South Africa’s lop-sided TB response: more attention to prevention of drug resistance required

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South Africa needs to spend a lot more money on directly observed therapy for TB (DOTS), according to experts, to avoid a lop-sided response that spends too much on MDR-TB as a result of spending too little on ensuring the success of first-line TB treatment.

While investments in case-finding are beginning to pay off, South Africa still needs to improve its cure rate in first-line treatment; despite spending more than any other high-burden country apart from Russia, South Africa has a far lower cure rate than the world's most populous country, China.

There has been a big scale-up in TB programming in South Africa in the past few years, largely as a result of an epidemic of extensively drug-resistant TB that was first identified in 2006.



To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease. A ‘sterilising’ cure would completely eliminate the virus. A ‘functional’ cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness. 

extensively drug-resistant TB (XDR-TB)

A form of drug-resistant tuberculosis in which bacteria are resistant to isoniazid and rifampicin, the two most powerful anti-TB drugs, plus any fluoroquinolone and at least one injectable second-line drug. 

first-line therapy

The regimen used when starting treatment for the first time.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

directly observed therapy (DOT)

When a health care professional watches as a person takes each dose of a medication, to verify that all doses are taken as prescribed.

Although South Africa's TB programme was turned down for a recent Round 8 Global Fund grant, PEPFAR (including the US Centers for Disease Control (CDC) and USAID), has provided support to the South African government, civil society and a range of partner organisations, including nongovernmental organisations such as the University Research Co.

PEPFAR has recently increased spending on TB/HIV in South Africa from $2,440,321 in 2005 to $32,439,910 in 2008, according to Dr Okey Nwanyanwu, the Country Director of the CDC in South Africa, who spoke during the opening plenary of the South African TB Conference a few months ago.

According to the former Minister of Health, Dr Tshabalala-Msimang, also speaking at Conference, these efforts have begun to bear some fruit.

Case finding and contact tracing

For instance, in his State of the Union Address earlier this year, South Africa’s former president Thabo Mbeki committed the country to reducing the TB treatment default rate down to 7%. To reach the goal “we shall be training over 3000 health personnel in the management of [TB] before the end of the year [and we] established 72 defaulter tracing team and deployed them in the sub-districts with the highest defaulter rates in February this year,” said former Health Minister Manto Tshabalala-Msimang said.

She added there is already evidence that the national defaulter rate has been falling. “Our TB defaulter tracing teams have this year been able to locate 92% of treatment defaulters in the sub-districts where they are deployed. Soon we will expand this tracer project to other districts in the country.”

After years of steady increase, the case rate of smear positive TB diagnosed stabilised in 2007 (at around 340,000 diagnoses, but note this does not include more difficult-to-diagnose extrapulmonary and smear-negative TB cases, which are common in people with HIV). Meanwhile, the government’s reported cure rate increased from 54.9 during the first six months of 2005 to 62.9 for the same period in 2006.

And in response to the extensively drug resistant (XDR)-TB outbreak in Tugela Ferry, in the Msinga health district of KwaZulu Natal, Dr Tshabalala-Msimang said “We then asked the WHO to assist to both explore why this area has so many cases and also what could be done to deal with XDR-TB. We ensured the availability of the drugs needed to treat XDR. We sent our clinicians to Latvia for training in the management of XDR-TB. We made 400 million Rand available to the provinces to improve infrastructure for both containment and to improve infection control, train personnel, purchase drugs and pay for laboratory tests.”

Resources from the local government and from international partners have been pouring in to help deal with the crisis in Tugela Ferry — with significant effect: The treatment defaulter rate has been brought down to zero in the Msinga health district.

At the recent World Lung Health conference in Paris, Dr Anthony Moll offered a clarification, “close to zero” he said, “every several months, we may miss one.”

It is important to note that this was accomplished with several teams of contact tracers, all with vehicles — although to reach some of the most rural hillside dwellings, much of the work has to be done on foot.

When speaking to healthcare workers from other districts in KZN about Msinga’s accomplishments, they roll their eyes. “We would have a zero defaulter rate too if we had the kind of resources that have been poured into Church of Scotland Hospital. As it is, we’ve been able cut our defaulter rate more than half with one tracer team and one vehicle that we share across a number of clinics,” said one.

South Africa’s investments relative to other countries

“We are doing our bit in terms of investing money into this disease,” said Professor Anton Stoltz of the University of Pretoria, and the Foundation for Professional Development. “If we look at the government’s contribution to total TB control costs, we are spending huge amounts of money on our TB control programme.”

He said that the costs of the TB control programme in South Africa are greater than those in any other high burden country with the exception of Russia. He also pointed out that around about 70% of the TB budget will be used for MDR/XDR-TB “and that is extreme compared to all the other countries.”

In fact, it’s about twice the proportion that Russia spends on drug-resistant TB. China, on the other hand, spends the next greatest amount on TB — but about 85% of the budget goes to directly observed therapy programmes (DOTS). Notably, China has a treatment success rate of over 90%.

Part of this expense is for the drugs alone. “It costs approximately R377 for 6 months of standard treatment, while the treatment for MDR-TB cost approximately R31,000 and that is not including the hospital costs, the laboratory costs or the human resource cost,” said Professor Stoltz

Improving cure rates the first time round

Both Prof Stoltz and Dr Matji stressed that this distribution of resources is somewhat lopsided — while there is a need to respond to the emergency at hand, the country should be devoting more resources to making certain that drug resistance doesn’t happen. In other words, the focus should be on programmes to support adherence to standard treatment.

“Instead of fixing a leaking tap, we are mopping water,” said Dr Matji. “But we need to close the tap - that means curing the patient the first time around. One of the major challenges for our country is that systems to support TB patients whilst on treatment are very weak. TB treatment takes a long time; therefore it is important that structures are set up at community level, at the work place or in any place that is convenient for the patients whilst on treatment.”

“South Africa has to decide whether it really wants to implement the DOTS programme or not,” said Dr Nwanyanwu. “Everybody’s trusting that patients should do the right thing but we can’t really assume that everybody out there will take their medication when asked. There has to be support to the patient from family, from community, from partnership to engage them to take their medication. It can be anyone, as long as treatment is observed.”

Several presentations and posters at the conference focused on methods to strengthen DOTS (by increasing the numbers of DOTS supporters) and other mechanisms to enhance adherence, such as direct provision of TB care through HIV programmes, utilisation of lay health workers to provide adherence counselling for the patient and family, and then making weekly follow-up visits to their home.

“I think that patient education is important — people do not understand the disease,” said Prof. Stoltz. “You can speak to the people on the street. They do not know what the disease actually is. It is really difficult for them to see what is happening to the body, they don’t understand it. Once they understand it, they will take their medicine. So we must spend much more time in trying to get to the patients teaching them what is this disease and how they can actually make sure that they complete their courses, take the right amount of medicines.”

Prof. Stoltz also noted a couple of areas of ongoing research to help improve standard treatment outcomes, including an electronic adherence reminder and monitoring device (eMum) in the lid of the pill bottle that is being evaluated in South Africa. These devices not only record how many times the bottle has been opened, but when it has been opened — allowing the nurse to assess whether the patient has been taking their medicine routinely. Other studies are evaluating the pharmacokinetics and the appropriate dosage of TB drugs for populations (adults and children) in southern Africa to achieve blood levels that may inhibit the development of drug resistance.