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Summary of Assessment of Public Health Risk to Canada Associated with Avian Influenza A(H7N9) Virus in China
11 Dec 2013
The risk assessment is reviewed on a regular basis and updated as required.
Risk Assessment
The public health risk posed by avian influenza A(H7N9) virus from China to Canada is considered low at this time. Cases have been reported in China from ten Provinces (Anhui, Guangdong, Hebei, Henan, Hunan, Fujian, Jiangsu, Jiangxi, Shandong, and Zhejiang) and two Municipalities (Beijing and Shanghai). In addition, a travel-related case was reported in Taiwan and Hong Kong. Poultry and environmental samples have tested positive for avian influenza A(H7N9) in all above mentioned provinces and municipalities, except for Hunan and Beijing.
There is still no evidence of sustained human-to-human transmission of avian influenza A(H7N9) virus. However, four clusters suggest that limited human-to-human transmission may occur where there is close contact between cases and other people.
There is no indication that international spread has occurred, although when infected people from affected areas travel, their infection may be detected in another country.
Event Summary
As of 4 December, 2013, WHO has reported 141 confirmed human cases, including 47 deaths. The case fatality rate (CFR) is 33%. With the exception of the cases in Beijing (2) and Hebei (1), all other cases have occurred in adjacent regions in eastern and south eastern China, including the travel-related case in Taiwan and Hong Kong. The majority of the cases have been reported by Zhejiang province (50), followed by Shanghai (34) and Jiangsu (27). Of the 138 cases with available demographic data the median age is 60 (range 2-91). Notably, 98 cases are male (71%) and 57 cases (41%) are ≥65 years of age.
The WHO’s Global Alert and Response websiteExternal Link maintains the latest updates on the total number of cases. The most recent case was reported on 3 December 2013, in Hong Kong Special Administrative Region (HK SAR), China. The case was a 36 year old female who was reported to have travelled to Shenzhen, Guangdong province, China, which is near the northern border of HK SAR, and had direct exposure to live poultry. This is the first case of avian influenza A(H7N9) reported in HK SAR, and the third case reported in association with Guangdong province since March 2013.
The source, reservoir, and communicability of the avian influenza A(H7N9) virus are currently under investigation; however, the WHO reports that human infection appears to be related to exposure to live poultry or contaminated environments for the following reasons:
◾The virus in humans is genetically similar to that found in animals and the environment (live bird markets).
◾Most human cases (approximately three out of four patients) report a history of exposure to birds, mostly chickens.
◾The virus has been detected in poultry in live bird markets.
◾The number of human cases has decreased after the implementation of public health measures, which included closure of live poultry markets.
Although four small human clusters have been reported, evidence does not support sustained human-to-human transmission. Monitoring and testing of more than 2,000 contacts of confirmed cases have detected few infections. Testing of more than 20,000 people with influenza-like-illness in March and April 2013 confirmed only six infections with avian influenza A(H7N9), suggesting that milder cases are not occurring in large numbersFootnote 1.
Closing of all live poultry markets was an effective control strategy in Shanghai, Jiangsu and Zhejiang as the number of reported human cases decreased following these closures. However, the continued decrease in the number of newly reported cases over the summer may be the result of the avian influenza A(H7N9) virus demonstrating a seasonal pattern, similar to other avian influenza viruses (e.g. H5N1), where cases are less frequent in the summer and more frequent in the winterFootnote 1. Live poultry markets have reopened, and as the influenza season progresses, more cases of avian influenza A(H7N9) virus are anticipated.
A scientific publication by the Infectious Diseases of Poverty indicates that it is necessary to regulate the poultry markets as long as poultry-to-poultry transmission is not well understoodFootnote 2. The Canadian Food and Inspection Agency (CFIA) published its “Preliminary Assessment of the Risk to Canadian Animals from the Novel H7N9 Influenza Virus Detected in China” and highlighted that: evidence to date strongly indicates that the novel H7N9 in poultry does not differ from other Influenza A viruses common in the animal population at the global level; this novel H7N9 virus is of avian origin and does not cause any severe clinical signs in poultry; and the risk to Canadian animals from the novel H7N9 influenza virus detected in China is considered to range from negligible to very low.
No vaccine is currently publicly available for this subtype of the H7N9 influenza virus; although several candidate vaccines are undergoing clinical trials. WHO has recommended that an A/Anhui/1/2013-like virus be used for the development of A(H7N9) vaccines for pandemic preparedness purposes. There are currently no recommendations on the large-scale manufacture of avian influenza A(H7N9) vaccineFootnote 3.
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. An analysis conducted on 14 patients in Shanghai showed that antivirals were able to clinically reduce viral load, however, the emergence of mutations known to confer resistance to neuraminidase inhibitors was also observed during the course of treatment in some individualsFootnote 6.
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 provincial/territorial colleagues allowing provinces to do their own testing should it be required.
Virus Characteristics
Sequencing of the avian influenza A(H7N9) virus by the World Health Organization (WHO) Chinese National Influenza Centre in Beijing revealed HA and NA genes from avian influenza A(H7N9) and remaining genes from A(H9N2), identifying this virus as a novel reassortant virus with all genes related to genes from Eurasian influenza A viruses from wild birds and poultry. Scientific publications in the LancetFootnote 4 and New England Journal of MedicineFootnote 6 suggest that poultry is a likely source of infection. This novel avian influenza A(H7N9) virus does not appear to cause severe illness in birds. This is different from previously identified and reported avian influenza A(H7N9) viruses in birds. Mutations in H7N9 strains have been identified that could favour high affinity interaction with human receptors in the upper respiratory tractFootnote 5 however, there has been no evidence of sustained human-to-human transmission. 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.
Recommendations for Canada
Surveillance
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 interim case definition for avian influenza A(H7N9) is 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 Advisory
A travel health advisory is posted on the Agency’s website. It does not recommend any restrictions on travel but encourages travellers to practice special precautions.
Infection Control
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.
Biosafety
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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Footnote 1 World Health Organization. WHO Risk assessment – Human infections with avian influenza A(H7N9) virus 7 June 2013.. http://www.who.int/influenza/human_a...r /> Footnote 2 Benyun S, Shang X, Guo-Jing Y, Xiao-Nong Z, Jiming L. 2013. Inferring the potential risks of H7N9 infection by spatiotemporally characterizing bird migration and poultry distribution in eastern China. BMC Infectious Diseases of Poverty 2013, 2:8 doi:10.1186/2049-9957-2-8
Footnote 3 World Health Organization. WHO recommendation on influenza A(H7N9) vaccine virus 26 September 2013. http://www.who.int/influenza/human_a...r /> Footnote 4 Chen Y, Liang W, Yang S, et al. 2013. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet. doi:pii: S0140-6736(13)60903-4. [Epub ahead of print]
Footnote 5 Qun Li, M.D., Lei Zhou, M.D. et al, 2013. Preliminary Report: Epidemiology of the Avian Influenza A (H7N9) Outbreak in China. The New England and Journal l of Medicine: April 24, 2013, at NEJM.org. DOI: 10.1056/NEJMoa1304617
Footnote 6Hu Y, Lu S, Song, et al. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet. 2013. http://download.thelancet.com/flatco...3613611253.pdf
11 Dec 2013
The risk assessment is reviewed on a regular basis and updated as required.
Risk Assessment
The public health risk posed by avian influenza A(H7N9) virus from China to Canada is considered low at this time. Cases have been reported in China from ten Provinces (Anhui, Guangdong, Hebei, Henan, Hunan, Fujian, Jiangsu, Jiangxi, Shandong, and Zhejiang) and two Municipalities (Beijing and Shanghai). In addition, a travel-related case was reported in Taiwan and Hong Kong. Poultry and environmental samples have tested positive for avian influenza A(H7N9) in all above mentioned provinces and municipalities, except for Hunan and Beijing.
There is still no evidence of sustained human-to-human transmission of avian influenza A(H7N9) virus. However, four clusters suggest that limited human-to-human transmission may occur where there is close contact between cases and other people.
There is no indication that international spread has occurred, although when infected people from affected areas travel, their infection may be detected in another country.
Event Summary
As of 4 December, 2013, WHO has reported 141 confirmed human cases, including 47 deaths. The case fatality rate (CFR) is 33%. With the exception of the cases in Beijing (2) and Hebei (1), all other cases have occurred in adjacent regions in eastern and south eastern China, including the travel-related case in Taiwan and Hong Kong. The majority of the cases have been reported by Zhejiang province (50), followed by Shanghai (34) and Jiangsu (27). Of the 138 cases with available demographic data the median age is 60 (range 2-91). Notably, 98 cases are male (71%) and 57 cases (41%) are ≥65 years of age.
The WHO’s Global Alert and Response websiteExternal Link maintains the latest updates on the total number of cases. The most recent case was reported on 3 December 2013, in Hong Kong Special Administrative Region (HK SAR), China. The case was a 36 year old female who was reported to have travelled to Shenzhen, Guangdong province, China, which is near the northern border of HK SAR, and had direct exposure to live poultry. This is the first case of avian influenza A(H7N9) reported in HK SAR, and the third case reported in association with Guangdong province since March 2013.
The source, reservoir, and communicability of the avian influenza A(H7N9) virus are currently under investigation; however, the WHO reports that human infection appears to be related to exposure to live poultry or contaminated environments for the following reasons:
◾The virus in humans is genetically similar to that found in animals and the environment (live bird markets).
◾Most human cases (approximately three out of four patients) report a history of exposure to birds, mostly chickens.
◾The virus has been detected in poultry in live bird markets.
◾The number of human cases has decreased after the implementation of public health measures, which included closure of live poultry markets.
Although four small human clusters have been reported, evidence does not support sustained human-to-human transmission. Monitoring and testing of more than 2,000 contacts of confirmed cases have detected few infections. Testing of more than 20,000 people with influenza-like-illness in March and April 2013 confirmed only six infections with avian influenza A(H7N9), suggesting that milder cases are not occurring in large numbersFootnote 1.
Closing of all live poultry markets was an effective control strategy in Shanghai, Jiangsu and Zhejiang as the number of reported human cases decreased following these closures. However, the continued decrease in the number of newly reported cases over the summer may be the result of the avian influenza A(H7N9) virus demonstrating a seasonal pattern, similar to other avian influenza viruses (e.g. H5N1), where cases are less frequent in the summer and more frequent in the winterFootnote 1. Live poultry markets have reopened, and as the influenza season progresses, more cases of avian influenza A(H7N9) virus are anticipated.
A scientific publication by the Infectious Diseases of Poverty indicates that it is necessary to regulate the poultry markets as long as poultry-to-poultry transmission is not well understoodFootnote 2. The Canadian Food and Inspection Agency (CFIA) published its “Preliminary Assessment of the Risk to Canadian Animals from the Novel H7N9 Influenza Virus Detected in China” and highlighted that: evidence to date strongly indicates that the novel H7N9 in poultry does not differ from other Influenza A viruses common in the animal population at the global level; this novel H7N9 virus is of avian origin and does not cause any severe clinical signs in poultry; and the risk to Canadian animals from the novel H7N9 influenza virus detected in China is considered to range from negligible to very low.
No vaccine is currently publicly available for this subtype of the H7N9 influenza virus; although several candidate vaccines are undergoing clinical trials. WHO has recommended that an A/Anhui/1/2013-like virus be used for the development of A(H7N9) vaccines for pandemic preparedness purposes. There are currently no recommendations on the large-scale manufacture of avian influenza A(H7N9) vaccineFootnote 3.
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. An analysis conducted on 14 patients in Shanghai showed that antivirals were able to clinically reduce viral load, however, the emergence of mutations known to confer resistance to neuraminidase inhibitors was also observed during the course of treatment in some individualsFootnote 6.
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 provincial/territorial colleagues allowing provinces to do their own testing should it be required.
Virus Characteristics
Sequencing of the avian influenza A(H7N9) virus by the World Health Organization (WHO) Chinese National Influenza Centre in Beijing revealed HA and NA genes from avian influenza A(H7N9) and remaining genes from A(H9N2), identifying this virus as a novel reassortant virus with all genes related to genes from Eurasian influenza A viruses from wild birds and poultry. Scientific publications in the LancetFootnote 4 and New England Journal of MedicineFootnote 6 suggest that poultry is a likely source of infection. This novel avian influenza A(H7N9) virus does not appear to cause severe illness in birds. This is different from previously identified and reported avian influenza A(H7N9) viruses in birds. Mutations in H7N9 strains have been identified that could favour high affinity interaction with human receptors in the upper respiratory tractFootnote 5 however, there has been no evidence of sustained human-to-human transmission. 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.
Recommendations for Canada
Surveillance
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 interim case definition for avian influenza A(H7N9) is 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 Advisory
A travel health advisory is posted on the Agency’s website. It does not recommend any restrictions on travel but encourages travellers to practice special precautions.
Infection Control
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.
Biosafety
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.
--------------------------------------------------------------------------------
Footnote 1 World Health Organization. WHO Risk assessment – Human infections with avian influenza A(H7N9) virus 7 June 2013.. http://www.who.int/influenza/human_a...r /> Footnote 2 Benyun S, Shang X, Guo-Jing Y, Xiao-Nong Z, Jiming L. 2013. Inferring the potential risks of H7N9 infection by spatiotemporally characterizing bird migration and poultry distribution in eastern China. BMC Infectious Diseases of Poverty 2013, 2:8 doi:10.1186/2049-9957-2-8
Footnote 3 World Health Organization. WHO recommendation on influenza A(H7N9) vaccine virus 26 September 2013. http://www.who.int/influenza/human_a...r /> Footnote 4 Chen Y, Liang W, Yang S, et al. 2013. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet. doi:pii: S0140-6736(13)60903-4. [Epub ahead of print]
Footnote 5 Qun Li, M.D., Lei Zhou, M.D. et al, 2013. Preliminary Report: Epidemiology of the Avian Influenza A (H7N9) Outbreak in China. The New England and Journal l of Medicine: April 24, 2013, at NEJM.org. DOI: 10.1056/NEJMoa1304617
Footnote 6Hu Y, Lu S, Song, et al. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet. 2013. http://download.thelancet.com/flatco...3613611253.pdf
