Christine King BVSc, MANZCVS (equine), MVetClinStud
Ivermectin and the Hendra virus
lessons from COVID-19
The coronavirus (COVID-19) pandemic has resulted in some surprising discoveries. One is that ivermectin (yes, that ivermectin, the anthelminthic drug) is a broad-spectrum antiviral agent, inhibiting a wide variety of viruses.
Ivermectin is antiviral
It's been known for awhile in research circles (e.g., in virology labs) that ivermectin has antiviral properties. However, it hasn't been used clinically (i.e., in patients with naturally occurring disease) as an antiviral agent until now.
Based on laboratory confirmation that ivermectin inhibits SARS-CoV-2 (the novel coronavirus that causes COVID-19), doctors in many different countries have been using ivermectin in the treatment and prevention of COVID. More on that in a bit.
A recent laboratory study showed that ivermectin also inhibits the viruses that contribute to the bovine respiratory disease (BRD) complex in cattle:
The way ivermectin inhibits viral activity within a cell is complex — because viral replication is a complex process. In essence, ivermectin blocks the virus from entering the cell's nucleus and disabling a key component of the cell's antiviral response. In other words, ivermectin blocks one of the critical steps involved in virus replication.
A note of caution before we go on: the molecule blocked by ivermectin — called importin alpha, or IMP𝛂 — is a nuclear transporter protein that aids the transport ('import') of molecules from the cytoplasm of the cell into the nucleus. However, IMP𝛂 is involved in a variety of normal cell functions, including antiviral responses. So, although many different viruses 'hijack' this transporter protein for their own purposes, it is not a good idea to persistenty or permanently block IMP𝛂 in order to block virus replication. To do so would block normal cell functions as well — including the ability to mount an antiviral response.
We don't yet know the optimal dosage of ivermectin as an antiviral agent. Its clinical use in this regard is still very new, and much is yet to be learned. However, we can begin to make some tentative deductions.
As of January 2021, there were almost 70 clinical trials underway worldwide on the safety and effectiveness of ivermectin for the treatment or prevention of COVID-19 in humans. (Most have been completed, but some are still ongoing.)
The striking thing to me is that many of those trials used ivermectin dosages that are the same as what we use in horses as an anthelminthic agent: 0.2 mg/kg (200 µg/kg) bodyweight. This dosage is also used for anthelminthic treatment in humans, which is probably why it was chosen in numerous studies: it is known to be well tolerated in humans.
Higher dosages (up to 0.6 mg/kg, or 600 µg/kg, bodyweight) are used in humans for certain parasitic diseases, and these higher dosages have been used in some of the COVID trials and in at least one current treatment protocol (see below).
Some trials used a single oral dose of ivermectin; others repeated the dose daily for up to 7 days, or gave 2 doses spaced at least 2 days apart (e.g., on Days 1 and 3). The optimal dosing regimen remains to be determined, but in none of these trials was dosing repeated for more than 7 days in a row.
Perhaps the most comprehensive review to date was published by the Front Line COVID-19 Critical Care Alliance (FLCCC), a group of critical-care physicians. The current (11 Aug 2021) FLCCC guidelines, which target the delta variant, recommend the following:
This early treatment protocol also includes supplemental vitamin D3, vitamin C, quercetin, melatonin, zinc, and aspirin, along with oral/nasal 'sanitation' treatments. It does not rely on ivermectin alone.
The FLCCC considers ivermectin to be a core medication for the treatment of COVID-19 in hospitalised patients and they advise giving it on admission to hospital. Even so, it is used in combination with numerous other medications and supplements.
This research raises a lot of questions for me. An obvious one is whether ivermectin might be useful in the treatment of serious viral infections in horses for which we don't currently have very good or cost-effective treatments, such as the neurologic form of equine herpesvirus type 1 (EHV-1), Murray Valley encephalitis virus, Kunjin virus (Australian strain of West Nile virus), and, of course, HeV. It is possible that horses with Ross River virus infection might also benefit, although I have not found definitive evidence that ivermectin blocks this particular virus.
Given the potential for HeV to spread to other horses and to humans, it is reasonable to ask whether we should even be attempting to treat HeV infection in horses. I would answer that with an emphatic yes! It's not the politically correct answer, but it's a medically sound one — not to mention a compassionate one.
As I discuss in the multi-part article on HeV in horses, HeV infection is not universally fatal in horses; some infected horses recover — and others don't even become ill when infected with HeV. Furthermore, experimental studies have shown that HeV is not highly contagious.
Yes, let's isolate any suspect case while awaiting HeV test results. And let's take all appropriate precautions with personal protective equipment to ensure that we don't become infected ourselves or spread the virus when handling these horses. But let's also treat these sick horses while we're waiting!
And even if the test comes back positive for HeV, where's the harm in continuing to treat the horse symptomatically and with ivermectin, guided by what we've learned from the human clinical trials of ivermectin for the treatment and prevention of COVID?
Just one note of caution about using ivermectin in horses to prevent HeV infection. Although it may turn out to be a worthwhile preventive strategy in still-healthy horses exposed to a HeV-infected horse, it is not a wise long-term strategy.
Quite apart from the fact that ivermectin blocks a normal and necessary nuclear transporter protein, ivermectin is still one of the most important anthelminthic drugs we have for horses. Overuse speeds the development of drug resistance in parasites, not just to ivermectin but to all other drugs in its class (abamectin, moxidectin, etc.).
If you are choosing not to vaccinate your horse against HeV, then save the ivermectin for situations in which there is a fairly high degree of risk that your horse has been exposed to HeV, whether from a sick horse or directly from flying-foxes. And then use it only for the period of high risk.
Because we need ivermectin to remain a highly effective anthelminthic drug in horses, it would be better to resolve the risk of HeV infection so that ongoing treatment with ivermectin is unnecessary. Rather than continuing with ivermectin every week*, as currently recommended for COVID-19 in high-risk people, do whatever is needed in the situation to prevent further exposure to HeV.
1. Since 2012, multiple in vitro studies have demonstrated that ivermectin inhibits the replication of many viruses, including influenza, Zika, Dengue, and others.
2. Ivermectin inhibits SARS-CoV-2 replication and binding to host tissue via several observed and proposed mechanisms.
3. Ivermectin has potent anti-inflammatory properties with in vitro data demonstrating profound inhibition of both cytokine production and transcription of nuclear factor-κB (NF-κB), the most potent mediator of inflammation.
4. Ivermectin significantly diminishes viral load and protects against organ damage in multiple animal models when infected with SARS-CoV-2 or similar coronaviruses.
5. Ivermectin prevents transmission and development of COVID-19 disease in those exposed to infected patients.
6. Ivermectin hastens recovery and prevents deterioration in patients with mild to moderate disease treated early after symptoms.
7. Ivermectin hastens recovery and avoidance of ICU admission and death in hospitalized patients.
8. Ivermectin reduces mortality in critically ill patients with COVID-19.
9. Ivermectin leads to striking reductions in case-fatality rates in regions with widespread use.
10. The safety, availability, and cost of ivermectin is nearly unparalleled, given its near nil drug interactions, along with only mild and rare side effects observed in almost 40 years of use and billions of doses administered.
11. T h e W o r l d H e a l t h O r g a n i z a t i o n