A global infectious disease killer existed long before COVID-19 and continues to wreak havoc on the lives of millions of people worldwide. Tuberculosis (TB) is a disease caused by the bacterium Mycobacterium tuberculosis, which was responsible for the deaths of 1.6 million people in 2021.
Unlike many bacterial infections that can be treated with several days of antibiotics, the standard treatment for TB lasts six months. Thankfully, in May 2021, researchers reported a new combination of drugs that worked as well as the standard course but can be taken for four months - a full two months shorter than the standard course.
Despite this landmark advance, many countries, including South Africa, have not taken robust action to pilot and evaluate this new regimen as a pathway to making it widely available. The slow implementation of this innovation among many others highlights the neglected status TB continues to occupy despite its devastating and disproportionate impact on impoverished populations around the world.
The new all-oral regimen consists of 8 weeks of daily treatment with the drugs: isoniazid, rifapentine, pyrazinamide, and moxifloxacin, followed by 9 weeks of daily treatment with isoniazid, rifapentine, and moxifloxacin. The notable differences from the standard six-month regimen are the substitution of rifampicin with rifapentine and ethambutol with moxifloxacin, and the continuation of three drugs instead of two drugs after the first two months of treatment.
In June 2021, one month after the four-month TB treatment course findings were reported, the World Health Organization (WHO) released rapid communication, notifying national tuberculosis programmes about the favourable results to allow for planning. The WHO followed up in May 2022 with updated tuberculosis treatment guidelines that recommended the four-month regimen as an option for TB treatment for patients that were similar to those enrolled in the study.
Now, as we just observed World TB Day on March 24, nearly two years after the initial findings, the shorter regimen has yet to be implemented in many high TB burden countries, including South Africa.
Extensive advantages
The advantages of a four-month course for TB are extensive. For patients, two months less of a complex combination of antibiotics that may have side effects and require frequent clinic visits is welcome news. Increased availability for work or school and issues related to disease stigma further increase the appeal of a shorter course of treatment.
One of the risks of any infectious disease that can be treated with medications is the development of drug resistance. Missed treatment doses increase the risk of developing resistance to TB, so shortening the total treatment course may help improve treatment completion as prescribed. In turn, this may decrease the risk of developing drug-resistant forms of TB. For TB programmes, a shorter duration of treatment may decrease the resources needed for patient follow-up and monitoring.
Chief among concerns about the new regimen is the high cost and availability of rifapentine. In addition to the historic deprioritisation of TB in many healthcare budgets, the direct benefits of biomedical research conducted in low- or middle-income countries must be considered. For example, clinical trials to study new diagnostic tests for TB and new drugs for the treatment of TB have been conducted in many low or middle-income countries such as South Africa. If the only people able to access new innovations arising from these research studies are those in countries with abundant resources, serious ethical concerns regarding exploitation of research subjects and populations arise.
These conversations are not new, but critical appraisal of systems that reinforce global inequity is necessary for change to occur. Since South Africa has been on the leading edge of research studies enrolling TB patients to study shortened TB treatment regimens (including for drug-resistant TB), South African TB patients should also benefit from access to these treatment options.
Addressing concerns
Of course, additional concerns need to be addressed before the new four-month regimen is fully implemented. The landmark study on the four-month regimen included few people living with HIV. A better understanding of how this new regimen works in people living with HIV, and especially potential interactions with HIV treatment medications, is critical.
The new treatment regimen does not yet have fixed-dose combinations (where several medications are combined into a single pill), so the number of pills a patient must take each day is much higher than with the standard six-month regimen. TB treatment programmes have been using the standard six-month regimen for decades, so training of staff, organising infrastructure and supply chains for the new medications, and educating patients about the need to take the medications with food will all need to occur.
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Additionally, one of the new drugs in the regimen, moxifloxacin, is used to treat drug-resistant TB and other bacterial infections. Strategic efforts to test for moxifloxacin drug resistance (and baseline resistance to other drugs in the regimen) and prevent development of resistance to moxifloxacin will be essential.
These challenges present tremendous opportunities for South Africa to lead the way in strategic evaluation and piloting of the new four-month TB treatment regimen.
Reinvigorated commitment
A reinvigorated commitment to eliminating TB will require intentional dedication of financial and health-sector resources to TB programmes for care of patients, implementation of innovations, and further research to optimise TB treatment.
Thankfully, a breakthrough four-month TB treatment regimen is available. The time is now to join together for the thoughtful implementation of this new regimen, with operational research to identify any problems early, and to improve the lives of those suffering from TB.
*Van der Heijden, Chihota, and Charalambous are all from the Aurum Institute.
