Francesca Conradie knew she wanted to be a doctor when she was eight years old. Well, that or a truck driver.

It was one of her family’s weekly trips to the local library that helped make the decision clear. While flipping through the pages of Dr Christiaan Barnard’s autobiography One Life and reading about the man who performed the world’s first heart transplant, Conradie knew she wanted to pursue a career in medicine.

Back then there were not many female doctors, something Conradie was determined to change.

A young Conradie with big dreams of saving lives had no idea that 50 years later she would be a global pioneer in her field. She recently led a landmark trial that changed how drug-resistant tuberculosis (DR-TB) is treated around the world. Her work paved the way for shorter treatment regimens – a move the World Health Organization (WHO) endorsed in May – meaning that people with drug-resistant TB can take fewer drugs for a shorter time.

A hunger to learn

Conradie grew up in the northern suburbs of Johannesburg in the 1960s. She is a middle child with two sisters. Her younger sister studied dramatic arts and is an author, while her older sibling is a graphic designer who also does quilting.

“I’m a little bit of a black sheep in the family because I’m not artistic at all,” says Conradie. On the wall behind her is a painting by her son.

She recalls how her father instilled in them a great appreciation of art through regular trips to galleries and the family frequently attended classical music concerts. While she says she possessed no artistic skills herself, Conradie believes this upbringing allowed her to have a broader view of the world.

Conradie says her father was one of her biggest supporters. “My father did not suffer fools,” she recalls. “He was determined that all of his children would be able to stand on their two feet, that they would qualify as something. He expected us to learn.”

That hunger to learn led Conradie to medical school at the University of the Witwatersrand. She graduated in 1988 and began her internship as South Africa was facing what would become one of the biggest global health challenges in decades – HIV/Aids.

The early days 

“HIV was far and away the biggest problem that any South African would face,” says Conradie. “I realised that if I was going to be an effective doctor, I needed to learn how to treat HIV.”

In the two decades since she qualified as a doctor, there have been massive strides in HIV treatment with more than 30 drugs entering the field. But the same could not be said for TB.

In 1987, six years after the first case of Aids had been identified in America, the US Food and Drug Administration (FDA) approved the first drug to treat the disease – zidovudine (AZT). But people taking AZT soon developed drug resistance, and it was only about a decade later in 1996 that triple therapy (combining three different antiretroviral medicines) was found to be highly effective in suppressing HIV. Despite the fact that effective HIV treatment existed by the late 1990s, the South African government was vehemently opposed to providing the medication and refused to make it available in the country.

Read more in Daily Maverick: “Women in Health: ‘I don’t like seeing anybody treated unfairly,’ says new head of HIV Clinicians Society”

This meant that when Conradie was starting up her practice, there were no options available to treat the disease, and being diagnosed with HIV was essentially a death sentence. More than 330 000 lives were lost in South Africa due to delays brought on by Aids denialism, estimates a 2008 study in the Journal of Acquired Immune Deficiency Syndromes.

“I saw a lot of women who were pretty much the same as me but had gotten infected with HIV,” Conradie recalls. “In the earliest days, when we had no treatment, they would ask things like, ‘can you not just give me something because I want to be alive when my child goes to school?’ That’s what drove me to HIV research – I really wanted to be able to help, particularly women, to survive.”

As Conradie was delving into HIV treatment research in the 2000s, South Africa’s own HIV landscape began to change. A landmark judgment from the Constitutional Court in 2002 mandated that the government provide pregnant women with an antiretroviral drug called nevirapine to better protect children from HIV infection. The following year, the government approved a plan that would provide medication and treatment to those who needed it (although the roll-out of the plan would still take several more years).

Conradie says she got lucky in the timing of her decision to switch to HIV research. “I was involved in the original trials for a lot of the medicines we use now in routine practice.”

But she feels her most significant contribution in the field was being a site leader for the HPTN052 trial, which was named the scientific breakthrough of the year in 2011 by the journal Science. The trial found that antiretroviral treatment also works as a prevention tool, reducing the risk of transmission to an uninfected partner by 96% if started early.

Visit Daily Maverick’s home page for more news, analysis and investigations

Around the time these results came out, Conradie was beginning to look for a new avenue to take her research – and she soon found one.

“I felt that many of the major breakthroughs for HIV had already occurred,” she explains. “What we needed to do was implement an HIV programme, to prevent infections and treat everyone who is infected. I’m more of a researcher than an implementer, so I decided to change to drug-resistant TB.”

Close encounters

Conradie’s first close encounter with the bacterial disease actually came a few years before her switch in focus, from the man who had shaped most of her life – her father.

In 1995, shortly after she had given birth to her youngest son, Rees, her father became quite ill with pneumonia. He recovered and was sent home. Then it happened again and again and again. After the fourth trip, when Conradie’s 18-month-old son was also admitted to hospital with pneumonia, her father was finally diagnosed.

Read more in Daily Maverick: “New TB testing strategy shows positive signs in early stages”

“In the last episode, I finally looked at his X-ray. His lungs were very badly damaged. I thought this [was] lung cancer.”

The new approach was a resounding success and reinvigorated Dr Francesca Conradie in her pursuit to transform TB treatment for those who needed it. (Photo: medicinenet.com / myhealth1st.com / Spotlight)

When the results came through and Conradie found out it was actually TB, she was overjoyed. But her dad didn’t feel the same way.

“My father was really, really ashamed of acquiring TB,” she recalls. “I think he would have preferred it to be lung cancer.”

The stigma attached to TB was just one of the many similarities it shared with HIV. Because of the parallels between the two diseases, Conradie felt the switch was a natural shift.

In the two decades since she qualified as a doctor, there have been massive strides in HIV treatment with more than 30 drugs entering the field. But the same could not be said for TB.

“Patients said to me if I had to choose between dying from TB and taking your medicines, it’s a very close call,” Conradie says. “If someone would rather die than take the treatment, that means the medicines are really intolerable.”

It didn’t seem like there was any rush to address the shortfalls in the options available to TB patients. That changed in 2012 when the FDA approved a new drug, bedaquiline. This was the first time in 40 years that a new medicine had been approved to treat TB. A second new drug, delamanid, was approved by the European Medicines Agency in 2014.

A third new drug called pretomanid was later approved by the regulatory body in 2019 to be used in combination with bedaquiline and linezolid to treat drug-resistant TB. Conradie was at the forefront of researching this three-drug combination, commonly referred to as BPaL. (Pretomanid is in the same class of drugs as delamanid, although it’s not yet clear which of the two is better in what context.)

A meal of pills 

Before the approval of bedaquiline, Conradie describes treating multidrug-resistant TB with a “kitchen sink approach”.

The options were to give people injections that caused hearing loss in half of the patients who received them, or put them on an extensive selection of pills. The default treatment was “a meal full of pills”, with people taking 23 tablets a day for 18 months – that means one person would be taking more than 12,000 tablets to try to beat the disease.

“We were giving people any medication possible, drugs we thought might work or hadn’t been used before. We tried to treat our patients, but the success rate was shocking.”

Only 27% of people in South Africa with extensively drug-resistant TB were successfully completing treatment in 2014, according to the WHO Global Tuberculosis Report. This form of TB is also the deadliest, with four in 10 people dying, according to the same 2014 data. The outlook for multidrug-resistant TB is slightly better with just more than half of patients being successfully treated in 2018. That meant the medications available weren’t working for the majority of patients.

Read more in Daily Maverick: “Shorter, simpler drug-resistant TB treatment expected in SA later in 2022”

So, Conradie, along with her colleagues at the TB Alliance, a non-profit organisation focused on changing the TB treatment landscape, began putting a plan together to pursue new approaches to treating these extremely resistant forms of the disease.

‘Out of the ballpark’

The answer came in the NiX-TB trial, which tested a combination of the three medications that make up the BPaL regimen. Conradie led the single-arm trial, which enrolled 109 patients across three sites in South Africa.

“I thought if we can successfully treat half of our patients, I would be happy because that’s better than what we had,” she says.

But nothing could have prepared her for what they found. The six-month treatment regimen of 23 pills a week had a 90% success rate. This was completely unheard of at the time and paved the way for an entirely new approach to treating drug-resistant TB. Conradie herself was shocked by the results.

“It was so out of the ballpark of what we expected,” she says. “It was way more successful than I thought, but it did come at a cost.”

Dr Francesca Conradie knew she wanted to be a doctor when she was eight years old. (Photo: Supplied / Spotlight)

Conradie says she faced a lot of backlash for the results, with many people accusing her of falsifying the data or paying people off to be in the study. The other cost came to the patients, who were not completely free of the downsides of treatment, with one of the drugs (linezolid) still carrying significant side-effects.

But overall, the new approach was a resounding success and reinvigorated Conradie in her pursuit to transform TB treatment for those who needed it. Many of her patients had been with her for years and the NiX trial meant finally bringing them some hope.

A follow-up trial called ZeNix, which Conradie also led, and the TB-PRACTECAL study led by Médecins Sans Frontières (Doctors Without Borders) confirmed the high levels of protection offered by regimens built around bedaquiline and linezolid. Findings from these and other studies are part of a growing body of evidence that led to these drugs becoming the backbone of drug-resistant TB treatment regimens recommended by the WHO – with the BPaL regimen recently receiving a new wider recommendation.

“We had a lot of people waiting in the wings for this magical new treatment that was coming along,” Conradie recalls. “There was a real sense of rescuing them from the brink of death.”

She has been working with the Health Department to integrate the new treatment regimen into South Africa’s TB programme and is hopeful that it will become easily accessible to everyone who needs it.

“That’s why I became a doctor, because people get sick and I want to help them to get better,” she says.

Note: As recently reported on Spotlight, the Department of Health intends to start rolling out the new regimen later in 2022, although it is not yet clear exactly how the country’s treatment guidelines will change. Bedaquiline and linezolid have been part of standard DR-TB treatment in South Africa for several years but administered with more accompanying drugs than BPaL or BPaLM (BPal plus moxifloxacin). DM/MC

This article is part of Spotlight’s 2022 Women in Health series that will run throughout August. The series celebrates and highlights the contributions to health and science made by women in South Africa.

This article was published by Spotlight – health journalism in the public interest.