Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which causes TB.Credit: NIAID
Two trials in South Africa and Vietnam are informing imminent updates to the World Health Organisation’s guidance on tuberculosis preventive treatment (TPT) initiatives. These showed that giving the antibiotic levofloxacin daily for six months to people of all ages living with people with drug resistant forms of TB (MDR-TB) protects them significantly from becoming infected.
WHO sees scaling up preventative treatment as critical to its End TB Strategy. While TB-related deaths have fallen worldwide by 19% since 2015, 10.6 million people (23% in Africa) still became ill in 2022, said the World TB Report 2023. The continuous spread of MDR-TB (a form of TB not responding to standard treatment with isoniazid and rifampicin) poses one of the most challenging and urgent obstacles to global TB control efforts, noted a 2024 study in BMC Infectious Diseases scrutinising the Global Burden of Disease 2019 database. There were 687,839 such cases worldwide in 2019, mostly in Southeast Asia and Sub-Saharan Africa.
Levofloxacin is often prescribed to treat drug-resistant TB and other bacterial infections in adults, such as pneumonia, sinusitis, skin and urinary tract infections. Its specific inclusion into WHO’s new TPT guidelines, expected in July 2024, marks the first time that the UN agency has provided detailed precautionary guidelines since 2017 when it conditionally started recommending preventative treatment for contacts of patients with MDR or rifampicin-resistant (MDR/RR-TB) TB.
The developments follow the Union World Conference on Lung Health in Paris in November 2023, where the combined results of South African and Vietnamese phase 3 clinical trials were presented. The VQUIN trial, led by the Woolcock Institute of Medical Research at the University of Sydney and the Vietnam National Tuberculosis Program, found that preventatively giving levofloxacin reduced the risk of MDR-TB infections by 45% among adult and adolescent household contacts. The TB-CHAMP study was conducted at five sites across South Africa – a country where TB remains the leading cause of death. The risk of children in the trial developing MDR-TB was reduced by 56% when preventatively receiving levofloxacin.
The drug is “incredibly safe” to use for TB prevention in especially children, says Anneke Hesseling, the TB-CHAMPS principal investigator and director of the Desmond Tutu TB Centre at Stellenbosch University (SU).
“This is a good news story in our fight against MDR-TB. We now need to work to translate these findings into practical impact for children affected by it.”
During the TB-CHAMPS trial, palatable, and easy to swallow formulations of levofloxacin were developed which are now commercially available.
“Eleven million dollars are saved for every 1000 children receiving it pre-emptively. Most importantly, you are saving lives and preventing TB in children,” notes Hesseling.
An estimated 30 000 children younger than 15 years develop MDR-TB disease each year. Less than 20% of young patients are currently diagnosed and treated globally. Most are infected by members of their own household. Children younger than two years old are especially vulnerable because of their underdeveloped immune systems. TB-exposed children must therefore be identified, screened, and treated.
Hesseling says treating MDR-TB in children with current medications is “still complex”. Many have serious side effects. Treatment comes at a high cost to health services and families. A 2022 study in the International Journal of Tuberculosis and Lung Disease however, found caregivers willing to walk the extra mile to give preventative treatment to children living with drug-resistant patients.
In 2022, research in South Africa led by the University of the Witwatersrand also informed WHO policy changes on drug-resistant TB. It saw treatment options change from injections to oral medication only, treatment time reduced from 18 months to six, and the 23 daily pill regime cut to 23 weekly.
Efforts continue worldwide to find unexplored treatment options against MDR-TB. In February the multi-dollar Grand Challenges Africa Drug Discovery Accelerator (GC ADDA) programme, funded by the medical research charity LifeArc and the Bill & Melinda Gates Foundation, announced that chemical biologist Erick Strauss from the Department of Biochemistry at Stellenbosch University and Gabriel Mashabela at the South African Medical Research Centre for TB Research will lead renewed drug discovery efforts. It includes South African researchers from Rhodes University and the University of KwaZulu-Natal. A Kenya Medical Research Institute team will search for natural products that could block the resistance mechanism that tuberculosis-causing bacteria can develop against existing anti-mycobacterial drugs.
Marieke Van der Zalm led a study which was the first to reveal the long-term damage of pulmonary TB on adolescents’ lungs.Credit: Marieke Van der Zalm
“All adolescents studied had lower than expected lung function. This is concerning as lung development starts during pregnancy and continues until adulthood. TB in adolescents might lead them to have chronic lung diseases early on in life,” she says.
Van der Zalm sees adolescence as a particularly vulnerable, yet often overlooked stage in terms of TB and lung health. Not only are their lungs still developing, but youngsters often start experimenting with smoking or vaping, thereby increasing their risk of subsequent respiratory morbidity. She urges lung health to be included as an outcome in all new treatment studies for children, adolescents, and adults.
