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H7N9 Minghang Cluster Raises Pandemic Concerns
Recombinomics Commentary 17:00
April 6, 2013

Wu Demao was bewildered when he heard that his son-in-law, Wu Liangliang, who died on March 10 at Shanghai No 5 People's Hospital, was a victim of H7N9 bird flu.

The hospital paid the family 130,000 yuan (HK$161,000) in compensation on March 26, saying it was for humanitarian reasons and for its minor responsibility in Wu Liangliang's treatment, without elaborating.

The above comments describe a payment to the family of the second H7N9 case (27M) who lived in the Minghang District and died at the Shanghai Number Five People’s Hospital in Minhang.  The first confirmed case (87M) was also treated on the same floor of the hospital.  In addition, his two sons (69M and 55M) were also treated at the hospital, so the family of the second victim claimed that their relative had been infected at the hospital by one of the three family members being treated at the hospital.

The three family members had been described earlier (in March 7 media reports) and prior to the announcement of confirmation of H7N9 in the father this week, their cluster had been a mystery.  The media reports noted that all three had developed pneumonia and two had died (87M and 55M).  Microblogers has suggested that deaths were due to the novel coronavirus (nCoV), which had been circulating in the Middle east, but transported to the UK via an index case on a commercial airline.  However, the cases in Shanghai tested negative for nCoV. 

Micobloggers then claimed that the deaths were due to influenza, which was denied.  Deaths were said to be due to pneumonia caused by changing weather.  The micoblogger was then arrested and fined for spreading false rumors.  However, the father was H7N9 confirmed, confirming the influenza “rumor”.

Controversy did not end with the H7N9 confirmation of the father because the sons tested negative and recently WHO said no additional samples were available.  Thus, the number of confirmed cases at the hospital remains at two and human to human transmission is denied.

The hospital payment suggests that the younger victim may have been infected while being treated at the hospital, and additional media reports cited additional cases at the hospital who had been H7N9 confirmed, including three deaths outside of the family cluster, as well as two cases discharged.

Sequences from the two confirmed cases were made public by the WHO Chinese Influenza Research Center.  Although the sequences from the first case, A/Shanghai/1/2013, and the second case, A/Shanghai/2/2013 were related (both had PB2 E627K, a 5 amino acid deletion in N9, and H9N2 internal genes, the sequences were distinct and did not support infection of the second case by the first case.  However, the presence of the other cases at the hospital may have been the source of the infection in the second case, which would involve human to human transmission (H2H) in the family cluster. 

In that cluster the confirmed case had not been outside of his residence in the two weeks prior to disease onset, which was five days after one or both of his sons were hospitalized.  Thus, the gap in the disease onset dates, coupled with the same symptoms and the lack of exposure by the index case strong supports H2H transmission within the family.  The above payment also suggests H2H transmission may have been the cause of the infection in the second confirmed case.

Moreover, the cluster of cases at the hospital beyond the two confirmed cases and contacts suggest that the Minghang District may have been the epicenter for the outbreak.  H7N9 has been detected in birds at three wet markets in the area, including one that is less than 2000 feet from the hospital (see map).  Although the avian sequences are closely related to the human sequences, it is unclear of the human adaptation changes such as PB2 E627K, H7 Q226L or L226I are in the bird sequences.
The genetic changes have much in common with H5N1 bird flu transmission studies.

However, the concentration of confirmed, probable, and suspect cases at the Minghang hospital suggest that considerable human transmission is occurring in the area, but only a small subset of cases are being reported.  Although there are 18 confirmed cases, including 6 deaths reported to date, none of the confirmed cases have been discharged, which gives a case fatality rate of 100%. 

This rate is due to a gross under-reporting / testing of milder cases, which provide evidence for sustained H2H transmission, WHO and CDC denials notwithstanding.

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