**1. Introduction**

Tuberculosis (TB), one of the most common deadly disease is caused by a bacterium called *Mycobacterium tuberculosis*. Robert Koch in 1882, isolated the mammalian strain and proved that the *Mycobacterium tuberculosis* plays a causative role in Tuberculosis. As per the latest WHO report approximately one-fourth of the world's population are infected with *Mycobacterium tuberculosis* (Mtb), whereas 5–10% of the total will develop TB disease during their lifetime [1, 2]. The WHO estimated that in 2018, about 10 million people were affected due to TB worldwide and 1.5 million people suffering from the ailment, including 2,51,000 people who additionally had HIV [3, 4]. In the past, TB was a major reason for death around the globe [5, 6]. In industrialized nations, TB is getting slow due to vast development and improvements in drugs and new antibiotics [5, 7].

TB may exist in two forms, active (dynamic) TB and Latent TB. Dynamic tuberculosis is a condition where MTB causes contamination; regularly, in the lungs, albeit numerous frameworks can be included. Dynamic TB is a multiorgan illness brought about by essential disease or as reactivation of inert tuberculosis. As need be, dynamic tuberculosis could be essential tuberculosis or reactivation tuberculosis.

Latent TB happens when an individual has the TB microscopic organisms inside their body, however, the microbes are available in tiny numbers. They are monitored by the body's safe framework and do not bring on any indications. Individuals with idle TB do not feel wiped out and are not irresistible. They cannot give the TB microscopic organisms to others. Moreover, they will generally have an ordinary chest x-ray and a negative sputum test. It is regularly just realized that somebody has latent TB since they have had a TB test, for example, the TB skin test. There are two kinds of test that can be utilized. These are the TB skin test (TST) and the fresher IGRA blood test. In nations where there is a significant degree of TB, (for example, the high weight TB nations) most individuals may have latent TB.

Fortunately, most of the TB patients have latent infection i.e., bacteria are present in the body but is not causing active disease. Hence at any one time, there are about 10 million people across the world with active tuberculosis infection and that causes deaths in about 10% of them. So, approximately there are 1 million deaths per year due to tuberculosis [8, 9]. The Mycobacteria principally target the lungs, moreover, it has been observed that *M. tuberculosis* may also reach and affect other parts of the body, such as the kidney, spine, and brain. A few people get tuberculosis ailment long after getting contaminated, even before their immune system can battle against the TB bacteria. Others may get the ailment years after the fact when their immune system gets frail for some other reason [8, 10].

Tuberculosis possesses a genuine risk to human wellbeing and one of the main reasons for significant human demise on the planet. Moreover, the emergence of drug resistance and its relationship with HIV infections have intensified worldwide circumstances. Unfortunately, despite advanced modalities for diagnosis and treatment of TB, people are still suffering a lot. There are specific properties associated with MTB that has presented vast challenges to develop an efficient drug against Tuberculosis [11]. The major obstacles in TB treatment like screening of compounds with anti-tubercular activity, the long duration medication, the lack of predictive animal models, and insufficient information on the physico-synthetic properties required for successful bacterial penetration [12], are being encountered by the pharmaceutical scientist.

The danger of creating dynamic (active) Tuberculosis ascends to 30% in diabetes victims. Usually, 80% - 90% of the patient having an infection of drug-resistant tuberculosis are relieved by taking concentrated anti-toxin treatment [2]. However, treatment by antibiotics is dependent on a load of drug-resistant *M. tuberculosis* in the patient [13]. Therapy of anti-drug or multidrug-resistant Tuberculosis (MDRTB: impervious to isoniazid and rifampin) is increasingly perplexing and takes nearly 2 years of chemotherapy amalgamation [14, 15]. Thus, progressively viable medicines are necessary to avoid or the emergence of tuberculosis. Treatment of the significant levels of drug-resistant *Mycobacterium tuberculosis* contamination, which incorporate rifampin-resistant (Rif-TB), MDR-TB, and extensively resistant TB (XDR-TB) requires new medications method and approaches to combat [5, 10]. The development of new methods of treatment is a complex process as antituberculosis drugs are mostly given in combination to inhibit the further emergence of drug-resistant TB [14]. Moreover, dormant TB has also been observed in many people in which TB is not in a dynamic position and do not show any symptoms in a patient [16] whereas dynamic TB happens when the body cannot possess the

**11**

*Challenges in Drug Discovery against Tuberculosis DOI: http://dx.doi.org/10.5772/intechopen.97857*

**2. Need of research on new TB vaccine**

hard to treat tuberculosis [17, 18].

respectively worldwide.

TB pathogen but at this condition, the bacteria can reproduce and cause wanted symptoms and people with dynamic TB can spread the contamination [9, 15]. In certain condition, some MTB strains are not affected by the treatment method and

In recent decades, advanced diagnosis and treatment method of TB has reduced

the mortality rate up to significant level but TB still exists in world population causing extensive human suffering, economic burden led to global inequity. There are neonatal BCG vaccines that can prevent infants and young children from severe forms of TB but this vaccine is unable to show its effect in adolescents and adults who are crucial in TB transmission. We need to develop new efficient vaccines which could work in all age group people that may assist to fulfill the WHO end TB strategy that aims to reduce the TB mortality and TB incidences by 95% and 90%

Now, WHO is putting much efforts to produce TB vaccines and the Product Development for Vaccines Advisory Committee (PDVAC) is asking to develop a WHO preferred Product Characteristics (PPC) for new TB vaccines. The WHO's PPC data was established to document the crucial and priority requirements for vaccines which may show better safety and efficacy compared to BCG vaccine which is given to neonates and infants against pulmonary TB in adults, and new TB vaccines. The major vaccine platforms like whole-cell vaccines, adjuvanted proteins, and recombinant subunit vector vaccines, are being considered in the pipeline of TB vaccine development. Now focus is on TB treatment in adolescents and adults by developing an effective candidate vaccine that may also replace the BCG in early life immunization. Many other aspects are in consideration in vaccine development, such as BCG boosters, reduction of treatment period using immunotherapeutic

adjuncts and vaccine to prevent diseases reoccurrence in TB patient.

with 50% efficacy over about 3 years of continuous monitoring.

**3. Globally situation of tuberculosis**

In recent developments, as per WHO report, there is TB vaccine candidate (M72/AS01E) developed by the pharmaceutical company GlaxoSmithKline, in partnership with AERAS and was observed substantially effective against Tuberculosis disease and these results came out in a Phase IIb trial carried out in Kenya, South Africa and Zambia in patients having latent tuberculosis. This vaccine was found

According to the report of WHO, a sum of 1.4 million individuals passed on from TB in 2019 (counting 208,000 individuals with HIV). Around the world, TB is one of the top 10 reasons for death and the main source from a solitary irresistible specialist (above HIV/AIDS). In 2019, an expected 10 million individuals became sick with tuberculosis (TB) around the world. 5.6 million men, 3.2 million ladies and 1.2 million youngsters. In 2019, 1.2 million kids became sick with TB worldwide. The youngster and juvenile TB is frequently ignored by wellbeing suppliers and can be hard to analyze and treat. In 2019, the 30 high TB trouble nations represented 87% of new TB cases. Eight nations represent 66% of the aggregate, with India driving the tally, trailed by Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa. Multidrug-safe TB (MDR-TB) stays a general wellbeing emergency and a wellbeing security danger. A worldwide all out of 206 030 individuals with multidrug-or rifampicin-safe TB (MDR/RR-TB) were identified and told in 2019, a 10% expansion

*Molecular Epidemiology Study of Mycobacterium Tuberculosis Complex*

their immune system gets frail for some other reason [8, 10].

tuberculosis.

TB may exist in two forms, active (dynamic) TB and Latent TB. Dynamic tuberculosis is a condition where MTB causes contamination; regularly, in the lungs, albeit numerous frameworks can be included. Dynamic TB is a multiorgan illness brought about by essential disease or as reactivation of inert tuberculosis. As need be, dynamic tuberculosis could be essential tuberculosis or reactivation

Latent TB happens when an individual has the TB microscopic organisms inside their body, however, the microbes are available in tiny numbers. They are monitored by the body's safe framework and do not bring on any indications. Individuals with idle TB do not feel wiped out and are not irresistible. They cannot give the TB microscopic organisms to others. Moreover, they will generally have an ordinary chest x-ray and a negative sputum test. It is regularly just realized that somebody has latent TB since they have had a TB test, for example, the TB skin test. There are two kinds of test that can be utilized. These are the TB skin test (TST) and the fresher IGRA blood test. In nations where there is a significant degree of TB, (for example, the high weight TB nations) most individuals may have latent TB.

Fortunately, most of the TB patients have latent infection i.e., bacteria are present in the body but is not causing active disease. Hence at any one time, there are about 10 million people across the world with active tuberculosis infection and that causes deaths in about 10% of them. So, approximately there are 1 million deaths per year due to tuberculosis [8, 9]. The Mycobacteria principally target the lungs, moreover, it has been observed that *M. tuberculosis* may also reach and affect other parts of the body, such as the kidney, spine, and brain. A few people get tuberculosis ailment long after getting contaminated, even before their immune system can battle against the TB bacteria. Others may get the ailment years after the fact when

Tuberculosis possesses a genuine risk to human wellbeing and one of the main reasons for significant human demise on the planet. Moreover, the emergence of drug resistance and its relationship with HIV infections have intensified worldwide circumstances. Unfortunately, despite advanced modalities for diagnosis and treatment of TB, people are still suffering a lot. There are specific properties associated with MTB that has presented vast challenges to develop an efficient drug against Tuberculosis [11]. The major obstacles in TB treatment like screening of compounds with anti-tubercular activity, the long duration medication, the lack of predictive animal models, and insufficient information on the physico-synthetic properties required for successful bacterial penetration [12], are being encountered by the

The danger of creating dynamic (active) Tuberculosis ascends to 30% in diabetes victims. Usually, 80% - 90% of the patient having an infection of drug-resistant tuberculosis are relieved by taking concentrated anti-toxin treatment [2]. However, treatment by antibiotics is dependent on a load of drug-resistant *M. tuberculosis* in the patient [13]. Therapy of anti-drug or multidrug-resistant Tuberculosis (MDRTB: impervious to isoniazid and rifampin) is increasingly perplexing and takes nearly 2 years of chemotherapy amalgamation [14, 15]. Thus, progressively viable medicines are necessary to avoid or the emergence of tuberculosis. Treatment of the significant levels of drug-resistant *Mycobacterium tuberculosis* contamination, which incorporate rifampin-resistant (Rif-TB), MDR-TB, and extensively resistant TB (XDR-TB) requires new medications method and approaches to combat [5, 10]. The development of new methods of treatment is a complex process as anti-

tuberculosis drugs are mostly given in combination to inhibit the further emergence of drug-resistant TB [14]. Moreover, dormant TB has also been observed in many people in which TB is not in a dynamic position and do not show any symptoms in a patient [16] whereas dynamic TB happens when the body cannot possess the

**10**

pharmaceutical scientist.

TB pathogen but at this condition, the bacteria can reproduce and cause wanted symptoms and people with dynamic TB can spread the contamination [9, 15]. In certain condition, some MTB strains are not affected by the treatment method and hard to treat tuberculosis [17, 18].
