The deadlycombination

Near incurable TB – thriving on on the biggest HIV positive population in the world – is South Africa’s new scourge


It’s no fun being HIV positive. It’s no fun having tuberculosis either. It’s even less fun having both at the same time: HIV is the world’s biggest infectious killer. TB occupies place number two. And it’s unfunny in the extreme having these illnesses, being a young mother living in a tin shack, with a precarious job, and the demands of a baby.
Helen is a researcher at a South African university, monitoring the effects of the novel diagnostic tool Quantiferon TB GOLD on possible TB patients. Every morning she drives out from Cape Town to the township of Khayelitsha, whose five hundred thousand residents suffer “the highest violence in South Africa, the highest HIV and highest TB rates”. And that’s saying something..
At the clinic she works at, the test she administers is more accurate than the classic century-old tuberculin skin test, which relies on inserting a sample of TB bacteria into the patient’s arm and assessing the immune response – a bump that appears shortly after. Her diagnostic tool on the other hand is expensive.
But the role Helen has found herself in is not only one of a researcher but as an activist. “It goes with the territory of researching in public health,” she says laconically.
Fifteen to twenty mothers come to her every day, often listless and with the gauntness and characteristic cough symptoms of early stage tuberculosis. It’s hearsay: Helen has acquired a reputation for being helpful.
She gives an example. Forget expensive diagnostics of babies, the fact is that if anyone in the family has had TB, then there’s a fifty percent chance that the baby will eventually catch TB also. The official protocol is to treat prophylactically. It’s quite painless: a once a month visit to the clinic for one dose of isoniazid, one of two main frontline antibiotics. But in the past, this has seldom happened.
Instead, many babies catch TB – and curing the active disease is a long six month daily drugs regimen. Helen finds the situation unbelievable. So every week she accompanies mothers to a TB clinic to get them preventative medicine.
Her activist task is a broader one: it’s about getting mothers into the healthcare system for treatment. Another doctor told me: it’s the legacy of apartheid, people don’t know how to be demanding.
When patients take time off work – if they do have a job, which will be at risk – they are often told to come back later for another appointment. TB diagnoses are often tested for HIV also, which becomes another appointment. Bewildered, the patients often give up, shrug, go back into the community. There are family duties calling; daily life makes its demands.
Helen says: “I want to help people who have fallen between the cracks.”

Yet the people whom Helen sees are the lucky ones, for once they are inside the health system – when they eventually get in - they have hope of a cure. Within a matter of weeks, the TB becomes asymptomatic and non infectious. According to Prof Salim Abdool Karim, pro-vice chancellor (Research) at the university of KwaZulu-Natal and the head of CAPRISA, the South African AIDS research organisation, TB diagnosis and treatment has become a way to bring South Africa’s HIV positives within the remit of treatment. He explains.
HIV weakens the immune system. More than one in three, perhaps as much as half, of South Africa’s population has what is known as latent TB: with no manifestations of the disease whatsoever, they have a couple of hundred of the rod-shaped tuberculosis bacilli, dormant and contained within their lungs by their immune systems.
In most healthy people the TB remains that way with a ten percent chance of latent TB morphing into its active variant in a lifetime. With HIV, however, the immune system is weakened and the TB bacteria more easily break out and multiply: making the TB active: destructive, infectious and symptomatic.
The chances of HIV positives developing spontaneous TB out of their latent infection is ten percent a year; a thirty-fold increase in probability.
The upshot is: a large proportion, perhaps sixty percent, of all active TB cases in South Africa are in HIV positive people. A further result is: catch a TB patient and the chances are that you will also catch an HIV positive one. Once on TB drugs, and on antiretroviral therapy, both in theory provided free of charge by South Africa’s health system, is less at risk of harm to himself and to others. Millions of South Africans remain outside the system, however: have undiagnosed HIV and are at great risk of catching active TB from other carriers in crowded bush taxis or homes – a TB which can kill virulently and quickly – and sometimes appears in an incurable form.

The highest impacting article in a science journal in recent years in the subject was a Lancet report describing tuberculosis infection in a population sample in the remote town of Tugela Ferry last year. It sent shockwaves around the medical world. It recorded an astonishing mortality rate: Within a few weeks of a diagnosis carried out one group of 53 TB patients, 52 had died. All were HIV positive. They were not on retrovirals, which afford some protection against TB. As students of Victorian literature know, people with TB can take years to die. HIV not only makes people more susceptible to active TB, but can speed up progression of the TB disease enormously. In contrast, on their own, HIV as well as TB kill slowly.
Worse, on autopsy, it was found after extensive culture testing – where coughed up TB bacteria in a sputum sample are incubated, allowed to grow, and tested against various antibiotics, it was found that the TB was resistant to all but the most expensive and toxic reserve drugs, which would have to be taken daily for two years to work. In practical terms, in African terms, this variant of TB was incurable.
Drugs resistant TB is not unknown – TB resistant to the first line, most commonly used drugs makes up 5% of TB cases worldwide. Resistance arises because people don’t take their antibiotics properly: in a six-month course of drugs, where the patient begins to feel well within weeks, it is easy to lapse.
But the high mortality rate, the fact that these cases were resistant to most second line “reserve drug” antibiotics also, and the knowledge that this was in South Africa, a dry tinderbox for the spread of the wildfire of TB, helped shock the World Health Organization into launching a global campaign into what has since been termed Extensively Resistant TB, XDR TB.

How many other Tugela Ferry-type incidents have there been?
South Africa is a big place; in the huge, impoverished hinterlands, away from the skyscrapers of Johannesburg and the chic seafront of Cape Town, tens of thousands die every year of HIV-related diseases, and TB is the most common opportunistic infection. Up to 40% of undiagnosed HIV positives die of TB, says Gary Maarten, chief specialist physician at the Groote Schuur hospital in Cape Town. The number of those TB-deaths that are XDR TB is anyone’s guess. Tugela Ferry was only discovered because that clinic was part of a monitoring programme involving the University of Yale.
So far there have been more than 400 confirmed XDR dead in South Africa, but the real number is likely to be higher – and there are people living, undiagnosed with XDR TB, spreading it to others in the defenceless HIV population.

Pharmaceutical companies were until very recently uninterested in new drugs against TB. Antibiotics were discovered in 1946 and initially seemed like the final solution. In previous centuries, in Europe, TB was the biggest infectious killer. But antibiotics seemed to consign it to history. Researchers started on different lines of work. The last TB drug was patented 40 years ago.
But now, in part due to the anxiety of Western governments, in part due to generous funding from the Bill Gates Foundation, there are half a dozen new antibiotics in advanced stages of the drugs pipeline, using novel molecular mechanisms which by definition no TB bacilli have acquired resistance to.
Several are in clinical trials, in South Africa, but may take a decade to reach approval. One drug at least, from Tibotec pharmaceuticals, could shorten treatment time to a few weeks so would eliminate the problems of non compliance that eventually lead to resistance. There is also work on a new vaccine, which may take twenty years. Several advanced diagnostic tools are also becoming available, but they are expensive.
The chances are that individuals in rich countries will be able to breathe a sigh of relief at a danger that will never materialise. (There are a handful of XDR cases in Germany under control in expensive marathon treatment programmes.) Whether the new treatment methods will penetrate into the townships of Africa is another matter. The lack of infrastructure and capacity to operationalise the latest pharmaceutical developments is partly a failure of political will: the South African government, says Marta Darder of Medecins sans Frontieres in Cape Town, has shown “poor willingness to tackle South Africa’s enormous health problems”, and sometimes advocates distinctly non-scientific solutions to the worst AIDS epidemic in the world: the health minister Manto Tshabalala-Msimang is on the record as saying a good dose of garlic will cure HIV.
For Helen, meanwhile, tomorrow is another day at the clinic.