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H5N1 Fujian Province Patient Lacks Poultry Contacts

Recombinomics Commentary

December 31, 2005

Zhou was already weak after an operation to remove a tumour in mid-October, the newspaper said.

But she had no contact with infected birds and no bird flu infections were found in Sanming. Zhou's relatives also said that she did not like chicken and duck meat.

"Zhou is unlikely to have been infected from poultry," the newspaper quoted Fujian disease control official Xu Longshan as saying.

Tests on December 23 were positive for the H5N1 bird flu virus but the case was not reported until December 29 "because experts could not explain how she caught the virus", it quoted an unidentified health ministry as saying.

The above comments of the first reported H5N1 case from Fujian Province raise additional concerns over human-to-human transmission of H5N1 in China in general and Fujian Province in particular.

Fujian Province has been associated with a high level of suspicion since it exported H5N1 via a family visiting from Hong Kong in 2003.  The daughter developed bird flu like symptoms and died in Fujian Province.  Her father and brother developed symptoms after her death, strongly suggesting human transmission.

Upon returning to Hong Kong, H5N1 was isolated from the father and brother.  The two isolates. A/Hong Kong/212/2003 and A/Hong Kong/213/2003 were closely related to each other and classified as genotype Z+.  This genotype is closely related to the Z genotype, but does not have the 20 amino acid deletion found in Z genotype isolates.

Export of H5N1 via visitor is a major red flag because the number of residents in Fujian Province far exceeds the number of visitors, so export signals significant levels of infection in the local population.  However, prior to the current case, China had never reported a human H5N1 case in Fujian Province.

Concern over human-to-human transmission was further increased because a recent report indicated that the two isolates from the Hong Kong family had the S227N polymorphism which increases affinity for human receptors and decreases affinity for avian receptors, properties that would lead to more efficient human-to-human transmission.

The first familial H5N1 cluster report by China further increased concern.  Like the cluster reported above, the disease onset dates formed a bimodal distribution suggesting human-to-human transmission between a 12 year-old girl and her 9 year-old brother,  The index case again died without being tested for H5N1, but her brother was positive for H5N1 antibodies and H5N1 was found in a family chicken. The sequence from the chicken isolate was closely related to H5N1 isolates from Fujian province which was also see in earlier isolates from Hunan Province.  However, the isolate had a novel HA cleavage site suggesting the number of different H5N1 strains capable of causing human infections that were transmissible was increasing.

The recent additional human cases in China have been in regions linked to poultry outbreaks linked to migratory birds. However, recent data has identified H5N1 sequences in tree sparrows, which are closely related to each other, but distinct.  Included in the isolates was an H5N1 that still retained the 20 amino acids in NA.  Most recent H5N1 have the deletion, but the tree sparrow sequence had the sequences found in the two Hong Kong patients, indicating that these older sequences were still circulating in Henan Province.  The number of provinces with human cases in China has quickly grown to six and these provinces are geographically clustered, raising the possibility of infections by similar but distinct H5N1 sequences.

The reports of human H5N1 cases in China have come at a time that precedes season and pandemic influenza outbreaks, raising the possibility of significant increases in the upcoming weeks.  Most of the recent reported cases initially tested negative for H5N1 raising questions about the sensitivity of current testing methods.

The failure to identify a source for the H5N1, coupled with the patient’s limited exposure to avian sources of H5N1 has led to increased concerns.  Tracing the origin of the infection can be greatly facilitated by the sequence of the H5N1, which has been isolated.  There have been a series of H5N1 outbreaks in mainland China, and OIE reports indicate HPAI H5N1 was confirmed using a biological IVPI test that allows for easy isolation and sequencing of the H5N1 causing the outbreaks.

Release of the sequencing data from both human and animal outbreaks will greatly facilitate the analysis of the H5N1 evolution and source of the current H5N1 infection.


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