New data published in Antimicrobial Agents and Chemotherapy show that the oral antiviral drug Tamiflu (oseltamivir) is effective against two currently circulating strains of H5N1 avian influenza viruses, preventing death if treatment is initiated within twenty four hours of virus exposure[1]. Conclusions drawn from the study data add to the bank of evidence showing Tamiflu is effective against H5N1 avian influenza strains[2], and lend support to the use of Tamiflu during an influenza pandemic.
"The results of this study confirm that oseltamivir can prevent mortality caused by infection with H5N1 avian influenza viruses, commented Dr. Elena Govorkova, St. Jude Children's Research Hospital, lead investigator of the study. "There was also no emergence of oseltamivir-resistant variants when the drug is administered at optimal dosages."
The study evaluated the administration of 5 mg/kg/day (equivalent to the half of recommended dose of 75 mg/kg in humans) of Tamiflu for five days in ferrets either four hours or twenty-four hours post-infection with either the highly pathogenic A/Vietnam/1023/04 (H5N1) virus strain, or the less pathogenic A/Turkey/15/06 (H5N1) virus strain. When administered within four hours, all ferrets survived inoculation.1 When treatment was delayed until 24 hours after inoculation, treatment with the higher dose of 25 mg/kg/day was required against the Vietnam H5N1 strain and the higher dose of 10 mg/kg/day against the less pathogenic Turkey H5N1 strain.1 This was associated with 100% survival against both strains and markedly reduced the severity of disease, weight loss and fever.1
The research also examined whether Tamiflu treatment affects immune responses for subsequent infections. All ferrets that survived were re-infected 21 days later with the virus, and were found to have developed an immune response that completely protected them from infection.1 Furthermore, no resistance to the drug was detected during the study.1
"The course of H5N1 infection in ferrets is very similar to that in humans," said Robert Webster, a member of the Infectious Diseases department and holder of the Rose Marie Thomas Chair at St. Jude and senior author of the report. "This model lets us study infection with a variety of H5N1 viruses," he added. "Since not all human cases of H5N1 infection are fatal, it is useful to evaluate drugs against viruses of different pathogenicity."
According to the World Health Organization (WHO), human cases of avian influenza A (H5N1) infection have remained rare and sporadic, but the disease can be very severe and the case fatality is high[3]. The H5N1 influenza viruses isolated in Southeast Asia and Turkey induce a severe infection in humans, which results in deaths of more than 50% of those infected. The WHO has confirmed 282 human infections (March 27th, 2007) which has resulted in 169 deaths[4].
This study provides further insights into this highly pathogenic virus, confirming both its efficiency at replicating and its virulence. Virologists expect that the H5N1 avian influenza virus must mutate before it becomes efficient in human-to-human transmission. Tamiflu is designed to be active against all clinically relevant influenza viruses[5], including the H5N1 virus, and has previously been shown to be effective in cell culture and in animals infected with the H5N1 virus isolated from humans[6].
The WHO assembled an international multidisciplinary panel of experts in March 2006 to develop rapid advice for the pharmacological management of patients with H5N1 infection by using innovative guideline development methods based on the best available evidence. The panel considered the benefits, harm, burden and cost of intervention in several patient and exposure groups when developing the recommendations. The WHO strongly recommends Tamiflu for the treatment of patients with confirmed or strongly suspected human infection with the H5N1 virus. The recommendations and pharmacological guidelines for the prophylaxis and treatment of patients with avian influenza have been published in the January 2007 issue of The Lancet Infectious Diseases[7
This study was supported by the National Institute of Allergy and Infectious Diseases, the U.S. Public Health Service (grants CA-21756, AI-57570, and AI-95357), by F. Hoffmann La-Roche Ltd., and by the American Lebanese Syrian Associated Charities.
About influenza
Influenza, commonly called the 'flu', is a serious disease and annual outbreaks and epidemics are caused by influenza A and B viruses[8]. Influenza is a highly contagious viral illness and is characterised by a sudden onset of debilitating clinical symptoms which affect the entire body. Up to 500 million people are infected by influenza[9] and up to 500,000 deaths are attributed to influenza each year[10]. Influenza complications occur in all patient groups and include bronchitis, sinusitis, otitis media, and pneumonia.
About Tamiflu
Tamiflu is designed to be active against all clinically relevant influenza viruses and works by blocking the action of the neuraminidase (NA) enzyme on the surface of the virus. When neuraminidase is inhibited, the virus is not able to spread to and infect other cells in the body.
It is licensed for the treatment and prophylaxis of influenza in children aged one year and above and in adults.
Roche and Gilead
Tamiflu was invented by Gilead Sciences and licensed to Roche in 1996. Roche and Gilead partnered on clinical development, with Roche leading efforts to produce, register and bring the product to the markets. Under the terms of the companies' agreement, amended in November 2005, Gilead participates with Roche in the consideration of sub-licenses for the pandemic supply of Tamiflu in resource-limited countries. To ensure broader access to Tamiflu for all patients in need, Gilead has agreed to waive its right to full royalty payments for product sold under these sub-licenses.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology
All trademarks used or mentioned in this release are legally protected.
Additional information
- Roche Health Kiosk, Influenza: health-kiosk.ch/start_grip.htm
- About Tamiflu: roche/med_mbtamiflu05e.pdf
- About influenza: roche/med_mbinfluenza05e.pdf
- WHO: Global influenza programme: who.int/csr/disease/influenza/en
- WHO: Avian flu: who.int/mediacentre/factsheets/avian_influenza/en
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References:
[1] Govorkova E.A. et al "Efficacy of oseltamivir therapy in ferrets inoculated with different clades of H5N1 influenza virus" Antimicrobial Agents and Chemotherapy, April 2007
[2] WHO, "Avian influenza: assessing the pandemic threat" January 2005.
who.int/csr/disease/influenza/H5N1-9reduit.pdf
[3] WHO, "Rapid Advice Guidelines on pharmacological management of humans infected with avain influenza" May 2006
who.int/csr/disease/avian_influenza/guidelines/pharmamanagement/en/
[4] WHO, "Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO" 27th March 2007
who.int/csr/disease/avian_influenza/country/cases_table_2007_03_27/en/index.html
[5] Oxford, JS et al, "Targeting influenza virus neuraminidase - a new strategy for antiviral therapy" Drug Discovery Today. 1998:3 (10) 448-456
[6] Yen H-L., et al, "Duration and Dosage of Oseltamivir Treatment of H5N1 (A/Vietnam/1203/04) influenza virus infection in mice" Journal of Infectious Diseases, 2005.
[7] WHO, "Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus" Lancet Infect Dis 2007; Vol 7 Issue 1, January 2007, Pages 21-31
infection.thelancet
View drug information on Tamiflu capsule.
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