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H5N1 Pandemic Increase to Phase Four?

Recombinomics Commentary

May 23, 2006

In cases dating back to late April, three of the man's siblings, two nephews, and two of his children became infected with the H5N1 virus. Only one family member who fell ill, a brother, has recovered from the infection.

The man's older sister, believed to be the first case in this cluster, died without being tested and is not on the WHO's official case count. With this latest case, the number of confirmed H5N1 cases in this family rises to seven, with six deaths.

The man, 32, is said to have nursed his son while the boy was dying, putting him in the path of blasts of virus-laced droplets.

The above information may be used as "proof" of human-to-human transmission of H5N1 (H2H) in North Sumatra, Indonesia, which could lead to the raising of the pandemic alert level to phase 4.  Technically, the pandemic level has been at phase 4 or higher since early 2005.  At that time the number of  H5N1 clusters in northern Vietnam began to be reported at a greater frequency and the size of the clusters began to grow.

However. WHO discounted most of these clusters because each bird flu cluster was analyzed individually, and most had a bird connection, which was used to discount the proof of H2H.  When there are clusters of H5N1 cases, distinguishing a common source from the alternative explnation of H2H is heavily dependent on disease onset dates.  By definition, clusters are two or more cases linked by time and space, so the sequence of the H5N1 usually does not provided conclusive evidence because the cases are closely related in time and a similar sequence would be expected regardless of source.

However, since most cases develop symptoms 2-4 days after exposure, gaps of 5-10 days in disease onset dates suggests two or more independent infections.  Since transmission from birds to humans is very rare, two independent infections in the same family is unlikely to be linked to birds.  Family members have frequent contact with infected family member(s), and therefore transmission within families is far more common than transmission from a bird source to a human.

Familial clusters were reported as early as the beginning of 2004 and the most cited case was in Thailand in August of 2004.  The cluster has been cited as H2H because the mother of the index case was an office worker in Bangkok, far from her daughter who was on a farm with her aunt hundreds of miles away. The mother became infected after visiting her daughter in the hospital and the aunt was infect after the mother, supporting the infection of one or both by the index case.  The adults did not develop symptoms until the daughter died, and the gap in disease onset dates was in the 5-10 day range.

Most other clusters involved a potential bird source, so the "proof" was not conclusive.  However, familial clusters accounted for about 1/3 of H5N1 cases in 2004 and early 2005 and almost all of the clusters had the 5-10 gap in onset dates.

Thus, the clusters as a group provided overwhelming evidence for H2H.  This evidence became stronger when H5N1 human cases in Indonesia began to be reported in July of 2005.  Most cases were in clusters and overwhelming majority had the gap in onset dates.

In 2006, larger clusters were being reported in Turkey and Azerbaijan, and these cluster had the same gap with evidence of growing transmission chains, including evidence for cluster-to-cluster transmission.  The current cluster in North Sumatra may have the transmission chain increased to H2H2H2H, providing more proof of H2H, which may now cause an increase in the pandemic level because the concurrent cluster in Iran may be signaling a widespread increase in larger clusters in multiple regions by multiple versions of H5N1.

The deployment of Tamiflu from the United Staes to Asia is another signal of a potentional pandemic phase increase.

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