Effect Measure

Flu in dogs again, but not H5N1

The index case was a 5 year old Miniature Schnauzer with 5 days of nasal discharge and sneezing. The dog recovered but the next case, a 3 year old Cocker Spaniel wasn’t so lucky, nor were the 2 Korean hunting dogs (Jindos) or a 3 year old Yorkshire terrier. Then 13 dogs in a shelter started to show signs of nasal discharge, cough and high fever. Antibody studies showed that they had all been suffering from influenza infection, subtype H3N2. These cases happened in the spring and summer of 2007 (NB: this is not flu season). H3N2 is the most common subtype involved in human seasonal influenza. Is that where the virus came from? A team of Korean researchers got specimens from the schnauzer, the cocker spaniel and the Yorkshire terrier and have just reported their findings in the CDC journal, Emerging Infectious Diseases (Song et al., Transmission of Avian Influenza Virus (H3N2) to Dogs).

The specimens were used to inoculate eggs and replicated influenza virus was isolated and subjected to genetic analysis and used to experimentally infect 9 beagle pups intranasally. The researchers were looking for signs of infection, including severe illness, development of antibodies (“seroconversion”) and viral shedding. They got all three. The pathologic findings were confined to the respiratory tract but they were relatively severe. The virus was shed in nasal discharge but not feces. And all inoculated dogs seroconverted.

This virus efficiently infected the dogs, as might be expected from the size of the kennel outbreak. The sequence analysis suggested the virus was of bird origin, not human origin. Certainly this is not the first time a bird flu virus has jumped from birds to mammals and become transmissible there. The 1918 Spanish flu is suspected to be of that kind and an H7N7 bird virus caused a fairly large outbreak of conjunctivitis (and one death) in The Netherlands in 2003. Cats, ferrets and marine mammals have also been infected with avian viruses. The current “bird flu” (H5N1) is also an avian virus. H3N8 has caused outbreaks of influenza in dogs, but this outbreak is H3N2, so it is different. The H3N2 designate only two of the proteins comprising the influenza A proteome and two viruses with serotype H3N2 can have very different “internal” genes. These genes in the Korean isolates bear similarities to internal genes of ducks in Hong Kong, Japan and southeast China.

So why did the dogs get infected with bird H3N2 viruses and not the ubiquitous H3N2 from humans? The authors suggest it is because the dog respiratory tract is mainly equipped with avian type receptors (alphas (2, 3) rather than alpha (2, 6); see our posts here on this topic). This is a reasonable explanation but more work needs to be done.

So how did the dogs get infected? It is common practice to feed them scraps from birds, including untreated duck and chicken muscle, internal organs, and heads. Dogs are not only pets but livestock in Korea, eaten as a delicacy. Fattening them up and selling and keeping them in live animal markets is a common practice:

Live-bird markets are thought to constitute “a missing link in the epidemiology of avian influenza viruses” because they bring together numerous hosts, such as chickens, ducks, turkeys, geese, and doves, in a high-density setting, which represents an ideal environment for virus interspecies transmission. (Song et al. Emerging Infectious Diseases)

So what is the lesson here? One is the usual humbling one: there is still a lot to learn about the influenza virus. Another is that there are a lot of potentially susceptible species that we have not looked for or at in a systematic fashion. In much of southeast asia and asia birds are ubiquitous companions of humans. They live together and sometimes sleep together. In the industrialized west dogs are common companion animals that live in close proximity to humans. If it turns out that they are a common reservoir for bird viruses, then much more of the world’s population could be liable to a virulent influenza virus that got into dogs just as H5N1 got into poultry. The H3N2 case is probably not a likely pandemic source (despite what the Korean scientists say in their Discussion) because there is widespread immunity to H3N2 in the global population, even though changes in the strain mean the protection varies as the virus mutates. On the other hand, H3N2 keeps infecting humans because it changes enough from year to year to make that immunity less effective and H3N2 is sufficiently virulent on its own that it and H1N1 kill an estimated 30,000 to 40,000 Americans yearly. If a variant that was much more virulent came around it could get nasty.

And there are other bird viruses that might also get into dogs or other companion animals. It’s about time a serious, systematic investigation and any indicated surveillance of many more animal species got underway.

Comments

  1. #1 herman
    April 3, 2008

    What about humans infecting animals? As you know this can happen. What about H5N1 infecting a tuberculosis bacteria?

    Please read:
    Just as men get infected, bacteria can get infected and the small tadpole shaped viruses that do this are called bacteriophages, viruses that infect regular bacteria and mycobacteriophages, viruses that infect tuberculosis, which is a mycobacteria. Or both can be called simply “phages”. Bacteria reproduce asexually, so there is no variation of genes in a colony, and no way for them to exchange genetic material. Phages, the viruses which live inside bacteria such as the mycobacteria called tuberculosis, can allow exchange of this genetic material, as well as force natural selection. The way bacteriophages or “phages” allow gene diversity is after they insert their own genetic material into their bacterial prey’s genome, they in essence highjack the manufacturing capacity of the bacteria for their own purposes, reproducing new viruses in the bacteria. However, when a virus makes copies of itself, sometimes it extracts some of the bacteria’s DNA and copies that into the virus. When these viruses infect other bacteria, usually of the same class, such as from bird tuberculosis to human tuberculosis inside the pig, they add the other bacteria’s genes to the new bacteria. This creates genetic diversity or “mutations”. Such genetic “mutations” can create far more virulent bacteria then either of the parent bacteria. This is what it is theorized happened in 1918 Haskell County, Kansas where genetic elements of human and avian tuberculosis combined inside hogs just prior to the pandemic of 1918.
    What exactly is the interaction between influenza A virus and tuberculosis? At present this interaction is not well understood. Could an influenza virus latch onto a tuberculosis bacteria in a dog or bird, and then be transmitted to a human? If it bacame a pandemic, would you call it a tuberculosis pandemic or an influenza pandemic?
    In 1918 it was the pig that was the host for this combination.

  2. #2 attack rate
    April 4, 2008

    Revere – you may also be interested in the recent paper from one of the virology journals about transmission and vaccination work in cats. I unfortunately don’t have the reference to hand and it isn’t showing up in my searches – it was in a journal I don’t normally read.

  3. #3 medmatters
    April 4, 2008

    Here are a few…

    http://vir.sgmjournals.org/cgi/content/abstract/89/4/968

    J Gen Virol 89 (2008), 968-974; DOI 10.1099/vir.0.83552-0

    Protection of cats against lethal influenza H5N1 challenge infection

    Thomas W. Vahlenkamp1,, Timm C. Harder1,, Matthias Giese1, Fengsheng Lin2, Jens P. Teifke1, Robert Klopfleisch1, Ralf Hoffmann2, Ian Tarpey2, Martin Beer1 and Thomas C. Mettenleiter1
    1 Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
    2 Intervet UK, Walton Manor, Walton, Milton Keynes, UK

    Correspondence
    Thomas W. Vahlenkamp
    thomas.vahlenkamp@fli.bund.de

    Highly pathogenic avian influenza virus (HPAIV) H5N1 of Asian origin continues to circulate in poultry and wild birds, causing considerable concern for veterinary and public health in Asia, Europe and Africa. Natural transmission of HPAIV H5N1 from poultry to humans, resulting in infections associated with high mortality, and from poultry or wild birds to large felids and domestic cats has been reported. Experimental infection of cats with HPAIV H5N1 derived from a human patient resulted in lethal disease. The role of cats in the adaptation of HPAIV H5N1 to mammals and vaccination regimens for the eventual protection of cats, however, remain to be elucidated. Here, it was shown that cats can be protected against a lethal high-dose challenge infection by an inactivated, adjuvanted heterologous H5N6 avian influenza virus vaccine. The challenge HPAIV H5N1 was derived from a naturally infected cat. In non-vaccinated cats, low-dose exposure resulted in asymptomatic infections with minimal virus excretion. As diseased cats can transmit the infection to na�ve contact animals, the epidemiological role of H5N1-infected cats in endemically infected areas as a link between wild birds, poultry and humans needs close inspection, and vaccination of cats should be considered to reduce possible human exposure.

    These authors contributed equally to this work.

    and..

    This article from China talks about making an H5N1 vaccine for the cat famialy (Felidae) using a recombinant with an adenovirus. This combination seems to have some advantages as a vaccine such as growth in cell culture and initiating both T-cell and B-cell responses and would seem to be easily adapted to humans. Also note the virus they are using A/tiger/Harbin/01/2003 (HSN1) HA. This is probably a typo with the HS supposed to be H5 as they are making an H5 vaccine. Harbin has a Siberian Tiger Park…

    There seems to be a recurrent theme of feeding poultry to animals….

    Here is a video showing people throwing birds to the tigers at the Harbin Tiger Park….

    http://www.youtube.com/watch?v=50rd9D8Yj6o

    http://lib.bioinfo.pl/pmid:16736595

    Wei Sheng Wu Xue Bao. 2006 Apr ;46 (2):297-300 16736595 (P,S,E,B)

    [Construction and experimental immunity of recombinant replication-competent canine adenovirus type 2 expressing hemagglutinin gene of H5N1 subtype tiger influenza virus]

    Yu-Wei Gao, Xian-Zhu Xia, Li-Gang Wang, Dan Liu, Geng Huang
    The Military Veterinary Institute of Academy of Military Medical Science of PLA, Changchun 130062, China. gywtext@yahoo.com.cn

    H5N1 highly pathogenic avian influenza virus was highly pathogenic and sometimes even fatal for tigers and cats. To develop a new type of vaccine for Felidae influenza prevention, recombinant replication-competent canine adenovirus Type 2 expressing hemagglutinin gene of H5N1 subtype tiger influenza virus was constructed. A/tiger/Harbin/01/2003 (HSN1) HA gene was cloned into PVAX1. The HA expression cassette which included CMV and HA and PolyA was ligated into the E3 deletion region of pVAXdeltaE. The recombinant plasmid was named pdeltaEHA. The pdelta EHA and the pPoly2-CAV2 were digested with Nru I /Sal I, respectively. The purified Nru I/Sal I DNA fragment containing the HA expression cassette was cloned into pPoly2-CAV2 to generate the recombinant plasmid pCAV-2/HA. The recombinant genome was released from pCAV-2/HA, and was transfected into MDCK cells by Lipofectamine. The recombinant virus named CAV2/HA was gained. Anti-H5N1 influenza virus HI antibody (1:8 – 1:16) was detected in the cat immunized with CAV-2/HA.

  4. #4 attack rate
    April 4, 2008

    Thanks MedMatters – The first reference you list was the one I was thinking of.

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