March 24, 1882 – Robert Heinrich Hermann Koch in Berlin, at the Physiological Society, delivered a talk ‘on the aetiology of tuberculosis’ (TB). Till then, the disease, TB had different names in different countries; phthisis in Greece, scrofula in Rome, yaksma in India or consumption in Britain – all indicating ‘wasting away’ – a course that an individual, struck with the disease, would experience. Robert Koch had identified the germ causing TB1. Referring to the toll TB was exacting from the society at the time – one in seven human beings dying from it – he presented the results of his experiments on guinea pigs. In commemoration of this event, since 1997, each year, March 24th is observed as World TB Day, to rally support of the stakeholders worldwide for the control and elimination of TB. Noticeably, four years prior, in 1993, the World Health Organization (WHO) declared TB as a global emergency2; this announcement was preceded by the TB epidemic returning as an opportunistic disease entity and a public health threat to industrialized nations such as the Scandinavian countries, the Netherlands, Switzerland and the USA3, close to the heels of HIV making its presence felt globally. Another disturbing development in the late 1990s was the identification of multidrug-resistant TB (MDRTB) in countries such as Peru, where directly observed treatment-short course (DOTS) for TB was implemented well4. Despite the availability of an effective strategy for the management of MDRTB, re-treatment of MDRTB cases with DOTS was touted as a programmatic recommendation in such a situation5. Holding suboptimal treatment with DOTS or poor adherence of patients to medication, as primarily responsible for emergence of MDRTB served as the justification for such a recommendation. On the contrary, clinical trial results suggested that exclusive use of DOTS had little or no efficacy against drug-resistant strains6.
The discovery of tubercle bacilli by Robert Koch marked a momentous occasion as it discounted the then-prevailing notion of TB being a hereditary disease and firmly established the causal link between tubercle bacillus and TB. Subsequently, Robert Koch spent several years in search of a ‘cure for consumption’7, which did not stand the test of critical evaluation; neither clinical nor pathological observations8,9. To put things in perspective, this special issue of the Indian Journal of Medical Research (IJMR) has re-printed some of these earlier investigations along with the current thinking, challenges and understanding around TB with a particular focus on India.
What we know now is that the Mycobacterium tuberculosis complex (MTBC) contains 11 genetically related mycobacterial species responsible for TB in humans and animals. Although phylogenetic analysis has revealed that these members share a common clonal ancestry and a close nucleotide identity (>95%); their respective host adaptation, geographic niche and pathologies differ10. Noticeably, one of these members has been culture adapted, M. bovis Bacillus Calmette–Guérin (BCG). This culture adapted strain was used to develop BCG vaccine – the only one licensed as yet against TB, which was administered first as three doses of oral vaccine to a child (born of a tuberculous mother who died shortly after delivery and was brought up by a grandmother, herself tuberculous) in 192111. Currently, over two dozen vaccine candidates are in pre-clinical and clinical development pipeline.
It is also important to note that the genomic analysis of more than 250 strains of MTBC suggested that the branching of different lineages of MTB evolved over 70,000 years12 and co-evolved with humans13. What such an evolution means for the natural history of TB in humans – about a tenth of whom, following infection, develop active disease and in the rest replication is successfully arrested; about 5-10 per cent of the latter group experience reactivation of the latent infection over decades - is yet not fully understood. At present the latent TB infection – a paucibacillary state, is diagnosed in public health investigations through indirect means such as measurement of the host response with poor positive predictive value for disease breakout rather than directly measuring low antigenaemia. One can also acquire re-infection following exposure to infected aerosol discharged during coughing, sneezing or talking by a TB patient.
The WHO Stop TB Strategy (2006-2015) was launched in 2005 through a series of key programmatic objectives including expansion and enhancement of the DOTS, addressing all of TB-HIV co-infection, MDRTB treatment, strengthening of the health system through engagement of care providers and boosting primary healthcare and empowering people with TB, as well as the communities through continuous partnership and research promotion14. At the 67th World Health Assembly in 2014, the WHO’s member States adopted the ‘End TB Strategy (2015-2035)’. This is a 20-year strategy for TB prevention, care and control with an emphasis on targets that would pave the path towards TB elimination at the global scale15.
Against this background of incremental accumulation of knowledge and understanding about the social determinants (poverty, migration and mobility, social displacement, gender inequality, etc) of MTB disease, its interplay with the host innate and adaptive immunity, which determines the diverse course of an infection, programmatic challenges pertaining to early diagnosis, treatment and prevention and global commitment towards disease control, India conducted its second national population-based TB prevalence survey (2019-2021)16. A similar large-scale survey was carried out in the country during 1955-58 following independence in 194717. The second survey followed a multi-stage cluster sampling design and covered the entire country (under 20 State groups) except two small archipelagos namely, Andaman and Nicobar, and Lakshadweep. A total of 322,480 individuals participated in this survey. Worth noting in this context is that while Delhi was the only State group, which completed the survey before the country was hit by the COVID-19 pandemic, the Haryana State group started the survey during the second wave of COVID-1916. Between the two aforementioned countrywide initiatives, separated by 64 years, several local, State and sub-national surveys took place18, which highlighted the gravity of the situation of TB in India.
The prevalence of microbiologically confirmed pulmonary tuberculosis (PTB) as estimated during the second national survey16 among individuals aged ≥15 yr was 316 per 100,000 population (95% confidence interval (CI): 290-342), the lowest being in Kerala (151 per 100,000) and the highest in Delhi (534 per 100,000). A higher prevalence of PTB was detected in the elderly, males, the malnourished, smokers, people with problem alcohol use and known diabetics16. The prevalence of TB infection (detected through interferon-gamma release assay; IGRA in a subsample of 34,648) among population aged ≥15 yr was 31.4 per cent (95% CI: 27.2-33.5%)16.
Two issues drew immediate attention, (i) about two third of the individuals with symptoms suggestive of TB during the second national TB prevalence survey reported not seeking healthcare services for various reasons (symptom neglect, self-treatment, inability to afford seeking care, etc.) and (ii) nine State groups had higher prevalence of all forms of TB as compared to the national average of 312 per 100,000 population (95% CI: 286-337)16.
Evidently, heterogeneity of the problem of TB between Indian States calls for socioculturally appropriate innovations at the national and State level. For example, in an effort to reduce the duration and costs of transporting sputum samples for investigation in hard-to-reach areas of Himachal Pradesh, public health professionals and researchers have explored the feasibility of deployment of drones19. Some of the articles published in this special issue of IJMR further highlight what India has been doing in facilitating prompt diagnosis and treatment. Re-analysis of dataset from the BCG trial adds to this knowledge base and suggests how re-vaccination with BCG in adolescents, adults and the elderly could boost the ongoing TB elimination programme in India. On the other hand, some of the perspectives written by national and international experts in this issue indicate what is going right and what would benefit from further programmatic innovation. Thus, we are poised to inform the discussion on policy, programme and practice pertaining to TB elimination in the country and beyond.
However, the road ahead is not easy, but cognizance from past experiences may come in handy. For instance, global political upheavals have time and again served as a reminder including the likes of World Wars I and II vis-a-vis their impact on the situation of TB; not limited to the context of scientific endeavours to find solutions20 but also in terms of morbidity and mortality related to TB which are well recorded in the literature21–23. Therefore, dealing effectively with the structural, macrosocial and political issues at the global and national level is as important for the elimination of TB as addressing its interface with various diseases such as HIV24 and diabetes25 in different sociocultural and community settings.
Financial support and & sponsorship: None.
Conflicts of Interest: None.
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