Influenza virus type A: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Alphainfluenzavirus influenzae (excluding 1918 influenza A (H1N1) strain and subtypes H5, H7 and H9).

Agent type

Virus

Taxonomy

Family

Orthomyxoviridae

Genus

Alphainfluenzavirus

Species

influenzae

Synonym or cross-reference

Orthomyxovirus, Influenza virus type A, grippe, and fluFootnote 1.

Characteristics

Brief description

Members of the Orthomyxoviridae family are segmented, negative sense, single-stranded RNA virusesFootnote 1Footnote 2. Influenza virus particles are enveloped and spherical with a diameter of 80-120 nmFootnote 3Footnote 4. The genome is divided into 8 segments that code for 10 structural and 9 regulatory proteinsFootnote 4.

Properties

Type A influenza viruses are subdivided on the basis of the antigenic nature of their membrane-bound surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA)Footnote 4. To date, 18 HA, and 11 NA subtypes have been found to exist in natureFootnote 4. Of the 144 possible HA-NA combinations, over 120 have been identified. Most subtypes have been isolated in wild aquatic birds, swine, horses, dogs, and sealsFootnote 4. Antigenic alterations occur frequently in influenza HA and NA antigenic sites and are the key mechanism for virus adaptation to the host and for survival. Small alterations are referred to as antigenic drift, whereas larger alterations caused by reassortment are referred to as antigenic shift. Influenza pandemics may occur as a result of antigenic shifts if the mutation of the virus leads to efficient human-to-human transmissionFootnote 2Footnote 5. There are 3 primary hemagglutinin subtypes (H1, H2, H3) and 2 neuraminidase subtypes (N1 and N2) that have established stable lineages in the human populationFootnote 6. Although less common, subtypes H4, H5, H7, H9, H10 and H11, have been reported to cause human infection Footnote 7Footnote 8 Footnote 9Footnote 10, as well as subtypes N6, N7, N8, and N9Footnote 10Footnote 11Footnote 12. The RNA genome of the influenza A virus is prone to mutation and reassortment of RNA segments during co-infections due to the high error rate of the RNA-dependent RNA polymeraseFootnote 13. The acquired mutations can facilitate entry and infection in a new host or allow for resistance to treatmentFootnote 13.

Section II – Hazard identification

Pathogenicity and toxicity

An acute viral disease of the upper respiratory tract characterized by fever (temperature 37.8ºC or above), headache, myalgia, malaise, sore throat, non-productive cough, sneezing and nasal dischargeFootnote 14. Most individuals experience an abrupt onset of symptoms after exposure but recover within a weekFootnote 13. Those who are immunocompromised or at an increased risk of infection may experience symptoms that last for several weeks. Among children, otitis media, nausea and vomiting are commonly experiencedFootnote 15, and musculoskeletal complications including myositis and rhabdomyolysis have been reported to occurFootnote 13. Pulmonary complications of influenza include pneumonia (viral and bacterial), croup, asthma and bronchitisFootnote 15. Myocarditis and pericarditis are occasional cardiac complications. Neurological complications such as encephalopathy, encephalitis, seizures, and transverse myelitis have been reported to occur and can lead to serious sequelae or fatalityFootnote 13. Premature labour or fetal loss can occur in pregnant people. The severity of disease can range from asymptomatic to fatal. Fatality due to influenza is generally low, except in those with chronic lung or heart conditionsFootnote 1. It is estimated that each year there are millions of cases of influenza A related illness and over 300,000 deaths worldwideFootnote 13. Secondary bacterial pneumonia after influenza is a leading cause of mortality worldwideFootnote 16. Illness can occur in several species besides humans, including pigs, dogs, cats, horses, marine mammals, and birds, with waterfowl being the natural reservoir of influenza A virusesFootnote 13. Symptoms in poultry include decreased egg production, severe multisystem disease, and sudden death. Swine have been reported to experience nasal and ocular discharge, coughing, sneezing, lethargy, weight loss, paralysis, pneumonia, and deathFootnote 17.

Epidemiology

In Canada, influenza causes approximately 12,200 hospitalizations and 3,500 deaths per yearFootnote 18. It is estimated that there are approximately 300,000 deaths worldwide associated with influenza each yearFootnote 13.

Influenza can occur in pandemics and epidemics, localized outbreaks, and as sporadic casesFootnote 1. In temperate climates, epidemics of influenza typically occur during the late fall and winter seasonsFootnote 2Footnote 15, whereas in tropical and subtropical regions influenza epidemics occur throughout the yearFootnote 15. The high frequency of antigenic drifts or shifts in the influenza virus genome leads to epidemics by introducing virulence factors the population does not yet have immunity toFootnote 19. Historical evidence suggests that more severe, worldwide pandemics have occurred at 10 to 40 year intervals since the 16th centuryFootnote 2.

A pandemic that occurred in 1957-1958 (Asian flu) was caused by influenza virus A subtype H2N2, that resulted from the reassortment of circulating human H1N1 and avian H2N2 virusesFootnote 20 and is estimated to have caused 70,000 deaths in the United StatesFootnote 21.

Another influenza pandemic that occurred in 1968-1969 (Hong Kong flu), was caused by an H3N2 strain of influenza that was the result of a reassortment between circulating human H2N2 and avian H3Footnote 25 viruses and is estimated to have caused 34,000 deaths in the United StatesFootnote 26. Together, the Asian and Hong Kong flu pandemics resulted in 1 to 2 million deaths worldwideFootnote 22.

Since the Hong Kong flu (H3N2) pandemic, the number of influenza-associated hospitalizations has typically been greater during seasonal influenza epidemics caused by influenza A/H3N2 viruses than during seasons in which other influenza A virus subtypes have predominatedFootnote 21.

During the summer of 2002, an epidemic of respiratory illness with 22,646 cases and a 3% case-mortality affected Madagascar and was attributed to a strain of H3N2Footnote 23.

The 2009 H1N1 pandemic resulted in rates of infection ranging from 11% (New Zealand) to 21% (Pittsburgh, USA) of the population, depending on locationFootnote 24Footnote 25. As of March 13, 2010, the U.S. Centers for Disease Control and Prevention estimate that in the United States 60 million people were infected with 2009 H1N1, resulting in 270,000 hospitalizations and 12,270 deathsFootnote 26. Overall mortality rate was less than 0.5%, and morbidity and mortality were predominant in young adults and less common for adults over 60 years oldFootnote 27Footnote 28Footnote 29.

Between 2010 and 2020, the seasonal outbreaks with the highest hospitalization rate associated with the H2N3 strain and occurred in 2012-2013, 2014-2015, and 2017-2018Footnote 30. Influenza A subtypes H1N1 and H3N2 are still currently circulating in the human populationFootnote 31Footnote 35 and are included in current vaccinesFootnote 15.

Age is a significant factor as children younger than 5 years and people of 65 years or older are at risk for more severe diseaseFootnote 13. Immunocompromised people and long-term care facility residents are also at increased risk for influenza A complicationsFootnote 13. The following chronic comorbidities are commonly associated with more severe symptoms: pulmonary, cardiac, neurological, metabolic, and haematological issues, and extreme obesity. Bacterial, fungal, or viral co-infections can also lead to severe diseaseFootnote 13.

Host range

Natural host(s)

Bats are the natural reservoir for 2 hemagglutinin (HA) and 2 neuraminidase (NA) subtypesFootnote 32. The other 16 HA and 9 NA are found in aquatic birds such as ducks, geese, swans, shorebirds, gulls, and alcids. Humans, swine, horses, dogs, cats, marine mammals, and domestic avian species including chicken, quail, and turkey can also harbour the influenza A virusFootnote 1Footnote 2Footnote 37.

Other host(s)

Mice, guinea pigs, and ferrets are common experimentally infected hostsFootnote 33.

Infectious dose

Unknown for specific influenza A subtypes. The infectious dose for the influenza A variant, influenza A2, is greater than 790 viral particles via the nasopharyngeal routeFootnote 34. Influenza A (subtype not specified) is more infectious by aerosol inhalation (50% human infectious dose (HID50) = 0.6 and 3.0 median tissue culture infectious doses (TCID50)) than by intranasal drop inoculation (HID50 = 127 and 320 TCID50)Footnote 19Footnote 35. ID50 was evaluated for 2 viruses in 3 poultry speciesFootnote 36. The median infectious doses for H7N1 are 102.2, 104.6, and ≤104.2, in turkeys, chickens, and ducks, respectively.

Incubation period

Short, usually 1 to 4 daysFootnote 13.

Communicability

Transmission of influenza in humans can occur via respiratory infection by aerosols, droplets, or contact transmissionFootnote 1Footnote 37. Aerosols and droplets that are expelled when an infected individual coughs or sneezes can remain airborne for up to several hoursFootnote 38. Inhalation of the particles can lead to infection as they are deposited in the respiratory tract. Closed environment and crowds favour transmissionFootnote 1. Droplets can also land on surfaces and remain infectious for hours to daysFootnote 19. Transmission of influenza virus from donors who are shedding large amounts of virus can be infective for 2 to 8 hours via stainless steel surfaces, a few minutes via paper tissues, and up to 48 hours on non-porous surfaces in the environmentFootnote 18Footnote 19Footnote 39. Indirect contact via fomites to mucosal surfaces leads to transmissionFootnote 18Footnote 19Footnote 20.

Influenza A is highly communicable. Infected persons can shed detectable amounts of influenza virus the day before symptoms beginFootnote 40Footnote 41. Adults usually shed the virus for 3 to 5 days, while young children and immunocompromised patients shed for up to 7 daysFootnote 18Footnote 19Footnote 21Footnote 22.

Section III – Dissemination

Reservoir

Humans are the principal reservoir of human influenza A virusesFootnote 42. The avian reservoir of influenza A viruses is wild birds, predominantly ducks, geese, and shorebirds. Bats are the natural reservoir for 2 HA and 2 NA subtypesFootnote 24. Animal reservoirs are suspected as sources of new human subtypes. Influenza A viruses are also frequently isolated in pigs, horses, marine mammals, dogs, and catsFootnote 24Footnote 42. Swine have been demonstrated to have receptors for both human and avian influenza viruses and as such are considered a potential mixing vessel for human and avian virusesFootnote 42Footnote 43. Serosurveys suggest that cats and dogs have been infected with H9N2 influenza virus from poultry and have sporadically transmitted this strain to humansFootnote 24. The cross-species transmission of avian influenza viruses could result in a reassortment which may be infectious to humans with antigenic characteristics for which the current population is immunologically naïveFootnote 42.

Zoonosis

Transmission from pigs to man has been demonstratedFootnote 44. There are documented cases of human infections with swine influenza viruses, and zoonotic infection may occur frequently in those involved directly or indirectly in swine farming; however, the illness is mild and person-to-person transmission is very limitedFootnote 44. Transmission from avian species to humans has been documentedFootnote 19. Human cases of H5N1 and H7N9 are associated with exposure to infected poultry through live bird markets and by butchering or preparing ill birdsFootnote 19. Person-to-person transmission of H5N1 and H7N9 have been reported but not sustained.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

Seasonal influenza viruses are sensitive to the neuraminidase inhibitors oseltamivir (Tamiflu), zanamivir (Relenza), and amantadine and rimantadine, which inhibit the M2 ion channel protein activity and block viral uncoatingFootnote 45. Peramivir and laninamivir, intravenous neuraminidase inhibitors, and baloxavir, a polymerase inhibitor to block viral replication, are also used to treat seasonal influenzaFootnote 13. The 2009 H1N1 virus is susceptible to neuraminidase inhibitors, including oseltamivir (Tamiflu) and zanamivir (Relenza), but usually resistant to amantadine and rimantadineFootnote 29Footnote 46Footnote 47Footnote 48. Sporadic instances of oseltamivir-resistant 2009 H1N1 viruses have been documentedFootnote 29Footnote 32. Oseltamivir is licensed in Canada for treatment and post-expose prophylaxis, zanamivir for treatment alone, and amantadine for prophylaxis aloneFootnote 49. Baloxavir is licensed in Canada for individuals 12 years or olderFootnote 50. A single dose of baloxavir can be used as prophylaxis after exposure and can be used for treatment after infection, but it is not recommended for pregnant people or as a monotherapy for the immunocompromisedFootnote 13. Peramivir is approved for use in Canada for treatment of patients 18 years or older within 2 days of developing symptomsFootnote 50. Rimantadine and laninamivir are not currently licensed for use in CanadaFootnote 13Footnote 41.

A significant increase in resistance to oseltamivir and adamantanes (amantadine and rimantadine) was observed between 2007 and 2009Footnote 51. Since then, oseltamivir resistant viruses have been detected sporadically. Oseltamivir resistance occur more frequently in the H1N1 viral strain than the H3N2Footnote 13. Resistance to baloxavir has been reported, it is more common in Japan where it is used more frequently, among children, and in the H3N2 virusFootnote 13Footnote 51.

Susceptibility to disinfectants

Influenza A is susceptible to disinfectants including sodium hypochlorite (freshly made 1:10 dilution of bleach), 60 to 95% ethanol, 2% alkaline glutaraldehyde, 5 to 8% formalin, and 5% phenolFootnote 52. The H1N1 strain was inactivated after one minute of exposure to 70% 1-propanol, 0.1 mol/L NaOH, and a solution of 0.3% tri (n-butyl)-phosphate and 1.0% Triton X-100Footnote 53. Chlorine dioxide in a solution or gaseous form can be used to inactivate influenzaFootnote 54. A quaternary small molecule (QSM)-based sprayable coating was recently developed and shown to inactivate influenza strain H1N1 within 30 minutes on a variety of surfacesFootnote 55.

Physical inactivation

Susceptible to moist heat at 121ºC for 20 minutes or dry heat at 170ºC for 1 hour, 160ºC for 2 hours, or 121ºC for at least 16 hoursFootnote 52. UV-C light at 254 nm can be used to disinfect air of influenza particlesFootnote 56. 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 minute. The strains were also killed after 30 minutes of UV exposure, or at a pH of less than 2 for 0.5 hour or pH 3 for 24 hoursFootnote 57.

Survival outside host

Influenza A virus can survive for 24 to 48 hours on hard, nonporous surfaces such as stainless steel and plastic, and for approximately 8 to 12 hours on cloth, paper and tissuesFootnote 20.

Section V – First Aid/medical

Surveillance

Monitor for symptoms of influenzaFootnote 1Footnote 28. Clinical diagnosis of influenza A can be confirmed through testing of specimens collected via nasopharyngeal, nasal, or throat swabsFootnote 13. Diagnostic tests such as RT-PCR, molecular assays, immunofluorescence assays, or point-of-care testing can be usedFootnote 58. Laboratory confirmation of the virus is not routinely performed and consists of inoculating cell cultures with swabs or washings taken from the nose during the first days of illnessFootnote 1.

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

Influenza A can be treated with fluids and rest. Antiviral agents (mainly oseltamivir) can be employed to treat influenza AFootnote 15Footnote 16Footnote 26. Antibiotic treatment (in combination with antiviral treatment) may also be used to prevent or treat secondary bacterial pneumoniaFootnote 16.

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

The most effective strategy for reducing the effect of influenza is through annual vaccination using a live, attenuated influenza vaccine (LAIV) or an inactivated influenza vaccine (IIV)Footnote 15. Both LAIV and IIV contain strains of influenza viruses that are antigenically equivalent to the annually recommended strains: 1 influenza A (H3N2) virus, 1 influenza A (H1N1) virus and 1 influenza B virusFootnote 15Footnote 49. Each year, one or more virus strains might be changed on the basis of global surveillance for influenza viruses and the spread of new strainsFootnote 15. LAIV is administered intranasally by sprayer, whereas IIV is administered intramuscularly by injection. LAIV is currently approved only for use among healthy persons aged 2 to 59 yearsFootnote 59Footnote 60. In 2012, the first cell-based influenza vaccine was developed, followed by the first recombinant influenza vaccine in 2013Footnote 61. There are several recombinant vaccines in development. LAIV and IIV quadrivalent vaccines have been developed to include 2 influenza A and 2 influenza B targetsFootnote 61. The first mammalian cell culture-based inactivated influenza vaccine was authorized for use in Canada in 2019Footnote 60. In 2021, the first recombinant quadrivalent (Supemtek) vaccine was approved for use in Canada for people 18 years and olderFootnote 60. Supemtek, manufactured by Sanofi Pasteur, is currently the only recombinant vaccine licensed in Canada. There were 9 vaccines available for the 2022-2023 season in Canada. A nucleoside-modified messenger RNA lipid nanoparticle vaccine was recently developed that encodes hemagglutinin antigens from all known influenza A and B subtypesFootnote 62. It has been effective in protecting mice and ferrets when exposed to various influenza virus strains.

Vaccination is recommended for all individuals above 6 months of age, but particularly for those at a high risk of influenza-related complications or hospitalization and those capable of transmitting influenza to high risk individualsFootnote 60. Vaccination is not recommended for people who have had an anaphylactic reaction to a certain influenza immunization or for those who have developed Guillain-Barré Syndrome within 6 weeks of a previous influenza vaccination. LAIV should not be administered to people with immune compromising conditions or severe asthma, pregnant individuals, individuals between 2 and 17 that are receiving aspirin, and those who have taken antiviral agents within 48 hoursFootnote 60.

Injectable influenza vaccines are available for a number of animals including poultry, swine, equines and caninesFootnote 63Footnote 64Footnote 65. Immunization of horses has also been tested via intranasal and oral methodsFootnote 66.

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

Prophylaxis

Although vaccines are available for influenza, chemoprophylactic drugs may be considered in the control or prevention of influenzaFootnote 15. Antiviral prophylaxis must be initiated within 3 days of the detected illness of the index cases to be effective in slowing transmissionFootnote 26. Available drugs for prophylaxis are the neuraminidase inhibitors, zanamivir (10mg twice daily for 5 days), oseltamivir (75mg once daily for 7 to 10 days), or a single dose of baloxavirFootnote 13Footnote 15. The M2 inhibitor, amantadine can also be used for chemoprophylaxis during outbreaks of seasonal influenzaFootnote 15.

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

Fifteen reported cases up to 1974Footnote 67. Animal-associated infections are not reported; however, risk is high from infected ferretsFootnote 68.

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

Respiratory tissues, human secretions, and infected animals. In addition, the virus may be present in the intestines and cloacae of infected avian species. Influenza A may be disseminated in multiple organs in infected animal speciesFootnote 68.

Primary hazards

Inhalation of infectious material is the primary hazard associated with exposure to influenza A. Aerosols are generated when aspirating, dispensing, or mixing virus-infected samples (tissues, faeces, secretions) from infected animalsFootnote 68. Aerosols and droplets are also present after an infected individual coughs or sneezes and can remain airborne for up to several hoursFootnote 19. Inhalation of the particles can lead to infection as they are deposited in the respiratory tract. Infection can also occur from contact with mucous membranes. In a laboratory, direct inoculation of mucous membranes via virus contaminated gloves following the handling of tissues, feces and/or secretions from infected animals can occurFootnote 68.

Special hazards

Genetic manipulation of virus has an unknown potential for altering host range, pathogenicity, and/or for introducing transmissible viruses with novel antigenic composition into humansFootnote 69.

Section VII – Exposure controls/personal protection

Risk group classification

Influenza A is a Risk Group 2 (RG2) Human Pathogen and RG2 Animal Pathogen (excluding 1918 influenza A (H1N1) strain and subtypes H5, H7, and H9)Footnote 70. This risk group applies to the species as a whole and may not apply to every strain. Please consult the ePATHogen Risk Group Database for the risk group classification of a specific strain.

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 highly pathogenic avian influenza (HPAI) subtypes) involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

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 is to be followed. The personal protective equipment could include the use of a lab coat and closed-toes 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 are 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.

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 and work activities must be documented.

Other precautions

A biological safety cabinet (BSC) or other primary containment devices are to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

The 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.

For diagnostic laboratories handling primary specimens that may contain Influenza virus type A, the following resources may be consulted:

Section VIII – Handling and storage

Spills

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 before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials should 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).

Storage

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 must be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Influenza virus type A require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada. Certain strains of influenza virus type A are non-indigenous animal pathogens in Canada; therefore, importation of such strains requires an import permit, issued by the Canadian Food Inspection Agency. Please consult the ePATHogen Risk Group Database for additional information.

The following is a non-exhaustive list of applicable designations, regulation, or legislation:

Last file update

November, 2022

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

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Footnote 20

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Footnote 22

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Footnote 23

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Footnote 24

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Footnote 25

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Footnote 26

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Footnote 51

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Centers for Disease Control and Prevention (CDC). 2006. Instructions for Monitoring Health of Laboratory Workers and for Destroying Influenza A (H2N2) Samples.

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Jefri, U. H. N. M., A. Khan, Y. C. Lim, K. S. Lee, K. B. Liew, Y. W. Kassab, C. -. Choo, Y. M. Al-Worafi, L. C. Ming, and A. Kalusalingam. 2022. A systematic review on chlorine dioxide as a disinfectant. J Med Life. 15:313-318.

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Lee, B. Y., McGlone, S. M., Bailey, R. R., Wiringa, A. E., Zimmer, S. M., Smith, K. J., & Zimmerman, R. K. 2010. To test or to treat? An analysis of influenza testing and antiviral treatment strategies using economic computer modeling. PloS One.5 (6): e11284.

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Centers for Disease Control and Prevention (CDC). 2022. Live Attenuated Influenza Vaccine (LAIV)/Nasal Spray Vaccine. 2022:. Available at https://www.cdc.gov/flu/prevent/nasalspray.htm

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Government of Canada. 2022. Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine for 2022–2023. 2022:. Available at https://www.canada.ca/en/public-health/services/publications/vaccines-immunization/canadian-immunization-guide-statement-seasonal-influenza-vaccine-2022-2023.html#a8

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Carascal, M. B., R. D. N. Pavon, and W. L. Rivera. 2022. Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response. Front. Immunol. 13:.

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Arevalo, C. P., M. J. Bolton, V. L. Sage, N. Ye, C. Furey, H. Muramatsu, Mohamad-Gabriel Alameh, N. Pardi, E. M. Drapeau, K. Parkhouse, T. Garretson, J. S. Morris, L. H. Moncla, Y. K. Tam, H. Y. F. Steven, S. S. Lakdawala, D. Weissman, and S. E. Hensley. 2022. A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science. 378:899-904.

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Yoo, S. J., T. Kwon, and Y. S. Lyoo. 2018. Challenges of influenza A viruses in humans and animals and current animal vaccines as an effective control measure. Clin. Exp. Vaccine Res. 7:1-15.

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Malter, K. B., Tugel, M. E., Gil-Rodriguez, M., Guardia, G., Jackson, S. W., Ryan, W. G., & Moore, G. E. 2022. Variability in non-core vaccination rates of dogs and cats in veterinary clinics across the United States. Vaccine. 40(7): 1001–1009.

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Whitlock, F., Murcia, P. R., & Newton, J. R. 2022. A Review on Equine Influenza from a Human Influenza Perspective. Viruses. 14(6): 1312.

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Collins, C. H., & Kennedy, D. A. 1999. Laboratory acquired infections. Laboratory acquired infections: History, incidence, causes and prevention (4th ed., pp. 1-37). Woburn, MA: BH.

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