Labs in the time of influenza

Aug. 1, 2009

In 2009, we have been witness to the first influenza
pandemic since 1968, and the first to be observed and reacted to in
'real-time.' It is too early yet to predict what the impact this novel
strain of influenza will have in the next months to years, and the
impact of past pandemics is only apparent in retrospect. Nonetheless,
this virus has already caused large-scale outbreaks in Mexico and the
United States, and has now spread globally where, at the time of this
writing, the Southern Hemisphere is just entering its winter influenza

Pandemic influenza has been a threat for centuries;
but with occurrences only every 40 years or so, prediction has proven
impossible and preparedness difficult to sustain. The perceived risk of
a flu pandemic developing from highly pathogenic avian flu virus
outbreaks over the past decade has spurred pandemic preparedness plans
globally. Yet, despite a massive increase in influenza surveillance and
genetic analysis, the emergence of the novel H1N1 influenza virus this
year took everyone by surprise.

While new events generate more media interest, yearly
outbreaks of seasonal flu continue to be a major cause of illness, lost
productivity, and death. An estimated 30,000 people die every year of
seasonal influenza in the United States — and yet this is, in general,

Our antiviral drug armamentarium against influenza
viruses has remained small. The older class of antiviral drugs (i.e.,
adamantanes) often is associated with side effects and, importantly,
viral resistance to them often rapidly develops during treatment. The
newer class of antiviral drugs (i.e., neuraminidase inhibitors) was
thought less susceptible to the development of antiviral resistance; but
in the past year, the seasonal human flu H1N1 strains have developed
near 100% resistance to the most common such drug, oseltamivir. Almost
all of the H3N2 seasonal strains and the new swine-origin H1N1 pandemic
strains are resistant to the adamantanes. During spring when the novel
H1N1 began circulating in the United States, it co-circulated with the
seasonal influenza A viruses of both H1N1 and H3N2 subtypes. As it
circulates in the Southern Hemisphere, the novel virus is also
co-circulating with seasonal flu.

This leads us to the importance of lab-based testing for
influenza virus diagnosis, treatment, and surveillance. Influenza outbreaks
are detected at an epidemiological level through the network of
influenza-surveillance labs, using serological reagents prepared in advance
of each season. These data follow the rapid antigenic evolution of flu
viruses and allow decisions to be made about the strain selection for the
next year's vaccine composition. At the individual patient level, however,
viral isolation and antigenic characterization is rarely performed; if it
is, results would not likely be useful in management of the acute illness.
In the subset of patients presenting with a flu-like illness for which a
diagnostic test is ordered, it is more likely to be a point-of-care rapid
test, which is generally less sensitive than viral culture but reasonably
specific. This would allow a patient to be treated early with an antiflu
drug if positively diagnosed, or, for example, a nursing home population to
be prophylactically treated if a positive index case is identified.

A problem with the current system is that subtyping
influenza A virus isolates (i.e., determining which one of the 16 different
hemagglutinin and nine different neuraminidase proteins are expressed on the
surface of the virus) is not done routinely. So, a patient presenting to the
emergency ward of a hospital with a flu-like illness in the last month may
have an influenza A virus rapid test ordered, but the lab and healthcare
providers involved would not know whether it reflected a seasonal H3N2 or
H1N1 flu subtype or the novel pandemic H1N1 virus (or another subtype we are
not even expecting). If the physicians treating the patient wanted to give
antivirals, should they use oseltamivir, knowing that seasonal H1N1 viruses
are resistant, or an adamantane, knowing that pandemic H1N1 viruses are

What is needed in this evermore complicated world in which we live are
rapid point-of-care tests that not only diagnose influenza A virus
infections but determine the particular subtype as well. The current
pandemic situation should be the spur to develop and implement such tests.
The technology is well within our reach, but will we let this opportunity
pass us by”

Dr. Jeffery K. Taubenberger, together with Ann H. Reid and colleagues at the Armed Forces Institute of Pathology, was the first to sequence the genome of the influenza virus which caused the 1918 pandemic of “Spanish flu.”