Eurosurveillance banner

Read our articles on the ongoing Ebola outbreak in West Africa

Follow Eurosurveillance on Twitter: @Eurosurveillanc

In this issue

Home Eurosurveillance Edition  2014: Volume 19/ Issue 18 Article 2 Printer friendly version
Back to Table of Contents
Previous Download (pdf) Next

Eurosurveillance, Volume 19, Issue 18, 08 May 2014
Review articles
Influenza at the animal–human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)
  1. National Institute for Public Health and the Environment (RIVM), Centre for Infectious Diseases Research, Diagnostics and Screening (IDS), Bilthoven, the Netherlands
  2. Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
  3. Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), OIE/FAO and National Reference Laboratory for Newcastle Disease and Avian Influenza, OIE Collaborating Centre for Diseases at the Human–Animal Interface, Padova, Italy
  4. Animal Health and Veterinary Agency (AHVLA), Surrey, United Kingdom
  5. Royal Veterinary College (RVC), London, United Kingdom
  6. United Nations Food and Agricultural Organization (FAO), Rome, Italy
  7. Institut Pasteur, Paris, France
  8. Universtiy of Ghent, Ghent, Belgium

Citation style for this article: Freidl GS, Meijer A, de Bruin E, de Nardi M, Munoz O, Capua I, Breed AC, Harris K, Hill A, Kosmider R, Banks J, von Dobschuetz S, Stark K, Wieland B, Stevens K, van der Werf S, Enouf V, van der Meulen K, Van Reeth K, Dauphin G, Koopmans M, FLURISK Consortium. Influenza at the animal–human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1). Euro Surveill. 2014;19(18):pii=20793. Available online:
Date of submission: 01 August 2013

Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of the World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure.


Influenza virus type A, a member of the family Orthomyxoviridae, is an enveloped virus with a negative-sense, single-stranded RNA genome organised in eight gene segments, which encode at least eleven proteins. Antigenic and genetic diversity of two surface glycoproteins, haemagglutinin (HA) and neuraminidase (NA), is used to classify type A influenza viruses into subtypes; 18 HA and 11 NA subtypes are known to date [1-5]. Water- and shorebirds were identified as reservoirs harbouring all subtypes, except A(H17N10) and A(H18N11) of which RNA was recently detected in bats from Guatemala and Peru, respectively [2,3]. Reservoir animals typically do not display symptoms. In contrast, the diversity of influenza viruses in mammalian hosts is limited to specific subtypes. Human-adapted seasonal influenza viruses since the beginning of the 20th century have had HA subtypes H1, H2 and H3, combined with NA subtypes N1 and N2.

The segmented nature of the genome facilitates the exchange of genetic material if a host is co-infected with two genetically different type A influenza viruses. This reassortment process, also known as antigenic shift if it involves the gene segment encoding the HA, can result in the generation of viruses with surface antigens against which the human population may not have pre-existing, protective antibodies. Additional flexibility is conferred by the accumulation of mutations during replication, potentially resulting in amino acid substitutions that can affect pre-existing immunity if the HA is involved (antigenic drift), host range, virulence, and other factors [6]. If this results in sustained human-to-human transmission of a virus against which a large proportion of the world’s human population is immunologically naïve a pandemic can develop resulting in a large number of human cases occurring simultaneously worldwide [7,8]. Such novel introductions of reassorted viruses were at the root of four influenza pandemics in the last 100 years, and claimed the lives of millions of people, namely the 'Spanish flu' A(H1N1) in 1918, the 'Asian flu' A(H2N2) in 1957, the 'Hong Kong flu' A(H3N2) in 1968, and the recent pandemic caused by influenza A(H1N1)pdm09 in 2009 [9,10]. Influenza A(H1N1)pdm09 has replaced previous human seasonal A(H1N1) viruses [11] and, together with A(H3N2) and influenza B viruses, has been causing seasonal influenza epidemics in humans since 2009. With the emergence of the influenza A(H3N2) pandemic in 1968, influenza A(H2N2) viruses ceased to circulate in humans, but H2 subtypes are still present in birds and were also recently isolated from diseased swine [12,13].

The factors that determine whether an animal influenza virus may acquire the ability to efficiently spread among humans are poorly understood [14]. Reassortment is not a necessary prerequisite for human infection, and there is clear documentation of direct transmission and human disease caused by animal influenza viruses, in particular avian (AIV) and swine (SIV) influenza viruses , such as AIV A(H5N1), A(H9N2) and various H7 subtypes, as well as European avian-like SIV A(H1N1) [15-22]. Early detection and in-depth investigation of such events may provide clues for (future) risk assessment of animal-to-human transmissions.

This review was conducted under the framework of the FLURISK project funded by the European Food Safety Authority (EFSA). The main objective of FLURISK is the development of an evidence-based influenza risk assessment framework (IRAF) to assess the potential of animal influenza viruses to cross the species barrier and cause sustained infections in humans. The work presented here aims at describing available evidence for animal-to-human influenza virus transmissions.


Search strategy
We performed a literature search using Medline, Embase, SciSearch and CabAbstracts. Search terms included 'influenza', 'influenza virus', 'animals', 'swine', 'birds', 'poultry', 'wild bird', 'water bird', 'waterfowl', 'goose', 'duck', 'chicken', 'turkey', 'environment', 'animal-to-human',
'transmission-to-humans', 'interspecies transmission', 'human', 'case', 'seroprevalence', 'serosurveillance', 'prevalence', 'incidence', 'risk factor', 'exposure' and various subtypes of influenza virus; the terms were used alone or in combinations using Boolean operators. Full search details are available from the corresponding author on request. Only articles published in English were included and the search covered all years available in the respective databases, Medline from 1946, Embase from 1947, SciSearch from 1980, CabAbstracts from 1973, all up to February 2012. The search algorithm automatically discarded duplicates. Newly published evidence that came to our attention between February 2012 and January 2014 was also included. Case counts of avian influenza A(H7N9) and A(H5N1) cases were updated on 31 January 2014 based on the latest figures reported by the European Centre for Disease Prevention and Control (ECDC) [23] and by the World Health Organization (WHO) [24]. Case counts of human infections with swine influenza variant A(H3N2)v were retrieved on 31 January 2014 from the website of the United States (US) Centers for Disease Control and Prevention (CDC) as posted on 18 October 2013 [25. Grey literature was searched in a non- systematic way.

Inclusion and exclusion criteria
Included were papers indicating evidence of human infection with animal influenza viruses (selection criterion 1, Figure 1). Two investigators first screened all papers by title and, when necessary, by abstract. All articles meeting this first criterion were reviewed for details of the methods used to diagnose the infection. Experimental and observational studies describing human infection with animal influenza viruses other than influenza A(H5N1) were included. Articles solely describing human infection with A(H5N1) were excluded, and for influenza A(H5N1) and A(H7N9), the official WHO and ECDC statistics from notifications under the International Health Regulations were used for completeness. Commentaries, reviews, articles dealing with influenza in animals only, studies solely assessing human-to-human transmission of an animal influenza virus (i.e. most of the literature on influenza A(H1N1)pdm09), and articles referring to study subjects described in prior original publications were excluded (selection criterion 2, Figure 1). Studies based on serological evidence only were excluded to ensure high specificity of the findings. Papers were screened for information on the time period when the study was conducted, total number of people sampled, patient information, nature of exposure (e.g. occupational, recreational), possible exposure to diseased animals, influenza virus subtypes included in testing, number of virologically confirmed cases, information on vaccination history if stated, methods used for confirmation, geographic region and study design. Available data were extracted and summarised in tables. Grey literature such as ProMED, and reference lists from articles were screened for possible additional relevant papers. Virus detection by culture or (real-time) reverse transcription polymerase chain reaction (rtRT-PCR) and sequencing was considered to be definitive proof of infection, listed as virological evidence (Tables 1 and 2).

Figure 1. Search strategy for the literature review on animal influenza A virus infections in humans

Table 1. Virological evidence of human infection with avian influenza A viruses, excluding high pathogenicity A(H5N1)


Table 2. Virological evidence of human infection with swine influenza A viruses


Search output and article selection
The initial search yielded 6,955 articles, with 4,905 articles resulting from the Medline search, and the others from additional searches (Figure 1). Search outputs from Embase, SciSearch and CabAbstracts yielded 631, 553 and 866 references, respectively. After screening of titles, abstracts and application of the second selection criterion, a total of 89 publications were selected. The majority of these would also have been identified solely through the Medline search.

Thirty additional studies were retrieved through scanning of reference lists of articles identified via the literature review, were retrieved from grey literature or came to our attention after February 2012. Of these 119, 59 publications and reports described virological evidence for infection of humans and met all other inclusion criteria; 60 papers provided some evidence for human infection, but only based on antibody testing and will therefore be described elsewhere.. Seven publications containing both serological and virological evidence were counted once in the total reference count but were included twice in the subdivision according to type of evidence in Figure 1.

Most studies discussed in a review of case reports of SIV infections in humans by Myers et al. [26] were also identified in our literature search. For completeness of the human case count, virologically confirmed civilian (n=23) and military cases of Fort Dix (n=5), although discussed in detail in the review by Myers et al. [26], were also included in the current review [21,27-42] (Table 2). For two virus-confirmed cases from the review by Myers et al. [26], the reference could not be retrieved or did not provide full confirmation; these cases were therefore excluded from our listing in Table 2 [43,44].


The evidence for virologically confirmed infections of humans with avian or SIV is listed in Tables 1, 2 and 3. The exposure status of infected patients is summarised in Table 4. A total of 386 cases of human infection with non-A(H5N1) AIV were described, of which 375 were caused by natural infection and 11 were infected experimentally (Table1).

Regarding human infections with SIV, a total of 401 naturally (n=396) and experimentally (n=5) infected cases were detected in the published and grey literature in English. This included, three virologically confirmed SIV A(H1N1) cases originally published in Russian by Chuvakova et al. [27] because they were listed in the review by Myers et al. [26]. The majority of cases (n=340) were naturally infected by a SIV variant A(H3N2)v [25]. Recognised in US swine in 2010, this variant combines seven genes from the contemporary North-American A(H3N2) SIV lineage and has acquired the M gene of the A(H1N1)pdm09 virus [25]. The remaining 56 naturally infected, virologically confirmed human cases were caused by different circulating SIV or SIV reassortants (Table 2). Five persons were experimentally infected with SIV [45]. The majority of AIV- and SIV-infected patients had been exposed to animals (Table 4).

Table 3. Humans naturally infected with avian influenza virus subtypes other than A(H5N1) and swine influenza virus subtypes, 1959–2014 (n=771)


Table 4. Exposure status of patients infected with avian influenza virus, excluding 251 A(H7N9) and including 11 experimentally infected cases, and with swine influenza virus, 1959–2014 (n=536)


Human infections with avian influenza viruses
Infections with highly pathogenic avian influenza virus A(H5N1)
To date, highly pathogenic avian influenza (HPAI) A(H5N1) viruses are the most frequently diagnosed zoonotic influenza virus infections related to avian exposure [46], although this picture may change in the near future given the recent upsurge in low pathogenic avian influenza (LPAI) A(H7N9) cases. The HPAI A(H5N1) viruses first attracted major attention in the scientific community in 1996, when a large number of domestic waterfowl died in the course of an A(H5N1) outbreak in Guangdong province in southern China. In 1997, HPAI A(H5N1) resurfaced in Hong Kong SAR, China (in the following referred to as Hong Kong); it caused a massive die-off in poultry and crossed the species barrier for the first time, infecting 18 humans, of whom six died [47,48]. From mid-2003 to March 2004, HPAI A(H5N1) spread to seven south-east Asian countries with outbreaks in poultry and waterfowl, and the first confirmed human cases, were reported in Thailand and Vietnam in 2004 [49]. In 2005, HPAI A(H5N1) accounted for the death of a large number of migratory waterfowl at Qinghai lake, China. Shortly after this event, the virus rapidly spread to other Asian countries, Africa, Europe, the Middle East, Mongolia and Russia [50]. Over time, the viruses evolved into multiple lineages, some of which persisted and have become endemic in China, Bangladesh, Egypt, India, Indonesia and Vietnam [51].

As of 10 December 2013, the WHO has listed 648 HPAI A(H5N1) infected cases from 15 countries, confirmed according to WHO criteria and covering a time span of 10 years [24]. In total, 59% of the reported cases died [24]. Indonesia, Egypt and Vietnam reported 195, 173 and 125 cases, respectively, accounting for about 75% of the total influenza A(H5N1) human case count. These three countries also reported the majority of fatalities [24].

Infections with H7 subtype avian influenza viruses
In total, we identified 353 human cases with virologically confirmed H7 infection (Table 1). The majority of these cases (n=251) were reported in China, followed by 95 cases in Europe, six in North America and one in Australia [17,18,23,52–59]. In China, all cases were caused by the recently emerged subtype A(H7N9) [23]. Of the remaining 102 cases, 93 cases had influenza A(H7N7), five had influenza A(H7N3) and four influenza A(H7N2) (Table 3). The first two human cases infected with influenza A(H7N7) were reported in 1959 and 1977. One of these patients had keratoconjunctivitis, thought to be caused by the AIV infection [52,53]. This predilection for the ocular mucosa was confirmed when a person involved in an experimental infection of a seal with an avian-like influenza A(H7N7) developed conjunctivitis, and virus was cultured from a conjunctival swab [54,60]. In the United Kingdom (UK) in 1996, LPAI A(H7N7) virus infection was associated with mild conjunctivitis in a woman who cleaned a duck house and mentioned getting a piece of straw in her eye [55].

Among European cases, 89 humans were infected in the course of a large outbreak with HPAI A(H7N7) in poultry in the Netherlands in 2003 [17]. In contrast to the severe consequences in poultry, only mild symptoms were seen in 88 of the infected people. There was one exception. a veterinarian who died of acute respiratory distress syndrome and multiple organ failure. This person had contracted a virus with several mutations, including a known virulence marker in PB2 [56]. Most of these mutations had accumulated during circulation of the virus in poultry, showing that the public health risk may change over the course of an outbreak [61]. In February 2004, a mixed LPAI and HPAI A(H7N3) virus outbreak was reported in poultry in British Columbia, Canada [18]. Enhanced surveillance for influenza-like illness (ILI) and conjunctivitis in the course of this outbreak led to the identification of two poultry workers showing symptoms of unilateral conjunctivitis. Neither had used the recommended goggles or taken prophylactic oseltamivir. Interestingly, both virus types led to human infection: the isolate cultured from the first worker had the LPAI phenotype, whereas the strain retrieved from the second worker was classified as HPAI [19,62,63]. In 2006 and 2012, LPAI A(H7N3) was associated with one patient in the UK and HPAI A(H7N3) with two patients in Mexico. In both instances, exposure to infected poultry was documented and all patients presented with conjunctivitis [57,59]. Finally, LPAI A(H7N2) was reported as the infectious agent causing mild influenza-like symptoms and conjunctivitis in four cases in the UK in 2007 [58].

The assumption that LPAI influenza viruses were mostly associated with mild disease was challenged with the emergence of influenza A(H7N9) viruses in March 2013, when China notified the WHO of three cases infected with LPAI A(H7N9) who were severely ill and eventually died [64]. During the first wave of infections from February to May 2013, 133 human cases were reported and an additional two cases in July and August [23]. Phylogenetic studies concluded that all genes of this newly detected virus were of avian origin [64]. In October 2013, the second wave started and was still ongoing at the time of writing (31 January 2014) [23]. Between February 2012 and 27 January 2014, a total of 251 influenza A(H7N9) cases were reported, 56 of whom died [23]. Infections occurred in Anhui (n=4), Beijing (n=3), Fujian (n=15), Guangdong (n=32), Guizhou (n=1), Hebei (n=1), Henan (n=4), Hong Kong (n=3), Hunan (n=4), Jiangsu (n=31), Jiangxi (n=5), Shandong (n=2), Shanghai (n=42) and Zheijang (n=102). Two cases were imported from mainland China into Taiwan [23]. In response to these events, China culled thousands of birds and closed several poultry markets [65], although only 39 of 48,000 samples representing 1,000 poultry markets tested positive. Most human cases had a history of exposure to birds or live bird markets [23]. As of 31 January 2014, no conclusive evidence of human-to-human transmission has been reported and the ecology of the viruses remains to be resolved.

Infections with H9 subtype avian influenza viruses
In total, we detected 15 human cases infected with AIV A(H9N2) (Table 1, Table 3). Since the mid-1990s, influenza viruses of the H9 subtype have established stable lineages in poultry in Asia and have occasionally infected humans and swine (Table 1) [16,66-69]. As of 31 January 2014, human A(H9N2) cases have only been detected in Asia, particularly in China. Six cases were identified via the literature search [16,66-68]. Of those, three reported poultry exposure and all presented with mild ILI (Table 1). Reviews conducted by Peiris [46] and Cheng et al. [68] identified six additional human infections in China reported in the Chinese literature [70,71]. Three additional cases from Bangladesh, Hunan and Shenzhen, two with and one without poultry exposure, complete the total count of fifteen human cases caused by AIV A(H9N2) [69,72,73] (Table 3). Infections with AIV A(H9N2) viruses gained public health interest when researchers found that strains circulating in Asian poultry had a receptor specificity similar to human influenza A viruses, which is considered one of the essential features of a human-to-human transmissible virus [74]. So far, however, no sustained human-to-human transmission of A(H9N2) influenza viruses has been reported.

Infections with other avian influenza virus subtypes
Experimental inoculation of human volunteers with influenza strains A(H4N8), A(H6N1) or A(H10N7) resulted in mild clinical symptoms and virus shedding in eleven volunteers [75]. In 2004, the National Influenza Center in Egypt and the WHO Influenza Collaborating Centre in the UK announced the isolation of influenza A(H10N7) virus from two children presenting with fever and cough in Egypt [76]. In Australia, virus of the same subtype could be detected by PCR in two abattoir workers with conjunctivitis who were exposed to infected poultry [20] (Table 3). In December 2013 and January 2014, human infection with A(H10N8) virus was reported for the first time in Jiangxi province, China [77,78]. Both patients were female and had visited a poultry and an agricultural market, respectively, before onset of illness. One of them was immunocompromised and had died whereas the other case was still in critical condition as of 31 January 2014. In 2013, CDC Taiwan reported a human case of AIV A(H6N1) infection causing mild pneumonia, although an avian source could not be identified [79,80] (Table 3).

Human infection with swine influenza viruses
An overview of all studies describing virologically confirmed human SIV cases is given in Table 2. In total, we identified 396 SIV-confirmed patients who were naturally infected (401 including experimental infections) (Table 2). Beare et al. [45] successfully recovered SIV from five of 20 human volunteers after experimental infection: of seven volunteers infected with SIV A(H3N2) related to A/Hong Kong/1/68, three tested virus-positive), and of 13 infected with a classical swine A(H1N1) virus strain, two tested positive. Of the naturally infected cases, 47 were infected with SIV A(H1N1), two with SIV A(H1N2), seven with SIV A(H3N2) and 340 with SIV A(H3N2)v (Table 2, Figure 2). The majority of these cases were reported in North America, 11 in Europe and six in Asia. One of the six Asian cases was infected with SIV A(H3N2) from the European lineage (Figure 2) [39]. SIV epidemiology differs between continents and was extensively reviewed for North America, Europe and Asia [81-84]. In addition to the studies discussed in the review by Myers et al. [26] we identified fourteen studies and reports describing a further 28 human SIV cases; 368 when taking into account 340 cases with SIV A(H3N2)v infection. Details on these studies are described in more detail in the following sections grouped by continent.

Figure 2. Timeline of emergence of swine influenza virus lineages circulating in Europe and North America indicating natural human infections from swine


Infections with swine influenza A H1 subtype viruses
Asia: A 25 year-old male from the Philippines and a four year-old male from Thailand were infected with swine-like A(H1N2) and A(H1N1), respectively [85]. The isolated viruses carried HA genes most closely related to classical swine viruses circulating in Asia and North America. NA genes were most similar to circulating European SIV. Both cases showed mild ILI and neither of them had direct contact with swine, although occasional contact with backyard swine could not be ruled out.

Europe: In Spain, a 50 year-old woman developed ILI after having been closely exposed to swine on a family farm [22]. No symptoms in swine were observed and sequencing of the isolate revealed that it was closely related to avian-like SIV A(H1N1) circulating in swine in western Europe. Three cases from Switzerland were detected who had worked with influenza-confirmed swine [86].

North America: For the US, 19 confirmed cases of SIV A(H1N1) infection were described in the published literature. This number could possibly be higher because Vincent et al. [87] reported on 26 human cases presenting with ILI after exposure to ill swine on a county fair in Ohio. The authors described that isolation and sequencing was performed for at least two of the human cases. Since the exact number of virologically confirmed cases was not given, we only added the two confirmed patients to the overall SIV A(H1N1) count (Table 3). Sequences from swine and human isolates from this outbreak were identical and were similar to triple–reassortant (tr) viruses currently circulating in swine herds in the US [87,88]. Another triple–reassortant A(H1N1) SIV was detected in a 17 year-old male from Wisconsin who assisted in butchering healthy appearing swine [89]. The patient presented with acute, mild respiratory illness without fever. Similarly, Dawood et al. [90] reported infection with trSIV A(H1N1) in a 19 year-old asthmatic male who visited a swine show in South Dakota. Symptoms included fever, ILI, vomiting and diarrhoea. No respiratory illness was observed in swine at this event. A trSIV A(H1N1) was also detected in three infected swine workers in Sasketchewan, Canada [91]. Household members did not report any signs of disease. Mild respiratory illness was reported in less than 1% of the swine; however, no confirmatory test had been conducted in ill swine. Unlike trSIV identified earlier in North America, this isolate contained an HA and a NA belonging to the A/Brisbane/58/2007 A(H1N1) lineage, whereas the remaining genes were derived from trSIV A(H3N2) viruses circulating in North America since 1998. Gray et al. [92] found another trSIV A(H1N1) in the course of a prospective survey, which was isolated from an ill swine farmer exposed to swine showing respiratory symptoms. Routine national influenza surveillance reported another 10 human cases infected with trSIV A(H1N1), distinct from A(H1N1)pdm09, and one case caused by trSIV A(H1N2). The majority of those twelve patients stated exposure to swine prior to disease onset and all made a full recovery [93].

The CDC reported additional human infections with SIV-variant viruses of subtype A(H1N1)v and A(H1N2)v identified in the US since 2005 [94]. These figures have not been included in this review due to missing case history and in order to avoid double counting of cases described in the published literature.

Human infections with swine influenza A H3 subtype viruses
North America: In our search we detected two cases of trSIV A(H3N2) from Canada [95,96] and one from Kansas, US [97] infected before 2011. In Canada, a six year-old boy who lived on a swine farm presented with parotitis, nasal congestion, cough and pharyngitis, but had no fever. The swine appeared clinically healthy [95]. No swine exposure was reported in the second Canadian patient, a seven month-old child, who lived on a community farm and showed ILI symptoms [96]. Similarly, the third case from Kansas presented with ILI and is likely to have contracted trSIV A(H3N2) from swine he was exposed to at a county fair [97]. It is assumed that swine harboured the virus; PCR results performed on swine samples were negative but sera showed raised titres against SIV A(H3N2) indicating prior infection.

Between July and August 2011, a SIV variant, which accounted for the majority of reported human SIV A(H3N2) cases, appeared in the US, possibly reflecting enhanced surveillance activities in the country. This SIV A(H3N2) variant, A(H3N2)v, was first found in two children presenting with fever and respiratory signs [98,99]. Sequencing showed that this variant contained seven genes derived from the contemporary trSIV A(H3N2), circulating in the US swine population since 1998, as well as the M,gene from the A(H1N1)pdm09 virus. Since its first occurrence in 2011, A(H3N2)v has been detected in 340 humans according to data as of 18 October  2013 [25]. Since July 2012, 17 patients have been hospitalised and one patient has died due to SIV A(H3N2)v infection. Most cases have reported prolonged exposure to swine before getting ill.

Human infections following exposure to other animals
We have identified three studies describing human susceptibility to equine influenza virus, demonstrated by experimental infection with equine subtype A(H3N8) [100-102]. The literature search did not reveal evidence of humans naturally infected with equine influenza virus.


Here we present a review of the literature for studies presenting any evidence for human infection with animal influenza viruses. Virological techniques, e.g. virus culture, PCR and sequencing provide more solid evidence of infection, whereas serological methods can help reaching a diagnosis after the virus has been cleared from the body. Virus isolation is still the gold standard in detecting AIV infection. Human cases with virological evidence identified by PCR only should be interpreted with caution as detection of viral RNA without additional serological evidence (seroconversion, more than fourfold rise in the titre of paired samples) does not necessary imply infection, although current diagnostic methods heavily rely on case identification by PCR [103,104]. Serological results can be misleading because of the existence of cross–reactive antibodies and thus provide less solid evidence than direct detection of the infecting virus itself [105]. Therefore, we limited the current paper to studies providing virological evidence only.

Most evidence of human infection with AIV is associated with subtypes H5 and H7. Both subtypes can be linked to devastating outbreaks in poultry with high mortality, if transition from a low to a highly pathogenic state occurs [106]. Pathogenicity shown in poultry clearly does not reflect disease severity in humans: before the emergence in LPAI A(H7N9) as a cause of severe human illness, LPAI and HPAI viruses of subtype H7 had in the majority of cases been associated with mild eye infections or ILI [107]. The LPAI A(H7N9) infections diagnosed to date, however, have been unusually severe [23,64]. In addition to the severity of illness associated with these and also A(H5N1) viruses, the widespread circulation of different lineages, made possible by mutations and reassortments, justifies enhanced surveillance activities, given that few genetic changes may lead to a human-to-human transmissible virus [108,109].

Nevertheless, the evidence from experimental infections and anecdotal natural infections shows that other AIV may infect humans as well. There is insufficient systematic surveillance data to address the question whether the identified human cases reflect the level of virus circulation among wild or domestic birds, or whether certain subtypes infect humans preferentially.

Regarding SIV, there is ample evidence of human infection with A(H3N2), A(H1N1) and A(H1N2) subtypes, as well as reassortants derived from these endemic SIV lineages. Nevertheless, one has to be aware that the true number of human SIV cases is probably higher than reported since clinical symptoms of SIV are indistinguishable from seasonal influenza [86]. Whereas recent human cases in Europe were detected almost accidentally, the larger number of cases reported in the US since 2005, especially for influenza A(H3N2)v since 2011, may be the result of increased surveillance activities [86,110]. Swine were assumed to play an important role as intermediate hosts or 'mixing vessels' for strains of human, avian and swine origin, because they possess avian and human influenza-specific receptors in the tracheal epithelium [111]. However, recent research showed that the distribution of sialic acid receptors in the porcine respiratory tract is similar to that in humans, leading to the conclusion that humans are equally likely to constitute 'mixing vessels' [112,113]. The fact that influenza viruses can circulate unnoticed in swine populations [114] warrants close surveillance in this animal species as well. Co-circulation of different influenza virus strains in swine may facilitate the generation of new variants that could potentially pose a threat for public health [115]. For instance, it is assumed that influenza A(H1N1)pdm09 was present in swine herds for months before it emerged as a pandemic strain in humans [116]. Conversely, Nelson et al. [117] reported at least 49 transmission events of influenza A(H1N1)pdm09 from humans to swine between 2009 and 2011, as well as at least 23 separate introductions of human seasonal influenza into swine since 1990.

Although there is some evidence for infection in swine with non-H1 and non-H3 subtype viruses (H9N2, H4N6) [115,118], we found no case reports describing human infection with these influenza A virus subtypes after swine exposure. Since most human infection events are associated with swine exposure, awareness of risk factors and personal protective equipment is paramount to limiting the chance of infection and preventing people working with or recreationally exposed to swine (including children) from becoming 'bridging links' between swine and community contacts and vice versa [92,119].

There are a few limitations to this review. The language restriction set to papers published in English only and the unsystematic search of the grey literature probably lead to the omission of additional documented human infections with animal influenza virus. Although this limitation may affect the total count of human cases, the aim of this review was to identify animal influenza subtypes, which crossed the species barrier to humans, and to our knowledge, all relevant subtypes were covered by this review.


There is evidence of infection of humans with animal influenza viruses belonging to various subtypes. All reported SIV cases have been exclusively associated with subtypes H1 and H3, and most AIV cases were caused by subtypes H5 and H7. Whether this reflects the prevalence of these viruses in birds kept or sold for consumption or a preferential ability to transmit to humans cannot be concluded from the available evidence. Given the often, mild illness associated with non-H5 and non-H7 animal influenza virus infections in humans, such cases likely are underreported [120]. Standardisation of diagnostic methods has significantly improved case ascertainment in recent years, but the monitoring of the evolution of these viruses is less advanced. Recent research pointed out that the majority of Asian and African countries have contributed only few sequences to surveillance networks and do not regularly sequence viruses as part of their surveillance programme [121]. Genetic sequencing is paramount to identifying changes with potential effect on the phenotype of circulating influenza viruses, and could thereby strengthen worldwide epidemic and pandemic preparedness [121]. To be prepared for a potentially emerging influenza virus of animal origin in humans, enhanced global surveillance in animal populations is therefore indicated to monitor evolution and circulation of viruses with yet unknown public health risks.

Note: Numbers on influenza H5N1 and H7N9 are as of 31 January 2014.
This work was conducted within the framework of the FLURISK project (CFP/EFSA/AHAW/2011/01), supported by the European Food Safety Authority. The sole responsibility of this review lies with the authors and the European Food Safety Authority shall not be considered responsible for any use that may be made of the information contained herein.

Authors' contributions
GF and MK drafted the analysis plan. GF performed the study of the literature and drafted the manuscript. MK, AM and EdB contributed to the analysis of the data and critically reviewed the manuscript. AM performed the final edit of the manuscript before submission, including an update of counts and addition of most recent evidence. All authors were involved in discussion of parts of the analyses that were presented during consortium meetings and critically reviewed drafts of the manuscript.

Conflict of interest
None declared.

  1. Fouchier RAM, Munster V, Wallensten A, Bestebroer TM, Herfst S, Smith D, et al. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol. 2005;79(5):2814-22.
  2. Tong S, Li Y, Rivailler P, Conrardy C, Castillo DAA, Chen L-M, et al. A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci U S A. 2012;109(11):4269-74.
  3. Tong S, Zhu X, Li Y, Shi M, Zhang J, Bourgeois M, et al. New World bats harbor diverse influenza A viruses. PLoS Pathog. 2013;9(10):e1003657.
  4. Zhu X, Yang H, Guo Z, Yu W, Carney PJ, Li Y, et al. Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site. Proc Natl Acad Sci USA. 2012;109(46):18903-8.
  5. Li Q, Sun X, Li Z, Liu Y, Vavricka CJ, Qi J, et al. Structural and functional characterization of neuraminidase-like molecule N10 derived from bat influenza A virus. Proc Natl Acad Sci USA. 2012;109(46):18897-902.
  6. Hale BG, Albrecht RA, Garcia-Sastre A. Innate immune evasion strategies of influenza viruses. Future Microbiol. 2010;5(1):23-41.
  7. Bouvier NM, Palese P. The biology of influenza viruses. Vaccine. 2008;26(Supplement 4):D49–53.
  8. Kelly H. The classical definition of a pandemic is not elusive. Bull World Health Organ. 2011;89(7):540-1.
  9. Smith GJD, Bahl J, Vijaykrishna D, Zhang J, Poon LLM, Chen H, et al. Dating the emergence of pandemic influenza viruses. PNAS, 2009;106(28):11709-12.
  10. Smith GJD, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M, Pybus OG, et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature. 2009;459(7250):1122-5.
  11. Neumann G, Kawaoka Y. The first influenza pandemic of the new Millennium. Influenza Other Respi Viruses. 2011;5(3):157-66.
  12. Munster VJ, Baas C, Lexmond P, Waldenström J, Wallensten A, Fransson T, et al. Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds. PLoS Pathog. 2007;3(5):e61.
  13. Ma W, Vincent AL, Gramer MR, Brockwell CB, Lager KM, Janke BH, et al. Identification of H2N3 influenza A viruses from swine in the United States. Proc Natl Acad Sci U S A. 2007;104(52):20949-54.
  14. Morse SS, Mazet JA, Woolhouse M, Parrish CR, Carroll D, Karesh WB, et al. Prediction and prevention of the next pandemic zoonosis. Lancet. 2012;380(9857):1956-65.
  15. Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA, et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet. 1998;351(9101):472-7.
  16. Peiris M, Yuen K, Leung C, Chan K, Ip P, Lai R, et al. Human infection with influenza H9N2. Lancet. 1999;354(9182):916-7.
  17. Koopmans M, Wilbrink B, Conyn M, Natrop G, van der Nat H, Vennema H, et al. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet. 2004;363(9409):587-93.
  18. Tweed SA, Skowronski DM, David ST, Larder A, Petric M, Lees W, et al. Human illness from avian influenza H7N3, British Columbia. Emerg Infect Dis. 2004;10(12):2196-9.
  19. Skowronski DM, Tweed SA, Petric M, Booth T, Li Y, Tam T. Human illness and isolation of low-pathogenicity avian influenza virus of the H7N3 subtype in British Columbia, Canada. J Infect Dis. 2006;193(6):899-900.
  20. Arzey G, Kirkland P, Edla A, Frost M, Maywood P, Conaty S, et al. Influenza virus A (H10N7) in chickens and poultry abattoir workers, Australia. Emerg Infect Dis. 2012;18(5):814-6.
  21. Gregory V, Bennett M, Thomas Y, Kaiser L, Wunderli W, Matter H, et al. Human infection by a swine influenza A (H1N1) virus in Switzerland. Arch Virol. 2003;148:793-802.
  22. Adiego Sancho B, Omenaca Teres M, Martinez Cuenca S, Rodrigo Val P, Sanchez Villanueva P, Casas I, et al. Human case of swine influenza A (H1N1), Aragon, Spain, November 2008. Euro Surveill. 2009;14(7):pii=19120.
  23. Centre for Disease Prevention and Control (ECDC). Updated rapid risk assessment: Human infection with a novel avian influenza A(H7N9) virus, China. Third update. Stockholm: ECDC; 2014. Available from:
  24. World Health Organization (WHO). Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO. Geneva: WHO; 2013. Available from:
  25. Centers for Disease Control and Prevention (CDC). Case count: detected U.S. human infections with H3N2v by state since August 2011. Atlanta: CDC; 2013. Available from:
  26. Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a review of the literature. Clin Infect Dis. 2007;44(8):1084-8.
  27. Chuvakova ZK, Rovnova ZI, Isaeva EI, Kim EV, Ignat'eva TV. [3 cases of isolating the influenza A virus with human hemagglutinin Hsw1 in 1983 in Alma-Ata]. Vopr Virusol. 1985;30(5):530-6. Russian.
  28. Gaydos JC, Hodder RA, Top FH Jr, Soden VJ, Allen RG, Bartley JD, et al. Swine influenza A at Fort Dix, New Jersey (January-February 1976). I. Case finding and clinical study of cases. J Infect Dis. 1977;136 Suppl:S356-62.
  29. Centers for Disease Control and Prevention (CDC). Influenza–Wisconsin and Washington, DC. MMWR Morb Mortal Wkly Rep. 1976;25:392.
  30. Centers for Disease Control and Prevention (CDC). Influenza—Wisconsin. MMWR Morb Mortal Wkly Rep. 1976;25:402.
  31. Dacso CC, Couch RB, Six HR, Young JF, Quarles JM, Kasel JA. Sporadic occurrence of zoonotic swine influenza virus infections. J Clin Microbiol. 1984;20(4):833-5.
  32. Patriarca PA, Kendal AP, Zakowski PC, Cox NJ, Trautman MS, Cherry JD, et al. Lack of significant person-to-person spread of swine influenza-like virus following fatal infection in an immunocompromised child. Am J Epidemiol. 1984;119(2):152-8.
  33. De Jong JC, Paccaud MF, de Ronde-Verloop FM, Huffels NH, Verwei C, Weijers TF, et al. Isolation of swine-like influenza A(H1N1) viruses from man in Switzerland and The Netherlands. Ann Inst Pasteur Virol. 1988;139(4):429-37.
  34. McKinney WP, Volkert P, Kaufman J. Fatal swine influenza pneumonia during late pregnancy. Arch Intern Med. 1990;150(1):213-5.
  35. Wentworth DE, Thompson BL, Xu X, Regnery HL, Cooley AJ, McGregor MW, et al. An influenza A (H1N1) virus, closely related to swine influenza virus, responsible for a fatal case of human influenza. J Virol. 1994;68(4):2051-8.
  36. Rimmelzwaan GF, de Jong JC, Bestebroer TM, van Loon AM, Claas ECJ, Fouchier RAM, et al. Antigenic and genetic characterization of swine influenza A (H1N1) viruses isolated from pneumonia patients in The Netherlands. Virology. 2001;282(2):301-6.
  37. Wentworth DE, McGregor MW, Macklin MD, Neumann V, Hinshaw VS. Transmission of swine influenza virus to humans after exposure to experimentally infected pigs. J Infect Dis. 1997;175(1):7-15.
  38. Kimura K, Adlakha A, Simon PM. Fatal case of swine influenza virus in an immunocompetent host. Mayo Clin Proc. 1998;73(3):243-5.
  39. Gregory V, Lim W, Cameron K, Bennett M, Marozin S, Klimov A, et al. Infection of a child in Hong Kong by an influenza A H3N2 virus closely related to viruses circulating in European pigs. J Gen Virol. 2001;82(6):1397-406.
  40. Olsen CW, Karasin AI, Carman S, Li Y, Bastien N, Ojkic D, et al. Triple reassortant H3N2 influenza A viruses, Canada, 2005. Emerg Infect Dis. 2006;12(7):1132-5.
  41. Claas EC, Kawaoka Y, de Jong JC, Masurel N, Webster RG. Infection of children with avian-human reassortant influenza virus from pigs in Europe. Virology. 1994;204(1):453-7.
  42. Smith TF, Burgert EO Jr., Dowdle WR, Noble GR, Campbell RJ, Van Scoy RE. Isolation of swine influenza virus from autopsy lung tissue of man. N Engl J Med. 1976;294(13):708-10
  43. Cooper LV, Olsen C, Xu W, Klimov A, Cox N, Subbarao K. Molecular characterization of human influenza A viruses bearing swine-like hemagglutinin genes. In: Program and abstracts of the Virus Evolution Workshop (Ardmore, OK). Ardmore: Samuel Roberts Noble Foundation; 1999.
  44. Gray G, McCarthy T, Capuano A. Population-based surveillance for zoonotic influenza A in agricultural workers. Program and abstracts of the Second North American Congress of Epidemiology. Seattle; 2006.
  45. Beare AS, Schild GC, Hall TS, Kundin WD. Antigenic characteristics of swine influenza virus closely related to human Hong Kong strain and results of experimental infection in volunteers. Lancet. 1971;1(7694):305-7.
  46. Peiris JS. Avian influenza viruses in humans. Rev Sci Tech. 2009;28(1):161-73.
  47. To KF, Chan PK, Chan KF, Lee WK, Lam WY, Wong KF, et al. Pathology of fatal human infection associated with avian influenza A H5N1 virus. J Med Virol. 2001;63(3):242-6.<242::AID-JMV1007>3.0.CO;2-N
  48. De Jong JC, Claas EC, Osterhaus AD, Webster RG, Lim WL. A pandemic warning? Nature. 1997;389(6651):554.
  49. Gillim-Ross L, Subbarao K. Emerging respiratory viruses: challenges and vaccine strategies. Clin Microbiol Rev. 2006;19(4):614-36.
  50. Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang XL, et al. Highly pathogenic H5N1 influenza virus infection in migratory birds. Science. 2005;309(5738):1206.
  51. Food and Agriculture Organization (FAO). Stamping out H5N1 avian influenza could take decades. Rome: FAO; 2011. Available from:
  52. Campbell CH, Webster RG, Breese SS Jr. Fowl plague virus from man. J Infect Dis. 1970;122(6):513-6.
  53. Taylor HR, Turner AJ. A case report of fowl plague keratoconjunctivitis. Br J Ophthalmol. 1977;61(2):86-8.
  54. Webster RG, Geraci J, Petursson G, Skirnisson K. Conjunctivitis in human beings caused by influenza A virus of seals. N Engl J Med. 1981;304(15):911.
  55. Kurtz J, Manvell RJ, Banks J. Avian influenza virus isolated from a woman with conjunctivitis. Lancet. 1996;348(9031):901-2.
  56. Fouchier RAM, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SAG, Munster V, et al. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. PNAS. 2004;101(5):1356-61.
  57. Nguyen-Van-Tam JS, Nair P, Acheson P, Baker A, Barker M, Bracebridge S, et al. Outbreak of low pathogenicity H7N3 avian influenza in UK, including associated case of human conjunctivitis. Euro Surveill. 2006;11(18):pii=2952.
  58. Editorial team. Avian influenza A/(H7N2) outbreak in the United Kingdom Euro Surveill. 2007;12(22):pii=3206.
  59. Centers for Disease Control and Prevention (CDC). Notes from the field: Highly pathogenic avian influenza A (H7N3) virus infection in two poultry workers-Jalisco, Mexico, July 2012. MMWR Morb Mortal Wkly Rep. 2012;61(36):726-7.
  60. Webster RG, Hinshaw VS, Bean WJ, Van Wyke KL, Geraci JR, St Aubin DJ, et al. Characterization of an influenza A virus from seals. Virology. 1981;113(2):712-24.
  61. Jonges M, Bataille A, Enserink R, Meijer A, Fouchier RAM, Stegeman A, et al. Comparative analysis of avian influenza virus diversity in poultry and humans during a highly pathogenic avian influenza A (H7N7) virus outbreak. J Virol. 2011;85(20):10598-604.
  62. Pasick J, Handel K, Robinson J, Copps J, Ridd D, Hills K, et al. Intersegmental recombination between the haemagglutinin and matrix genes was responsible for the emergence of a highly pathogenic H7N3 avian influenza virus in British Columbia. J Gen Virol. 2005;86(3):727-31.
  63. Hirst M, Astell CR, Griffith M, Coughlin SM, Moksa M, Zeng T, et al. Novel avian influenza H7N3 strain outbreak, British Columbia. Emerg Infect Dis. 2004;10(12):2192-5.
  64. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Eng J Med. 2013;368(20):1888-97.
  65. ProMED-mail. Avian influenza (41): (China) zoonotic LPAI H7N9, animal, RFI. Archive Number 20130420.1659952. 20 April 2013. Available from:
  66. Butt KM, Smith GJ, Chen H, Zhang LJ, Leung YH, Xu KM, et al. Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003. J Clin Microbiol. 2005;43(11):5760-7.
  67. Centers for Disease Control and Prevention (CDC). Avian influenza (flu). Avian influenza A virus infections of humans. Atlanta: CDC; 2008. Available from:
  68. Cheng VC, Chan JF, Wen X, Wu WL, Que TL, Chen H, et al. Infection of immunocompromised patients by avian H9N2 influenza A virus. J Infect. 2011;62(5):394-9.
  69. International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). Outbreak of mild respiratory disease caused by H5N1 and H9N2 infections among young children in Dhaka, Bangladesh, 2011. Health and Science Bulletin. 2011;9(2):5-12.
  70. Guo Y, Li J, Cheng X. [Discovery of men infected by avian influenza A (H9N2) virus]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 1999;13(2):105-8. Chinese.
  71. Guo Y, Xie J, Wang M. [A strain of influenza A H9N2 virus repeatedly isolated from human population in China]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2000;14(3):209-12. Chinese.
  72. ProMED-mail. Avian influenza, human (164): China (HK) H9N2. Archive Number 20131230.2143709. 30 Dec 2013. Available from:
  73. ProMED-mail. Avian influenza, human (02): China (HK) H9N2 ex (HN). Archive Number 20140102.2148327. 2 Jan 2014. Available from:
  74. Matrosovich MN, Krauss S, Webster RG. H9N2 Influenza A Viruses from Poultry in Asia Have Human Virus-like Receptor Specificity. Virology. 2001;281(2):156-62.
  75. Beare AS, Webster RG. Replication of avian influenza viruses in humans. Archives of Virology. 1991;119(1-2):37-42.
  76. Pan American Health Organization (PAHO). Avian influenza virus A(H10N7) circulating among humans in Egypt. Washington: PAHO; 2004. Available from:
  77. ProMED-mail. Avian influenza, human (157): China (ZJ) H10N8, fatal. Archive Number 20131217.2121718. 17 Dec 2013. Available from:
  78. ProMED-mail. Avian influenza, human (36): China (JX) H10N8. Archive Number 20140126.2233164 . 26 Jan 2014. Available from:
  79. Centers for Disease Control (CDC). Laboratory-confirmed case of human infection with avian influenza A(H6N1) virus in Taiwan recovered; Taiwan CDC urges public to take precautions to stay healthy. Taipei City: CDC; 2013. Available from:
  80. Wei S-H, Yang J-R, Wu H-S, Chang M-C, Lin J-S, Lin C-Y, et al. Human infection with avian influenza A H6N1 virus: an epidemiological analysis. Lancet Respir Med. 2013;1(10):771-8.
  81. Vincent AL, Ma W, Lager KM, Janke BH, Richt JA. Swine influenza viruses a North American perspective. Adv Virus Res. 2008;72:127-54.
  82. Brown IH. History and epidemiology of swine influenza in Europe. Curr Top Microbiol Immunol. 2013;370:133-46.
  83. Van Reeth K. Avian and swine influenza viruses: our current understanding of the zoonotic risk. Vet Res. 2007;38(2):243-60.
  84. Choi YK, Pascua PN, Song MS. Swine influenza viruses: an Asian perspective. Curr Top Microbiol Immunol. 2013;370:147-72.
  85. Komadina N, Roque V, Thawatsupha P, Rimando-Magalong J, Waicharoen S, Bomasang E, et al. Genetic analysis of two influenza A (H1) swine viruses isolated from humans in Thailand and the Philippines. Virus Genes. 2007;35(2):161-5.
  86. European Center for Disease Prevention and Control (ECDC). Update–Swine-origin triple reassortant influenza A(H3N2) variant viruses in North America. Stockholm: ECDC; 2012. Available from:
  87. Vincent AL, Swenson SL, Lager KM, Gauger PC, Loiacono C, Zhang Y. Characterization of an influenza A virus isolated from pigs during an outbreak of respiratory disease in swine and people during a county fair in the United States. Vet Microbiol. 2009;137(1-2):51-9.
  88. Yassine HM, Khatri M, Zhang YJ, Lee CW, Byrum BA, O'Quin J, et al. Characterization of triple reassortant H1N1 influenza A viruses from swine in Ohio. Vet Microbiol. 2009;139(1–2):132-9.
  89. Newman AP. Human case of swine influenza A (H1N1) triple reassortant virus infection, Wisconsin. Emerg Infect Dis. 2008;14(9):1470-2.
  90. Dawood FS, Dong L, Liu F, Blau DM, Peebles PJ, Lu X, et al. A pre-pandemic outbreak of triple-reassortant swine influenza virus infection among university students, South Dakota, 2008. J Infect Dis. 2011;204(8):1165-71.
  91. Bastien N, Antonishyn NA, Brandt K, Wong CE, Chokani K, Vegh N, et al. Human infection with a triple-reassortant swine influenza A(H1N1) virus containing the hemagglutinin and neuraminidase genes of seasonal influenza virus. J Infect Dis. 2010;201(8):1178-82.
  92. Gray GC, McCarthy T, Capuano AW, Setterquist SF, Olsen CW, Alavanja MC, et al. Swine workers and swine influenza virus infections. Emerg Infect Dis. 2007;13(12):1871-8.
  93. Shinde V, Bridges CB, Uyeki TM, Shu B, Balish A, Xu X, et al. Triple-reassortant Swine influenza A (H1) in humans in the United States, 2005–2009. N Eng J Med. 2009;360(25):2616-25.
  94. Centers for Disease Control and Prevention (CDC). Reported infections with variant influenza viruses in the United States since 2005. Atlanta: CDC; 2013. Available from:
  95. Bastien N, Bowness D, Burton L, Bontovics E, Winter A-L, Tipples G, et al. Parotitis in a child infected with triple-reassortant influenza A virus in Canada in 2007. J Clin Microbiol. 2009;47(6):1896–8.
  96. Robinson J, Lee B, Patel J, Bastien N, Grimsrud K, Seal R, et al. Swine influenza (H3N2) infection in a child and possible community transmission, Canada. Emerg Infect Dis. 2007;13(12):1865-70.
  97. Cox C. Swine Influenza Virus A (H3N2) Infection in human, Kansas, USA, 2009. Emerg Infect Dis. 2011;17(16):1143-4.
  98. Centers for Disease Control and Prevention (CDC). Swine-origin influenza A (H3N2) virus infection in two children -- Indiana and Pennsylvania, July-August 2011. MMWR Morb Mortal Wkly Rep. 2011;60(35):1213-5.
  99. Centers for Disease Control and Prevention (CDC). Update: Influenza A (H3N2)v transmission and guidelines - five states, 2011. MMWR Morb Mortal Wkly Rep. 2012;60(51-52):1741-4.
  100. Kasel JA, Alford RH, Knight V, Waddel GH, Sigel MM. Experimental infection of human volunteers with equine influenza virus. Nature. 1965 Apr 3;206:41-3.
  101. Couch RB, Douglas RG, Kasel JA, Riggs S, Knight V. Production of the influenza syndrome in man with equine influenza virus. Nature. 1969;224(5218):512–4.
  102. Alford RH, Kasel JA, Lehrich JR, Knight V. Human responses to experimental infection with influenza a/Equi 2 virus. Am J Epidemiol. 1967;86(1):185-92.
  103. Wallace LA, Collins TC, Douglas JDM, McIntyre S, Millar J, Carman WF. Virological surveillance of influenza-like illness in the community using PCR and serology. J Clin Virol. 2004;31(1):40-5.
  104. World Health Organization (WHO). WHO information for molecular diagnosis of influenza virus in humans - update. Geneva: WHO; 2012. Available from:
  105. Allwinn, Preiser, Rabenau, Buxbaum, Stürmer, Doerr. Laboratory diagnosis of influenza - virology or serology? Med Microbiol Immunol. 2002;191(3):157-60.
  106. Swayne DE, Suarez DL. Highly pathogenic avian influenza. Rev - Off Int Epizoot. 2000;19(2):463-82.
  107. Olofsson S, Kumlin U, Dimock K, Arnberg N. Avian influenza and sialic acid receptors: more than meets the eye? Lancet Inf Dis. 2005;5(3):184-8.
  108. Imai M, Herfst S, Sorrell EM, Schrauwen EJA, Linster M, De Graaf M, et al. Transmission of influenza A/H5N1 viruses in mammals. Virus Res. 2013;178(1):15-20.
  109. Herfst S, Schrauwen EJA, Linster M, Chutinimitkul S, de Wit E, Munster VJ, et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012;336(6088):1534-41.
  110. Shu B, Garten R, Emery S, Balish A, Cooper L, Sessions W, et al. Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990–2010. Virology. 2012;422(1):151–60.
  111. Subbarao K, Katz J. Avian influenza viruses infecting humans. Cell Mol Life Sci. 2000;57(12):1770-84.
  112. Van Poucke SG, Nicholls JM, Nauwynck HJ, Van Reeth K. Replication of avian, human and swine influenza viruses in porcine respiratory explants and association with sialic acid distribution. Virol J. 2010;7:38.
  113. Nelli RK, Kuchipudi SV, White GA, Perez B, Dunham SP, Chang K-C. Comparative distribution of human and avian type sialic acid influenza receptors in the pig. BMC Vet Res. 2010;6:4.
  114. Gray GC, Bender JB, Bridges CB, Daly RF, Krueger WS, Male MJ, et al. Influenza A(H1N1)pdm09 virus among healthy show pigs, United States. Emerg Inf Dis. 2012;18(9):1519-21.
  115. Peiris JSM, Guan Y, Markwell D, Ghose P, Webster RG, Shortridge KF. Cocirculation of avian H9N2 and contemporary' human' H3N2 influenza A viruses in pigs in southeastern China: potential for genetic reassortment? J Virol. 2001;75(20):9679-86.
  116. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325(5937):197-201.
  117. Nelson MI, Gramer MR, Vincent AL, Holmes EC. Global transmission of influenza viruses from humans to swine. J Gen Virol. 2012;93(Pt 10):2195-203.
  118. Karasin AI, Olsen CW, Brown IH, Carman S, Stalker M, Josephson G. H4N6 influenza virus isolated from pigs in Ontario. Can Vet J. 2000;41(12):938-9.
  119. Gray GC, Kayali G. Facing pandemic influenza threats: the importance of including poultry and swine workers in preparedness plans. Poultry science. 2009;88(4):880-4.
  120. Wang TT, Parides MK, Palese P. Seroevidence for H5N1 Influenza infections in humans: meta-analysis. Science. 2012;335(6075):1463.
  121. Escorcia M, Attene-Ramos M, Estrada M, Nava G. Improving global influenza surveillance: trends of A(H5N1) virus in Africa and Asia. BMC Res Notes. 2012;5:62.
  122. Lange J, Groth M, Kanrai P, Pleschka S, Scholtissek C, Dürrwald, et al. Circulation of classical swine influenza virus in Europe between the wars? Arch Virol. 2013; Dec 15 [Epub ahead of print]. DOI 10.1007/s00705-013-1950-x
  123. Han L, Lu W, Han Y, Li S, Yin J, Xie J et al. Evolutionary characteristics of swine-origin H1N1 influenza virus that infected humans from sporadic to pandemic. J Public Health Epidemiol. 2011;3(6):254-70.

Back to Table of Contents
Previous Download (pdf) Next

Disclaimer:The opinions expressed by authors contributing to Eurosurveillance do not necessarily reflect the opinions of the European Centre for Disease Prevention and Control (ECDC) or the editorial team or the institutions with which the authors are affiliated. Neither ECDC nor any person acting on behalf of ECDC is responsible for the use that might be made of the information in this journal.
The information provided on the Eurosurveillance site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her physician. Our website does not host any form of commercial advertisement.

Eurosurveillance [ISSN] - ©2007-2013. All rights reserved

This website is certified by Health On the Net Foundation. Click to verify. This site complies with the HONcode standard for trustworthy health information:
verify here.