Surviving Bird Flu: The Drugs that Work04 March 2008
SWITZERLAND - Physicians from countries worst-affected by the deadly bird flu (H5N1 influenza virus) have reported an increased survival rate in patients treated with the oral antiviral Tamiflu (oseltamivir).
These data reinforce the World Health Organization (WHO) advisory that Tamiflu is the only antiviral strongly recommended for the treatment of humans infected with the H5N1 virus. The physicians’ report was revealed this week at the International Symposium on Respiratory Viral Infections (ISRVI) in Singapore.
According to the WHO the H5N1 virus has already killed 234 people in 12 countries. Tamiflu is the only antiviral reported to have been used against H5N1 in humans outside the laboratory and actually in the field.
In Indonesia, of the total of 119 H5N1 human cases reported, 22 survived - an 18 percent survival rate overall. Of these, 33 patients received no Tamiflu, all of whom died. Tamiflu was administered to 86 patients with a 26 percent survival rate overall. Time from onset of illness to initiation of treatment appeared to influence survival.
Of the 2 patients who received Tamiflu within 24 hours of illness onset both survived. 55 percent survived if given the drug within four days , and 35 percent survived if given Tamiflu within six days 3.
The survival rate of those receiving it later than 6 days after illness onset was 18 percent2 Recent information on 8 Vietnamese patients infected with H5N1, was also presented. All 8 patients received Tamiflu. However, all 8 patients presented to the hospital later than 5 days after onset of illness.
Only 3 of the 8 patients survived reinforcing that treatment benefit is reduced for patients that receive the drug later in the course of illness. In 2 patients who were unable to take the drug orally due to the severity of their illness physicians administered the drug by nasogastric tube and found it was well absorbed and there was a reduction in H5N1 virus in these patients.
Susceptibility of circulating H5N1 strains to Tamiflu
These clinical findings are supported by new animal data, also presented at ISRVI, which shows that oseltamivir treatment was effective against H5N1 influenza viruses representing different clades/subclades. However higher doses were required for the more pathogenic H5N1 viruses.
"Multiple factors can affect the susceptibility of antiviral therapy with highly pathogenic H5N1 influenza viruses and it is reassuring that oseltamivir, in mouse models, demonstrates activity even to the most pathogenic circulating strains," comments study author Dr. Elena Govorkova, St. Jude Children’s Research Hospital, Memphis, US. "Antiviral drugs are an essential component for the early control of an influenza pandemic."
Data also confirms the low level of resistance reported to date with Tamiflu to H5N1 avian influenza in the field ; there are only five cases of published reports of H5N1 resistance or reduced susceptibility to Tamiflu to date. Laboratory results have shown 96 percent of H5N1 strains tested in the laboratory were sensitive to Tamiflu.
This compares to the around 14 percent of isolates tested this year of the seasonal influenza A H1N1 virus showing resistance to Tamiflu, reported at the conference. It is important to note that these increased levels of resistance have only been reported spontaneously in this year’s H1N1 (Solomon Islands) seasonal strain, and not an avian strain such as H5N1 and not in patients who have been administered Tamiflu.
"Currently, we are seeing that Tamiflu has been used as part of the clinical management of patients infected with H5N1 with only isolated cases of resistance being reported," comments Dr David Reddy, Global Pandemic Task Force Leader at Roche. "This is reassuring for governments that have stockpiled Tamiflu for pandemic use. It is however critical that both Roche and the medical community remain vigilant so that we can understand this mutating virus and be best prepared for defence against a potential pandemic strain."
Roche has undertaken several research initiatives to study the use of Tamiflu against the evolving H5N1 avian influenza virus, including collaborations with the National Institutes of Health (NIH), the Southeast Asia Influenza Clinical Trials Research Network and other research institutions.
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