​​Prof Paul van Helden talks about tuberculosis (TB ) the way a military strategist might speak about an adversary. During more than 25 years of research he has come to know the disease intimately and has been instrumental in changing the way in which conventional healthcare views, approaches and treats it. More recently he has started waging war on TB in South Africa's wildlife, thereby marrying his determination to fight a treacherous disease with a lifelong love for conservation and wildlife.

As Head of the Department of Biomedical Sciences of the Faculty of Medicine and Health Sciences (FMHS), he directs the Department of Science and Technology's Centre for Excellence in Biomedical TB Research. He has received multiple awards and in 2009 Thomson Reuters identified him as the fourth most influential TB scientist in the world.

"TB is difficult to control due to a number of characteristics. It hides away, which is one of the peculiarities that renders it so unlike diseases like Zika or Ebola that attract public attention because they happen immediately and patients die quickly.

"People with TB become ill over a  relatively long period of time and die monthsor years later. It doesn't attract your attention and that is part of the problem. Even if you treat 100% of people with the active disease now, a large body of people are going to become ill later in life.

 "Furthermore, you can't simply treat it  with one antibiotic. It has to be treated withmultiple antibiotics for a very long time, and a  whole variety of healthcare delivery problemsarise because of the long duration of the  treatment."

His work in TB commenced in the late 1980s at the dawn of DNA studies, when he and a doctoral student were among the first African scientists to use the newly-invented polymerase chain reaction (PCR ) to study the DNA of a diarrhoeal disease for diagnostic purposes. "But then we decided we wanted to apply this technology to a far more important disease and we chose TB . That is really how it all started."

Know your enemy

Van Helden has stuck with TB for decades precisely because it is such a tough nut to crack and poses such a dire threat to global health. South Africa has nearly half a million active TB cases every year, which renders it a global hotspot and places a huge burden on the healthcare system.

 "Purely from an intellectual and academic point of view it is an incredibly complicated and complex organism; its interaction with the host is very complex. It is very stimulating to work with something really interesting with so many facets. It is also a field where you can work from the very basic to the very applied. And we are working on a disease that is really important and where we hope to make a difference."

He believes medical science has made significant advances in combating TB .

"There have been improvements from bench to bedside. Because we understand it better, we have better diagnostics. Because we understand drug resistance so much better, we can customise treatment better  and we can come up with more effectiveregimens for drug-resistant cases."

Due to improved healthcare systems more people are diagnosed and treated, and more patients are completing their treatment.

Multiple drugs

Drug-resistant TB has been an obstacle in TB treatment for many years. It is now being compounded by the increase in antibioticresistant microbes as well as a lack of new antibiotics.

"You need at least four active antibiotics to really cure TB , so whichever bug you are treating must be susceptible to all four. When you have only one or two antibiotics that work in individual patients, the chances of curing them are not great. We are not down to the last antibiotic, but once we get down to the last four, we are in big trouble."

There is little incentive for drug companies to develop new antibiotics. The greatest need is in the poorest countries and the potentially small profit margin may not justify the enormous development costs.

"We are trying to circumvent this problem by engaging in public-private partnerships in which companies and academics work together to advance the development of new antibiotics. Even so, the money available for this is a fraction of what it really needs to be."

Such a scenario may seem hopeless to some, but Van Helden is undeterred.

"When I started TB research more than 25 years ago, the thinking was that you need  dirt cheap, simple diagnostic, otherwise it would never fly. This has been superseded by the realisation that new, better diagnostics cost a lot more, but we are even using them in South Africa because they are so much better that it justifies the extra costs. Having seen that, I can say if we do come up with a really good diagnostic or antibiotic, even if it is expensive, it will fly."

According to Van Helden new frontiers in TB research are manipulating patients' own immune system and developing TB vaccines.

"I never feel the situation is hopeless. I have been in the game so long and have seen so many dogmas come and go, that I have no doubt we should persevere."

Threat to nature reserves

Van Helden completed his PhD studies in biochemistry at the University of Cape Town in 1978 and joined Stellenbosch University in January 1979. Aside from a postdoctoral fellowship in the USA in 1981 and 1982, he has been with the Department ever since.

He met his wife, Eileen (Hoal) van Helden, during his fellowship in America and she also joined the Department of Biomedical Sciences.

"We have been working together since 1982 and it's a huge privilege. She studies the genetics of TB susceptibility and its manifestation in the population groups of South Africa."

They are also both involved in the  department's programme on animal TB , focusing on wildlife. They are wildlife enthusiasts and honorary rangers of SAN Parks. TB is a growing problem in particularly the Kruger Park and the Natal parks, where naïve populations were infected by imported cattle.

"We need to know how important this disease is in a free range system. We know it will kill individual animals, but will it make a difference to the population at large and will it affect the ecosystem? If not, it is one of the many diseases wildlife develop. If it does affect the ecosystem, we need to think about what to do; we don't have the answer to that question. We are especially worried about  rare and endangered species, because every individual counts."

Van Helden is retiring from fulltime management and research in 2017 and is currently clearing out his office. He will continue his research after his official retirement.

"It is going to take me a year to clear my office because I am still running the place. Unfortunately, I am also inclined to be a hoarder."

In the clearing-out process he came across the Honours research project of the FMHS's Senior Director for Research and Innovation, Dr Therina Theron, as well as the experimental work of Prof Mark T. Bedford of the University of Texas' Department of Epigenetics and Molecular Carcinogenesis.

"It is lovely to see people I've been a mentor to succeeding in life, and not only academically speaking. I am still in contact with some of my early students, and it is really rewarding to share in their lives. I think of them as my family."

Caption: Tuberculosis has been an intractable disease for centuries and still poses such a dire threat that the World Health Organisation considers it a priority worldwide. Prof Paul van Helden has devoted most of his distinguished career to TB and is a world-leader in the field.

Photo credit: Damien Schumann