Perspective Chapter: Tuberculosis Drugs Doses from Indian Scenario – A Review

Abstract

Tuberculosis is an infectious disease spread through the air that is treated with a combination of drugs. Compliance to long-term antituberculosis therapy is vital for sustaining adequate blood drug level. Inadequate medical management of patients is a major factor in the emergence and dissemination of drug-resistant Mycobacterium TB strains. The necessity to understand the context of individual and collective health when considering tuberculosis treatment remains a difficulty. Furthermore, when it comes to treatment success, social and economic factors have been demonstrated to be aspects that must be considered. Because of the poor, expensive, ineffective, and toxic alternatives to first-line medications, the therapeutic approach for drug-resistant tuberculosis is complicated. New antituberculosis medications (bedaquiline and delamanid) have recently been licenced by health authorities; however, they do not constitute a definitive answer for the clinical management of drug-resistant tuberculosis forms, especially in middle-income countries where drug resistance is common (China, India, and former Soviet Union countries). There is an immediate need for new research and development initiatives. To sustain both new and ancient therapeutic choices, public health policies are essential. We did a thorough review of national and international literature on tuberculosis treatment in India in recent years with the goal of providing advice to health care providers based on the scenario.

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, 2, 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 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 resource-constrained 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-middle-income) 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].

3. Multi-drug-resistant tuberculosis and RNTCP

Tuberculosis (TB) continues to be a major global public health issue that requires immediate response. There are three separate but overlapping components to current global efforts to control tuberculosis: humanitarian, public health, and economic. The main humanitarian concern for a patient-centred approach to TB control is to reduce TB-related sickness, suffering, and mortality. To reduce disease transmission, the public health dimension focuses on correct identification and treatment of patients with tuberculosis. This involves the creation of well-structured tuberculosis control programmes (responsive and adaptable to the reforming health sector). The advent of medication resistance to treat tuberculosis, particularly multidrug-resistant tuberculosis (MDR TB), has become a major public health issue and a roadblock to successful TB control [2]. In the presence of pharmaceuticals, drug resistance manifests itself as a selective expansion of resistant mutants among the actively growing bacillary population. The prevalence of drug resistant mutants in the susceptible bacillary population, the size of the actively growing bacillary population in the lesions, and the antimicrobial quality of the medications utilised all influence the formation of drug resistance [35, 36].

4. Fixed-dose combination antituberculosis therapy

The World Health Organisation and the International Union Against Tuberculosis and Lung Disease (IUATLD) endorsed FDC anti-TB therapy in 1994 [11]. Concerns were raised about proper bioavailability of the component medications following the release of this proposal and its more widespread application, particularly rifampicin (RIF) due to its accelerated breakdown in the presence of isoniazid (INH) [12, 13]. Despite the potential benefits of FDC anti-TB medicines, questions about their efficacy remain unanswered. Many observational studies and clinical trials have been done to determine the efficacy of FDC medications in preventing treatment failure, illness relapse, and drug resistance. The use of FDC medications has resulted in favourable [37], unfavourable [38], or no therapy outcomes in various investigations [39, 40]. Despite current conflicting findings, the WHO [41], the International Standards for Tuberculosis Care (Standard 8) [42], and the American Thoracic Society all endorse FDC formulations for active TB treatment [10, 43].

5. Treatment of latent tuberculosis infection in India

Because it can sterilise latent infection, LTBI chemotherapy is the sole biological TB control intervention. Isoniazid, at a dose of 10 mg/kg/day for 6 months, is suggested by the IAP for the treatment of LTBI. The following people should receive treatment:

• Regardless of their TST, BCG, or nutritional state, asymptomatic contacts (under 6 years of age) of a smear-positive case who have no evidence of active disease should be administered in.

• After screening out active TB, all HIV positive children in contact with an infectious TB case or TST positive (5 mm induration).

• Immunosuppression was planned for or received by TST positive children (e.g., acute leukaemia and nephrotic syndrome).

• If there is no evidence of congenital TB in the new-born child born to a TB positive mother [44].

In adults, individuals with RA and LTBI who are scheduled for immunosuppression should be treated (biologicals). This is in accordance with the ACR’s recommendations [45]. Chemotherapy is started in HIV patients as stated above. However, because there are no defined rules for India, therapy for immunocompromised people and close contacts of active cases is done on a case-by-case basis. In nations with a high incidence of tuberculosis, treatment options include isoniazid monotherapy for 6 months, rifampicin and isoniazid combination daily for 3 months (in children 15 years), and rifapentine and isoniazid weekly for 3 months. Isoniazid is administered to adults at a dose of 5 mg/kg and to children at a dose of 10 mg/kg up to a maximum of 300 mg. When utilised, rifampicin is administered at a dose of 10 mg/kg for adults and 15 mg/kg for children, with a maximum dose of 600 mg [31]. All of the following regimens were shown to be non-superior in the majority of studies undertaken to date. However, some regimens may be favoured over others on a case-by-case basis. Rifapentine/rifampicin-containing regimens, for example, are not recommended for HIV patients due to the significant risk of medication interactions. In some cases, these may be preferable because they are shorter and patients are more likely to comply. However, the financial ramifications must also be considered [32].

6. Surgical treatment of tuberculosis

Although tuberculosis is usually treated with drugs, it can also be treated surgically in select situations, particularly in cases of drug resistance and some pulmonary tuberculosis sequelae. Surgical lung biopsy can be used to distinguish between pulmonary tuberculosis and lung cancer. Endobronchial tuberculosis, as well as significant adverse responses, severe haemoptysis, empyema, pneumothorax, and bronchopleural fistula, are all surgical indications. Surgical intervention may be indicated in situations of symptomatic pulmonary residual, fungal ball, and haemoptysis in tuberculosis sequelae [46, 47].

7. Treatment services under national TB elimination programme in India

The National Tuberculosis Elimination Program (NTEP) aims to reach every TB patient for free diagnosis and treatment. In 2019, 94% of TB patients who had been notified were started on treatment for the disease [16]. According to current policy, universal DST is supplied to informed TB patients (including private sector TB patients) to determine the presence of Rifampicin resistance at the time of TB diagnosis in order to provide an appropriate regimen based on the Drug Susceptibility Test (DST). Further tests are offered based on the DST result, as part of the integrated DR TB methodology, to rule out resistance to additional medications. UDST was offered to 58% of all reported TB patients in 2019 [16]. As a result of DST, suitable changes in the regimen are made in accordance with the PMDT standards in India [16].

7.1 Treatment of drug sensitive TB

When a patient is diagnosed with tuberculosis, a standard first-line anti-TB regimen in the form of Fixed Dosage Combination (FDC) is given to them right away, usually from the centre where the diagnosis was made or while the patient is being transferred to the appropriate health facility for treatment initiation, especially when the diagnosis is not the same as the TB patient’s relapse (e.g. Mobile or migrant population). The NIKSHAY digital surveillance system enables for the tracking of tuberculosis patients who are referred or transferred from one health unit to another across multiple geographic locations. Through several means, including the PPSA, the National TB Elimination Program has expanded free access to anti-TB drugs to patients seeking care in the private sector. The National TB Elimination Programme uses the services of a contact centre to provide patient counselling and connect them with suitable public resources for patients who are unaware of the nearest diagnostic or therapy institution [16].

7.2 Programmatic Management of Drug Resistant TB services (PMDT)

PMDT services were first offered in 2007, and by 2013, the programme had expanded to encompass the entire country. During 2011–2012, a systematic approach to scaling up all of these facilities was implemented, with coordinated efforts from numerous stakeholders resulting in national coverage by 2013. Line Probe Assay (LPA) was first presented in 2009, followed by CBNAAT in 2012, and both technologies have now been scaled up to 64 LPA labs, 1180 CBNAAT sites, and 350 TrueNAT sites by the end of 2019. By implementing Guidelines for PMDT in India 2017, DRTB treatment services are delegated to district DRTB centres with the goal of bringing drug resistant TB treatment closer to TB patients’ homes. By the end of 2019, 711 DR TB centres, including 154 Nodal DR TB centres, will be operational, allowing for decentralised DR-TB treatment. This decentralisation will enable districts to use the “test and treat approach” to shorten diagnostic and treatment delays, reduce travel costs, and speed early MDR/RR-TB patient care within their district [16].

8. Drugs for tuberculosis

As the disease has refused to go away over the previous five decades, there has always been a need for innovative medications and combinations. Many medications are in various stages of development and are being tested. Efforts are being made to produce newer medications, as well as newer regimens that use these drugs [1].

8.1 New applications of existing drugs

8.1.1 Rifamycins

Rifampicin, Rifabutin, and Rifapentine are among the medications in this class. It has been proposed that a greater dose of Rifampicin than the standard 10 mg/kg may be required to reduce treatment duration in new tuberculosis patients. Some mouse trials have provided promising findings in evaluating the role of high-dose rifampicin (15–30 mg/day) in the intense phase of ATT [40]. For the first two months of ATT, a phase II randomised trial comparing rifampicin in dosages of 20 mg/kg/day and 15. mg/kg/day to the usual 10 mg/kg/day is continuing [48]. Preliminary research suggests that greater dosages of Rifampicin are tolerated well, with proportionately higher serum concentration levels [49]. Adults have also been given higher doses of Rifampicin as part of a regular ATT regimen, as well as when combined with other newer medications like Moxifloxacin and SQ-109 [50]. With such high rifampicin doses, there is the potential for a shorter treatment duration, according to current findings. Rifabutin is often preferred over Rifampicin for individuals with TB and HIV since it has fewer medication interactions and negative effects [51]. In children, the dose is 5 mg/kg, while in adults, it is 150–300 mg/day [52].

Rifapentine, another medicine in the same class, has a longer half-life and has been explored for latent tuberculosis infection (LTBI) rather than active tuberculosis. In adults, a three-month preventive regimen of 300 mg Rifapentine and 900 mg Isoniazid was found to be as efficacious as nine months of 300 mg daily Isoniazid [53]. Doses ranging from 300 to 900 mg have been administered in children with adequate tolerance. In order to obtain systemic exposures consistent with successful treatment of LTBI in adults, higher weight-adjusted dosages are required in children [54].

8.1.2 Flouroquinolones

Moxifloxacin and Levofloxacin are the most important medications in this class, and their superiority over other quinolones has been thoroughly established [55]. There have been multiple trials with promising results using quinolones in combination with other first-line medicines to reduce the length of ATT [56]. In the intensive phase, a typical ATT regimen was compared to a Gatifloxacin/Moxifloxacin-containing regimen with the goal of reducing the treatment period to four months, however the latter had greater relapse rates than the former. Furthermore, children under the age of five are known to clear quinolones from the body more quickly in the urine and have a lower serum concentration than adults. There is a scarcity of pharmacokinetic data, particularly in children under the age of five. As a result, optimising their use in children for the prevention of drug resistance becomes more important [55]. Children’s usage of quinolones has traditionally been restricted due to worries of arthropathy, however there is no evidence of such side effects in either children or adults treated with long-term quinolones, according to available data.

8.1.3 Oxazolidinones

This family of medicines works by inhibiting protein synthesis by competing with an enzyme involved in translation [57]. Cycloserine was the first oxazolidinone to be used as an antitubercular medication, although linezolid is now the most widely used. Sputum conversion rates in patients with XDR-TB improved in two recent randomised control trials with linezolid [58]. However, higher failure rates at lower doses (300 mg/day) and more severe adverse effects at higher doses (600 mg/day) limit its long-term use. Common side effects include peripheral neuropathy, gastrointestinal problems, and myelosuppression [59]. Both Cycloserine and Linezolid are currently designated by WHO as core medicines for the treatment of drug-resistant tuberculosis. There is not much information on their use as anti-tubercular agents in youngsters.

8.1.4 Beta-lactams and Macrolides

The medications included in WHO group D for treating drug-resistant tuberculosis are amoxycillin-clavulanate, imipenem-cilastin, and meropenem. Meropenem and Clavulanate show substantial synergistic antibacterial action against M. tuberculosis in vitro because Clavulanate suppresses â-lactamase and increases Meropenem’s antibacterial activity [60]. In vitro activity against tuberculosis bacilli was demonstrated in a recent research using a triple therapy consisting of amoxicillin, clavulanate, and meropenem [61]. Macrolides, particularly Clarithromycin, have previously proven beneficial in treating non-tubercular mycobacteria, but the outcomes in M. TB have been poor due to fast resistance development [62].

8.1.5 Newer drugs Bedaquiline

After nearly four decades, the Food and Medicine Administration (FDA) has approved this drug as the first antitubercular agent. It blocks the proton pump, which is essential for ATP generation, as well as the mycobacterium’s metabolism [62]. Bedaquiline should only be utilised when the typical MDR regimen cannot be constructed due to in vitro resistance to these medications, known adverse drug reactions, poor tolerance, or contraindications to any of the combination regimen’s components. It can only be used as part of second-line ATT in patients over the age of 18 years, according to WHO guidelines. However, in the same dosage as advised for adults, it has been found to be effective and safe in children and adolescents [63]. The dose is 400 mg once a day for two weeks, then 200 mg three times a week for the next 22 weeks, for a total of six months, which is the longest time bedaquiline can be given. The Indian government’s Revised National Tuberculosis Control Program (RNTCP) is introducing this medicine through a limited access programme across the country. Nausea, vomiting, dizziness, arthralgia, myalgia, elevated serum amylase and transaminase levels, QT prolongation, and dark urine are all known side effects of bedaquiline. Bedaquiline toxicity is increased by drugs that decrease liver function via CYP3A4 metabolism (e.g., ketoconazole and ritonavir) [64].

8.1.6 Delamanid and pretomanid

Both of these medications are nitroimidazoles, which work by preventing mycobacterial cell wall formation [65]. Delamanid has been investigated significantly more thoroughly than pretomanid. In patients with MDR-TB/XDR-TB who have a high baseline risk for poor outcomes, WHO recommends using delamanid for just six months of rigorous treatment at a dose of 100 mg twice a day [66]. When delamanid was given in combination with an improved background regimen in patients with drug resistant tuberculosis, higher rates of sputum conversion and lower mortality were seen [67]. Pretomanid, on the other hand, is a prodrug that requires bio-reductive activation of an aromatic group in order to be effective against tuberculosis. In an experimental mouse model of tuberculosis, it also showed significant bactericidal activity during both the intense and continuation stages of treatment. In 2016, the World Health Organisation (WHO) published guidelines for the use of delamanid in children and adolescents, stating that children with MDR-TB who are resistant to quinolones or second-line injectables (or both) should be candidates for this treatment. This medicine should be used as an add-on treatment in longer MDR-TB regimens (18–24 months) in children rather than as part of the shorter MDR-TB regimens introduced by WHO in 2016 [3]. Not only has the use of bedaquiline, delamanid, and pretomanid transformed the treatment of drug-resistant tuberculosis, but it has also revolutionised the treatment of HIV-TB coinfection.

8.1.7 Other drugs

SQ-109 is an ethambutol analogue with 1, 2 ethylenediamine. This drug is now being tested in people after showing promising results in both in vitro and in vivo mice models of tuberculosis [68]. With isoniazid, rifampicin, and streptomycin, SQ-109 has been demonstrated to have a synergistic effect. SQ-109 reduces Rifampicin’s Minimum Inhibitory Concentration (MIC), and this synergy may be important in patients with Rifampicin-resistant TB [1, 69].

9. Preventive measures of MDR-TB through high quality treatment

Drug-resistant tuberculosis (DR-TB) poses a significant national and international programmatic challenge as well as a significant risk to individuals residing in TB-endemic countries. Only about 30% of the 490,000 people estimated to have developed multidrug-resistant tuberculosis (MDR-TB) (along with an additional 110,000 cases of rifampicin [RMP]-resistant TB) in 2016 had their diagnosis, and only about 25% had their treatment for MDR-TB started, according to the World Health Organisation (WHO) [3, 70].

Although existing drug-resistant cases must also be treated, mathematical modelling reveals that best-practice shortcourse chemotherapy can control isoniazid- or rifampicin-resistant disease while preventing the formation of MDR-TB by obtaining cure rates over 80% in new cases [71]. Focusing on enhanced and quality-controlled bacteriology with universal drug susceptibility testing (DST), quality therapy, removal of healthcare access barriers, and appropriate monitoring and evaluation can avoid the occurrence of MDR-TB in addition to high rates of case-detection and cure (WHO, 2015). This patient-centred strategy is further supported by the International Standards for Tuberculosis Care and its regional variations [72, 73].

Since patients with suspected DR-TB are what drives transmission, the cornerstone of MDR-TB transmission prevention should concentrate on earlier diagnosis and prompt initiation of effective therapy for all DR-TB patients (this includes patients on treatment for DS-TB who have undiagnosed DR-TB as well as those who remain both undiagnosed and untreated)[74]. Making these patients non-infectious will enhance individual outcomes and reduce transmission. A 90% decrease in TB incidence is one of the lofty goals put forth in the WHO’s End TB Strategy, which was introduced in 2015 [75]. The End TB Strategy mandates that all individuals being tested for TB, not just those with recognised risk factors for developing DR-TB disease, undergo universal drug susceptibility testing (DST). This method necessitates a large expansion of the use of molecular diagnostics for TB, which allow an early evaluation of treatment resistance at the time of TB diagnosis [70].

Early diagnosis and efficient treatment are essential components of an effective MDR-TB (Multi Drug Resistant Tuberculosis) control approach, similar to DS-TB (Drug Susceptible Tuberculosis). One of the main causes of continued TB transmission is diagnostic delay. Drug susceptibility testing (DST), which is necessary for the diagnosis of drug-resistant tuberculosis (DR-TB), was previously unavailable in the majority of high-prevalence settings until the recent introduction of rapid genotypic DST using GeneXpert MTB/RIF® or Line Probe Assays (such as INNO-LiPA® and Genotype MTBDRsl®) [76]. However, there is still a sizable case detection gap, and it is estimated that in 2014, 75% of MDR-TB patients were unreported [77]. Only 12% of newly diagnosed TB cases with bacteriological confirmation and 58% of TB people who have already received treatment around the world have DST done. The 2016 WHO MDR-TB treatment recommendations include a strong recommendation for universal DST for all TB patients at the time of initial diagnosis [3]. The proposed “F-A-S-T” strategy, which is based on rapid DST (drug susceptibility testing), is designed to find cases actively by cough monitoring and rapid molecular sputum testing, separate securely, and treat efficiently. This improved guidance is applicable to all settings and age categories [78]. Since these techniques will require significant investment from health systems to become a reality, more study is needed to determine their usefulness [79].

10. Another strategy we can follow is prevent transmission through infection control

Effective infection control measures are crucial in clinical facilities that treat TB and M/XDR-TB patients, according to the WHO Policy on Infection Control [71, 80, 81]. The plan of action comprises administrative, environmental, and management controls [73, 77, 81].

It is well recognised that poverty increases M. tuberculosis transmission, TB mortality rates, and TB incidence [71, 82]. Even in wealthy nations, detecting and treating MDR-/XDR-TB can be expensive. However, using new medications may be more affordable [73]. The correct application of modern diagnostic tools and medications, along with the fundamental measures provides the foundation for the prevention and control of MDR-TB [72, 77, 83, 84, 85, 86, 87, 88, 89]. Recently, efforts to end TB have concentrated on latent TB infection (LTBI) diagnosis and treatment as well as TB control in risk groups (displaced populations) [71, 73]. To identify LTBI in high risk and vulnerable groups, interferon-gamma release assays (IGRAs) or Mantoux tuberculin skin test (TST) are both advised, while novel regimens comprising rifampicin and rifapentine are currently advised, being especially helpful in isoniazid resistant cases [73]. The majority of TB infections are found among migrants and refugees in various high-income nations, and these populations are the main source of new cases among locals [71, 73]. Those vulnerable groups should have unrestricted access to TB services after moving to a new country, and quick, excellent TB and LTBI management should be ensured. Clinical professionals have a moral obligation to properly manage both drug-susceptible and MDR-TB in order to meet TB elimination targets [73].

11. Conclusion

It is commonly acknowledged that TB management in India will continue to face significant hurdles as long as TB treatment is dominated by such a vast and fragmented private sector. Approaches like the ones discussed here, when combined with already available surveillance techniques, could help to create a comprehensive picture of the state of the private sector, how it develops over time, and where interventions are most needed. Future interventions to harness the private sector for the benefit of TB patients in India and worldwide will benefit greatly from such monitoring.