SA research makes dramatic strides in eradicating deadly TB but challenges remain

In the lead up to world tuberculosis (TB) awareness day on 24 March, researchers at the Clinical HIV Research Unit (CHRU), deputy director Dr Mohammed Rassool and senior medical officer Dr Pauline Howell, provide insights into the TB burden in South Africa, how clinical research is addressing it and where the challenges still lie.  

Tuesday, 23 March 2021: The SA TB prevalence study released earlier this year shows an extraordinarily high TB prevalence. SA has the sixth-highest TB burden worldwide and Covid-19 has had a significant affect. According to TBFacts.org, 58 000 people in SA died of tuberculosis (TB) in 2019, and in the same year, the World Health Organisation estimated a TB incidence rate for SA of 615 per 100 000 people.

Around two thirds of South Africans have been infected with TB however, only a proportion of these progress to having active TB disease. Children less than 5 years old, HIV-positive people and those living with diabetes have a greater chance of getting sick with TB.

CHRU’s goal is to end morbidity and mortality as well as TB disease. We are achieving this by enrolling participants into clinical trials to test safer, shorter and more tolerable regimens that inform treatment guidelines and standards of care. Together with the international research community, CHRU is involved with several clinical trials to improve cure rates which we are achieving by testing shortened treatments and finding ways to minimise the side-effects of TB drugs. Our clinical studies cover all types of TB from drug sensitive (DS-TB) to the most difficult form of TB to treat: extensively drug resistant TB.

Our studies usually involve adult participants, but we are also establishing the dosing and safety of new TB drugs in pregnant women and children. CHRU is also involved in studies to treat TB infection (as opposed to TB disease), referred to as TB preventive treatment. Studies to shorten the treatment for normal TB are also coming in.

Research benefits to TB patients
TB research has delivered significant benefits for patients, clinicians and the health system. There is ongoing work that is proving successful in further reducing treatment duration for DS-TB. Until 2016, the treatment of all drug resistant TB (DR-TB) disease used to be 20 months of medicines which involved daily painful injections and a significant risk of permanent hearing loss. It was not surprising that only 50% of DR-TB patients were successfully treated. Major strides have been made in lessening side-effects and treatment timeframes for DR-TB.

Research has produced a safer, more tolerable and effective all-oral regimen. SA has been lauded internationally for its inclusion of bedaquiline – the first new medication registered in over 50 years for the treatment of rifampicin resistance (RR) TB – in the national guidelines within three years of registration. Providing bedaquiline to South Africans with RR-TB has halved the mortality of patients with DR-TB in South Africa.

Coronavirus impact on TB
The Covid-19 pandemic has significantly affected SA’s TB programme. TB diagnosis rates declined. Now it seems that the health system is seeing an increase in patients presenting with more advanced TB disease. With TB testing as the mainstay of SA’s TB programme, Dr Francesca Conradie, a principal investigator at CHRU, recently called for a renewed focus on TB testing to make up the testing backlog that the Covid-19 lockdowns in 2020 caused.

While treatment and care of all trial participants continued, enrolment for clinical studies was put on hold and fewer patients came forward to participate in clinical studies.

There are still TB questions that research has not answered, yet funding for TB research is limited. The fact remains that TB is infectious and can be fatal. It will be with us long after the Covid-19 pandemic abates.

TB-HIV coinfection
SA has a TB-HIV co-infection rate of over 60%. HIV-infected individuals, especially those with low CD4 counts, have a far higher risk of developing TB than people who don’t have HIV. We are working on several studies to address this, and are therefore particularly interested in TB treatment outcomes based on HIV status and interactions with antiretroviral treatment (ART).

Stigma
Adherence to ART is often linked to socio-economic issues, and this extends to adherence to TB treatment. The challenge is social stigma: those who hide their disease fearing discrimination. This is one of the main causes of delayed diagnosis. Crowded living spaces drive both TB infection and social stigma. People living in informal settlements, prisons, mines or orphanages are especially affected. To end TB, we need to end the stigma and increase social awareness and tolerance of the disease. CHRU’s community outreach teams work hard to deal with this.

Recent TB research outcomes
The final results for the Nix-TB trial that CHRU was part of were reported at the annual Conference on Retroviruses and Opportunistic Infections held earlier this month. It was revealed that nine out of ten participants with DR-TB have durable cure that extends to two years after finishing treatment.

Known as the BPaL (bedaquiline, pretomanid and linezolid) regimen, 109 participants were enrolled for treatment with a three-drug, six-month, all-oral regimen which is significantly shorter, more efficacious and tolerable than conventional treatment. Side-effects were manageable and resolved in the majority of participants.

Five different countries including SA are already using the regimen (either under observational research or registration) since it received US Food and Drug Administration approval in August 2019. In the world of DR-TB, that’s lightning fast!

With funding from USAID, the South African National Department of Health is now rolling out a BPaL clinical access programme to provide the BPaL regimen to patients with highly drug-resistant forms of TB.

It’s exciting that research findings are translating into access for non-trial patients.

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