Report: H5N1 mutated rapidly in Indonesian cluster

Jul 12, 2006 (CIDRAP News) – Genetic studies show that the H5N1 avian influenza virus mutated multiple times as it spread through an Indonesia family in May, but the significance of the changes is uncertain, according to a news report today in Nature.

The journal, basing its report on confidential genetic sequence data, published a chart showing that a total of 32 mutations were identified in viruses collected from six patients in the family case cluster. Previous reports from the World Health Organization and other experts gave the impression that only a few mutations had been found.

The case cluster in North Sumatra involved a 37-year-old woman who apparently contracted the virus from poultry and then passed it to six relatives before she died. One of those six, a 10-year-old boy, then passed the virus to his father. WHO officials said last month that a specific mutation found in the boy and his father marked the first laboratory confirmation of human-to-human transmission of the virus.

On May 23, the WHO said genetic sequencing of two viruses from the case cluster had shown "no evidence of genetic reassortment with human or pig influenza viruses and no evidence of significant mutations." A month later, at the end of an avian flu conference in Jakarta, WHO officials told reporters the virus had mutated slightly when it infected the 10-year-old boy, and the same mutation showed up in his father. The mutation didn't make the virus more transmissible or virulent, officials said.

The genetic data obtained by Nature came from a presentation by University of Hong Kong virologist Malik Peiris at a closed session of the Jakarta meeting in June, the article says.

The magazine says that 21 mutations were identified in a virus from the father of the 10-year-old boy, involving seven of the virus's eight genes, suggesting that the virus was evolving rapidly as it spread. In addition, from one to four mutations were found in viruses collected from five other patients.

The story says one of the mutations confers resistance to the antiviral drug amantadine, a finding not reported by the WHO.

However, the virus did not spread beyond the extended family, as the article notes. "Many of the genetic changes did not result in the use of different amino acids by the virus," the story says. "And there were no amino-acid changes in key receptor binding sites known to affect pathogenicity and transmissibility."

According to the magazine, viruses from six of the eight cases in the cluster have been sequenced, but the WHO has not shared the findings, saying they belong to Indonesia. The data have been released only to a few researchers linked to the WHO and the US Centers for Diseases Control and Prevention, the story says.

Virologists quoted by the journal asserted that the withholding of sequence data on H5N1 is hindering scientists' understanding of the virus. But WHO staff member Paul Gully replied, according to the article, that the agency's job is investigating outbreaks, not doing academic research, and that labs don't have the time or resources to do "high-quality sequencing" during outbreaks.

See also:

May 23 WHO statement on genetic data from the case cluster
http://www.who.int/csr/don/2006_05_23/en/index.html

Jun 23 CIDRAP News story "H5N1 mutation showed human transmission in Indonesia"

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