Tuesday, 11 March 2014

H7N9 and human infections: not just a paltry matter

Jones and an all-star cast of colleagues from Hong Kong, Shenzen, Beijing and Tennessee have looked at songbirds and their susceptibility to a human isolate (infectious virus recovered from a human case of H7N9 influenza) H7N9 infection (1).

But before I note the good bits of their study, this paper is one of importance for adding a lot to our understanding of how H7N9 is jumping to people from poultry/live bird/wet markets. It's also a great reference if you want to better understand influenza and birds overall. 


We've read much about human cases of this avian virus having had contact with "poultry" and bird markets and  from that we assume that poultry are the pool in which H7N9 is swimming (reservoir); but where did the poultry get it from (source/natural host)? Its also interesting to note that: 
  1. Very few poultry test positive for the virus; may simply be because of a test-based problem including using a test that is insensitive or sampling from the wrong end of the bird (testing the cloaca instead of throat as was discussed ). 
  2. Looking at the sequences of the H7N9 gene segments suggested that wild birds (bramblings) played a part in the evolution of the virus currently infecting humans in south east China (4)
  3. Pigeons have tested H7N9-positive (2,3)
So it might be that at least some of the human exposures are not from poultry but from other birds.

The authors of this latest article note the songbirds are common pets and so are in close contact with their owners. In the wild, such birds are likely to interact with farm birds.

Some key findings of this new study are:
  • A/Anhui/1/2013 was the strain used for H7N9 studies; it was an isolate from a human but early on and similar to bird (6) strains. H5N1 (A/Vietnam/1203/05) and H3N8 (A/songbird/Hong Kong/SV102/2001) were also used for comparisons
  • Zebra finches (Taeniopygia guttata), society finches (Lonchura striata domestica), parakeets (Melopsittacus undulates) and wild-caught house sparrows (Passer domesticus) were kept isolated for 3-weeks prior to experiments to let any naturally acquired infections burn out; none of the birds had antibodies suggestive of previous infection by an H3, H5, H7 influenza A virus (is that low prevalence normal?)
  • Birds were inoculated with 105 50% egg infectious doses of virus via nose, eye and mouth (that should do it) and then put in the same cages, sharing water and food, with uninfected birds
  • Virus testing was by growth using eggs (3/sample collected)
  • All inoculated birds shed virus (only) from the oropharynx; finches shed most virus at 2-days post inoculation (dpi); parakeet viral shedding could be detected by culture for 2-days and from finches for 6-days
  • Communal water troughs yielded culturable virus; zebra finches shed most virus but water consumption and drinking frequency were not measured and may have differed among bird species
  • No virus could be detected at 8dpi
  • 1 sparrow showed signs of disease and died; 1 zebra finch died without signs of disease (some loss of appetite)
  • Birds in contact with infected birds did not often acquire infection but when they did, they also shed via the oropharynx
  • In finches that were killed for organ testing, virus was mostly found in the trachea; some was isolated from brain and eye tissues of 1 society finch and in the small and large intestine and a high titre form the lung of the other. H7N9 was grown from the brain, lung and intestines of zebra finch. H7N9 was not found in surviving sparrow organ tissues; in the dead sparrow, some H7N9 was found only in the lungs
  • Nearly all inoculated birds mounted a specific antibody response to H7N9 after inoculation. Among the contact birds, 3/3 zebra finches, 1/3 society finches (had highest amount of antibody), 2/3 sparrows and 0/2 parakeets mounted a response to virus indicating that they were infected but did not show signs of illness nor did they shed virus, at least at culture-detectable levels
So songbirds, can be infected by a human H7N9 isolate, they can shed the virus into the environment, they can die (presumably) due to H7N9 infection, 33-66% of songbirds in contact with an experimentally infected songbird acquire aninfection (even if it was rare to grow infectious virus from that contact which may be a sensitivity issue of the testing) and they mount an immune response to the infection. Given that H7N9 acquisition seems to be a numbers among humans, this degree of transmission among birds fits well.

It was also very interesting that water troughs often contained lots of shed H7N9 virus. This is not new in the world of influenza virus but its nice to cross the 't' for H7N9. The authors note that studies of transmission from songbirds to poultry via communal water sources are yet to be conducted. Seems like this would be a very important piece of the influenza puzzle and with broad application to future outbreaks and seasonality in birds via migration. 

Add to all of this that songbirds are present in many markets (thanks to @Crof, @Laurie_Garrett and @debmackenzie1 for supporting info via Twitter this morning; also see refs from Jones et al (1) and a related story from New Scientist (8)) and that older males are a key demographic for keeping songbirds as luck-enticing (and cute) pets. They are also over-represented among H7N9 cases (see adjacent chart). A good fit.

Another recent study (7) shows chickens and quail (a possible amplification host helping bridge the gap between wild birds and poultry) shed a lot of H7N9 after experimental inoculation via an intranasal route. Also, quail (but not pigeons) shed enough H7N9, for long enough, to pass it along to their contacts; less so ducks.

None of this may be very new to some of you, but it's nice to see data that confirm it all for H7N9. After all, as someone reminded me recently on Twitter, data is just how we roll.

It's not hard to see the circle of life for influenza viruses is there for the interpreting and that non-poultry birds may be important intermediate hosts of H7N9 and act as a source of other influenza A viruses. 

Just how many human cases of H7N9 are acquired by songbirds vs chickens/ducks/quail/geese remains unquantified....perhaps unquantifiable.

References...

  1. Possible Role of Songbirds and Parakeets in Transmission of Influenza A(H7N9) Virus to humans.
    http://wwwnc.cdc.gov/eid/article/20/3/pdfs/13-1271.pdf
  2. A summary of Influenza A(H7N9) virus findings in birds and humans
    http://virologydownunder.blogspot.com.au/2013/10/a-summary-of-influenza-ah7n9-virus.html
  3. Emergence of avian influenza A(H7N9) virus causing severe human illness - China, February-April 2013.
    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6218a6.htm
  4. Sunny summer or birds on the wing?
    http://virologydownunder.blogspot.com.au/2013/05/sunny-summer-or-birds-on-wing.html
  5. Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
    http://press.thelancet.com/H7N9genetics.pdf
  6. Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20453
  7. Role of poultry in spread of novel H7N9 influenza virus in Chinahttp://jvi.asm.org/content/early/2014/02/20/JVI.03689-13.long
  8. Budgies may be behind latest spread of H7N9 bird flu
    http://www.newscientist.com/article/mg22129542.000-budgies-may-be-behind-latest-spread-of-h7n9-bird-flu.html#.Ux5CnvmSx8F