Ivermectin was discovered in 1975. It is a powerful antiparasitic drug that has the potential to be used to cure diseases caused by parasites, among other uses. It was discovered by William Campbell and Satoshi Omura both of whom won the Nobel Prize for Physiology or Medicine in 2015 due to the hugely beneficial impact the drug they found was having on the world.
One of the groups who have benefited most from this novel compound is patients with onchocerciasis (river blindness). This disease is caused by infection with Onchocerca volvulus roundworms and affects over 18 million people in Africa, Arabia, and South America. It is one of six neglected tropical diseases that was targeted for eradication by 2020 under an initiative launched in January 2012 at the London Summit on Neglected Tropical Diseases (NTDs).
The Global Network for Neglected Tropical Diseases (Global Network) welcomed the London Summit’s reaffirmation that all people with onchocerciasis and lymphatic filariasis should receive treatment with the medicines they need as a foundation of NTD control, elimination, and eradication.
In 1987 Merck & Co., Inc., through its affiliate Merial Limited, donated Ivermectin for use in programs to eliminate lymphatic filariasis (LF) from selected countries in Africa. In subsequent years, donations were provided by both Merck and The Mectizan Donation Program (MDP) to support the goal of total elimination of LF as a public health problem in Africa within 10–15 years. These donations have totaled approximately $3 billion since 1988 and have resulted in more than 1 billion treatments being delivered throughout the African continent.
Ivermectin was found to be highly effective against several species of parasitic worms that cause river blindness, lymphatic filariasis, onchocerciasis, and strongyloidiasis. Ivermectin also kills some arthropods (e.g., scabies mites) that cause itching and may reduce pruritus in patients with chronic skin disease.
The drug was marketed under the brand name Stromectol by Merck & Co., Inc., which was patented until 2015. Now that the patent has expired, any pharmaceutical company can produce generic versions of it. Currently, in 2021, ivermectin is marketed by many pharmaceutical companies under many brand names.
Ivermectin has had an amazing effect on the world of medicine since its discovery in 1975, it has been used to cure diseases caused by parasites and treat some other medical issues that affect people all around the world. The impact this drug has had on society is monumental and will likely continue into the future as Ivermectin continues to be researched and discovered to have even more uses than it already does.
The Discovery of Ivermectin
Ivermectin was discovered by Satoshi Ōmura, Ph.D. (born September 1, 1939, in Tokyo) and William C. Campbell, Ph.D. (born February 19, 1931, in Sault Ste. Marie, Michigan, USA), both of whom are Americans. These scientists shared the Nobel Prize for Physiology or Medicine in 2015 with Youyou Tu for “the discovery of a novel therapy against infections caused by roundworm parasites [entamoeba]”.
Ivermectin became available in 1981 in Japan under the brand name Stromectol(R) On 5 August 1987 Merck & Co., Inc. through its affiliate Merial Limited began donating ivermectin annually to medicate children against parasitic worms that cause lymphatic filariasis and onchocerciasis in certain developing countries. In subsequent years, ivermectin use expanded to include the treatment of onchocerciasis in all endemic countries and for lymphatic filariasis in some of them.
Donations continued on as recently as 2013 at the request of The Carter Center, which coordinates onchocerciasis programs in West Africa.
Ivermectin was approved by the US Food and Drug Administration in February 1981 for the treatment of strongyloidiasis in combination with two other anti-infectives. It is also used in veterinary medicine to treat parasitic infections of domestic animals.
Ivermectin has been used more recently to treat people who are infected with distant species of intestinal helminths (worms), including Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Enterobius vermicular (pinworm), Trichuris trichiura (whipworm), Taenia saginata (beef tapeworm), Diphyllobothrium latum (broad fish tapeworm) and Hymenolepis nana (dwarf tapeworm).
Ivermectin in the Treatment of Parasitic Diseases
The mycelium (part of the fungal body) is cultured in large, cylindrical tanks with agitating baffles inside to keep the fungus growing in suspension throughout the fermentation process. Solid-state fermentation is conducted when growth stops or when nutrients become depleted.
Solid-state fermentation is a method used to produce metabolites from microorganisms by culturing them on a solid support matrix such as rice, sawdust, or any other form of biomass. The method has been used for thousands of years to produce fermented foods and beverages such as bread, yogurt, cheese, and soy sauce.
Once the mycelium is grown, it is harvested and dried before a purified water extraction can take place to obtain the desired metabolites from the fungal culture.
The process through which Ivermectin is isolated from cultured fungi includes five main steps: production of a liquid fermenter culture; milling of the solid fermentation substrate into a fine powder; preparation of a homogenate from this substrate; separation of insoluble fraction by centrifugation; concentration and further purification steps may be needed.
Ivermectin belongs to a class of macrocyclic lactone drugs that are mainly used in antiparasitic therapy to eliminate parasitic worms (helminths).
Ivermectin is a mixture of at least 80% 22-membered macrolides making it difficult for the parasite to uptake ivermectin. It works by opening glutamate-gated chloride ion channels that are localized on the invertebrate neuromuscular membrane, leading to hyperpolarization and paralysis of the parasite muscles.
The drug has low toxicity for mammals yet dissociates slowly from its site(s) of action, allowing prolonged exposure. This allows for its use against parasites with shorter life cycles, such as Strongyloides stercoralis. Ivermectin is safe for use in both the young and old, including children as young as six months of age. It is effective against a broad spectrum of parasites at all developmental stages including adult worms.
Ivermectin comes in oral pill form that must be taken with water. Side effects are generally minimal at therapeutic doses although infrequent adverse reactions include dizziness, headache, itchiness, nausea, and allergic reactions.
Ivermectin reduces microfilariae by 99% within 16 hours after administration with a maximum effect between days 4 and 6. It is most effective when there are few microfilariae present in the blood circulation.
Ivermectin does not have any sterilizing activity, which means that adult worms may continue to produce new microfilariae until they die after 2 to 3 months.
After a single dose of oral ivermectin, 98% of patients with onchocerciasis are found to have no live parasites detectable by microscopy 60–72 hours later. Ivermectin kills all stages of the worm so it will be effective for life if given annually or semi-annually.
It can be used for both lymphatic filariasis and loiasis but because L3 larvae are more sensitive to ivermectin than adult worms, the treatment produces better results when it is used to prevent the development of lymphatic filariasis by killing microfilariae.
Ivermectin kills larvae and adults of Brugia malayi but not their microfilariae. However, a single dose of oral ivermectin given annually or semi-annually reduces microfilaremia for up to 12 months after treatment in infected individuals.
It kills fourth-stage larvae (L4) of Dirofilaria immitis but does not kill the adult worms so it must be administered once yearly to prevent heartworm disease. This drug has been proven safe and effective for use dogs at a dosage rate of 6mg/kg once a year.
One of the WHO’s Most Essential Medicines
Ivermectin is on the WHO’s list of the world’s Most Essential Medicines. The WHO’s Expert Committee on the Selection and Use of Essential Medicines recommended Ivermectin in November 1987, and it remains on the list until this very day.
It was approved by the U.S. Food and Drug Administration in 1996 under the brand name Stromectol for the treatment of various parasitic diseases, including strongyloidiasis, ascariasis, trichuriasis, hookworm infection, and lymphatic filariasis.
In early studies conducted between 1981-1983 atlingame County Hospital involving 638 people with ocular onchocerciasis, ivermectin was found to reduce the number of microfilariae in the blood circulation by 99% within 4 weeks and skin snips were negative for microfilariae 12 weeks after treatment. More than 95% of patients were reported cured 4 years later.
In 1987, Merck & Co. applied for a patent for using Ivermectin as an antiparasitic drug and received its first patent protecting it until 2003. The FDA approved another Ivermectin patent in 1993 which extended protection until 2015. Ivermectin is still used today as an important public health tool.
Ivermectin and Coronavirus
Recent studies and use in real-life applications show Ivermectin to be effective against coronaviruses. Even before covid-19, it was known that Ivermectin had a powerful effect in eliminating other coronavirus variants. It is suggested that Ivermectin inhibits the release of viral particles by reducing envelope glycoprotein expression.
Ivermectin was discovered to be effective against covid-19 by a number of doctors around the world, yet despite this, a smear campaign has been run against this wonder drug, in an attempt to destroy its reputation so that other drugs and vaccines that are more profitable can be used instead.
Despite the WHO and CDC’s best efforts to make Ivermectin appear to be unsafe to use, decades of research and studies make it clear that this is not the case, and the drug has so far shown to be extremely effective in combating SARS-COV-2 and has also shown to have a positive effect against the spike protein in patients who are suffering the side effects of vaccines.