Epidemiology

In late March 2013, three human cases of novel influenza A(H7N9) virus infection were reported by Chinese health authorities.[40] This was the first time A(H7N9) virus infection had been identified in humans and the first time a low-pathogenic avian influenza (LPAI) virus infection had caused critical illness with fatal outcomes in humans. The current risk to the public’s health posed by Asian lineage A(H7N9) virus is low.[44] However, the pandemic potential of this virus is concerning. Influenza viruses constantly change and it is possible that this virus could evolve to gain the ability to spread easily and sustainably among people, triggering a widespread pandemic.[45][46]

Five distinct epidemic waves of Asian lineage A(H7N9) virus infections were observed in humans in China between 2013 and 2017, with cases peaking in the fifth wave (2016 to 2017). Between October 2017 and June 2019, only a small number of sporadic human cases were reported. No cases have been reported since 2019. A total of 1568 human infections have been reported since 2013, with 616 fatal cases (case fatality rate 39%).[44] Human infections with A(H7N9) virus have generally coincided or overlapped with annual outbreaks of seasonal influenza in China, with sporadic cases detected at other times of the year.[2][38][47]

There has been a marked decline in reported cases since the end of the fifth wave. The decrease in reported cases is associated with decreased Asian lineage A(H7N9) virus detections in birds and the environment. Closure of live bird markets in urban areas contributed to reducing human exposures to A(H7N9) virus and zoonotic transmission.[48][49] However, closure of live bird markets has also been reported to result in the spread of A(H7N9) virus among poultry to other areas.[50] It is likely that implementation of a bivalent H5-H7 poultry vaccination programme in China has contributed to the sharp reduction in human infections with A(H7N9) viruses.[51][52]

The majority of Asian lineage A(H7N9) virus infections in humans have occurred in the eastern half of mainland China, although cases have also been reported by provinces in south-west and north-west China. Large case-series have shown that all evaluated case-patients had histories of recent travel to affected provinces in mainland China.[2][38][53][54] Asian lineage A(H7N9) virus infections have been detected outside China, with one case reported by Malaysia in February 2014, two cases reported by Canada in 2015, and five cases reported by Taiwan between 2013 and 2017.[38][55][56] All of these cases were travel-associated and the infections were thought to have been acquired in mainland China.

In one large case-series, the mean age at presentation was 55.5 years (range 2-91 years) and infection had occurred more commonly in men than in women (male:female ratio 2:1). High frequencies of comorbidities have been observed in infected patients, and the presence of at least one comorbidity has been identified as a risk factor for infection with Asian lineage LPAI A(H7N9) virus.[7][57] However, the risk of death is not greater among those with comorbidities than in those without underlying chronic conditions. From 2013 to 2017, the number of incident cases had shifted from predominantly older to middle-aged adults and from urban locations to semi-urban and rural areas; however, the severity of illness among hospitalised patients had not changed.[46]

Chickens appear to be most susceptible to Asian lineage LPAI A(H7N9) virus infection, but the virus has been detected in other poultry species including ducks and quail. Although pigs can be infected, exposure to pigs has not been implicated in the epidemiology of human infections with Asian lineage LPAI A(H7N9) virus.[58][59][60] Many infected patients reported contact with poultry or markets where live birds are sold and/or slaughtered. Genetic similarity has been demonstrated in Asian lineage LPAI A(H7N9) viruses isolated from patients and Asian lineage LPAI A(H7N9) viruses obtained from live chickens in epidemiologically linked markets.[5] Chickens and ducks account for most positive detections of Asian lineage A(H7N9) LPAI in studies of live poultry markets, but Asian lineage A(H7N9) LPAI virus RNA has also been detected in samples from quail and pigeons, as well as in environmental and water samples obtained from the same markets.[61] Songbirds and small terrestrial birds have been shown to be susceptible to infection with Asian lineage LPAI A(H7N9) virus, but their role in zoonotic transmission to humans is not known.[62] The prevalence of LPAI and highly pathogenic avian influenza (HPAI) Asian lineage A(H7N9) virus infections in migratory birds within China and elsewhere remains unclear. Asian lineage LPAI A(H7N9) virus was detected in a healthy tree sparrow in Shanghai, but the virus was not detected in over 2000 samples from other wild birds in Shanghai that were tested in the same study.[63] This suggests that monitoring of infection in non-poultry birds is required and that infection in migratory birds or export of infected poultry could spread Asian lineage A(H7N9) viruses beyond China. The emergence of Asian lineage A(H7N9) viruses with high-pathogenicity properties reflects, by definition, increased pathogenicity in birds, but not necessarily in humans. Human infection with Asian lineage A(H7N9) virus after exposure to sick and dying birds may serve to increase awareness of the potential increased risk and lead to earlier health-seeking or diagnosis. No difference in disease severity has been seen among people with Asian lineage HPAI or LPAI A(H7N9) virus infection.[21][64]

Retrospective epidemiological analyses suggest that at least 75% of confirmed Asian lineage LPAI A(H7N9) virus-infected case-patients had recent contact with domestic poultry.[65] An ecological study utilising statistical modelling suggested that deliberate closures of poultry markets were effective in curtailing human outbreaks of Asian lineage LPAI A(H7N9) virus infections in several Chinese cities.[49] In contrast to HPAI A(H5N1), many Asian lineage LPAI A(H7N9) virus infections have occurred in urban areas and have not been associated with rearing or slaughtering 'backyard' poultry. Asian lineage LPAI A(H7N9) virus infection does not cause sickness or death in poultry, leading to 'silent' zoonotic transmission. By contrast, the recently emerged Asian lineage HPAI A(H7N9) virus does cause sickness and death in poultry, similar to HPAI A(H5N1) virus infection. It is not clear yet as to whether the HPAI virus will become the predominant circulating Asian lineage A(H7N9) virus in poultry in China, but if it becomes prevalent, then outbreaks in poultry should be easier to detect. 

One study of 396 poultry workers from areas where Asian lineage LPAI A(H7N9) virus is known to circulate among poultry found that 25 of 396 (6%) workers had detectable antibodies (haemagglutinin inhibition titres ≥80) against A(H7N9) virus. By contrast, antibodies were not detected in over 1000 samples tested from the general population.[66] Other retrospective studies have reported lower seroprevalence of antibodies to A(H7N9) virus or low incidence and seroconversion among Chinese poultry workers.[67][68][69]​ An additional retrospective study did not find serological evidence of A(H7N9) virus infection in poultry workers from eastern China prior to November 2012.[70] One systematic review and meta-analysis of serosurveys of avian influenza A(H7N9) virus infection reported that the seroprevalence of antibodies to the A(H7N9) virus was 0.10% in poultry workers, 0.20% in close contacts of confirmed case-patients with A(H7N9) virus infection, and 0.02% in the general population.[71]

Case-clusters of confirmed infection have been detected in China, but to date there is no evidence of sustained human-to-human transmission of Asian lineage A(H7N9) virus.[11] Fatal Asian lineage LPAI A(H7N9) virus infection in a healthcare worker has been reported, but a confirmed source of infection was not identified and there was no known contact with a confirmed case.[72] Nosocomial transmission, including patient-to-healthcare worker, and patient-to-patient, is possible with human infections with novel influenza A viruses, and has been reported for Asian lineage LPAI A(H7N9) viruses.[73][74][75]

Other avian influenza A viruses (e.g., H5, H6, H7, H9, H10 viruses) have caused human illness ranging from mild (e.g., conjunctivitis, uncomplicated influenza-like illness) to fatal disease.[13][14][15][18][76][77][78][79][80][81] However, a discussion of these infections is beyond the scope of this topic.

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