H5N1 spreading among humans?

Epidemiology in Vietnam raises the possibility of human-human spread;
sequence data to be published soon
By Katherine Schlatter

Avian influenza (H5N1) virus is possibly spreading between humans in
Vietnam, the World Health Organization (WHO) said in a document made
public on its website on Thursday.

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 noted 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.

Among them are scientists from the US Centers for Disease Control and
Prevention. The Scientist has been told that within weeks they are
likely to publish their findings on how genetic changes to the HA
receptor binding site affected the virus's ability to spread between
humans.

But 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 CDC's Chief of the
Molecular Genetics Section Influenza Branch in an email 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 firm that .

Niman has analyzed all 610 gene sequences from H5N1 isolates uploaded
to Genbank in 2004. He said 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.

Links for this article
WHO Inter-country Consultation, Influenza A/H5N1 in Humans in Asia,
Manila May 6 th -7 th 2005
http://www.who.int/csr/disease/avian_influenza/en/

YUEN Kwok Yung http://www.hkupasteur.hku.hk/hkuip/CVs/yuen_K_Y.html  

Genbank http://www.psc.edu/general/software/packages/genbank/genbank.html  

Influenza Sequence Database, Los Alamos National Laboratory
http://flu.lanl.gov/about.html

Recombinomics http://www.recombinomics.com