Influenza A virus subtypes H5, H7, and H9: Infectious substances pathogen safety data sheet

Section I: Infectious agent

Name

Influenza A virus subtypes H5, H7, and H9

Agent type

Virus

Taxonomy

Family

Orthomyxoviridae

Genus

Alphainfluenzavirus

Species

Alphainfluenzavirus influenzae

Synonym or cross-reference

Formerly Orthomyxovirus, influenza virus, influenza virus A, influenza A virusFootnote 1,Footnote 2. Also known as influenza virus type A, avian influenza, avian influenza A, pandemic influenza; causative agent of influenza (flu)Footnote 2,Footnote 3.

Characteristics

Brief description

Influenza A virus subtypes H5, H7, and H9 are members of the Orthomyxoviridae family of segmented, negative-sense, single-stranded RNA virusesFootnote 1,Footnote 2. Virions are enveloped and pleomorphic; they are generally spherical or elliptical in shape, ranging from approximately 80-120 nm in diameter, but are occasionally filamentous, reaching more than 20 µm in length, or irregularFootnote 4,Footnote 5. The genome is approximately 13.5 kb in length and comprises 8 single-stranded, negative-sense RNA segments: polymerase basic protein 2 (PB2), PB1, polymerase acidic (PA), hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix (M), and non-structural (NS)Footnote 6,Footnote 7. These segments code for 10 structural and 9 regulatory proteinsFootnote 8.

Properties

Influenza A viruses (IAVs) are divided into subtypes based on the antigenicity of their membrane-bound surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA)Footnote 9, Footnote 10. Sixteen distinct HA subtypes (H1-H16) and 9 NA subtypes (N1-N9) have been identified that circulate in wild bird populationsFootnote 9,Footnote 10. There are three primary HA subtypes (H1, H2, H3) and two NA subtypes (N1 and N2) that have established stable lineages in the human populationFootnote 11. Although less common, humans may be sporadically infected by IAVs of the H5, H7, and H9 subtypesFootnote 12. IAVs are further divided into highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI), which refers to their ability to cause disease in domestic poultryFootnote 13,Footnote 14. All HPAI viruses identified to date belong to the H5 and H7 subtypesFootnote 15,Footnote 16.

The HA, PB2, NS1 and PB-F2 proteins are known determinants of host-range restriction and pathogenicity, along with other contributing viral proteinsFootnote 12. In avian IAVs, HA is a critical determinant of pathogenicity. The HA proteins of HPAI viruses contain multiple basic amino acids at the cleavage site, forming a polybasic motif that is recognized by ubiquitous proteases; the presence of a polybasic HA cleaving site greatly expands IAV tropism in poultry, thereby leading to systemic infection in poultryFootnote 12. Conversely, HA proteins of LPAI viruses and non-avian IAVs contain a single arginine residue at the HA cleavage site and are only cleaved in a few organsFootnote 12. Reassortment, the swapping of gene segments between alphainfluenzaviruses during co-infection, occurs frequently and generates viruses with significantly altered antigenicity and pathogenicityFootnote 17. IAVs also undergo antigenic drift, the gradual change in the HA and/or NA proteins as a result of accumulation of point mutations in the antigenic epitopes, further contributing to virus evolutionFootnote 12. The emergence of novel IAVs with the ability to infect and transmit efficiently between humans could result in a pandemicFootnote 18.

The influenza virus infection cycle starts with the attachment of virus through the HA glycoprotein to sialic acid-containing glycan receptors on the host cell surfaceFootnote 19. Avian IAVs preferentially bind the avian α2,3-galactose linked sialic acid receptors, whereas mammalian IAVs preferentially bind the mammalian α2,6-galactose linked sialic acid receptorsFootnote 20. The virus is then internalized and, after fusion of the viral envelope to the endosomal membrane, viral RNAs are translocated into the cell nucleus, transcribed, and replicated to direct the production of new viral componentsFootnote 19. The NA is critically important during the final stages of infection, where it cleaves off sialic acid from glycans on the target host cell, as well as from newly formed budding virions, thus preventing virus aggregation and facilitating progeny release from the host cellFootnote 19. Host specificity among IAVs is due to the type of sialic acid receptor on the cell surfaceFootnote 19.

Section II: Hazard identification

Pathogenicity and toxicity

Influenza A viruses are pathogens of humans, avian species, and a wide range of other non-avian animals. Avian influenza A viruses that have caused infection in humans include subtypes H5N1, H5N6, H5N8, H7N2, H7N3, H7N4, H7N7, H7N9, and H9N2Footnote 21. In humans, clinical presentations resulting from infection by IAV subtypes H5, H7, and H9 range from asymptomatic or mild illness, such as conjunctivitis or mild upper respiratory tract illness, to severe respiratory illnessFootnote 22,Footnote 23,Footnote 24,Footnote 25. Initial symptoms of mild upper respiratory infection generally include cough and fever and may rapidly progress to severe pneumonia, acute respiratory distress, shock, and deathFootnote 18. Human infection with A(H5) or A(H7N9) IAVs often follows an aggressive clinical course, with initial symptoms including high fever and cough followed by symptoms of lower respiratory tract disease, including dyspneaFootnote 18. Upper respiratory tract symptoms are less common but may include sore throat or coryza; other symptoms include diarrhea, vomiting, abdominal pain, bleeding from the nose or gums, and chest painFootnote 18. Severe cases of disease can also lead to hypoxemic respiratory failure, multi-organ failure, including kidney and liver dysfunction, cardiac impairment, septic shock, secondary bacterial and fungal infections, and deathFootnote 18,Footnote 25. In addition, neurological symptoms (encephalitis, changed mental state, seizures) may manifest in patients infected with H5N1Footnote 18,Footnote 25. Adverse fetal outcomes, such as spontaneous abortion, preterm birth, and fetal distress have been reported in pregnant women, whom are at increased risk of severe complications and deathFootnote 25. Of the human cases of H5N1 reported to date, the case fatality rate is 52%Footnote 26; however, this may be an overestimate of disease severity due to selection bias of severe and/or hospitalized casesFootnote 27. Clinical presentations of human infections with IAV H5N6 virus often begin with fever, upper respiratory tract symptoms, and myalgia, and may rapidly progress to lower respiratory tract illness, resulting in pneumonia, multi-organ failure, acute respiratory distress syndrome, and oftentimes death, with an estimated case fatality rate of 44% to dateFootnote 28. Human infections with IAV H7N9 were first detected in 2013 and are characterized by lower respiratory tract disease, which may progress to severe pneumonia with respiratory failure, multi-organ failure, and death in approximately 40% of reported casesFootnote 3,Footnote 21.

LPAI viruses primarily replicate in the digestive and respiratory epithelium, often resulting in mild disease in poultry and wild birdsFootnote 29. Conversely, HPAI viruses replicate in many internal organs, leading to severe systemic disease in poultryFootnote 29, with clinical signs including drop in egg production, diarrhea, hemorrhages on the hock, quietness and extreme depression, swelling of the skin under the eyes, wattle and comb swelling and congestion, and high and sudden mortalityFootnote 30. HPAI viruses (i.e., certain H5 and H7 subtypes) can result in mortality rates of up to 90-100% in poultry within 48 hoursFootnote 10. Wild birds may be resistant to certain HPAI viruses; however, since December 2003, circulating HPAI H5N1 viruses have caused infection in wild birds accompanied by high mortalityFootnote 29. Although HPAI H5N1 viruses primarily infect poultry and wild birds, sporadic infections have been reported in mammals, including but not limited to dogs, cats, tigers, leopards, stone martens, civets, bears, foxes, skunks, raccoons, coyotes, lynx, bobcats, mice, rats, weasels, mink, badgers, pigs, opossums, fishers, and raccoon dogs, as well as several aquatic animals including otters, dolphins, porpoises, seals, and sea lionsFootnote 31. Neurological disease has been reported as the primary illness in some animalsFootnote 29,Footnote 32,Footnote 33. Infection of pigs with HPAI H5N1 has been confirmed; however, they were reported as healthy with no symptoms of diseaseFootnote 34. In cats and dogs, infection is associated by direct contact with infected birds, especially from ingestion of raw poultryFootnote 35,Footnote 36. Symptoms of disease in felids include pyrexia, depression, labored breathing, conjunctivitis, protrusion of the third eyelid, neurological signs such as convulsions and ataxia, and deathFootnote 35, while high fever, panting, lethargy, and death have been reported in dogsFootnote 36.

Epidemiology

Influenza A virus subtypes H5, H7, and H9 circulate in wild bird populationsFootnote 9,Footnote 10, and they can spread geographically through wild bird migration. H5, H7, and H9 viruses can spread to poultry, with HPAI viruses (i.e., certain H5 and H7 subtypes) causing severe disease and high mortalityFootnote 13,Footnote 14. Sporadic infections have occurred in humans and other mammals following direct contact with infected birds or with virus-contaminated environments. Among H5, H7 and H9 IAVs, H7N9 and H5N1 subtypes are responsible for the majority of human cases of disease reported to dateFootnote 52.

The first cases of H5N1 infection in humans were reported in 1997 in Hong Kong, coincident with a large outbreak of HPAI H5N1 in domestic poultry, resulting in 18 cases of human infection and 6 deathsFootnote 53,Footnote 54. In 2003, another outbreak occurred in Hong Kong and resulted in 3 human infections, 2 of which were fatalFootnote 54. In December 2003, an outbreak of H5N1 was reported in poultry in South Korea and subsequently in Vietnam, Japan, Thailand, Laos, Cambodia, China, Indonesia, and MalaysiaFootnote 55. Three waves of avian-to-human transmission were recorded from December 2003 to November 13, 2006, with 258 human cases reported, including 153 deaths, in Vietnam, Thailand, Cambodia, Indonesia, China, Turkey, Iraq, Azerbaijan, Egypt, and DjiboutiFootnote 55. The first reported human case of H5N1 infection in North America was in 2014 in an Alberta resident returning from a trip to Beijing, China, resulting in deathFootnote 40. H5N1 viruses spread in wild birds to Europe and into the Americas in 2021, resulting in a large epizootic event with sporadic infections in humans and other animalsFootnote 56. Since 1997, more than 800 cases of human infection have been reported, with a case fatality rate of 52%; the majority of cases were identified prior to 2016 and occurred primarily in Egypt, Indonesia, China, and VietnamFootnote 57,Footnote 58.

Since 2014, more than 80 laboratory-confirmed human cases of H5N6 infection, including over 30 deaths, have been reported globallyFootnote 58. Over 50 cases have been reported worldwide since 2021, with nearly all cases reported from ChinaFootnote 58.

In 2021, the first known human cases of HPAI H5N8 were reported in Russia, with 7 confirmed cases of mild infection in poultry farm workers from a farm in Southern Russia where outbreaks had been reportedFootnote 59. There was no indication of human-to-human transmission and the World Health Organization (WHO) confirmed that all cases remained asymptomatic during the follow-up period.

Human infection with various IAV H7 subtypes has been reported. LPAI H7N2 virus infection was reported in a small number of people with mild disease in the United Kingdom and the United States since 2002Footnote 21. Since 2002, four human cases have been identified in the United States, two of which resulted from cat-to-human transmission of LPAI H7N2 circulating among cats in 2016Footnote 21. A few cases of human infection with H7N3, involving conjunctivitis and mild upper respiratory tract symptoms, have been reported in the United Kingdom and Canada since 2004Footnote 21. A case of H7N4 infection was reported in an individual with pneumonia in China in 2017. Over 90 cases of HPAI H7N7 infection have been reported since the first human infection was identified in the United States in 1959; most infections were associated with conjunctivitis and resulted from exposures during widespread poultry outbreaks in the Netherlands in 2003Footnote 21. Over 1,500 cases of LPAI H7N9 infection have been reported in China (case fatality rate of 40% in hospitalized patients), notably during epidemics from 2013-2017, with cases exported in Hong Kong, Macau, Malaysia, Taiwan, and CanadaFootnote 21. During the fifth epidemic wave in 2016-2017, HPAI H7N9 strains were detected in mainland China, with at least 33 human cases detected since 2017 and a case fatality rate of approximately 50%Footnote 60.

Since the emergence of LPAI H9N2 in human populations in 1988, 107 cases have been reported in China, Bangladesh, Cambodia, Egypt, India, Oman, Pakistan, and Senegal, with a case fatality rate of 2%Footnote 21,Footnote 58. The most recent case was reported in December 2022 from ChinaFootnote 58.

Children younger than 5 years and adults aged 65 years or older, pregnant women up to 2 weeks post-partum, immunocompromised individuals, people with certain chronic comorbidities (e.g., pulmonary, cardiac, neurological, metabolic, hematological, and extreme obesity), and long-term care facility residents are at increased risk for influenza A-related complicationsFootnote 37. Based on serosurveillance of poultry-exposed individuals in Egypt, chronic lung disease is a significant risk factor for infection with H5N1Footnote 38. Individuals with occupational or recreational exposures to wild birds and poultry are at higher risk of infectionFootnote 39. Activities that may increase risk of exposure include working with infected poultry in a commercial poultry farm or having a backyard flock, hunting, de-feathering, butchering infected wild birds and wild mammals, working with wild birds for research, conservation or rehabilitation purposes, working with wild mammals, and visiting live bird marketsFootnote 40.

Host range

Natural host(s)

Primarily domestic and wild avian speciesFootnote 10,Footnote 12,Footnote 30. Viral transmission of H5N1 has been reported in terrestrial mammals, including humans, dogs, cats, tigers, leopards, stone martens, civets, bears, foxes, skunks, raccoons, coyotes, lynx, bobcats, mice, rats, weasels, mink, badgers, pigs, opossums, fishers, and raccoon dogs, and aquatic mammalsFootnote 31.

Other host(s)

Ferrets are experimentally infected hostsFootnote 61.

Infectious dose

The median infectious dose (ID50) was experimentally determined for H5N1 and H7N1 in three poultry speciesFootnote 62. The median infectious doses for H5N1 are 101, 103.4, and <101, and for H7N1 are 102.2, 104.6, and ≤104.2, in turkeys, chickens, and ducks, respectively.

Incubation period

For H5N1 infection in humans, average incubation period of 2-5 days, ranging up to 17 daysFootnote 63. For H7N9 virus, incubation period of 1-10 days (average of 5 days) in humansFootnote 63. In poultry, the incubation period for IAVs ranges from 2-14 days following exposureFootnote 30.

Communicability

Human infection with IAVs of H5, H7, and H9 subtypes primarily occurs through exposure of mucous membranes to secretions or excreta from infected birdsFootnote 15,Footnote 41, and can also occur by inhalation of aerosols, droplets, or contact transmissionFootnote 42,Footnote 43. Transmission by contact with virus-contaminated environments and fomites is plausibleFootnote 44. Ingestion of fresh duck blood and undercooked poultry products has been suspected in some cases of human infection with IAVsFootnote 45; oral ingestion of contaminated water during swimming is a possible route of H5N2 infection in humansFootnote 44. Currently circulating H5, H7, and H9 viruses are not well adapted to humans; they are able to infect and cause disease in humans but have not gained the ability for sustained transmission among humansFootnote 46. Human-to-human transmission is thought to have occurred in a few cases of H5N1 and H7N9 infection involving very close and prolonged contact between a critically ill patient and a care giver during the critical phase of illnessFootnote 43. Transplacental transmission of H5N1 virus from mother to fetus was also reported, with evidence of dissemination to other organs including the brainFootnote 47.

Infected birds shed avian IAVs in their saliva, nasal secretions, and fecesFootnote 48. Avian IAVs are highly contagious among birds. Susceptible birds and mammals can become infected following direct contact with infected birds, or through contact with virus-contaminated environmentsFootnote 49. Transmission of H5N1 to non-avian animals has been reported following ingestion of infected animalsFootnote 50. Suspected animal-to-animal transmission of H5N1 was reported on a mink farm in SpainFootnote 51.

Section III: Dissemination

Reservoir

Wild waterfowl and shorebirds of the orders Anseriformes and Charadriiformes are the natural reservoirs of IAVsFootnote 12.

Zoonosis

Zoonotic transmission of IAV subtypes H5, H7, and H9 from avian species to humans has been documented, and occurs primarily through direct exposure of mucous membranes to secretions or excreta from infected birds, or through environmental contaminationFootnote 27,Footnote 64. Cat-to-human transmission of LPAI H7N2 was reported in 2016Footnote 21.

Vectors

Flies may act as mechanical vectors for the transmission of LPAI virusesFootnote 48.

Section IV: Stability and viability

Drug susceptibility/resistance

Influenza A viruses are susceptible to neuraminidase inhibitors, including oseltamivir, zanamivir, peramivir and laninamivirFootnote 65.

Oseltamivir-resistant viruses have been isolated from H5N1-infected patients treated with this drugFootnote 12. High-level resistance to oseltamivir and peramivir and moderate resistance to zanamivir and laninamivir has been reported in H7N9 viruses with an R292K mutation in viral neuraminidase, conferring resistance to neuraminidase inhibitorsFootnote 66. Extensive adamantane resistance has been documented in H5N1 and H7N9 influenza strainsFootnote 64.

Susceptibility to disinfectants

IAVs are generally susceptible to sodium hypochlorite (200 ppm), benzalkonium chloride (1,000 ppm), iodophor as I2 (75 ppm), 0.12% ortho-phenylphenol, and 0.02% glutaraldehyde solutions, showing virucidal inactivation in 10 minutesFootnote 67. Other disinfectants shown to inactivate IAVs include 1:16 dilution of PREvail™ (accelerated hydrogen peroxide), Vesphene®IIIse (phenol), VERT2GO SABER Concentrated (hydrogen peroxide), NEUTRAQUAT 256 and Quat-3 (quaternary ammonium compounds)Footnote 68.

Physical inactivation

Incubation at 56-60°C for 60 minutes inactivates various H5, H7, and H9 subtypesFootnote 58. Incubations in low (1-3) or high (10-14) pH solutions is reportedly effective at inactivating IAV subtypes H5, H7, and H9, although the medium in which the virus is suspended may interfere with the effect of pH on virus infectivityFootnote 58. H7N9 strains lost infectivity after heat treatment of 56°C for 30 minutes, 65°C for 10 minutes, 70°C, 75°C and 100°C for 1 minuteFootnote 69. The strains were also killed after 30 minutes of UV exposure, or at a pH of less than 2 for 30 minutes or pH 3 for 24 hours.

Survival outside host

HPAI H5N1 has been shown to survive up to 18 hours at 42°C, 24 hours at 37°C, 5 days at 24°C, and 8 weeks at 4°C in dry and wet poultry fecesFootnote 70. In experimentally infected chickens, H5N1 may survive up to 240 days in feather tissues, 160 days in muscle, and 3 days in liver at 4°C, while the virus remained viable for up to 30 days in feather tissues, 20 days in muscle, and 3 days in liver at 20°CFootnote 71. The survival time for H5N1 is ~26 hours on plastic surfaces and ~4.5 hours on human skin surfaces, while subtypes H5N3, H5N9, and H7N9 are completely inactive on plastic surfaces within 10 hours, and within 1.5 hours on human skinFootnote 72.

Section V: First aid/medical

Surveillance

Monitor for symptoms of influenzaFootnote 37. Clinical diagnosis is difficult as symptoms range in severity and overlap with those caused by other respiratory viruses, but can be confirmed through testing of nasopharyngeal, nasal, or throat specimensFootnote 64. Diagnostic tests such as RT-PCR (preferred), molecular assays, antigen tests, immunofluorescence assays, or point-of-care testing can be usedFootnote 37,Footnote 64. Upper-respiratory-tract specimens from outpatients should be collected within 4 days of illness onset, although viral RNA may be detectable for longer periods; nasopharyngeal specimens have the highest yield for influenza virusesFootnote 37.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

IAV infections can be treated with neuraminidase inhibitors, including oseltamivir, zanamivir, peramivir and laninamivir, and are recommended for individuals with suspected or confirmed IAV infection with or at risk of severe illness, including those with pandemic and zoonotic influenzaFootnote 65. Antiviral treatment is most effective when started at symptom onsetFootnote 65. For hospitalized patients with severe disease, clinical management may also include supportive care of complications, including advanced organ support for patients with severe pneumoniaFootnote 73.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine currently available in Canada. However, AUDENZ, an adjuvanted IAV H5N1 monovalent vaccine indicated for active immunization for prevention of disease, was approved in the United States for use in persons 6 months of age and older at increased risk of exposureFootnote 74. Under the Pandemic Influenza Preparedness (PIP) framework, the WHO coordinates the development of candidate vaccine virusesFootnote 75. Several candidate vaccine viruses have been developed against various H5, H7, and H9 subtypesFootnote 75. H7N9 and H9N2 candidate vaccines have also been evaluated in various studiesFootnote 76,Footnote 77,Footnote 78.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

Post-exposure chemoprophylaxis is recommended for persons with recent exposure (within 10 days) to IAV subtypes H5, H7, and H9, including direct exposure to infected birds or surfaces contaminated with feces or bird parts from infected birds, direct exposure to an infected person, and unprotected exposure in a laboratoryFootnote 79. Available drugs for chemoprophylaxis include oral oseltamivir or inhaled zanamivir (twice daily for 5 or 10 days) and should be administered as soon as possible (within 48 hours) after initial exposure to a confirmed or probable caseFootnote 80.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI: Laboratory hazard

Laboratory-acquired infections

Five reported cases. In 1979, four field workers performed post-mortem examinations on harbour seals, which revealed hemorrhagic pneumonia associated with an IAV antigenically similar to A/Fowl Plague/Dutch/27 (H7N7), and developed purulent conjunctivitis within two days of known contamination of the eyesFootnote 81. Subsequently, during studies on harbour seals experimentally infected with A/Seal/Mass/1/80 (H7N7), an infected seal confirmed to be shedding the virus sneezed directly into the researcher's face and right eye. Within 40 hours, the researcher developed severe conjunctivitis of the right eye, with enlargement of the preauricular lymph nodes by 96 hoursFootnote 81.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Tissues, secretions and excreta from infected birds (e.g., saliva, nasal secretions, feces, intestines, cloacae)Footnote 15,Footnote 41,Footnote 48,Footnote 82. Human nasopharyngeal, nasal, and throat specimensFootnote 64.

Primary hazards

Exposure of mucous membranes/skin to infectious material and inhalation of airborne or aerosolized infectious material are the primary hazards associated with exposure to influenza A virus subtypes H5, H7, and H9Footnote 81,Footnote 82.

Special hazards

Genetic manipulation of IAVs may alter host range, pathogenicity, and antigenic composition (e.g., H5N1 transmissible engineered strain); the potential for introduction of influenza viruses with novel genetic composition into humans is unknownFootnote 82.

Section VII: Exposure controls/personal protection

Risk group classification

Influenza A viruses from subtypes H5, H7, and H9 are a Risk Group 2 or 3 Human Pathogen and Risk Group 2 or 3 Animal Pathogen, depending on the subtype and strainFootnote 83,Footnote 84. The risk group classifications of various subtypes and strains are available in the ePATHogen Risk Group Database.

Influenza A virus subtypes H5N1, H5N6, and H7N9 are Security Sensitive Biological Agents (SSBAs).

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS for work with circulating strains of influenza A virus (excluding the 1918 H1N1 strain, subtype H2N2, and HPAI subtypes) involving infectious or potentially infectious materials, animals, or cultures.

Containment Level 3 facilities, equipment, and operational practices outlined in the CBS and in the Biosafety Directive for New and Emerging Influenza A Viruses for all in vivo and in vitro activities involving wild type HPAI strains (notably, from subtypes H5 and H7) classified as Risk Group 3 Human Pathogens and/or Risk Group 3 Animal Pathogens.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

For Risk Group 2: The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the CBS and the Biosafety Directive for New and Emerging Influenza A Viruses are to be followed. The personal protective equipment could include the use of a lab coat and closed-toe cleanable shoes, gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes. Respirators to be worn where there is a risk of exposure to infectious aerosols that can be transmitted through the inhalation route, as determined by a local risk assessment.

For Risk Group 3: The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the CBS are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

Containment Level 2: A biological safety cabinet (BSC) or other primary containment devices is to be used for activities with open vessels. Use of needles and syringes is to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes is to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large scale activities.

Containment Level 3: All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects is to be strictly limited. Additional precautions must be considered with work involving animals or large-scale activities.

For diagnostic laboratories handling primary specimens that may contain influenza A virus subtypes H5, H7, and H9, the following resources may be consulted:

Section VIII: Handling and storage

Spills

Containment Levels 2 and 3: Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with disinfectant before clean up (CBH).

Disposal

Containment Level 2: All materials/substances that have come in contact with the regulated materials are to be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) are to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Containment Level 3: Regulated materials, as well as all items and waste are to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

Containment Level 2: The applicable Containment Level 2 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone are to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Containment Level 3: The applicable Containment Level 3 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

SSBA: Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

Section IX: Regulatory and other information

Canadian regulatory information

Controlled activities with influenza A virus subtypes H5, H7, and H9 require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada. Influenza A virus subtypes H5, H7, and all HPAI IAVs are considered non-indigenous animal pathogens in Canada; therefore, importation of these viruses requires an import permit, issued by the Canadian Food Inspection Agency.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

Last file update

March 2023

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright© Public Health Agency of Canada, 2023, Canada

References

Footnote 1

International Committee on Taxonomy of Viruses. 2021. Alphainfluenzavirus influenzae. 2023.

Return to footnote 1 referrer

Footnote 2

Hampson, A. W., and J. S. Mackenzie. 2006. The influenza viruses. Med. J. Aust. 185:S39-S43.

Return to footnote 2 referrer

Footnote 3

Centers for Disease Control and Prevention. 2022. Influenza Type A Viruses. 2023. Available at https://www.cdc.gov/flu/avianflu/influenza-a-virus-subtypes.htm.

Return to footnote 3 referrer

Footnote 4

Sugita, Y., T. Noda, H. Sagara, and Y. Kawaoka. 2011. Ultracentrifugation deforms unfixed influenza A virions. J. Gen. Virol. 92:2485-2493.

Return to footnote 4 referrer

Footnote 5

Noda, T., Y. Sugita, K. Aoyama, A. Hirase, E. Kawakami, A. Miyazawa, H. Sagara, and Y. Kawaoka. 2012. Three-dimensional analysis of ribonucleoprotein complexes in influenza A virus. Nat. Commun. 3:1-6.

Return to footnote 5 referrer

Footnote 6

Ghedin, E., N. A. Sengamalay, M. Shumway, J. Zaborsky, T. Feldblyum, V. Subbu, D. J. Spiro, J. Sitz, H. Koo, P. Bolotov, D. Dernovoy, T. Tatusova, Y. Bao, K. St George, J. Taylor, D. J. Lipman, C. M. Fraser, J. K. Taubenberger, and S. L. Salzberg. 2005. Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution. Nature. 437:1162-1166.

Return to footnote 6 referrer

Footnote 7

Bouvier, N. M., and P. Palese. 2008. The biology of influenza viruses. Vaccine. 26:D49-D53.

Return to footnote 7 referrer

Footnote 8

Kosik, I., and J. W. Yewdell. 2019. Influenza hemagglutinin and neuraminidase: Yin-yang proteins coevolving to thwart immunity. Viruses. 11:1-18.

Return to footnote 8 referrer

Footnote 9

Kalonda, A., M. Phonera, N. Saasa, M. Kajihara, C. G. Sutcliffe, H. Sawa, A. Takada, and E. Simulundu. 2021. Influenza A and D viruses in non-human mammalian hosts in Africa: A systematic review and meta-analysis. Viruses. 13:1-18.

Return to footnote 9 referrer

Footnote 10

Kanaujia, R., I. Bora, R. K. Ratho, V. Thakur, G. K. Mohi, and P. Thakur. 2022. Avian influenza revisited: concerns and constraints. Virusdisease. 33:456-465.

Return to footnote 10 referrer

Footnote 11

Naeem, A., K. Elbakkouri, A. Alfaiz, M. E. Hamed, H. Alsaran, S. AlOtaiby, M. Enani, and B. Alosaimi. 2020. Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015. J. Med. Virol. 92:3016-3027.

Return to footnote 11 referrer

Footnote 12

Neumann, G., J. J. Treanor, and Y. Kawaoka. 2021. Orthomyxoviruses, p. 596-648. P. M. Howley and D. M. Knipe (eds.), Fields Virology: Emerging Viruses, 7th ed., vol. 1. Wolters Kluwer Health.

Return to footnote 12 referrer

Footnote 13

Criado, M. F., K. A. Moresco, D. E. Stallknecht, and D. E. Swayne. 2021. Low-pathogenicity influenza viruses replicate differently in laughing gulls and mallards. Influ. Other Respir. Viruses. 15:701-706.

Return to footnote 13 referrer

Footnote 14

Negovetich, N. J., and R. G. Webster. 2010. Thermostability of subpopulations of H2N3 influenza virus isolates from mallard ducks. J. Virol. 84:9369-9376.

Return to footnote 14 referrer

Footnote 15

Liu, Q., D. -. Liu, and Z. -. Yang. 2013. Characteristics of human infection with avian influenza viruses and development of new antiviral agents. Acta Pharmacol. Sin. 34:1257-1269.

Return to footnote 15 referrer

Footnote 16

Public Health Agency of Canada. 2018. Biosafety Directive for New and Emerging Influenza A Viruses. 2023. Available at https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/biosafety-directives-advisories-notifications/new-emerging-influenza-a-viruses.html.

Return to footnote 16 referrer

Footnote 17

Lowen, A. C., and J. Steel. 2014. Roles of humidity and temperature in shaping influenza seasonality. J. Virol. 88:7692-7695.

Return to footnote 17 referrer

Footnote 18

World Health Organization. 2018. Influenza (Avian and other zoonotic). 2023. Available at https://www.who.int/news-room/fact-sheets/detail/influenza-(avian-and-other-zoonotic)

Return to footnote 18 referrer

Footnote 19

Zhu, X., H. Yang, Z. Guo, W. Yu, P. J. Carney, Y. Li, L. -. Chen, J. C. Paulson, R. O. Donis, S. Tong, J. Stevens, and I. A. Wilson. 2012. Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site. Proc. Natl. Acad. Sci. U. S. A. 109:18903-18908.

Return to footnote 19 referrer

Footnote 20

Lorusso, A., A. L. Vincent, M. R. Gramer, K. M. Lager, and J. R. Ciacci-Zanella. 2013. Contemporary epidemiology of north american lineage triple reassortant influenza a viruses in pigs. Curr. Top. Microbiol. Immunol. 370:113-131.

Return to footnote 20 referrer

Footnote 21

Centers for Disease Control and Prevention. 2023. Reported Human Infections with Avian Influenza A Viruses. 2023. Available at https://www.cdc.gov/flu/avianflu/reported-human-infections.htm.

Return to footnote 21 referrer

Footnote 22

Chan, P. K. S. 2002. Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clin. Infect. Dis. 34:S58-S64.

Return to footnote 22 referrer

Footnote 23

Koopmans, M., B. Wilbrink, M. Conyn, G. Natrop, H. Van Der Nat, H. Vennema, A. Meijer, J. Van Steenbergen, R. Fouchier, A. Osterhaus, and A. Bosman. 2004. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet. 363:587-593.

Return to footnote 23 referrer

Footnote 24

Lin, Y. P., M. Shaw, V. Gregory, K. Cameron, W. Lim, A. Klimov, K. Subbarao, Y. Guan, S. Krauss, K. Shortridge, R. Webster, N. Cox, and A. Hay. 2000. Avian-to-human transmission of H9N2 subtype influenza A viruses: Relationship between H9N2 and H5N1 human isolates. Proc. Natl. Acad. Sci. U. S. A. 97:9654-9658.

Return to footnote 24 referrer

Footnote 25

Liu, S., J. Sha, Z. Yu, Y. Hu, T. -. Chan, X. Wang, H. Pan, W. Cheng, S. Mao, R. J. Zhang, and E. Chen. 2016. Avian influenza virus in pregnancy. Rev. Med. Virol. 26:268-284.

Return to footnote 25 referrer

Footnote 26

Public Health Agency of Canada. 2023. Human emerging respiratory pathogens bulletin: Issue 73, January 2023. Available at https://www.canada.ca/en/public-health/services/surveillance/human-emerging-respiratory-pathogens-bulletin/2023/january.html.

Return to footnote 26 referrer

Footnote 27

Chen, X., W. Wang, Y. Wang, S. Lai, J. Yang, B. J. Cowling, P. W. Horby, T. M. Uyeki, and H. Yu. 2020. Serological evidence of human infections with highly pathogenic avian influenza A(H5N1) virus: a systematic review and meta-analysis. BMC Med. 18:1-16.

Return to footnote 27 referrer

Footnote 28

Public Health Agency of Canada. 2022. In-Depth Analysis: Human Respiratory Disease Associated with Avian Influenza A(H5N6). 2023. Available at https://www.canada.ca/en/public-health/services/surveillance/human-emerging-respiratory-pathogens-bulletin/2022/january/in-depth-analysis-avian-influenza-a-h5n6.html.

Return to footnote 28 referrer

Footnote 29

Bordes, L., S. Vreman, R. Heutink, M. Roose, S. Venema, S. B. E. Pritz-Verschuren, J. M. Rijks, J. L. Gonzales, E. A. Germeraad, M. Engelsma, and N. Beerens. 2023. Highly Pathogenic Avian Influenza H5N1 Virus Infections in Wild Red Foxes (Vulpes vulpes) Show Neurotropism and Adaptive Virus Mutations. Microbiol. Spectr. 11:1-13.

Return to footnote 29 referrer

Footnote 30

Canadian Food Inspection Agency. 2022. Fact Sheet – Avian Influenza. 2023. Available at https://inspection.canada.ca/animal-health/terrestrial-animals/diseases/reportable/avian-influenza/fact-sheet/eng/1356193731667/1356193918453#a1.

Return to footnote 30 referrer

Footnote 31

Centers for Disease Control and Prevention. 2023. Highlights in the History of Avian Influenza (Bird Flu) Timeline - 2020-2023. Available at https://www.cdc.gov/flu/avianflu/timeline/avian-timeline-2020s.htm.

Return to footnote 31 referrer

Footnote 32

Elsmo, E., A. Wunschmann, K. Beckmen, L. Broughton-Neiswanger, E. Buckles, J. Ellis, S. Fitzgerald, R. Gerlach, S. Hawkins, H. Ip, J. Lankton, E. Lemley, J. Lenoch, M. Killian, K. Lantz, L. Long, R. Maes, M. Mainenti, J. Melotti, M. Moriarty, S. Nakagun, R. Ruden, V. Shearn-Bochsler, D. Thompson, Mia Kim Torchetti, A. Van Wettere, A. Wise, and A. Lim. 2023. Pathology of natural infection with highly pathogenic avian influenza virus (H5N1) clade 2.3.4.4b in wild terrestrial mammals in the United States in 2022. bioRxiv.

Return to footnote 32 referrer

Footnote 33

Vreman, S., M. Kik, E. Germeraad, R. Heutink, F. Harders, M. Spierenburg, M. Engelsma, J. Rijks, J. v. d. Brand, N. Beerens, and VPDC pathologie. 2023. Zoonotic Mutation of Highly Pathogenic Avian Influenza H5N1 Virus Identified in the Brain of Multiple Wild Carnivore Species. Pathogens (Basel). 12:168.

Return to footnote 33 referrer

Footnote 34

Meseko, C., A. Globig, J. Ijomanta, T. Joannis, C. Nwosuh, D. Shamaki, T. Harder, D. Hoffman, A. Pohlmann, M. Beer, T. Mettenleiter, and E. Starick. 2018. Evidence of exposure of domestic pigs to Highly Pathogenic Avian Influenza H5N1 in Nigeria. Sci. Rep. 8:1-9.

Return to footnote 34 referrer

Footnote 35

Marschall, J., and K. Hartmann. 2008. Avian influenza A H5N1 infections in cats. J. Feline Med. Surg. 10:359-365.

Return to footnote 35 referrer

Footnote 36

Songserm, T., A. Amonsin, R. Jam-On, N. Sae-Heng, N. Pariyothorn, S. Payungporn, A. Theamboonlers, S. Chutinimitkul, R. Thanawongnuwech, and Y. Poovorawan. 2006. Fatal avian influenza A H5N1 in a dog. Emerg. Infect. Dis. 12:1744-1747.

Return to footnote 36 referrer

Footnote 37

Uyeki, T. M., D. S. Hui, M. Zambon, D. E. Wentworth, and A. S. Monto. 2022. Influenza. Lancet. 400:693-706.

Return to footnote 37 referrer

Footnote 38

Gomaa, M. R., A. S. Kayed, M. A. Elabd, D. A. Zeid, S. A. Zaki, A. S. El Rifay, L. S. Sherif, P. P. McKenzie, R. G. Webster, R. J. Webby, M. A. Ali, and G. Kayali. 2014. Avian Influenza A(H5N1) and A(H9N2) seroprevalence and risk factors for infection among Egyptians: a prospective controlled seroepidemiological study. J. Infect. Dis. 29:1399-1407.

Return to footnote 38 referrer

Footnote 39

Centers for Disease Control and Prevention. 2022. March 7, 2022 Update: H5N1 Bird Flu Poses Low Risk to the Public. Available at https://www.cdc.gov/flu/avianflu/spotlights/2021-2022/h5n1-low-risk-public.htm#:~:text=Since%202003%2C%20the%20World%20Health%20Organization%20%28WHO%29%2C%20has,
over%20the%20years.%20Information%20on%20Current%20H5N1%20Viruses

Return to footnote 39 referrer

Footnote 40

Public Health Agency of Canada. 2023. Avian influenza A(H5N1): Prevention and risks. Available at https://www.canada.ca/en/public-health/services/diseases/avian-influenza-h5n1/prevention-risks.html.

Return to footnote 40 referrer

Footnote 41

Li, Y. -., M. Linster, I. H. Mendenhall, Y. C. F. Su, and G. J. D. Smith. 2019. Avian influenza viruses in humans: Lessons from past outbreaks. Br. Med. Bull. 132:81-95.

Return to footnote 41 referrer

Footnote 42

Acha, P. N., and B. Szyfres. 2003. Chlamydioses, rickettsioses, and viroses, p. 183. J. Navarro and D. J. Reynolds (eds.), Zoonoses and Communicable Diseases Common to Man and Animals, 3rd ed., vol. 2. Pan American Health Organization HQ Library, Washington, D.C.

Return to footnote 42 referrer

Footnote 43

Heymann, D. L. 2008. Control of Communicable Diseases Manual. American Public Health Association, Washington, D.C.

Return to footnote 43 referrer

Footnote 44

The Writing Committee of the World Health Organization (WHO). 2005. Consultation on human influenza A/H5: Avian influenza A (H5N1) infection in humans. N. Engl. J. Med. 353:1374-1385.

Return to footnote 44 referrer

Footnote 45

Hayden, F., and A. Croisier. 2005. Transmission of avian influenza viruses to and between humans. J. Infect. Dis. 192:1311-1314.

Return to footnote 45 referrer

Footnote 46

Centers for Disease Control and Prevention. 2023. Technical Report: Highly Pathogenic Avian Influenza A(H5N1) Viruses. 2023. Available at https://www.cdc.gov/flu/avianflu/spotlights/2022-2023/h5n1-technical-report.htm.

Return to footnote 46 referrer

Footnote 47

Gu, J., Z. Xie, Z. Gao, J. Liu, C. Korteweg, J. Ye, L. T. Lau, J. Lu, Z. Gao, B. Zhang, M. A. McNutt, M. Lu, V. M. Anderson, E. Gong, A. C. H. Yu, and W. I. Lipkin. 2007. H5N1 infection of the respiratory tract and beyond: a molecular pathology study. Lancet. 370:1137-1145.

Return to footnote 47 referrer

Footnote 48

World Organisation for Animal Health. 2019. Low pathogenic avian influenza viruses (all subtypes). 2023. Available at https://www.woah.org/app/uploads/2022/02/low-pathogenic-avian-influenza-viruses-all-subtypesinfection-with.pdf.

Return to footnote 48 referrer

Footnote 49

Centers for Disease Control and Prevention. 2022. Avian Influenza in Birds. 2023. Available at https://www.cdc.gov/flu/avianflu/avian-in-birds.htm.

Return to footnote 49 referrer

Footnote 50

World Organisation for Animal Health. 2023. Avian influenza Situation Reports. Available at https://www.woah.org/en/disease/avian-influenza/#ui-id-2

Return to footnote 50 referrer

Footnote 51

Agüero, M., I. Monne, A. Sánchez, B. Zecchin, A. Fusaro, M. J. Ruano, M. Del Valle Arrojo, R. Fernández-Antonio, A. M. Souto, P. Tordable, J. Cañás, F. Bonfante, E. Giussani, C. Terregino, and J. J. Orejas. 2023. Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022. Euro Surveillance : Bulletin Européen Sur Les Maladies Transmissibles. 28:1.

Return to footnote 51 referrer

Footnote 52

Centers for Disease Control and Prevention. 2022. Bird Flu Virus Infections in Humans. 2023. Available at https://www.cdc.gov/flu/avianflu/avian-in-humans.htm

Return to footnote 52 referrer

Footnote 53

Buxton Bridges, C., W. W. Thompson, M. I. Meltzer, G. R. Reeve, W. J. Talamonti, N. J. Cox, H. A. Lilac, H. Hall, A. Klimov, and K. Fukuda. 2000. Effectiveness and cost-benefit of influenza vaccination of healthy working adults: A randomized controlled trial. J. Am. Med. Assoc. 284:1655-1663.

Return to footnote 53 referrer

Footnote 54

Peiris, J. S. M., W. C. Yu, C. W. Leung, C. Y. Cheung, W. F. Ng, J. M. Nicholls, T. K. Ng, K. H. Chan, S. T. Lai, W. L. Lim, K. Y. Yuen, and Y. Guan. 2004. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet. 363:617-619.

Return to footnote 54 referrer

Footnote 55

Thomas, J. K., and J. Noppenberger. 2007. Avian influenza: A review. Am. J. Health-Syst. Pharm. 64:149-165.

Return to footnote 55 referrer

Footnote 56

Caliendo, V., N. S. Lewis, A. Pohlmann, S. R. Baillie, A. C. Banyard, M. Beer, I. H. Brown, R. A. M. Fouchier, R. D. E. Hansen, T. K. Lameris, A. S. Lang, S. Laurendeau, O. Lung, G. Robertson, H. van der Jeugd, T. N. Alkie, K. Thorup, M. L. van Toor, J. Waldenström, C. Yason, T. Kuiken, and Y. Berhane. 2022. Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021. Scientific Reports. 12:11729.

Return to footnote 56 referrer

Footnote 57

Shi, J., X. Zeng, P. Cui, C. Yan, and H. Chen. 2023. Alarming situation of emerging H5 and H7 avian influenza and effective control strategies. Emerg. Microbes Infect. 12:1-12.

Return to footnote 57 referrer

Footnote 58

Public Health Agency of Canada. 2023. Human emerging respiratory pathogens bulletin: Issue 74, February 2023. Available at https://www.canada.ca/en/public-health/services/surveillance/human-emerging-respiratory-pathogens-bulletin/2023/february.html.

Return to footnote 58 referrer

Footnote 59

World Health Organization. 2021. Human infection with avian influenza A (H5N8) – the Russian Federation. 2023. Available at https://www.who.int/emergencies/disease-outbreak-news/item/2021-DON313#:~:text=Human%20infection%20with%20avian%20influenza%20A%20(H5N8)%20%2D%20Russian%20Federation,
-26%20February%202021&text=On%2018%20February%202021%2C%20the,A(H5N8)%20in%20humans.

Return to footnote 59 referrer

Footnote 60

He, D., M. Gu, X. Wang, X. Wang, G. Li, Y. Yan, J. Gu, T. Zhan, H. Wu, X. Hao, G. Wang, J. Hu, S. Hu, X. Liu, S. Su, C. Ding, and X. Liu. 2021. Spatiotemporal Associations and Molecular Evolution of Highly Pathogenic Avian Influenza A H7N9 Virus in China from 2017 to 2021. Viruses. 13:1-13.

Return to footnote 60 referrer

Footnote 61

Herfst, S., E. J. A. Schrauwen, M. Linster, S. Chutinimitkul, E. De Wit, V. J. Munster, E. M. Sorrell, T. M. Bestebroer, D. F. Burke, D. J. Smith, G. F. Rimmelzwaan, A. D. M. E. Osterhaus, and R. A. M. Fouchier. 2012. Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 336:1534-1541.

Return to footnote 61 referrer

Footnote 62

Aldous, E. W., J. M. Seekings, A. McNally, H. Nili, C. M. Fuller, R. M. Irvine, D. J. Alexander, and I. H. Brown. 2010. Infection dynamics of highly pathogenic avian influenza and virulent avian paramyxovirus type 1 viruses in chickens, turkeys and ducks. Avian Pathol. 39:265-273.

Return to footnote 62 referrer

Footnote 63

Heymann, D. L. 2015. Control of Communicable Diseases Manual. APHA Press, Washington, D.C.

Return to footnote 63 referrer

Footnote 64

Paules, C., and K. Subbarao. 2017. Influenza. Lancet. 390:697-708.

Return to footnote 64 referrer

Footnote 65

World Health Organization. 2022. Guidelines for the clinical management of severe illness from influenza virus infections. 2023. Available at https://apps.who.int/iris/bitstream/handle/10665/352453/9789240040816-eng.pdf?sequence=1&isAllowed=y.

Return to footnote 65 referrer

Footnote 66

Marjuki, H., V. P. Mishin, A. P. Chesnokov, J. Jones, J. A. De La Cruz, K. Sleeman, D. Tamura, H. T. Nguyen, H. -. Wu, F. -. Chang, M. -. Liu, A. M. Fry, N. J. Cox, J. M. Villanueva, C. T. Davis, and L. V. Gubareva. 2015. Characterization of drug-resistant influenza a(H7N9) variants isolated from an oseltamivir-treated patient in Taiwan. J. Infect. Dis. 211:249-257.

Return to footnote 66 referrer

Footnote 67

Block, S. S. 2001. Disinfection, sterilization, and preservation. Lippincott Williams & Wilkins, Philadelphia.

Return to footnote 67 referrer

Footnote 68

Canadian Food Inspection Agency. 2022. Cleaning and disinfection process for premises declared infected with highly pathogenic avian influenza (HPAI). 2023. Available at https://inspection.canada.ca/animal-health/terrestrial-animals/diseases/reportable/avian-influenza/cleaning-and-disinfection-hpai-/eng/1654910525183/1654910526144

Return to footnote 68 referrer

Footnote 69

Zou, S., J. Guo, R. Gao, L. Dong, J. Zhou, Y. Zhang, J. Dong, H. Bo, K. Qin, and Y. Shu. 2013. Inactivation of the novel avian influenza A (H7N9) virus under physical conditions or chemical agents treatment. Virol. J. 10:1-5.

Return to footnote 69 referrer

Footnote 70

Kurmi, B., H. V. Murugkar, S. Nagarajan, C. Tosh, S. C. Dubey, and M. Kumar. 2013. Survivability of highly pathogenic avian influenza H5N1 virus in poultry faeces at different temperatures. Indian J. Virol. 24:272-277.

Return to footnote 70 referrer

Footnote 71

Yamamoto, Y., K. Nakamura, and M. Mase. 2017. Survival of highly pathogenic avian influenza H5N1 virus in tissues derived from experimentally infected chickens. Appl. Environ. Microbiol. 83:1-8.

Return to footnote 71 referrer

Footnote 72

Bandou, R., R. Hirose, T. Nakaya, H. Miyazaki, N. Watanabe, T. Yoshida, T. Daidoji, Y. Itoh, and H. Ikegaya. 2022. Higher Viral Stability and Ethanol Resistance of Avian Influenza A(H5N1) Virus on Human Skin. Emerg. Infect. Dis. 28:639-649.

Return to footnote 72 referrer

Footnote 73

Centers of Disease Control and Prevention. 2023. Ask the Expert: Highly Pathogenic Avian Influenza A(H5N1) Viruses. Available at https://www.cdc.gov/flu/avianflu/spotlights/2022-2023/avian-flu-highly-pathogenic.htm.

Return to footnote 73 referrer

Footnote 74

U.S. Food and Drug Administration. 2021. AUDENZ. 2023. Available at https://www.fda.gov/vaccines-blood-biologics/audenz.

Return to footnote 74 referrer

Footnote 75

World Health Organization. 2021. Pandemic influenza preparedness Framework for the sharing of influenza viruses and access to vaccines and other benefits. Available at https://www.who.int/initiatives/pandemic-influenza-preparedness-framework.

Return to footnote 75 referrer

Footnote 76

Fries, L. F., G. E. Smith, and G. M. Glenn. 2013. A recombinant viruslike particle influenza A (H7N9) vaccine. New Engl. J. Med. 369:2564-2566.

Return to footnote 76 referrer

Footnote 77

Dong, J., Y. Zhou, J. Pu, and L. Liu. 2022. Status and Challenges for Vaccination against Avian H9N2 Influenza Virus in China. Life. 12:1-19.

Return to footnote 77 referrer

Footnote 78

Stephenson, I., K. G. Nicholson, R. Glück, R. Mischler, R. W. Newman, A. M. Palache, N. Q. Verlander, F. Warburton, J. M. Wood, and M. C. Zambon. 2003. Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: Phase I randomised trial. Lancet. 362:1959-1966.

Return to footnote 78 referrer

Footnote 79

Centers of Disease Control and Prevention. 2022. Interim Guidance on Influenza Antiviral Chemoprophylaxis of Persons Exposed to Birds with Influenza A Viruses Associated with Severe Human Disease or with the Potential to Cause Severe Human Disease. 2023. Available at https://www.cdc.gov/flu/avianflu/guidance-exposed-persons.htm.

Return to footnote 79 referrer

Footnote 80

Centers of Disease Control and Prevention. 2022. Interim Guidance on Follow-up of Close Contacts of Persons Infected with Novel Influenza A Viruses and Use of Antiviral Medications for Chemoprophylaxis. 2023. Available at https://www.cdc.gov/flu/avianflu/novel-av-chemoprophylaxis-guidance.htm.

Return to footnote 80 referrer

Footnote 81

Webster, R. G., J. Geraci, G. Petursson, and K. Skirnisson. 1981. Conjunctivitis in Human Beings Caused by Influenza A Virus of Seals. New Engl. J. Med. 304:911.

Return to footnote 81 referrer

Footnote 82

Centres of Disease Control and Prevention. 2020. Biosafety in Microbiological and Biomedical Laboratories (BMBL) 6th edition. U.S. Department of Health and Human Services, United States.

Return to footnote 82 referrer

Footnote 83

Government of Canada. 2009. Human Pathogens and Toxins Act. S.C. 2009, c. 24. Government of Canada, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009.

Return to footnote 83 referrer

Footnote 84

Public Health Agency of Canada. 2018. ePATHogen - Risk Group Database. 2023. Available at https://health.canada.ca/en/epathogen.

Return to footnote 84 referrer

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