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H5N1 Clade 7 Clusters Cause Concerns
Recombinomics Commentary 15:15
February 6, 2009

January 7 children in Hunan fever symptoms January 11 Back Shanxi Xiaoyi, January 14 to Fenyang hospital because of exacerbations that night immediately transferred to hospital for treatment of children in Shanxi Province. Children's Hospital in accordance with children have a history of exposure to live poultry markets, his mother died and because of severe pneumonia in children with the disease characteristics, a high degree of alertness suspected pneumonia of unknown causes, the rapid organization of nosocomial expert consultation, and in the morning on the 15th report of the Ministry of Health. Provincial Health Office received a report immediately after the organization of provincial expert consultation, diagnosed as pneumonia of unknown causes, do not rule out SARS and avian flu.

The above translation from China’s Ministry of Health website, which originated with the Shanxi Ministry of Health, indirectly acknowledges that the familial cluster involving mother and daughter (3F), was a case of human to human transmission.  The pneumonia death of the mother increased the level of suspicion, and the increased level was validated by the lab confirmation of H5N1 in the daughter.

The husband and father of the two victims also indicated that the symptoms in both were identical, and the disease onset date of the daughter match the date of death for the mother, leaving little doubt that the mother infected her daughter, WHO comments on poultry exposure notwithstanding.

The human to human transmission was also supported by a similar cluster in northern Vietnam, where one family member (8F) was lab confirmed and her sister (13F) died with bird flu symptoms.  The cluster in Beijing also supported H2H, where the patient (19F) died, but a health care worker at the hospital recovered after exhibiting bird flu symptoms.

Recent reports from Hong Kong suggested that the human cases in China were due to the “northern China” strain of H5N1 that was not the two common Fujian sub-clades, 2.3.2 and 2.3.4, which were recently identified in Hong Kong.  The comments strongly suggest that the human cases were due to clade 7, which is the clade responsible for the most recent confirmed H5N1 in poultry in China, two asymptomatic outbreaks in Jiangsu in December.

Moreover, clade 7 has also been recently reported in northern Vietnam, suggesting that all recent human cases in China and Vietnam were due to clade 7, which increases concern over the spate of recent human cases in China and Vietnam (see updated map).  Prior to the recent cases, the only confirmed human clade 7 case was in Beijing in 2003.

The current clade 7 cases have likely evolved from the human case inn 2003 as well as more recent poultry isolates from Shanxi or Hunan in 2006.  The Hunan and Shanxi sequences are quite distinct from clade 1 and 2, which are the targets of most human and poultry vaccines.  Thus clade 7 infections are likely to be vaccine resistant, which was noted for the poultry outbreaks in northern China in the 2005/2006 season as well as the recent outbreaks in Jiangsu.

The recent human clusters suggests that the 9 confirmed cases include three clusters that involve 3 additional infections, raising the percentage of H5N1 infections linked to clusters to 50% (6/12 cases).  In each cluster the index case died, but the subsequent case survived, in part to more rapid treatment as well as a likely lower dose because the efficiency of human to human transmission is low, but higher than most previous cases as evidenced by the high percentage of cases linked to clusters, as well as the number of cases that died ro were infected in January, 2009.

Thus, the number of cases, as well as the number of cases linked to clusters is cause form concern, ProMED and WHO statements notwithstanding.

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