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Extended Human to Human H5N1 Transmission in North Sumatra

Recombinomics Commentary

May 23, 2006

The case occurred in a 32-year-old man. He developed symptoms on 15 May and died on 22 May.

The case is part of a family cluster in the Kubu Sembelang village, Karo District, of North Sumatra.

His 10-year-old son died of H5N1 infection on 13 May. The father was closely involved in caring for his son, and this contact is considered a possible source of infection.

Although the investigation is continuing, preliminary findings indicate that three of the confirmed cases spent the night of 29 April in a small room together with the initial case at a time when she was symptomatic and coughing frequently. These cases include the woman's two sons and a second brother, aged 25 years, who is the sole surviving case among infected members of this family. Other infected family members lived in adjacent homes.

The above WHO description of the North Sumatra familial cluster suggests that H5N1 bird flu was transmitted human-to-human (H2H) through three generations.  Most H2H of H5N1 has a 2-4 day incubation period, which explains the 5-10 day gap between the index case and other family members in the vast majority of clusters since 2004. The incubation range would explain all of the transmissions in the above Indonesian cluster.

The index case developed symptoms on April 27 and was symptomatic and coughing on April 29 when she could have infected her two sons (19M and 18M) and one brother (25M) generating H2H..  Media reports indicated they developed symptoms at the beginning of May, consistent with a 2-4 day incubation period.  Disease onset dates were not included in the earlier WHO update.

The index case died May 4 so additional family members could have been infected at that time by the members who developed symptoms at the beginning of May.  The new infections would extend the chain to H2H2H.  Included would have be the nephew of the index case (10M) who died May 13. The nephew could have then infected his father (32M) who developed symptoms on May 15.  This last infection would extend the chain to H2H2H2H.

The above scenario requires no tortured logic or unusual incubation times.  This is in marked contrast to WHO updates, which tried to explain clusters using common source and incubation times that fell outside of the 2-4 day period, which explains the extended chain above.

One earlier example was in late December of 2004.  It also involved a family gathering and the cases were linked to duck blood pudding.  However, the index case developed symptoms one day after the meal, which requires an unusually short incubation time.  His brother developed symptoms 17 days after the meal, requiring an unusually long incubation.  The brother-in-law who was the third person to eat the pudding developed no symptoms or detectable antibody.  A third brother who did not eat the pudding did develop antibodies.  The epidemiological data clearly pointed away from the duck blood pudding as a source, yet WHO subsequently used the 17 day incubation period as an outside value for incubation times.

The same logic was applied to another cluster that also involved duck blood pudding.  The index case developed symptoms 5 days after the meal and his younger sister developed symptoms 10 days after the meal.  The older sister who also had the pudding developed no symptoms or detectable antibody, but the grandfather who did not eat the pudding had antibodies and the nurse of the index case developed symptoms and was H5N1 positive.  Another nurse also developed symptoms, but she tested negative.

These two clusters and almost all familial clusters from Vietnam, Thailand, Cambodia, Indonesia, China, Turkey, Iraq, and Azerbaijan have the same 5-10 day gap and are readily explained using a 2-4 day incubation period coupled with transmission 2-6 days after symptoms.

The H5N1 transmission chain of H2H2H2H is among the longest reported, and generates yet another signal indicating the H2H transmission within families is common and several recent clusters are uncommonly large and have uncommonly long H2H transmission chains.

The H2H transmission placed the pandemic phase at four or higher over a year ago and the "proof" of H2H has been in the disease onset dates in the WHO updates since early 2004.

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