Thursday, February 23, 2012

H5N1 influenza viruses: Facts, not fear

[editing is mine]

Peter Palesea,b,1 and Taia T. Wanga
Departments of aMicrobiology and bMedicine, Mount Sinai School of Medicine, New York, NY 10029

The ongoing controversy over publication of two studies involving the transmission in ferrets of H5N1 (H5) subtype influenza viruses and the recommendations of the National Science Advisory Board for Biosecurity to redact key details in the manuscripts call for an examination of relevant scientific facts. In addition, there are calls in the media to destroy the viruses, curtail future research in this area, and protect the public from such “frightening” research efforts. Fear needs to be put to rest with solid science and not speculation.

Is the Case Fatality Rate for Human H5
Infections Truly Greater than 50%? At the
heart of this controversy is the notion that
the case fatality rate for human H5 infections
is in the range of 50% to 80%. This
rate is derived from the list of H5 cases that
have been “confirmed” under World
Health Organization (WHO) guidelines;
the list tallies 573 cases in 15 countries (as
of December 15, 2011), with nearly 60% of
total cases resulting in death (28). The
frequency and certainty with which this
staggering fatality rate is reported is troubling
when one considers how the numbers
are generated; in order for a case to
be confirmed by WHO, a person must
have an acute, febrile respiratory illness
(temperature >38 °C/100.3 °F) with known
H5 exposure in the 7 days preceding
symptom onset and have molecular confirmation
of H5 infection by a WHO-approved
laboratory (e.g., virus isolation,
PCR, serology) (29). This definition does
not allow for asymptomatic infections and
essentially requires that a person actively
seek medical help at a hospital that is
equipped to draw samples and ship them
to an approved laboratory. Given that rural
populations in developing countries are
most commonly affected by H5 viruses, it
seems unlikely that even a small fraction
of the total number of infected cases has
been accounted for under the WHO surveillance
system. Also, the fatal cases that
have been reported are most likely caused
by mega-doses of H5 virus inhaled by the
patients, who are living in very close contact
with infected poultry. Transmission
involving small doses of virus (as observed
under regular aerosol transmission conditions)
may not result in overt disease. Of
the 10 largest studies of which we are
aware (N ≥ 500) (30–39), which document
seroevidence in humans for H5 infections,
two studies report no seropositivity and
the other eight report rates ranging from
0.2% to 5.6%; the studies are mostly
conducted in rural areas where H5 infections
have been previously documented
(30–39). Even if only a low percentage of
the rural population is asymptomatically/
subclinically infected, the case fatality rate
that is offered by the WHO—and that is
driving this controversy—is likely orders of
magnitude too high. This suggests that
more work should be done to determine
an accurate case fatality rate for H5 infections,
which takes into account mild
and asymptomatic cases.
Why These Papers, Why Now? The type of
work performed in the studies under
evaluation is quite common in virology
because it is a useful way to study molecular
determinants of virus adaptation, pathogenesis,
and transmission. The reasoning
behind the selection by the National Science
Advisory Board for Biosecurity of
these specific papers for redaction/censorship
seems somewhat arbitrary relative
to what has previously been published in
the field of influenza.
In 2005, the complete sequences for the
1918 pandemic influenza virus were published
in Nature and methods describing
the rescue of the 1918 virus were published
in Science (40, 41). In 2006, both
Science and Nature published reports of
specific mutations that enable the H5 viral
hemagglutinin to bind human, rather than
avian, tissues (42, 43). In 2012, a report
from the Centers for Disease Control
and Prevention that bears striking resemblance,
in principle, to the works by
Fouchier and Kawaoka was already published
in Virology; it describes mutations
in an H5N1 virus that confer airborne
transmissibility between ferrets (44).
Studies have also been published recently
that describe mutations enabling other
potential pandemic strains to transmit
between ferrets (45, 46) or that make
currently circulating virus strains more
virulent (47).
These are a small fraction of studies
published during the past decade that
could have been considered controversial
(some were controversial at the time, but
all were published in full). We know from
studies like these that, for example, the
2009 pandemic vaccine protects against the
1918 pandemic virus and thus the 1918
strain is not a pandemic threat at this time
(48), nor would it be of any advantage for
a bioterrorist to lay his/her hands on it.
Other striking examples of achievements
based on the free exchange of potentially
controversial information are the elimination
of SARS corona virus in only 6
months and the fact that the dangers of
HIV have been dramatically reduced by
the development of effective antiviral
treatments. None of this would have been
possible without the uncensored exchange
of scientific data.

No comments: