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

GFF’s Forde and Williams happy over CFU approval

first_imgPRESIDENT of the Guyana Football Federation (GFF), Wayne Forde has expressed his delight at the approval by CFU of the Leonora Stadium,for Guyana’s crucial 3rd round Caribbean Cup match against defending Champions, Jamaica.In a Press Release from the Federation,the GFF’s boss expounded on how much a plus it is for the sport.“I think, apart from the venue being available for the Jamaica game, we now have one additional venue in Guyana that is certified for International football, and I think that gives us a second set of options,and it couldn’t have been any timelier… I think Guyana needed to have home court advantage. We all know that Jamaica is a formidable opponent and apart from the advantage that we needed, it has been almost forty years since we last played Jamaica in Guyana”.Also sharing the happy feelings on the ‘Green Light’ for the venue is Operations Manager, Trevor Williams.“We are grateful to be able to have the facility stand scrutiny and reviewed by the CFU. It is very encouraging for us because a lot has been invested in this facility and to know that outside of the National Stadium, we can actually play International football, is good news for Guyana, the Government,and the GFF who has done a lot to encourage the growth and development of the sport. “So we are very happy and I am sure the entire Government will be pleased”.last_img read more

Kiev to Host 2018 UCL Final

first_imgKiev’s Olympic Stadium will host the final of the 2018 Champions League, the head of Ukraine’s soccer federation announced yesterday.The 70, 000-capacity stadium, which hosted the final of the 2012 European Championship, will be confirmed officially following a meeting of UEFA officials in Athens but Andriy Pavelko, head of Football Federation of Ukraine, announced the news on his federation’s website.“The historical decision for the Ukrainian football was taken in Athens,” Pavelko said.“The final of the Champions League is the common win of every Ukrainian citizen. Now we can greet each other with this feast of football to be held in Kiev.“This is an incredible event that will take its place in the history of the country,” Pavelko added. “We will do all possible for this final to become exemplary.”Share this:FacebookRedditTwitterPrintPinterestEmailWhatsAppSkypeLinkedInTumblrPocketTelegramlast_img read more

ASA’s new guidelines set to protect problem gamblers

first_img Ministers expected to raise National Lottery age limit August 17, 2020 Share Share ASA monitoring sweep marks gambling as the worst underage advertising offender August 26, 2020 UK gambling adopts toughest online advertising code to protect underage audiences August 27, 2020 StumbleUpon Submit Related Articles UK advertising regulators CAP and BCAP are ready to roll out new standards, set to come into force on 1 April, which will change the ways in which gambling operators can promote their products. The new advertising standards will prevent the display of online adverts for gambling products and services that uses data on consumer online interests and browsing behaviour that may be targeted towards minors and those susceptible to gambling-related harm.In a letter sent to the former Minister for Sport Tourism and Heritage, Tracey Crouch, the Chief Executive of the Advertising Standards Agency (ASA), detailed: “From Q2, CAP will focus on protections for problem gamblers, people at risk of problem gambling and others who might be vulnerable to problem gambling behaviours.”The new strategy is primarily aimed at limiting the accessibility of gambling advertisements to minors, with plans to “extensively list unacceptable types of content, including certain types of animated characters, licensed characters from movies or TV and sportspeople and celebrities that are likely to be of particular appeal to children, and references to youth culture”.ASA’s guidelines will add to “existing guidance on the responsible targeting of ads, covering all media (including social networks and other online platforms)”, by also prohibiting the use of celebrity endorsement from those under the age of 25.The guidelines detail: “Gambling-like games or games that feature elements of simulated gambling activity are often popular with children and young people. “Such games should not be used to promote real money gambling products, for instance, by offering a trial version that plays a similar role to an advergame. Where social and online games feature marketing communications for gambling games, they should not be directed at under-18s.”“Gambling operators sometimes feature sports people or celebrities in marketing communications. This can often be through an endorsement agreement between the operator and the individual. Such individuals who are or appear to be under 25 are explicitly prohibited from appearing in gambling marketing communications by CAP Code rule 16.3.14 and BCAP Code rule 17.4.6.”last_img read more