**1. Introduction**

Tuberculosis (TB) continues to have a major influence on global healthcare. For more than five decades, anti-tubercular treatment (ATT) is available but still, about one-third of the world's population continues to be infected with tuberculosis [1]. In the last decade, the rise of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has sparked global alarm [1–3]. Patients who are infected with strains resistant to isoniazid and rifampicin, called multidrug-resistant (MDR) TB, are practically incurable by standard first-line treatment (Seung et al. 2015).

Tuberculosis (TB) is a global health concern that causes 8.7 million new cases and 1.4 million deaths each year [4]. Furthermore, resistant *Mycobacterium tuberculosis* strains are appearing in practically all places reported to the World Health Organisation (WHO) [5]. Noncompliance with treatment regimens and incorrect TB therapy prescriptions are thought to be key contributors to this public health issue [6, 7]. Fixed-dose combination (FDC) tablets, each combining two or more anti-TB drugs, have been manufactured since the 1980s [8] to simplify TB therapy and facilitate physician and patient compliance with treatment recommendations [9] due to the large number of tablets used in TB treatment regimens. These Fixed-dose combination (FDC) pills also avoid unintended monotherapy, which can happen due to prescription errors, insufficient regimens, or patient error in taking only one medicine [10]. Furthermore, dealing with a single combined formulation including all needed medications streamlines drug procurement, storage, and delivery, potentially lowering drug supply management errors and costs. The World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) approved FDC anti-TB therapy in 1994 [11]. Concerns were raised about adequate bioavailability of the component drugs following the announcement of this recommendation and its more widespread implementation, particularly rifampicin (RIF) due to its enhanced decomposition in the presence of isoniazid (INH) [12, 13]. As a result, the WHO and the IUATLD set bioavailability standards for FDC anti-TB medication components [14]. Two-drug formulations (INH + RIF and INH + ethambutol), three-drug formulations (INH + RIF + ethambutol and INH + RIF + pyrazinamide), and a four-drug formulation (INH + RIF + ethambutol + pyrazinamide) are currently on the WHO Model List of Essential Drugs [10, 15].

The first three years of implementation of the National Strategic Plan (2017–2025) to eradicate tuberculosis in India have been completed. The programme has had a lot of success over this time [16]. Through the NIKSHAY portal, the initiative has made significant progress toward near-complete online notification of all TB cases in the country. The system has notified 24.04 lakh patients, an increase of 11% over previous year, with 6.7 lakh patients from the private sector being notified. For 22.7 lakh (94.4%) of the declared drug-sensitive TB cases, first-line standard treatment was started. Early case discovery has improved as a result of mapping high-risk groups, properly planned systematic screening, and aggressive case finding for active TB, resulting in lower transmission risks, poor treatment outcomes, and negative social and economic implications. This year, 27.74 crore people were examined in 337 districts across 23 states, yielding 62,958 TB cases [16].

Tuberculosis (TB) is a disease that has been around for a long time. Despite the availability of tubercle bacillus chemotherapy, our fight against this ancient human foe is far from ended. Because of the pathogen's peculiar biological properties [17]. Springett [18] describes the disease as having a distinct natural history and a sluggish response to currently available chemotherapeutic treatments [17, 19, 20]. Since the beginning of chemotherapy, poor treatment adherence, developed drug resistance, treatment failure, and relapse have all been reported [21]. A series of seminal experiments in Madras (now Chennai), Africa, Hong Kong, and Singapore led to create the now widely used 6-month standard regimens administered under supervision [22]. These research set the groundwork for the World Health Organisation's (WHO) global comprehensive TB control strategy, known as directly observed therapy, short-course (DOTS), which was announced in 1993 alongside a proclamation of tuberculosis as a global emergency [23]. Despite some recent debates on the exact

*Perspective Chapter: Tuberculosis Drugs Doses from Indian Scenario – A Review DOI: http://dx.doi.org/10.5772/intechopen.108247*

importance of the act of directly observed treatment (DOT) [24, 25], no other mode of drug administration has been shown to provide a comparable high rate of treatment success as DOTS in functional programme settings [26]. Since the introduction of DOTS, intermittent drug delivery has been frequently used to facilitate treatment oversight on an outpatient basis, either throughout the 6-month course or solely during the continuation phase in the last 4 months [21]. The fewer treatment visits reduces both operational and patient-related costs, particularly when extensive travel distances are involved. Patients can go about their daily routines and work as usual because intermittent treatment has a lower impact on their everyday lives [21]. This facilitates patient access to therapy and treatment adherence, particularly in resourceconstrained places or for underserved groups [21]. The scientific basis for intermittent TB treatment in clinical settings has been established by in vitro evidence of the post-antibiotic effect (PAE), which showed that exposure to medicines, particularly isoniazid, for a few hours resulted in suppression of mycobacterial growth for several days [27, 28]. The free peak drug concentration to minimum inhibitory concentration (MIC) ratio best correlates with the PAE and resistance suppression for rifampicin and perhaps other TB treatments [21, 28].

### **2. Current status in India**

The persistence of an immune response to *M. tuberculosis* antigen stimulation without any clinically active disease is known as latent tuberculosis infection (LTBI) [29]. LTBI is expected to affect roughly one-third of the world's population [30]. There are no estimates of the frequency of LTBI in the general population in India; however, according to WHO data, around 3.5 lakh children under the age of five years were eligible for LTBI treatment [31]. Although the majority of infected people do not show symptoms, they are at high risk of developing active infection and so serve as a bacterium reservoir. Reactivation of tuberculosis is believed to be 5–10% of the time [32]. This risk is substantially higher in HIV-positive people, who face a 10% annual risk of reactivation, and in young children (10%). If left untreated, 40% of LTBI children under the age of one develop active disease, compared to 24 per cent in children aged one to ten years and 16% in children aged eleven to fifteen years [33]. Infected people are thought to congregate in a pool of LTBI, from which those with latent TB emerge with active TB. The size of the pool of latent infection must be reduced in order to regulate the active infection [32, 34].

The elimination of tuberculosis (TB) has received a lot of attention in recent decades. While treating active disease is by far the most significant intervention, LTB treatment is an important but underestimated component. The cost of testing, a lack of consensus on the tests that should be used, and treatment side effects all make it difficult to diagnose and treat LTBI [32]. Treatment of LTBI in low-prevalence (high- to upper-middleincome) countries is possible, as removing the infection reservoir reduces the disease's burden. In high-prevalence countries like India, however, the situation is completely different [32]. Here, rather than reactivation, reinfection due to contact with current cases contributes to a high disease burden. This is why there is no national policy on the treatment of LTBI. In this case, LTBI treatment must be tailored to the person [32]. Those at high risk of reactivation should be given priority, especially when the predisposing condition is reversible in the short term. As a result, the probability of reactivation vs. reinfection should be considered while deciding whether or not to treat LTBI [32].
