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High CFR In Maryland Cluster Raises H5N1 Concerns
Recombinomics Commentary 11:00
March 7, 2012

Dr. Gio Baracco, associate professor of infectious diseases at the University of Miami’s Miller School of Medicine, speculated, based on the very limited amount of information available, that the cause is non-infectious and could be something environmental.

“The reason is that for most infections, transmission rate is not 100 percent and the fatality rate is not 100 percent,” he said. If the woman’s hospitalized daughter dies, the case fatality rate will be 100 percent, he explained.

The above comments note the high case fatality rate (CFR) in the flu cluster in Calvert County, Maryland and suggest the deaths were not due to an infectious agent.  However, most or all of the symptomatic family members have tested positive for influenza A which has raised H5N1 concerns due to the high CFR and the reports of cases coughing up blood upon admission.  Human H5N1 cases have a high CFR in part because of D225G and recent transmission studies have demonstrated the ability of H5N1 to transmit in a ferret model using three different H5s (clade 2.2 from Egypt, clade 2.1 from Indonesia, clade 2.3 from Vietnam), all of which have D225G.

Moreover, clade 2.3 has moved into migratory birds and expanded its geographical reach to south Asia and Europe, raising concerns of expansion into North America.  The index case for the Maryland cluster was in a rural region adjacent to the Chesapeake Bay, which is home to a large migratory bird population at this time of year.  Similarly, the adjacent Delmarva peninsula has a high density of poultry farms, although no H5N1 has been reported in poultry in the Americas.

However, D225G has also been reported in severe and fatal H1N1pdm09 cases, including those in Ukraine in 2009 as
well as the Duke Medical Center death cluster.  However, most fatal H1N1pdm09 cases are in patients under the age of 65, and the index case in Maryland was 81, decreasing the liklihood pf H1N1pdm09 involvement.

A more likely possibility would be H3N2v which also has D225G.  Although only 20 confirmed cases have been reported in the United States, there is no widely available direct test for H3N2v.  Although it can be detected in various influenza A tests, additional PCR testing depends on cross-reactivity with seasonal H3 or H1N1pdm09 NP targets, and levels are likely markedly higher than those reported.  Moreover, there have been widespread reports of pneumonia throughout the United States, including Maryland, raising concerns that a more virulent H3N2v may appear in human populations.

An increase in H3N2v cases is also supported by the explosion of H3N2 low reactors in the week 8 CDC report.  H3N2v has a human H3 that jumped to swine in the 1990’s and therefore would produce a low reactor profile in the CDC’s antigen characterization test as seen in 63.8% of the newly reported case last week.  The CDC was silent on the spike in low reactors, and none of the 22 isolates from 2012 were listed as low reactors, although all were collected in January and only 1/3 had antigen results and all were Perth/16-like.

Samples from the Maryland death cluster have been sent to the CDC for analysis.  Release of sequences from the current cluster as well as the low reactors listed in the week 8 FluView report would be useful.

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