“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
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
“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
“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
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.