SARS in the Context of Emerging Infectious Threats: References and Resources

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SARS in the Context of Emerging Infectious Threats: Home Page - SARS in the Context of Emerging Infectious Threats: A Web archive developed by Columbia DKV for a conference hosted by the New York Academy of Sciences.

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http://www.nyas.columbia.edu/sars/web/s2/index.html SARS in the Context of Emerging Infectious Threats: Topics and Speakers - Research Report SARS Aetiology: A Research Update from Malik Peiris Welcome Ellis Rubinstein, Chief Executive Officer, New York Academy of Sciences Introductory Remarks W. Ian Lipkin, Director of the Center for Immunopathogenesis and Infectious Diseases, Mailman School of Public Health, Columbia University, New York Session I: Coronavirus Biology and Pathogenesis Moderated by Scott Hammer Speakers Paul Masters, Wadsworth Center, NY State Dept. of Health, Albany Molecular Biology of Coronaviruses Kathryn V. Holmes, Department of Microbiology, University of Colorado Health Sciences Center, Denver Coronavirus Pathogenesis Linda Saif, Professor, Food Animal Health Research Program, Ohio State University, Wooster Coronavirus Transmission and Persistence Thomas Ksiazek, Centers for Disease Control and Prevention, Atlanta Technology in SARS Discovery Panel 1 Discussion Session II: On the Front Lines Moderated by Scott Hammer Speakers Larry Anderson, Centers for Disease Control and Prevention, Atlanta. Clinical Spectrum of SARS Infection Donald Low, Mt. Sinai Hospital, Toronto Clinical Experience in Toronto Chen Zhu, Shanghai Second Medical University, People's Republic of China. Delivered by Dr. Scott Hammer SARS: An Update from China Panel 2 Discussion Session III: Approaches to Vaccines and Drug Development Moderated by Scott Hammer Speakers David Ho, Aaron Diamond AIDS Research Center, New York Blocking SARS Virus Fusion Frederick Hayden, University of Virginia School of Medicine, Charlottesville Lessons in Interventions for SARS Catherine Laughlin, National Institute of Allergy and Infectious Diseases, Bethesda Status of Drug Screening vs. SARS C. Richter King, GenVec Inc., Gaithersburg, VA Adenovirus Vector Technologies for Vaccines Thomas Monath, Acambis, Cambridge, MA Some Approaches to Vaccine Development Panel 3 Discussion with Richard Colonno (Bristol-Myers Squibb), Michael Dunne (Pfizer) and Emilio Emini (Merck) Session IV: Future Perspectives on Emerging Infections Moderated by Allan Rosenfield Speakers C.J. Peters, University of Texas Medical Branch, Galveston Special Pathogens in Three Cultures Marcelle Layton, NY City Department of Health SARS and Public Health Systems John La Montagne, National Institute of Allergy and Infectious Diseases, Bethesda A View from the Field and the Bridge Panel 4 Discussion

http://www.nyas.columbia.edu/sars/web/s3/index.html SARS in the Context of Emerging Infectious Threats: Session I - Ellis Rubinstein, Chief Executive Officer, New York Academy of Sciences The NYAS will be launching in Fall 2003 a series of seminars in the hottest fields of science. Seminars and conferences will be presented on the Web with educational materials and other resources. This event is the start of an exciting partnership at the Academy to bring together industry and academic scientists. The SARS epidemic has brought out acts of heroism on the part of those on the front lines, including scientists, doctors, and journalists. W. Ian Lipkin, Mailman School of Public Health, Columbia University, New York Dr. Lipkin phoned into this conference because he had contracted a fever and cough after a visit to China. Although expert consensus is that he does not have SARS, Dr. Lipkin remained in quarantine until May 25, 2003. Dr. Lipkin serves as a special advisor on SARS to the Ministries of Science and Technology and Health in China and is helping to coordinate international research efforts. Coronaviruses owe their crown-like appearance to a multitude of spike (S) proteins studding their surfaces, explained Paul S. Masters, Ph.D., an investigator and professor of molecular genetics at the Wadsworth Center of the New York State Department of Health. These S proteins take on the task of fusing the virus to a victim's cells, enabling the pathogen to set up shop in the cell. The coronavirus' other three proteinsthe membrane (M) protein, envelope (E) protein, and nucleocapsid (N) proteinthen go to work, essentially turning the host cell into a factory that manufactures and exports newly formed coronaviruses which can attack other cells in the body. Coronaviruses are highly species-specific, noted Kathryn V. Holmes, Ph.D., a molecular biologist at the University of Colorado Health Sciences Center in Denver. They cause a variety of respiratory, gastrointestinal, and neurologic infections in animals and humans. But because host cell receptors differ between species, a coronavirus that causes a respiratory infection in a pig, for example, has no effect on humans or chickens . . . unless the virus mutates. Such mutation might explain the origin of the SARS virus, which researchers speculate may have come from an animal in south China, where the first SARS cases materialized. "Many of these viruses have probably been with their hosts for a long time," Holmes said. "But how much change does there have to be for a virus to jump to a different host?" Holmes studies the mouse hepatitis virus, a coronavirus that may shed light on the behavior of the SARS virus. She outlined several potential targets for treating the SARS coronavirus, including those that interfere with its replication machinery as well as vaccines. "If we can develop these therapies, they will be applicable not only to SARS, but also to a large number of diseases in animals," she concluded. Two species that could be especially helped by such treatments are pigs and cows. Linda J. Saif, Ph.D., a professor and researcher with Ohio State University's Agricultural Research and Development Center, described coronaviruses that cause severe and often fatal respiratory and gastrointestinal infections in these animals, gleaning information about coronavirus infection progression and potential modes of treatment. Studies have shown that these infections may be exacerbated when the virus is administered via aerosol, at high doses, with immunosuppressive drugs, or in the presence of other viral or bacterial infectionsdata that may yield clues about who is most vulnerable to SARS infection. Moreover, cows that co-mingle with other cattle from different farms and/or have experienced stress during shipping (causing "shipping fever") are more susceptible to coronaviral infections. "We see something similar to this in SARS patients who recently experienced the stress of travel," noted Saif. She described various vaccines that have been developed for these infections in animals, some of which are effective but most of which offer limited protection. Thanks to a mix of classic and modern techniques, scientists are refining the way the SARS virus is being detected, explained Thomas G. Ksiazek, D.V.M., Ph.D., acting chief of the Special Pathogens Branch in the Division of Viral and Rickettsial Diseases at the Centers for Disease Control and Prevention (CDC). He chronicled the efforts of medical detectives to isolate and characterize the virusinitially using immunohistochemical staining, and later confirming its identity and genome with RT-PCR sequencing and array technology. Indirect fluorescent antibody testing and ELISA have been employed to garner more information. "The sequencing of the virus' genome so rapidly is a good use of modern technology, and will make diagnosis of the infection and therapy with vaccines possible in the future," concluded Ksiazek.

http://www.nyas.columbia.edu/sars/web/s4/index.html SARS in the Context of Emerging Infectious Threats: Session II - The first appearance of SARS in people began last fall, when sporadic cases began to emerge in the southern Chinese province of Guangdong. But the seminal event triggering the current epidemic took place on February 21, when a doctor from Guangdong stayed on the ninth floor of Hong Kong's Metropole Hotel. Ten other people contracted his infection, taking it with them as they continued to travel. Within weeks, the illness popped up in other nations, including Vietnam, where it took the lives of healthcare workers such as Carlo Urbani, the World Health Organization doctor who first identified the outbreak. The virus most frequently has been spread in hospital settings, indicating that community transmission is less likely, said Larry Anderson, M.D., chief of the CDC's Respiratory and Enteric Viruses Branch. "There is a likelihood that with good infection control practices, we can control the spread of SARS," he contended. Indeed, the infection has already been controlled in Canada, Singapore, Thailand, Vietnam, and the United States. "The good news is that the SARS outbreak has been controlled in some settings, but not in others. We still have a great deal to learn," he added. For example, who is most likely to develop severe, if not fatal, SARS? Evidence to date indicates that elderly patients and those with diabetes or certain other co-existing chronic medical conditions are more likely to succumb to the illness, but more data is needed to confirm and explain these associations. Investigators also want to know more about the optimal time during the illness to collect specimens such as urine, respiratory secretions, and stool samples so they can correlate their findings with disease progression. In Toronto, investigators are analyzing the blood of 100 healthcare workers who were exposed to SARS and 100 others who were not, to see if they can pinpoint any indicators of early SARS infection. Donald E. Low, M.D., chief microbiologist at Toronto's Mount Sinai Hospital, explained the SARS outbreak that, as of the date of the conference, had taken 23 lives and caused economic hardship for the city. Their saga began when a woman returned to Toronto after visiting Hong Kong. She developed SARS symptoms and died on March 5, but not before infecting her husband and her son. Her son in turn infected two other men in nearby hospital beds, who set off a chain of infection that included relatives, members of a church group that had been visiting the hospital emergency room, and patients at other hospitals in Toronto before all was said and done. The infection is now under control there. "The outbreak is over. It is safe to come to Toronto," Low asserted, noting the valuable lessons learned from Toronto's SARS experience. One is that strict infection control is a must. Second, the disease is more often spread in hospitalsvia droplets and contactthan via casual contact in the community. And finally, Low called SARS "a disease of tribes," whether those tribes include family members, hospital workers, or close communities such as religious groups. Recent reports from China indicate that the outbreak there may be abating as well. Scott Hammer delivered a presentation prepared by Chen Zhu, Sc.D., vice president of the Chinese Academy of Sciences, who could not be at the meeting. According to his presentation, China has established a central command and ten task forces and is also evaluating potential treatments (including the serum of convalescent patients), building international collaborations, and establishing research centers to study the virus. "The situation in China illustrates the awakening and the multidimensional approach that China is taking to control SARS," said Hammer. "It's not just a public health event, but a major political and economic event for China."

http://www.nyas.columbia.edu/sars/web/s5/index.html SARS in the Context of Emerging Infectious Threats: Session III - Despite more than two decades of research, the clever HIV pathogen has continued to elude us. But some new good may come out of all those years of study: The coronavirus that causes SARS appears to fuse to host cells in much the same way as HIV. Harnessing this knowledge, David Ho, M.D., scientific director of the Aaron Diamond AIDS Research Center at The Rockefeller Universitywho has scrutinized HIV for 22 yearsand his team have designed a peptide that may inhibit this fusion. Preliminary studies in Hong Kong are producing promising results in tissue culture. Ho speculates that this peptide would have little toxicity in clinical applications. "There are still many obstacles in the way, but this is an example of what one can do in a very short time," he concluded. Since so little is known about the virus' behavior, some doctors have been treating SARS patients with ribavirin and steroids such as dexamethasone, a treatment approach that has not been effective. In fact, corticosteroids may actually delay viral clearance in patients with viral respiratory infections, explained Frederick G. Hayden, M.D., professor of internal medicine and pathology at the University of Virginia School of Medicine. "One has to be very cautious about the effects of corticosteroids on viral replication, particularly in the absence of antiviral drugs," he asserted. Antiviral agents that appear intriguing for use in SARS patients include oseltamivir, zanamivir, and interferon. "We need a better understanding of the natural history of the infection, including mechanisms of injury and host immunopathologic responses," he added. "Controlled clinical trials are going to be essential to understand what really works in this illness." Drugs with the potential for treating SARS will go through an intensive screening process jointly coordinated by the CDC, the U.S. Army Medical Research Institute of Infectious Diseases, and the NIAID. "There are many steps in the viral life cycle where fusion inhibitors might play a role," said Catherine Laughlin, Ph.D., chief of the Virology Branch of the Division of Microbiology and Infectious Diseases at the NIAID. Other potential drug targets include cysteine protease, RNA-dependent RNA polymerase, helicase, genome replication and transcription, and the N protein. Laughlin hypothesized that the most effective treatment will probably be a combination of an antiviral agent and another drug that interferes with the viral replication process. The race is on between pharmaceutical companies setting out to make a name for themselves in the SARS arena. GenVec, Inc., a Maryland-based biopharmaceutical company, is developing a vaccine against SARS using its adenovector technology, in collaboration with the Vaccine Research Center of the NIAID and the U.S. Navy Medical Research Center. C. Richter King, Ph.D., vice president of research at GenVec, explained that the "AdVaccine" is based on an adenovirus that is modified to contain a therapeutic protein. The resulting adenovector bears a therapeutic gene capable of triggering an immune response. Moreover, King noted that the highly targeted vaccine is safe and well tolerated, and easily manufactured. Acambis, a pharmaceutical company specializing in vaccine development, has begun its own investigations into a vaccine for SARS, hoping to build on the success it has had creating vaccines against smallpox and travel-related diseases. Thomas Monath, M.D., chief scientific officer at Acambis, noted the scarcity of effective vaccines to treat coronavirus infections in animals, and highlighted the need for a suitable animal model of SARS. (So far, macaque monkeys have been the only animals offering promise in this regard.) He cautioned that it could take at least five to six years to develop an effective vaccine, at a cost of some $60-100 million and requiring the collaboration of academic and industrial scientists. "We need to understand the natural history of this disease and develop appropriate animal models, and that will allow us to develop rational approaches," he advised. The session concluded with a panel discussion that also included representatives from Bristol-Myers Squibb Company, Pfizer Inc, and Merck Research Laboratories.

http://www.nyas.columbia.edu/sars/web/s6/index.html SARS in the Context of Emerging Infectious Threats: Session IV - Ebola. West Nile. And now SARS. "Every year or two we see a new virus, an old virus that wasn't supposed to be here, or an old virus doing something new," noted C.J. Peters, M.D., professor of microbiology, immunology, and pathology at the University of Texas Medical Branch in Galveston. He described how viruses travel with their hosts, bringing them to areas they may not have been able to get to on their own. "Viruses can't just pick up and gothey are ecologically constrained. The age of exploration started mixing viruses. But today we don't have to wait for Columbusthere's the airplane." Peters explained how the genetic variability of viruses, multiple ecologic niches, urbanization, and global travel have combined to create evolutionary opportunities for viruses. But we have to learn to understand social, cultural, and economic differences among populations in order to control viruses effectively. "We have to find a way to get ahead of this. If SARS gets into certain areas of the world, we will not eradicate it," he contended. When SARS does strike, especially in a major urban area, an effective public health response is critical for controlling its spread, said Marcelle Layton, M.D., assistant commissioner for communicable diseases for the New York City Department of Health. Such a response includes prompt detection of the outbreak, notification of key partners (including the medical community and law enforcement agencies), epidemiologic surveillance, medical and public health interventions (such as mass treatment or mass prophylaxis), andmost importantlyaccurate and ongoing public communication. "Effective communication underlies every aspect of a successful response," emphasized Layton. "If you don't communicate well, and if you lose trust with misinformation, it's extremely hard to regain." "We really are facing an important problem," added John La Montagne, Ph.D., Deputy Director of the NIAID. "SARS is an unpredictable and serious disease with dramatic impacts. It could have happened here (in this country)we're very lucky." La Montagne supported continued collaboration both nationally and internationally, and credited the toils of SARS investigators. "It is an unbelievable testimony to the effectiveness of our public health institutionsnot just nationally, but globallythat so much work and so much progress have been achieved in such a short period of time."

http://www.nyas.columbia.edu/sars/web/s7/index.html SARS in the Context of Emerging Infectious Threats: References and Resources - Research Report SARS Aetiology: A Research Update from Malik Peiris Academic Information Coronavirus Taxonomy, from The National Center for Biotechnology Information Complete Genome of the SARS Coronavirus, from the National Center for Biotechnology Information Information on SARS, from the New England Journal of Medicine Progress on SARS, from Science magazine SARS, from the Center for the Study of Emerging Infections World Health Organization Resources Situation Updates on Severe Acute Respiratory Syndrome (SARS) Cumulative Number of Reported Probable Cases Severe Acute Respiratory Syndrome (SARS), from the World Health Organization WHO Global Scientific Meeting on Severe Acute Respiratory Syndrome (SARS) Argentina SRAS | Noticias (SARS News, in Spanish and English) Asia China Ministry of Health (in Chinese) Hong Kong Department of Health SARS Site Hong Kong Department of Health SARS Site (in traditional Chinese) Hong Kong Department of Health SARS Site (in simplified Chinese) Malaysia Ministry of Health SARS Site Philippines National Epidemiology Center SARS Site Republic of Indonesia Ministry of Health Republic of Indonesia Ministry of Health (in Indonesian) Singapore Ministry of Health SARS Site South Korea National Institute of Health SARS Site Taiwan Center for Disease Control SARS Site Taiwan Center for Disease Control SARS Site (in Chinese) Thailand Ministry of Public Health Thailand Ministry of Public Health (in Thai) Vietnam Ho Chi Minh City SARS Site Canada Health Canada SARS site Health Canada SARS site (in French) Toronto Public Health, SARS Information Europe France Ministry of Health (in French) Germany Ministry of Health (in German) Italy Ministry of Health (in Italian) Spain Ministry of Health SARS site (in Spanish) Switzerland Federal Office of Public Health SARS site (in French) Switzerland Federal Office of Public Health SARS site (in German) UK Department of Health SARS site United States Armed Forces Institute of Pathology SARS Site Food and Drug Administration SARS Site NIAID Research on Severe Acute Respiratory Syndrome (SARS) Severe Acute Respiratory Syndrome (SARS), from the Centers for Disease Control The United States Office of Global Health Affairs Speakers' References Paul Masters, Wadsworth Center, NY State Dept. of Health, Albany Kathryn V. Holmes, Department of Microbiology, University of Colorado Health Sciences Center, Denver Linda Saif, Professor, Food Animal Health Research Program, Ohio State University, Wooster Larry Anderson, Centers for Disease Control and Prevention, Atlanta Donald Low, Mt. Sinai Hospital, Toronto David Ho, Aaron Diamond AIDS Research Center, New York Frederick Hayden, University of Virginia School of Medicine, Charlottesville C. Richter King, Genvac Inc., Gaithersburg, VA Thomas Monath, Acambis, Cambridge, MA Marcelle Layton, NY City Department of Health

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