“Beware of false knowledge: it is more dangerous than ignorance."
- George Bernard Shaw
“Objective truth is under attack. For COVID-19, this has taken the form of unsubstantiated claims about the origins of the disease-causing coronavirus, rejection of evidence-based information on prevention with masks and vaccines, and embrace of highly questionable, potentially harmful ‘treatments.’”
- Francis Collins, M.D., former director, National Institutes of Health
The U.S. Food and Drug Administration (FDA) has not approved ivermectin for use in preventing or treating COVID-19 My intent in writing this Germ Gems post is not, however, to add a further warning against taking ivermectin for COVID-19, but to discuss the cost of false claims of drug effectiveness for COVID-19—and not just in monetary terms. Additionally, I want to set the record straight—ivermectin actually is a “miracle drug” for a parasitic disease called river blindness.
What is ivermectin? If you are a dog or cat owner, chances are your pet is given ivermectin monthly to prevent dirofilariasis (heartworm disease). In the 1980s, the FDA approved the drug for this use. In 1996, the FDA approved ivermectin to treat roundworm and other parasitic infections in humans and in some large animals. Ivermectin is formulated differently for use by humans from use in animals.
In 2015, U.S. parasitologist William C. Campbell and Japanese microbiologist Satoshi Omura received a Nobel Prize for their discovery of ivermectin in the 1970s and its subsequent use to treat diseases caused by parasites. The award announcement declared, “The importance of ivermectin for improving the health and well-being of millions of individuals with River Blindness and Lymphatic Filariasis, primarily in the poorest regions of the world, is immeasurable.”
Lymphatic filariasis is one of the parasitic diseases that is treated with ivermectin. It is caused by a nematode (round worm) that induces swelling of lymphatic vessels leading to the disease called elephantiasis. While the therapeutic role of ivermectin in this grossly disfiguring condition is impressive, in my opinion, it is ivermectin’s role in the prevention of a second parasitic disease, river blindness, that merits its classification as a “miracle drug.”
Brief overview of river blindness. Onchocerciasis, commonly known as “river blindness,” is caused by the parasitic worm Onchocerca volvulus. It is transmitted to humans through the bites of infected blackflies. Symptoms include visual impairment that ultimately leads to permanent blindness. While this disease may not be well-known in North America outside the medical community, it is a huge problem in many developing countries. According to the World Health Organization (WHO), more than 99% of infected people live in 31 African countries with the remainder living in Latin America. In 2017 alone, at least 220 million people required preventive therapy against onchocerciasis.
Population-based treatment (also known as mass drug administration) with ivermectin is the core strategy to eliminate onchocerciasis. At least 12-15 years of treatment with ivermectin (administered at least once annually) are needed to eliminate transmission. For achievements in reaching this goal, kudos go to the pharmaceutical giant Merck. In 1987 Merck started donating ivermectin—as much as needed and for as long as needed—to African and other low-income countries to control river blindness. (Merck’s profits from the ivermectin given to our dogs and cats evidently helps support this corporate generosity.)
The benefits of this on-going program are enormous, as witnessed by the millions of people afflicted by river blindness or at risk of getting it. Because of ivermectin treatment programs, the WHO declared these South and Central American countries free of onchocerciasis: Colombia (2013), Ecuador (2014), Mexico (2015), and Guatemala(2016).
Why did anyone think ivermectin would be effective to treat COVID-19 in the first place? To understand why doctors latched onto the anti-parasitic drug ivermectin for the treatment of a viral disease (COVID-19), it is useful to remember that in the early months of the COVID-19 pandemic, patients and doctors alike were desperate for effective treatments. There were, however, no approved therapies at that time.
Therefore, drugs that were already FDA-approved, albeit for indications other than COVID-19, were tested in clinical trials for treatment of COVID-19. Such “repurposing” of drugs is how the anti-viral agent remdesivir became the first medication to receive FDA Emergency Use Authorization (EUA) in May 2020 for hospitalized patients with COVID-19. (In 2014, scientists had tested remdesivir for the treatment of Ebola virus disease [EVD]. In these treatment trials, the researchers demonstrated that while remdesivir was infective in treating EVD, it was safe for human use.)
Very commonly, before researchers carry out randomized clinical trials (RCTs) of drugs—commonly considered to be the “gold standard” method for determining efficacy and safety of drugs—they perform studies of drugs in cell cultures. In the case of ivermectin, researchers had conducted an impressive number of such “in vitro” studies before the pandemic which demonstrated that ivermectin had very broad antiviral properties. Thus, scientists were hopeful that this drug might be an effective treatment for those suffering from COVID-19. Research conducted early in the pandemic showed that ivermectin inhibited replication of SARS-CoV-2, the cause of COVID-19, in cell cultures.
In addition to in vitro studies demonstrating ivermectin’s antiviral properties, “in vivo” (animal) studies showed promising anti-viral effects. But disappointedly such encouraging findings often do not translate into successful new treatments for humans. (It is estimated that the chance of a new drug to make it to market is only 1 in 5,000.)
Nonetheless, ivermectin’s antiviral properties in the laboratory coupled with early anecdotal reports of clinical benefits in severely ill COVID-19 patients, catapulted the drug’s popularity. Social media further propelled this enthusiasm. But then negative studies began rolling in, although they received less attention in social media platforms. A preprint of a large clinical trial in Brazil that seemed to show ivermectin reduced COVID-19 death rates by more than 90% was retracted after Internet sleuths raised concerns about plagiarism and data manipulation. How much harm was done before retraction of this preprint is unknown.
In an article in the September 2021 issue of the National Geographic titled “The shaky science behind ivermectin as a COVID-19 cure,” the authors review the story of ivermectin’s rapid rise and disappointing fall in the treatment of COVID-19. Additionally, in an October 2021 BBC Reality Check article “Ivermectin: How false science created a Covid ‘miracle’ drug,” Dr. Kyle Sheldrick, a medical doctor and researcher at the University of New South Wales, said that his research group “had not found ‘a single clinical trial’ claiming to show that ivermectin prevented Covid deaths that did not contain ‘either obvious signs of fabrication or errors so critical they invalidate the study.’”
The Cochrane Collaboration, recognized as the highest standard in evidence-based healthcare, also reviewed many of these studies. It concluded: “Overall, the reliable evidence available does not support the use of ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials.”
The costs of shaky science. We can all understand the hopes and enthusiasm that drugs like ivermectin generated in the desperate early months of the COVID-19 pandemic. (You may recall that former President Trump hyped the benefits of another anti-parasitic “miracle drug,” hydroxychloroquine, for which the FDA went so far as to issue an EUA in March 2020. It too was subsequently found useless.) But bogus claims arising from poorly controlled treatment trials come with substantial costs.
In the article “US Insurer Spending on Ivermectin Prescriptions for COVID-19” published in the January 13, 2022 issue of the Journal of American Medical Association, the authors reported that in one week in August 2021 private insurers and Medicare paid almost $2.5 million for prescriptions of ivermectin to treat COVID-19. The expenditures by insurance companies and Medicare for ivermectin for COVID-19 were estimated at an annualized cost of almost $130 million.
In addition to these monetary costs are direct and indirect costs to human health. The FDA has reported that it “received multiple reports of patients who have required medical attention, including hospitalization, after self-medicating with ivermectin intended for livestock.” In an August 2021 health advisory titled “Rapid Increase in Ivermectin Prescriptions and Reports of Severe Illness Associated with Use of Products Containing Ivermectin to Prevent or Treat COVID-19,” the Center for Disease Control and Prevention detailed the toxicity of ivermectin, including gastrointestinal effects (nausea, vomiting, abdominal pain, and diarrhea), headache, blurred vision, dizziness, tachycardia, hypotension, visual hallucinations, confusion, loss of coordination and balance, and central nervous system depression. And, as was stated in the BBC investigative report: “[I]ndirect harm can come from giving people a false sense of security, especially if they choose ivermectin instead of seeking hospital treatment for Covid, or getting vaccinated in the first place.”
On April 17, 2020 the National Institutes of Health (NIH) launched a public-private partnership to develop a coordinated research strategy for prioritizing and speeding the development of the most promising treatments and vaccines for COVID-19. Since then, hundreds of carefully controlled RCTs of promising therapeutic agents have been and continue to be carried out. ACTIV-6 is one of the series of studies the NIH started.
As a part of this program, last summer doctors at Duke University embarked on a comprehensive study into repurposing three drugs for use in fighting COVID-19—ivermectin is one of them. As Dr. Adrian Hernandez, one of the leaders in the study, said “There were some early studies that showed that [ivermectin] could be potentially helpful with COVID-19, but they were not large enough to be definitive…so we want to know either way, is it potentially beneficial or not.” (Under the COVID-OUT study, the University of Minnesota is also evaluating three common drugs, ivermectin being one, to see if they have any utility as a treatment for COVID-19.)
It may take some months before the results of the research at Duke (or the University of Minnesota) are known. In the meantime, we do know that ivermectin is highly effective in fighting serious parasitic infections. It prevents countless cases of heartworm disease in dogs and cats. More important, it prevents blindness in tens of thousands in Africa as well as in Latin America. In the battle against river blindness, it is a “miracle drug.”
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