Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : SARS and Avian Flu -- Ignore unavailable to you. Want to Upgrade?

To: Biomaven who wrote (962)	8/27/2003 6:09:32 PM
From: Biomaven	Read Replies (2) \| Respond to of 4232

New Scientist report: Uncertainty clouds Canada's SARS declaration 15:31 27 August 03 NewScientist.com news service Worrying uncertainty has arisen in laboratory work aimed at deciding whether a mystery Canadian outbreak is related to SARS or not. The World Health Organization, as well as the authorities in British Columbia, say the outbreak is not SARS and "has no international public health implications". But there is still a troubling lack of explanation for why several of the patients tested positive for SARS virus. The northern hemisphere is now entering the flu season and thousands of people with respiratory infections will have to be tested to ensure SARS does not make a comeback. Confusing test results would make this hard. The National Microbiology Laboratory (NML) in Winnipeg says the virus that killed six people in British Columbia may be a cross between the SARS virus and a less dangerous relative. But the NML's findings are disputed by another leading Canadian laboratory. Unique sequence In July, residents and staff at a nursing home in Surrey, near Vancouver, started getting what looked like a cold. Ten elderly residents developed pneumonia, and six died. Such deaths are not particularly unusual, and the symptoms of the victims were not typical of SARS. But tests were still run as a precaution. In eight of the patients, using the PCR technique for amplifying fragments of genes, the NML found a sequence of 235 base pairs identical to one in the "M" gene of the TOR2 strain of the SARS virus that was responsible for the outbreak in Toronto earlier in 2003. In another sample, they found a 589 base-pair sequence identical to one in the "N" gene of SARS, including a sequence not known in any other virus. "SARS coronavirus is pretty unique," says Tim Booth, head of viral diseases at the NML. The team also found that antibodies from recovering patients in Surrey bound strongly to SARS proteins. But last week the Genome Sciences Centre in Vancouver, the lab that first sequenced the SARS virus, announced it could find no gene sequences similar to SARS in the patients. Caroline Astell, at the GSC, told New Scientist that the lab found about 1000 base pairs in three separate fragments which were 97 per cent identical to regions of the N and M genes of OC43, a virus that causes colds in people and belongs to the coronavirus family most closely related to the SARS virus. The British Columbia Centre for Disease Control in Vancouver also saw traces of OC43, but not SARS, and also found no SARS antibodies. Viral hybrid The different results could be explained if the patients were infected by both viruses, says Booth, or a viral hybrid of SARS and OC43. Another possibility is that the mystery virus is a previously unknown relative of both SARS and OC43. Evidence that SARS may indeed have many previously unknown relatives was announced by WHO in Beijing last week. Chinese scientists have discovered viruses in many birds and animals that test positive for SARS, by both PCR and antibody methods. Usually one virus does not infect many different hosts, so these could represent a whole range of SARS-like viruses. If this is the case, great care will be needed to monitor them, warns Booth. But this will be difficult without reliable tests. Astell says she cannot yet explain why her lab and the NML got different results. The two labs used different fragments of viral genes - "primers" - to get their PCR results, and are only now starting to exchange information that will allow them to try to replicate each others' results. It is not even clear yet if the conflicting tests came from the same patients. If the NML is merely getting false positives, this could change our understanding of how the SARS virus behaves, as the NML was also the only lab to find evidence of the virus in people who did not develop the full-blown SARS during the epidemic. If it really has uncovered a virus that does not cause SARS, but can test positive for it, then surveillance for true SARS will be much harder. Debora MacKenzie newscientist.com

To: Biomaven who wrote (962)	8/27/2003 9:02:05 PM
From: Henry Niman	Respond to of 4232

Peter the two genes, M and N are fairly close to each other. For M 235 bp were sequenced and for N it was 589. Thus, the actual sequence is 844 nucleotides. In twelve samples the sequence was an exact match (844/844) for Tor 2 (and many other SARS CoVs isolated after the virus broke out internationally) and the other sample was identical (844/844) to Frankfurt 1 (and 3 other known sequences, all linked to the Metropole Hotel). The region sequenced is about 3000 nt from 5' to 3' so the two regions cover about 10% of the SARS CoV genome. The fact that two viruses were identified strongly suggests that they are not recombinants or mutants because the Winnipeg labs have identified TWO SARS CoVs. The simplest explanation is probably correct. There are at least two SARS CoVs in Surrey. BC and they look just like the viruses that started the outbreak in Toronto (Tor2) or the virus from the physician who was quarantined in Frankfurt when he was returning from an infectious disease meeting in NYC. Some patients also are infected with OC43, a cold virus sharing limited homology with Tor2 or Frankfurt 1 but certainly not enough to explain the sequence data and probably not enough to explain the antibody data.

To: Biomaven who wrote (962)	8/28/2003 12:00:49 AM
From: Henry Niman	Read Replies (1) \| Respond to of 4232

SARS CoV Analysis and Implications With the limited amount of data presented, quite a bit can be learned about the SARS CoV sequence found in patients in Surrey, BC. Assuming that the positions sequenced were 26427-26662 and 28768-29357 the following is true for the two or more SARS CoVs identified: The sequence range crossed over 5 positions of common polymorphisms. The sequence of the SARS CoVs in Surrey is not consistent with CUHK-Su10, the virus isolated from the mother of the Prince of Wales index case, because they do not have T26477G. For the same reason they are not another unpublished isolate from Hong Kong or a series of isolates from Taiwan (TC1, TC2, TWJ, TWK, TWS, TWY, TWH, TWC2, TWC3). The SARS CoVs are more closely related to two masked palm civet isolates (SZ1, SZ3)than another masked palm civet isolate (SZ16) or a raccoon dog isolate (SZ13). The sequence is not consistent with several unpublished early isolates from Guangzhou (GZ43, GZ60) or the initial GZ01 isolate. One of the SARS CoV from Surrey has the mutation C26600T that is also found in Frankfurt 1, FRA, TWC, HKU39849, and another unpublished sequence from Hong Kong. Thus, there are at least two SARS CoVs in the Surrey patients and they have mutations that are in common with more recent isolates, including several closely tied to the Metropole Hotel. The profile of these two or more SARS CoVs in Surrey, BC suggests the following: The SARS CoVs causing SARS in the spring are not "back in the box". The recent SARS transmissions did not involve a re-emergence from an animal reservoir. The SARS CoVs are easily transmitted by patients with "summer cold" symptoms. Reliance on symptoms associated with the SARS CoVs in the winter and spring does not identify cases in the summer. The ratio of the two SARS CoV subtypes suggests they may be be traced back to more than two sources in Hong Kong. Seasonal cofactors may be required for the SARS presentation seen last winter and spring. Two of five antibody tests failed to detect antibodies to the virus. One of the failed tests is used by the CDC which only detected 8 SARS cases in the US this year. Nursing home cases in the Toronto area that initially tested positive for SARS CoV may be true positives, although they were declared negative by health officials. PCR test by Vancouver groups produce false negatives. The SARS CoVs have been transmitted undetected in Vancouver in May and June. Detection in July and August was met with comments on OC43 detection and a number of false negative tests. In spite of SARS CoV detection by 3 antibody tests, PCR tests, and exact matches for regions of four SARS CoV genes, health officials lifted the quarantine on the two nursing homes and allowed visitors. The officials also refused to identify one of the nursing homes with "summer cold" transmission. Press releases trying to spin the data don't stop transmission. The SARS CoV is quite happy with health officials in denial. It is going to be a VERY long fall and winter.