Wednesday, 7 August 2013

A detailed report of a Jiangsu H7N9 infection family cluster and the probable involvement of human-to-human transmission

Qi and colleagues describe in the British Medical Journal (BMJ), their detailed analysis of a likely human-to-human (h2h) transmission event by influenza A(H7N9) virus. The infection is likely to have traveled a 60-year old father to his 32-year old daughter, but not to any close contacts-1 "passage" of transmission. 

This event was previously defined as a family cluster, but the new BMJ report adds to the information published in the NEJM article by Li et al in April (see "Jiangsu Family Cluster", Figure 3).

The conclusion is that H7N9 likely spread to one other person but no further, in this instance, using these tests to define infection. As the accompanying editorial by Rudge and Coker notes, it's not surprising to see this happen. The media have become somewhat carried away in suggesting this is the first case of h2h transmission. That "honour" probably goes to the family of the first announced case, the 87-year old male from Shanghai and his family cluster

To be pedantic, this new BMJ analysis does not actually prove h2h transmission (hence the word "probable" in the title I suspect) highlighting just how hard it is to do that in the "wild" and after the transmission event has occurred. It is probable though. However, we know for certain that H7N9 can be transmitted between the 4-legged furry kind of animal (see related posts here, here and here).

Some key take home messages...

  • 2 patients (60M and his daughter 32F) 13 samples of the environment were tested by PCR
  • 60M, who had hypertension, developed respiratory disease March 8th and was hospitalized March 11th. He died of multi-organ failure and disseminated coagulation May 4th.
    • An endotracheal aspirate (ETA) was H7N9 POS, but a throat swab was NEG
    • No diarrhoea was linked to infection 
  • 32F was an otherwise healthy developed symptoms March 21st and was hospitalized March 24th. She died of multi-organ and heart attack on April 24th
    • Throat swab and ETA were H7N9 POS
  • 3 viral isolates were able to be grown in culture and 2 complete genomes (8 segments each) were deposited onto, but not yet released from, GenBank
    • The sequences from eh two human cases reportedly differ a little, mostly in the NS and NA segments whereas the environmental isolate's M segment showed the most divergence from the 2 human cases. The genome details are...
      • KF034916-KF034923 - 60M (A/Wuxi/2/2013)
      • KF034908-KF034915  - 32F (A/Wuxi/1/2013)
      • KF150605-KF150612 - (A/Environment/Wuxi/1/2013)
  • All samples were negative for other respiratory viruses
  • The study did not include interviews with the 2 cases as they were too ill so some avenues of infection could not be excluded
  • Both cases were treated with oseltamivir 3-10 days after symptom onset-the US CDC recommends commencement within 48-hours of symptoms, which can be difficult to achieve as patients may present some time after disease is well underway
  • Of 43 close contacts, none were RNA positive for H7N9 nor were any positive for antibodies to H7N9 suggesting they had not hosted an infection that was missed by PCR
  • The in-house ("home made") antibody test was considered, by the authors, to be insufficiently sensitive and may have missed evidence of exposure in contacts. Prospective screening of contacts was not done.

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