Despite being a preventable and curable disease, tuberculosis (TB) continues to claim millions of lives worldwide, ranking among the top infectious killers. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has made treatment increasingly complex, particularly in low-resource settings. Traditional diagnostic methods and lengthy treatment regimens have posed significant barriers to timely detection, adherence and cure.
In recent years, the global TB response has seen remarkable progress. A wave of innovative diagnostic tools, shorter and safer drug regimens and promising new therapeutics have begun to shift the landscape of TB control. From AI-powered diagnostics to targeted drug-resistant testing and novel oral drug combinations, these advancements are poised to enhance the accuracy, accessibility and effectiveness of TB diagnosis and treatment.
This article explores the latest breakthroughs in TB diagnostics and therapy, highlights ongoing clinical trials and distinguishes between what’s currently available to physicians and what remains in development offering a comprehensive overview of the future of TB care.
Revolutionary Advances in Diagnostic Technologies
1. Xpert MTB/RIF Ultra
Xpert MTB/RIF Ultra is a rapid, cartridge-based molecular test used to detect Mycobacterium tuberculosis DNA and rifampicin resistance directly from sputum samples.
Prequalified by the WHO in 2024, it is an enhanced version of the original Xpert test with improved sensitivity, especially in paucibacillary cases (low bacterial load) such as in children or people with HIV.
The test is performed using the GeneXpert platform, where a sputum sample is mixed with a reagent, placed into a single-use cartridge and then loaded into the machine. The device performs automated real-time PCR (polymerase chain reaction) analysis and delivers results within 90 minutes to 2 hours.
The simplicity of the procedure, minimal biohazard risk and speed make it ideal for decentralized and resource-limited settings. It is currently in widespread clinical use and helps guide early treatment decisions, particularly in regions with a high TB burden.
2. Fujifilm SILVAMP TB LAM (FujiLAM)
FujiLAM is a rapid, urine-based diagnostic test developed to detect lipoarabinomannan (LAM), a component of the TB cell wall in individuals with suspected tuberculosis, particularly those living with advanced HIV. It is especially useful in diagnosing extrapulmonary and smear-negative TB, where traditional tests often fall short.
The test is simple to perform: a small urine sample is applied to a test strip and results are available within an hour. Unlike earlier LAM tests, FujiLAM offers improved sensitivity and accuracy, making it a powerful tool for early TB detection in immunocompromised patients.
Recommended by WHO, FujiLAM is currently in the rollout phase across several high-burden countries and is already being used in clinical practice to enhance case detection and reduce diagnostic delays among vulnerable populations.
3. Targeted Next-Generation Sequencing (NGS)
Targeted NGS (Next-Generation Sequencing) is a molecular diagnostic technique that analyzes the genetic material of Mycobacterium tuberculosis to identify mutations linked to drug resistance. Unlike conventional culture-based methods, which can take weeks, NGS offers a faster and more detailed resistance profile, allowing clinicians to tailor treatment plans based on the specific mutations present.
In 2024, the WHO issued official guidance endorsing its use, particularly in reference laboratories and specialized settings. The method involves sequencing selected regions of the TB genome that are known to harbor resistance-associated mutations. This enables precise detection of resistance to both first-line and second-line TB drugs.
Currently in clinical use within advanced laboratory networks, targeted NGS is a key step toward personalized TB care, helping to improve treatment outcomes and prevent the spread of drug-resistant strains.
4. AI-Powered Portable X-Ray Systems
AI-powered portable X-ray systems combine digital chest radiography with artificial intelligence algorithms to rapidly detect signs of pulmonary tuberculosis. Designed for use in mobile screening units, these systems are especially valuable in hard-to-reach and underserved communities, where access to traditional diagnostic facilities is limited.
The technology uses lightweight, battery-operated X-ray devices paired with AI software that automatically analyzes the chest images for TB-related abnormalities. This allows on-the-spot interpretation, even in the absence of radiologists and provides results within minutes.
Now in active clinical use, these systems are being deployed in community-based TB screening programs around the world. They are helping to expand diagnostic coverage, accelerate case detection and bridge diagnostic gaps in remote and high-burden settings.
5. Siiltibcy Serological Test (rdESAT-6/CFP-10)
The Siiltibcy Serological Test is a blood-based diagnostic tool that detects immune responses to specific TB antigens, rdESAT-6 and CFP-10, which are absent in the BCG vaccine strain. This makes it especially effective for distinguishing TB infection in BCG-vaccinated individuals, where conventional tests like the tuberculin skin test may yield false positives.
Approved for use in the European Union in 2025, this test can help identify both latent and active TB through a relatively simple laboratory process that measures antibody responses.
It offers a faster and less invasive alternative to traditional methods and is currently in clinical use across Europe, particularly in screening programs and occupational health settings. Its adoption marks a step forward in streamlined TB detection, especially in low-incidence regions aiming for better surveillance and control.
6. Raman Spectroscopy with AI
Raman Spectroscopy with AI is an emerging diagnostic approach that uses light-scattering technology to detect unique molecular signatures of Mycobacterium tuberculosis in clinical samples such as sputum. By analyzing these spectral patterns with machine learning algorithms, the system can differentiate between TB-positive and TB-negative samples with high accuracy, potentially without the need for culture or molecular amplification.
Currently in the preclinical and early clinical trial stages, this technology has shown promising results in research settings, offering a non-invasive, rapid and highly specific method of TB detection. Though not yet approved for clinical use, it holds significant potential for low-cost, point-of-care diagnostics in the future especially in areas where lab infrastructure is limited.
If proven successful, it could revolutionize TB screening by providing fast, culture-free diagnosis with minimal resource requirements.
7. TAINT-TB Imaging (Nanotechnology-Enhanced CT Contrast)
TAINT-TB Imaging is an experimental diagnostic technique that integrates nanotechnology with high-resolution CT scanning to enhance the visibility of tuberculosis lesions, particularly in extrapulmonary sites. It uses specially engineered TB-specific contrast agents that bind to mycobacterial components, improving lesion contrast and making subtle disease manifestations easier to detect.
Currently under development in Spain, this technology remains in the research and development phase and is not yet approved for clinical use. However, early studies suggest that it could play a pivotal role in diagnosing complex TB presentations such as those involving lymph nodes, bones or the central nervous system.
If successfully translated into clinical practice, TAINT-TB could become a powerful imaging tool for improving diagnostic accuracy and guiding targeted treatment strategies in difficult TB cases.
New and Emerging TB Drug Regimens
1. BPaLM Regimen (Bedaquiline, Pretomanid, Linezolid, Moxifloxacin)
The BPaLM regimen is a transformative six-month all-oral treatment for multidrug-resistant tuberculosis (MDR-TB). It combines Bedaquiline, which targets the bacterial ATP synthase; Pretomanid, a nitroimidazole active against replicating and non-replicating TB; Linezolid, a protein synthesis inhibitor and Moxifloxacin, a fluoroquinolone with strong bactericidal activity.
Endorsed by the WHO in 2022, the regimen gained momentum in global rollout programs after 2023, thanks to mounting evidence from studies like the ZeNix and TB-PRACTECAL trials, which demonstrated its high cure rates (up to 90%), even in patients with extensively drug-resistant TB (XDR-TB).
Unlike traditional MDR-TB regimens that can last up to 20 months and involve painful injections, BPaLM is injection-free, better tolerated and dramatically reduces treatment burden. While some patients may still experience side effects, especially from linezolid (e.g., peripheral neuropathy or myelosuppression), ongoing dose optimization is helping to minimize these risks.
Already in clinical use across several high-burden countries, BPaLM is viewed as a milestone in MDR-TB care, offering a shorter, safer and more effective treatment pathway that improves patient outcomes and supports global TB control goals.
2. BPaZ Regimen (Bedaquiline, Pretomanid, Pyrazinamide)
The BPaZ regimen is an emerging three-drug combination designed for the treatment of both drug-sensitive (DS-TB) and drug-resistant tuberculosis (DR-TB). It consists of Bedaquiline, which disrupts bacterial energy metabolism; Pretomanid, which has activity against both active and latent TB bacilli and Pyrazinamide, which is effective in acidic intracellular environments.
As of 2025, the regimen remains in advanced Phase 2B clinical trials, with ongoing evaluations focused on its effectiveness, safety profile and treatment duration across various TB populations. Initial trial results have shown promise and researchers continue to explore whether BPaZ can reduce total treatment time to just three months, a major advancement compared to the standard 6-month or longer regimens.
Though not yet approved for routine clinical use, BPaZ represents a potential breakthrough in universal TB therapy, offering hope for a shorter, simplified treatment option for both drug-sensitive and drug-resistant TB cases in the future.
3. GSK3036656 (Ganfeborole)
GSK3036656, also known as Ganfeborole, is a promising oral anti-tuberculosis drug currently in Phase IIa clinical trials. It represents a first-in-class leucyl-tRNA synthetase inhibitor, a novel mechanism that disrupts bacterial protein synthesis by interfering with the enzyme responsible for attaching leucine to its corresponding tRNA, a critical step for TB bacilli survival and replication. This new mode of action makes Ganfeborole particularly valuable in the fight against drug-resistant TB, as it does not share resistance pathways with existing treatments. Its oral formulation and potential for once-daily dosing add to its appeal as a future frontline therapy.
Though not yet approved for clinical use, Ganfeborole is being closely monitored for its safety, tolerability and bactericidal activity. If successful, it could become a key component in shorter and more effective TB regimens, especially for resistant strains.
4. Delpazolid
Delpazolid is an oxazolidinone antibiotic currently under Phase IIb clinical trials as a potential alternative to linezolid for the treatment of multidrug-resistant tuberculosis (MDR-TB). This drug works by inhibiting bacterial protein synthesis, similar to linezolid but with a potentially improved safety profile.
While linezolid is highly effective against resistant TB strains, its use is often limited by adverse effects such as peripheral neuropathy and myelosuppression. Delpazolid is being tested to determine whether it can offer similar efficacy with fewer side effects thus enhancing patient tolerance and adherence to treatment.
Although not yet available for clinical use, Delpazolid’s development could play a crucial role in expanding treatment options for resistant TB, especially for patients who cannot tolerate current therapies.
5. BTZ-043
BTZ-043 is a benzothiazinone compound that targets the enzyme DprE1 (Decaprenylphosphoryl-β-D-ribose 2′-epimerase), which plays a key role in the biosynthesis of the mycobacterial cell wall. By inhibiting this enzyme, BTZ-043 disrupts the growth of Mycobacterium tuberculosis in a novel manner, offering a potential solution for treating drug-resistant tuberculosis (DR-TB).
Having completed Phase IIa clinical trials, BTZ-043 has demonstrated encouraging bactericidal activity and promising safety profiles. While it is not yet available for clinical use, its unique mechanism of action which does not overlap with existing drug resistance pathways could be instrumental in overcoming multidrug-resistant TB and extensively drug-resistant TB (XDR-TB).
Further studies are needed to confirm its effectiveness and optimize its dose regimen, but BTZ-043 represents an exciting step forward in the development of novel TB therapies.
6. Sudapyridine (WX-081)
Sudapyridine (WX-081) is a Diarylpyridine compound and a structural analog of Bedaquiline, designed to treat multidrug-resistant tuberculosis (MDR-TB). Similar to Bedaquiline, Sudapyridine targets the ATP synthase enzyme in Mycobacterium tuberculosis, disrupting bacterial energy production and leading to cell death.
However, Sudapyridine offers the potential advantage of reduced cardiotoxicity, a side effect that has been associated with bedaquiline, particularly in patients with preexisting heart conditions.
Currently undergoing Phase III clinical trials in China, Sudapyridine is not yet approved for routine clinical use but is being considered for compassionate use in certain cases where no other treatment options are available. If successful, this drug could become a valuable option in the treatment of MDR-TB, especially in patients who cannot tolerate Bedaquiline due to cardiac concerns.
7. TBAJ-876
TBAJ-876 is a next-generation diarylquinoline, structurally related to Bedaquiline, and is currently undergoing Phase 2 clinical trials in five countries. Like Bedaquiline, TBAJ-876 targets the ATP synthase enzyme in Mycobacterium tuberculosis, disrupting energy production and leading to bacterial death.
What sets TBAJ-876 apart is its designed improvements over Bedaquiline, with a focus on enhanced safety and increased efficacy, potentially minimizing the risk of side effects such as cardiotoxicity. This next-generation drug aims to provide a more tolerable and effective treatment option for drug-resistant TB, particularly in patients who have limited treatment alternatives.
Although not yet available for clinical use, TBAJ-876 holds promise as a key treatment in the fight against multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) if its trials confirm its benefits over existing therapies.
8. ERA4TB (European Regimen Accelerator for TB)
ERA4TB is a collaborative initiative focused on accelerating the development of short-course tuberculosis regimens that can be universally applied to various forms of TB, including drug-resistant strains. The project is in the preclinical and early clinical trial stages, with several promising drug candidates in its pipeline. These drugs are being tested to reduce treatment duration and improve efficacy while minimizing side effects.
The compounds under development aim to target multiple bacterial processes such as cell wall synthesis, protein synthesis and energy production within Mycobacterium tuberculosis. This multi-target approach is designed to overcome the challenges of drug resistance and treatment failure seen in current regimens.
The formulation of ERA4TB’s pipeline drugs includes both oral and injectable options, with a focus on simplifying treatment regimens. These are being designed to provide a short-course, once-daily dosing regimen that improves patient adherence and accessibility especially in high-burden TB settings. The initiative is also exploring combination therapies to increase synergy between drugs, further enhancing the overall effectiveness.
While not yet available for clinical use, ERA4TB has the potential to revolutionize TB care, offering a more effective, faster and more convenient treatment solution for both drug-sensitive and drug-resistant tuberculosis.
Therapy for Special Populations
1. TB in Pregnancy
Tuberculosis (TB) in pregnant women presents significant challenges due to the lack of trial data for this population. Historically, pregnant women have often been excluded from clinical trials, which has led to a gap in understanding the safety and effectiveness of TB treatments during pregnancy. This has made it difficult to establish clear, pregnancy-specific treatment protocols.
In response to this issue, the WHO formed a working group in 2024 to specifically address the diagnosis, treatment and management of TB during pregnancy. This group aims to generate much-needed safety data for pregnant women with TB, with ongoing trials focused on determining safe regimens that can be used without harming the mother or the fetus.
Currently, there are limited protocols available, and treatment strategies must be carefully tailored to each case. The goal is to develop evidence-based guidelines that ensure safe and effective treatment for pregnant women, while preventing transmission and complications for both the mother and the baby.
Vaccines in Development
1. MTBVAC
MTBVAC is a live-attenuated vaccine developed using Mycobacterium tuberculosis, the bacterium responsible for TB. Unlike the BCG vaccine, which uses a live strain of Mycobacterium bovis, MTBVAC is designed to provide broader protection against both drug-sensitive and drug-resistant TB. Its development aims to address the limitations of the BCG vaccine, which offers partial protection especially in adults.
Currently undergoing Phase II clinical trials in infants and adults, MTBVAC is being evaluated for its safety, immunogenicity and efficacy. If successful, it could serve as a more effective alternative or replacement for BCG, potentially offering longer-lasting protection against TB, including pulmonary TB which is harder to prevent with current vaccines.
Although it is not yet available for clinical use, MTBVAC holds significant promise for the future of TB prevention particularly in high-burden regions where a more potent vaccine is urgently needed.
2. M72/AS01E
The promising tuberculosis vaccine candidate M72/AS01E, developed by the Bill & Melinda Gates Medical Research Institute, is showing rapid progress in its Phase 3 clinical trial. This vaccine, which blends the M72 antigen with the AS01E adjuvant, is being evaluated for its ability to protect adults and adolescents from pulmonary TB. Notably, the trial has already reached 90% of its targeted 20,000 participants and is progressing nearly a year ahead of schedule. If the results confirm its effectiveness, M72/AS01E may become the first major advancement in TB vaccination in more than 100 years, offering hope for improved global TB control.
Conclusion
The journey from detection to cure in tuberculosis management has witnessed tremendous advancements, bringing renewed hope for the global fight against this age-old disease. With TB continuing to be a leading cause of morbidity and mortality, particularly in resource-limited settings, the integration of innovative diagnostic technologies and novel drug regimens represents a major breakthrough in TB care.
The development of rapid diagnostic tools such as Xpert MTB/RIF Ultra and FujiLAM has significantly enhanced early detection particularly in vulnerable populations like children and those with HIV. Furthermore, the use of AI-powered portable X-ray systems and targeted Next-Generation Sequencing (NGS) are helping streamline diagnosis, making it more accessible and precise, especially in remote areas where resources are scarce.
In parallel, the evolution of TB treatments has led to the emergence of shorter, more effective regimens like BPaLM and BPaZ, which promise to revolutionize the care of multidrug-resistant and extensively drug-resistant TB. New drugs such as Ganfeborole and Delpazolid also offer hope for patients with limited treatment options, improving both efficacy and patient adherence. Additionally, special initiatives like ERA4TB are working toward a more universal and faster regimen further improving global TB control.
The advent of MTBVAC, a promising new TB vaccine, holds the potential to provide broader protection and serve as a more effective alternative to the traditional BCG vaccine. If proven effective, M72/AS01E could also signal a historic breakthrough in the fight against tuberculosis.
As these innovations continue to evolve, the future of TB management is becoming brighter, offering both improved outcomes for patients and a stronger global response to combat this infectious killer. However, challenges remain particularly in ensuring equitable access to these innovations, especially in low-resource settings. Continued global collaboration, investment in research and strengthening of healthcare infrastructures are critical to making these advancements a reality for all affected by TB. With ongoing efforts, the hope of a TB-free world is becoming more tangible than ever.
