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H5N1 Human to Human Transmission Comparison

Recombinomics Commentary
December 22, 2007

Doctor Heymann says an analysis of the information is not yet complete. But preliminary results indicate there was human-to-human transmission of the virus. He says there could have been a common source of the infection.
"The team feels, we have not seen all their evidence yet, but they feel that this could be an instance of close contact of human-to-human transmission in a very circumscribed area and not sustained," he explained. "Just like happened in Indonesia and in Thailand."

The above comments reference the clusters in Indonesia and Thailand, which have been called proven human to human transmission (H2H) in other media reports, but really are only slightly more "proven" than the dozens of other H5N1 H2H clusters.

The cluster in Thailand was somewhat unusual because the mother of the index case was an office worker and did not have exposure to poultry.  She had close contact with her daughter after hospitalization, and then developed symptoms after her daughter died.  The index case's aunt also was infected, and the cluster might have been H2H2H, but the New England Journal of Medicine report focused on transmissions from the index case, and discounted the scenario where the index case infected her mother and her mother infected her aunt.  The index case was never tested for H5N1 because she was misdiagnosed as having dengue fever, but the cluster was characterized as the first proven case of H5N1 H2H transmission.

The cluster in Karo, Indonesia was larger and had two time gaps indicating H2H2H.  The source of the infection of the index case was unknown, but her condition deteriorated just the day before a family barbeque and many blood relatives slept in the same small room with the index case.  They developed symptoms within a day or two of each other, and the final case was the son of one of the family members infected by the index case.  Once again the index case wasn't tested before she died, but the family members were H5N1 positive and all but one died.

However, the differences between these clusters and the dozens of other clusters were minor. Other clusters did not involve an obvious source, had significant time gaps between the disease onset dates, and had contact between the index case and infected family members.

Thus, the evidence for H2H in most of the other clusters was similar to that for the two cited clusters.  The cited clusters did not have obvious genetic changes in the H5N1 sequences.

However, many of the clusters associated with the Qinghai strain did have receptor binding domain changes, and the Pakistan cluster almost certainly involves the Qinghai strain.  Thus, a comparison with those clusters would be more appropropriate.  In Turkey and Azerbaijan there were multiple clusters that developed at the same time, as was seen in media reports of the Pakistan outbreak.  These Qinghai outbreaks also had receptor binding domain changes in the H5N1 isolates from the cluster members.  Therefore comparison with those clusters would seem to be more appropriate.

In Turkey, the locations of the clusters was concentrated in eastern Turkey, but was not limited to one geographic location.  The same pattern was seen in the Azerbaijan clusters.  In Iraq, there was only one official cluster, but media reports raised questions about additional clusters.  Sample collection in Iraq was less than ideal, and the one cluster may have not have been unique.

Media reports indicate that new infections in Pakistan have not been found since December 6.  However, there is no situation update with specifics, and comments have already been made about infections being mild.  Detection of mild cases has been difficult because of similarities with other respiratory diseases, coupled with limited testing and application of Tamiflu blankets.

Media reports indicate this outbreak has been sustained for the longest period reported to date, and the delay in release in a situation update following confirmed H5N1 clusters is without precedent.

The first case was reported have been exposed two months ago, lab confirmed almost two months ago, and reconfirmed a week ago.

These extensive delays remain cause for concern.

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