The mis-and dis information pandemic
I applaud Dr. Marthinus Viljoen for providing an extensive overview of his thoughts on the use of
Ivermectin in the treatment of COVID-19. We are lucky enough in South Africa to have a free press
where debate is possible. To this end I would like to add some facts to Dr Viljoen’s communication
that will help the public make up their own minds.
Dr Viljoen is correct when he says the COVID-19 has been shadowed by a sinister pandemic of mis
and dis information that has exacerbated the suffering of people across the globe. What he doesn’t
realise is that he could well be unwittingly participating in it along with other mainstream media,
social media and regulatory authorities. As thinking citizens who do we believe? Any thinking citizen
would know to be sceptical of social media, the mainstream media have joined forces to decide
what they think is mis or dis information and regulatory authorities have conservative agendas that
they defend in what they define as the interests of the public. It is clear, that we need to take
responsibility for ourselves, find accurate information so that we can think for ourselves and make
well informed decisions. And bear in mind that even those experts we have respected and have had
blind faith in for decades, are human and have opinions that they may pass off with authority as fact.
I agree with Dr Viljoen, truth can make one uncomfortable, and I would like to add some
uncomfortable truths to his communication.
When one talks of a drug being popular, the implication is that it is based purely in anecdotal tittle-
tattle. Let’s ask why Ivermectin has remained popular for approaching a year now. Why it did not
disappear from conversation after SAHPRA’s letter in December which warned that Ivermectin could
be lethal? Could it be that doctors are successfully treating COVID-19 with regimens which include Ivermectin? Or that patients who have been treated with it, when no other option was offered to them, got better and now they want the same for their families and friends? Those in authority will say Ivermectin is being kept alive by anecdotes and emotion. Anecdotal evidence is the spoken truth of those with experience and forms the lowest reliable medical information. But when hundreds of doctors and patients have the same anecdotes to share, the evidence cannot be ignored. And yes, I guess emotion has something to do with it, especially when the stakes are as high as a person’s life.
However, there is much more than anecdotal evidence for the efficacy and safety of Ivermectin in
treating COVID-19. In early drug repurposing experiments, Caly et al found that Ivermectin was a
good potential drug to follow up with further research. After they published their laboratory-based
experiment where they showed that Ivermectin killed the SARS-COV-2 virus in a petri dish, doctors
at the coalface of COVID-19 treatment, who had experience in using Ivermectin as an antiparasitic
drug, started using it with varying levels of success. Ivermectin is registered for use in countries
where parasitic disease is endemic, so it stands to reason that the first research would come from
countries like Egypt, India and South American countries etc. These were studies carried out without
major funding, by the clinicians in the front line and are not the large big-pharma financed studies
carried out for novel drugs in the West. To call these studies poor quality is nothing short of
academic snobbery, especially when at least 36 of them have been published in peer-reviewed
journals.
Current research into Ivermectin on COVID-19 treatment
On 31 August, I carried out a comprehensive search of PubMed, Ebsco Host, Web of Science and
Scholar.Google with the search string (SARS-COV-2 OR Coronavirus OR COVID-19) AND (Ivermectin)
to find published research to provide a more accurate picture of the state of research on Ivermectin
in COVID-19 treatment. I deliberately excluded pre-print research because of the recent debacle
with the Elgazzar study. The search rendered 36 human trials. Five of these did not reach statistical
significance. These included the often quoted Villejos and Lopez-Medina studies which, if the
readers read the entire studies, state in the limitations of their studies, had protocol design factors
that may have influenced the poor outcomes for Ivermectin and both suggested further research
which would address these confounders. The other 31 studies, which included pilot studies, case
studies, case series, retrospective and prospective cohort studies as well as randomised control
trials, all showed positive outcomes. There is not a single study out of these 36 that has stated that
the pursuit of Ivermectin as a treatment in COVID-19 is futile or that it causes any harm. And I
certainly have not found the research Dr Viljoen refers to that says Ivermectin renders the COVID-19
patient worse off.
The large double-blind randomised control trial that is a requirement for authorities to make up
their minds about Ivermectin one way or the other, is and will remain elusive. Merck carried out all
the trials on the safety of Ivermectin in the last century and early in this century. Dr Viljoen provides
an excellent background to the discovery of Ivermectin and to Merck’s noble Mectizan program
which improved the quality of life of so many peoples across the globe and which ultimately led to
the discoverer and developer receiving the Nobel Prize for medicine six years ago. Merck has lost the
patent to Ivermectin now and are developing a new antiviral, molnupiravir, which they hope to
launch soon for emergency use.
Merck was also the company that created the drug Vioxx, a nonsteroidal anti-inflammatory. They
were aware of Vioxx’s cardiovascular risks early on, which resulted in up to 139 000 heart attacks
and strokes, 30-40% of them likely fatal. Not only did Merck hide the scale of this problem, they also
condemned those who cautioned on these serious adverse events. According to Moynihan in his
article on this scandal in the BMJ in 2009, one Merck executive emailed another: “We may need to
seek them out and destroy them where they live.” Merck provided a $410 million budget
disinformation campaign to keep Vioxx in the market. It was eventually withdrawn in 2004.
A company is as noble as those in charge at the time. Merck pulled out of the vaccine race earlier
this year. Could Ivermectin be seen to obstruct Merck’s anticipated profits from its new COVID drug?
Reviews and Meta-analyses have been regarded as high reliability evidence, surpassing double-
blinded randomised control trials on the evidence-based medicine pyramid…until now. It has
become clear that although the writers of these analysis hide behind the rigour of methodology,
there is subjectivity involved. Hill et al published a review where the data and conclusions were
unmatched and Dr Hill admitted that the discussion was not written by him. Kory et al and Bryant et
al followed with publications of their own and then the Elgazzar debacle struck. Most authors of
meta-analyses withdrew the Elgazzar data from their analyses. Only Hill et al state that their results
have changed to a point where Ivermectin is no longer seen to be effective. All others have had the
figures changed for efficacy, but the overall results, even using Bayesian theory, still point to
Ivermectin being an effective treatment. The Cochrane review authors, Popp et al, criticised Bryant
et al who have responded again. This has made me realise that we have to look at the primary
research ourselves. The only reviews we can trust are those we do ourselves. Dr Viljoen I believe
should come to the same conclusion when he gets to read them all.
In research, as data emanates, a doctor may make a Type 1 or a Type 2 error decision. Doctors that
remain Ivermectin hesitant have made a Type 2 error decision and they have every right to do so.
For them, they have weighed up the evidence they have selected and decided that rejecting
Ivermectin is their verdict. I agree that referring to them as monsters, as Dr Hill implied in his video
to a South African Audience in January is harsh.
But what is also harsh is the denigration of those doctors who have made a Type 1 error decision, to prescribe Ivermectin based on their consideration of the totality of evidence and the safety profile of the drug. These doctors have indeed done their homework, courageously defying the disparaging comments from the media, colleagues and regulatory authorities.
Dr Viljoen is correct when he says that just as a doctor should not prescribe an antibiotic for a virus,
an antiparasitic should not be used be used either. Indeed, the virus does not have gaba-receptors
which is the target for the mechanism of action of Ivermectin in parasites. However, the literature
abounds with several other mechanisms of action of Ivermectin in viruses. Ivermectin has been
found to be effective in many other human and animal viral diseases including Zika, Wet Nile Virus
and indeed HIV. The research exists. Look it up.
The Caly et al experiment mentioned above receives further attention by Dr Viljoen. As he quotes,
people read part way into the paper and no further. Experts and others who are afraid that
Ivermectin might be proven to work have quoted this research as indicating that too high a dose
would be required to use Ivermectin in humans based on the concentrations used in the experiment.
If they had indeed read the entire article and understood it well, they would realise that the research
question was simple; Does Ivermectin affect SARS-COV-2 in a petri dish? It was never meant to be
used to extrapolate values for human use. Ivermectin doses used in COVID-19 in the beginning were
based on the doses given for parasite disease. These were very low doses, and lead to many studies
not showing statistical significance. However, the Guzzo et al research from 2002 has established
that higher doses are well tolerated with minimal and transient side effects, and this has lead
doctors on the ground to find more effective dosage regimens. The in vitro studies that Dr Viljoen
refers to on Ivermectin dosage concentrations do not hold water anymore. In my literature search of
31 August there are several in vivo, in vitro and in silico studies that have a different conclusions.
Dr Viljoen asks the question, Why do people believe in Ivermectin? He goes on to explain
mathematically why people would have improved without Ivermectin anyway. This does not explain
how doctors who had a mortality rate amongst their patients before they started prescribing
Ivermectin, that dropped as soon as they started using it in their prescribing regimens. I have been
working with a doctor in Zimbabwe who last lost a patient with oxygen saturations over 50% over a
year ago. She started using Ivermectin in August last year, has been through their second and third
waves, and that is her experience. Her results are being prepared for publication, but alas, they will
be ignored because they come from a developing world country and the study is not a large double-
blind randomised control study.
Dr Viljoen explains why we need studies; to have absolute proof that a good number of people get
better on Ivermectin compared to those who are not. He ignores the 31 published studies, and
concludes that Ivermectin has not been able to show a benefit. He is wrong in this statement.
He is further disparaging of the Ivermectin adopters who tout the safety of Ivermectin .
VigiAccess.org is the WHO record of adverse events for all drugs. It’s easy to look up for yourself.
Scroll to the bottom of the page and click the box that says you are not a computer and you can look
up side effects of every drug you can think of. You will notice that in the last year the side effects for
Ivermectin have increased in number, which shows the current use of Ivermectin globally. Look up
paracetamol. Compare the number of reports for the existence of the drugs too. It’s true that
Ivermectin has not been tested in pregnant women, however, there is a paper that reports in the
inadvertent use of Ivermectin by pregnant women during the Mectizan program and reported no
teratogenicity. This being the case, it has not been specifically tested in pregnancy nor at the
dosages recommended for antiviral treatment, so like most other drugs on the market, it should not
be used in pregnancy. Nor in children under 15 kg in weight. Safety in long term use has been
established where Ivermectin has been used in cancer studies.
Dr Viljoen is correct regarding animal formulations and black-market products. SAHPRAs Controlled
Compassionate Access program was put in place to prevent people from resorting to these sources.
When people do not have access to the drug, they will use what they can get hold of. Ivermectin can
be legally prescribed through the Compassionate use program or off label since Soolantra was
registered earlier this year. It’s a schedule 3 prescription drug that people can have access to if their
doctors prescribe it. The NEMLC and SAHPRA continue to state that they only endorse the use of
Ivermectin in clinical trials, but this is because they have to be seen to be conservative. If a patient
wants to receive Ivermectin they should be directed to where they can get it properly prescribed in a
proper regimen.
Dr Viljoen may think Ivermectin has a placebo effect, and he is entitled to his opinion. Based on the
published literature I have read, I have to disagree with both him and Prof Mahdi. There is good
DRAFTJS_BLOCK_KEY:5c725up side effects of every drug you can think of. You will notice that in the last year the side effects for
His final statement is to go and get your vaccination. We have lost several colleagues since they were
vaccinated to Covid-19. Last week, an eminent vascular surgeon succumbed to COVID-19 after
receiving his jab during the Sisonke trial. We cannot deny that although vaccines might reduce
morbidity or mortality, they are not the only answer. We need therapeutics too and its irresponsible
to dismiss potential drugs without doing the proper in-depth research required.