A Systematic Review and Meta-Analysis of the Seroprevalence of Influenza A(H9N2) Infection Among Humans

The first known infection by influenza A(H9N2) occurred in 1966 among turkeys in Wisconsin. Since the 1990s, the virus has readily circulated among domestic poultry populations in several Asian countries and is now considered to have a near global, albeit sporadic distribution among poultry. Influenza A(H9N2) has also been identified in wild birds, domestic mammals, and, occasionally, in humans [1, 2]. Zoonotic transmission of influenza A(H9N2) was not considered a concern until 1998–1999, when the virus was first isolated from pig samples [2]; seropositive human cases were detected in Guangdong Province, China [3]; and the virus was isolated from hospitalized patients in Hong Kong [1]. Although human influenza A(H9N2) cases have only been reported in Hong Kong and mainland China, and more recently in Bangladesh [1, 4, 5], serological evidence of human infection has been reported in Asia, the Middle East, Africa, and parts of North America (Figure ​(Figure11). Figure 1. Reported global distribution for influenza A(H9N2) in humans and animals from 1997 to 2013. Countries that detected influenza A(H9N2) in poultry have an orange background. Species-specific symbols were assigned to each country. When a human or animal ... Human infection with influenza A(H9N2) generally results in mild or asymptomatic illness and often goes unnoticed [6]. However, influenza A(H9N2) is a potential pandemic threat because of its rapid evolution, ability to acquire and transfer genetic materials from other pathogenic subtypes, and efficiency in poultry-to-human transmission [7, 8]. Currently, influenza A(H9N2) infections in poultry have led to multiple reassortments, resulting in many novel genotypes of influenza A(H9N2) with gene segments from various lineages and serving as a constant reminder of its ability to acquire and transfer pandemic potential among the circulating influenza strains [9, 10]. Molecular analyses of the recently emerged influenza A(H7N9) and influenza A(H10N8) suggest that they have acquired gene segments from influenza A(H9N2) [11, 12], which probably enabled them to survive and be repeatedly transmitted among poultry before adapting to humans. Unlike other avian influenza viruses (eg, influenza A[H5N1]) that chiefly bind to human receptors in the lower respiratory tract, influenza A(H9N2) binds to α-2,6 sialic acid receptors that are abundant in the human upper respiratory tract [13], allowing for much greater infection efficiency. Given the pandemic potential of influenza A(H9N2), it is important to know the burden of human infections. However, the variation attributed to serological assays makes it difficult to accurately estimate the overall burden of influenza A(H9N2) infections. Hence, for this systematic review we sought to evaluate the overall burden of influenza A(H9N2) infection among avian-exposed human populations by summarizing serological data identified in the published literature. In addition, we compared the disease burden revealed by the 2 assays with that yielded by a standardized case definition for serological evidence of influenza A(H9N2) infection.