The TB activist agenda in southern Africa: more from the South African TB conference

Participants at the Treatment Action Campaign, SECTION27, Médecins Sans Frontières and Oxfam pre-meeting we mentioned last week identified five crucial interventions to reduce TB cases and mortality in South Africa.

“The partnership between science, community, and policy makers is the only thing that changes reality,” said Dr. Gustaaf Wolvaardt, of the Foundation for Professional Development, as he and Professor Martie van der Walt, Chairperson of the 3rd South African Tuberculosis (TB) Conference (SATB) accepted a memorandum delivered by Treatment Action Campaign (TAC), SECTION27, Médecins Sans Frontières (MSF) and Oxfam just before the opening of the meeting on last Tuesday afternoon, 12 June in Durban.

The memorandum highlighted five interventions that civil society had identified as critical for the reduction of TB cases and mortality in South Africa, based upon presentation and discussions at their conference pre-meeting.

Some of presentations that morning will be discussed more detail in upcoming HATIPs. To quickly review the morning’s proceedings, this post will describe the demands as presented by Leka Dlamini on behalf of TAC, augmented with a sometimes horrifying factoid or two from the presentations and from discussions among participants during the tea breaks, where it may be important to consider the source.

Diagnose all people living with TB and drug-resistant TB (DR-TB)

“In terms of diagnosis of people living with TB and DR-TB, we need active case finding coupled with better diagnostics. We welcome the use of GeneXpert but we must put pressure on Cepheid to reduce the cost of the machinery and cartridges,” Dlamini said.

The Gene Xpert situation in southern Africa is discussed in a bit more detail in a separate blog post that you can read here.

Ensure access to the best available medicines and regimens

“There are new TB medicines that show promising results – for instance bedaquiline and delaminid. These important medicines really need to be looked at by the Department of Health and the Medicines Control Council, to facilitate access to patients dying because of DR-TB,” said Dlamini.

Dr Helen Cox from MSF had described the ongoing process to get bedaquiline approved for compassionate use. Bedaquiline is being developed by Janssen at the same time as Otsuka is developing delaminid, a novel antibiotic which inhibits synthesis of mycolic acid, a critical component of the mycobacterial cell wall. (Data from the phase 2b study of delaminid were published earlier this month in the New England Journal of Medicine). HATIP has wondered why both drugs can’t be offered on compassionate use together, increasing the possibility of a more rapid cure. However, Dr. Cox said that the two drugs have overlapping toxicities, and may not be well tolerated together.

Janssen wrote to TB advocates last week to outline its development plans for the two drugs, and to address concerns about the need for safety studies. In particular the company stressed that a short safety study of the two drugs in combination in healthy volunteers would not be sufficient, and that a longer safety study, possibly in patients with MDR-TB, would be necessary.

It is peculiar that Janssen found no interactions when it tested bedaquiline with a compound from its own library from the same class as delaminid, and found no drug interactions. Could this be another case of a pharmaceutical company not wanting to study their drug with another company's drug because they own a similar drug in the same class (even though it is nowhere near clinical approval), as we have seen recently in the hepatitis C field? Would it rather co-formulate its own drugs together, even if patients might have to wait?

Regardless, one has to wonder whether the two drugs could really be more toxic together than the second-line regimens currently available, and the lack of available data does not negate the argument that XDR-TB patients who have no other options should have the right to try it, unless they can show us the data from safety studies suggesting they are horribly toxic together.

Improve affordability of medicines 

“The medicines are very expensive. And while the Department of Health has successfully brought down the prices of a number of TB medicines during a previous tender, South Africa continues to pay high prices and needs to look at different strategies to drop prices,” said Leka Dlamini

Dr Cox had reviewed much of this during her presentation at the pre-meeting.  For instance, linezolid [a second or rather, third-line TB drug — often one of last recourse for extensively drug resistant-TB—] costs about R282 per pill at South Africa’s public tender price, or R8460.00 per month (over $1000). One particular bit of unpleasantness is that MSF has around five South African patients on the drug but, as outrageous as the price is, the South African government won’t let MSF purchase it at the tender price. Instead, they have to pay the private sector price: R676 per tablet.

“Pfizer, the company that makes linezolid, has not responded to a request to lower the price for use among XDR-TB patients,” she said.

While Dr Norbert Ndjeka who manages the drug-resistant TB programme for the Department of Health detailed how the government has obtained significant price reductions on several of the drugs through its tender process, the prices are still outrageous compared to what the country would pay if it started importing lower cost medicines from overseas or pooling procurement with other high burden countries.

When you consider how many people are showing up as having drug-resistant TB on GeneXpert — around 7% — it is hard to understand why the government is so reluctant to do this. That would mean, if Xpert were being rolled out all at once (and it isn’t), that 7% of the annual burden of around 400,000 cases (28,000 people) would have drug-resistant TB. However, Dr Ndjeka told HATIP that he doesn’t think it is anywhere near that — partly because South Africa’s figures for the last five years are being down-revised by the National Health Laboratory Service. Apparently there was significant double counting of patients, which isn’t surprising given the mobility of much of the population. (Men go to the gold mines, get TB, are counted up there, get sent home, and are then counted again at home.)

So, the actual number of MDR-TB cases in 2009 was more like 5600 and not over 8000. Dr Ndjeka doesn’t believe they will be diagnosing more than 12,000 MDR-TB cases per year for all of the provinces excluding KwaZulu Natal (KZN).

But KZN has a country’s worth of MDR-TB on its own. GeneXpert has rolled out more rapidly in parts of that province, and is adding large numbers of patients to the tally.

What to do with all these drug-resistant TB patients? Decentralise DR-TB care!

“Decentralise DR-TB care —we only have 2500 beds in SA for admitting patients with DR-TB, so we need care to be decentralised to facilities that are closer to people, so that people who don’t need to be admitted can just be administered with treatment at their own home,” said Leka Dlamini.

Given the numbers of MDR-TB patients, the country really has little choice but to decentralise care. Bruce Margot of the KZN Department of Health told HATIP that they have several hundred more MDR-TB patients diagnosed this year than in previous years — and Xpert is only partially rolled out — and they are continually playing catch-up trying to get the patients on treatment. At present, they have 100 mobile injection teams in operation, but need to put 100 more into the field by year end. He noted however, that Xpert was not outstripping the province’s capacity to manage drug-sensitive TB. However, he has done some modelling of the figures for other provinces, and thinks “a few such as the Eastern Cape, are in for a shock for both drug-sensitive and DR-TB."

The Department of Health has developed a policy framework for decentralised care of TB — however some provinces are lagging behind developing their own operation plans.

HATIP will cover this issue in more detail in the future, but one thing that was clear in the meeting — to scale up decentralised MDR-TB care in the country, nurses will have to be trained to initiate and manage treatment for drug-resistant TB, and community health care workers will need to be trained to support care.

Reduce crowding in prisons and implement active case finding and infection control measures 

“The last point is reducing crowding in prison and implementing active case finding and infection control measures. For instance, in Pollsmoor prison, prisoners are commonly held in mass cells in extremely close proximity for up to 23 hours per day,” said Dlamini.

Indeed, Professor Robin Wood gave the most harrowing presentation of the morning on this issue, which merits more detailed coverage in the near future.

Scientists and activists in union

“We’d really appreciate if the people at this conference continue deliberating on these issues because it’s important for all of us, and also for the pharmaceutical companies who are here, to continue manufacturing treatment but to not only think of making profits but also to think of our lives, of people who are infected with TB and DR-TB,” concluded Dlamini.

“What the patients in South Africa need is what stands here,” responded Professor Martie van der Walt who accepted the memorandum from Dlamini. “It’s also what we at the conference would like to see addressed at the policy making level. As for the scientists what we need to do there is determine the impact it will have individual and specific patient impact. But we’ve reached a stage where patients need to take ownership of their own health; we need community mobilisation.”

Professor van der Walt singled out the high cost of treatment. “We will need to address this, going forward as civil society, advocacy and the scientists together.”

“I think that’s why it’s so important that you’re here at the conference,” said Dr. Wolfaardt. “If you look back at the 2000 conference that was in Durban, remember what impact that had on the prices of drugs? Before the conference it was about twelve to sixteen thousand dollars for treatment a year, and after the conference it had come down to about five hundred dollars. “

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