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Updated on Fri, August 8, 2003 §ó·s
«D¨å«¬ªÍª¢ (Atypical Pneumonia) SARSªº¯f·½Åé
ÄY««æ©Ê©I§l¨t²Îºî¦X¯g (SARS: Severe Acute Respiratory Syndrome)
Coronavirus from SARS isolated in FRhK-4 cells. Thin section electron micrograph and negative stained virus particles.
·sÅܺثaª¬¯f¬r ( Mutated Coronavirus )
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Update 31 - Coronavirus never before seen in humans is the cause of SARS (WHO)
Unprecedented collaboration identifies new pathogen in record time
16 April 2003 (French)
(ARCHIVES)
GENEVA -- Today, the World Health Organization announced that a new pathogen, a member of the coronavirus family never before seen in humans, is the cause of Severe Acute Respiratory Syndrome (SARS). The speed at which this virus was identified is the result of the close international collaboration of 13 laboratories from 10 countries. While many lines of evidence have found strong associations between this virus and the disease over the last weeks, final confirmation came today.
¡§The pace of SARS research has been astounding,¡¨ said Dr. David Heymann, Executive Director, WHO Communicable Diseases programmes. ¡§Because of an extraordinary collaboration among laboratories from countries around the world, we now know with certainty what causes SARS.¡¨
The successful identification of the coronavirus means that scientists can now confidently turn to other SARS challenges. For example, various laboratories continue to work to unravel the genetic information of the SARS virus and compare the sequences obtained from viruses in different parts of the world. Experts are gathering at WHO this week to map future work on SARS.
¡§Today, the collaboration continues as top laboratory researchers have come to WHO to design the next steps, a strategy for transforming these basic research discoveries into diagnostic tools which will help us to successfully control this disease,¡¨ said Heymann. ¡§Now we can move away from methods like isolation and quarantines and move aggressively towards modern intervention strategies including specific treatments and eventually vaccination. With the establishment of the causative agent, we are a crucial step closer.¡¨
This collaboration has brought together leading scientific expertise, and was established after WHO issued a global alert on SARS on 12 March 2003. The priority has been to find the cause and to develop diagnostic tests. Two laboratories in China recently joined this network of laboratories from Canada, France, Germany, Hong Kong Special Administrative Region of China, Japan, the Netherlands, Singapore, the United Kingdom, and the United States of America.
¡§Today, the first part of the mission of our network has been fulfilled, as researchers have both detected a hitherto unknown virus and established it as the cause of SARS. The new coronavirus has been named by WHO and member laboratories as ¡§SARS virus, ¡¨ said Dr Albert Osterhaus, the Director of Virology at Erasmus Medical Center in Rotterdam. Erasmus completed the work to definitely prove that the new coronavirus causes SARS.
Over the past three weeks, due to the urgency surrounding the worldwide threat to health of SARS and early indications this was a new member of the coronavirus family, research has proceeded under the assumption that SARS was caused by a new coronavirus.
The 13 laboratories have been working on meeting Koch¡¦s postulates, necessary to prove disease causation. These postulates stipulate that to be the causal agent, a pathogen must meet four conditions: it must be found in all cases of the disease, it must be isolated from the host and grown in pure culture, it must reproduce the original disease when introduced into a susceptible host, and it must be found in the experimental host so infected.
Credit for the coronavirus findings, which definitively pinpoints the cause of SARS, is attributed to the 13 laboratories, working in conjunction with WHO.
¡§The people in this network have put aside profit and prestige to work together to find the cause of this new disease and to find way new ways of fighting it,¡¨ said Dr Klaus Stohr, WHO virologist and the coordinator of the collaborative research network. ¡§In this globalized world, such collaboration is the only way forward in tackling emerging diseases.¡¨
WHO and the network of laboratories dedicate their detection and characterization of the SARS virus to Dr Carlo Urbani, the WHO scientist who first alerted the world to the existence of SARS in Hanoi, Vietnam, and who died from the disease in Bangkok on 29 March 2003.
For more information contact:
Dick Thompson - Communication Officer
Communicable Disease Prevention, Control and Eradication
WHO, Geneva
Telephone: (+41 22) 791 26 84
Email: thompsond@who.int
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¡@¡@¨¿¤O»¡¡A¬ì¬ã¤Hû±N¼W¥[¯f¤H¦å²M¼Ð¥»ªº±Ä¶°¶q¡A¶i¤@¨B±q¦å²M¬y¦æ¯f¾Ç¨¤«×ÃÒ©ú¦¹¦¸¬Ì±¡ªº¯f¦]¡A¨Ã®i¶}¯fìÅ骺§Ö³t¶EÂ_§Þ³N¬ã¨s¡A¥]¬A¯fìÅ骺¤ÀÂ÷Ų©w¡B¤À¤l¥Íª«¾ÇÀË´ú¡B§ÜÅéÀË´úµ¥¡A¦P®É®i¶}¯fìÅ骺°Êª«¹êÅç¬ã¨s¡A¬d©ú¯fìÅ骺·P¬V¾÷²z¡AÁÙ±N¹ï¯fìÅé®i¶}¤À¤l¥Íª«¾Ç¬ã¨s¡A±q°ò¦]¤ô¥ÄÄ©ú¯f쪺P¯f¾÷²z¤Î¹ï¾÷Å骺¦M®`µ¥¡C
SARS
Coronavirus Sequencing (CDC)
April 13, 2003, 4:00 PM ET
The CDC coronavirus sequencing team has completed and assembled 17.5 kilobases of nucleotide sequence of the Urbani strain of SARS associated coronavirus. These sequences represent all of the genome except for the 1a region of the polymerase gene. The availability of this sequence provides important information relating to rapid diagnosis, treatment, and prevention of SARS. The complete genome of the Urbani strain should be available on Monday, April 14, 2003.
It should be noted that analysis of sequences from three different regions of the genome confirm the initial observation that the Urbani strain of the SARS-associated coronavirus is distinct from all previously recognized coronaviruses and sequence studies are not likely to identify a source for this novel coronavirus.
Sequence information provided by collaborators at National Microbiology Laboratory, Canada, University of California at San Francisco, Erasmus University, Rotterdam and Bernhard-Nocht Institute, Hamburg facilitated this sequencing effort.
Nucleotide Sequence of Human Coronavirus, CoV-SARS PDF (Apr 13, 2003, 4:00 PM ET)
Coronavirus Protein Analysis Phylogenetic Trees PDF (Apr 13, 2003, 4:00 PM ET)
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SARS: Identifying
the cause
Amina Ali and Rachelle Younglai, CBC
News Online | April 4, 2003 | Updated April 11, 2003
Three weeks after the World Health Organization declared severe acute respiratory syndrome (SARS) to be a worldwide threat, researchers are coming a little closer to identifying the cause. Hundreds of scientists in 11 disease control centres in nine countries are working around the clock, pooling their resources and findings via a secure Web site and daily teleconferences. Because so little is known about the transmission of the disease, WHO has limited the research to labs that are equipped to handle deadly pathogens.
Identifying the cause of the disease has been difficult. There is much debate surrounding the type of virus involved and many questions need to be answered before any type of conclusion can be drawn and any type of treatment developed.
The process of identifying a new pathogen is rigorous. It is not enough to simply identify the microbe by how it looks. It must be isolated, grown in isolation and then the cultured germs must be able to recreate the disease in a test animal. If scientists can meet these three conditions, it is the ultimate proof that the microbe is the cause of the illness. This course of proof is known as Koch's postulates, initially designed for anthrax in the late 19th century by German scientist Robert Koch.
Here's where scientists are as of early April.
Scientists have taken tissue and blood samples from patients and compared the infected samples to samples from healthy individuals. Once the aberration was detected they started the process of trying to identify its shape and structure and determine what category and family its source belongs to.
Scientists found two types of viruses in SARS patients - paramyxovirus, the family of viruses that includes the one causing measles, and coronavirus, a family of viruses that includes the second most common cause of colds.
On March 18, doctors in Germany and Hong Kong said they had found signs of a paramyxovirus in blood samples from SARS patients. Canadian researchers identified genetic signs of human metapneumovirus, a family of microbes that can cause measles, mumps and canine distemper, but this turned out to be a dead end.
However, a week later, scientists in Geneva and the U.S. said they found a coronavirus new to humans in the lungs and other tissue of some victims. Canadian scientists have found the coronavirus in about half of their samples.
In early April, researchers with the U.S. Centers for Disease Control and Prevention (CDC) said they were 90 per cent positive that the virus is a coronavirus, identified by its crown-like appearance.
The debate has been raging as to which virus is the cause: is paramyxovirus a byproduct of coronavirus or vice versa? Does one or both cause the microbe to mutate and become more infectious or easier to spread? Is it a new agent? And the questions go on.
"When you see both you don't know what you're dealing with," said Dr. Bhagirath Singh, director of the Institute of Infection and Immunity at the University of Western Ontario. "Labs have been running tests to learn what causes the disease, and have been unable to find anything conclusive."
Antibody and genetic tests
CDC researchers developed antibody and genetic tests to help confirm SARS cases. If a patient has a positive antibody response to the new coronavirus, scientists say it may be evidence there is a link with SARS.
"When we see a positive test at the end of illness and a negative test at the beginning of the illness, that's really strong evidence of coronavirus infection. It still doesn't mean it's the cause of SARS, but it's pretty strong evidence that that's what we have," said Dr. Julie Gerberding of CDC. "It's a good clue, but again, it's just not proof."
The antibody test is in its infancy and the accuracy of the test still needs to be verified. To draw any conclusions CDC must have thousands of samples from those who are infected as well as from those who are not.
Isolating the virus
Hong Kong scientists were able to isolate the virus. Isolating the virus allowed scientists to start characterizing the agent, to determine its relationship with known viruses and subsequently define the identity.
Culturing the virus
Although culturing viruses is difficult because they only replicate within a living cell, there have been reports that researchers at labs across the world, including Canada's microbiology lab in Winnipeg, have been able to culture the virus.
According to the CDC, scientists in the Netherlands have successfully infected an animal, however results are not yet available.
Sequencing Virus
Scientists are also working on identifying the genetic makeup of the virus and are expecting results in the next week or so. If they are successful, this could aid in the creation of a rapid diagnostic test and reduce death rates by allowing doctors to identify affected patients sooner.
Transmission
What the public finds so difficult is not so much the ferocity of the outbreak but the ambiguity surrounding the transmission of the disease.
At first WHO said the virus was transmitted by face-to-face exposure to droplets released when an infected person coughs or sneezes. But then dozens of people who live in the same Hong Kong residence became infected raising concerns that the virus may be carried by water or by vaporized droplets that remain in the air and are then inhaled. Another theory is that the virus may live outside of the body for two to three hours thus contaminating surface areas.
Doctors are using anti-viral therapy to try to prevent the virus from replicating but so far this has not been successful.
Theories
Despite the progress, there are many other questions that need answering in order to draw any conclusions: how are the outbreaks linked to other countries? How does the disease spread? At what stage is the virus the most active? Is the cause a single or multiple agent?
- One theory suggests that the SARS virus jumped to humans from an animal species.
- Another suggests a microbe mutated into the more virulent form in humans.
- There has also been some speculation that it could be a manmade virus but CDC dismisses this theory.
Now that China has permitted a team of WHO experts to enter the country, much more remains to be discovered.
WHO experts will start tracking the source of SARS in Foshan city, where the first case was reported in November 2002, and Guangzhou city.
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¡@¡@³ø¾É»¡¡A¥Ø«e¥u¦³»´ä¤Î¼s¦{³¡¤À¯f¨Ò¡AÃÒ¹ê«aª¬¯f¬r»P³oÓ¦a°Ï¬y¦æªºSARS¦³ª½±µÃö«Y¡A¦ý¨ÃµLÃÒ¾ÚÅã¥Ü¥@¬É¨ä¥L¦a°Ï©Òµo¥ÍªºSARS¡A³£¬O¥Ñ«aª¬¯f¬r¤Þ°_¡C¦Ó¥Ø«e»´ä³¡¤ÀSARS¯f¤HÄY«¸¡Âm¦Ü¨C¤Ñ¤T¤Q¦¸¡A³o¬O¼s¦{¦PÃþ±wªÌ©Ò¤Ö¦³ªº¡A³o¤]ªí¥Ü¯f¬r¥i¯àµo¥ÍÅܲ§¡C
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Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome. (source) (April 10, 2003) (Full Text in PDF)
Background: The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent.
Methods Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques.
Results A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated.
Conclusions The novel coronavirus might have a role in causing SARS.
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Pro
Med Comment -
(This report does not provide much clarity but rather adds to the confusion
regarding the nature of the infectious agent responsible for SARS. The candidates
so far include, an unspecified paramyxovirus, the recently discovered human
metapneumovirus (representing the two subfamilies of the family _Paramyxoviridae_,
and now an unspecified coronavirus (representing the family _Coronaviridae_).
A common feature of the families _Paramyxoviridae_ and Coronaviridae_ is that
they contain viruses that are ubiquitous respiratory tract pathogens. Consequently
it would not be unexpected to detect such viruses in clinical samples entirely
fortuitously, particularly where a diagnostic technique of limited discriminatory
potential such as electron microscopy is employed.
The paramyxoviruses and coronaviruses are quite distinct viruses with different
biological potential. The paramyxoviruses are negative-sense RNA viruses, which
do not recombine, whereas the coronaviruses are positive-sense RNA viruses,
which undergo recombination at high frequency.
In the UK, at least, coronaviruses are second only to rhinoviruses as causes
of the common cold. In the case of the four types of human parainfluenza viruses
(sub-family _Paramyxovirinae_), human respiratory syncytial virus and human
metapneumovirus (sub-family _Pneumovirinae_) infection occurs in infancy and
early childhood, but does not confer prolonged immunity. In the case of human
respiratory syncytial virus it has been estimated that reinfection occurs on
average every 36 months.
The outcome of infection can be serious in infancy (bronchiolitis) and in the
elderly (pneumonia), At other ages infection is usually asymptomatic or mild
URTI. The recently discovered human metapneumovirus appears to behave similarly,
but is less prevalent than respiratory syncytial virus (see: Human metapneumovirus
infections in young and elderly adults by Falsey et al., in Journal of Infectious
Diseases, 187, (5), 785-790, 2003). These authors conclude that: "Human
metapneumovirus infection occurs in adults of all ages and may account for a
significant portion of persons hospitalized with respiratory infections during
some years."
Continued caution is required in evaluation of the competing claims of identification
of the etiologic agent of SARS. - Mod.CP)
ProMED-mail promed@promedmail.org
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Human CoronaViruses, represented by the two prototype strains HCV-OC43 and HCV-229E, are important human respiratory Pathogens, also associated with Necrotizing Enterocolitis.
SECTION I - INFECTIOUS AGENT (source)
NAME: Human coronavirus
SYNONYM OR CROSS REFERENCE: Viral respiratory disease, viral gastroenteritis
CHARACTERISTICS: Coronaviridae; first isolated in 1965, spherical enveloped virion, 80-160 nm in diameter, crown-like in appearance, club-shaped peplomars, single-stranded, linear, non-segmented, positive-sense RNA genome;
SECTION II - HEALTH HAZARD
PATHOGENICITY: Usually produce an afebrile cold in adults, characterized by nasal discharge, and malaise; may exacerbate respiratory symptoms in asthmatic and chronic pulmonary disease patients; implicated in gastroenteritis; greater occurrence in children; maybe associated with pneumonia and pleural reactions, rarely manifests in neurological complications; immunity is serotype specific; antigenic heterogeneity allows for multiple symptomatic reinfections
EPIDEMIOLOGY: Worldwide; major cause of respiratory disease between late fall and early winter; accounts for 10-30% of all colds