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SARS Etiology - They
Still Don't KNOW?

From Patricia Doyle, PhD
dr_p_doyle@hotmail.com
4-6-3


Hello Jeff: We still don't know the identity of the SARA causitive agent. We do know, as exhibited by George W. Bush's signing of an Executive Order to quarantine suspected cases of SARS, that the medical community hasn't a clue about the disease.
 
Health Canada has proclaimed that people who believe they have SARS must NOT report to hospitals, but stay home without treatment.
 
Connecting the dots, I believe that George W. and many of the scientists working on identifying SARS agent KNOW the virus is lab altered, lab manipulated.
 
The virus will infect and projecting expoentially we can determine within one month that we can expect as many as 6,000+ cases worldwide. We are, already, up to almost 3,000 worldwide. I also believe that many cases are going to go unrecognized or undiagnosed. When the death toll begins to mount, I cannot help but wonder how funeral parlors, and forensic pathologists will manage victims? Will cremation be mandatory?
 
I did find it interesting that Loudon County, Virginia has a hospital that can offer BSL 4 isolation to their patients. Of course, Loudon County is home to the "Bell labs of biotech" namely Howard Hughes Medical Institute and many other biotech companies, including Ken Alibek's. Perhaps, hospitals had been equipped with BSL 4 features because it was feared a pathogen might escape one of the labs.
 
The SARS patient from Loudon County was treated and cared for in the hospital's isolation room attended by staff using BSL 4 equipment. It is a shame that cities like, New York, Los Angeles, Chicago etal do not have hospitals with a BSL 4 capability.
 
Although, the Promed article tries to rationalize the appearance of SARS and equate it with a 10 year emergence of various influenza viruses from Asia, I find it difficult to believe that the agent causing SARS is just a natural emergence from Asia. The genome tells another story.
 
I do forsee a great economic downturn should the virus spread rapidly through major US cities, like New York City. IF the death toll and cases rise dramaticallly and people are not admitted to hospital or given any care, we can be sure civil unrest will overtake cities like New York and the highways "out of town" will be bogged down with fleeing residents.
 
I do hope that people who exhibit signs of the illness will voluntarily "take themselves out of circulation" and stay home until it can be determined they are SARS-free. We can prevent spreading the illness by some common sense measures. Frequent handwashing and wiping them frequently with alchol wipe will help. Avoid touching your face, especially eyes, nose, and mouth. Again, if someone begins to have cold or flulike symptoms, call your doctor and follow your doctor's instructions.
 
Patricia Doyle
 
[1] Date: 4 Apr 2003 From: ProMED-mail <promed@promedmail.org> Source: OIE press release [edited] http://www.oie.int/eng/press/en_last.htm
 
Atypical pneumonia: Severe acute respiratory syndrome (SARS) ------------------------ A human epidemic of atypical pneumonia called severe acute respiratory syndrome (SARS) is currently raging across the globe and particularly in South-East Asia.
 
The causative agent has not yet been identified. It appears to be a Paramyxovirus, a Coronavirus, or a mixture. The World Health Organization (WHO) has hypothesised that the causative virus(es) may be of animal origin, from domestic or wild animals located in Guangdong Province (in South China).
 
This is why the World Organisation for Animal Health (OIE) has contacted the Chinese Veterinary Authorities to obtain information on the animal health situation in China over the past 6 months and, in particular, in Guangdong Province.
 
The OIE has also approached its Reference Laboratories and Experts specialising in Paramyxovirus and Coronavirus diseases.
 
As soon as it is available, the OIE, in close collaboration with the WHO, will communicate the scientific information needed to confirm or invalidate the animal origin of SARS and to evaluate, if necessary, the risks incurred by the international community.
 
-- ProMED-mail <promed@promedmail.org>
 
[We look forward to hearing the results of the OIE investigation. - Mod.MPP]
 
****** [2] Date: Fri 4 Apr 2003 From: Steve Berger <mberger@post.tau.ac.il>
 
 
SARS - Deja vu ? ---------------- As SARS enters its fifth month, a number of questions remain unanswered. Why Asia? Why now? Why young adults? To these I would add a fourth question (Why the panic?) and an hypothesis.
 
Every 10 years or so, a pandemic spreads out from China and surrounding countries. The 'Asian flu' of 1957 claimed 98 000 lives worldwide, and the 'Hong Kong flu' of 1968 an additional 45 000 lives. Although the world community was rightly concerned, I do not recall a collapse of air travel, imposition of quarantine, or daily front-page headlines. To date, SARS has claimed 79 lives, and the etiological agent appears to be far less contagious than Influenza A virus.
 
Current evidence suggests that new strains of Influenza A virus evolve as recombinants when they pass between swine and ducks, a process favored by close species proximity on Asian farms. Thus, I was surprised to learn in a recent ProMed-mail posting that coronaviruses also exist in poultry and swine, as well as cattle, cats, dogs, and rodents (see: Coronavirus, Chicken, New - Brazil 20030403.0816). I do not know whether coronaviruses are capable of recombination in the manner of influenza viruses, but such a mechanism would partially explain the origin of SARS.
 
3 years ago, a 'new' human infection was described in the Netherlands. It soon became evident that Human metapneumovirus [HMP] was neither new nor exotic, and seems to have affected most humans in every country investigated, going back decades. The clinical features of this infection mimic those of Human respiratory syncytial virus, and infant deaths are not uncommon. Indeed, it may well be that more people die of HMP than from SARS each year. These facts only became evident when serological tests were developed. I suspect that use of serological and other tests for SARS developed over the next few weeks will reveal: (1) a high degree of sero-positivity in the 'healthy' community of Asia, if not other countries; and (2) the existence of an animal (Porcine? Avian?) reservoir.
 
During the H1N1 pandemic of 1977, there were suggestions that elderly persons had a lower rate of complications than would be expected. It was theorized that persons who had survived the prior H1N1 pandemic of 1918 had retained partial immunity into old age. If, as noted above, background immunity exists from a SARS outbreak several decades ago, relatively low disease rates among the elderly during the current epidemic would not be surprising. The fact that few children are affected is also not surprising, when we recall that viral diseases (measles, varicella, poliomyelitis, mumps) are often more overt and severe among adults.
 
-- Steve Berger Tel Aviv Medical Center, Israel <mberger@post.tau.ac.il>
 
[Steve Berger has posed some interesting questions and made some relevant comments. My response is limited to consideration of the genetic characteristics of coronaviruses. High frequency recombination is a characteristic property of coronaviruses, and is probably restricted to closely related coronaviruses. An example is Feline infectious peritonitis virus, a coronavirus that exists as 2 serotypes and causes peritonitis, pneumonia, meningoencephalitis, and other immunopathologic complications in cats. Serotype 2 of feline infectious peritonitis virus appears to be a recombinant virus incorporating genetic information from a canine coronavirus, which causes diarrhea in dogs. The serotype 2 virus, in addition to causing peritonitis, etc., in cats can -- unlike serotype 1 -- infect pups (but does not cause acute disease).
 
That said, it is not necessary to hypothesize origin of the putative SARS-associated coronavirus by recombination with an animal or avian coronavirus. There are many coronaviruses in the natural environment that could become pathogenic in humans as a result of progressive mutation, or perhaps have existed undetected.
 
The origin of pandemic influenza A viruses by "recombination" is an entirely different process and can occur between dissimilar viruses. The genome of influenza viruses exists as a complement of sub-units which can be interchanged when genetically distinct viruses replicate in a common (or intermediate) host, generating progeny with non-parental combinations of genes (and potentially expressing novel combinations of antigens and causing an explosive pandemic). Consequently there could be abundant opportunity for exchange of sub-units between human and avian viruses where humans, domesticated mammals, and birds live in close proximity. This is a gross oversimplification, of course, but the origin of pandemic strains of influenza A virus in east Asia in the past should not be used as an argument favouring the origin of the SARS agent by recombination between a human virus and an animal virus.
 
At this stage we simply do not know. Nor is it certain that the coronavirus (and/or the human metapneumovirus) present in SARS patients is the pathogenic agent. As Steve Berger points out, coronaviruses and pneumoviruses are ubiquitous in the human population. Caution is required in advancing hypotheses at this stage until more data become available. - Mod.CP]
 
***** [3] Date: 5 Apr 2003 From: ProMED-mail <promed@promedmail.org> Source: CDC press briefing 4 Apr 2003 [excerpted and edited] <http://www.cdc.gov/od/oc/media/transcripts/t030404.htm>
 
 
Update on the ongoing laboratory investigation: -------------------------------------- CDC is part of an international collaborating network of laboratories led by WHO. There are 12 laboratories and 10 companies participating in this network.
 
Evidence for a previously unrecognized Coronavirus has been found now in at least 10 laboratories, including the laboratories here at CDC. The preponderance of the evidence continues to mount and continues to favor an etiologic role or this previously unrecognized Coronavirus in the cause of SARS.
 
So far, in looking at specimens from the suspect cases in the United States, we now have evidence of infection with this agent in a total of 4 people, and we are working with the state health departments in the states where these people reside, so that they are provided with the information and they, in turn, will provide the clinicians and the patients with the information.
 
We have cultured this Coronavirus from a total of 4 patients. We have electron microscopic evidence from 2 patients of this virus. We have PCR (Polymerase Chain Reaction) results -- , the amplification technique -- where we find evidence of Coronaviral nucleic acid in 11 patients.
 
Looking at the antibody tests, of which we have 2 --an IFA [immunofluorescent antibody] test and Allose test -- there is evidence for infection in a total of 5 patients. And from the standpoint of histopathology, looking through the microscope at tissue from deceased patients, we have seen evidence of an entity that the pathologist call diffuse alveolar damage, which is the pathologic correlate for the clinical syndrome of Acute Respiratory Distress Syndrome, which has appeared in patients with severe forms of SARS.
 
We have seen that evidence in a total of 4 specimens. Don't try to add those numbers up and get a grand total because some patients, in some cases, have more than one positive result.
 
[In response to a question on whether there were samples that tested negative for coronavirus]:
 
There are negative results. I don't have numbers. For example though, when you think about antibody tests, what you really need, [in order] to be able to interpret those and to say that something's negative, is 2 serum specimens collected 2 or 3 weeks apart. So any negative that we have now for the most part represents a single serum that's negative. So we're not in the position to say that evaluation is complete. Part of our effort now, working with the states, is to get paired serum specimens from patients so they can be tested.
 
[In response to a question re: the information that some of the earlier cases had eaten wild game]:
 
[Dr. Hughes had not heard the reports about the wild game consumption.] But, we don't know the source, the original source of this previously unrecognized virus. There are a number of Coronaviruses that do infect animals, though. So it may well be that there is an animal origin for this, and it's the sequencing of the full virus that will tell us this. So I'm interested actually to follow up and see what sort of wild game this is and what the evidence might be.
 
[In response to the question if they have run the tests on controls] : In terms of PCR, yes, we have negative controls that we run, both for the PCR and for the serologic tests that we have done, and it looks like these tests are performing quite well, but it is early in their use.
 
There are several diagnostic tests that look promising. There is the ELISA test for antibody, there's the Indirect Fluorescent Antibody -- or IFA -- test, again, for antibody, and then there's a PCR assay [for viruse] that look like they have potential to be useful.
 
We will be collecting and testing as many specimens as we can acquire from suspect cases, from health care workers exposed to them, from household contacts, and from healthy controls over time to further validate them.
 
We are going to be trying very soon to transfer some of these tests to state public health laboratories through the Laboratory Response Network so we can get the diagnostics, such as they are at the moment, closer to where the illnesses are occurring. So that's a high priority
 
[In response to the question on reports ot the isolation of Chlamydia]: The outbreak in Guangdong Province initially was reported based on some lab evidence that I don't know the details of, to be caused by _Chlamydia and [sic] pneumoniae_. My impression is that they had relatively few positive results for that. We certainly put _Chlamydia and [sic] pneumoniae_ on our long list of differential diagnostic possibilities when we first heard about the situation in Vietnam, Hong Kong and Canada. We, in our laboratories, looked for evidence of _Chlamydia and [sic] pneumoniae_ infection in suspect cases, and so far have not found it.
 
-- ProMED-mail <promed@promedmail.org>
 
[The new information provided in this briefing from CDC is consistent with the hypothesis that a novel (or perhaps previously unrecognized) human coronavirus is the etiologic agent of SARS, either alone or in combination with another agent still to be identified. The supporting evidence is far from conclusive, however. If at the CDC only specimens from suspected cases in the United States have been examined so far, an undetermined proportion of whom may not be SARS patients, this would be a limitation.
 
The RT-PCR amplification of coronavirus sequences produced 11 positive results and was the most sensitive diagnostic procedure employed, but even with this technique an unspecified number of negative results was obtained. The most encouraging result is successful propagation of virus from 2 of the suspected SARS cases. This will allow the entire genome of the virus to be sequenced and its phylogenetic position in the family _Coronaviridae_ to be established. It will be possible then to deduce whether this virus is a new human pathogen derived by recombination with an animal coronavirus, or whether it has evolved by progressive mutation from either of the 2 known human coronaviruses, which are associated with upper respiratory tract infections, or from one of the known animal coronaviruses. It is curious that a virus, which has such devastating pathological potential in some people, is present in these specimens in such low abundance.
 
Specific antibodies were detected in five patients by ELISA and/or IFA tests, but samples suitable for demonstrating seroconversion appear to have been lacking. The response to the question on controls is confusing. It should be a priority to extend these diagnostic procedures to a matched series of non-SARS patients to exclude the possibility that this novel human coronavirus is no more than a ubiquitous resident in the human respiratory tract. Several respiratory viruses, such as the common cold-associated coronaviruses and human respiratory syncytial virus, are distributed world-wide and affect individuals of all ages. At the moment the single fact that best identifies this virus as the etiologic agent of SARS is its apparent low nucleotide sequence homology with other coronaviruses. - Mod.CP]
 
 
Patricia A. Doyle, PhD Please visit my "Emerging Diseases" message board at: http://www.clickitnews.com/emergingdiseases/index.shtml Zhan le Devlesa tai sastimasa Go with God and in Good Health


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