Researchers have announced a drug that has the potential to shorten and improve treatment for nearly all forms of TB, on the second day of The Union World Conference on Lung Health. Research led by TB Alliance showed that a new compound, TBAJ-876, could be part of a new combination of drugs that could result in a potential “universal regimen” leading to both drug-sensitive and drug-resistant TB being treated with the same therapy.
Results from preclinical and Phase 1 studies presented at the Union World Conference showed that TBAJ-876, when compared with bedaquiline (similar TB medicine), eliminated TB bacteria faster and had a potentially safer profile. Based on these results, a new “Pan-Phase 2” trial is underway to test a potential “universal regimen”.
If successful, TBAJ-876 could prove to be part of the backbone for a regimen capable of unifying treatment for drug-sensitive and most drug-resistant TB with a single, short, and safe treatment combination.
TBAJ-876 is one of several new treatments being hailed as a potential gamechanger and a much-needed step forward in the global fight against TB.
PREVENTATIVE THERAPY EFFECTIVE TO REDUCE THE RISK OF MULTI-DRUG RESISTANT TB IN CHILDREN
The Union World Conference also heard from researchers from Desmond Tutu TB Centre, University of Stellenbosch, who shared how the risk of developing multi-drug resistant TB (MDR-TB) can be prevented in children.
Their study, which was funded by global health initiative Unitaid among other funders, focused on the antibiotic levofloxacin. The team showed that a drug regimen of six months was both safe and effective in preventing the development of MDR-TB in children. This community-based trial focused on child and adolescent household contacts of adults with MDR-TB in South Africa.
The study found levofloxacin to be 60% effective in reducing the risk of TB in a noteworthy step for controlling and – eventually – helping to eradicate MDR-TB in children. MDR-TB disease in children is complex to treat, requires several antibiotics, and can result in catastrophic costs to families. Children with MDR-TB remain one of the most neglected populations affected by TB.
The researchers’ findings lead the way in demonstrating the value of preventative measures for childhood MDR-TB in the face of this global public health issue.
AFRICAN GIANT POUCHED RATS ABLE TO DETECT TB
APOPO researchers from Tanzania, Belgium, Mozambique, and Ethiopia presented analysis into rats that could sniff out the presence of TB.
Researchers discovered that African giant pouched rats could identify the presence of TB in saliva samples using their sense of smell – even when the TB load within the sample was low.
Utilising the animals’ natural strengths allowed the scientists to increase rates of TB diagnosis in some of the world’s most vulnerable communities and subsequently improve the population’s quality of health.
The researchers found that the rats were also more sensitive to the presence of TB in samples from children than adults, in an alternative methodology for rapidly identifying and treating cases of childhood TB.
BATTERY-OPERATED LAB-IN-TUBE DETECTS COMMUNITY TB CASES
The Union World Conference on Lung Health heard from Dr Tony Hu, Professor at Tulane University, who shared how rapid portable, battery-operated tests could be a new tool for point-of-care TB testing requiring minimal equipment and user expertise.
Point-of-care testing does not require specialised clinical or laboratory equipment, making this an invaluable tool in preventing the spread of a disease through early detection. Additionally, it has the potential to be scaled up quickly if disease hotspots are identified, allowing scientists to respond rapidly to TB outbreaks.
Like the African giant pouched rat, the battery-operated test offers new possibilities for making the diagnosis of TB quicker, which is crucial for controlling the disease.
Dr Tony Y. Hu, Director, Center for Intelligent Molecular Diagnostics, Professor of Biochemistry and Molecular Biology, Tulane University: “We are confident that this assay will improve TB diagnosis in all patient populations, including diagnosis of early disease in young children, and allow consistent evaluation of Mtb-cfDNA dynamics that should reflect the systemic effect of anti-TB treatment, both of which are required to improve TB control efforts in resource-limited areas with high endemic TB levels.”
The Union World Conference on Lung Health is convened by the International Union Against Tuberculosis and Lung Disease, the world’s first global health organisation, committed to eradicating tuberculosis and lung disease.
The scientific discoveries come at a crucial moment for the TB community after world leaders pledged funding and agreed targets for the next five years towards ending the global TB epidemic at UN High-Level meeting on health in New York in September.
Professor Guy B. Marks, President and (Interim) Executive Director, International Union Against Tuberculosis and Lung Disease (The Union) said: “As the tuberculosis community looks to the Union World Conference this year, we’re delighted to witness vital breakthroughs in fighting this fatal disease. The groundbreaking results of clinical trials is further evidence that scientists are working together to solve this pressing global health challenge.”
Established in 1920 as the world’s first global health organisation, the International Union Against Tuberculosis and Lung Disease is committed to eradicating tuberculosis and lung disease, leading to a healthier world for all. Its members, staff, and consultants work in more than 140 countries globally.
The Union aims to improve the world’s lung health by prioritising prevention and care, through bringing together clinicians, patients, survivors, policy makers, scientists, and managers to disseminate and implement knowledge in practice. The Union’s work is exemplified by its core values of quality, transparency, accountability, respect, and independence.
domised-controlled trials on preventive treatment in people exposed to multidrug-resistant tuberculosis (MDR-TB). TB-CHAMP was a community-based multi-site household cluster-randomised placebo-controlled trial assessing the efficacy and safety of 24 weeks’ daily levofloxacin in child and adolescent household contacts of MDR-TB across five South African sites.
Background: Multidrug-resistant (MDR) tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) resistant to rifampicin and isoniazid, threatens global TB control. Approximately 2 million children are infected with MDR-Mtb, with about 30,000 progressing to disease annually. There is currently no evidence from randomised-controlled trials on TB preventive treatment in people exposed to MDR-TB.
Design/Methods: TB-CHAMP (Tuberculosis Child Multidrug-resistant Preventive Therapy ISRCTN92634082) was a community-based multi-site household cluster-randomised placebo-controlled trial assessing the efficacy and safety of levofloxacin, conducted in South Africa between 2017-2023. Children were aged 0-4 years regardless of Mtb infection or HIV status, and 5-17 years if Mtb-infected or HIV-positive, with household exposure to an adult (≥18 years) diagnosed in the preceding 6 months with bacteriologically confirmed pulmonary MDR-TB. Households were randomized 1:1 to levofloxacin vs. placebo (250 mg tablets, MacLeods Pharmaceuticals) daily for 24 weeks. The primary endpoint was incident TB (confirmed/unconfirmed) including TB death, by 48 weeks post-randomisation, assessed by a blinded endpoint review committee
Results: 922 participants from 497 households were randomly assigned to receive levofloxacin (n=453) or placebo (n=469); 90% were <5 years, 27% with evidence of Mtb infection, 2% HIV-positive. Five (1.1%) in the levofloxacin and 12 (2.6%) in the placebo arms developed TB (hazard ratio, respectively [HR] 0.44; 95% confidence interval[CI] 0.15-1.25; p=0.121);Figure. In the pre-specified sensitivity analysis of incident TB based on site-adjudication, 4 (0.9%) children in the levofloxacin and 13 (2.8%) in the placebo arms developed TB. Four levofloxacin-arm participants vs. 8 placebo-arm participants developed grade ≥3 adverse events at least possibly related to study drug (HR 0.52; 95% CI 0.16-1.71; p=0.285). Only one child developed tendonitis (grade 2, levofloxacin-arm), resolving after stopping drug.
Conclusions: There was a strong trend for levofloxacin efficacy in preventing TB in children/adolescents with household MDR-TB exposure. Levofloxacin was safe. This trial informs the evidence-base for MDR-TB preventive treatment.
Increased tuberculosis case detection using African giant pouched rats among children and adults in Tanzania
Background: African giant pouched rats (Cricetomys ansorgei), trained by Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling (APOPO) to identify tuberculosis (TB) by smell, have demonstrated their ability to detect TB from sputum. We evaluated rat-based case detection and compared mycobacterium bacillary load (MB-load) among children and adults.
Results: A total of 46,048 samples from 35,766 patients were screened by rats, 3,929 TB cases were detected, and 52% (2029/3929) were additional TB cases contributed by APOPO rats that were missed by routine program smear testing. Compared to DOTs clinics, the APOPO rats were six times more likely to detect TB among Acid Fast Bacilli (AFB) smear +1 or scanty, [90% (1829/2029) versus 60% (1139/1900), Odds ratio, OR=6.11, 95% confidence interval, CI: 5.14-7.26].
The odds of identifying additional TB cases by rat among children were two times higher than adults, [71% (91/129) versus 51% (1795/3542), OR=2.3, 95% CI: 1.59-3.42]. Furthermore, the odds of identifying additional TB cases by rats among children with AFB +1 or scanty were two times higher than adults with the same MB-load range, [75% (86/114) versus 61% (1617/2656), OR=2.0, 95% CI: 1.28-3.03].
Conclusions: Rats contributed for over half of the additional TB cases in a high TB burden setting. Increased TB detection was higher among children, especially among patients with lesser bacillary load.
Portable, battery-operated lab-in-tube detection of active TB and drug prevalence-resistance
·Background: Tuberculosis (TB) remains a leading cause of global mortality, and despite the urgent need for accurate and reliable case identification, 4.2 million (39.6%) of active TB cases were missed in 2021 and only 57% of diagnosed cases are confirmed by gold-standard TB tests. Rapid and reliable assays are needed at the point-of-care (POC) to accomplish TB diagnosis at sites of patient care and sample collection in resource-limited settings without the need for sample transportation, specialized personnel, and expensive, bulky equipment.
Results: The lab-in-tube and battery-powered device can diagnose TB infection and detect drug resistant mutations from patient sputum samples following a protocol than can be performed without highly skilled technicians. Utilizing DNA isolation-free approach, the LIT-TB system displayed 89% sensitivity and 100% specificity in patient sputum samples. With specific design of CRISPR gRNAs to detect SNPs, rifampicin-resistant mutation S450L of the rpoB gene is accomplished to inform clinicians on treatment choice.
The LIT-TB device is a lightweight, field-deployable microincubator and smartphone imager, that can be transported to sites of sample collection and performed by individuals with minimal training at the point-of-care. We believe the enhanced portability and inexpensive equipment will improve accessibility to TB healthcare in developing countries.