E-DRUG: Avian influenza should be ruffling our feathers
[Forget Bin Laden! The *BIG* terrorist is going to be the next influenza
pandemic. With a vaccine production delayed for 8 months, the world only has
the neuraminidase inhibitors zanamivir and oseltamivir as potentially effective
drugs. The existing stockpiles of antivirals are nowhere near adequate to cope
with a pandemic.
Are these essential drugs? Anybody planning to write a review about
anti-influenza drugs for the 2005 WHO Essential Drugs List of these drugs?
Copied as fair use from the Lancet Infectious Diseases. WB]
Avian influenza refuses to go away. The outbreak of highly pathogenic influenza
A H5N1 was first reported in poultry in South Korea in December of last year,
and subsequently spread to another seven Asian countries. After a quiet period
in the second quarter of this year, the ProMed wires have been buzzing since
July with news of outbreaks of the virus in poultry in China, Thailand,
Vietnam, Indonesia, and Malaysia. Fortunately, only Thailand and Vietnam have
reported human cases (13 cases with nine deaths, and 27 cases with 20 deaths,
respectively, as of September 10), indicating that the virus transmits poorly
from birds to people.
Reports from China that H5N1 is widespread in domestic ducks and wild birds
suggest that the virus is deeply entrenched in the environment and may be
impossible to eliminate. Experimental infection of cats with H5N1 indicates
that these animals could serve as a transmission bridge between poultry farms
or between poultry and people. Perhaps we should not give too much weight to
disease produced in the laboratory, but cats should be studied in future
epidemiological investigations of H5N1 transmission.
Of more importance potentially was the announcement, made on August 20 by a
researcher from China's Harbin Veterinary Research Institute, that H5N1 has
been isolated from pigs on farms in various parts of China. Pigs can also be
infected with human influenza A viruses, such as H3N2. The co-circulation of
influenza viruses of avian, human, and pig origin in pigs might lead to genetic
reassortment between the viruses, and, in the worse-case scenario, emergence of
a new pandemic influenza strain.
It has since emerged that H5N1 was isolated once from material collected from
pigs in Fujian province in 2001, and that of 1936 samples collected from pigs
in 14 Chinese provinces in 2003 only one was positive for H5N1, also from
Fujian. A further survey involving 4447 samples from pigs in ten provinces,
including Fujian, done between April and August this year revealed no cases of
H5N1 infection. Moreover, testing earlier this year for H5N1 in pigs on
Vietnamese farms where the disease was rife among poultry, found no evidence of
infection. And during regular testing in Hong Kong of pigs imported from
mainland China, no H5 avian influenza subtype has been isolated. So the
implications for human health of the discovery of H5N1 in pigs in China remain
Nevertheless, there is absolutely no room for complacency in the international
response to, what now seems to be endemic, highly pathogenic avian influenza.
The great fear is that avian disease will give rise to a human influenza
pandemic. Of the three prerequisites for a human pandemic, two have been met:
emergence of a new influenza virus to which the population has little or no
immunity and against which there is no effective vaccine; and ability of the
virus to replicate in human beings and cause disease. As yet, there is no
evidence of the third prerequisiteefficient human-to-human transmissionbeing
There has not been an influenza pandemic since 1968 (so called Hong Kong flu).
However, sources within WHO believe that we are as close to the next pandemic
as we have been at any time in the past 36 years, with all the necessary
ingredients currently mixing in Asia. Epidemiological modelling suggests that a
future influenza pandemic will cause 2774 million deaths worldwide. The severe
acute respiratory syndrome outbreak of 2003 merely hinted at the likely
economic consequences of pandemic influenza.
The WHO pandemic preparedness plan was published in 1999 and is in the process
of being revised. Early detection of unusual outbreaks by the WHO network of
112 national influenza centres will be key to containment of potentially
pandemic strains. As Iain Stephenson and colleagues said in this journal in
August, vaccination is likely to remain the principal means of combating
pandemic influenza (Lancet Infect Dis 2004; 4: 499509). However, production
of a vaccine against the H5N1 strain is complicated by numerous technical,
safety, and regulatory considerations. Indeed, it may be 8 months or more into
a pandemic before a vaccine is available. Antiviral drugs could be used to
contain the pandemic and reduce fatalities while vaccine supplies are prepared.
H5N1 seems to be resistant to the M2 inhibitors (amantadine and rimantadine);
the neuraminidase inhibitors zanamivir and oseltamivir are effective, although
oseltamivir-resistant influenza H3N2 in children treated for the disease was
reported recently. What is certain is that existing stockpiles of antivirals
are nowhere near adequate to cope with a pandemic.
The threat to human health from pandemic influenza is likely far greater than
that from bioterrorism. Responsible governments must be prepared to invest in
global preparedness for the next pandemic.
The Lancet Infectious Diseases