31 May 2013

Eliminating TB in South Africa

Tuberculosis (TB) in South Africa is at 'horrifying' rates, say experts, but the good news is much research is being done in this field.


“South Africa is faced with a dual HIV-TB epidemic where the high rate of HIV infection is fuelling the tuberculosis or ‘TB’ epidemic. In addition to this, increasing numbers of people are becoming infected with drug-resistant TB strains,” says Dr Bavesh Kana Head of the Wits University node of the DST/DRF Centre of Excellence for Biomedical TB Research.

Dr Kana and specialist physician Professor Gavin Churchyard of the Wits-Aurum Coalition – both of whom are world leaders in the TB field – delivered their incisive ‘hope versus truth’ presentation at the Wits Faculty of Health Sciences 2013 Prestigious Research Lecture on 29 May at the New School of Public Health Building.

The presentation entitled ‘Eliminating TB’ highlighted the complexity of the TB epidemic and the urgent steps required by South Africa if we hope to achieve the World Health Organisation’s ‘Stop TB’ goal of stabilising and ultimately eliminating this disease by 2050.

TB in SA is ‘horrifying’

What they said about TB in South Africa was horrifying and at the same time reassuring from the perspective that the highest level of TB research is being undertaken in South Africa by researchers of their calibre to develop new TB drugs, diagnostics and vaccines, and to accelerate TB preventive therapy.

 It was horrifying for a number of reasons, including the hard-hitting reality that any one of us can be infected with this killer disease and we might not even know it.

“TB is caused by the bacterium Mycobacterium tuberculosis, commonly referred to as ‘tubercle bacteria’. It knows no social, economic or geographic boundary and anyone who comes into contact with a person with active TB can be infected by the tubercle bacteria,” Dr Kana explains. If, for example, a person with active TB coughs or sneezes in a public space like the office or a shopping mall or bus, the disease can be transmitted.

It comes as no comfort that South Africa has the highest incidence of TB in the world, per capita population. “The World Health Organisation lists us as third to India and China, but when you correct for population size, we are the highest,” says Professor Churchyard.

While TB can be successfully treated with antibiotics for at least six months, the drugs need to be taken exactly as prescribed, and for the full duration of the course. If the drugs are not taken correctly they may not work and the person may develop multi-drug-resistant TB.

New drugs needed urgently

“We urgently need new TB drugs because multi-drug-resistant forms of TB, in other words, strains of the bacteria that are resistant to two of the four most effective firstline TB antibiotics currently on the market, are on the increase. In 2002, the prevalence of multidrug resistant TB in South Africa was approximately 3% of total TB presented; by 2008 that had risen to 9%. Extensively drug resistant TB is also on the increase where the bacteria are resistant to first and secondline antibiotics.

 Firstline antibiotics are generally used in the first two months of TB treatment, and if drug resistance is detected then secondline antibiotics are used.

There are numerous new TB drugs in the development pipeline, many of them being tested here in South Africa in clinical trials. “We may see the introduction of new drugs in the next few years, but we are still some way from a completely new treatment regimen that will shorten the duration of TB treatment,” says Dr Kana.

Professor Churchyard commented that “South Africa needs to start preparing for the roll out of new drugs that can be included in the treatment of MDR TB”.

“In addition to this, the majority of drugs that we use to treat TB are targeted against bacteria that are actively growing and do not work well on dormant bacteria” says Dr Kana. Many individuals infected with the tubercle bacteria have latent TB infection, that is, they do not display symptoms, presumably because the tubercle bacteria are dormant. 

80% in SA have TB

Professor Churchyard added that “In South Africa up to 80% of young adults are infected with TB and we need to find better, shorter treatment regimens to treat those at greatest risk of developing active TB disease”. In this case, treatment with the current drugs is challenging.

Symptoms that are very suggestive of TB include a persistent cough, night sweats, weight loss and fever. Other symptoms that may also suggest TB include loss of appetite, tiredness and muscle weakness, coughing up blood and chest pains. Anyone experiencing these symptoms must get tested.

“What makes TB especially complex is that many people who have contracted TB do not even know it, either because they have not gone to the clinic or hospital and it has therefore not been diagnosed, or because they have latent TB,” continues Dr Kana whose lab is engaged in critical research to determine why some people develop latent TB while others develop the active form, as well as why a significant percentage of the bacteria in people with active TB are dormant.

People with latent TB do not transmit TB, but if they happen to become infected with HIV, it drives up their chance of the latent TB becoming active. “When a person is diagnosed with TB and HIV together, it is especially problematic as the body reacts horribly,” says Dr Kana. “Normally when you have active TB alone, you have a strong inflammatory response with lesions developing in your lungs. This inflammation is different with HIV, and disease not only occurs in the lungs but all over the body.”

However, in a strange twist of disease fate “people with HIV reduce their risk of TB infection by two-thirds if they are on antiretroviral therapy (ART),” Professor Churchyard explains. “And if they are on both ART as well as the current TB preventive therapy (such as isoniazid TB preventive therapy or IPT), it reduces the risk of TB by 40%.”

IPT is an important intervention for preventing and reducing active TB in communities affected by HIV. Taken in pill form, IPT is given for six to nine months. The World Health Organisation (WHO) has also recommended scaling up IPT to all at risk individuals, which, it believes could play an important role in TB control.

Churchyard highlighted that “IPT is one of the ‘Stop TB’ strategies advocated by the WHO as part of its campaign to achieve TB elimination worldwide by 2050.” But this can only be achieved by a widespread acceleration in IPT and other current TB preventive strategies, including a well-managed national programme, with efficient administration and distribution.

“It has to be done in combination with the development of new TB drugs, far more proactive diagnostic programmes and new vaccines that are effective for a lifetime,” says Dr Kana.

 The current injected vaccine known as BCG, which is administered soon after birth, is effective in protecting children against tuberculosis meningitis (TB in the brain) but it does not protect against lung TB, particularly in adolescence when immunity wanes. A lot of research is being done to try and understand why the vaccine wanes and to develop a new generation of BCG that offers extended protection. “Although we have had a recent disappointment with the first new TB vaccine tested for efficacy that showed no benefit in infants who received the vaccine, we should remain optimistic as there are a number of other promising vaccines that are still under development” say Professor Churchyard.

Hurdles in SA

Researching and coming up with solutions for all this is complicated enough without another huge hurdle in TB treatment in South Africa: adherence to the treatment programme. “The standard six months of TB treatment leads to poor adherence as patients require treatment every day during those six months,” explains Dr Kana. “The logistics are prohibitive for many patients who live in rural areas or far away from their nearest hospital and clinic. And in some cases the patients show up but the drugs haven’t arrived. They become despondent and don’t return.”

Another problem with the TB management programme in South Africa is that the diagnosis takes too long. “In people with HIV, the TB bacterium is often not detectable under the microscope and it takes 3-4 weeks to grow the TB culture, and in the meantime the patients are out there, sick and transmitting TB” Dr Kana explains. “A newer method that detects TB DNA, and which produces results in about two hours, is currently being rolled out in South Africa as a replacement for the old method for diagnosing TB using a microscope.”

There are a significant number of people in the country with TB who never receive treatment because South Africa does not have the resources to engage in active case finding in communities. “We have to wait for them to come to us,” says Dr Kana. 

 The Department of Health needs to resource and promote case finding and the roll out of new diagnostics while ensuring that TB drugs are available all over the country at all times. 

 Dr Kana and Professor Churchyard eloquently conveyed the message that despite widespread BCG vaccination and a WHO-approved drug treatment programme, there is so much more to TB elimination in our country than is being undertaken. Decisive action is required in terms of policy and management to combat this increasingly complex disease that continues to cause long-term suffering and death in South Africa. Without this, the stabilisation and elimination of TB will remain a hope rather than an achievable reality.


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