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Date: Fri 15 Jul 2005
From: ProMED-mail <>
Source: Nature, News, Fri 15 Jul 2005 [edited]

Viet Nam: Conflicting Results Cause Concern
The world last week seemed to edge closer to the brink of a flu pandemic. On 30
Jun 2005, officials at the World Health Organization (WHO) revealed that they
recently considered raising the threat level of a global pandemic, from the
current 3 on a 6-point scale, to 4 or even 5.

The scare was triggered a few weeks ago when several research groups visiting
Viet Nam filed preliminary reports that many people with mild cases of
influenza -- and those in contact with them -- were testing positive for avian
H5N1 influenza virus infection. This suggested that there was widespread human-
to-human transmission of the virus.

Subsequent tests have so far failed to confirm this, and WHO spokesman Dick
Thompson is keen to play down the incident. "It was just unpublished
information provided to us in preliminary form that spurred an investigation,"
he says. "We thought about upgrading the alert. We looked at it fast and
strongly, and based on that decided not to upgrade."

But take a closer look, and the picture in Viet Nam is one of confusion rather
than reassurance. The first signs of trouble came in May 2005, with reports of
small clusters of human cases of H5N1 [virus infection], including a rise in
the infection of older people and an increase in milder cases -- all signs
consistent with the possibility that the virus had mutated to achieve improved,
although still inefficient, human-to-human spread (see Nature 435, 390; 2005).

Concern mounted in subsequent weeks as several international groups
investigated the clusters using different methods, including the polymerase
chain reaction (PCR), which amplifies DNA sequences, and Western blots, which
use antibodies to detect proteins. Despite using different tests, each of the
teams reported that: "Substantial proportions" of the hundreds of people it had
tested seemed to be infected with H5N1.

That led the WHO to consider upgrading the pandemic threat level to 4 (small,
localized clusters of human infection) or 5 (large clusters of infection) --
just one step away from a full-blown global pandemic. But first it asked an
international team of experts, including Masato Tashiro, a virologist at the
National Institute of Infectious Diseases in Tokyo, to retest many of the
samples and some new ones, using the WHO's own PCR tests.

They found no evidence of clusters of human-to-human transmission. "This is
good news," Tashiro says, relieved that his worst suspicions weren't confirmed.
But it remains unclear why the various groups got different results.

Samples have now been sent to a WHO laboratory in Hong Kong for the last word
in confirmation: antibody neutralization assays. These take time, as they
involve growing large amounts of the virus for analysis, but a firm conclusion
is expected by the end of the month [July 2005]. In the meantime, the WHO is
holding off raising the alarm.

"Because of the consequences of such a change, the WHO is following a cautious
approach," it declared in a statement last week. Pushing the level to 4 for the
first time would mean deploying the international stockpile of antiviral drugs
to try to contain or stamp out the spread, and would probably result in
countries restricting travel to Viet Nam.

But Tashiro remains concerned that he and his colleagues didn't have enough
time to check all of the clinical and epidemiological information associated
with the initial lab samples. Follow-up work is also complicated by the fact
that recovered patients have now returned home, making it hard to track down
people they might have infected. "We still have a big problem collecting enough
good data," he says.

Jeremy Farrar, director of the Wellcome Trust Clinical Research Unit at the
Hospital for Tropical Diseases in Ho Chi Minh City, says that much of the
uncertainty over the prevalence of H5N1 could be avoided if Viet Nam had better
facilities for testing samples locally. "The international community continues
to suggest that countries ship samples out somewhere else," he says, "while
doing absolutely nothing to invest in enhancing the scientific capacity of the
Vietnamese to respond to the epidemics themselves."

In the meantime, Tashiro adds that even if final tests confirm his negative
results, "the fundamental situation has not changed." Many are concerned that
July and August [2005] will bring a new and bigger wave of influenza cases in
Viet Nam, as happened in 2004 during the hot rainy season. And recent events in
China bode just as ill. Scientists investigating migratory birds infected with
H5N1 avian influenza virus in western China are now warning that these pose an
explosive risk of spreading the virus along their migration routes as they fly
south in September (see "Infected birds poised to take flu virus south"
or ProMED-mail post archived as "Avian influenza, wild waterfowl - China (09)

At a UN meeting on avian influenza held this week in Kuala Lumpur, Malaysia,
the WHO's western Pacific regional director, Shigeru Omi, warned that H5N1
remains at a "tipping point".

[Byline: Declan Butler]


[It is disappointing that there are still no hard data concerning the
prevalence of asymptomatic avian H5N1 virus infection in the Vietnamese
population. - Mod.CP]

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