21 March 2013

South Africa: When Dated Drugs Are the Only Weapon

Photo: Sue Valentine
Phumeza Tisile

Somewhere between walking out her front door in Cape Town, taking a taxi to college and hanging out with friends, Phumeza Tisile caught tuberculosis.

It was during her first semester as a student at the Cape Peninsula University of Technology that Tisile began to cough and lose weight. She was soon so weak she could barely walk. She went to a private doctor who treated her for pneumonia and then sent her to a government health clinic where she tested positive for TB.

That was in May 2010, just months before South Africa hosted the football World Cup, the first time the finals had been held on African soil. While the rest of the country was celebrating, Tisile became increasingly ill. She was taking her TB medication as prescribed, but she was not getting better.

"I'm not a soccer fan, but I remember that time clearly," she says, "I was in Karl Bremer Hospital, but then they had to transfer me to the Brooklyn Chest hospital. I was too weak, but at least I was able to walk. The other patients were enjoying [the World Cup], they even had the energy to blow vuvuzelas. I couldn't care less, but it was nice to have people around, unlike Karl Bremer where you live in a closed room alone."

Tisile's admission to hospital followed her body's failure to respond to standard TB treatment. By this time she was desperately ill with TB in her brain and chest and required a major operation and long-term chest drain.

TB is so widespread in South Africa that simply breathing carries a risk. According to the World Health Organisation's 2012 Global TB Report there are half a million new cases of TB in South Africa each year, and the South African National Aids Council reports a 400 percent rise in TB over the past 15 years.

In most patients, a dose of two to three tablets a day for a minimum of six months cures drug-sensitive TB. In Tisile's case, further tests found that even though she was HIV-negative and had never had TB before, she was diagnosed with multi-drug-resistant TB (MDR-TB) - or so she thought.

Until 2011, South African health guidelines required that patients with multi-drug resistant-TB (also referred to as drug-resistant or DR-TB) receive their treatment as in-patients in one of the country's handful of dedicated TB hospitals. However, with new cases of DR-TB outstripping the bed capacity, the government has been forced to re-think.

At the South African TB conference in June 2012, the director of TB, DR-TB and HIV in the national health department, Dr. Norbert Ndjeka, acknowledged the need to change.

"We will never have enough beds in our lifetime to admit all the MDR-TB cases and we can't keep building more hospitals," Ndjeka told a United Nations news agency. "The first success has been getting the right policies in place. The next success will be when we declare that there are no more waiting lists."

The lack of beds in dedicated TB hospitals meant that not only were people in need of treatment being turned away and left to die in the community, but without treatment they were still infectious and liable to spread MDR-TB to anyone with whom they came in contact.

In 2012, almost 7,400 DR-TB cases were diagnosed in South Africa, but health officials recognise that it is likely that many more cases go undetected.

A small prevalence survey carried out by the international medical humanitarian organization, Médecins Sans Frontières (Doctors Without Borders) in the sub-district of Khayelitsha in 2008 estimated that there were more than 400 DR-TB cases each year in Khayelitsha alone.

Khayelitsha is a poor, densely populated area that is home to more than half a million people, close to a fifth of the population of Cape Town.

But, according to Dr. Jenny Hughes, a DR-TB specialist with MSF, because widespread screening for DR-TB is difficult and patients don't always come to clinics when they are not well, health officials were diagnosing about 200 cases a year in Khayelitsha - half the estimated number.

In an effort to improve the diagnosis, treatment and prevention of DR-TB, MSF set up a pilot, decentralized model of treatment in Khayelitsha. The organization already had an established history of working with the provincial and city health departments in the area, having pioneered prevention of mother-to-child HIV transmission and antiretroviral therapy for people in poor communities there in the early 2000s.

Part of MSF's intervention focused simply on getting the basics right.

"It was about collaboration with the local department of health and integration of DR-TB care into the existing TB/HIV primary health care programme; it involved introducing paper DR-TB registers into all clinics, training staff to record and monitor cases, and then training doctors and nurses how to diagnose DR-TB, what treatment to start and how to monitor patients over their course of treatment. A lot of mentoring and training was involved," says Hughes.

The model also introduced improved infection control measures in facilities because, according to Hughes, current evidence shows that in the majority of cases in South Africa, "probably about 80 percent of MDR-TB patients have caught it from somebody else".

Treatment for MDR-TB takes about two years and includes a daily injection of kanamycin for six months and anything from 20 to 40 tablets a day.

The intramuscular injection is so painful that some patients can't walk, sit or lie down, and many develop an abscess, says Hughes. Over a prolonged period, someone receiving the injection may go deaf, permanently.

Tisile recalls the morning, after several months of her daily kanamycin injection, when she lost her hearing.

"I was at Brooklyn Chest [hospital]. I'd been on the injection for five months and then one morning I woke up, I switched on the television and I couldn't hear anything. The volume was up, but there was nothing. I was like 'what's going on?' Then they told me that was one of the side effects of the injection."

Throughout her treatment no one had warned Tisile about this possible side effect, although the hospital was monitoring patients for hearing loss. "We used to go to the audiologist, they used to test, but I didn't know why," she says. "They didn't tell us anything."

The antiquated drug regimen available for DR-TB treatment poses a crude - and cruel - conundrum to both patient and doctor: take the treatment and risk deafness; refuse the treatment and die.

"I can talk about side effects until the cows come home, it's just terrible," says Hughes. "These drugs were first produced decades ago for normal TB. They have developed better drugs since then, which they now use for normal TB, but because DR-TB is resistant to those drugs, we have nothing else and so we have to use these old drugs against DR-TB and they're horrendous."

A key part of MSF's treatment programme is to provide support to patients to complete their treatment. "To tell a patient that you have to stop working, you have to walk to your clinic every day, take an average of 20 pills and an injection which makes you go deaf - every single day for two years, it's impossible. So you need to find ways to enable patients to do that," says Hughes.

The MSF programme includes helping patients to access disability grants, drug and alcohol abuse services, and support groups where patients can meet to encourage each other through the two-year treatment period. And because the decentralized DR-TB model offers those patients who are well enough the chance to take their medication at their local clinic close to home, there is family counselling and support.

"Each patient who is diagnosed gets an individual counselling session and a home visit where they can look at infection control in the home, screen contacts to see if they also have DR-TB, educate the family and encourage them to support the patient," says Hughes.

Sticking to two years of treatment requires commitment and perseverance.

"Ask any DR-TB patient here in Khayelitsha which of their drugs they would prefer not to take and they will all point to the little yellow one, ethionamide," says Hughes. "It makes you feel so nauseous, you feel like vomiting every single day for two years. You smell it on your hands, everywhere."

But stopping just one out of the large daily handful of prescribed drugs can be disastrous because it creates a gap for further resistance to develop, leading to extensively-resistant (XDR) TB.

Despite MSF's multiple levels of support in Khayelitsha, a third of patients default on treatment at some point in their two years.

"It's complex, there are lots of different reasons" says Hughes. "It's never just one, but I do think that side effects is quite high up there.

You can try to think of all sorts of different strategies to help people take their treatment, but in the end, you need a better drug regimen."

By comparison, treating "normal" TB is relatively simple with just two or three tablets a day, but because people feel so much better after three or four months, it's often a challenge to ensure that they take their treatment for the full course of six months.

Tisile had no trouble taking her normal TB drugs; she followed the doctors' instructions diligently, but to no effect. Like more than 80 percent of MDR-TB cases in South Africa, Tisile caught this resistant strain simply by breathing the air around her.

After nearly three months of MDR-TB treatment, results from the initial culture of Tisile's TB showed that, from the start of her infection, she had extensively drug resistant TB (XDR). This had not been picked up due to inherent delays in diagnostic techniques. The net effect of her different TB treatments - first for normal TB, then MDR-TB, was that she continued to develop greater resistance to the available TB medicines due to ineffective treatment.

Once diagnosed with XDR-TB, Tisile was given a new regimen of drugs and began to make a slow recovery. She remained in hospital for eight months before she was eventually discharged to continue the rest of her treatment in her local clinic. However, two months later, her monthly sputum test showed that the TB was continuing to grow in her lungs. Even the XDR-TB treatment was no longer working. This was when she came to the attention of MSF.

Tisile was admitted to MSF's Lizo Nobanda TB Care Centre - a short-stay facility for patients in the heart of Khayelitsha with just 10 beds. It is dedicated to treating clinically stable drug-resistant TB patients for a short period within their community until they are well enough to continue their treatment at their local primary health care clinic.

At Lizo Nobanda, MSF attempted to construct a drug regimen for Tisile that combined as many drugs as possible that would still be effective.

This involved accessing drugs that show some limited evidence for treating DR-TB, but which are not routinely available in the government sector, such as clofazimine and linezolid. "Linezolid is probably what saved her," says Hughes.

"Here at Lizo Nobanda they managed to get me the expensive drugs which government doesn't have - clofazimine and linezolid," says Tisile. "I also started with the capreomycin injection. It didn't seem to work, so they stopped it. I continued with the other treatment, and now it is still working fine."

Tisile is one of a fortunate, tiny minority of patients in the public health care system who can access linezolid, but only because MSF buys it privately. Other DR-TB patients in public facilities cannot access this drug because it is not "coded" for the treatment of TB. The pharmaceutical manufacturer, Pfizer, has specified that linezolid is a treatment for lower respiratory tract infections only and it holds a patent on the drug until 2014.

"If you happen to be lucky enough to have private medical insurance, then a TB specialist can say, 'ok, you might benefit from this drug' and your health care will pay for it, and you'll get it," says Hughes.

In order to include linezolid in the daily regimen of those select DR-TB patients who need it because they have no other effective treatment options, MSF pays private sector prices, at an "extortionate" U.S.$85 a tablet, says Hughes. Through the government tender, linezolid costs much less, around U.S.$25 per pill, but because of its coding access, linezolid through the public sector is still restricted.

Hughes is quick to add, however, that linezolid should not be seen as a "wonder drug" that will save everybody. "But it is a possible option which should be used in combination with other possible options to make a better regimen for patients in whom existing drug regimens are inadequate. It's all about better combinations rather than individual drugs," says Hughes.

While some new DR-TB drugs are on the horizon and health workers and activists are urging the South African Medicines Control Council to fast track their approval, the best infection control method is to find TB and to treat it. Effective treatment greatly reduces the infectious risk, says Hughes.

"For families of patients that we diagnose, we say the best thing you can do to protect yourselves is support your family member in continuing their treatment," she says.

Tisile's faithful adherence to her treatment is finally paying off.

"It's been difficult, I can't change anything now," she says. "But we are looking forward to the cure because the XDR drugs are working."

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