Tuberculosis (TB) is a potentially serious infectious disease that mainly affects the lungs. It is caused by the bacterium Mycobacterium tuberculosis. TB is spread from person to person through the air when someone with active TB coughs, speaks, or sneezes. According to the World Health Organization (WHO), TB remains one of the world’s deadliest infectious killers, with around 10 million people falling ill with TB each year. An estimated 1.5 million people died from TB in 2020. So what comes after TB? What is the future of prevention, diagnosis and treatment for this deadly disease?
What is the current state of TB prevention?
The only available vaccine for TB currently is the Bacillus Calmette-Guérin (BCG) vaccine. BCG provides protection against severe forms of TB in children, such as TB meningitis and miliary TB. However, its protection against lung TB in adults is variable. BCG is not commonly used in the United States but is often given to infants and small children in other countries where TB is more common. Research is underway to develop new and improved vaccines against TB. Some promising vaccine candidates in clinical trials include:
- MIP: A protein subunit vaccine designed to boost BCG’s effectiveness.
- VPM1002: A live genetically modified vaccine derived from BCG.
- MVA85A: A viral vectored vaccine designed as a booster to BCG.
These new vaccines aim to provide longer lasting and more reliable protection than BCG alone. However, it will likely take years before any new TB vaccines are available for widespread use.
What diagnostic tests are emerging for TB?
Current standard tests for diagnosing active TB include:
- Sputum smear microscopy: Looking at sputum samples under a microscope for visible TB bacteria.
- Nucleic acid amplification tests: Molecular tests that can detect small amounts of TB bacteria by amplifying their genetic material.
- Culture: Growing TB bacteria from sputum or tissue samples.
While these tests work well, they have limitations in speed, sensitivity, and specificity. New diagnostic technologies in development for TB include:
- Rapid molecular tests: New cartridge-based PCR tests can detect TB and resistance genes within hours instead of days.
- Whole genome sequencing: Sequencing all DNA of TB bacteria can provide a complete resistance profile.
- Volatile organic compound detection: Devices that can “sniff out” compounds produced by TB bacteria.
- Side stream dark field imaging: Video microscopy of sputum samples to visualize TB bacteria.
- Fine needle aspirates: Using fine needles to take lung tissue samples for rapid diagnosis.
Faster, more portable, and sensitive point-of-care tests will allow earlier diagnosis and treatment of TB patients. This is critical to curb transmission and improve outcomes.
What new TB treatments are in development?
Current first-line treatment for drug-susceptible TB involves taking four antimicrobial drugs – isoniazid, rifampin, ethambutol, and pyrazinamide – for 6-9 months. While mostly effective, issues around long treatment duration, pill burden, side effects, and antimicrobial resistance have spurred work on new TB therapies. Some promising pipeline drugs and regimens include:
- Bedaquiline: A new drug that inhibits TB bacterial energy production.
- Delamanid: Another new drug that disrupts TB cell wall formation.
- Pretomanid: Related to isoniazid but more potent and with fewer side effects.
- Rifapentine-containing regimens: Longer-acting rifamycin antibiotics that allow shorter treatment courses.
- Injectable agents: Studies of once-weekly injected drugs like rifapentine to avoid daily pills.
- Combination regimens: Using multiple new and existing drugs to shorten and simplify treatment.
Treatment advances like these will hopefully make curing TB safer, faster, and more reliable. This is key to stopping transmission and drug resistance development.
How can we improve detection and treatment of latent TB infection?
Around one quarter of the world’s population has latent TB infection (LTBI). This means they are infected with M. tuberculosis but do not have active disease and cannot transmit it. However, they are at risk for progression to active TB later on. Identifying and treating LTBI is an important TB control strategy. Current LTBI testing relies on the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs). While useful, these have accuracy issues in some populations. Emerging approaches include:
- New IGRAs: More specific blood tests to detect TB infection are in development.
- RNA expression signatures: Gene expression patterns in blood may predict TB risk.
- TB breathalyzers: Devices to detect vapor biomarkers of TB bacteria.
- TB skin patches: Adhesive skin patches that change color in response to TB antigens.
For LTBI treatment, a 12-dose 3-month regimen of isoniazid is standard of care. But shorter and safer regimens are needed to improve completion rates. Promising new treatments in trials include:
- 1-month isoniazid + rifapentine
- 1-month rifampin alone
- 3-month rifampin + isoniazid
- 3-month isoniazid + rifapentine
- 4-month rifampin alone
More convenient and tolerable LTBI treatment options will help expand screening and prevention of active TB cases.
What novel approaches are being used against drug-resistant TB?
The growing threat of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) has spurred innovative countermeasures including:
- New rapid molecular tests to quickly detect resistance mutations.
- Artificial intelligence to analyze resistance patterns and predict effective treatments.
- Machine learning-optimized regimens using computational models and big data.
- Novel drug combinations and repurposed drugs based on synergies and mechanisms.
- Inhaled antibiotics that deliver high lung concentrations with less systemic toxicity.
- Bacteriophage therapy using viruses that infect and kill TB bacteria.
Creative solutions like these will be vital to overcoming the threat of drug resistance and curing even the most challenging TB cases.
Key innovations on the horizon
- New preventive vaccines to replace or boost BCG.
- Rapid point-of-care diagnostic tests for quick, accurate results.
- Shortened, all-oral regimens for drug-susceptible TB.
- Novel drugs and combinations to treat MDR and XDR-TB.
- Biomarker tests and targeted treatments for latent TB infection.
How can we improve TB prevention, detection, and treatment in low resource settings?
Most TB cases and deaths occur in low and middle income countries, especially in Africa and Asia. Challenges like limited healthcare access, equipment shortages, and inadequate surveillance hamper TB control efforts in these settings. Potential solutions include:
- Point-of-care and mobile diagnostic tools that work outside lab settings.
- Rapid drug susceptibility testing to guide proper treatment faster.
- Digital x-ray and ultrasound devices that don’t require much power.
- Electronic medical records and digital adherence monitoring using mobile devices.
- Enhanced case finding through community health workers.
- Strengthened reporting systems using SMS and mobile apps.
Innovations tailored to resources and conditions on the ground will maximize the impact of TB programs.
What role can WHO and global partnerships play against TB?
Groups like the WHO, Stop TB Partnership, and Global Fund have pivotal roles bolstering global TB efforts through:
- Setting norms, guidelines, and targets for TB strategies.
- Advocating and raising funds from governments and donors.
- Promoting collaboration and cooperation between stakeholders.
- Supporting research into new tools and interventions.
- Implementing programs in high-burden countries.
- Monitoring and reporting worldwide TB data.
Robust leadership and coordination from these partners will continue to be essential to defeat TB worldwide.
How can we reduce stigma and raise awareness about TB?
The stigma and myths surrounding TB infection impedes prevention and control. Many incorrectly view it as a “disease of the past” or one that only affects marginalized populations. Effective awareness and destigmatization approaches include:
- High profile “TB champions” sharing stories.
- Culturally appropriate educational materials.
- Empowering TB affected communities.
- Celebrity endorsements and mass media campaigns.
- School and community outreach programs.
- Policymaker engagement on TB issues.
Progress reducing stigma must coincide with biomedical advances to maximize impact against the epidemic.
Conclusion
The global fight against TB stands at a crossroads. Will we continue making slow progress against this ancient foe? Or will new tools, strategies, and political will converge to end TB once and for all? The innovations profiled here offer hope we can dramatically accelerate toward elimination within our lifetimes. But this will require commitment from political leaders, funders, scientists, healthcare providers, and affected communities alike. Together, a TB-free future is possible.