Analysis: How does SA measure up against new TB recommendations?
A new report from the Lancet Commission on Tuberculosis (TB) titled ‘Scientific advances and the end of tuberculosis’ makes several recommendations for how governments should go about fighting the deadly, but curable, disease. The report was published last week ahead of the second United Nations High-Level Meeting on TB.
The World Health Organization (WHO) estimates that over 10 million people fell ill with TB in 2021 and 1.6 million died of the disease. In South Africa, they estimate 304 000 fell ill in 2021 and 56 000 died. The WHO is expected to publish estimates for 2022 within the next month or so.
South Africa has in several respects been ahead of the curve over the last decade when it comes to making the latest TB tests and treatments available to people who need it. But, in some cases, the introduction of new treatments has lagged and some experts have suggested to Spotlight that at least some of the momentum has been lost in the last two or three years. To get a clearer sense of where we stand, we put the Spotlight on how South Africa measures up against several of the Lancet Commission’s key recommendations. We focus specifically on recommendations highlighted in this media release.
TB screening and testing
The Lancet Commission on TB recommends “immediate scale-up in access to molecular diagnostics and AI-assisted chest X-ray technology”.
Molecular diagnostics is one of the areas where South Africa is well ahead of most other high TB-burden countries. The rollout of molecular testing using the GeneXpert platform started here a little over a decade ago. While GeneXpert testing has been routine in South Africa for some years now, access to molecular testing in several other countries remains limited. In addition, recently published drug-resistant TB guidelines indicate that South Africa will be using new molecular tests that can pick up a wider range of drug resistance patterns once drug resistance is detected using the standard molecular test.
Community-based screening with chest X-rays, particularly in high burden districts, using mobile or hand-held chest X-rays, has the potential to detect prevalent TB, including infectious subclinical TB. – Prof Gavin Churchyard
While using X-rays to detect TB is of course nothing new, new mobile X-ray technology and accurate TB detection machine learning models are new. Research published in 2021 found that AI-assisted X-ray technology can outperform humans in determining whether or not an X-ray image is indicative of TB. The WHO has endorsed the use of these X-ray TB screening technologies (a confirmatory molecular TB test is still required) and, as Spotlight has reported, some of these X-ray technologies are being piloted in South Africa – but they are not yet in wide use here.
Further scale-up of digital X-ray screening is required to accelerate progress towards ending TB in South Africa, says Professor Gavin Churchyard, Group Chief Executive Officer at the Aurum Institute and a co-author of the new Lancet Commission on TB report.
“Community-based screening with chest X-rays, particularly in high burden districts, using mobile or hand-held chest X-rays, has the potential to detect prevalent TB, including infectious subclinical TB,” says Churchyard. “Chest X-ray screening has been included in Global Fund and USAID projects and unified algorithms for screening in health facilities and communities are being developed to ensure maximum impact of these interventions. It is also important to learn lessons from the initial phases of the digital chest X-ray implementation and internalise these to have more impactful expansion and scale-up of this technology to support TB case finding.”
Dr Norbert Ndjeka, Chief Director of TB Control and Management at the National Department of Health, confirms that South Africa is using AI-assisted digital X-ray technology in Global Fund-supported districts. In addition, he says, “Some of our provinces like Limpopo have purchased these equipment.” He says progress is slow because the equipment is expensive.
Whether provincial health departments will have money to purchase and effectively use more X-ray equipment in the current context of public sector cost-cutting is unclear.
TB preventive therapy
The Lancet Commission on TB also recommends “endorsement of the 1/4/6×24 campaign” – essentially a campaign aimed at getting countries to switch to new shorter drug regimens for the prevention and treatment of TB by 2024.
The 1 in 1/4/6 refers to TB prevention therapy that is taken either once a day for a month or once a week for three months (called 1HP and 3HP, respectively). These shorter regimens replace older ones where therapy was taken for six or more months. South Africa’s new TB infection guidelines published earlier this year endorse the use of 3HP and dramatically widen eligibility for TB preventive therapy.
“We have 3HP implemented,” says Ndjeka. “We have a lot of rifapentine in the country as well as isoniazid. Uptake is slow in our provinces. We are working hard to improve uptake,” he says. (Rifapentine and isoniazid are the two medicines used in the 3HP regimen.)
Churchyard also says that “the uptake of short course regimens in South Africa has been slow”. But he also points out that the scale-up of 3HP has been included in the post-COVID-19 Recovery plan.
“Generic fixed-dose combination tablets are available for 3HP at a price of $14.50 per patient course, which modelling suggests is cost effective,” he says. “1HP requires rifapentine to be taken daily with isoniazid, which makes the regimen more expensive. Modelling suggests, however, that in South Africa 1HP should be cost effective.”
Treatment of drug-susceptible TB
The 4 in 1/4/6 refers to four-month treatment regimens for TB in children and adults, respectively. The current standard in South Africa is still six months for both groups.
Spotlight reported in September last year that South Africa would be switching to a four-month treatment regimen for most children and that draft guidelines to this effect were to be circulated before the end of 2022. Asked about progress with this, Ndjeka last week told Spotlight that “guidelines are being revised to include this option”. He says implementation will be next year (2024).
Things are somewhat more complicated with the four-month regimen for adults. Whereas the four-month regimen for children contains the same combination of medicines as the current six-month regimen, the four-month regimen for adults contains some medicines that are different from the current standard of care.
“The four-month regimen contains high dose rifapentine, which makes the cost of the regimen expensive compared to the current first-line regimen,” explains Churchyard. This difference is acknowledged by the Lancet Commission, but their report includes modelling that suggests the four-month regimen may nevertheless be cost-effective in South Africa.
Churchyard points out that the new four-month regimen is recommended by the WHO as an alternative to the current six-month regimen – in other words, both are acceptable according to the WHO.
He notes some reasons for reluctance regarding the four-month regimen, including that there is little evidence regarding the regimen’s effect on the antiretroviral drug dolutegravir (taken by well over four million people in South Africa), the need for moxifloxacin resistance testing (moxifloxacin is one of the medicines in the four-month regimen), and that routine TB treatment currently does not include culture testing at the end of treatment or follow-up of patients. He says the current thinking is to evaluate the four-month regimen more carefully in a group of clinics.
In line with this, Ndjeka says the decision taken through the TB Think Tank (a national network of TB experts) was to pilot the four-month regimen for adults rather than rolling it out right away.
That the four-month regimen for adults is to be piloted is no doubt progress, but some will feel that we should have moved more quickly. As pointed out in an op-ed published as part of Spotlight’s World TB Day coverage in March this year, it has been more than two years since the four-month regimen was shown to be effective in a pivotal clinical trial.
Treatment of drug-resistant TB
The 6 in 1/4/6 refers to providing a six-month treatment regimen for drug-resistant TB (DR-TB). As with the introduction of molecular diagnostics, South Africa has over the last decade been a world leader in researching and making new DR-TB treatments available to people who fall ill with the disease.
According to Ndjeka, implementation of the six-month DR-TB regimen started on 1 September this year. The switch to the new six-month regimen is also reflected in South Africa’s recently updated treatment guidelines for DR-TB. Previously, DR-TB treatment lasted for nine months or longer.
In summary, Ndjeka says the department is doing well against the 1/4/6X24 targets. Of four boxes, he says the department has already ticked two (short-course preventive therapy and six-month DR-TB treatment), one will be ticked by the end of the year (four-month TB treatment for children), and one will be piloted (four-month treatment for adults).
TB and malnutrition
The Lancet Commission on TB also recommends “addressing malnutrition as a major risk factor for TB”. The recommendation comes soon after headline-making findings from a cluster randomised trial (called RATIONS) conducted in India that found that providing people at high risk of TB with nutritional support helped to prevent people from falling ill with TB.
“With high levels of food insecurity and undernutrition in South Africa, fuelled by the highest levels of inequality, it is critical that South Africa includes social benefits for people with TB and those in their households to reduce the prevalence of TB in the country and to meet the Sustainable Development Goals for 2030,” wrote Dr Yogan Pillay and Professor Madhukar Pai in an article published in the Conversation reflecting on the RATIONS study.
“We are excited to receive the findings of this study,” Ndjeka tells Spotlight.
Regarding what is to be done about TB and malnutrition in South Africa, Ndjeka only says that he is “planning engagements with local stakeholders to review what has been happening with SASSA (South African Social Security Agency) interventions and discuss the way forward on the matter”. While Ndjeka did not provide more details on the health department’s plans in this area, his answer does nod to the thorny reality that addressing social determinants of health such as malnutrition is probably not a problem that the health department can successfully take on without the help of other government departments.
NOTE: Dr Yogan Pillay is quoted in this article. Pillay is an employee of the Bill and Melinda Gates Foundation. Spotlight receives funding from the foundation. Spotlight is editorially independent and a member of the South African Press Council.