Passive surveillance: People receiving a Covid-19 vaccine will be urged to report any negative side effects
Covid-19 vaccines will only be registered for use in South Africa if their common side effects are mild. To qualify as a ‘very rare’ side effect, the symptom needs to affect fewer than one in 10,000 people.
On 17 May, South Africa will start to roll out Covid-19 vaccines to people over the age of 60, as well as to the 700,000 health workers not covered by the country’s vaccine implementation study, the Sisonke trial.
Health workers are covered by the study because they’re the most likely group to get infected with Sars-CoV-2, the virus that causes Covid-19, as they deal with infected patients. Older people, on the other hand, are more vulnerable to falling severely ill with Covid, or more likely to die of the disease than younger people, which is why they’re the next group to be prioritised.
South Africa will be using two types of shots: Pfizer/BioNTech’s, in urban areas, and Johnson & Johnson’s (J&J), in more rural areas.
The Sisonke trial, which uses the J&J jab, was recently paused because of concerns about a potential link to unusual blood clots. International researchers and regulators call the clots an “extremely rare” side effect. But how rare is rare, and why are these blood clots unusual? We break down what you need to know.
Why was the roll-out of J&J paused?
On 13 April, the US medicines regulator, the Food and Drug Administration (FDA), along with the American government’s Centers for Disease Control (CDC), recommended that the use of the J&J jab be paused. This came after six vaccinated women aged 18 to 48 (out of a total of about seven million vaccinated women and men) developed a rare type of blood clot alongside a condition that lowered their blood platelet levels. Platelets are blood cells that help with forming clots, the US nonprofit, the Mayo Clinic, explains.
On 23 April, the FDA and CDC reported that blood clot cases had increased to 15 by the time that around eight million people had been vaccinated and three of the affected people had died. The age group of the women who had developed blood clots had also widened from 18 to 59.
Shortly after the FDA/CDC’s pause, South Africa’s medicines regulator, the South African Health Products Regulatory Authority (Sahpra), paused the country’s Sisonke trial as a precautionary measure – even though no rare blood clot cases had been reported among the estimated 330,000 health workers who had been vaccinated. (Experts say one of the reasons we didn’t have cases is because we hadn’t yet vaccinated enough people for a very rare side effect to show up.)
An extremely rare adverse event is when an unintended symptom affects fewer than 1 in 10,000 people, according to Hannelie Meyer, the chair of the health department’s independent National Immunisation Safety Expert Committee.
About two weeks after the pauses had been announced, both the FDA and Sahpra recommended that the use of J&J’s jab be continued because data showed that benefits outweighed potential risks and that the vaccine was safe to use.
The FDA and CDC found that the risk of a blood clot that is accompanied by low platelet levels for someone who had been vaccinated with the J&J vaccine is one in a million. For women between the ages of 18 and 49, it found the risk had increased to about seven out of a million.
According to a report in the journal Stroke, the risk of developing blood clots as a result of Sars-CoV-2 infection is eight to 10 times higher than in the case of a Covid vaccine.
In South Africa, Sahpra initially recommended that women who are pregnant or breastfeeding don’t receive the jab, but then changed its decision. The Sisonke researchers are in the process of submitting new documents for approval so that these groups can be included in the trial.
Vaccinators also have to intensify their screening of high-risk groups and do more detailed monitoring of people who have been vaccinated to ensure their safety.
What exactly are blood clots?
The unusual blood clots that led to the temporary hiatus for J&J’s jab have also been seen in people who received AstraZeneca’s vaccine in Europe.
So how do these blood clots differ from other blood clots? Normally, when you cut yourself and start bleeding, your body sends out a signal to its platelets – the platelets help “plug” the injury and stop the bleeding by forming a gel-like clump of blood (or a blood clot).
But the blood clots – called vaccine-induced thrombosis and thrombocytopenia – associated with the J&J vaccine are different.
The combination of these two events is extremely rare and very unexpected, explains Linda-Gail Bekker, one of the lead investigators of the Sisonke trial.
Writing for the New England Journal of Medicine’s Journal Watch, Paul Sax, a professor of medicine at Harvard University, explains that these clots can differ widely in severity. What makes them dangerous is that they tend to occur in “bad” locations.
In the case of the J&J jab, vaccine-related blood clots have mainly occurred in people’s brains. This is called cerebral venous sinus thrombosis, and it essentially stops the blood from draining out of your brain, which could lead to haemorrhaging and become fatal.
This is further complicated by the fact that these blood clots cannot be treated in the normal way. Ordinarily, people with blood clots are given the blood thinner heparin to thin their blood and prevent clots from forming. But because of the low platelet count accompanying the vaccine-related cases, heparin could in fact make the condition worse. So other treatment options are being explored by haematologists.
What is South Africa doing?
Adverse effects picked up as a result of any medicine used in South Africa have to be reported to Sahpra.
In April, Sahpra launched the Med Safety app, which allows people to report adverse effects suffered from medicines and vaccines, to complement the country’s existing paper-based system.
“It’s not that the vaccines aren’t safe,” Sahpra’s board chair, Helen Rees, explained during a public briefing on 13 April. It’s more of a numbers game. Efficacy and safety trials show how a vaccine works in tens of thousands of people, but a widespread roll-out allows the jab to reach millions of people, and adverse events that weren’t picked up in a trial are bound to show up then.
“When you roll it out to millions of people, you have to be able to not just look for safety signals, but you also have to be able to say: Is that safety signal actually to do with the vaccine, or is it just because things happen when you roll out things to millions of people?” Rees explained.
The difficulty with staying on top of potential vaccine side effects is that detecting them is entirely dependent on people recognising their symptoms and reporting the incident.
Although Sahpra’s existing pharmacovigilance system (the monitoring of medicines for safety) is relatively good, it will be bolstered for the national vaccine roll-out, says Meyer.
A call centre, which will be in operation by 17 May for the launch of phase 2 of the roll-out, will be set up so that people who have been vaccinated can use it to report concerns or any side effects they’ve experienced.
And since a large pool of reports is necessary to link rare vaccine events, South Africa’s data will be pooled with information from Nigeria, Ghana and Ethiopia. A committee of experts from the four countries will be in charge of reviewing the pooled reports, Meyer says.
How will we scale up changes after the Sisonke trial?
The Sisonke trial will provide a blueprint for South Africa’s mass roll-out to follow.
“We really are dependent on people letting the safety desk know [about side effects such as blood clots] because not everybody is being followed up individually,” Bekker says. This is called passive surveillance.
Opting for a more active surveillance model would mean following up with millions of people individually on a regular basis to find the handful that may have a more severe reaction to the vaccine.
“It would be a massive waste of resources,” Bekker cautions. “You have to be pragmatic and the best option is passive surveillance.”
Bekker’s team is now encouraging trial participants to use all platforms (such as the Med Safety app) to report the symptoms they experience after vaccination.
Very rare symptoms to look out for include a severe headache, weakness on one side, difficulty speaking, swelling or pain in one leg, shortness of breath or chest pain, or blood spots at the site of injection, according to the South African Medical Research Council.
Sisonke researchers now also send all participants an SMS at two, seven and 14 days after vaccination to encourage them to report side effects either online or via a phone line.
South Africa’s mass roll-out is expected to follow the same rules.
Bekker says: “The idea is just to remind people, first of all, to be aware if they are showing symptoms of a possible blood clot event (such as a severe headache), but second, to remind them that we want them to report.” DM/MC
This article was produced by the Bhekisisa Centre for Health Journalism. Sign up for their newsletter.
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