To conduct her research, she has been using the zebrafish – a 5cm long tropical fish native to Southeast Asia. She says “they are globally becoming immensely popular in drug discovery research, as well as research into drug safety.”
She adds, “What makes zebrafish such an amazing research tool is that they are genetically more like humans than rodents – and can be used to match behavioural data to physiology. In other words, we can probe specific physiological mechanisms and correlate it with the behavioural outcome it will facilitate.”
Neurological risk
She describes how ivermctin is a known anti-parasitic, and that even when used at the low doses indicated for use against parasites, it is linked to many adverse effects suggestive of neurological risk. This includes dizziness, headache, seizures, and loss of consciousness.
“We decided to probe different potential neurological risks, she says.
Methods
Three methods were used.
“Firstly, we treated zebrafish larvae with pure ivermectin and veterinary ivermectin – using a specific test to probe GABA function. We saw that both formulations resulted in seizures in zebrafish at the higher doses which are suggested to be anti-viral,” she says.
“This outcome is in line with the adverse effects reported by humans after ivermectin use and suggest a direct effect to inhibit GABA. GABA is an inhibitory neurotransmitter which protects the brain from excitotoxicity – an overstimulation of neurons which eventually lead to neuronal death.”
They also exposed larvae to alternating bright light or darkness. “Normally, this will induce anxiety-like behaviour in the zebrafish (they show a startled response to bright light and freeze, and then when the light is removed, they show increased hyperlocomotion, which is interpreted as anxiety and escape behaviour.
“We found that ivermectin-treated larvae showed a dulled response to this protocol, suggesting limited cognitive function,” she explains.
Lastly, she says, “they probed the effect of ivermectin when the blood brain barrier is leaky, as this happens during viral infection such as Covid-19. Literature has shown ivermectin to interact with SARS viruses to make the blood brain barrier – a layer that keeps unwanted substances from the bloodstream out of the brain – even more penetrable.”
Findings
“Our data indicated that even a short-duration exposure to ivermectin in these conditions, resulted in long-lasting neurocognitive limitations,” says Professor Smith.
“Thus, our research shows that ivermectin – and specifically the veterinary formulation – should not be used at the high doses thought to be effective against viruses.
“Even at the doses indicated as anti-parasitic, should be investigated a bit more thoroughly, given the symptoms reported, which are in line with the neurological risk we have demonstrated.”
Smith says the research is unique in that it specifically aligns with a real-life problem.
She adds that zebrafish as research tool has only really been used for about 10 years globally and is much more recent in South Africa.
Ivermectin now prohibited
Shortly after the study, SAPHRA – the medicines control body in South Africa – prohibited the use of ivermectin under any condition.
“Ivermectin will always have a place to prevent or treat parasitic infections in animals, for example as a dip. It is important to note that the effect of a periodical acute application of ivermectin in animals is different from a long-term daily/weekly dose of ivermectin in people using it as preventative treatment in the context of viral infection.
“Thus, human use of ivermectin especially as prophylactic, should not be encouraged.”
DID YOU KNOW?
A new study conducted on zebrafish has confirmed that the consumption of rooibos tea – and specifically unfermented or green rooibos – helps to reduce anxiety. Rooibos tea (Aspalathus linearis) is a uniquely South African product which grows mainly in the Cederberg area of the Western Cape. Its beneficial properties range from its caffeine-free and anti-inflammatory nature to the antioxidants, vital minerals and vitamins it contains. It also plays a positive role in pain and allergy reduction and in heart health.