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Bird Flu Beneath the Microscope: A Physicians View

05 March 2008

INDONESIA - Physicians from countries affected by the deadly H5N1 influenza virus have presented case reports about antiviral use in patients infected with H5N1, including treatment with the oral antiviral TAMIFLU(R) (oseltamivir).

The physicians' reports were revealed this week at the International Symposium on Respiratory Viral Infections (ISRVI) in Singapore.

According to a report from the symposium, studies supporting the approval of TAMIFLU are based in seasonal influenza. The magnitude of effect of TAMIFLU in treating and preventing novel strains of influenza (such as those that may be involved in a pandemic or associated with avian flu) cannot be predicted as it has not been studied or approved in a pandemic scenario.

In conclusion the World Health Organization (WHO) has recommended that higher doses and longer treatment durations may be required to combat novel strains of influenza.

According to the WHO, the H5N1 virus has already killed 234 people in 12 countries.In the most recent clinical management guidelines issued by the WHO, TAMIFLU remains the primary antiviral agent of choice for the treatment of H5N1 virus infections.

Symposium findings

In Indonesia, of the total of 119 H5N1 human cases reported, 22 survived an 18 per cent survival rate overall. Of the 119, 33 patients received no TAMIFLU, all of whom died. TAMIFLU was administered to the other 86 patients, with a 26 per cent survival rate overall. Time from onset of illness to initiation of treatment appeared to influence survival.

Of the two patients who received TAMIFLU within 24 hours of illness onset, both survived. If given the drug within four days, 55 per cent survived, and 35 per cent survived if given TAMIFLU within six days.(4) The survival rate of those receiving it later than six days after illness onset was 18 per cent.

Recent information about eight Vietnamese patients infected with H5N1 was also presented. All eight patients received TAMIFLU, however, all eight patients presented to the hospital later than five days after onset of illness. Only three of the eight patients survived reinforcing that treatment benefit is reduced for patients that receive the drug later in the course of illness. In two 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 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 per cent of H5N1 strains tested in the laboratory were sensitive to TAMIFLU.

This compares to the around 14 per cent 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.

Further Reading

       - You can visit the Avian Flu page by clicking here.

ThePoultrySite News Desk



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