Can you explain ivermectin?
During the 1970s, the Kitasato Institute in Japan and Merck & Co collaborated to develop Ivermectin, an anti-parasitic medication. Satoshi Omura and William Campbell spearheaded the project on their respective sides. With its ability to combat internal and external parasites, Ivermectin significantly enhanced animal health and productivity, leading to its rapid success as a widely used drug in the veterinary industry.
In the 1970s, the global community was engaged in a battle against river blindness, scientifically called onchocerciasis, which inflicted severe hardships on rural communities due to the Onchocerca volvulus parasite. The World Bank played a significant role in achieving certain accomplishments in this fight. However, it was observed that introducing ivermectin as a commercial drug led to a remarkable decline in the prevalence of Onchocerca cervicalis, the causative agent of onchocerciasis in horses, in the regions where this innovative medication was utilized.
authorities in the early 1980s marked a turning point in the efforts to test ivermectin in humans. This led to an unprecedented decision by Merck & Co. to generously donate as much ivermectin as necessary to eradicate river blindness. Thus, the Mectizan donation program was born. Over the past 30 years, this program has successfully distributed over 3 billion treatments, resulting in the saving of numerous lives. Furthermore, the program has expanded its scope to include Lymphatic filariasis, another debilitating disease caused by filarial worms.
In 2015, the Nobel Prize for Physiology or Medicine was bestowed upon Omura and Campbell for their groundbreaking discovery. This prestigious recognition was also shared with Tu Youyou, the esteemed Chinese researcher who uncovered the antimalarial artemisinin.
What are the applications of ivermectin in human medicine?
In this article, we will outline several of the authorized applications worldwide.
In the United States, ivermectin is available in doses of up to 200 mcg/kg once annually for specified medical conditions.
Strongyloides stercoralis is a gastrointestinal parasite with the potential to induce serious systemic illness.
Onchocerciasis or river blindness
In Europe, ivermectin is additionally available for the treatment of Lymphatic filariasis and scabies, with recommended single doses of up to 400 mcg/kg.
To effectively treat severe crusted scabies in Australia, it is recommended to administer three or more doses of 200 mcg/kg within a month.
Are there any other verified or possible applications?
Despite not being specifically promoted for these purposes, ivermectin demonstrates limited effectiveness against various prevalent intestinal parasites in humans, including Ascaris lumbricoides and Trichuris trichiura. Additionally, it is occasionally utilized off-label to combat ectoparasites like head lice and Tunga penetrans, along with numerous internal or external parasites.
A noteworthy area of research, in which ISGlobal scientists have actively participated, involves the utilization of ivermectin on a population scale to eradicate mosquitoes that feed on individuals or animals treated with the drug, thereby reducing the transmission of malaria.
Is the safety of ivermectin assured?
Ivermectin is considered a highly safe medication when used for its intended purposes and at the recommended dosages. The Mectizan Donation Program has distributed over three billion treatments, highlighting its widespread use and positive safety record. Adverse reactions, if any, are typically mild, temporary, and primarily linked to the elimination of parasites rather than the drug's direct effects.
Ivermectin specifically acts on the glutamate-gated chloride channels found exclusively in invertebrates. However, mammals possess a similar channel, the GABA-gated chloride channel, which may have some interaction with ivermectin. Nevertheless, these channels are only found in the central nervous system of mammals and are safeguarded by the blood-brain barrier. The blood-brain barrier is a system of pumps that prevents potential toxins from entering our nervous system. Despite these protective measures, Rebecca Chandler reported a series of 28 cases where severe neurological adverse reactions occurred after administering ivermectin outside of areas endemic to onchocerciasis.
Ivermectin specifically targets the glutamate-gated chloride channels that are exclusively present in invertebrates. However, mammals have a similar channel known as the GABA-gated chloride channel, which may have some interaction with ivermectin. Nevertheless, these channels are only found in the central nervous system of mammals and are protected by the blood-brain barrier. The blood-brain barrier is a system of pumps that prevents potential toxins from entering our nervous system. Despite these protective measures, Rebecca Chandler documented a series of 28 cases where severe neurological adverse reactions occurred after the administration of ivermectin in areas not endemic to onchocerciasis.
There is insufficient evidence to endorse the utilization of ivermectin in children weighing less than 15 kg. Furthermore, there is no evidence to support the administration of ivermectin during pregnancy.
Is it safe to use higher doses of ivermectin than what is approved?
Guzzo et al. carried out a research study involving increasing amounts of ivermectin. Several participants were administered doses of up to 2,000 mcg/kg, which is equivalent to ten times the recommended dosage for onchocerciasis, without experiencing any adverse effects.
Transient visual disturbances have been occasionally reported by individuals who have received doses of ivermectin at 800 mcg/kg or higher in various studies, despite Guzzo not providing any description of such occurrences.
Is ivermectin effective against viruses?
Indeed, Ivermectin has demonstrated its efficacy in suppressing the replication of various RNA viruses, including:
Dengue
Zika
Yellow fever
West Nile
Chikungunya
Venezuelan equine encephalitis
Semliki Forest virus
Sindbis virus
Porcine reproductive and respiratory syndrome virus, and recently
SARS-CoV-2
Is there a potential for ivermectin to be utilized in the management or prevention of COVID-19?
However, the solution is not simple.
The in vitro experiments conducted by Caly et al. involved the addition of ivermectin into a cellular culture infected with the virus on a petri dish. In these experiments, the concentrations of 2.8 and 5 microMolar were found to reduce the viral replication by 50% and 99% respectively.
To provide a comparison, it is important to note that the highest level of concentration reached in the bloodstream following a single oral dosage of 200 mcg/kg (which is the typical dosage for treating river blindness) is 40 ng/ml. On the other hand, 2.8 microMolar is equivalent to 2,450 ng/ml, meaning it is 60 times greater than the maximum concentration achieved with usual doses or 10 times higher than the maximum concentration observed in the high-dose Guzzo study.
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