"The incidence of influenza A (H1N1) viruses that carry the neuraminidase H274Y mutation has increased by 30% this year in the Netherlands. Influenza A (H1N1) viruses that carry this mutation are resistant to oseltamivir but remain sensitive to zanamivir. However, these mutant viruses are considered to have attenuated pathogenicity."
"Oseltamivir was administered for the influenza virus infection, beginning on the sixth hospital day, but it was discontinued on day 13 because sequence analysis revealed the H274Y mutation, and no decrease in the viral load was observed. In retrospect, the H274Y mutation was present in the specimen obtained before oseltamivir therapy was initiated. The patient's hospital record and his family indicated that he had had no contact with patients who had received oseltamivir. On day 15, amantadine was added to the patient's treatment regimen. Four days later, the neutrophil count increased, indicating bone marrow recovery. Mechanical ventilation was discontinued on day 20, and zanamivir by inhalation was initiated. However, respiratory failure occurred on day 22, mechanical ventilation was reinstituted, and therapy with zanamivir was discontinued. On day 26, the influenza virus was no longer detectable. Because sequence analyses showed an amantadine-resistance mutation in the viral M2 protein (L26F) and zanamivir therapy had been limited to three doses, clearance of the virus was probably due to recovery of the immune system. A second CT scan, obtained on day 28, revealed progression of the pulmonary infiltrates. Because of the poor prognosis, mechanical ventilation was discontinued on day 34. The patient died 3 days later.
It has been suggested that the H274Y mutation, which confers resistance to oseltamivir, leaves the influenza A (H1N1) virus severely compromised. However, the case we describe suggests that this oseltamivir-resistant virus can be pathogenic, at least in an immunocompromised patient."
http://content.nejm.org/cgi/content/full/359/10/1074
What a pity intravenous relenza wasn't an option. GSK are more motivated by the money they can make developing a vaccine.
From early 2007,
"Glaxo has stopped development of injectable forms of Relenza, which health officials had said might help treat severely ill avian-flu patients, Stout said.
``We asked people if they were going to buy any and they said `No, we want it to be there just in case,'' he said. The company faced ``huge, expensive clinical programs without any buyer.''
"It's just on hold,'' he said. Orders for the available, inhaled drug have slowed, he said. "
http://www.bloomberg.com/apps/news?pid=20601109&sid=amEj8Gs9hVNg&refer=news
"GlaxoSmithKline, which makes Relenza, has shelved plans to test an intravenous form of the drug in the United States, but is in discussions with a WHO-organized treatment network in Southeast Asia to test the new formulation there."
http://www.cbc.ca/cp/health/070318/x031806A.html
The Southeast Asia Influenza Clinical Research Network had a clinical trial using IV Relenza, organized in March 2007( http://web.archive.org/web/20080209225213/http://www.ciras-sea.org/study003.asp ), but subjects were never recruited and it's been removed fron their approved projects list.
http://www.ciras-sea.org/projects.asp
"Oseltamivir was administered for the influenza virus infection, beginning on the sixth hospital day, but it was discontinued on day 13 because sequence analysis revealed the H274Y mutation, and no decrease in the viral load was observed. In retrospect, the H274Y mutation was present in the specimen obtained before oseltamivir therapy was initiated. The patient's hospital record and his family indicated that he had had no contact with patients who had received oseltamivir. On day 15, amantadine was added to the patient's treatment regimen. Four days later, the neutrophil count increased, indicating bone marrow recovery. Mechanical ventilation was discontinued on day 20, and zanamivir by inhalation was initiated. However, respiratory failure occurred on day 22, mechanical ventilation was reinstituted, and therapy with zanamivir was discontinued. On day 26, the influenza virus was no longer detectable. Because sequence analyses showed an amantadine-resistance mutation in the viral M2 protein (L26F) and zanamivir therapy had been limited to three doses, clearance of the virus was probably due to recovery of the immune system. A second CT scan, obtained on day 28, revealed progression of the pulmonary infiltrates. Because of the poor prognosis, mechanical ventilation was discontinued on day 34. The patient died 3 days later.
It has been suggested that the H274Y mutation, which confers resistance to oseltamivir, leaves the influenza A (H1N1) virus severely compromised. However, the case we describe suggests that this oseltamivir-resistant virus can be pathogenic, at least in an immunocompromised patient."
http://content.nejm.org/cgi/content/full/359/10/1074
What a pity intravenous relenza wasn't an option. GSK are more motivated by the money they can make developing a vaccine.
From early 2007,
"Glaxo has stopped development of injectable forms of Relenza, which health officials had said might help treat severely ill avian-flu patients, Stout said.
``We asked people if they were going to buy any and they said `No, we want it to be there just in case,'' he said. The company faced ``huge, expensive clinical programs without any buyer.''
"It's just on hold,'' he said. Orders for the available, inhaled drug have slowed, he said. "
http://www.bloomberg.com/apps/news?pid=20601109&sid=amEj8Gs9hVNg&refer=news
"GlaxoSmithKline, which makes Relenza, has shelved plans to test an intravenous form of the drug in the United States, but is in discussions with a WHO-organized treatment network in Southeast Asia to test the new formulation there."
http://www.cbc.ca/cp/health/070318/x031806A.html
The Southeast Asia Influenza Clinical Research Network had a clinical trial using IV Relenza, organized in March 2007( http://web.archive.org/web/20080209225213/http://www.ciras-sea.org/study003.asp ), but subjects were never recruited and it's been removed fron their approved projects list.
http://www.ciras-sea.org/projects.asp
