Tuberculosis (TB) is a disease which has plagued humanity for centuries, claiming millions of lives every year. As per the WHO, an estimated 5.8 million people developed active TB and 1.5 million died with the disease including 0.214 million deaths associated with HIV co-infection in 2020.

Globally, it is one of the leading causes of mortality and morbidity in developing countries, including India. TB is caused by bacterium Mycobacterium tuberculosis, which primarily affects the lungs but also has the tendency to attack other parts of the body. While TB is curable, the effectiveness of treatments has been hampered by the development of deadly antibiotic-resistant strains. This has led to a growing need for effective drug treatment and diagnosis. Despite the significant progress made in TB diagnosis and treatment, the disease still remains to be a major public health concern, especially in low-income countries. However, the recent advances in TB drug discovery and diagnosis have provided a beacon of hope for a TB free world.

The treatment of TB involves a multidrug, multimodal long duration therapy, which comprises of first and second-line drugs. The complex and lengthy treatment regimen leads to poor patient compliance resulting in the emergence of drug resistant bacteria causing extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant tuberculosis (MDR-TB) that has outpaced the available treatment options. The transmission of MDR and XDR strains is most acute in region with poor social and economic backgrounds, and where it is very difficult to combat and control TB and are the highest and are intensified by the high rates of HIV coinfection.

 In 2020, about 0.157 million people got infected with drug resistant Mtb strains globally.

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Research & Advancements in TB Drug Discovery

Drug discovery refers to the process of developing compounds through research and trials that may be used as drugs in healthcare sector. There has been increased and renewed scientific focus on TB drug research, led by the rise of drug-resistant forms of the disease. There are several approaches to TB drug discovery, including molecular genetics, high-throughput screening, and repurposing or modifying existing drugs. Molecular genetics involves studying the various genes of the M. tuberculosis bacterium, with the aim of identifying new targets for drugs. High-throughput screening uses large chemical libraries to identify compounds that are effective against TB. Finally, repurposing or modifying existing drugs, such as antibiotics, can also lead to new TB treatments.

Ø  Advancements in TB Diagnosis

For the diagnosis and effective treatment of the disease early diagnosis is required.  Unfortunately, current methods used for diagnosis are slow, and costly, and sometimes not even accurate. However, there are several innovative approaches that are revolutionizing TB diagnosis. One such approach is the GeneXpert MTB/RIF test This is a new molecular diagnostic tool that can identify TB and resistance to the antibiotic Rifampin within 2 hours. This test has been a game-changer in TB diagnosis, especially in resource-limited settings.

Another innovative approach is the use of artificial intelligence (AI) for the detection of TB. Researchers from the University of Surrey in the UK have developed an AI system that can detect TB with 96% accuracy. The system uses a simple cough sound recording to identify TB in patients, which can be a game-changer for TB diagnosis, especially in areas with limited healthcare resources. These tests are more accurate and can be done is shorter time duration than the traditional diagnostic methods, allowing for earlier detection and treatment.

According to Techsci Research report “Tuberculosis Therapeutics Market - Global Industry Size, Share, Trends, Opportunity, and Forecast, 2018-2028F Segmented By Disease Type (Active Tuberculosis, Latent Tuberculosis), By Therapy (First Line Therapy, Second Line Therapy), By Route of Administration (Oral, Parenteral, Others), By Dosage Form (Tablets, Capsules, Injection, Others), By Distribution Channel (Hospital Pharmacy, Retail Pharmacy, Online Pharmacy), By Region and Competition,” the Global Tuberculosis Therapeutics Market is expected to grow at an impressive rate during the forecast period on account of the growing need to find new therapeutic solutions to combat the spread of tuberculosis and improve patient outcomes. Moreover, supportive government policies and schemes are further expected to support the growth of Global Tuberculosis Therapeutics Market.

Standard treatment for drug susceptible TB involves taking a combination of antibiotics for six months, while the treatment for drug resistant TB can take up to two years. This long duration of treatment can be a barrier to treatment adherence, that can cause failure of the treatment, disease relapse, and the development of drug resistance, thereby slowing down the growth of Global Tuberculosis Therapeutics Market.

 Based on Therapy the market is divided into first line therapy segment and second line therapy segment. The first line therapy segment is expected to be the dominant segment during the forecast period until 2028. This can be attributed to the development of a large number of first line therapeutics drugs such as isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), streptomycin, and ethambutol. However, the second line therapy segment is expected to register the fastest growth owing to growing drug resistance among the population.

Ø  New Approaches to TB Drug Discovery

Phenotypic whole cell screening has been long been used for TB drug discovery leading to the introduction of current drugs in market and in clinical trials. With the emergence of the genomic era, the focus of drug discovery efforts has shifted to validated drug targets indispensable for the survival and pathogenicity of Mycobacterium tuberculosis (Mtb).

In addition, there has been a renewed interest in natural products as potential sources of new TB drugs. Natural products are compounds that are produced by living organisms such as plants, bacteria, and fungi. Historically, natural products have been a major source of drugs, and many important drugs, such as penicillin, have been derived from natural sources. In the case of TB, there has been a recent focus on natural products produced by bacteria that live in symbiosis with other organisms. These bacteria have evolved to produce compounds that help protect their hosts from TB and other diseases. Researchers have isolated several promising compounds from these bacteria that show activity against TB and are now in preclinical development.

Ø  Introduction of Targeted Therapies

The development of targeted therapies is a recent development in the field of TB drug discovery. Targeted therapies include drugs which are designed to inhibit specific aspects of the TB bacterium's life cycle. For example, Bedaquiline, a drug approved by the United States Food and Drug Administration (FDA) for use in the treatment of TB, targets the bacterium's energy metabolism. It is mainly used for the treatment of multi-drug-resistant tuberculosis (MDR-TB) along with other medications for tuberculosis. Similarly, Delamanid, another TB drug, which has received approval from the FDA, targets cell wall synthesis. These targeted therapies have the potential to be more effective and have fewer negative side effects than traditional antibiotics.

There is a need to focus on potent drugs, targets and approaches to combat with TB and vitalize the drug discovery pipeline. There is an increased focus on novel drug targets and compounds since pre-existing resistance against them would not be encountered.

Ø  Repurposing Existing Drugs

Another strategy which is gaining traction in TB drug development is the repurposing of existing drugs. Researchers have found that some drugs that are currently approved for other diseases, such as cancer and diabetes, show promise in the treatment of TB. For example, one study found that the anti-cancer drug, imatinib, could be used to treat drug-resistant TB. This research is significant because it can save time and resources in the drug discovery and development process.

Ø  Advancements in Drug Delivery Systems

The medicine given for TB can have unpleasant side effects and require frequent dosing. This makes it challenging for patients to adhere to treatment plans. Several recent developments in drug delivery systems are helping to address this issue. One such innovation is Rifampicin-loaded liposomes, which can improve drug efficacy and reduce the frequency of drug dosing. Additionally, researchers have developed inhalable dry powder formulations that can deliver TB drugs into the lungs. These advancements in drug delivery systems make treatment more comfortable and effective for patients.

Ø  The Role of Artificial Intelligence

Artificial intelligence (AI) has the potential to revolutionize TB diagnosis and treatment. A research study has shown that a test combining artificial intelligence and nanotechnology can enhance the tuberculosis diagnosis process among pediatric patients, detecting 89 percent of cases. Machine learning algorithms can be trained to predict drug efficacy and resistance, and AI can be applied to identify patterns in patient data leading to early detection and diagnosis. Other potential applications of AI in TB treatment include simulating drug interactions to reduce treatment duration and cost.

Ø  Continued Investment

Despite the recent advancements in TB drug discovery and diagnosis, there is still a need for continued investment in research and development. Drug-resistant TB remains a major global health threat, and there is a need for new, effective treatments. Additionally, many low- and middle-income countries still lack access to diagnostic tools and effective treatment. Continued investment in the research and development of TB is important to improve health outcomes.

Ø  Vaccination to Control TB

At present there is only one licensed TB vaccine, the Bacille Calmette-Guerin (BCG) vaccine. Although the vaccine provides partial protection against TB, it is not always effective, especially in adults. However, there are several new vaccines under development that could provide better protection against TB.

One promising vaccine candidate is the M72/AS01E vaccine, developed by GlaxoSmithKline. This vaccine has shown significant protection against TB and has been approved for use in South Africa. Another vaccine candidate is the VPM1002 vaccine, which is a modified version of the BCG vaccine. This vaccine has shown better protection than the BCG vaccine and is currently being evaluated in clinical trials.

To control TB, it is important to have a comprehensive approach that involves detection, prevention and treatment. However, the measures to control TB are often inadequate, especially in low-income countries. To overcome this challenge, new strategies are being developed that are more effective and sustainable.

One such strategy is community-based TB care. This strategy involves engaging local communities in TB prevention and treatment. This approach has been successful in several countries, including India, where community health workers have been trained to identify and treat TB cases in their communities. Another strategy is the use of mobile health (mHealth) technologies, such as text messaging and apps, to improve TB detection and treatment.

According to TechSci Research report “Therapeutic BCG Vaccine Market – Global Industry Size, Share, Trends, Opportunity, and Forecast, 2018-2028 Segmented by Type (Immune BCG, Therapy BCG), by Demographics (Adults, Pediatrics), By End User (Clinics, Hospitals), by region, and Competition,” the Global Therapeutic BCG Vaccine Market valued at USD45.60 million in 2022 and is anticipated to witness an impressive growth in the forecast period with a CAGR of 3.30% through 2028. A single dosage of Bacillus Calmette-Gurin (BCG) vaccine is administered in newborn in nations where TB is common shortly after delivery. In nations where it is rare, the vaccine is only administered to high-risk newborns. After birth, healthy infants, who should receive a vaccination dose are given one because of their high risk and recommended age for immunization.

Clinical trials are exploring the efficacy of BCG vaccines for different therapeutics applications. Positive clinical outcomes have driven investment and interest in BCG vaccine development. BCG vaccines continue to be an effective tool in the global effort to control tuberculosis (TB). Initiatives and programs aimed at TB prevention and treatment drive the production and distribution of BCG vaccines. The advancements in biotechnology have improved the manufacturing and quality control processes for BCG vaccines, making them more reliable and accessible. Healthcare professionals’ awareness of the therapeutic potential of BCG vaccines and patient education about treatment options have driven the adoption of BCG immunotherapy.

Ø  Social Determinants of Health

TB is a disease that is linked to social determinants of health. This means that the conditions in which people live, and work have a significant impact on their risk of developing the disease. For example, factors such as poor housing conditions, lack of access to healthcare, and inadequate nutrition can all increase the risk of TB. Addressing social determinants of health is critical to reducing the burden of TB.

Ø  Monitoring Patients

After the diagnosis, TB patients need require extensive monitoring to ensure that the treatment was successful. Artificial Intelligence (AI)-assisted patient monitoring technologies like remote vital signs monitoring, wearables and telemedicine provide significant benefits in the management of TB patients. This can eliminate the need for frequent face-to-face consultations with the healthcare personnel and instead using AI to monitor and manage the disease symptoms. This technology can also reduce hospital readmissions, offer better patient outcomes, and reduce treatment costs.

The role of AI in the treatment of tuberculosis is rapidly growing. AI can assist with early diagnosis, treatment adherence, drug discovery, disease surveillance and patient monitoring. While AI is not meant to replace human doctors, the synergy between AI-powered technologies and medical professionals could revolutionize tuberculosis diagnosis and treatment. The potential benefits of AI-assisted TB treatment include faster diagnoses, better patient outcomes, reduced treatment costs, and the development of new treatment options. AI could help in unlocking the secrets of tuberculosis and move one step closer to eradicating this deadly disease.

Addressing the Disease is a Global Health Priority

Addressing TB is a critical global health priority. TB affects people in every region of the world, but it is particularly prevalent in low- and middle-income countries. Addressing TB requires a coordinated global effort, including investments in research and development of new tools, increased funding for TB programs, and partnerships with stakeholders across sectors.

Conclusion

Working towards a TB free world is not only a health issue but also a social and economic issue. However, addressing TB requires a coordinated global effort, including investments in research and development, increased funding for TB programs, and partnerships with stakeholders across sectors. With the right strategies and resources, TB can be eradicated for all and a healthier, more prosperous world for all can be created.