to Guizhou for the Chinese New Year the next day. He went to seek medical care, but deteriorated rapidly and died on day 8 after his illness onset. The influenza virus A/Guizhou/01502/2014 isolated from the patient had 99% identity with viruses circulating in the Yangtze River Delta region. Selected amino acids substitutions, well-known to be associated with mammalian adaptation, viral replication and drug resistance were similar to other H7N9 viruses circulating in humans. Epidemiology investigation and laboratory results confirmed it was the first imported case of H7N9 infection in Guizhou Province. This finding further indicated that more human H7N9 cases may be detected in other regions due to frequent travel both domestically and internationally.