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Phasing Out H5N1 Bird Flu Pandemic Phase 4 and 5?
June 3, 2006
Dr. David Nabarro, chief pandemic flu coordinator for the United Nations, said that even if some unexplained cases were human-to-human, it does not yet mean that the pandemic alert system, now at Level 3, "No or very limited human-human transmission," should be raised to Level 4, "Increased human-human transmission."
Level 4 means the virus has mutated until it moves between some people who have been only in brief contact, as a cold does. Right now, Dr. Nabarro said, any human transmission is "very inefficient."
Level 6, meaning a pandemic has begun, is defined as "efficient and sustained" human transmission.
The above comments from Donald McNeil Jr's New York Times report, "Human Flu Transfers May Exceed Reports," suggests that movement from Level 3 to Level 4 is not necessary because Level 4 and Level 5 are being phased out. Once H5N1 achieves efficient transmission as defined by transmittion by causal contract on a pare with transmission by a cold virus, the final Pandemic level will have been reached.
The current system, which uses six phases, is designed to identify two intermediate phases (4 and 5) which represent increasing efficiencies of transmission. These changes mark progress toward increased efficiency, but at an early stage when intervention may limit progression.
The description of level 4 above, is really the current phase 6, which is efficient and sustained human transmis8sion. Transmission of a cold virus is efficient and sustained, which would also apply to H5N1.
Currently H5N1 can efficiently replicate within humans, but transmission between humans is inefficient. However, these efficiencies have been increasing, as seen in large clusters in Turkey, Azerbaijan, and north Sumatra, Indonesia. The turkey cluster was linked to a change, S227N, in the receptor bindin4g domain, which increases efficiencies and generated the largest and most sustained cluster recorded to date.
Azerbaijan also had a large sustained transmission chain, but the sequence of the H5N1 has not been released. Although these transmission chains are among the largest recorded, the transmission was limited to family members or close contacts. This limited spread was also seen in north Sumatra, and again the sequences have been withheld, so genetic remains unclear.
The increased concentration of H5N1 in the nose and throat may signal a PB2 E627K acquisition, which is another small change associated with increased virulence which may translate into increase transmission because of the preference of E627K for cooler temperatures of 33 C.
The changes in the H5N1 associated with these changes have been small incremental changes, such as those that would be measured by a pandemic phase system the distinguished the incremental steps. Since these incremental steps have been taken previously but not acknowledge, the definition above simply eliminates these intermediate phases.
However, the local response to these small changes has been to flood the region with Tamiflu and treat the outbreak as it would be treated if it were at a higher phase.
Thus, phase 4 and 5 appear to be phased o6ut, and the current status of the pandemic is one step away from the old pandemic level, 6, which is now being called level 4.
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