Summary of Assessment of Public Health Risk to Canada Associated with Avian Influenza A(H7N9) Virus in China
The risk assessment is reviewed on a regular basis and updated as required.
29 June 2017
- The event summary, epidemiologic curve and spatial distribution map have been updated to reflect cases reported since the last update (May 30, 2017): 47 new human cases of A(H7N9) were reported and two cases were reported from Shaanxi with potential exposure in Inner Mongolia. This is the first report of human exposure to the virus in Inner Mongolia.
- The public health risk posed by avian influenza A(H7N9) virus to Canada remains low
- Human infection with avian influenza A(H7N9) in China follows a seasonal pattern with increases ("waves") typically between October and May each year
- A total of 739 cases have been reported in the current (fifth) wave: the highest number of cases reported during any wave since emergence in March 2013. In addition, cases are more spatially distributed relative to previous waves
- The number of cases in the fifth wave peaked in January 2017
- Infection is associated with exposure to infected poultry or contaminated environments, and most often results in clinically severe disease
- The most likely risk to Canadians at this time remains the risk of travel-acquired infection and importation from China through exposure to infected poultry or contaminated environments
The public health risk posed by avian influenza A (H7N9) virus to Canada is considered low based on available information at this time. The risk may change as new information arises.
Avian influenza A (H7N9) is a novel reassortant virus that was not previously known to circulate in humans. Sporadic transmission of avian influenza A (H7N9) to humans is thought to be associated with exposure to infected poultry or contaminated environments.
Available information suggests that this virus does not have the ability to transmit easily among humans. Clusters that have been reported suggest that limited human-to-human transmission may occur when there is unprotected close contact with cases. However, there is no evidence of sustained human-to-human transmission of avian influenza A (H7N9) virus.
Avian influenza A (H7N9) remains a widespread zoonotic virus in China. The most likely threat to Canadians remains a risk of importation to Canada from travelers infected while in China. Canada reported the first travel-related human cases of H7N9 in North America on January 2015. Although travel related cases have been reported in other countries including Canada, there is no indication that international spread has occurred.
The fifth wave began on October 1, 2016 and is ongoing. Eight cases were reported between October 1 and November 30, which was within the expected range for that time period (Zhou et al., 2017). Beginning December 1, 2016 there was a marked increase in the number of cases: a total of 739 cases have been reported, which is higher than the total number reported during each prior wave (Figure 1)(World Health Organization, 2017c) .
Figure 1. Global incidence of human cases of avian influenza A(H7N9) by month of symptom onset or earliest recorded date, March 2013 to June 15, 2017.
Text Equivalent - Figure 1
Figure 1. Global incidence of human cases of avian influenza A(H7N9) and by month of symptom onset or earliest recorded date, 2013-2017, as June 15, 2017.
Epidemic curve of avian influenza A(H7N9) event. Since 2013 five waves of avian influenza A(H7N9) have occurred : Wave 1 (February 2013 –September 2013), Wave 2 (October 2013- September 2014), Wave 3 (October 2014-September 2015), Wave 4 (October 2015- September 2016), and Wave 5 (October 2016-present). The distribution of cases over each wave has followed a seasonal pattern with cases increasing in December and peaking in January. The highest number of cases has been observed in wave 5. To date, the epidemiological curve captures 1246 cases and 296 deaths: 103 cases and 32 deaths in wave 1; 258 cases and 61 deaths in wave 2; 185 cases and 47 deaths in wave 3; 90 cases and 31 deaths in wave 4; 608 cases and 125 deaths in waves 5.
Note: Data for waves one to four were prepared using information compiled by the Public Health Agency of Canada's Global Public Health Intelligence Network (GPHIN) (n=809). Data for wave five were obtained from the WHO Influenza at the Human-Animal Interface Monthly Risk Assessment Summary (data as of 15 June 2017) and includes 739 cases for which date of symptom onset was reported (World Health Organization, 2017c). This figure excludes 23 cases for which onset date was not available.
Twenty-seven administrative regions in China have reported cases during wave 5 (range for previous waves 12 to 15) (Figure 2). Where information is available, the majority of cases reported high risk exposures (e.g., exposure to poultry). Similar to previous waves, clusters of possible human-to-human transmission involving both family members and hospital patients have been reported; however, there is still no evidence of sustained human-to-human transmission (World Health Organization, 2017a). The age and sex distribution is comparable to that from previous waves.
Figure 2. Spatial distribution of human cases of avian influenza A(H7N9), China, March 2013 to June 15, 2017.
Note: Data for waves one to four were prepared using information compiled by the Public Health Agency of Canada's Global Public Health Intelligence Network (GPHIN) (n=809). Data for wave five were obtained from the WHO Influenza at the Human-Animal Interface Monthly Risk Assessment Summary (data as of 15 June 2017) and includes 739 cases
Text Equivalent - Figure 2
Geographic distribution cases of A(H7N9) by wave. Across all five waves, cases have predominantly occurred in the southeast region of China. In wave 5, the occurrence of cases has become more intense and widespread in comparison to previous waves.
The first human cases with the novel reassortant avian influenza A (H7N9) virus were reported to the World Health Organization (WHO) by China on March 31, 2013. Since then, additional cases have been reported in China from twenty Provinces (Anhui, Guangdong, Guangxi, Guizhou, Hebei, Henan, Hubei, Hunan, Fujian, Jiangsu, Jiangxi, Jilin, Liaoning, Shandong, Sichuan, Yunnan, Gansu, Shaanxi, Shanxi and Zhejiang), four Municipalities (Beijing, Chongqing, Tianjin and Shanghai) and in four autonomous regions/territories (Hong Kong, Macao, Tibet and Xinjiang Uyghur). Poultry and environmental samples have tested positive for avian influenza A (H7N9) in all above mentioned areas, except for Beijing (Food and Agricultural Organizations of the United Nations (FAO), 2017). Most human infections are believed to have occurred after exposure to infected poultry or contaminated environments. In addition, travel-related cases have been reported in Malaysia, Taiwan, and Canada.
Since March 2013, the WHO has reported over 1500 confirmed human cases, including at least 592 deaths (World Health Organization, 2017c). For the latest updates on cases and deaths please visit WHO's Disease Outbreak News website.
Since the virus first emerged in 2013, outbreaks of H7N9 in humans have occurred in five waves. The beginning of the first wave was marked by the detection of the novel avian influenza A (H7N9) in three patients from China in March 2013: two cases from Shanghai and one from Anhui. Subsequent cases reported were concentrated in the Eastern Chinese Provinces of Shanghai, Zhejiang, and Jiangsu. The first wave lasted to May 2013.
The second wave of human avian influenza A (H7N9) infections began in October 2013 and ended in the spring of 2014. A change in the epidemiologic profile of H7N9 was observed in the second wave. There was a geographic shift in the distribution of H7N9 cases to the Southern Chinese Province of Guangdong, suggesting the virus became more widespread in its domestic bird reservoir. Additionally, the second wave had significantly larger amplitude than the first wave, both in terms of number of cases and deaths.
The third wave of human infections began in October 2014 with declining number of cases by the spring of 2015. The majority of cases were reported during the months of January and February in the Southern Chinese Province of Guangdong. On January 26, 2015, the first imported human case of avian influenza A (H7N9) from China was confirmed in Canada. A second case was confirmed on January 29, 2015. They are the first North Americans known to have been infected with this virus. The individuals were from British Columbia and travelled together to China. Both cases did not require hospitalization and have since fully recovered. The number of cases and deaths reported in this third wave was similar to those observed in the second wave.
The fourth wave of influenza A (H7N9) was announced by the Food and Agriculture Organization (FAO) of the United Nations on October 15th, 2015 after the report of two new cases of influenza A(H7N9) in China. A total of 121 cases including 34 deaths were reported during the fourth wave which is less than the total in each of the previous waves. There was no change in epidemiologic profile relative to waves two and three.
Although the majority of human cases have resulted in clinically severe disease, human infections with avian influenza A (H7N9) can present with a variety of symptoms that range from mild illness to more severe disease. Children infected with the virus have mainly presented with mild or asymptomatic disease (Yi et al., 2015). Given the detection of several less severe cases through ILI surveillance, along with continued reporting of severe cases, continued vigilance is warranted (World Health Organization, 2014b). The WHO continues to advise countries to move forward in strengthening influenza epidemiological and virological surveillance, reporting of human infections as applicable under the IHR (2005), and other national health preparedness actions.
Summary of literature
Evidence to date suggests a seasonal pattern to H7N9 infections in humans, peaking in the winter months and sporadic cases in the summer. The seasonal pattern observed is not unexpected as previous studies have reported greater circulation of avian influenza viruses in cooler weather and lower circulation in warmer temperatures (Q. Li et al., 2014).
The sex and age distribution of human cases of avian influenza H7N9 is skewed to middle aged or elderly males. This gender bias is not well understood, however it has been attributed by some researchers to cultural practices, such as live poultry markets (LPMs) predominantly being visited by males (Jernigan & Cox, 2015). There is a growing body of evidence that points to infected poultry, and contaminated environments including LPMs to be a key source of H7N9 infections in humans(Jernigan & Cox, 2015; J. Li et al., 2015; Spackman, Pantin-Jackwood, Swayne, Suarez, & Kapczynski, 2015; Yi et al., 2015). The vast majority (~85%) of all reported cases have had exposure to poultry or LPMs (Jernigan & Cox, 2015; Qin et al., 2015). Studies have shown that circulation of the virus may be amplified in LPMs with poultry to poultry transmission which may then serve as an ongoing source for H7N9 infection in humans (Jernigan & Cox, 2015). Poultry and environmental samples from several LPMs in China have tested positive for the virus with genomic sequences similar to those found in infected humans (Jernigan & Cox, 2015; Kang et al., 2015; Spackman et al., 2015; World Health Organization, 2017a; Yi et al., 2015). Unlike human infections with H7N9, the virus has not been reported to cause severe disease in poultry. The absence of disease in poultry makes it challenging to detect and control the virus in the poultry population.
Although the vast majority of cases have been linked to poultry exposure, there have been 24 clusters (2-3 cases) reported in waves one to four associated with close contacts of infected cases (World Health Organization, 2013a; World Health Organization, 2015). Epidemiologic investigations suggest secondary transmission may have occurred in some instances in family members and care givers exposed to infected cases (Y. Liu et al., 2015; World Health Organization, 2013a; World Health Organization, 2015; Yi et al., 2015). Of note, a healthcare associated cluster reported during wave 4 in Shantou, China in February 2015 points to a risk for healthcare workers (Farooqui et al., 2016; Y. Liu et al., 2015). A study published in May 2015 reported that secondary cases of H7N9 were younger and presented with milder disease than sporadic/index cases (Jernigan & Cox, 2015; Qin et al., 2015). These results further support other studies that indicate the detection of H7N9 cases to be biased towards older, more severe cases and are likely not capturing younger populations (Centre for Health Protection of the Department of Health HK, 2017b). Epidemiologic investigations of these clusters are suggestive of possible limited human-to-human transmission with no evidence of sustained transmission in the community.
Candidate influenza vaccine viruses (CVVs) have been developed by WHO Collaborating Centres for pandemic preparedness purposes. These include both A/Anhui/1/2013-like and A/Shanghai/2/2013-like viruses (World Health Organization, 2014a). Two new CVVs were recommended by the WHO in March 2017 (World Health Organization, 2017a). There are currently no recommendations on the large-scale manufacture of avian influenza A(H7N9) vaccine(World Health Organization, 2013b).
Laboratory testing has confirmed that the avian influenza A(H7N9) virus is susceptible to the neuraminidase inhibitors oseltamivir and zanamivir, two antiviral medications that are available in the National Antiviral Stockpile and National Emergency Stockpile System should they be needed to treat Canadians. WHO has issued guidance on the use of post-exposure antiviral chemoprophylaxis for avian influenza A (H7N9) (PDF Document). Recent human cases with mutations conferring resistance to neuraminidase inhibitors have been reported in wave 5.
The Agency's National Microbiology Laboratory (NML) has developed diagnostic assays (tests) allowing NML to rapidly detect the novel avian influenza A(H7N9) virus. These assays have been shared with the provincial/territorial laboratories allowing provinces to do their own testing should it be required.
Zoonotic circulation in North America
Presently, this avian influenza A(H7N9) virus is considered a Foreign Animal Disease (FAD) agent as there may be consequences if this pathogen were to circulate in avian populations in Canada. No North American circulation of Eurasian strain A (H7N9) has been detected in wild or domestic birds. The North American high and low pathogenic avian influenza A (H7N9) detected in poultry in the United States differs from the Eurasian strain associated with the fifth wave in China (United States Department of Agriculture., 2017)(Alabama Department of Agriculture and Industries, 2017).
Avian influenza A (H7N9) is a triple reassortant avian influenza A virus with HA genes from Eurasian A(H7) avian influenza virus lineage, NA genes from avian influenza A(H11N9) and A (H7N9), and internal genes from A(H9N2), that emerged in poultry populations in China(European Centre for Disease Prevention and Control, 2017; D. Liu et al., 2013; Wu et al., 2015). Scientific publications suggest that poultry is a likely source of infection (Chen et al., 2013)(Q. Li et al., 2014). Until February 2017, this novel low pathogenic avian influenza virus did not appear to cause severe illness in birds. However, mutations in the hemagglutinin protein have since been detected that may make the virus more pathogenic in poultry. This is not expected to have an impact on severity of human illness (World Health Organization, 2017b). Mutations in H7N9 strains have been identified that could favour high affinity interaction with human receptors in the upper respiratory tract however, there has been no evidence of sustained human-to-human transmission (World Health Organization, 2013b). In February 2017, a mutation in the neuraminidase protein was detected in virus samples from human cases in China that conferred resistance to oseltamivir (WHO press conference: Expert briefing on the current waves of avian influenza outbreaks - march 1, 7:30 EST2017; World Health Organization, 2017b).
Recommendations for Canada
Health care professionals are encouraged to maintain vigilance for cases of avian influenza A(H7N9) infection and notify the appropriate local public health unit in their jurisdiction of any persons under investigation. The national case definitions for avian influenza A(H7N9) are to be used for the surveillance of avian influenza A(H7N9). For guidance on surveillance objectives and activities, please refer to the interim national surveillance guidelines for avian influenza A(H7N9).
Provinces and Territories are asked to report confirmed cases of avian influenza A(H7N9) infection to the Public Health Agency of Canada using the Emerging Pathogens and Severe Acute Respiratory Infection (SARI) Case Report Form.
Travel Health Notice
The Agency releases Travel Health Notices outlining potential risks to Canadian travellers and to the Canadian public, and recommends measures that can be taken to help reduce these risks. A travel health notice for avian influenza A(H7N9) is posted on the Government of Canada's website travel.gc.ca.
The Agency provides recommendations for infection prevention and control measures for patients presenting to hospitals, doctors offices and other clinics with suspected or confirmed infection with the avian influenza A(H7N9) virus in its Interim Guidance - Infection Prevention and Control Guidance for Acute Care Settings document. This guidance will be updated as new evidence becomes available.
Based on the clinical presentation of severe respiratory illness and death in humans, the potential for this virus to be a pandemic agent, and that the virus is currently considered a foreign animal disease agent, this avian influenza A(H7N9) virus is classified as a Risk Group 3 human and animal pathogen requiring Containment Level 3 for all proliferative in vitro or in vivo activities. Non-proliferative diagnostic/clinical activities can be conducted at Containment Level 2 with additional requirements. In the event of a non-negative human sample, it is strongly recommended that the work with the sample be stopped and the sample be transferred to the National Microbiology Laboratory (NML). In the event that a veterinary diagnostic laboratory detects a non-negative sample, the work is to be stopped and the sample be transferred to the National Centre for Foreign Animal Disease (NCFAD) as per the policy in the Foreign Animal Disease Diagnostic Laboratory Containment Standard. The biosafety advisory can be found on the Agency website.
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