Most of South Africa’s long suffering, 8 000 newly detected TB-drug-resistant patients every year are in for a potentially life-saving New Year’s gift, writes Chris Bateman for MedicalBrief.
The National TB Programme (NTP) has developed a TB recovery plan that reduces the DR-TB regimen from nine, (and sometimes 18 months), to six months by adding a highly effective new WHO-approved drug called pretomanid, manufactured by Viatris in India. According to Dr Norbert Ndjeka, chief director for TB Control and Management, Viatris has promised to deliver pretomanid directly to all provinces by the New Year, if not sooner. The National Department of Health was currently helping the NTP revise DR-TB guidelines and secure approval.
While a small percentage of drug-resistant tuberculosis (DR-TB) and pre-extensively drug- resistant tuberculosis (pre-XDR TB) patients are currently getting pretomanid, (in combination with bedaquiline and linezolid, known as BPaLM), the vast majority are not. This is part of a small NTP Programme with access in four facilities in four provinces. Clinicians say that without pretomanid, patients have a greater chance of dying – more especially if they’re in the advanced stages of HIV co-infection. Ndjeka hopes consignments of pretomanid will begin arriving before Christmas, enabling the launch of a carefully prepared provincial distribution and treatment plan. This shorter oral regimen will dramatically boost adherence, saving countless lives.
Ndjeka said “more than 95% of our adult drug resistant cohort will get this (pretomanid) in combination with bedaquiline, linezolid and moxifloxacin. It’s not yet indicated for children under fifteen, but we’re hoping something will become available for them as the global research continues and gets WHO approval.”
MDR TB and pre-XDR TB are responsible for almost one third of all TB mortality in South Africa. Historically difficult to treat with debilitating and even potentially lethal drug side effects, drug resistant TB makes up about 6% of the national TB burden. However, it consumes 80% of the TB drug budget costs and 1% of GDP ($3.45bn). Scientists, researchers, public health experts and clinicians are elated at the development which will initially be bankrolled by the Global Fund for TB, HIV and malaria. Due to the greater drug combination efficacy and shorter treatment duration, it will end up costing provincial Health Departments less than current treatment costs when they do pick up the budget tab, says Ndjeka.
“We’re hoping to introduce it by early next year but in the meantime, we’re working with the WHO, the Global TB Alliance, and our National Essential Medicines List Committee to adapt the WHO guidelines to our context. They need to explain and guide us on findings from the trials conducted by the TB Alliance and MSF (Doctors without Borders). I also need a bunch of signatures from higher up,” Ndjeka confided.
He said the introduction of bedaquiline, registered locally in 2014, had revolutionised drug resistant TB treatment by reducing mortality among extensively drug-resistant tuberculosis (XDR-TB) from 60 % to 20%. A substantial mortality decrease was also observed among other drug-resistant tuberculosis (DR-TB) categories (from 25 to 17%). The appropriate use of the pretomanid combination is expected to drop the mortality rate to below 10%.
Coal-face HIV/TB physician Dr Francois Eksteen confirmed this. Together with the now-retired Dr Tony Moll, he helped uncover Extreme Drug Resistant TB at the Church of Scotland Hospital at Tugela Ferry in February 2005. Ten of 45 sputum samples taken from their bed-ridden TB patients responding poorly to TB treatment and ARV’s showed extreme resistance to all TB drugs used. The discovery caused a global sensation and resulted in XDRTB being uncovered nation-wide and globally.
Ndjeka said drug resistant TB had decreased from nine thousand cases per annum pre-COVID, to 8 000 detected cases last year while drug susceptible (ordinary) TB cases had declined from 200 000 per annum pre-Covid, to 160 000 drug susceptible cases last year.
GeneXpert cartridge crisis prospect
Although COVID resulted in almost universal mask wearing, it also led to far less treatment adherence and presentation at clinics. Between April 2020 (COVID landed in SA a month earlier) and August 2020, 448 000 fewer GeneXpert TB tests were conducted, but they later exceeded upper forecast bounds between December 2021 through to June this year.1 A surge in demand for the GeneXpert cartridges as part of the global TB recovery impacted by the pandemic may be the reason for a well-documented current global shortage.
Ndjeka confirmed the cartridge shortage but said it was not yet a local crisis, though it would be, ‘if more cartridges can’t be sourced.’
Dr Shaheed Vally Omar, Acting Head of the Centre for TB which incorporates the TB Reference Laboratory at the National Institute for Communicable Diseases, said Cepheid, the GeneXpert manufacturers, had committed to delivering 200 000 cartridges to SA per month.
“That’s too low. We test between 230 000 and 250 000 people a month. They need to increase it, so we’re trying to redivert cartridges.”
Ndjeka said a host of factors contribute to ‘leakages’ in the treatment cascade.
“We’re not treating the numbers we’re supposed to. Which is why we want to do an extra million GeneXpert (diagnostic) tests this year. Last year we did 1.9m GeneXpert tests and this fiscal year we’re going for 2.9m (by 31 March 2023). To get there we must do 700 000 tests every three months, (233 333 per month). We managed 650 000 tests over the first quarter.”
Omar says 90% of GeneXpert test results can be made available within 48 hours. Research in the Western Cape by Prof Keertan Dheda, a globally renowned UCT-based TB researcher, has shown that mobile TB testing teams with internet connectivity can lead to results within two hours – matching many clinics with the appropriate technology. Omar said SMS notification almost identical to that used during COVID was now widely available for TB testing clients. Dedha estimates SA’s total MDR TB burden at between 10 and 15 000 people but emphasises that “we’re detecting about 60% – and treating even less.”
The 2020 prevalence of all pulmonary TB in SA was measured at 328 people per 100 000 population, making it the second hardest hit TB country in the world behind Lesotho. It is SA’s most lethal disease and the second leading cause of mortality globally.
Dedha cautioned against resistance amplification, over 5-7 years with new drugs, saying monitoring of patient progress was vital. Last week a sputum test on a platform called GenoScreen which tests for 15 drugs simultaneously was approved locally, dramatically boosting the advent of personalised medicine for TB patients. Coalface testing is, however, needed to validate its efficacy.
Global health experts agree that SA’s contribution will help shift the current 55% global MDR-TB treatment success rates closer to WHO goal of eliminating the TB epidemic by 2035.2
Citations.
- Omar S; Communicable Diseases Communique, July 2022, Volume Number 21 (7). Centre for Tuberculosis, NICD, NHLS.
- Ndjeka N, Hughes J et al: NT J Tuberc lung Dis 24 (10): 1073–1080 Q 2020 The Union http://dx.doi.org/10.5588/ijtld.20.0174