Important points that can be taken from this abstract...
- There are not only high-pathogenic and low-pathogenic H5N1 viruses, but “lesser pathogenic” viruses. That is, lesser pathogenic than high-pathogenic.
- It appears that a higher dose may be necessary to fight the “more virulent” high pathogenic strains. A higher dose is also needed to achieve the same protection once time has lapsed from beginning of infection.
The viruses tested came from Vietnam 2004 and Turkey 2006, but no strains from Indonesia or Egypt were included, where partial resistance to Tamiflu may be developing in some isolates.
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Antimicrob Agents Chemother. 2007 Apr;51(4):1414-24. Epub 2007 Feb 12
Efficacy of oseltamivir therapy in ferrets inoculated with different clades of H5N1 influenza virus.
Govorkova EA, Ilyushina NA, Boltz DA, Douglas A, Yilmaz N, Webster RG.
Department of Infectious Diseases, St. Jude Children’s Research Hospital, and Department of Pathology, University of Memphis, Memphis, TN 38105-2794, USA.
Highly pathogenic H5N1 influenza viruses have infected an increasing number of humans in Asia, with high mortality rates and the emergence of multiple distinguishable clades. It is not known whether antiviral drugs that are effective against contemporary human influenza viruses will be effective against systemically replicating viruses, such as these pathogens. Therefore, we evaluated the use of the neuraminidase (NA) inhibitor oseltamivir for early postexposure prophylaxis and for treatment in ferrets exposed to representatives of two clades of H5N1 virus with markedly different pathogenicities in ferrets. Ferrets were protected from lethal infection with the A/Vietnam/1203/04 (H5N1) virus by oseltamivir (5 mg/kg of body weight/day) given 4 h after virus inoculation, but higher daily doses (25 mg/kg) were required for treatment when it was initiated 24 h after virus inoculation. For the treatment of ferrets inoculated with the less pathogenic A/Turkey/15/06 (H5N1) virus, 10 mg/kg/day of oseltamivir was sufficient to reduce the lethargy of the animals, significantly inhibit inflammation in the upper respiratory tract, and block virus spread to the internal organs. Importantly, all ferrets that survived the initial infection were rechallenged with homologous virus after 21 days and were completely protected from infection. Direct sequencing of the NA or HA1 gene segments in viruses isolated from ferret after treatment showed no amino acid substitutions known to cause drug resistance in conserved residues. Thus, early oseltamivir treatment is crucial for protection against highly pathogenic H5N1 viruses and the higher dose may be needed for the treatment of more virulent viruses.
PMID: 17296744 (enter at http://www.ncbi.nlm.nih.gov/sites/entrez)
Why is the world so poorly prepared for a pandemic of hypervirulent avian influenza?
Authors: Olav Albert Christophersen; Anna Haug a
Affiliation: a Norwegian University of Life Sciences. Ås. Norway
DOI: 10.1080/08910600600866544
Publication Frequency: 4 issues per year
Published in: Microbial Ecology in Health and Disease, Volume 18, Issue 3 & 4 December 2006 , pages 113 - 132
Subject: Biotechnology;
Abstract
The world is now extremely poorly prepared to counter a possible pandemic of hypervirulent H5N1 influenza. Most countries are planning for nothing worse than the Spanish flu pandemic. It may be possible that this can in large measure be explained as a consequence of an epidemic of wishful thinking, which may already have infected the health authorities (and parts of the scientific community as well) in most countries in the world. However, it may also be possible that it can have happened as a consequence of too little contact between medical scientists and more general biologists (natural scientists) from disciplines such as ornithology, ecology and evolutionary biology. This may have led to a lack of proper understanding among medical scientists (and health bureaucrats) of the nature of evolutionary processes affecting influenza viruses, as regards the evolution of host species adaptation, infectivity and virulence properties, and also a lack of appreciation of the ways in which such forms of evolutionary adaptation depend on ecological boundary conditions that have radically changed, comparing the world in 2006 to the world in 1918. While the Spanish flu virus possibly might be compared to a one-headed monster, it may be possible that highly virulent varieties of H5N1 virus might better be compared to a three-headed one - because there is evidence of at least three independent virulence factors connected with three different genes. It is highly unlikely that all of the high-virulence alleles will simultaneously mutate and disappear if and when the haemagglutinin gene changes so as to make the haemagglutinin molecule better adapted for the human-type (alpha-2,6-linked) receptor (which is a necessary prerequisite in order that a pandemic with H5N1 virus may start). It is more probable that evolutionary adaptation of the haemagglutinin of H5N1 viruses to the human-type receptor will happen without any simultaneous change in those other genetic properties that now are important for explaining the exceptionally high virulence of certain strains of avian-adapted H5N1 influenza virus. The change of the haemagglutinin molecule from avian adaptation to human adaptation must be expected to act as an additional virulence factor because it will enhance the total number of cells that can be infected (per host organism), increase the total rate of virus replication and potentiate the effects of the other virulence factors already present. The monster will then have four heads, not three, and case fatality rates must be expected to become even higher than they have been until now, perhaps reaching as high as 98-99% (at least in poor countries with less than optimal nutrition).