Tracking the next pandemic: Avian Flu Talk |
12 test positive for MERS-Cov in Italy |
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So the question now is how many that tested negative are tested again to confirm they are negative since it seems that the test procedures or the test itself may produce inaccurate results. I bet they don't test the negative patients twice and that a second test is done ONLY after a positive test result to confirm the positive result. Qatar comes to mind with it's 300 cases of "Sars like illness" that tested negative. Or is the virus mutated hence a negative result.
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coyote
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Sars [MERS], according to test negative for eight patients Rezza: "There are no new cases." Lorenzin: "No scaremongering."
original link: http://www.lettera43.it/beness... link to translated article: : http://translate.google.com/tr... Tuesday, June 4, 2013 According to the World Health Organization, the cases reported so far around the planet would be about fifty. No need to panic and, above all, accurate information on lung virus from Jordan and already nicknamed 'new' Sars. Gianni Rezza, director of the infectious diseases department of the ISS, the National Institute of Health, assured that "the samples of eight people in contact with ip atients affected by the virus and hospitalized in Florence were negative on the second test. " On the other hand, the first test result was positive. Rezza reiterated that "there are no new clinical cases confirmed so far, but continues monitoring by the Region of individuals who come in contact with patients." VIRUS LESS AGGRESSIVE THAN EXPECTED. Minister of Health, Beatrice Lorenzin has pointed out that "the people who came in contact with the three infected individuals are all well. There is no kind of scaremongering, the situation is under control. " "At the moment there is no evidence of a new mutation of the coronavirus responsible for SARS," he explained Rezza explaining that the ISS "has so far not confirmed any positive to the virus in asymptomatic patients reported and await the final analysis." The experts are in fact questioning the behavior of the virus that appears to be more easily transmitted than you knew but less aggressively than had appeared in the past. NO EVIDENCE OF MUTATION. "To be able to say with absolute certainty that the virus has mutated," said Rezza, "we need to sequence it and analyze it and so far this has not been done. Of this virus does not yet know much and we have therefore for comparison purposes to say that looks like more aggressive than in other cases. For now we can only say that there is no scientific evidence of a mutation or particular aggressiveness of the virus. " However, the expert added, "the situation is at present under control. The three confirmed cases of patients who contract the new SARS cases are mild and there are no new confirmed cases from Saturday, June 1. " |
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Albert
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Yes, something very odd with this. We've been tracking similar events for years and have never seen this one before. False positives? False negatives are significantly more common so it does make you wonder about the neg results coming back at this point.
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LOPPER
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When they start saying they have it under control numerous times and in the same article say that they don't have any evidence of MERS-CoV mutating makes me think they are not in control since they can even identify the method of transmission nor an exact incubation period and it appears the test for MERS-CoV is less than reliable. But they have it under control I call BS.
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jacksdad
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Seems the inconsistencies with the testing kits are going to be muddying the water considerably until they get their act together. I wonder if they're still doing nasal swabs instead of sputum tests and missing infections deeper in the airway?
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"Buy it cheap. Stack it deep"
"Any community that fails to prepare, with the expectation that the federal government will come to the rescue, will be tragically wrong." Michael Leavitt, HHS Secretary. |
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Albert
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False negs I can understand, but how exactly do you get a false positive? Those lab techs doing the original testing in this case are seriously inept, or need to layoff the drugs at work.
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LOPPER
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So if a highly contagious lethal virus was in the early stages of spreading among the population and containment was impossible due to the nature of transmission and incubation period would the government tell you the truth or try to prevent panic and lie? I think we all know the answer to that one.
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Albert
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Quite frankly, a gov't lie about the negatives seems a lot more probable then false positives. Have never seen a false positive in the last near 8 years here, and still wondering how it's possible to get a false positive. Assuming it's possible for that to happen, this has to be one of the strangest situations to date, and we've seen our share around here.
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jacksdad
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"Buy it cheap. Stack it deep"
"Any community that fails to prepare, with the expectation that the federal government will come to the rescue, will be tragically wrong." Michael Leavitt, HHS Secretary. |
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coyote
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Lopper said:
So if a highly contagious lethal virus was in the early stages of spreading among the population and containment was impossible due to the nature of transmission and incubation period would the government tell you the truth or try to prevent panic and lie? I think we all know the answer to that one. Yaaaa,We know. They will try to prevent panic and lie,lie,lie! |
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LOPPER
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So what are the chances of 8 false positives happening in a row? Gotta be some pretty high odds and a lot of math involved. Incidentally wasn't it reported as 10 positives intitially? So the other two positive cases? Of course conversely it maybe the case that the test itself is not reliable due to the sample collection area tested, sample handling or mutation of the virus itself.
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Albert
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Ya, I caught that too regarding 8 cases instead of 10. This is getting a little strange.
Whether they're lying or they don't know how to test, very odd, and both not good. |
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Albert
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Perhaps they should also go back and re-check the original 3 cases from a few days ago. Would hate to think that all 3 cases are actually neg and they're all currently on dialysis and ventilators, being read their last rights, meanwhile they had no symptoms.
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KiwiMum
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It seems to me that the problem lies with the test for MERS. If more was known about the disease and its incubation period then more informed diagnosis could be made. I suspect they need to map out the progression of MERS from day of suspected infection, as they may well find that, for example, on days 1-4 all tests show neg, days 5-9 faint positive with no symptoms etc etc.
Every one needs to be singing from the same song sheet to supply reliable data on this disease for mutual benefit.
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Those who got it wrong, for whatever reason, may feel defensive and retrench into a position that doesn’t accord with the facts.
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debbiencusa
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Other more positive possibilities are that there have been far more people exposed all along that have not ever become ill, that only a small amount of people do. No one is saying much about the sick, no back rounds we have a rumored link to possible Kidney Dialysis. That it is as far as I can recall.
The other possibility is that if it has mutated enough so that many people are now catching it, it has changed in ability to kill. Either way, I have been so nervous about this that I didn't think it through, I tried to do that yesterday, I am not sure of these numbers but when I have heard the 65% death rate, I am thinking sixty five percent of the worlds population gone. I think that was skewed thinking on my part, isn't it so that typically only 30% of all of the population get sick to begin with, so the sixty five percent death rate would come out of that number? If one would use the number 100 then thirty people out of one hundred are the ones who become ill, out of those thirty 18-20 die, which means that eighty out of one hundred live. Is this how I should be thinking of it??
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God Bless
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carbon20
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Latest reports put the figures at 51 confirmed cases of infection and 30 deaths—or a mortality rate of 60 percent. The SARS-like virus first detected in Saudi Arabia in 2012, initially named novel coronavirus or nCoV but now officially dubbed the Middle East respiratory syndrome coronavirus (MERS-CoV), has killed 24 persons in the kingdom; it has also spread to eight other countries, Italy being the latest to report a MERS-CoV infection that afflicted a 45-year-old man who had traveled to Jordan. The other countries with reported cases of the ailment now include Jordan, Qatar, the United Kingdom, France, Germany, and the United Arab Emirates. What do these countries have in common, especially those in the Middle East? They all have sizable OFW populations, with some 1.5 million Filipinos working and residing in Saudi Arabia alone. Given what is known so far of the virus—that, as pointed out by Keiji Fukuda, assistant director general for health security and the environment of the World Health Organization, “the different clusters seen in multiple countries increasingly support the hypothesis that when there is close contact this novel coronavirus can transmit from person-to-person”—Filipino workers in the kingdom and in other countries with a similar outbreak are at risk of contracting the ailment. President Aquino must thus heed the call of the OFW group Migrante-Middle East for the Philippine government to send medical attachés to Saudi Arabia to educate the workers and prepare them for contingencies. “There are lots of medical concerns by our fellow OFWs not only in Saudi Arabia but also in other Mideast countries. Giving them right information, education, and guidance would be of help to prevent work-related diseases,” said John Leonard Monterona, Migrante-ME regional coordinator for the Middle East and North Africa, in a statement. An information and education campaign is the least the government can do to prepare OFWs for any health emergency in their host countries. While virologist Nathan Wolfe, in a National Geographic interview, has said that there is still much to be discovered about the virus—“We do not know how MERS originated, and while human-to-human transmission has been confirmed, we do not know the precise mechanism of transmission. We still don’t know definitively what percentage of people who are infected will die (i.e., the case mortality rate)”—the rapid rate of transmission and the ease with which it has crossed borders has also left scientists like him worried. A “threat to the entire world” was how Dr. Margaret Chan, the director-general of WHO, recently described the virus. “We understand too little about this virus when viewed against the magnitude of its potential threat. Any new disease that is emerging faster than our understanding is never under control,” she said. MERS-CoV is from the same viral family as the bug behind SARS or Severe Acute Respiratory Syndrome, the outbreak that leapt out of China and East Asia in 2003, spread to other parts of the world and eventually killed 775 people. Like SARS, the Middle Eastern virus is said to produce severe respiratory symptoms from fever and cough to pneumonia, as well as gastrointestinal symptoms and kidney failure. It was eventually established that the SARS virus infected humans from their original animal hosts, and was spread through coughing or sneezing. In the case of MERS-CoV, Wolfe said “human-to-human transmission has been reported… particularly in cases with sustained contact such as health-care workers.” As new cases have been reported with increasing frequency, the Philippine government must take a proactive stance and prepare for the possibility that any one or two of the millions of OFWs in the Middle East and other affected countries will not only come down with the disease but also unknowingly bring it home. Some 25,000 OFWs are deployed every month to Saudi Arabia alone. They need to be alerted to take extra precautions in their personal health and hygiene, and to keep themselves updated on new developments, health measures and warnings about the illness. Migrante has another sensible suggestion: Make the deployment of a team or teams of medical attachés in Saudi Arabia permanent, to continuously serve the needs of the OFW population there, outbreak or no outbreak. Meanwhile, in the Philippines, it’s time for the Department of Health to put in place contingency measures, and to officially alert the public about the deadly MERS-CoV. |
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Elver
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If this keeps growing, we're in big trouble. It seems that the health care workers and near contactees are getting it pretty easy.
The only way to keep from getting this is to isolate for months and even that may not be enough. We could have several waves of it. I'm not comfortable with a 60+ death rate at all.
Lucky me, I don't work anymore, so I can stay home.
You can read about the 8 clusters here.
"There is clear evidence of human-to-human transmission, possibly involving different modes, such as droplet and contact transmission."
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oriel
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Right now all that the data says is that: of the 51 confirmed cases of infection 30 of those cases have died so far.
Clearly not all the people who have been exposed to the disease and actual get it, even in mild firm, are captured by testing (they simply may not be tested or even falsely so)(the nature of this game is that you don't and rarely can find them all, and certainly not at first). Keeping track of their fatality rate is a little easier because you know who to follow and death is pretty easy to detect :) ....or perhaps :( is a better emoticon There may be even some who have gotten the the disease and died and were not tested and therefor not in the confirmed cases of infection list or in the list of those who have died from it. In the early stages of any outbreak data is missing. People seem awfully worried about a 60 percent CFR but let me tell you that even a CFR of only 6 percent could be a huge deal if even only 10% of the population is infected. Think about the mess hospitals would be in if that many people got sick to the point of death never mind the freaking out 10% that would be infected. Then think about the freaking out 90 percent who would not get it but are still worried about it.... At some point the panic is as bad as the disease. Feel free to disagree, I admit I may be wrong but let us hope we don't find out who is right. |
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Elver
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"A team of researchers from Australia, Hong Kong and Japan estimate that the global cumulative incidence of pandemic H1N1 influenza infection before vaccines was 11 to 21 percent."
http://vaccinenewsdaily.com/news/258453-global-h1n1-influenza-infection-rate-as-high-as-21-percent/
Even if we had a coronavirus infection rate of around 10% and half of those died, that would be 5% of the world's population, which is HUGE! Even numbers less than this would be huge.
Large numbers of deaths would spell disaster for the world economy too, but who cares if you're one of the lucky ones to have survived.
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Albert
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I still want an answer on the false positives.
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Albert
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Anyone have any research on false positives?
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jacksdad
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Nope - this is a new one on me. Makes no sense
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"Buy it cheap. Stack it deep"
"Any community that fails to prepare, with the expectation that the federal government will come to the rescue, will be tragically wrong." Michael Leavitt, HHS Secretary. |
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Albert
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Can't wait to hear niman on this one. Good luck.
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EdwinSm,
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The main point seems to be: Since the samples came from asymptomatic cases, the viral RNA levels would be expected to be near the limits of detection and if two labs used assays with different sensitivities, the more sensitive test would generate weak positives, while the less sensitive test would generate false negatives. Full text: MERS-CoV
Asymptomatic Cases Raise More Testing Concerns Detection end points were two copies per reaction for the upE assay, and 10 copies per reaction for the confirmatory, ORF1b gene, assay. The above translation (in red) provide additional detail on the testing of the asymptomatic cases in Italy which generated weak positives in the PCR testing done by the Laboratory of Virology by the University of Florence. The samples were subsequently tested by Italy’s Superior Health Institute (ISS) which used a different set of primers which produced a negative result. Since the samples came from asymptomatic cases, the viral RNA levels would be expected to be near the limits of detection and if two labs used assays with different sensitivities, the more sensitive test would generate weak positives, while the less sensitive test would generate false negatives. As seen in the comments (in blue) titration of various sets of MERS-CoV primers produce sensitivities which differ by five fold. Thus, the ISS should retest the samples using the primers used by the University of Florence, which would produce confirmatory positives if there wasn’t extensive cross contamination in the positive tests. Full sequences have been generated for four previously confirmed MERS-CoV cases and partial sequences have been generated for at least four additional cases by sequencing the inserts generated in PCR tests. The sequences have been identical or closely related to the consensus sequence and sequencing of the inserts from the weak positives in Italy would confirm that the weak positives were due to MERS-CoV RNA. The testing protocol requires positive results in two sets of primers and the likelihood that another coronavirus would generate positives for both sets is near zero. However, testing samples with RNA levels at the limits of detection would generate weak positives for the more sensitive assay and false negatives for the less sensitive assay. MERS-CoV RNA in samples collected from asymptomatic cases may be detected during a small window of opportunity, and use of the most sensitive sets of primers may be required. Retesting using the primers which generated the weak positives should be done immediately, and the inserts should be sequenced. http://www.recombinomics.com/News/06041303/MERS_Italy_Asymp_Test_More.html |
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Albert
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Got it. So how did they get the false positive? niman lost me at The
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Kyle
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Wonder if they'll actually go through with re-testing all of them. I read an article stating that over 1,300 SARS-like cases were negative, wondering...
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jacksdad
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Lol...
I'm lost here too. If the patients were infected and asymptomatic, but the virus (or viral RNA as the article puts it) was at a threshold where one lab using a more sensitive test got a positive while another labs test failed to detect it, isn't that a false negative? If I'm reading this right, they're infected, but at such a low level as to be be borderline detectable and asymptomatic. Doesn't that still mean that they're infected though - it's just that one lab's testing procedure was better than the other? |
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"Buy it cheap. Stack it deep"
"Any community that fails to prepare, with the expectation that the federal government will come to the rescue, will be tragically wrong." Michael Leavitt, HHS Secretary. |
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Albert
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Well, I suppose they can flip a coin in the end to resolve it. Neg or positive.
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Albert
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If niman is saying that they don't know how to run tests, I ain't buying it.
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EdwinSm,
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My reading of it was:
a) The asymptomatic results would just be at the edge of detection, and there is jsut a short window of oppurtunity to get any results. b) the first testing produced a weak positive c) the first testing was 5 times more sensitive than the second testing (I don't understand his logic on this point as I don't have the technical knowledge of the testing process). d) the second testing, being less sensitive produced a negative result. He was recommending that the second institute re-run the tests using a more sensitive test. For me the implications of the above was that the second set of testing was set up to fail by using a process that was not sensitive enough. I do not have the technical or medical knowledge to know it this is a reasonable claim or not. A milder implication would be that the viral load of an asymptomatic case is just on the boarderline of the capablities of the tests used so it would be easy to get false negatives. I am at a loss to know what is really happening. (ps I use DuckDuckGo for searching and this site came in no2 when I searched on "MERS Italy false positive") |
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Rors
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Here are my comments:
1- They say that the samples were from asymptomatic cases: is it bad wording and what they meant was "suspected" cases? because that's a huge difference. If these cases are confirmed to be asymptomatic (we need to learn how they reached that conclusion), and they were only looking to confirm that diagnosis by PCR testing, then the positive essay is reliable and the negative essay is just not sensitive enough as the infectious load is not significant enough (hence the lack of symptoms) 2- The ISS (which used the assay generating negative results) should retest the samples using the primers used by U. of Florence (which produced the weak positives). If the results come up negative, it could potentially mean that the weak positives from Florence were the result of mis-handling and contamination. I personally would retake fresh samples and reexamine them using both assays in 2 different labs. Matching results from the 2 labs would confirm the results whether positive or negative. If they give positive results, the fragments should be isolated and amplified by PCR then sequenced, then compare the resulting sequence to the MERS-CoV consensus sequence which is available as per the article. If they are identical, we'll know without a shred of a doubt that these people are in fact infected and carry the viral genome, even if in few copies. Then it should be determined if they can infect other people or not and take necessary precautions. I hope I didn't lose you guys, it's been about 4 years I haven't worked in molecular biology techniques and my scientific expression skills might be a little rusty |
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Dutch Josh
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My impression from Henry Nimans commentary; there were no false negatives. The testmethods seem to be failing. If the corona-virus also is responsible for the common cold that virus spreads human-to-human. University of Florency test might indicate that mostly people that get infected do not get ill. Only a small group develops severe symptoms.
Since most testing-labs depend on taxpayers money and finding a big health problem indicates high costs labs do think twice before ringing an alarm. Bringing bad news still does not make anybody popular ! The bad thing might be that the MERS-virus is far more widespread and only shows up if someone develops severe symptoms.
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carbon20
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In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical infections. The term clinically silent is also used. Knowing that a condition is asymptomatic is important because:
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Dutch Josh
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According to the ISS, Italian Health Institute, there are only three carriers of the MERS-virus due two their rule that a second test has to confirm a first positive test. Eventhough they know that the second test is five times less sensitive...There are now no "asymptomatic cases" left !
Cynicly, that saves a lot of costs and enables Italy to "kick the ball to another country or health-institute".
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coyote
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With regard to rumours appeared on the press -- and published on ProMED -- about positivity for MERS-CoV among close contacts of confirmed cases detected in Florence, we would like to specify that the reference lab of Istituto Superiore di Sanita has not confirmed any of the samples from asymptomatic contacts of the cases.
Moreover, the virus has not been characterized yet. Thus, significant mutations in the viral genome that might explain changes in virulence on transmissibility cannot be confirmed as yet. Clinical surveillance of close contacts contagiousness is ongoing. -- Giovanni Rezza and Isabella Donatelli Department of Infectious Diseases Istituto Superiore di Sanita Rome, Italy <giovanni.rezza@iss.it> Link here... [link to www.promedmail.org] |
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Long time lurker since day one to Member.
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Albert
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Maybe Giovanni Rezza and Isabella Donatelli can explain how they got the false positives to begin with. Still have never seen that one before.
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niman
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Here is a quick summary of what happened in Florence, Italy. There are three MERS-CoV confirmed cases. The index case had been in Jordan and he returned to Italy. He had contacts with family members in Italy on the weekend of his return and he went to work on Monday (at the reception desk of a hotel). His flu-like symptoms continued to worsen and he went to one hospital on Tuesday and had bi-lateral pneumonia. He was subsequently transferred to a second hospital.
His niece (2F) developed symptoms as did a co-worker (42F) and both tested positive. In addition to these two positives, there were 60 people who had contact with one of the three positives (most were relatives or hospital workers at the two hospitals that treated the index case - and they may have been a few on his airplanes used to return from Jordan). None of these 60 contacts had symptoms. Thus, they were all asymptomatic. Usually, asymptomatic contacts are simply monitored for symptoms. However, Italy decided to test all 60 contacts using upper respiratory samples (almost certainly nasopharyngeal swabs). The University lab identified at least 8 weak positives using primers from MERS-CoV sequences. These tests are described in a link to the WHO website and there are multiple sets of probes identified which have been tested and published. Typical PCR testing using two sets of primers target two different regions of the viral RNA. It is extremely unlikely that a positive result for both sets would be due to anything other than MERS-CoV. Different sets of primers have different sensitivities, which can vary five fold. WHO requires confirmation by TWO labs. The second lab to test these samples used a DIFFERENT set of primers, which were negative. They did not simply repeat the tests of the first lab. Since the samples were from asymptomatic cases who had been exposed to MERS-CoV a few days prior to sample collection, the level of MERS-CoV would be expected to be low. The finding of eight (or ten) weak positives from these cases would strongly suggest that these cases were positive and the second lab should have used the same primers. Instead, the negative data using a different set of primers may simply reflect a lower sensitivity. Thus, the patients should be retested, and the inserts from the weak positives should be sequenced. A sequence would confirm that the weak signals were due to MERS-CoV sequences.
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niman
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Five of the 8 weak positives were from health care workers (2 doctors and 3 nurses) from the two hospitals
http://www.recombinomics.comews/06041301/MERS_Italy_Asymp_HCW. - http://www.recombinomics.com/News/06041301/MERS_Italy_Asymp_HCW.html
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oriel
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Dr Niman,
Your summary, assumptions and conclusion are very reasonable, and I suspect also correct. I have reviewed all the available material in English and Italian (my first language) and can find no obvious discrepancy or possible error except perhaps the very reasonable assumptions about the tests used which I can not confirm since I can not find specific mention yet. |
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niman
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The WHO approved primers are described here
http://www.virology-bonn.de/index.php?id=40 - http://www.virology-bonn.de/index.php?id=40 The media quotes citing 2 different regions by the two different labs in Italy are in the latest commentary http://www.recombinomics.comews/06041303/MERS_Italy_Asymp_Test_More. - http://www.recombinomics.com/News/06041303/MERS_Italy_Asymp_Test_More.html
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carbon20
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s..t now i know this is serious,
never seen Dr Niman ,(Welcome )post on here before . |
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Albert
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Niman posted here 7 years ago and we follow his commentaries often at Recombinomics. If you have questions you better ask them now. Dr. Niman is a straight shooter, which is why we like him and value his input.
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debbiencusa
Adviser Group Joined: April 25 2013 Location: nc Status: Offline Points: 2100 |
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Is it possible that the eight who tested positive (because they are health care workers who wash their hands, sanitize etc) tested pos simply due to exposure, they had a small but initially detective amount of virus in their nose or upper resp. . The first test being so sensitive caught that through the luck of a swab taken from where the germ first landed so to speak (entry way to the nose or lung)?
Then bc the health care workers aware of the danger of exposure gargled and cleaned nasal passages with something such as hydrogen peroxide. I am not a HC worker but have access to several things due to different family conditions. If I were exposed I would change clothes right away, shower with betadyne, gargle with hydrogen peroxide, clean my sinus with hydrogen peroxide via a sterile disposable cup, I would put hydrogen peroxide in a nebulizer and do neb treatments every few hours, I would take thirteen thousand mg of vitamin C every hour on the hour along with vitamin D-3 ten thousand mg every hour, bee populace and pray, pray pray. I would also use colloidal silver. I would hole up in a room separate from family, stop exchange of air through the home, open a window for fresh air. I would use oregano oil, sambucol, ashaswaga and any other known flu killer. I would also put several drops of hydrogen peroxide in distilled water and drink it to cleanse my intestines. This would result in diarrhea which would empty the colon well of its contents. Could it be possible that a health professional could have gone to extreme methods of prevention which could have killed off the first few viral cells to make the second test come out negative? I know I would share my routine with my fellow workers for two reasons, one to help them also, two to pick their brains about safety or other ideas I did not think about. I have stopped the spread of highly contagious disease like Pink eye, chicken pox dead in its tracts in my own home amongst pre schoolers and young school age kids, one of the hardest groups to stop the spread of illness in. It is possible, when your life is on the line most people will do about anything to save it, especially since the other alternative is pretty much sure death, you don't have much to loose and all to gain in the attempt to try to save. Just a thought.
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God Bless
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debbiencusa
Adviser Group Joined: April 25 2013 Location: nc Status: Offline Points: 2100 |
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One would also need to flush the eye with sterile water and you can also use the solution which is supposed to sterilize contact lenses to flush the eye with, making sure to cleanse lashes and brows which could have virus also.
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God Bless
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jacksdad
Executive Admin Joined: September 08 2007 Location: San Diego Status: Offline Points: 47251 |
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Thanks for posting the summary. So the cases that were characterized as false positives were in fact ones that simply didn't meet the WHO's criteria of confirmation by two different labs? I agree - under the circumstances, the single positive should have been sufficient to warrant retesting.
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"Buy it cheap. Stack it deep"
"Any community that fails to prepare, with the expectation that the federal government will come to the rescue, will be tragically wrong." Michael Leavitt, HHS Secretary. |
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