MAIL AND GUARDIAN
How South Africa’s ivermectin use slips through the cracks
Masilo Mopai’s shift never ends. He’s been on-call around the clock for 14 years.
The compliance officer works at the South African Health Products Regulatory Authority (Sahpra), the country’s medicines regulator.
Masilo always keeps an overnight bag packed and ready in case he needs to leave. When his phone rings at night, it’s usually someone from the directorate for crime investigation on the line, also known as the Hawks. In the daytime, it’s Port Health that calls — with tip-offs.
Port Health is a health department agency and monitors the entry of diseases into South Africa. It also tracks the movement of harmful substances and unregistered medicines into the country’s harbours and airports.
One morning early in January this year, Port Health called from Durban with information from the police’s crime intelligence unit.
Two hours later, by the time the two smugglers reached Durban’s airport, Mopai was there, waiting for them.
A nation tackles 2021 with a new variant, and no vaccines
In January, as the second Covid-19 wave hit the country, South Africa didn’t have a single dose of the one biomedical intervention that could slow down the pandemic: vaccines.
A new, more infectious variant, called Beta, had emerged causing a record high of 839 daily deaths reported by the middle of that month.
The situation in richer countries was entirely different — more than 39-million vaccine doses had been administered in wealthier nations at this point.
Considerably larger budgets than those of poorer countries, and the ability to take financial risks, enabled affluent governments to pre-order so many vaccine doses, that there were hardly any left for middle- and low-income countries to buy.
When South Africa finally found 1.5-million AstraZeneca Covid-19 jabs to procure, it emerged that the jabs didn’t work as well as expected against the Beta variant, and the country placed the roll-out of the shots on hold.
South Africa would be stuck without vaccines for another five months.
People were desperate for help and grasped at almost anything they thought could protect them from ending up in an intensive care unit.
It was one such — unproven — drug that Masilo Mopai flew to King Shaka International to intercept. Ivermectin.
What is ivermectin?
The anti-parasitic medicine is a pandemic anomaly.
In agricultural circles, ivermectin isn’t hard to come by; it’s an over-the-counter medication widely used to treat parasites such as worms or lice in cattle.
At the time of Mopai’s airport raid, millions of people around the world had started to use the drug to prevent and treat Covid-19 — caused by a virus (as opposed to a parasite). Back then, there was no conclusive research or evidence that ivermectin worked against Covid-19.
Nearly a year on, considerably more ivermectin studies have been done, but whether the medicine works remains blurry.
A review of 14 ivermectin studies published in July found that the medicine, compared to a dummy drug, had “little to no effect” with regard to preventing or treating Covid.
But by the time South Africa’s second wave hit, ivermectin had come to represent an escape out of the pandemic for some. People smuggled it in from overseas or queued at their local veterinarian to get the version of the drug used for animals.
Now, as the fourth Covid wave approaches, South Africans can legally get human ivermectin to treat or prevent Covid if their doctors prescribe it, even though that’s not the condition ivermectin was registered to treat.
Or worse, they’ll get the animal formulation cheaper.
Fakes and take-backs: ivermectin research is terrible
Ivermectin research hasn’t been straightforward.
Eight papers on the medicine’s use for Covid prevention or treatment have been retracted since May 2020.
In July, a group of researchers in the United Kingdom analysed 24 ivermectin studies.
This type of research, called a meta-analysis, tries to answer a bigger question — for example, whether ivermectin works against Covid — by assessing several smaller studies on the same topic. This way, researchers can balance out the results of trials with small sample sizes, which can skew data.
The meta-study was published in the journal Open Forum Infectious Diseases.
The authors’ initial findings showed that ivermectin boosted people’s chances of surviving Covid-19 by 51%.
But one of the biggest studies included in the analysis was retracted for fraud.
When the UK researchers removed this fake study and redid their analysis, the results were far less promising — the drug only held a 38% survival benefit for patients.
And, when they removed all the research that was fake or biased (three of the trials were run badly, and they found another paper that included duplicated data), that figure dropped to 4%. In other words, ivermectin made no difference.
In short, the drug only had an effect on Covid-19 when researchers included the data of studies with a high risk of medical fraud in their analysis.
But such findings have done little to dissuade ivermectin fans.
A baaaad call: why animal meds aren’t good for people
A glass of ivermectin a day keeps the doctor away, was what one Western Cape farmer’s philosophy appeared to be.
The man was caught when a prominent politician in the province tipped off Mopai’s unit at Sahpra.
The farmer was mixing his own formulation of animal ivermectin and water and giving it to his farmworkers daily.
Mopai says: “It’s hard to believe that this farmer really had his workers’ safety in mind, it’s reckless.”
Because ivermectin is an over-the-counter medication to treat parasites in animals, it’s easy to come by without a doctor’s prescription.
Afrivet, one of the suppliers of ivermectin for animals in South Africa, says they don’t sell the medication to farmers directly but instead supply co-ops and vets.
Says Afrivet’s chief executive, Peter Oberem: “We saw massive demand over the past year. Our sales doubled — at least.”
When Afrivet noticed the uptick in sales, the company began putting pamphlets into all their shipments warning that the medication was not for human use — but “people can just ignore that”.
The high concentration of ivermectin required for a large animal such as a cow or a horse is far more than a person should take.
This poses the danger that people who are self-medicating with the animal version of the drug and without a doctor’s supervision could potentially overdose or have a toxic reaction to the amount of ivermectin ingested.
Sahpra’s chief executive, Boitumelo Semete-Makokotlela, says the regulatory body has received reports of liver damage in people that have taken too high a dose of ivermectin.
Medications for animals also have to meet different standards to those for people. “The conditions are less stringent for animal formulation than for humans,” Semete-Makokotlela said.
What’s more, all ivermectin is not created equal. Additional ingredients could be put into the liquid formulation given to animals that may not be safe for humans.
Human tablets, on the other hand, include harmless powders that are safe for human consumption.
Essentially, each ivermectin product has its own recipe, and its own mix of ingredients.
Oberem says the liquid version that’s given to animals contains extra ingredients in its formula. “Those formulations have never been tested in humans. So, you can never recommend the use of an animal formulation in humans, that would be wrong.”
Popping pills: The ivermectin pharmaceutical playground
It’s December 2020 in Johannesburg, and the city of gold has started to empty out for the festive season after the first nine months of Covid-19 lockdowns in South Africa.
As always, Mopai is on duty. He’s at a general practice in Randburg, Johannesburg. He walks in, introduces himself to the receptionist and explains his role at the medicines regulator.
He had made an appointment to see the doctor, but the man was away on holiday.
Luckily, a private audience with the doctor wasn’t necessary to find the loot Mopai was looking for. Bags of pre-packed ivermectin were standing on the counter behind the receptionist’s desk. Ready for collection without a consultation in exchange for cash – R30 a pill or R300 for a pack of 10.
Says Mopai: “They were handing it out like sweets.”
At the end of January 2021, a month after Mopai’s raid of the Randburg practice, public interest in the use of ivermectin as a Covid-19 treatment was skyrocketing.
At this stage the only promising evidence that it worked was based on lab research, not the human clinical trial data that Sahpra requires to clear a medicine for the market.
Sahpra introduced a compromise. Ivermectin could now be safely accessed through acompassionate use programme.
This didn’t mean you could just walk into a pharmacy and grab a pack of pills. Nor did it allow doctors to prescribe the medication as they saw fit. Instead, it provides a more controlled way for people to get the drug.
Under this type of authorisation, doctors have to submit an application to Sahpra explaining why they believe ivermectin is the correct treatment for their patient, why nothing else can be used, and they have to show that the patient consents to the experimental treatment.
There are strings attached to the compassionate use application. For example, doctors must update Sahpra on any side-effects that their patient experiences. The regulator also expects a report from the doctor every six months and another review must be submitted one month after the patient stopped using ivermectin.
This arrangement was not sufficient for those who backed the use of the drug. Intensive care doctors, political parties such as the African Christian Democratic Party and the lobby group AfriForum began gearing up to take Sahpra to court to make ivermectin easier to access.
Three months after the compassion project launched, in April, a high court ruling gave doctors the loophole they needed to prescribe ivermectin for Covid-19 patients legally – without Sahpra’s safety nets.
Looking for loopholes: A doctor’s cheat sheet to getting hold of ivermectin
The loophole in question is called Soolantra.
Sahpra registered the product in March.
Soolantra is a cream used to treat rosacea, which causes redness and bumps on your face. The active ingredient in Soolantra is ivermectin.
Was it registered in 2021 because of claims its active ingredient can treat Covid-19?
No. It’s an unfortunate coincidence. Here’s what happened.
Sahpra relaunched in 2018 but inherited a backlog of 16 000 applications from its predecessor the Medicines Control Council. More than half of the applications were at least five years old, Sahpra estimates. And so Soolantra, which is part of the 85%, joined the medicine market.
(About 85% of the backlog has been cleared, according to a June report.)
Once a medical ingredient is registered in the country, doctors can prescribe it for their patients freely, according to South Africa’s Medicines and Related Substances Act.
The high court ruling allowed for ivermectin to be accessed through the compassionate use programme or something called “compounding”.
Pharmacists sometimes compound medicines for patients who are, for instance, allergic to a dye used in the medication, says Dhivia Naidoo, the managing director at the Compounding Pharmacy of South Africa.
That pill would then be put together without the dye and tailored to that specific patient.
As of April, there was no need for Sahpra approval or applications for ivermectin. All doctors had to do was write a script and send their patient to a compounding pharmacy — no raiders would intervene.
Although special pharmacies can make ivermectin, they’re not allowed to advertise that they do so, nor can they distribute pills to people without a script from a doctor. That’s because doctors should be prescribing a customised dosage of ivermectin for each patient.
So, the compounding loophole didn’t change Mopai’s work day much.
Shortly after Soolantra was registered, he was called to Phoenix, a neighbourhood in Durban.
“We found a long line of people queuing outside a pharmacy, all waiting for ivermectin,” he says.
The medicine had been compounded in the country (which is legal) but this facility was also handing out the medicine “like sweets” to patients without scripts (that’s not legal).
Mopai arrived, closed the pharmacy for inspection, and confiscated the ivermectin.
The pills would be destroyed as medical waste.
Those in the queue didn’t like having their hopes dashed after queuing for hours, but Mopai is used to this type of anger.
He says: “The community doesn’t always understand that we’re trying to protect them. They don’t know the danger.”
Taking a toxic turn: The dangers of an unmonitored drug
By August 2021, doctors in the United States were writing 88 000 scripts for ivermectin each week. That’s 24 times more than the US Centres for Disease Control recorded before the pandemic, according to a CDC report.
Simultaneously, ivermectin-related calls to US poison control centres increased five-fold, and some of those calls resulted in people being admitted to hospital.
In September, the US medicines regulator, the Food and Drug Administration, warnedthat the high doses of ivermectin used for animals could be toxic for people — and there isn’t any information on how the amount of other ingredients put into the formula for animals could alter people’s reaction to the drug.
Although Sahpra claims to not know of any overdosing incidents, there have beenmedia reports of two people being admitted to hospital after taking too much ivermectin.
Meanwhile, South Africa’s fourth wave of SARS-CoV-2 infections (the virus that causes Covid-19) is looming.
Doctors are, however, prescribing less ivermectin, for now, says Naidoo. Sahpra has noted a drop in applications for its ivermectin compassionate use project too.
Whether it’s because the country is in between waves of infections, or because vaccines are available for free, Semete-Makokotlela says, is hard to know.
As South Africa’s fourth wave approaches, the demand isn’t dying down
People could be opting for animal ivermectin instead, but that’s difficult to establish.
Sahpra hasn’t had to monitor animal medication in this way before, so there’s no system to track it.
Oberem says Afrivet isn’t seeing a decline in the number of orders they’re filling for ivermectin and he doesn’t expect them to.
For many South Africans, Oberem says, getting permission through the compassionate use programme is complicated, and going to a doctor for a script is expensive. “The human tablets cost may be 10 times more than the animal health ones.”
The regulator is working with the department of agriculture, which is in charge of overseeing the use of the drug. The department did not respond to Bhekisisa’s requests for comment.
The department does not track abuse of the medicine.
Why not?
“It’s an impossible task really to monitor [the use of animal ivermectin],” Oberem explains. “Because it’s an over-the-counter medicine, anybody can go into their shop and purchase ivermectin.
“Perhaps farmers are doing that for their friends and colleagues in the town, I don’t know.”
In Durban, the two ivermectin smugglers Mopai intercepted at King Shaka International airport have been waiting for their day in court since January. They are out on bail.
Sahpra has confiscated millions of rands worth of illegal ivermectin at South Africa’s borders and at pharmacies and doctors rooms.
Mopai is, as always, doggedly tracking the medicine — day and night. It’s passion for the job that fuels his stamina, he says.
“We’re playing a very important role, if we didn’t have this type of organisation in the pandemic – that would be a catastrophe.”
This story was produced by theBhekisisa Centre for Health Journalism. Sign up for thenewsletter.
No comments:
Post a Comment