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Jump In H1N1 Low
Reactors In United States Raises Concerns
The above comment from today’s CDC week 8 report indicates the number of low reactors reported by the CDC has jumped from 2 to 5 in a week that reflected an all time low in H1N1 testing. The per cent positive is on the rise and is at the highest level in 2010, and as high as it has been since mid-December (week 50), so the number of positive samples is up, in spite of the very limited testing.
Increases in low reactors are expected as the H1N1 evolves away from the current immunity as well as the California/7 based vaccine. The first two low reactors reported by the CDC had N159D and a phylogenetic tree by the US Air Force School for Aerospace Medicine had an isolate, A/Texas/732/2009, from week 47 which had N159S (listed as N156S in tree), which may also be a low reactor. In addition, another isolate, A/OCONUS4/4081/2009 from week 5, had N159K but since the isolate was outside of the continental US it is unlikely to be one of the new low reactors. However, as of Feb 2, 472 HA sequences had been sent to the CDC, so additional examples of N159K in the US may be present. Moreover, the detection of three different changes at the same position (N159D, N159S, N159K) suggest that this position may play a significant role in immunological escape in the upcoming wave. This change is adjacent to G158E, which has also been linked to low reactor status in isolates from Germany, as determined by the CDC and Mill Hill. The changes are in addition to K157E, which has been reported as another low reactor.
These recent reports of low reactors, in addition to D225G which has been designated a low reactor by Mill Hill and was recently shown to have a statistically significant association with severe and fatal cases in Norway, and higher frequencies have been reported for Ukraine, raise concerns that current vaccinations and immunity from prior H1N1 infections will have limited efficacy against newly emerging variants of H1N1.
All three pandemics last century had a fall and spring wave. Therefore, a wave is expected to begin in the near term, and several data sets, including this week’s uptick in samples testing positive for H1N1, suggest this third wave may have already begun. Unfortunately, H1N1 surveillance at this time remains weak. Last year the first H1N1 was from a late March collection, even though data from Mexico indicates the pandemic began 1-2 months earlier. The limited testing in the US and other countries worldwide increases the likelihood of delayed detection again. A year ago that delay led to a late start in vaccine production, which delivered product after the fall outbreak had peaked, creating a large surplus.
Although this vaccine has been recommended for the 2010/2011, it is likely to have limited utility, because the low reactors which are being identified now will likely lead to a vaccine target that is not well recognized by an immune response directed at the current target.
The jump in low reactors when surveillance is at an all time low raises concerns that additional changes are not well represented in current reports, and these latest developments are cause for concern.