Influenza virus, one of the most important respiratory viruses presenting globally annual seasonal epidemics, causes fatal respiratory diseases to humans. The estimated number of global annual influenza-associated respiratory deaths were 291,243–645,832 per year during the 1999–2015 period, and 9,243–105,690 deaths occur annually among children younger than 5 years (1). The mortality related to influenza virus infections adhere to a cyclic pattern fluctuating with seasonal changes in temperature and humidity, or occasional pathogenicity changes due to new gene mutations or exchanges (2–5). It is well-recognized that bacterial co-infection was frequent and critically led to the mortality in influenza virus infection (6, 7). In contrast, previous reports indicated that medical manifestations in cases of dual influenza infection and simple infection are similar (8). Recent ferret model study implied that prior infection antigenically related and unrelated viruses protected from subsequent infection or modified the infection kinetics of the challenge virus (9). The epidemiological and virological study of dual influenza infection cases is of major interest particularly for monitoring emerging influenza strains, which could perpetuate epidemic or pandemic events. However, co-infection with different influenza type/subtype viruses is rare (8, 10), and remain to be fully elucidated due to some limitations of many studies. Co-infections with influenza A subtypes or/and influenza B virus were detected in several surveillance areas regarded as rare events (11). The epidemic of influenza in Anhui Province, China generally exhibited Influenza B, H3N2 and H1N1pdm09 alternating or co-prevalence trend and presented obvious seasonal characteristics, showing single and double peaks, i.e., the peak is bound to occur every winter and spring, while the summer peak occurs in alternate years. In the present study, we described the epidemiological pattern of influenza A and B by surveillance network in Anhui province, eastern China from 2009 to 2014. In addition, we also investigated co-infection of influenza A and B and identified the ssusceptible population.

Effective influenza surveillance systems could help us decipher epidemiology and seasonality of influenza and further optimize possible influenza control strategies. The ILI consultation rates reported by Chinese influenza surveillance network in Anhui province of eastern China showed that ILI affected all aged people through whole year and was remarkably higher in 2009–2010 than in other surveillance years. To be consistent with ILI epidemics, influenza positive rates were the highest in 2009–2010 since H1N1pdm09 outbreak (14, 15). In addition, the data showed that ILI consultation were the highest in children aged <5 years. However, lab detection showed that influenza infections were the most predominant in school aged patients in the surveillance years instead of the youngest patients. In contrast, the most slightly affected people were the youngest patients among the monitored population. The data suggested that other respiratory pathogens may induce youngest ILI patients more frequently than influenza viruses as recent report (16, 17), and school-aged children should be the mainly concerned points for influenza controls in Anhui province China. In addition, the senior school-aged people were more increasingly affected during pandemic year, that is consisted with the previous reports where inpatients in the pandemic season were significantly younger compared with those in the pre-pandemic or post-pandemic seasons (18–20). It may be partially associated with that young adult in the pandemic season were less likely to have been vaccinated (20).

Influenza seasonality in Anhui province China was manifested by seasonal variations in different surveillance years. Except 2009–2010 surveillance year with H1N1 pandemic, two different epidemic patterns were present in the post the 4 surveillance years. Besides the normal winter and spring peaks, a summer peak presented in both 2010–2011 and 2012–2013 surveillance year. Similar recommendations of vaccination have been proposed for China recently (21). Recent data from countries in south and south-eastern Asia also indicate that countries consider vaccination with newly recommended vaccine in May-June prior to seasonal epidemic (22). In addition, the surveillance system presented a high sensitivity on monitoring the activity of the influenza viruses. An H7N9 case who was one of the earliest confirmed cases in mainland China was reported by the system (23, 24). Consequently, the surveillance networks would play a positive role in making evidence-based policy of control and prevention.

In the present study, human co-infections caused by several influenza viruses were detected in the surveillance epidemics. However, live dual viruses were merely detected in a few cases. It means that there was a prepotent virus in the infections with dual influenza viruses associated with viral interference or cross-reactive immune responses (25). Infections with heterosubtypic influenza A viruses presented shortening of virus shedding in previous studies (26). In addition, Cross-reactive epitopes have been found between influenza A and B viruses in the fusion peptide of the HA and enzymatic region of neuraminidase (25). Notably, the possibility of dual virus infection with similar replication level in vivo may be more frequent in young patients, that may be associated with host immune response to the infected virus. Previous studies shed a light on the immune response to influenza virus was weaker in the younger children and those without preexisting immunity (27). Theoretically, dual influenza virus infections represent a potential source of multiple viral transmission and constitutes a basis for virus recombination between two human strains or one human and one avian viral strain (28, 29). So, it may be valuable to monitor the potential reassortment due to co-infection in pediatric patients or those without preexisting immunity.

In the aggregate, we elaborated two different patterns of influenza circulation in different surveillance years in Anhui province, China. In view of school-aged children were the mainly affected patients in ILI associated with influenza viruses, we propose to implement a vaccination program in school-aged population in Anhui province. Influenza B, H3N2 and H1N1pdm09 co-circulated in annual epidemics, and the co-infections with influenza viruses were frequent in epidemic peaks. These data help us implement strategies to select vaccine formulations and monitor potential recombinant viruses in surveillance programs.

Influenza surveillance data used and analyzed in the current study are available from the corresponding authors on reasonable request.

R-BG and H-FP conceptualized the review. Literature search was performed by J-BW and X-EH. Supervision was performed by LG and JL. The first draft and editing of the manuscript were performed by JH, SH, and YC. Visualization/data presentation were performed by J-LY, Q-QC, and LH. All authors commented on previous versions of the manuscript, read, and approved the final manuscript.

This work was supported by the Scientific Research Projects of Health Commission of Anhui Province in 2021 (grant number: AHWJ2021a030).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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