@jjchamie (on twitter) found this article. It isn't as big as the actual paper, which is probably going through the peer review process now, but it's confirmation that CONCENTRATION TOO HIGH is nonsesne.

The first inkling Kylie Wagstaff had that something unprecedented was happening came when she opened her inbox to find thousands of emails from people all around the world.

It was April and the Monash University virologist, a specialist in antiviral drug development, had just published a study on anti-parasite drug ivermectin.

At high concentrations in a Petri dish, she found, the drug stops the growth of the virus that causes COVID-19.

As scientists like to joke, there are lots of things that can kill a virus in a Petri dish – including bullets. Most lab-dish results do not work in humans, otherwise scientists would have cured cancer many times over. Dr Wagstaff thought the study might be of interest to scientists but few others.

“[The emails] were from everyone – doctors, scientists, companies, everyday people, ” she told The Sunday Age. Many were from doctors asking for treatment guidelines – which Dr Wagstaff, a scientist, did not have.

The day the ivermectin study was published, Melbourne's Herald Sun had put it on its front page, under the headline "CURE HEAD START". The next day, Victoria’s health minister was warning people not to take the drug.

But in April, people around the world were scared and desperate. And Dr Wagstaff had just named a cheap, readily available and reasonably safe medication as a potential COVID cure.

The story was picked up by media locally and around the world. Google trends data showed a huge spike in interest, much of it from Bangladesh – where a local doctor was soon claiming a 98 per cent cure rate.

A few days after Dr Wagstaff’s study was published, a separate team of researchers published a study claiming a database of hospital records showed ivermectin more than halved death rates in COVID-19 patients.

Scientists were immediately suspicious. How could ivermectin already be saving lives when the link had only just been made to COVID-19?

The company behind the database, Surgisphere, quickly became the subject of intense scrutiny after scientists found huge inconsistencies in its hospital records. When the company would not release the full database to prove its authenticity, major publications in the Lancet and the New England Journal of Medicine were retracted; the Surgisphere ivermectin paper disappeared too.

The Surgisphere study was the second study endorsing ivermectin after Dr. Wagstaff's April 3 article (here PDF). There was a (IMO politically-motivated) scandal about Surgisphere after their Lancet article trashed HCQ.

But the damage had already been done. The Peruvian government added ivermectin to its treatment guidelines based on the now-disappeared study; the Bolivian government added ivermectin to its guidelines, citing Peru.

BS: Ivermectin saved lives in Peru.

In May, some 350, 000 doses were handed out by healthcare workers in Bolivia. Peruvian police seized about 20, 000 bottles of animal-grade ivermectin being sold on the black market; thousands of indigenous Peruvians were injected with a veterinary version of the drug. A year’s worth of the drug was sold in Brazil in June alone.

Peruvian public health researcher Elmer Huerta told Peruvian TV the government had led people to think “if I don’t have ivermectin, I’m going to die. ” Juan Celis, a Peru-based infectious diseases specialist, told The Scientist his country was gripped with “ivermectin fever”.

And yet there is still no robust evidence the drug works. It may – but many scientists are skeptical.

“The evidence we have seen so far certainly does not support its use in current practice, ” says Professor Andrew McLachlan, the University of Sydney’s dean of pharmacy.

That's a great qualifier, "the evidence we have seen." 99.9% aren't aware of the evidence. You, /r/ivermectin readers, are more expert about ivermectin that 99.9% of the world medical/public health community.

University of NSW cancer biologist Associate Professor Darren Saunders voiced concerns over presentation of the study's findings.

“The research itself stands on its own and appears entirely valid. . . [but] the scientists themselves should have been a little more careful in the way their study was presented and promoted publicly, ” he said.

Widespread use of an unproven drug “raises questions around raising false hope and expectations [and] diversion of resources, ” says Professor Saunders.

The Age revealed in April two scientists asked to informally review the study before it was published. Professor Mark Sullivan and Dr Craig Rayner, raised major concerns about dosing.

I get all conspiracy-minded (not my usual way) about Sullivan and Rayner here.

To get to the levels in Dr Wagstaff's initial study, a person would need to take a dose 10 to 30 times higher than ever studied in humans, Professor Sullivan says.

Dr Wagstaff rejects this, and says she has unpublished data showing "the drug works at lower concentrations which are definitely achievable based on all published modelling".

US President Donald Trump told reporters that he was taking zinc and hydroxychloroquine on May 18. US President Donald Trump told reporters that he was taking zinc and hydroxychloroquine on May 18. CREDIT:AP

Professor David Jans, Dr Wagstaff’s co-author, says the existing data for ivermectin is much better than that for approved COVID-19 drug Remdesivir.

For which a BIG trial showed no effect, one week before the FDA approved Remdesivir. Gee, were politics involved? The last number I saw was about $800 million on sales.

He believes his ivermectin work is attracting criticism because “Big Pharma hates the idea of a cheap drug that might work”. (Monash University has received federal government and philanthropic funding to do further work on the drug. )

A volunteer sprays disinfectant on a train, in an effort to prevent coronavirus, at the Kamlapur Railway Station in Dhaka, Bangladesh in March. A volunteer sprays disinfectant on a train, in an effort to prevent coronavirus, at the Kamlapur Railway Station in Dhaka, Bangladesh in March. CREDIT:EPA/ MONIRUL ALAM

“The trials for ivermectin are happening – results looking positive, ” he says.

“Maybe it is time for the world to start trying to save lives rather than continuing to exploit the situation as an ‘opportunity’. ”

In a recent review they authored, Dr Wagstaff and Professor Jans point to several small studies showing the drug is effective against COVID-19.

“We still have not had the really big, really well-done randomised controlled trial that we need to conclusively say one way or another. But there has been a lot of evidence all pointing in a promising direction since then, ” says Dr Wagstaff.

Australia’s national COVID-19 clinical evidence taskforce says the drug should not be used outside clinical trials, as the benefits are unknown.

Dr Wagstaff’s supports Australian authorities waiting for robust evidence. She is wary of patients self-medicating. But she defends the rights of doctors to prescribe the drug off-label for COVID-19.

“I am all for science. Science is important, ” says Dr Wagstaff. “We don’t have the definitive answers yet as to whether it works or not. But I haven't seen any good evidence that it does not work. ”

permalink

It's not a negative article, it's neutral. I didn't get the impression that invermectin doesn't work, instead that they are not enough studies

permalink

Bottom line: many clinical studies and national data in Peru show that IVM is effective against COVID-19. Good that Caly-Wagstaff helped spur initial interest. It is a badge of honor for a scientist to put forth a theory that advances study, even if ultimately found flawed. Other points that are tenuous, confounding, and at this point hinder wider acceptance of IVM for COVID:

1) If Caly-Wagstaff have in vitro data at 1x clinical tissue concentration, not 1000x, they should publish them. 2) Effects in the cell nucleus, e.g. on importin, would typically not apply to RNA viruses. There are credible, better-supported biological mechanisms for IVM, e.g. blocking viral spike protein, as supported in six studies (see http://ssrn.com/abstract=3706347 )

3) A group of authors published and then retracted studies on HCQ and IVM based upon questionable or fabricated Surgisphere data. The retracted conclusions were positive for efficacy of IVM and negative for HCQ. We can't pick and choose and somehow tout the questionable data supporting IVM. Best not to mention this. Also absolutely best not to muddy this discussion by announcements by any political leaders of zero scientific credibility of their personal experience with any of these agents.

Reiteration of bottom line: Let's keep coherently summarizing the compelling clinical data on IVM for COVID-19 and stick to credible scientific studies.

permalink

•IVM-RodRWA-Comment1of2• 1.   The subject item provides a 20201106 article from an Australian newspaper named THE AGE. 2.   This is one of the very few articles out of Australian mainstream media that I've seen & that not only uses the "heinous" word IVERMECTIN, but it actually discusses this medication without totally condemning it outright. Admittedly, the text is spattered with warnings such as: 2.1.   Victoria’s health minister was warning people not to take the drug. 2.2.   “The evidence we have seen so far certainly does not support its use in current practice,” says Professor Andrew McLachlan, the University of Sydney’s dean of pharmacy. 2.3.   To get to the levels in Dr Wagstaff's initial study, a person would need to take a dose 10 to 30 times higher than ever studied in humans, Professor Sullivan says. 2.4.   Australia’s national COVID-19 clinical evidence taskforce says the drug should not be used outside clinical trials, as the benefits are unknown. 3.   However, for all these warnings that paint this incredibly benign & efficacious pill as if it ranks with the World's worst poisons, the article does at least provide some remarks that are slightly positive about IVERMECTIN, such as: 3.1.   "Dr Wagstaff supports Australian authorities waiting for robust evidence. She is wary of patients self-medicating. But she defends the rights of doctors to prescribe the drug off-label for COVID-19. 3.2.   "Dr Wagstaff (says) “We don’t have the definitive answers yet as to whether it works or not. But I haven't seen any good evidence that it does not work.” " 4.   Dr Wagstaff may well say ".... I haven't seen any good evidence that it does not work”, but I assume this has been said without much awareness of what goes on outside of her sacred Clinical Test environment. There, she & her cohorts tinker with their "double blind tests" & "placebos", full of confidence that what they are doing has been established & condoned by the Old Testament according to the almighty Universities of the World. In this way, Dr Wagstaff & associates are shielded from & are oblivious to the Covid-19-infected sinners who are dying in their thousands because of no IVERMECTIN! WHAT A TRAVESTY! 5.   Dr Wagstaff also says that ".... she defends the rights of doctors to prescribe the drug off-label for COVID-19....", but it appears that she has done nothing to make the AuGov aware of this attitude as their legislation continues to restrict it in a draconian fashion. In some ways, you can't blame the AuGov for this extremely negative response about IVERMECTIN because it was Dr Wagstaff's initial study that stated ".... a person would need to take a dose 10 to 30 times higher than ever studied in humans .... (for it to be successful)." 6.   This is one of the most extremely negative reports that's ever been published about IVERMECTIN. To make matters worse, this negativity is backed by the names of two auspicious authorities: Monash University & The Doherty Institute. Detractors of IVERMECTIN love quoting this report because of its extreme condemnation & its high level credentials. Yet it is so erroneous that it's embarrassing & aggravating to anyone who has a reasonable knowledge of IVERMECTIN. 7.   For all that, Dr Wagstaff has never offered a retraction or an amendment to this extremely damaging report. As a result, I take her pleasantries about IVERMECTIN that are quoted above as being without any real conviction. 8.   Well before this article in The Age was printed, I realised the damage that Dr Wagstaff’s misleading findings were doing to the valuable properties of IVERMECTIN. As a result, I sent an email on 06/10/2020 to Dr Wagstaff, challenging her to explain why the following two contrasting statements exist in her report or about the report: 8.1.   Dr Wagstaff reported ".... ivermectin could be a useful antiviral to limit SARS-CoV-2 ...." 8.2.   Associate Professor Tong has concerns that "The initial studies seem to suggest you need a very high level of ivermectin to be able to reduce replication of the virus, and those levels in those initial studies are very difficult or impossible to achieve in a person...." 9.   My email is presented below in •IVM-RodRWA-Comment2of2•. Just over a month has passed since it was sent, but I have received no answer to my query. Embarrassment may be one explanation to this no response, but I suspect it is more likely to be associated with money! 10.   Professor David Jans, Dr Wagstaff’s co-author, has hit the nail on the head when he says in The Age article: 10.2.   "He believes his ivermectin work is attracting criticism because “Big Pharma hates the idea of a cheap drug that might work”. 11.   The Age also states: 11.1.   Monash University has received federal government and philanthropic funding to do further work on the drug. 12.   Like Big Pharma, the Australian federal government doesn't want their Au$billions of investment in their Long-Way-Off vaccine to be threatened by that Cheap-But-Very-Safe-&-Efficacious IVERMECTIN. I don't know how much funding the Australian federal government provides to Monash University, but I bet it's a mere token compared to the bonanza given to the vaccine developers. Even though it's a splash in the ocean, I imagine that Monash University don't want to lose it, so I guess that they're dutifully following instructions not to report any findings in favour of IVERMECTIN! 13.   While on the subject of COVID-19 cures, there are many sceptics who understandably have doubts about the "magical properties" of numerous medications that are touted on the web. The internet is the modern version of the Snake-Oil Salesmen in this regard! I was sceptical too until I made a cold phone call to a doctor (Dr Mickey) in her clinic in USA. I happened to see her name mentioned in a nondescript article online. It mentioned that she was using IVERMECTIN in off-label applications to cure COVID19. 14.   The phone number that I called was genuinely her clinic. It was answered by her nurse / secretary. She was able to grab Dr Mickey between patients. I arranged a more convenient time to call, & managed to have a couple of long conversations with the good doctor & with her nurse. They happily recounted their 100% success rate using IVERMECTIN, & that it was totally genuine. Dr Mickey has no agenda to push, & according to her nurse, she's a very committed individual who does enormous amounts of study with the intention of helping her patients. She has a radical streak, & doesn't care that her off-label use of IVERMECTIN is receiving criticism from her more conservative contemporaries, because ".... damn their claims that it should be properly tested first, when it's already been proven to be safe by many years of use as a antiparasitic, & it just happens to work extremely well with COVID-19!" The alternative is to let the patients die without it, while Clinical Trials fiddle around trying to prove it's safe! 25.   Check out more about Dr Mickey in URL: https://gumshoenews.com/2020/09/01....(etc). It's one of the URLs that I've listed below. Most of those URLs provide access to documents that I have written & which relate to IVERMECTIN. •NOTE•: URLs listed below & which are presented as: "||https://" provide access to documents authored by yours truly (UserName: RWA). Those presented as: "|https://" are authored by other individuals.

•Realcoronanews URLs• ||https://realcoronanews.com/2020/10/28/ivermectin-the-immediate-need-for-authorisation-as-treatment-for-covid-19/

•Gumshoenews URLs• ||https://gumshoenews.com/2020/10/23/ivermectin-one-story-of-superb-success-and-one-story-of-sordid-skullduggery/#more-26161 ||https://gumshoenews.com/2020/10/02/urgent-make-ivermectin-available-and-lets-get-back-to-normal/ ||https://gumshoenews.com/2020/10/01/ivermectin-risk-versus-reward-panacea-for-covid-19/ ||https://gumshoenews.com/2020/09/21/letter-to-ass-prof-senanayake-regarding-efficacy-of-ivermectin-and-the-double-blind-event-at-toronto-nursing-home/ ||https://gumshoenews.com/2020/09/01/open-letter-to-health-minister-about-ivermectin-one-dose-is-normally-sufficient-for-recovery/

|https://gumshoenews.com/2020/08/30/ivermectin-professor-borody-the-94-year-old-woman-and-the-federal-government/p |https://gumshoenews.com/2020/08/23/life-saving-medical-options-denied-to-elderly-who-is-culpable-for-covid-deaths/

•IVM-RodRWA-Comment1of2•                ENDS •IVM-RodRWA-Comment2of2•     SEE NEXT COMMENT

permalink

•IVM-RodRWA-Comment2of2• EMAIL 06/10/2020 TO: •kylie.wagstaff@monash.edu •steven.tong@mh.org.au •catherine.somerville@unimelb.edu.au CC •doherty-reception@unimelb.edu.au

Email Subject: IVERMECTIN: Conflicting Attributes out of Monash Uni (Doherty Inst)

TO: •Dr Leon Caly •Dr Kylie Wagstaff •Associate Professor Steven Tong

REFERENCES    See at bottom of this document.

1.   I am a freelance journalist who lives in South Eastern Queensland. I have been investigating IVERMECTIN for some months & the role it may be able to play in the future in association with SARS-CoV-2, or the role that it possibly already plays in off-label SARS-CoV-2 situations. I have already completed four articles on the subject. They are available on request. 2.   The Monash University & the Peter Doherty Institute feature frequently in my investigations. I heartily congratulate you who are the addressees of this email, & your learned colleagues for the many significant achievements of your clinical studies. Keep up the good work! 3.   During my most recent investigations, I have detected what appears to be some conflicting information regarding the potential attributes of IVERMECTIN in association with SARS-CoV-2. The confliction appears to exist between the Document given in Reference 1 & that given in Reference 7. 4.   Reference 1 is authored by Dr Leon Caly & Dr Kylie M. Wagstaff. As a result, this enquiry is directed to your good selves. Reference 7 involves quotes from Associate Professor Steven Tong, so this enquiry is directed to the good Professor. I trust that you are each able to explain or resolve this confliction. 5.   To aid in comprehending the conflict that may exist, I will list the various paragrahs or parts of those paragrahs from each Document, & within which I believe there is a conflict. 6.   The following statements have been copied directly from Reference 1: 6.1.   .... these results demonstrate that ivermectin has antiviral action against the SARS-CoV-2 clinical isolate in vitro, with a single dose able to control viral replication within 24–48 h in our system. 6.2.   Ultimately, development of an effective anti-viral for SARS-CoV-2, if given to patients early in infection, could help to limit the viral load, prevent severe disease progression and limit person-person transmission. 6.3.   This Brief Report raises the possibility that ivermectin could be a useful antiviral to limit SARS-CoV-2, in similar fashion to those already reported (Dong et al., 2020; Elfiky, 2020; Gordon et al., 2020; Li and De Clercq, 2020; Wang et al., 2020); until one of these is proven to be beneficial in a clinical setting, all should be pursued as rapidly as possible. 6.4.   Ivermectin has an established safety profile for human use (Refs 2, 3, 4), and is FDA-approved for a number of parasitic infections (Refs 2, 4). Importantly, recent reviews and meta-analysis indicate that high dose ivermectin has comparable safety as the standard low-dose treatment, although there is not enough evidence to make conclusions about the safety profile in pregnancy (Refs 5, 6). 7.   Meanwhile, the following statements have been copied directly from Reference7: 7.1.   Associate Professor Steven Tong is an infectious diseases clinician at Royal Melbourne Hospital, the principal investigator for the AustralaSian COVID-19 Trial (ASCOT) and a co-lead of clinical research at the Doherty Institute. 7.2.   While there are discussions on the potential use of ivermectin as a therapy for COVID-19 in humans, Associate Professor Tong has concerns about its use in that context. 7.3.   ‘The initial studies seem to suggest you need a very high level of ivermectin to be able to reduce replication of the virus, and those levels in those initial studies are very difficult or impossible to achieve in a person,’ he said. 7.4.   He is also concerned that these laboratory findings were not performed on human cells. 7.5.   ‘They were done initially with monkey cells, so we await work with human cell lines to confirm the effect and confirm whether the dose is achievable,’ he said. 8.   I will now compare the more specific segments of Ref1 & Ref7 that appear to be in conflict. Firstly Ref1: 8.1.   Ref1-Para6.1 states in part:   ".... a single dose (is) able to control viral replication within 24–48 h in our system ...." 8.2.   Ref1-Para6.2 states in part: "....  could help to limit the viral load (&) prevent severe disease progression ...." 8.3.   Ref1-Para6.4 states in part ".... high dose ivermectin has comparable safety as the standard low-dose treatment ...." 9.   In contrast to the Ref1  statements listed in para 8, here are the Ref7 statements: 9.1.   Ref7-Para7.3 states in part:   "....need a very high level of ivermectin to be able to reduce replication of the virus, and those levels in those initial studies are very difficult or impossible to achieve in a person ...." 9.2.   Ref7-Para7.5 states in part: ‘.... confirm the effect and confirm whether the dose is achievable." 10.   As can be seen, Ref1 suggests very positive expectations for the ability of Ivermectin in combatting the COVID-19 virus while Ref7 suggests quite the opposite. This negative attitude is somewhat reflected in the title of Ref7: "Insufficient evidence to support ivermectin as COVID-19 treatment." 11.   Given all the above evidence, I now make this request to Dr Leon Caly, Dr Kylie M. Wagstaff & Associate Professor Steven Tong. I request that you explain or resolve these conflictions & advise me accordingly. 12.   Best regards, thanks for your help, & trusting that I shall hear from you in the very near future.

REFERENCES **1.   "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro."  https://doi.org/10.1016/j.antiviral.2020.104787    Volume 178 dated June 2020. Document is current wef 05Oct2020. Authors:    A1. Dr Leon Caly    Senior Medical Scientist within the Virus Identification Laboratory of the Victorian Infectious Diseases Reference Laboratory (VIDRL) & the Peter Doherty Institute for Infection and Immunity.    A2. Kylie M.Wagstaff Biomedicine Discovery Institute, Monash University, Clayton, Vic, 3800, Australia Corresponding author. kylie.wagstaff@monash.edu

**2   Gonzalez Canga et al., 2008;   https://www.sciencedirect.com/science/article/pii/S0166354220302011#bib7

**3   Jans et al., 2019;    https://www.sciencedirect.com/science/article/pii/S0166354220302011#bib11

**4   Buonfrate et al., 2019   https://www.sciencedirect.com/science/article/pii/S0166354220302011#bib1

**5   Navarro et al., 2020;    https://www.sciencedirect.com/science/article/pii/S0166354220302011#bib18

**6   Nicolas et al., 2020   https://www.sciencedirect.com/science/article/pii/S0166354220302011#bib19

**7   https://www1.racgp.org.au/newsgp/clinical/insufficient-evidence-to-currently-support-ivermec    RACGP - Insufficient evidence to support ivermectin as COVID-19 treatment dated 15/08/2020 by Dr Evelyn Lewin.

•IVM-RodRWA-Comment2of2• COMMENT ENDS

permalink