Clinical study points to cytokine storm in H5N1 cases

first_imgSep 11, 2006 (CIDRAP News) – A controlled study of H5N1 influenza patients in Vietnam has provided fresh evidence that explosive viral growth and the resulting cytokine storm, or excessive immune response, account for the often lethal nature of H5N1 disease.The study underlines the importance of early antiviral treatment to stop the viral population explosion. The authors, led by Menno de Jong of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam, suggest that treatment to blunt the late-stage immune response should also be explored.”Our observations point to a central role for high viral burden in the pathogenesis of human H5N1 disease and suggest that timely suppression of viral replication should remain the mainstay of treatment of influenza H5N1,” states the report, published online yesterday by Nature Medicine.The study has also prompted experts to mention the possibility of using intravenous antiviral treatment in an effort to move drugs to the sites of viral activity faster than is possible with oral drugs like oseltamivir (Tamiflu).De Jong’s team conducted virologic and immunologic studies on 18 H5N1 patients and eight patients with ordinary seasonal flu (H3N2 and H1N1 viruses) in 2004 and 2005. Thirteen of the 18 H5N1 patients died of the illness. The H5N1 patients presented for treatment an average of 6 days after the onset of illness—well beyond the recommended 2-day window for starting antiviral treatment. The researchers looked for the virus in samples from the nose, throat, blood, and rectum.Among the virologic findings:H5N1 patients had more viral material (viral RNA) in the throat than in the nose, and they had more viral RNA in the throat than patients with ordinary flu had.H5N1 patients who died had the highest levels of viral RNA.Viral traces were found in blood samples from 9 of the 16 H5N1 patients whose blood was tested; viral RNA in blood was associated with high viral loads in throat specimens.Viral RNA was found in rectal samples from 5 of 7 H5N1 patients, and three of these had diarrhea.The researchers also examined the blood levels of seven cytokines and chemokines—molecular messengers that call various kinds of immune cells into action, triggering inflammation. They found that H5N1 patients had significantly higher levels of 6 out of 7 of these substances than seasonal flu patients had. In addition, levels of four chemokines were particularly high in H5N1 patients who died.”Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis,” the authors write. “The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment.”They add that the limited effectiveness of antiviral treatment in H5N1 patients when started late may reflect the inability of the drugs to stop the cytokine storm at that point. At that stage, they suggest, treatment to limit or change the immune response “has potential benefits.” But they emphasize that the main focus should be on early diagnosis and antiviral treatment.The central question raised by the study, according to infectious disease expert Michael T. Osterholm, PhD, MPH, is, “At what level of viremia does the cytokine storm get triggered? Once that happens, does it matter what the ongoing level of viral activity happens to be? Once the cytokine storm begins, it’s already too late to have any impact with antivirals.”Osterholm, who is director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of the CIDRAP Web site, said he doesn’t know of anyone who has tried immunosuppressive or anti-inflammatory drugs to stop the cytokine storm in H5N1 patients.”No one knows what the consequences of that might be,” he said. Reducing the immune response could backfire by allowing the virus to run wild, he suggested.Virologist Frederick G. Hayden, MD, said intravenous administration might improve the effectiveness of antiviral treatment in H5N1 disease, according to a Canadian Press report published yesterday.”A potent parenteral agent . . . is really needed and will give us the ability, I hope, to more rapidly control replication in patients with these kinds of severe infections,” Hayden was quoted as saying.Hayden, of the University of Virginia in Charlottesville, heads a World Health Organization research network that plans to assess various treatment regimens for H5N1 patients, the story said. The report said injectable forms of two antivirals—peramivir and zanamivir (Relenza)—are in development.Osterholm said intravenous drugs move into the system faster, but giving drugs intravenously is harder than giving them orally.  In a flu pandemic, he said, “Will there be IV bags available? If you give a drug that’s only IV, and then you run out of IV sets, you’ve got a problem.”De Jong MD, Simmons CP, Thanh TT, et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nature Med 2006 Sep 10 (early online publication) [Abstract]See also:Nov 16, 2005, CIDRAP News story “Lab study supports idea of ‘cytokine storm’ in H5N1 flu”Oct 11, 2005, CIDRAP News story “Experts cite differences between H5N1 and ordinary flu”Dec 22, 2005, CIDRAP News story “Tamiflu resistance in avian flu victims sparks concern”last_img read more

New South Wales legalizes abortion

first_imgThe legislation, which decriminalizes abortion, generated weeks of heated debate in New South Wales, Australia. GETTY IMAGES The law makes it legal for terminations to beconducted up to 22 weeks into a woman’s pregnancy – or later if two doctorsagree.(BBC) The legislation was passed 26-14 in thestate’s lower house after discussions about more than 100 possible amendments.It has already been approved by the upper house. AUSTRALIA – Abortion was decriminalized acrossAustralia after the last remaining state where it was illegal, New South Wales(NSW), voted to reform its laws.center_img Previously, abortions were possible in NSWonly if a doctor deemed there was “serious risk” to a woman’s health.     The bill on Thursday overturns a 119-year-oldlaw that generated weeks of heated debate.last_img read more

Stoke concerns over Begovic fitness

first_img Hughes told the club’s website, www.stokecityfc.com: “Asmir is the big worry for us at the moment, because of a knock he has picked up to his thigh on Tuesday. “He has a bit of bleeding in there, so we need to nurse him and then assess him tomorrow to see where he is at. “It is a bit of a concern because he has been outstanding for us this year, but we will see what happens over the course of the next 24 hours.” Sorensen, 37, has been restricted to domestic cup ties in the past two seasons but Hughes has no doubts over the Dane’s readiness to play. He said: “If Asmir isn’t ready then I will have no qualms in throwing Thomas into the team. “He is a top keeper in his own right who has an abundance of experience behind him.” The Hull game will come too soon for midfielder Matthew Etherington despite his return to training this week after a back injury. Hughes said: “Matty has joined the squad again in training this week but I think it will be more worthwhile letting him recuperate back here this weekend, rather than sitting in a coach for three hours. Manager Mark Hughes has revealed the Bosnia international is doubtful for the KC Stadium clash after suffering the injury in training. Thomas Sorensen, who has not started a league game since the final day of the 2011-12 season, is on standby to replace him. Press Association “We will hopefully get him involved in the under-21 game for a spell tomorrow afternoon, which will help him build up his match fitness again.” Full-back Erik Pieters is fit again after a groin strain but Hughes may opt to retain Marc Muniesa, who impressed in the Dutchman’s absence in last week’s shock win over Chelsea. Hughes said: “It’s a very nice problem to have two quality players battling for one position. “Erik has been fantastic this season, but Marc was outstanding against Chelsea. It’s one that I will have to sleep on.” Stoke goalkeeper Asmir Begovic could miss Saturday’s Barclays Premier League trip to Hull with a thigh problem.last_img read more