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Extended Human to Human H5N1 Transmission Review

Recombinomics Commentary

May 24, 2006

"If we can't find an external source that explains all seven confirmed cases, then we have to go with the theory that this is human to human," says Peter Cordingley, the spokesperson for the WHO's Western Pacific regional headquarters. Human to human transmission within a family is believed to have occurred at least twice before, in Thailand and Vietnam, although never involving this many people. But if the 10-year-old boy was infected by a family member, and then went on to infect his father, it would represent the first known time the virus had passed from human to human to human. "It's certainly possible," says Gregory Hartl, a WHO spokesperson in Geneva.

The above comments contain qualifiers that keep the statements true, but misleading.  The qualifiers are "at least" for the number of cases of human-to-human (H2H) transmission, and "known" for the number of times longer chains (H2H2H) been reported.

There has been a long list of H2H clusters.  The vast majority of familial clusters have a 5-10 day gap between the disease onset date of the index case and other family members.  In many instances, the index case has contact with poultry, and this link is used to discount the H5N1 in the family members. The current cluster has been acknowledged to be H2H because the poultry source has not been identified and the length of time between the disease onset date of the index case (April 27) and the most recent fatality (May 15) is long and the number of fatal cases in between is large (five plus one H5N1 confirmed survivor).

However, the number of transmission is still cloudy because WHO has failed to release the disease onset dates for the six family members between the first and last case.  The incubation time for H5N1 is 2-4 days, which suggests the chain was H2H2H2H or H2H2H2H2H, which is also supported by contact hisptory in the WHO update.  Both of these chains are long, but may not be the longest.

Earlier this year there were two large clusters involving several families. The first began at the end of 2005 and extended well into January.  This cluster was in Turkey and confirmed cases were identified in three families of cousins.  However, the WHO updates failed to indicate that the three family members were related and failed to mention the hospitalizations of family members when other family members were confirmed.  Media reports suggest the index case infected his three siblings.  The index case and two siblings died and were H5N1 confirmed.  Cousins were at a family gathering, and they also developed symptoms and 10 family members were hospitalized.  Two were placed in intensive care and tested positive for H5N1.  The timing of the cases suggested that these two families represented H2H2H2H.  However, these cases were followed by the hospitalization of two more cousins who also tested positive and one died.  Thus the chain would then be extended to H2H2H2H2H.  However, there hospitalization was followed by the hospitalization of yet another set (five) of cousins who were said to have tested negative.

The reports from Turkey stopped suddenly when the members of the fourth family were hospitalized and the number of negative cases, including the fourth sibling of the index case, raised credibility issues.  However, WHO announced in January that they were planning on collecting 10,000 serum samples from contacts of the cases to determine the level of H5N1 transmission.  Most patients infected with H5N1 will develop peak serum antibodies about 3 weeks after infections.  Thus, samples should have been collected in late January and February.  The results from that testing has not been disclosed.

Since the cases had connections with poultry. These cases were not considered as H2H (or H2H2H2H2H), but there is little reason for the cases to be focus in these three related families.  In Azerbaijan, cases extended over a month, and although wild bird feathers may have led to infection of the index case, it is likely than transmission to family members over such an extended time period was a long H2H chain.

Thus, the current cluster in Indonesia may not be the longest chain, but it is the deadliest, with seven fatal cases in the eight member cluster.  This may be due to a combination of a cleavage site common in Asian H5n1 isolates, coupled with a PB2 E627K polymorphism that is usually not found in birds and is almost always fatal when coupled with the H5N1 cleavage site.

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