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

Q&A with Josh Walfish of The Daily Northwestern

first_imgSyracuse opens its season Saturday against Northwestern, a team that features an explosive dual-threat quarterback and a defense looking to improve from a disappointing 2011 season. The Daily Orange spoke to Josh Walfish of the The Daily Northwestern at Northwestern University to get a better look at what to expect from the Wildcats:The D.O.: What needs to happen for the Northwestern defense to improve from last season’s disappointing performance?Walfish: The key for Northwestern’s defense this season will be the front seven. They are the most experienced unit on the team and will need to lead by example. A poor pass rush last season left a shaky secondary out to dry and the whole defense suffered. In its upset over Nebraska last season, Northwestern’s defensive front seven probably had its best game, limiting how much damage the potent Cornhuskers running game was able to inflict. If the front seven come to play, the Northwestern defense will make tremendous strides.The D.O.: How much of an upgrade does Dean Lowry bring to the defensive line?Walfish: Dean Lowry has certainly been impressive this fall to earn a spot on the two-deep as a true freshman. However, his biggest asset may be he adds depth to a defensive line that did not have that luxury last season. The other backup defensive end, redshirt freshman Deonte Gibson, came back from a knee injury and really impressed people in the spring which gives the Wildcats some capable fresh legs to rush the quarterback on third downs.AdvertisementThis is placeholder textThe D.O.: How much does Kain Colter elevate Northwestern’s spread offense? Also, how does he compare to Dan Persa?Walfish: Kain Colter’s athleticism makes him one of the most dangerous quarterbacks to ever run the spread at Northwestern. His ability to make plays with his feet is superior to that of Dan Persa. The only thing Colter does not do better than Persa is arm strength and accuracy because he is still building it back up from shoulder surgery in high school. His strength has improved since last season and he is not all that inaccurate, although it is tough to follow in the footsteps of the most accurate passer in NCAA history. Nonetheless, Colter allows offensive coordinator Mick McCall to really use more wrinkles to his offense he couldn’t use with Persa at the helm.The D.O.: Does Northwestern look like a team prepared to make any strides in the Big Ten?Walfish: Although we may not see it this year, Northwestern has stepped up in recruiting and might have the most talented team in the last 10 years. Getting players like Ifeadi Odenigbo to come play in Evanston builds a solid foundation for the Wildcats to take a run at a Big Ten title in the next couple of years. If Pat Fitzgerald can continue to recruit good talent to Northwestern, he could put the dark ages of the 1970s way in the rear view mirror and make this team a perennial bowl participant.The D.O.: What’s going to be the biggest key for Northwestern to get to a bowl game and finally win one this season?Walfish: If Northwestern wants to win a bowl game this season, they will need to put together a full 60 minutes. It struggled to do that last season outside of the game against Nebraska and it cost them at least three wins. No surprise the play of the defense, especially an inexperienced secondary,  will also be a key to winning a bowl game.– Compiled by Chris Iseman, asst. sports editor, Comments Related Stories Cover 2: Syracuse defense focused on limiting dual-threat Colter Published on August 30, 2012 at 2:56 amcenter_img Facebook Twitter Google+last_img read more