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It’s Time To Talk About Ivermectin

I’d like to start this article with a couple of disclaimers and a caveat. First of all, I am not a medical doctor. This article is not intended as medical advice. It’s a layman’s account of how an extremely cheap, safe and widely available off-patent medicine called ivermectin appears to be saving the lives of countless Covid-19 patients across Latin America and beyond. Yet hardly anybody is talking about it.  Here’s the caveat: The first section of the article, which was completed on Friday, is about Mexico City’s recent deployment of ivermectin in its fight against Covid-19. On Saturday, Mexico’s Ministry of Health jacked up its total excess death count due to Covid (for the whole country) by 60%, from 182,000 to 294,000. However, most of these deaths took place before Mexico City began

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I’d like to start this article with a couple of disclaimers and a caveat. First of all, I am not a medical doctor. This article is not intended as medical advice. It’s a layman’s account of how an extremely cheap, safe and widely available off-patent medicine called ivermectin appears to be saving the lives of countless Covid-19 patients across Latin America and beyond. Yet hardly anybody is talking about it. 

Here’s the caveat: The first section of the article, which was completed on Friday, is about Mexico City’s recent deployment of ivermectin in its fight against Covid-19. On Saturday, Mexico’s Ministry of Health jacked up its total excess death count due to Covid (for the whole country) by 60%, from 182,000 to 294,000. However, most of these deaths took place before Mexico City began using ivermectin as part of its its test-and-treat approach to Covid.

Covid-19 vaccines are reaching most emerging and developing economies in only drips and drabs, with a few notable exceptions such as Chile. In many countries, locking down entire cities or regions and paying millions of non-essential workers not to work while front-line doctors and nurses battle to contain the virus is not an option. There simply isn’t enough money available. This has left doctors and health authorities with little choice but to try out cheap, widely available generic medicines. Those drugs include ivermectin, a “well-studied, well tolerated,” (in the words of a 2013 FT article) off-patent anti-parasitical.

The results have been extremely promising, according to almost all of the clinical studies conducted thus far. Many of the studies took place in Latin America where around half of the countries in the region have used or are using ivermectin to some degree or another. A meta analysis of 42 clinical trials, involving approximately 15,000 patients, found that 83% showed improvements with early treatment, 51% improved during late-stage
treatment and there was an 89% prevention of onset rate noted. Yet the studies have received scant attention in more advanced economies — so much so that the vast majority of the people I talk to here in Europe have still not even heard of the medicine. 

Bucking the Trend

On December 29th of last year, Mexico’s Institute of Socal Security (IMSS) allowed ivermectin to be prescribed to outpatients with Covid. On the same day the Secretariat of Health of Mexico City and the State of Mexico decided to adopt a protocol in which anyone testing positive at any one of the city’s 250 rapid testing sites would be given ivermectin. As you can see in the graphs below, courtesy of Juan Chamie, a data scientist from EAFIT University in Colombia, based on data provided by Mexico City authorities, the number of hospitalizations due to Covid and excess deaths peaked shortly after the New Year and have been falling sharply ever since. They are now almost back to their prior base line. 


Mexico City is the first major global city to adopt what amounts to a test-and-treat approach to covid-19 involving ivermectin. But it was the largely indigenous southern state of Chiapas that led the way last summer. In July 2020, as Mexico was buckling under its first wave of the pandemic, the state decided to distribute ivermectin as a Covid-19 treatment, having already deployed the medicine in its battle against mosquito-borne RNA viruses such as Zika and Chikungunya. Since October Chiapas has consistently occupied the lowest risk level on the federal government’s coronavirus stoplight map.

Thanks to ivermectin’s apparent success in Chiapas, IMSS allowed the medicine to be prescribed nationwide. It also helped launch the pilot program in Mexico City, for which it received a barrage of criticism. An official group of health experts argued that there’s no scientific evidence that the drug is effective, and called for the immediate repeal of its use. To their credit, both the Secretariat and IMSS have stuck to their guns.

Playing With Lives

Of course, there’s no way of definitively proving that the rapid falloff in hospitalizations and deaths, first in Chiapas and then Mexico City, is due to the use of ivermectin. Correlation, as we well know, is not causation. It’s also true that Mexico City authorities have introduced tougher social distancing measures and travel restrictions since December. But similar dramatic drop offs have been witnessed in other regions and countries where ivermectin has been used widely, including across the length and breadth of Peru and Iran as well as parts of Brazil, Paraguay, Bolivia, the Dominican Republic and India.

In Peru, ivermectin was used in eight states during the very early stages of the pandemic (May-July). Its use was then extended to the whole country except Lima, which did not start deploying the drug until months later. For the 24 states with early IVM treatment (and Lima), excess deaths dropped 59% (25%) at +30 days and 75% (25%) at +45 days after day of peak deaths. But in October, after the first wave had been brought under control, the new government in Peru took the inexplicable step of withdrawing a number of medicines, including ivermectin, from its treatment guide for the disease. Within weeks hospitalizations and deaths were soaring once again.

The following graph, taken from a study by Juan Chamie, Jennifer Hibberd of the University of Toronto and David Scheim of the US Public Health Service, shows the sharp rise, fall and resurgence in excess deaths (among the over 60 year-old cohort) in Peru as the virus waxed, waned and waxed again. Between August and December case fatalities dropped sharply in all states but Lima, yet six indices of Google-tracked community mobility rose over the same period, before rising once again. In other words, the treatment appeared to be working even as the country reopened. 


In the Brazilian city of Belem authorities began using ivermectin way back in June 2020. Since then the city has managed to escape the massive surge in covid-related deaths that has plagued Brazil since early November, as the graphic below shows. In another study a like-for-like comparison of cities in similar regions of Brazil showed that the cities that began distributing ivermectin in June last year were, by September, registering much lower case counts than those that didn’t.    


Iran has also seen a sharp fall in covid-related deaths since late November followed by a flattening of the curve. Earlier that month the country, with a similar population to Germany and an urban population density twice as high, succeeded in gaining the technical knowledge to produce ivermectin and began distributing it to hospitals in the country. 


What is Ivermectin?

First discovered in 1975 and launched onto the market in 1981, ivermectin is a safe, broad-spectrum anthelminthic drug registered for the treatment of a number of neglected tropical diseases (NTDs) including river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis, and lymphatic filariasis. It is also used widely in veterinary medicine. In recent years it has been discovered to have strong anti-viral properties against RNA viruses such as zika and yellow fever. In its use against river blindness in Africa it is estimated to have prevented 7 million years of disability.

The medicine is not only extremely effective in treating a broad range of illnesses, including RNA viruses; it is also well tolerated. To date, more than 3.7 billion doses have been distributed with an excellent safety profile. Most adverse reactions are mild, transitory and associated with parasite death rather than with the drug itself.

“The reason why this medicine is distributed in Africa not by doctors and nurses but mainly by volunteers is that it is extremely safe,” says Japanese microbiologist Satoshi Omura, who jointly with the Irish parasitologist William C. Campbell, led the team that isolated a strain of Streptomyces avermitilis that produce the anti-parasitical compound avermectin, the active ingredient in ivermectin. Omura and Campbell were awarded the Nobel Prize for Medicine in 2015 for their discovery.

Dr. Omura himself believes there’s already enough evidence of the benefits of ivermectin against Covid-19 for it to be granted approval as a therapeutic. One of its biggest benefits is that it appears to work in the early stages of the disease, he co-writes in an article published earlier this month in the Japanese Journal of Antibiotics:

“Currently, there are no therapeutic agents available for mildly ill patients who are being treated at home (or in self-isolating accommodations) or for moderately ill hospitalized patients. Nothing is as helpless as a disease without a cure.”    

Anti-Viral, Anti-Inflammatory, Anti-Long Haul

Another major ivermectin proponent is the Frontline Covid-19 Critical Care Alliance (FLCCC), which has been trying to repurpose medicines already on the market for the treatment of Covid-19. In October it created the I-MASK+ protocol for prevention and early outpatient treatment, which includes ivermectin, vitamin D3, vitamin C, zinc, melatonin and quercetin. 

The FLCCC believes that ivermectin is not only “one of the world’s safest, cheapest and most widely available drugs,” it is also the most effective against Covid. “The studies we presented to the NIH revealed high levels of statistical significance showing large magnitude benefit in transmission rates, need for hospitalization and death,” says Dr. Pierre Kory of the FLCCC, who twice gave testimony to the US Congress on Covid-19.

Besides the dozens of clinical studies conducted so far on the efficacy of ivermectin against Covid, the FLCCC also cites “natural experiments” in Peru, Brazil, Paraguay, the Dominican Republic and Mexico where ivermectin was distributed widely, with “large decreases in case counts … soon after distribution began.”

Another recent convert to the cause is Dr Alessandro Santin, a renowned cancer researcher who runs a large laboratory at Yale. Santin believes that ivermectin is a game-changer that could significantly reduce Covid’s toll on human health.

“The bottom line is that ivermectin works. I’ve seen that in my patients as well as treating my own family in Italy,” Santin said, in reference to his father, 88, who recently suffered a serious bout of COVID. “We must find a way to administer it on a large scale.”

In an interview with Italian daily Il Fatto Quotidiano, Santin explains why he believes ivermectin is so effective against Covid:

  • Its powerful anti-viral properties: “The theory behind the main mechanism of action is that ivermectin attaches itself to Sars-Cov2’s Spike1 protein as well as at various strategic points used by the virus to bind and enter our cells. This is why it can also work against variants, unlike monoclonal antibodies.”
  • Its anti-inflammatory activity: “Ivermectin has a powerful anti-inflammatory effect similar to that of cortisone. But unlike with cortisone, the effect is not immunosuppressive. Therefore the immune response of both T cells and B cells (producing antibodies) continues to function under ivermectin, acting on the transcription factor NF-KB (which informs our body to produce cytokines and causes a real cytokine storm when hyperactivated by Covid). This is why the drug also works well during the advanced phase of the disease”.
  • It even seems to help long-haulers: “I have treated and am treating ‘long haulers’, including people who have been sick for a year and who do not breathe well, who have tried out everything to no avail. Within two weeks of starting them on ivermectin… these people have started to live again, with practically no side effects. The virus is an intracellular parasite; only if it enters our cells can it use the cellular machine to replicate. If it can’t get in and hack our immune system, then it stays out on the doormat and gets attacked by our immune system much more easily.”

More Evidence Needed, Say Regulators

Yet despite the growing body of evidence supporting ivermectin’s therapeutic effects against SARS-Cov2, national and supranational health authorities, particularly in more advanced economies, are dragging their feet. The European Medicines Agency (EMA) concluded this week that the available data “do not support its use for COVID-19 outside well-designed clinical trials”. The decision comes just two months after Slovakia and Czechia became the first EU countries to approve the temporary use of ivermectin against Sars COV-2.

In the US Ivermectin is not yet FDA-approved for the treatment of COVID-19, but in January the NIH changed their recommendation for the use of ivermectin in COVID-19 from “against” to “neutral”. This is a major step forward. As a result, doctors are at liberty to prescribe ivermectin for Covid patients. 

But most regulators and expert panels insist that definitive proof is still lacking, despite the abundance of real world data, and have called for randomized placebo controlled double blinded studies. But that is time consuming and time is a luxury most doctors and their patients can ill afford right now. As covid continues to rage and patients continue to die, growing numbers of doctors feel that the risk of doing nothing, particularly in the early stages of the illness, significantly outweighs the risk of doing something — especially if that something has already been shown to work across multiple trials and real-world experiments. 

“Clinical trials take time, but because of the abundance of overseas data, it may not be necessary to conduct clinical trials in Japan,” says Omura. “Experts have shown the numbers and announced that they are working. Therefore, I would like [the Japanese health authority] to grant it special approval. If you do not use it here, what is the special approval system for? Some people will die if they are waiting for a clinical trial.”

According to a WHO-sponsored review and meta-analysis of 18 clinical studies, the drug could cut the number of deaths from Covid-19 by as much as 75%. Crucially, some of the studies suggest that it is effective not only as a treatment in the early and later stages of the virus but also as a prophylactic. Yet the conclusion of the WHO-sponsored review is that more studies are needed.

Contrast this with the FDA and EMA’s mad rush to approve the anti-viral medicine Remdisivir for use against SARS-CoV-2 last October, despite the medicine’s lackluster performance in clinical studies and unproven safety record. On October 15, results from WHO’s Solidarity trial suggest that remdesivir does not even reduce mortality or the time COVID-19 patients take to recover. Yet a week later the FDA approved the drug for use against SARS-CoV-2 in the US, becoming the first drug to receive that status.

With a five-day course of treatment costing around $2,600 per person, there’s a lot of money to be made for remdesivir’s manufacturer, Gilead. Once remdesivir was approved in the US and the EU, it set off a cascade of approvals across the world, including in countries such as Brazil and Mexico whose public health systems cannot possibly afford to administer it on a large scale. In this case that is a good thing given how ineffective the drug appears to be. 

Meanwhile, a Nobel-prize winning medicine that has been used extensively for four decades and costs just a few dollars per course of treatment could prove to be one of our best lines of defense again covid. Time and again it has been shown to work. Yet for the moment most health authorities in advanced economies — and quite a few in less advanced ones (South Africa, the Philippines, Peru…) — do not seem to be interested. In the coming days the World Health Organization is expected to come out with a definitive recommendation for or against ivermectin. If it opts for the latter, the pressure on doctors to stop using it will only increase.

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