How a rural KZN site is helping the world find a TB jab

Sicelo Masangwana closes his office door in Somkele village, a settlement of about 6,000 people, near Mtubatuba in northern KwaZulu-Natal.

He walks the 10 or so steps towards the foyer of the building where a room full of young people, all around 20 years old, await him, swipes across his forehead and takes a deep breath.

“It’s going to be a long day!” he smiles.

Outside, Somkele’s children are playing football barefoot in the dusty street that leads into the village from the tarred highway. Every now and again people are seen popping in and out of their homesteads while doing their daily chores, as they usually do by midmorning on weekdays.

Today’s a typical Tuesday in March — it’s autumn, around 10.30am.

In the Mtubatuba municipality, roughly 50km north of Richards Bay, about 1% of people are sick with TB; the disease usually shows up as someone losing weight, having night sweats, an ongoing fever or a never-ending cough.

TB disease rates here are high, at least partly, because of the HIV infection rate being high too: about three in 10 people have contracted the virus, which ups their chance for getting TB too (people with HIV are up to 20 times more likely to get TB than people without HIV).

Masangwana is a researcher at the Africa Health Research Institute (Ahri). He’s co-ordinating a clinical trial here that’s part of a big study that will test how well a potential new TB vaccine, called M72/AS01E, works.

An earlier, smaller trial of the vaccine (called a phase 2 trial), showed that the jab could protect at least half of people who are infected with the TB germ from falling ill. The vaccine was also shown to be safe. This finding told scientists that the vaccine has great promise and is worth testing in another round, this time in a bigger group of people.

This step, called a phase 3 trial and which involves testing the vaccine in thousands of people, is what Masangwana is focusing on now. It will be no small feat. But, he says, “we have a very experienced team [for running] clinical trials and we’re known in this community — we’ve been here for more than 20 years. We think that gives us an advantage, as people trust us.”

7 countries, 60 sites, 20 000 people

The trial started in South Africa in late March, and at Ahri, researchers are starting to get participants signed up. In the end, the study will test the potential new vaccine in about 20,000 people between the ages of 15 and 44 across seven countries. (Apart from South Africa, the trial will also run in Zambia, Kenya, Mozambique, Malawi, Indonesia and Vietnam, which are in the two regions that account for more than two-thirds of the world’s TB cases.) 

The Ahri site has to recruit about 1,000 participants by the end of the year. As at each of the other sites in the study, half of the volunteers will get two shots of the actual vaccine, one month apart, and half will get two dummy jabs (called placebos). The results of the two groups will then be compared to see if the vaccine can prevent people from falling ill.

At the moment, the only anti-TB jab available (called the Bacille Calmette-Guérin (BCG) vaccine) is one that’s given to babies when they’re born. However, the protection doesn’t last until adulthood, and the BCG shot doesn’t work if given after childhood.

In 2022, more than 9-million adults across the world fell ill with TB, which means they were able to spread it to someone else when they coughed or sneezed. This is why having a vaccine that can prevent this group of people from getting sick is so important.

M72, as the shot is called for short, may give us a real chance to end the disease that killed 1.3-million people worldwide in 2022, about twice as many as HIV; in South Africa, about 150 people died from TB every day that year.

Researchers hope to have the final results of the phase 3 trial in the next four to five years.

Here are four things researchers in a rural part of South Africa are keeping in mind while rolling out the trial.

1. Start slow, then ramp up

As the researcher co-ordinating the trial at Ahri, Masangwana has to make sure that they get enough people who meet the study requirements signed up and keep everything running smoothly.

It’s a big task, which is why they’re starting slow, he says. “We’re aiming to sign up about 100 people by the end of April”, after which they’ll ramp up the process to get to their goal before the end of the year.

Some of the requirements for taking part in the study is that someone has to be at least 15 years old, never have had TB, have no plans to move away from the area while the trial runs and must agree to stay in touch with the facility for regular health check-ups for the entire time that the study is going on (which can be up to five years).

In a trial like this, participants are randomly divided to get either the real or the dummy shot and neither they nor the researchers know who is in which group. This is called a randomised double-blind study, which is the best way to make sure that if the study shows that people are protected from TB, the result can confidently be linked to the vaccine and not another factor.

During the first month of the trial at Ahri, researchers will screen five participants each day and give another three people their first shot.

With a big trial like this, scientists want to see how the jab works in people from many different places across the world, says Willem Hanekom, the institute’s director and one of the two lead investigators of the South African arm of the study.

“Ultimately the aim is that this vaccine will get recommended by the World Health Organisation,” he says, which means that countries are likely to write it into their policies for dealing with the disease.

2. Get on your feet

Anne Derache, who is the lead study co-ordinator of Ahri’s clinical trials unit, says their search for participants will focus on Somkele, Mtubatuba, KwaMsane and Dukuduku, as these areas have the highest rates of TB.

While looking for people to sign up for the trial, researchers will try hard to get men to make up 50% of the group, especially because data shows that TB can be about three times more common in men than in women.

Yet because men tend to go to a clinic or health worker for help less easily than women, the researchers think that they might struggle to recruit enough men.

To solve this problem, field workers will go to taxi ranks, sports stadiums, shops, shebeens and car washes when they ask people whether they’re willing to sign up.

3. Make it worth people’s while

To help make sure that people can participate for as long as the trial has to run, participants are transported to and from the research site for visits, get regular health check-ups and blood tests, including for HIV, and some money to compensate them for the time they spent being part of the trial and any inconvenience or other costs they may have had in the process.

Compensating participants for the time and money they spent on being part of a study is standard practice and is approved by the South African Health Products Regulatory Authority (Sahpra), which is responsible for tracking how all clinical trials in the country are run (including overseeing how much people should get to cover their time and costs).

The amount people get is in line with Sahpra’s guidelines, which, depending on how far someone lives from the research centre, can start from R400 and go up to R600 (plus some extra if the distance is more than 50km).

The first four months of the trial “will be very intense”, says Derache.

After the first jab, participants will be checked up on within seven days to see if they had any side effects. A month after the first shot, they’ll get their second one, and again have a check-up within a week. A month after the last injection, health workers will examine them once more, and then again a month later. From then on, until the end of the trial, they’ll get check-ups every six months. This means that, in total, someone may have to visit the research site up to 14 times over the course of the trial (including for the initial sign-up).

The special focus on men already seems to be paying off.

Sibongiseni Dube*, 23, who will have his first jab next week, says that apart from getting a reimbursement to cover his costs and time for every visit to the research site, it’s the free health checks that enticed him to join the study.

“When I go to the clinic [where I live] there aren’t always doctors, and even if there are, the queues are always so long. Having regular medical tests in a less crowded space is a bonus.”

Losing his best friend to HIV has left him fearful of sickness and death, says Dube, who “jumps at every opportunity to get an HIV test”.

“He died when we were in Grade 7 after he stopped taking his ARVs [antiretrovirals], which he had been on since childhood. I’m always reminded of him [when I go for a check-up].”

4. Understand your community

Crime, getting teenagers enrolled and working within communities’ traditional rules and value systems are just some of the issues researchers face when recruiting study participants from a rural area like this. But, says Simangaliso Zulu, one of the field workers helping with signing people up for the trial, “understanding the community is important as it prevents hindrances in our work”.

For example, in trials that include teens, like this one, getting permission for them to participate in the area where Ahri works can be difficult, says Derache. Because their parents often work in cities away from home, many teens here live with their grandparents. But as they usually aren’t the official legal guardians of the children, they can’t give permission for them to sign up.

“Without parents’ consent, we can’t enrol these teenagers,” Derache explains.

Crime has also put a spanner in the works. Earlier this year, in the space of a month, three of Ahri’s vehicles used to transport people to and from the research centre were hijacked in the area.

“Such incidents are distressing, as they disturb the work we do in communities. But we have to [carry on],” says Zulu.

Hanekom agrees: “If we are to see positive results from the trial, it’s likely that South Africa will be the first country in the world in which this vaccine gets rolled out. That will be a huge success.”

* Not his real name

The Bill & Melinda Gates Foundation (BMGF) is one of the funders of the clinical trial mentioned in this article. Bhekisisa receives funding from the BMGF, but is editorially independent.

This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.