Published Date: 2004-01-25 23:50:00
Subject: PRO/AH/EDR> Avian influenza A (H5N1) virus, drug resistance
Archive Number: 20040125.0298
AVIAN INFLUENZA A (H5N1) VIRUS, DRUG RESISTANCE
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Date: Sat 24 Jan 2004
From: ProMED-mail <promed@promedmail.org>
Source, The New York Times, Sun 25 Jan 2004 [edited]
<http://www.nytimes.com/2004/01/25/health/25BIRD.html?th>
Avian Influenza Virus Exhibits Resistance to Amantadine and Rimantadine
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New tests have turned up a disturbing problem with the avian influenza
virus that is spreading in Asia: the strain appears resistant to one of the
2 main classes of drugs used to fight influenza viruses, a World Health
Organization (WHO) official said yesterday [Sat 24 Jan 2004].
Meanwhile, avian influenza A(H5N1) virus has been detected among birds in a
6th Asian country, Cambodia, and 2 more human cases have been diagnosed in
a new area of Vietnam, the official, Dr. Klaus Stoehr, said. Both
Vietnamese cases were in children in Ho Chi Minh City, bringing to 7 the
total in that country. 6 have been fatal. 5 earlier Vietnamese cases were
in Hanoi. Thailand has reported 2 human cases. All the human cases are
believed to be from contact with chickens or their waste, not from eating
them or their eggs. The agency said it knows of no person-to-person spread
of the disease.
The number of human cases is small, and the avian influenza A (H5N1) virus
strain contains only avian genes. But WHO officials are concerned that the
bird strain might exchange genes with a human virus to create an entirely
new virus that could spread easily among people. It would take a
combination of events, each of low probability, to produce a large
outbreak. But the health agency said the implications for public health
were so important that precautionary measures must be taken.
Because a virus [reassortment event] could occur at any time, and the
threat is likely to last for some time, WHO is establishing systems for a
long vigil through its influenza surveillance network, said Dick Thompson,
a spokesman in Geneva. The organization, other United Nations agencies, and
health groups are emphasizing that infected Asian countries must kill all
poultry, a standard measure to stop avian influenza from becoming endemic.
Laboratories in the WHO network are using new techniques to try to develop
a human vaccine. The agency hopes to develop in a month a seed virus for
possible vaccine production. Dr. Nancy J. Cox, an influenza expert at the
Centers for Disease Control and Prevention (CDC) in Atlanta, which is
helping prepare a seed virus, said there was no guarantee on that time
frame. "That would be the best-case scenario," Dr. Cox said. Once the seed
virus is ready, it will take months to produce a new vaccine and test it in
animals and human volunteers.
Knowing that anti-influenza drugs may be needed in an outbreak of human
bird flu, and as part of the surveillance process, laboratories in the
network have been testing which of a small number of such drugs may be
effective against the A (H5N1) strain. The tests are being done at the CDC
in Atlanta, and in in London and Hong Kong.
Dr. Stoehr said on Friday night that his agency had learned that initial
genetic tests showed that the A(H5N1) was resistant to the less expensive
class of anti-influenza drugs. The class includes amantadine (Symmetrel)
and rimantadine (Flumadiine). Earlier studies by Dr. Malik Peiris of the
University of Hong Kong showed that the resistance results from a single
amino acid change. Additional tests are expected to be conducted this week
to confirm the early findings, said Dr. Stohr. However, A(H5N1) is believed
to be susceptible to the costlier class of anti-influenza drugs known as
the neuraminidase inhibitors. Tamiflu (Oseltamivir) is the main drug in
this class.
Before Cambodia was added to the list, A(H5N1) had been officially reported
in birds from 5 countries: Hong Kong, Japan, South Korea, Thailand, and
Vietnam. The WHO suspects that the virus is also present in other Asian
countries.
Taiwan has reported that a different strain of avian influenza, A(H5N2), is
causing mild illness among poultry. Tests show that the strain's genes are
closely related to those in a vaccine that is widely used for poultry in
Hong Kong and China, Dr. Stoehr said. He said that one possibility was that
the Taiwan bird cases were from a poor-quality vaccine.
[Byline: Lawrence K. Altman]
--
ProMED-mail
<promed@promedmail.com>
[Amantadine and rimantadine are not particularly effective drugs for
control of influenza virus infection. Drug resistance appears quickly
because a single amino acid replacement may be sufficient to render the
virus resistant to the inhibitory effects of the compound. Treatment with
amantadine in particular has associated side-effects, and its use is not
recommended in the UK by the National Institute for Clinical Excellence
(NICE). The neuraminidase inhibitors Oseltamivir (Tamiflu) and Zanamivir
(Relenza) are less prone to select for resistant virus but are not
universally recommended for treatment of influenza in all circumstances.
Oseltamivir has an advantage: it can be can be administered orally. - Mod.CP]
See Also
Avian influenza, Eastern Asia (03): RFI 20040118.0206Avian influenza, falcon - China (Hong Kong) 20040121.0243
Avian influenza, human - Thailand (02): confirmed 20040123.0262
Avian influenza, human - Thailand (03) 20040123.0268
Avian influenza, human - Thailand: suspected 20040122.0247
Avian influenza, human - Vietnam (02) 20040113.0138
Avian influenza, human - Vietnam (03) 20040114.0154
Avian influenza, human - Vietnam (04) 20040114.0155
Avian influenza, human - Viet Nam (05) 20040117.0181
Avian influenza, human - Vietnam (06) 20040118.0193
Avian influenza, human - Vietnam (07) 20040119.0213
Avian influenza, human - Vietnam (08) 20040119.0216
Avian influenza, human - Vietnam (09) 20040120.0225
Avian influenza, human - Vietnam (10) 20040122.0251
Avian influenza, human - Vietnam (11) 20040122.0258
Avian influenza, human - Vietnam: RFI 20040112.0127
Avian influenza, Taiwan - OIE 20040123.0273
Avian influenza, Thailand - OIE 20040124.0276
Avian influenza, WHO fact sheet 20040116.0171
Avian influenza - Eastern Asia 20040114.0145
Avian influenza - Eastern Asia (02) 20040116.0176
Avian influenza - Eastern Asia (04): RFI 20040119.0208
Avian influenza - Eastern Asia (05) 20040120.0222
Avian influenza - Japan (02) 20040112.0125
Avian influenza - Japan (03): OIE 20040114.0151
Avian influenza - Japan: RFI 20040111.0124
Avian influenza - Taiwan: not 20040114.0148
Avian influenza - Taiwan ex mainland China: susp. 20040101.0001
Avian influenza - Thailand (02): not 20040109.0097
Avian influenza - Thailand: RFI 20040105.0051
Avian influenza - Vietnam (02) 20040110.0106
Avian influenza - Vietnam: OIE 20040109.0101
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