Indian J Med Res 157, February and March 2023, pp 111-113 Quick Response Code:

DOI: 10.4103/ijmr.ijmr_541_23

Editorial
Downloaded from http://journals.lww.com/ijmr by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AW

Tuberculosis: National survey in India & elimination challenges reflected through

global learning
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 05/11/2023

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 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

© 2023 Indian Journal of Medical Research, published by Wolters Kluwer - Medknow for Director-General, Indian Council of Medical Research
111
 112 INDIAN J MED RES, FEBRUARY AND MARCH 2023

successfully arrested; about 5-10 per cent of the latter surveys took place18, which highlighted the gravity of
group experience reactivation of the latent infection the situation of TB in India.
over decades - is yet not fully understood. At present the
The prevalence of microbiologically confirmed
latent TB infection – a paucibacillary state, is diagnosed
pulmonary tuberculosis (PTB) as estimated during
in public health investigations through indirect means
Downloaded from http://journals.lww.com/ijmr by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AW

the second national survey16 among individuals

such as measurement of the host response with poor
aged ≥15 yr was 316 per 100,000 population (95%
positive predictive value for disease breakout rather
confidence interval (CI): 290-342), the lowest being
than directly measuring low antigenaemia. One
in Kerala (151 per 100,000) and the highest in Delhi
can also acquire re-infection following exposure to
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 05/11/2023

(534 per 100,000). A higher prevalence of PTB was

infected aerosol discharged during coughing, sneezing
detected in the elderly, males, the malnourished,
or talking by a TB patient.
smokers, people with problem alcohol use and known
The WHO Stop TB Strategy (2006-2015) diabetics16. The prevalence of TB infection (detected
was launched in 2005 through a series of key through interferon-gamma release assay; IGRA in a
programmatic objectives including expansion and subsample of 34,648) among population aged ≥15 yr
enhancement of the DOTS, address all of TB-HIV was 31.4 per cent (95% CI: 27.2-33.5%)16.
co-infection, MDRTB treatment, strengthening of the
Two issues drew immediate attention, (i) about
health system through engagement of care providers
two third of the individuals with symptoms suggestive
and boosting primary healthcare and empowering
of TB during the second national TB prevalence survey
people with TB, as well as the communities through
reported not seeking healthcare services for various
continuous partnership and research promotion14. At
reasons (symptom neglect, self-treatment, inability to
the 67th World Health Assembly in 2014, the WHO’s
afford seeking care, etc.) and (ii) nine State groups had
member States adopted the ‘End TB Strategy (2015-
higher prevalence of all forms of TB as compared to
2035)’. This is a 20-year strategy for TB prevention,
the national average of 312 per 100,000 population
care and control with an emphasis on targets that
(95% CI: 286-337)16.
would pave the path towards TB elimination at the
global scale15. Evidently, heterogeneity of the problem of
TB between Indian States calls for socioculturally
Against this background of incremental
appropriate innovations at the national and State level.
accumulation of knowledge and understanding about
For example, in an effort to reduce the duration and
the social determinants (poverty, migration and
costs of transporting sputum samples for investigation
mobility, social displacement, gender inequality, etc)
in hard-to-reach areas of Himachal Pradesh, public
of MTB disease, its interplay with the host innate and
health professionals and researchers have explored
adaptive immunity, which determines the diverse course
the feasibility of deployment of drones19. Some of the
of an infection, programmatic challenges pertaining to
articles published in this special issue of IJMR further
early diagnosis, treatment and prevention and global
highlight what India has been doing in facilitating
commitment towards disease control, India conducted
prompt diagnosis and treatment. Re-analysis of
its second national population-based TB prevalence
dataset from the BCG trial adds to this knowledge
survey (2019-2021)16. A similar large-scale survey was
base and suggests how re-vaccination with BCG in
carried out in the country during 1955-58 following
adolescents, adults and the elderly could boost the
independence in 194717. The second survey followed
ongoing TB elimination programme in India. On
a multi-stage cluster sampling design and covered
the other hand, some of the perspectives written by
the entire country (under 20 State groups) except two
national and international experts in this issue indicate
small archipelagos namely, Andaman and Nicobar, and
what is going right and what would benefit from
Lakshadweep. A total of 322,480 individuals participated
further programmatic innovation. Thus, we are poised
in this survey. Worth noting in this context is that while
to inform the discussion on policy, programme and
Delhi was the only State group, which completed the
practice pertaining to TB elimination in the country
survey before the country was hit by the COVID-19
and beyond.
pandemic, the Haryana State group started the survey
during the second wave of COVID-1916. Between the However, the road ahead is not easy, but
two aforementioned countrywide initiatives, separated cognizance from past experiences may come in handy.
by 64 years, several local, State and sub-national For instance, global political upheavals have time and
 PANDA: GLOBAL LEARNING & TUBERCULOSIS IN INDIA 113
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
Downloaded from http://journals.lww.com/ijmr by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AW
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
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 05/11/2023
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.
Samiran Panda1,2
Editor-In-Chief, Indian J Med Res & 1ICMR-Dr A. S.
Paintal Distinguished Scientist Chair, 2Indian Council
of Medical Research, New Delhi 110 029, India
pandasamiran@gmail.com
Received March 21, 2023
References
1. Koch R. The etiology of tuberculosis. From the Berliner
Klinische Wochenschrift, Volume 19 (1882). Zentralbl
Bakteriol Mikrobiol Hyg A Med Mikrobiol Infekt Parasitol
1982; 251 : 287-96.
2. World Health Organization. WHO tuberculosis programme:
Framework for effective tuberculosis control. Geneva: WHO;
1994.
3. Rieder H, Raviglione M. TV visits the industrialized world.
TB revisits the industrialized world. World Health 1993; 46 :
20-1.
4. Farmer P, Kim JY, Kleinman A, Basilico M. MDRTB and
limits of cost-effectiveness analysis. In: Reimagining global
health: An introduction. California: University of California
Press; 2013. p. 234-41.
5. Kim JY, Mukherjee JS, Rich ML, Mate K, Bayona J,
Becerra MC. From multidrug-resistant tuberculosis to DOTS
expansion and beyond: Making the most of a paradigm shift.
Tuberculosis (Edinb) 2003; 83 : 59-65.
6. Seung KJ, Gelmanova IE, Peremitin GG,
Golubchikova VT, Pavlova VE, Sirotkina OB, et al. The effect
of initial drug resistance on treatment response and acquired
drug resistance during standardized short-course chemotherapy
for tuberculosis. Clin Infect Dis 2004; 39 : 1321-8.
7. Koch R. A further communication on a remedy for tuberculosis.
Br Med J 1891; 1 : 125-7.
8. Goetz T. The remedy: Robert Koch, Arthur Conan Doyle, and
the quest to cure tuberculosis. New York: Avery; 2014.
9. Virchow R. Remarks on the effect of Koch’s remedy on the
internal organs of tuberculous patients. Br Med J 1891; 1 :
127-32.
10. Gagneux S. Ecology and evolution of Mycobacterium
tuberculosis. Nat Rev Microbiol 2018; 16 : 202-13.
11. Calmette A. Preventive vaccination against tuberculosis with
BCG. Proc R Soc Med 1931; 24 : 1481-90.
12. Comas I, Coscolla M, Luo T, Borrell S, Holt KE,
Kato-Maeda M, et al. Out-of-Africa migration and Neolithic
coexpansion of Mycobacterium tuberculosis with modern
humans. Nat Genet 2013; 45 : 1176-82.
13. Brites D, Gagneux S. Co-evolution of Mycobacterium
tuberculosis and Homo sapiens. Immunol Rev 2015; 264 :
6-24.
14. Raviglione MC, Uplekar MW. WHO’s new stop TB strategy.
Lancet 2006; 367 : 952-5.
15. Uplekar M, Weil D, Lonnroth K, Jaramillo E, Lienhardt C,
Dias HM, et al. WHO’s new end TB strategy. Lancet 2015;
385 : 1799-801.
16. Indian Council of Medical Research. National Institute for
Research in Tuberculosis. National Health Mission. Ministry
of Health and Family Welfare, Government of India. National
TB prevalence survey in India (2019-2021). Available from:
https://tbcindia.gov.in/showfile.php?lid=3659, accessed on
March 22, 2023.
17. Indian Council of Medical Research. Tuberculosis in India:
A national sample survey; ICMR special report series No 34,
1955-1958. New Delhi: ICMR; 1959.
18. Chadha VK, Anjinappa SM, Dave P, Rade K, Baskaran D,
Narang P, et al. Sub-national TB prevalence surveys in India,
2006-2012: Results of uniformly conducted data analysis.
PLoS One 2019; 14 : e0212264.
19. Thakur V, Ganeshkumar P, Lakshmanan S, Rubeshkumar P.
Do unmanned aerial vehicles reduce the duration and costs in
transporting sputum samples? A feasibility study conducted in
Himachal Pradesh, India. Trans R Soc Trop Med Hyg 2022;
116 : 971-3.
20. Bynum H. Spitting blood: The history of tuberculosis. Oxford,
UK: Oxford University Press; 2012.
21. Dubos R, Dubos J. The white plague: Tuberculosis, man, and
society. Boston, MA: Little, Brown, and Company; 1952.
22. Drobniewski FA, Verlander NQ. Tuberculosis and the role of
war in the modern era. Int J Tuberc Lung Dis 2000; 4 : 1120-5.
23. Barr RG, Menzies R. The effect of war on tuberculosis.
Results of a tuberculin survey among displaced persons
in El Salvador and a review of the literature. Tuber Lung
Dis 1994; 75 : 251-9.
24. Rao A, Mamulwar M, Shahabuddin SM, Roy T,
Lalnuntlangi N, Panda S. HIV epidemic in Mizoram, India:
A rapid review to inform future responses. Indian J Med Res
2022; 156 : 203-17.
25. Amberbir A. The challenge of worldwide tuberculosis control:
And then came diabetes. Lancet Glob Health 2019; 7 : e390-1.