Beijing H7N9 Cluster Raises Pandemic Concerns

Recombinomics Commentary 12:00 April 15, 2013 The boy, surnamed Zhu, was tested positive for H7N9 flu virus by the Beijing Center for Disease Control and Prevention Sunday evening. Zhu has so far shown no flu symptoms and is receiving medical observation in Beijing Ditan Hospital. Local health officials said a neighbor of the boy had bought chicken from the family whose seven-year-old girl became Beijing's first H7N9 case. The carrier was discovered after local disease control authorities tested 24 people who raise poultry in a village of Cuigezhuang township, Chaoyang District. The above comments provide information on the relationship between the first confirmed H7N9 case (7F) in Beijing, and the second (4M), who isasymptomatic.  Both are being treated and/or observed in the same hospital in northeastern Beijing area (see map), further suggesting they both live in the same neighborhood.  This cluster raises serious pandemic concerns. The WHO statements on the absence of sustained H7N9 transmission is based on limited detection of H7N9 in contacts of confirmed cases.  Two familial clusters in Shanghai have been acknowledged.  One clusterinvolved the first confirmed H7N9 case (87M).  Two of his sons (69M and 55M) were hospitalized for pneumonia and one, 55M, died (as did the index case).  However, the two sons tested negative.  The second cluster involved a husband and wife.  The index case (64F) also died and her husband initially tested negative.  A subsequent sample from the lower respiratory tract was positive.  Both of the clusters raise serious lab detection issues.  Moreover, media reports suggests that most of the contacts of confirmed cases are being monitored via phone interviews, which may not identify milder cases.  Thus, the WHO claim of no sustained transmission is based on negative data generated by highly suspect methodologies. The two cases in Beijing are relatively mild (one is asymptomatic and the other has been transferred out of the ICU).  The current case fatality rate for H7N9 is 93% because 14 of the 15 outcomes of confirmed cases have been fatal.  The two cases In Beijing will lower that rate when discharged, but the majority of cases have been reported as critical or severe.  Moreover, the most recent death was for a case that was initially reported as stable, raising concerns that some cases WHO has classified as mild will also be fatal. Sequences from four fatal cases have been released and all have PB2 E627K.  In contrast, E627K was not found in the three avian sequencesmade public.  However, the avian sequences have Q226L, which is a receptor binding domain change that increases affinity for receptors in the human upper respiratory tract.  Thus, it is possible that some human cases have an H7N9 infection lacking E627K. However, E627K increases the polymerase activity at lower temperatures, leading to higher levels of virus in the upper respiratory tract and the Beijing screening primarily involved samples collected from the upper respiratory tract, suggesting that the asymptomatic case described above has E627K. Release of sequences from the Beijing cases would be useful.  The presence of E627K would raise serious questions about the WHO claim of no sustained H7N9 transmission and would increase pandemic concerns.