APPENDIX 1: Evidence Review on Occupational Exposure of Swine and Poultry Workers: An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI).

the national advisory Committee on immunization (naCi) provides the public Health agency of Canada (hereafter referred to as the agency) with ongoing and timely medical, scientific and public heath advice relating to immunization. the agency acknowledges that the advice and recommendations set out in this statement are based upon the best currently available scientific knowledge and is disseminating this document for information purposes. people administering the vaccine should also be aware of the contents of the relevant product monograph(s). naCi recommendations for use and other information set out herein may differ from that set out in the product monograph(s). manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. naCi members and liaison members conduct themselves within the context of the public Health agency of Canada’s policy on Conflict of interest, including yearly declaration of potential conflict of interest.


I.
Executive Summary in mid-2012, in response to the emergence of several swine variant influenza strains in humans in the united states of america (usa) (H3n2v, H1n1v, H1n2v) and in Canada (H1n1v) the public Health agency of Canada (pHaC) requested the influenza Working Group (iWG) of the national advisory Committee on immunization (naCi) to consider a recommendation for immunization of individuals with occupational exposure to swine and poultry. in Canada, naCi's process for development of influenza immunization recommendations takes into consideration a broad range of available studies and data to make evidence-based recommendations in the evaluation of the safety and efficacy of vaccines for humans. professional judgment, clinical experience and an overall analysis of risk also influences recommendations. For animal health concerns, the reader should refer to appropriate animal health resources.
to inform this discussion, pHaC and naCi iWG undertook various methods of exploring the question including scientific evidence, best practices, and expert opinion. this report outlines the process, studies, and data used by naCi to develop its recommendation for seasonal vaccination of swine and poultry workers. the evidence includes: • a rapid review conducted by the Canadian agency for drugs and technologies in Health titled "influenza Vaccination for prevention of Cross-species infection: a review of the Clinical evidence" • a literature review was conducted to identify the prevalence and risk of cross-species transmission of animal influenza a.
• a meeting with animal health experts to understand current vaccination practices of swine and poultry workers, the biosecurity measures used in the industry, and the risk of cross-species influenza transmission.

I.1 OvERvIEw Of majOR fInDIngS
• no studies were identified that examined the effectiveness of vaccination of swine and poultry workers on genetic reassortment of influenza virus.
• transmission of avian or swine influenza from animal populations to occupationally exposed humans occurs, but not frequently.
• occupationally exposed workers are more likely to be seropositive for avian or swine influenza than unexposed individuals.
• the potential for limited human-to-human transmission exists from infected workers to unexposed household members.
• there is a wide range of seasonal influenza vaccination rates among workers.
• most Canadian swine veterinarians are members of professional associations that already have position statements in favour of seasonal vaccination, and most veterinarians are aware of these recommendations.
• Canadian farms have strict bio-security measures that are their major means of avian/swine influenza prevention.

I.2 OvERvIEw Of majOR lITERaTuRE REvIEw lImITaTIOnS
• large amount of heterogeneity between studies impacted comparability • lack of standard testing protocols for seroresponse to non-human, non-H5n1 strains • studies use different titre cut-offs to identify a positive response • potential for waning immunity and/or cross-protection to impact detection • Cross-reactivity between swine, avian and human influenza viruses • many of the studies were cross-sectional seroprevalence surveys • prevalence of avian or swine influenza viruses in the animal populations or the region was usually not known or its presence was not confirmed • some studies established control groups, but there were comparability issues I.3 COnCluSIOnS after discussing the available body of evidence, naCi unanimously decided on the following recommendations: • "NACI concludes that there is insufficient evidence at this time to specifically recommend routine influenza immunization for swine workers (

II. Introduction
the genetic reassortment of influenza a viruses from different animal species is thought to be a mechanism for the development of influenza viruses with pandemic potential. Human influenzas and influenza viruses of avian and swine origin mostly circulate exclusively within their respective species. However, influenza viruses possess the ability to infect and potentially transmit themselves in species other than their native host. influenza a viruses are categorized based on combinations of the two surface proteins hemaglutinin and neuraminidase. in a statistical analysis of 3,874 full-length neuraminidase sequences (n1-n9), Yan et al. (2010) 1 found that there is greater intraspecies variation than inter-species variation in some host species. While a number of virus subtypes do not appear to be transmissible between species, some subtypes have a weak barrier, and some have virtually no barrier between species, in nature and in laboratory experiments.

II.1 EPIDEmIOlOgy Of anImal-ORIgIn InfluEnza vIRuSES
Humans working with live or dead animals that are also reservoirs for influenza, including, but not limited to, poultry and swine, are presumably at higher risk for infecting and being infected by the animals they work with due to their high degree of interaction. the role of animal-origin influenza viruses in causing human illness has been recognized for some time; however, it is unclear how frequently animal influenza viruses are transmitted to humans, or vice versa. the majority of existing surveillance systems are not set up to detect asymptomatic or mild illness in humans caused by human or animal influenzas. as well, swine influenza is not federally reportable in Canada and there is no national human surveillance systems set up to specifically identify swine origin influenza in humans. despite this, routine testing done in animals and humans does identify emergent influenza strains and some have generated significant interest. avian influenza has economic and health implications. notifiable avian influenza (nai) are identified as all H5 and H7 and any highly pathogenic avian influenza (Hpai) viruses. low pathogenicity avian influenza (lpai) viruses are associated with mild or no apparent disease in poultry. Hpai viruses can cause severe illness and high mortality in poultry flocks. extensive culling measures are usually taken to control nai viruses (naiVs), which can be devastating to poultry operations. Currently, the most prolific aiV is highly pathogenic H5n1. since its emergence in 1997, H5n1 has caused 371 deaths out of 622 confirmed human cases 2 (as of march 12, 2013) and has been heavily monitored as an influenza strain with pandemic potential. to date, however, it has yet to develop the capacity for efficient human-tohuman transmission, although it continues to have a high case fatality rate when contracted by humans.
surveillance of naiV is fairly well established. the Canadian notifiable avian influenza surveillance system (Cannaiss) is a joint initiative between government, industry and farmers to prevent, detect, and eliminate H5 and H7 aiV subtypes. Cannaiss meets the notifiable avian influenza guidelines established by the World organization for animal Health (oie) and trade requirements from the european union. 3 unlike aiVs, swine influenza viruses (swiVs) generally cause few deaths in pigs, but can cause high levels of illness in pig herds. swine are of particular interest in interspecies transmission of influenza because they possess receptors in the respiratory tract that allow them to contract both human and avian influenza viruses. transmission of influenza between swine and humans is known to occur, as is transmission from poultry to swine. swine have historically been considered the ideal mixing vessel for the production of novel viruses; however, recent research reveals that based on receptors alone, swine and humans are equally likely to act as mixing vessels for viral reassortment. 4,5 in Canada, there are no federal surveillance programs for the detection of influenza in swine, and existing provincial and territorial surveillance programs may vary. a voluntary swine influenza surveillance program was initiated in the us in 2008, operated through the united states department of agriculture in collaboration with states and industry. between october 1, 2010 through July 31, 2012, the program tested 12,662 samples taken from 3,766 swine diagnostic lab submissions (multiple samples from each submission), and found that 1,488 were positive for influenza a infections. 6

II.2 PanDEmIC RISk
an influenza pandemic is an unpredictable but recurring event that can have a significant impact on the population. 7 it occurs when a novel influenza virus, transmissible to and amongst humans, and against which humans have little to no immunologic protection, spreads widely across the world. since the 16 th century, pandemics have occurred at intervals of 10-50 years. 8 there is no way to predict when a novel influenza strain will emerge and become a pandemic concern, and how severe it may be. the H1n1 influenza strain in the 2009 pandemic was antigenically similar to H1n1 viruses circulating among north america swine, and distinct from seasonal human H1n1 viruses; its genome comprised a reassortment of genes of avian, human and swine origin influenza a viruses. 9 this highlights the role genetic reassortment plays in the evolution of pandemic influenza strains.

II.3 PuRPOSE
the objective of this review is to assess the body of evidence around the risk and prevalence of cross-species influenza transmission to and from humans. this review includes a rapid response report from the Canadian agency for drugs and technologies in Health, a literature review on cross-species influenza transmission, and a meeting with members of the avian Flu task Group from the joint committee of the Chief medical officers of Health, as well as the Chief Veterinary officers.

III.1 CaDTH RaPID RESPOnSE REPORT
in February 2012, pHaC requested that the Canadian agency for drugs and technologies in Health (CadtH) review the clinical evidence regarding the effectiveness of immunization of animal workers to reduce the risk of cross-species influenza infection in humans, and the risk of co-infection with human and animal influenza. there were two research questions: 1. What is the clinical evidence regarding the effectiveness of immunization of animal workers to reduce the risk of cross-species influenza infection in humans?
2. What is the clinical evidence regarding the effectiveness of immunization of animal workers to reduce the risk of co-infection with human and animal influenza? a limited literature search was conducted using pubmed, the Cochrane library, university of York Centre for reviews and dissemination databases, Canadian and major international health technology agencies, as well as a focused internet search. all study types were considered, and the search was limited to studies published in the english language between January 1, 2007 and January 11, 2012. For a more detailed methodology, please refer to the report. 10

III.2 lITERaTuRE REvIEw
two searches were conducted in each of the following four databases: medline, embase, Global Health, and agricola, for literature published in the english language up until July 3, 2012. the first search focused on swine or avian influenza infection in agricultural or farm workers who work with livestock, and the second search focused on crossspecies influenza infection. a total of 273 and 1163 articles were retrieved from the first and second searches respectively. the searches were kept broad to assess the size of the body of evidence that exists on the subject. Following this assessment, additional criteria were applied to narrow the scope of the review. the inclusion criteria for articles of interest were for those that involved crossspecies influenza infection to or from humans who raise and/or work with live or dead animals. articles were excluded if they were not conducting primary research, involved experimental influenza infection, conducted analysis for influenza strains native to the study population (e.g. avian influenza in poultry, human influenza in humans), or were published prior to the year 1997. please refer to appendix a for the evidence tables.
a rapid review limited to the english and French language was also conducted to determine which countries currently make an explicit recommendation for animal workers to receive the seasonal influenza vaccination (appendix b).

III.3 Iwg mEETIng wITH anImal HEalTH ExPERTS
the influenza Working Group (iWG) held an ad hoc meeting in december 2012 in order to discuss the current vaccination practices of swine and poultry workers, the biosecurity measures used in the industry, and risk of cross-species influenza transmission with members of the avian Flu task Group from the joint committee of the Chief medical officers of Health, as well as the Chief Veterinary officers. please refer to the discussion for further information.

Iv. Results
Iv.1 CaDTH RaPID RESPOnSE REPORT the literature search yielded a total of 219 citations, 215 of which were excluded after reviewing the titles and citations. Four potentially relevant articles under-went a full text review, as did an article identified in the grey literature. none of these five articles met the inclusion criteria. some studies examined the effect of influenza vaccines in the general population, healthy volunteers, children, older people, or focused on health care workers, but none focused on animal workers.

Iv.2 PHIwg lITERaTuRE REvIEw
a total of 44 articles meeting the inclusion and exclusion criteria were selected for the review. thirty-one articles assessed the seroprevalence of aiV in individuals occupationally exposed to poultry flocks or wild birds, and 13 articles assessed swiV in individuals occupationally exposed to swine. a broad range of individuals with the potential to be occupationally exposed to aiV or swiV were surveyed including backyard farmers, farmers or workers in commercial farm operations, cullers/ slaughterers, meat processors, veterinarians, laboratory analysts, researchers, government workers, 11 firefighters, 11 migratory bird handlers, and bird banders. in both avian and swine exposed individuals, immunological indications of cross-species infection were not detected at high frequencies. low levels of antibody response in the study population to an animal influenza were detected in a majority of the studies, although some may have been the result of cross-reactivity to exposure to human influenzas. a small number of studies also included an assessment of household members of individuals with confirmed aiV or swiV as study participants or as control groups.
Iv.2.1 Avian influenza virus in individuals occupationally exposed to poultry or wild birds of the 31 articles assessing the seroprevalence of aiV in humans, eight assessed seroprevalence of aiV in cullers, slaughterers or individuals collecting dead birds. 11-17 eighteen articles assessed commercial poultry workers, seven articles assessed non-commercial poultry workers (i.e. backyard farmers), and four studies assessed other workers including bird banders, 18 handlers of migratory birds, 19 firefighters, 11 and government workers 11 involving in culling.
of the 18 articles involving commercial poultry workers, eight articles considered an individual seropositive if antibody titres were at least ≥1:10. another eight articles characterized seropositivity with titers at least ≥1:80. one article had undisclosed seropositivity conditions, and another article collected information on symptoms only. noting the difference in use of titre thresholds is important as at present, a titre of ≥1:80 is the recommended threshold for assessing potential H5n1 infection. no other recommendations exist for other avian influenza strains, although some articles used the H5n1 recommendations as a guideline for their laboratory tests. a few of the other studies used a threshold of ≥1:80, but these were grouped with the 1:80 studies for comparative purposes.
overall, the seroprevalence of aiV was typically low (<1% of participants), but some serological activity was detected in a majority of the studies. two articles using an antibody titre threshold ≤1:80 did not find any evidence of serological activity. Four articles using a threshold of ≥1:80 reported having participants with low levels of serological activity, but none met the conditions for seropositivity.
in the small number of studies assessing both poultry workers and cullers, cullers constituted the majority of seropositive cases. alizadeh et al (2009)  among studies looking at non-commercial poultry workers (i.e. backyard farmers), four of the seven studies found low levels of serological activity to aiV, but the remaining three did not.
the four studies investigating aiV in other workers (i.e. non-farming) demonstrated serological activity against aiV in a small number of their participants.

Iv.2.2 secondary transmission of AIv
Four of the 30 avian studies tested household contacts of workers for potential aiV infection. among 28 family members of five confirmed H5n1 cases, only one individual produced a positive sample by mn assay. 21 in another study, 56 out of 62 household members (who had no exposure to poultry) of poultry workers with confirmed a/ H7n7 submitted a serum sample at least three weeks after diagnosis of the primary case. of the 62 individuals, eight reported health complaints and two met the case definitions for both conjunctivitis and ili. of the 56 individuals who provided a serum sample, 33 had detectable antibodies against H7. 22 a sample of workers taken from an existing agricultural Health survey being conducted in iowa used the unexposed spouses of the rural agriculture workers exposed to poultry as their comparison group. over a 24 month period, three individuals in the control group demonstrated titre levels ≥1:20 for H4, H5, H6, and H9. one individual had a titre of ≥1:80 to H9. 23 outbreak surveillance during an H7 outbreak in the netherlands in 2003 confirmed a/H7 in three household contacts of a poultry worker or farmer. 24 Iv.2.3 swine influenza virus in individuals occupationally exposed to swine thirteen of the 43 articles assessed the seroprevalence of swiV in humans. eleven studies were conducted in workers from commercial farms, and two studies were conducted in community farms. seropositive individuals were detected in all studies, and Gray et al (2007) was able to isolate swiV from a symptomatic individual. 25 the number of individuals found to be seropositive to at least one swiV ranged between 1-2 individuals to up to 47 individuals, depending on the study.
beaudoin et al (2010) compared employees from two large, comparable swine farms, where one farm was known to have H2n3-positive swine. Four participants were H2n3 positive, only one of which worked on the exposed farm. it was postulated that seropositivity may have been unrelated to recent exposure. three of the four participants were born before 1968, with the individual who worked on the exposed farm born in 1949; serological activity could be the result of cross-reactivity to previously circulating human H2n3.
although individuals with swine exposure did produce a greater serological response, Gerloff et al (2011) 26 did not detect a statistically significant difference between the serological responses of healthy individuals with past or present professional exposure to swine and control serum samples from the general population.

Iv.2.4 secondary transmission of swIv
two articles evaluated potential household transmission of swiV from workers. using a sample of swine workers and their unexposed spouses from the iowa agriculture Health survey, spouses were at an increased risk for H1n1 swiV compared to unexposed university controls, with adjusted odds ratio of 28.2 (95% Ci: 6.1, 130.1). swine workers had an adjusted odds ratio of 54.9 (95% Ci: 12.0, 232.6). 25 robinson et al (2007) 27 investigated members of a communal farm where an infant had been hospitalized due to a swine-related influenza virus (confirmed). eight members from three households (including four members from the household of the index patient) were seropositive (titres ≥32). most had no exposure to swine or <1 hour per week of exposure. one of ten swine serum samples tested was seropositive for the same strain that infected the index patient. 27 Iv.2.5 Influenza vaccination among all occupationally exposed individuals information on vaccination history was collected in 22 of the studies and results ranged from workers receiving seasonal influenza in the past year, to never having received seasonal influenza vaccine. one study asked specifically about receiving the 1976 swine influenza vaccine. Vaccination rates ranged from 0 to approximately 60% in the study population. in control groups, vaccination rates were as high as 76%. 18 the wide variation in vaccination rates can potentially be attributed to factors such as vaccine access, living in an urban or rural region, keeping a backyard farm or working on a commercial farm.

Iv.2.6 Existing influenza vaccination recommendations for occupationally exposed individuals
From a rapid review limited to the english and French language, a small number of countries have existing national recommendations for seasonal influenza vaccination that specifically mention workers with occupational exposure to animals (appendix b).
in Canada, naCi recommends that people in direct contact with infected poultry during culling operations, such as cullers, supervising veterinarians and inspectors, receive influenza vaccination. the Canadian Food inspection agency (CFia) uses the broader naCi statement that encourages all healthy Canadians aged 6 months and older get the seasonal vaccine, to encourage all individuals involved in the food production system (e.g. producers and their families, farm workers, veterinarians, farm service personnel, people visiting swine operations) to receive the vaccine as a biosecurity measure.
in the united states, the Centers for disease Control and prevention (CdC) issued a statement in 2010 that made a universal recommendation for seasonal influenza vaccination which also explicitly recommended that persons who are charged with responding to avian influenza outbreaks in poultry receive the seasonal influenza vaccine. 28 the 2012 update to the statement did not address this recommendation. 29 With the recent activity involving the 2011 H3n2 variant virus, the CdC released interim guidance for workers employed at commercial swine farms recommending seasonal influenza vaccination for the purposes of reducing the risk of transmitting seasonal influenza viruses from ill people to pigs. 30 in australia, the australian immunisation Handbook recommends seasonal influenza vaccination during confirmed avian influenza activity to individuals involved in the commercial poultry industry or in culling. However, this recommendation is not stated in the annual seasonal influenza statements produced by the australian technical advisory Group on immunisation (ataGi).
the Hong Kong department of Health recommends seasonal influenza vaccine for poultry farmers and additionally to pig farmers and individuals in the pigslaughtering industry.
beginning in the 2006/07 season, an annual seasonal influenza program was implemented in the united Kingdom for poultry workers. However, because of difficulties running the program and low vaccine uptake, the program ended after the 2010/11 season. the recommendation for vaccinating poultry workers, considered a low priority group, was also rescinded. swine workers were assessed in 2006 and 2009 as a potential target group for vaccination, but no recommendation has been made by the Joint Committee on Vaccination and immunisation due to limited evidence.
the number of countries sampled was limited by the language restrictions placed on the search. an analysis was conducted by the Vaccine european new integrated Collaboration effort project of national influenza vaccination polices across the european union, norway and iceland in 2009. 31 of the 27 countries surveyed, 13 (48%) recommended seasonal influenza vaccine for workers in the poultry industry, and 9 (33%) recommended vaccination for individuals in veterinary services. in a second survey, to which 26 countries responded, 4 countries (15%) recommend that families raising poultry also receive the influenza vaccine. However, recommendations are often in flux and the authors noted that several countries had modified their vaccination policies since the initial surveys were conducted.

Iv.3 Iwg mEETIng wITH anImal HEalTH ExPERTS
the iWG held an ad hoc meeting in december 2012 in order to discuss the current vaccination practices of swine and poultry workers, the biosecurity measures used in the industry, and risk of cross-species influenza transmission with members of the avian Flu task Group from the joint committee of the Chief medical officers of Health, as well as the Chief Veterinary officers. the following is a synopsis of that discussion. 32,33 most Canadian swine veterinarians are members of professional associations that already have position statements in favour of seasonal vaccination, and most veterinarians are aware of these recommendations. the uptake is unknown, however. the Canadian swine Health board issued a press release encouraging all barn staff and veterinarians to be vaccinated. they held a vaccination clinic at their october 2012 meeting, and some Canadian swine workers are aware of the board's encouragement to have their influenza vaccination.
many larger farms in the swine industry already require their staff to be vaccinated against influenza, but it is difficult to mandate and so, in general, they make recommendations, offer vaccination clinics and try to educate staff. after H1n1, it has become more widely accepted that humans may be a source of influenza infection for swine. some swine farms now will not allow people to enter the barns if they have symptoms of influenza like illness.
the way humans and pigs interact in Canada is slightly different than the way they interact in the usa. Canada has a smaller pig industry, a smaller human population, and fewer farm fairs. as a result, there are fewer human-swine interactions involving the general public. Canadian farms generally have stricter biosecurity measures and most swine are confined to the indoors all year due to the colder weather. many areas vaccinate their swine, although not always on an annual basis due to cost. swine influenza strains do not tend to change rapidly from year to year in many regions of Canada. However in areas where high numbers of pigs are produced in large farming systems, influenza strains change rapidly, often requiring autogenous vaccination to control symptoms. this is a more common scenario in the usa with its much larger pig production industry. swine vaccines have the same efficacy challenges as those made for humans; they do not induce protection against other influenza virus strains that can affect the herd. in regions where farms are more spread out, there is less swine influenza virus transmission than in regions where farms are located closer together. there are much regional variation in the distance between farms across both the usa and Canada.
bio-security is the major means of prevention of avian influenzas as well. notifiable avian influenza is reportable in Canada and there is surveillance and the authority to respond if an outbreak is detected, regardless of the pathogenicity. some producers have their own recommendation that a worker be vaccinated before starting to work with poultry, but these recommendations are not mandatory. in contrast to swine, influenza viruses are not routinely found in commercial poultry in Canada. birds are not as susceptible to infection with human influenza viruses due to differences between avian and mammalian receptors. mammals (e.g. swine, ferrets, dogs, cats) are more likely to share influenza viruses with humans.
there is also a growing segment of the human population in both Canada and the usa that is raising pigs and poultry on a smaller scale outside of the commercial industry. these are often referred to as "backyard producers" and usually sell their products at local farmer's markets or directly to the public. they frequently advertise their products as being healthier than products from the commercial industry, and thus do not always see a need for biosecurity or disease control. these producers may not be as well informed about biosecurity or disease, and often apply fewer biosecurity measures. the general public often can directly contact the live animals on these farms. because this segment is not represented by an industry organization, they can be more difficult to reach and educate.
v. Discussion the rapid response report conducted by CadtH was based upon a limited literature search and was not a comprehensive, systematic review. it did provide a summary of the current lack of evidence on the topic of influenza vaccination of animal workers for prevention of cross-species infection. as there is no evidence, no conclusions can be drawn regarding the effectiveness of vaccinating this group of workers. the transmission of avian and swine influenza to the humans that handle these animals is documented in the literature, but because of a number of study limitations, the true extent of the burden of cross-species transmission is difficult to determine.
one limitation of the literature review is due to the fact that standard testing protocols for assessing human immune response to influenza strains that have not adapted to human-to-human transmission do not exist, with the exception of H5n1. 34 this is a significant issue impacting study comparability as authors take different approaches to assess immunological outcomes. some authors assume that an individual infected with an animal influenza strain would generate low antibody titres that return to preinfection levels within a short period of time. in these cases, lower cut-offs were used to determine seropositivity (e.g. titres ≥1:10 or ≥1:20). other studies used existing testing protocols as a guideline, and used higher cut-offs (e.g. titres ≥1:80 or ≥1:160), which could potentially underestimate the frequency of cross-species infection.
the type of assay used to titre antibody responses also affects results. mn assays were considered by some studies to be the preferred assay for assessing seroresponse because it is highly sensitive and specific. almost all studies used the hemaglutination inhibition (Hi) assay, 35 but varied the erythrocyte species used. the Hi assay is strain dependent, and if there is a mismatch between the assay and sample strains, the assay is limited in its ability to detect an immune response in an individual who was otherwise infected and capable of mounting a response.
Cross-reactivity between swine, avian and human influenza viruses is another confounding factor that only one study accounted for, which may lead to an erroneous increase in positive results. it can be difficult to identify the potential cross-reactions that could occur, thereby limiting the ability to tease out the impact it may have on the outcome. Cross-reactivity may be more significant in swiV-related studies. although there were a limited number of studies, seroresponse to swiV appeared to be more prevalent than seroresponse to aiV. one study noted that age may be a factor as older individuals may have acquired immunity to influenza strains of interest that possibly re-emerged after a dormant period, 36 and another alluded to the role of influenza vaccination causing cross-reactions during testing.
the discussion with the members of the avian Flu task Group and the Chief Veterinary officers indicated that there are current seasonal vaccination recommendations in place by the various professional associations, and that most veterinarians are aware of these recommendations. the uptake, however, is unknown. the strict biosecurity measures in Canada are the major means of prevention of avian and swine influenza infection.

vI. Recommendations/Rationale
direct contact with infected poultry, or surfaces and objects contaminated by their droppings, is currently considered the primary route through which workers become infected with avian influenza. as cullers are in an environment with a high concentration of infected poultry, surfaces and objects, this presents an opportunistic setting for viral transmission. infected poultry can shed large quantities of virus in their droppings and respiratory secretions, and the culling process may result in a higher than normal exposure to these secretions. influenza is endemic to the swine population and infections are often mild or asymptomatic. swine and poultry workers are not likely to experience the same intensity of exposure to virus particles as are cullers. it was noted in the literature review that poultry cullers had more frequent positive serology results against avian influenza than other poultry workers. For these reasons, the recommendations for poultry works involved in culling operations differ from those made for poultry and swine workers.

vI.1 POulTRy wORkERS
NACI continues to recommend immunization against seasonal influenza for people in direct contact during culling operations involving poultry infected with avian influenza (NACI recommendation grade I); however NACI encourages influenza vaccine for all Canadians age 6 months and older.
based on a review of the literature and a discussion with animal health experts, naCi has concluded that there is no direct evidence of the efficacy of vaccinating poultry workers to prevent reassortment of avian and seasonal human strains in humans leading to emergence of pandemic viruses. However, the literature documents the transmission of avian influenza to humans that manipulate poultry as a food source. the contact is usually close and sustained with the animal (for example, culling); and the risk of transmission is relatively low. in the small number of studies that assessed both poultry workers and cullers, cullers constituted the majority of the seropositive cases. it can be hypothesized that contact between a worker involved in culling poultry that are infected with avian influenza would be more prolonged and significant than other types of contact with poultry.
there is evidence that avian and human viruses can reassort and that this reassortment can occur in humans. influenza does not usually circulate in commercial poultry in Canada and all highly pathogenic avian and any avian strain of H5, H7 are reportable in Canada according to the animal health experts that naCi consulted. many jurisdictions internationally have a similar recommendation. based on what is currently known about influenza viruses and reassortment, naCi is of the opinion that immunizing poultry workers against seasonal influenza could prevent reassortment in humans between the avian strain in an outbreak and seasonal strains in humans. However, given the variable efficacy of the seasonal influenza vaccine in healthy adults and in adults with chronic health conditions, the two week period from immunization to development of immunity and the theoretical benefit, seasonal influenza immunization to prevent reassortment of viral strains should be used as a complementary measure to other biosecurity measures that have been described elsewhere (e.g. antivirals and personal protective equipment). 37 also, seasonal influenza vaccine should not be expected to be efficacious against avian strains of influenza given the significant antigenic difference between strains (e.g. H7n3, H9n2).

vI.2 SwInE wORkERS
NACI concludes that there is insufficient evidence at this time to specifically recommend routine influenza immunization for swine workers (NACI recommendation grade I); however NACI encourages influenza vaccine for all Canadians age 6 months and older.
based on a review of the literature and a discussion with animal health experts, naCi has concluded that there is currently no direct evidence that immunizing these workers would prevent the emergence of pandemic strains. this would also not be feasible to study. However, based on what is known about transmission and reassortment of swine and human strains, from a theoretical perspective there could be a benefit.
notwithstanding this statement, naCi continues to encourage influenza vaccine for all Canadians six months of age and older to provide protection to those who wish to take advantage of this vaccine.
the provision of recommendations regarding immunization of swine workers as a means to protect swine herds is not within the scope of naCi. For animal health concerns, the reader should refer to appropriate animal health resources.
objectives of immunization of swine workers against seasonal influenza can vary: • protecting the herds against human strains of influenza; • protecting the workers against antigenically related emerging swine strains; and/or • preventing reassortment of swine and human strains into pandemic strains.
the burden of transmission between swine and workers in Canada is not well known. unlike influenza outbreaks in poultry, swine outbreaks of influenza are not reportable in Canada. one study carried out in alberta in a limited number of commercial farms concluded that the transmission risk from swine to workers and vice versa was low. 38 according to the animal experts with whom naCi consulted, farming operations in Canada involving swine usually apply several biosecurity measures. However, the protection attributable to the human vaccine compared to the other biosecurity measures is unknown. also, compared to other jurisdictions, the opportunity for direct contact between live swine and the general public is limited in Canada. However, not all farms will apply biosecurity measures equally and there will be some unprotected workers exposed directly to swine in close quarters on a daily basis in Canada. transmission of swine virus variants to swine workers and their close contacts has been documented in the literature. because many influenza infections in humans and swine are likely not reported or confirmed, transmission may be underreported in the literature. in conclusion, the risk of influenza transmission between people and swine is likely low for the general public in Canada. swine workers in both commercial and backyard operations will be at a higher risk than the general public.
Few countries have implemented a recommendation for the seasonal vaccination of swine workers. during the 2006/2007 influenza season, the united Kingdom implemented an annual seasonal influenza program for poultry workers, but the program ended after the 2010/2011 season due to logistical issues, low vaccine uptake, and the consideration that poultry workers are seen as a low priority group. in Canada, recommendations vary: some provinces currently recommend immunization of swine workers; one province recommends against immunization, and one province had a recommendation and then removed it following studies in 2009 that showed an association between receipt of seasonal immunization and infection with pandemic H1n1 strain. 39 some studies have shown similar results in ferrets and swine after receiving a seasonal vaccine and being challenged with the pandemic H1n1 2009 strain. 40,41 CFia recommends immunization of swine workers against seasonal influenza. one reason for this is to protect the herds against infection with human influenza strains. However, this is outside of the scope of naCi.
in the context of the emergence of a swine variant virus, the effectiveness of influenza immunization of swine workers would largely depend on the antigenic similarity between the emergent strain and the seasonal influenza vaccine formulation available that particular season.
naCi concludes that with the emergence of a swine variant virus, the virulence of the disease for both swine and humans and vaccine effectiveness in humans are likely to vary and would need to be assessed on a case by case basis to determine if the risk benefit profile favors an immunization recommendation.
Finally, the safety of the influenza vaccine has been documented in adults and important adverse events are quite uncommon, the most common side effect being minor pain at the site of injection for a few days following intra muscular injection. the safety section of the 2013-2014 influenza statement can be consulted for more details about the safety of these vaccines.
(2) World Health organization. Cumulative number of confirmed human cases of avian influenza a(H5n1) reported to WHo, 2013 www.who.int/influenza/ human_animal_interface/H5n1_cumulative_table_ archives/en. Hi (CdC protocol, guinea pig rbC used for human strains and turkey rbC used for swine strains; positive at titres ≥1:40 considered initially, but spectrum also evaluated) >90% aHs swine-exposed individuals have worked with swine for >10 years at enrollment: swine-exposed had higher titres against swine influenza subtypes of H1n1 than other groups Compared to university controls, swine-exposed had increased risk for swine H1n1 adjusted or 54.9 (13.0, 232.6); non-swine exposed had adjusted or of 28. II-1 evidence from controlled trial(s) without randomization.
II-2 evidence from cohort or case-control analytic studies, preferably from more than one centre or research group using clinical outcome measures of vaccine efficacy.
II-3 evidence obtained from multiple time series with or without the intervention. dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.
III opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.
QualITy (InTERnal valIDITy) RaTIng Of EvIDEnCE good a study (including meta-analyses or systematic reviews) that meets all design-specific criteria* well.
fair a study (including meta-analyses or systematic reviews) that does not meet (or it is not clear that it meets) at least one design-specific criterion* but has no known "fatal flaw".
Poor a study (including meta-analyses or systematic reviews) that has at least one design-specific* "fatal flaw", or an accumulation of lesser flaws to the extent that the results of the study are not deemed able to inform recommendations.
* General design specific criteria are outlined in Harris et al., 2001. 73 appendix B: national seasonal influenza vaccination recommendations for workers occupationally exposed to animals Country Organization Recommendation Reference Canada public Health agency of Canada-national advisory Committee on immunization (pHaC-naCi) people in direct contact during culling operations involving poultry infected with avian influenza direct involvement may be defined as sufficient contact with infected poultry to allow transmission of avian virus to the exposed person. the relevant individuals include those performing the cull, as well as others who may be directly exposed to the avian virus, such as supervising veterinarians and inspectors.
an advisory Committee statement (aCs). national advisory Committee on immunization (naCi): statement on seasonal influenza Vaccine for 2011-2012 Canadian Food inspection agency (CFia) Vaccination for those involved in the food production system for biosecurity.
(CFia uses the naCi statement that all healthy Canadians get the seasonal vaccine as the rationale for producers and their families, farm workers, veterinarians, farm service personnel (including feed truck drivers and vaccination and insemination crews), and other people visiting swine operations to get seasonal vaccine.) CFia website on animal biosecurity ww.inspection.gc.ca/english/anima/ biosec/20111207inde.shtml australia national Health and medical research Council, department of Health and ageing people involved in the commercial poultry industry or in culling poultry during confirmed avian influenza activity.
Vaccination using the current influenza season vaccine composition is recommended for poultry workers and others in regular close contact with poultry during an avian influenza outbreak. although routine influenza vaccine does not protect against avian influenza, there is a possibility that a person who was infected at the same time with avian and human strains of influenza virus could allow reassortment of the 2 strains to form a virulent strain that could spread from human to human (ie. initiate a pandemic