11 November 2005
A joint FAO/OIE/WHO statement
Two groups of antiviral drugs are available for the treatment and prophylaxis of influenza. These are the adamantanes (amantadine and rimantadine) ion channel inhibitors that prevent virus replication and the neuraminidase inhibitors (oseltamivir and zanamivir), which prevent virus release and spread.
The first H5N1 strain that infected humans in Hong Kong in 1997 was sensitive to the amantadine, but since then amantadine resistant avian flu strains have been identified in China and South East Asia from both humans and birds.
According to international livestock regulations, amantadine is licensed only for human use; however prophylactic use of amantadine in poultry production has been reported in news articles in Asia. Once resistance is acquired it can persist, thus eliminating the possibility to use amantadine to treat humans H5N1 influenza cases. Current H5N1 strains now appearing both inside and outside of Asia seem to be sensitive to amantadine but the emergence of a human-infectious resistant virus in animals in one part of the world represents a public health threat of global significance. Continued and rapid genetic assessment of the emerging H5N1 isolates is very important, but the drug of choice in a human outbreak of H5N1 avian influenza (HPAI) is likely to be a more expensive family of antivirals, including oseltamivir (Tamiflu) and zanamivir (Relenza) to which all of the H5N1 strains have thus far been sensitive. If generic amantadine is being used in chickens, there is a possibility that generic oseltamivir or generic zanamivir may also be produced and used.
Establishing a clear link between the use of amantadine in animals and resistance emergence will require more data on the usage of this drug in terms quantities and periods of usage. Misuse and overuse of antiviral however increase the risk of resistance.
Following recommendations from FAO/OIE/WHO tripartite consultations on non-human usage of antimicrobials and antimicrobial resistance, the concept of "critically important antimicrobials" for humans was developed by WHO with a view to enable specific management strategies for the use of these antimicrobials in animals to delay emergence of resistance. Critically important antimicrobials (CIA) are those antimicrobials used to treat severe human infectious diseases and for which there are no or few alternatives. Antiviral drugs used for treatment or prophylaxis of influenza are critically important antimicrobials for humans.
As a matter of precaution, given the threat of a human influenza pandemic and the scarcity of influenza drugs WHO, FAO and OIE urge Member States not to use antiviral drugs in animals in order to preserve the efficacy of these drugs for the treatment of influenza infections in humans. They strongly request Member States to ban the use of antiviral drugs in animals.
The best way to control H5N1 (or other highly pathogenic avian influenza viruses) outbreaks in animals is early detection of the disease, humane culling, disposal of dead animals, improved hygiene on the farm and at the market place, improved biosecurity measures and vaccination.
Giving antiviral drugs to poultry may leave many countries without low-cost options for treating important emerging viruses in humans.