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Flawed Surveillance of H5N1 Human Transmission Chains
May 24, 2006
WHO assumes that the incubation time for bird flu in humans is 7 to 10 days, longer than that of regular flu, she said.
Henry Niman, who runs recombinomics.com, a Web site tracking the genetics of flu cases, argues that the incubation period is closer to the two to four days of regular flu, so the boy may have been infected by another family member, meaning that the virus may have made three consecutive human-to- human jumps.
But Cheng said the health agency's "working hypothesis" was still that it had jumped only twice.
The WHO working hypothesis on a limited transmission chain is similar to its investigations of earlier clusters, which focused on common sources other than humans, leading to a gross underestimate of the number of cases of human-to-human transmission (H2H) and length of transmission chains. The clusters in Turkey and Azerbaijan also involved long transmission chains, but the WHO used tortured arguments to eliminate H2H, which created faulty data, which then created additional faulty data such as the 7 to 10 day incubation time.
The two clusters that WHO linked to duck blood pudding are good examples. None of the H5N1 positive patients had the meal within the common 2-4 day incubation period. In the cluster in Hanoi in 2004/2005, the time between the meal and symptoms was 1 and 17 days. A WHO committee review of H5N1 in the New England Journal of Medicine stated "The case-to-case intervals in household clusters have generally been 2 to 5 days, but the upper limit has been 8 to 17 days, possibly owing to unrecognized exposure to infected animals or environmental sources". However, this upper limit of 17 days is due to WHO's efforts to link the brother to the meal, instead of the index case. The brother developed symptoms when the index case died, which is a common feature of the familial clusters that involve H2H. Moreover, the use of 7-10 days as indicated above, reduces the number of links in the transmission chain.
The shorter incubation time of 2-5 days also explains the 5-10 day gap between the onset date for the index case and other family members. H5N1 is still not efficiently transmitted H2H, so transmission peaks several days after disease onset, which when coupled to the incubation time, creates the 5-10 day gap between the index case and other family members, which was common in the first 15 clusters which were documented in an H5N1 familial cluster paper by WHO and the CDC.
These shorter incubation periods not only support H2H in the smaller cluster of 2 or 3, but also indicate that the clusters that have long intervals between the first and last member involve a number of transmission. These long intervals were clearly present in the larger clusters in Turkey and Azerbaijan.
However, the current cluster in north Sumatra is the deadliest. Only one of the eight members has survived, raising concerns in the changes in the eight H5N1 gene segments. Those sequences have been sequestered at a private WHO database. Two sequences from the first confirmed case in Indonesia were released, but the sequences of the other six gene segments, as well as full sequences from the other H5N1 cases in Indonesia should be release immediately.
At least two distinct H5N1 sequences are co-circulating in Indonesia, creating conditions fro dual infections and recombination. Therefore the sequences should be available to the scientific community for detailed analysis.