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

Asset management roundup: AXA IM’s quant arm nets CalPERS mandate

first_imgCredit: Steve BuissinneS&P DJI aims to integrate future carbon prices into its new indicesIndex provider S&P Dow Jones Indices (S&P DJI) has launched a range of equity benchmarks weighting companies by exposure to the projected price of carbon in 2030.S&P DJI has created 12 indices, including global, regional and national benchmarks. Markets covered include the US, Europe, Asia Pacific, emerging markets and South Africa.The company claimed the indices were the “first of their kind” in their use of predicted carbon price data, supplied by Trucost’s Corporate Carbon Pricing Tool.Hannah Skeates, senior director for ESG and strategy indices at S&P DJI, said: “As the efforts to achieve the commitments of the Paris Agreement and the transition to a low carbon economy progress, future carbon prices could lead to significant increased costs for companies that have not managed their global emissions.“The S&P Carbon Price Risk Adjusted index series was developed to help market participants understand the financial risks embedded among the higher carbon emitters of the current global economy.”The index series in full:S&P 500 Carbon Price Risk 2030 Adjusted indexS&P MidCap 400 Carbon Price Risk 2030 Adjusted indexS&P SmallCap 600 Carbon Price Risk 2030 Adjusted indexS&P Europe 350 Carbon Price Risk 2030 Adjusted indexS&P Global 1200 Carbon Price Risk 2030 Adjusted index S&P South Africa Composite Carbon Price Risk 2030 Adjusted indexS&P Global LargeMidCap Carbon Price Risk 2030 Adjusted indexS&P Developed LargeMidCap Carbon Price Risk 2030 Adjusted indexS&P Emerging LargeMidCap Carbon Price Risk 2030 Adjusted indexS&P Europe Developed LargeMidCap Carbon Price Risk 2030 Adjusted indexS&P North America LargeMidCap Carbon Price Risk 2030 Adjusted indexS&P AsiaPac Developed LargeMidCap Carbon Price Risk 2030 Adjusted indexSwiss bank acquires UK manager The US’s biggest state pension fund has hired AXA Investment Managers to run a $1bn (€854m) quant-driven global sustainable equity mandate.The California Public Employees’ Retirement System (CalPERS) selected AXA IM’s Rosenberg quantitative equities business to manage the allocation in line with its environmental, social and corporate governance (ESG) requirements. The strategy focuses on low volatility and high earnings indicators, according to Rosenberg.Heidi Ridley, chief executive of AXA IM Rosenberg Equities, said: “We believe that ESG information is economic in nature; it helps orient us toward companies that are using their resources well – human, physical, and technological – and away from those who are not in step with long-horizon trends.”CalPERS runs $351bn (€299.8bn) and recently reported an 8.6% net investment return for the 12 months to 30 June. Geneva, Switzerland, where UBP is basedSwiss private bank UBP is to acquire ACPI Investments, a UK-based asset manager. Subject to regulatory approvals, the transaction should close in the fourth quarter of this year.UBP indicated it stood to gain an additional £2bn (€2.2bn) in assets under management from the deal, although no other terms were disclosed. The company already runs CHF128.4bn (€110.2bn).ACPI runs a range of strategies for private and institutional clients including fixed income, equities and alternatives. It was founded in 2001 by former Goldman Sachs partners Alok Oberoi and Joseph Sassoon.Guy de Picciotto, chief executive of UBP, said: “This acquisition reaffirms our long-term commitment to the UK and our intention to continue broadening our footprint in this pivotal market.“London remains a hub for international investors, as well as for UBP which provides both foreign and UK-based clients with innovative solutions. ACPI is recognised as an investment manager of reference in the wealth management sphere with extensive expertise that will complement the range of services we already offer our clients out of London.”center_img S&P seeks to integrate future carbon prices in indiceslast_img read more

Friends of Thunder Bay National Marine Sanctuary Receives Grant to Help ‘Get Into Your Sanctuary’

first_imgAddThis Sharing ButtonsShare to FacebookFacebookShare to TwitterTwitterShare to MoreAddThis Hollings Grant the Friends received to promote a “Get Into Your Sanctuary” Campaign. Thanks to the grant, there will be:New website under development10 billboards from I-75/Saginaw to Indian River, Rogers City, Standish, Tawas, Harrisville, and entry ways to Alpena.Advertising linked to Alpena Shipwreck Tours (digital screens, signage, brochure, print advertising, short videos)Besser matching grantWhen it comes to protecting the Great Lakes here are some upcoming events and projects that are going on.4-H and local 5th graders, NEMGLSI working to reduce the use of one-time use plastics such as straws to protect the Great Lakes from micro plasticsHuron Pines, students and NEMIGLSI removing invasive species such as frog bit, garlic mustard and phragmitesGreat Lakes Divers and PADI women divers removing trash from Thunder BayBay Athletic Club’s Sweat for a Cause to support the Friends of Thunder BayAddThis Sharing ButtonsShare to FacebookFacebookShare to TwitterTwitterShare to MoreAddThis Tags: Friends at Thunder Bay National Marine Sanctuary, get into your sanctuary, NOAA, Thunder Bay National Marine SanctuaryContinue ReadingPrevious Alcona Community Schools Welcomes 2 New PrincipalsNext Fitness Friday: WBKB Reporter, Star Connor Skates, Roller Derby Stylelast_img read more