H5N1 spreading among humans?

Epidemiology in Vietnam raises the possibility of human-human spread

By | May 20, 2005

Avian influenza (H5N1) virus is possibly spreading among humans in Vietnam, the World Health Organization (WHO) said in a document made public on its Web site on Thursday (May 19).

Reporting on an international meeting held in the Philippines last week, WHO officials said worrying changes in the epidemiology of the virus had been seen between January and April this year in the north of Vietnam. "Investigators were not able to prove that human-to-human transmission had occurred, [but] they expressed concerns, which were shared by local clinicians," they said.

The document notes concerns that the latest H5N1 strains could be resistant to the antiviral oseltamivir, previously thought effective in fighting infection. It also discusses changes to the hemagglutinin (HA) protein that have been noted in 2005 H5N1 isolates, but had not been seen in 2004 sequence data. "The changes are consistent with the possibility that recently emerging H5N1 viruses may be more infectious for humans," the document's authors wrote.

"Recent viruses circulating in Northern Vietnam have lost an arginine residue in the mutibasic amino cluster at the proteolytic cleavage site of the HA protein," they warned. "The structure of the cleavage site is typical of highly pathogenic viruses." Epidemiological data also suggest the virus is "behaving" differently.

Kwok Yung Yuen, who heads the University of Hong Kong Microbiology Department—which operates a WHO designated laboratory—said, however, that epidemiological studies support the possibility that the virus pathogenicity has been somewhat reduced. "Fewer people are dying than before, and the disease is affecting a wider age group," he told The Scientist.

According to the WHO document, human bird flu clusters show a lag time between infections. This raises the possibility of incubation periods typical for human to human transmission of flu.

The epidemiology and genetic analysis of viral isolates from Northern Vietnam and other areas in Southeast Asia have been carried out by dozens of international scientists working under WHO auspices. Vietnam has also hosted independent teams, which have jointly investigated H5N1 with Vietnamese scientists, said Hitoshi Oshitani, WHO regional adviser to the Western Pacific Regional Office.

The new 2005 gene sequences are taken from only a handful of isolates. WHO says scientists have had technical problems in trying to derive isolates from the hundreds of serum samples collected in over the past few months in Vietnam.

"CDC has only one isolate and sequence for H5N1 from North Vietnam cases reported in 2005," said Ruben O'Donis, US Centers of Disease Control and Prevention's Chief of the Molecular Genetics Section, Influenza Branch, in an E-mail to The Scientist.

Meanwhile, other scientists outside the WHO network of communicating flu labs await data eagerly. "This time last year, there was a lot more [H5N1 sequence] available on Genbank, [for analysis]," said Henry Niman, founder of Recombinomics, a biotech firm set up to develop vaccine against flu. Niman analyzes data by looking for the possibility that flu viruses are evolving swiftly due to a recombination mechanism.

Niman has analyzed all 610 gene sequences from H5N1 isolates uploaded to Genbank in 2004. He's hopeful sequence data from at least one isolate will likely be made available on Genbank or on Influenza Sequence Database of the Los Alamos National Laboratory in coming weeks.

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