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Confirmed H2H2H H5N1 Transmission in Pakistan
Recombinomics Commentary 17:14
April 3, 2008

The recently released WHO update on the H5N1 transmission in Pakistan in late 2007 confirms it was human to human to human (H2H2H).  The transmission chain is supported by disease onset dates, contacts, and laboratory confirmation of three of the four members in the transmission.  This chain would match the largest confirmed chain, which involved more family members, but was limited to two distinct transmission events in Karo, Indonesia.

For the Pakistan cluster, the index case was a veterinarian, who was infected while leading a cull of poultry in October, 2007.  He developed symptoms on October 29, several days after the cull.  He infected one of his brothers who cared for him.  The brother developed symptoms on November 12 and died November 19.  This brother infected two other brothers, who both developed symptoms November 21.  One brother died November 27, while the other brother recovered.

Thus, of the four cases, two died and two recovered.  Of these four, three were laboratory confirmed, but only one of the three (the second dead brother) was confirmed with PCR and virus isolation.  The other two were confirmed serologically.  The first brother to die was not laboratory confirmed and therefore is officially a probable case, based on clinical course, including pneumonia and death.

The latest update should clear up some of the confusion generated by the delays in reporting, false negatives linked to sample degradation, and conflicting and/or confusing statements, due in part to the delays (first media reports were in early January) and degradation.

This cluster also highlights weaknesses in testing.  If this was not a cluster, it is likely that only one of the four cases would be confirmed instead of three of four.  The three create a cluster, although the link between the index case and two brothers developing symptoms is the first fatality, who was not lab confirmed.

The identification of serious testing shortfalls through cluster analysis is not unusual.  Most clusters have one or more aspects which involve false negatives or lack of sample collection / testing.

There are two such recent examples in Indonesia.  In both clusters, no sample was collected from the index case, who died, and both clusters have H5N1 confirmed family members.  One cluster was specifically denied and the denial was accepted at face value in a Promed commentary.  The second index case has not been identified in the English language media. Neither suspect cluster was mentioned in the WHO update on Indonesia.

These failures to confirm obvious H2H in current clusters remains a cause for concern.  Similarly, the confirmed H2H2H cluster in Pakistan raises additional questions about failures to report or confirm additional human H5N1 cases in Pakistan, India, and Bangladesh.

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