The emergence of influenza A H7N9 in human beings 16 years after influenza A H5N1: a tale of two cities

Abstract

Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9 virus in 2013 caused severe pneumonia that did not respond to typical or atypical antimicrobial treatment, and resulted in high mortality. Both viruses are reassortants with internal genes derived from avian influenza A H9N2 viruses that circulate in Asian poultry. Both viruses have genetic markers of mammalian adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced binding to human-type receptors and improved replication in mammals, respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9 in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing in human population and poultry consumption before the outbreaks. Both cities are located along the avian migratory route at the Pearl River delta and Yangtze River delta. Whether the widespread use of the H5N1 vaccine in east Asia-with suboptimum biosecurity measures in live poultry markets and farms-predisposed to the emergence of H7N9 or other virus subtypes needs further investigation. Why H7N9 seems to be more readily transmitted from poultry to people than H5N1 is still unclear.

Figure 1

Geographical areas with laboratory-confirmed cases of human infection by the avian influenza A H7N9 virus, as of June 26, 2013 *One case in Beijing (case A1) was asymptomatic. † The details of six additional deaths were not available and thus not shown in the map. Data from , .

Figure 2

Subtyping of influenza A virus by surface protein genes of influenza A virus (A) Phylogenetic tree of the haemagglutinin gene. (B) Phylogenetic tree of the neuraminidase gene. Subtypes in bold colour represent those that have been found in human beings. Subtypes in blue have caused human seasonal or pandemic influenza. Subtypes in red are avian-origin influenza. Subtypes in green have caused both human seasonal and pandemic influenza or avian-origin influenza. Number in parenthesis shows number of human real-time-PCR or culture-confirmed avian influenza infections reported, but not including the 2013 influenza A H7N9 cases. The sequences were retrieved from the NCBI database and the phylogenetic trees were constructed by the neighbour-joining method with bootstrap replication (1000 bootstraps) with MEGA 5.1. Numbers at nodes show levels of bootstrap support calculated from 1000 trees. Scale bars show the estimated number of substitutions per ten bases.

Figure 3

Phylogenetic associations of avian H7 viruses that have been reported to cause human infections (A) Haemagglutinin gene. (B) Neuraminidase gene. (C) PB2 gene. The haemagglutinin, neuraminidase, and PB2 genes of the human isolates and the most closely related avian isolates, which are possible candidates as the gene source for reassortment, are shown. Only representative H7 isolates from human and the closely related isolates from avian species of preceding years are shown. The phylogenetic trees were constructed by the neighbour-joining method with bootstrap replication (1000 bootstraps) with MEGA 5.1. The neuraminidase gene sequence of 1996 influenza A H7N7 is not available in the public domain. Human strains are highlighted in red. Number of poultry culled is highlighted in blue. Scale bars show the estimated number of substitutions per 20 bases.

Figure 4

Comparison of poultry meat consumption between mainland China and Hong Kong and human population between Shanghai and Hong Kong (A) Poultry meat consumption in Hong Kong peaked just before 1997 but markedly decreased after the H5N1 outbreak. Poultry meat consumption in China is catching up. (B) Similar human population growth rates in Shanghai and Hong Kong. Data of poultry consumption for China are not available before 1987. Data from , , .