Tuberculosis (TB) is caused by bacteria (Mycobacterium tuberculosis) that most often affect the lungs. Tuberculosis is curable and preventable. TB is spread from person to person through the air. When people with lung TB cough, sneeze or spit, they propel the TB germs into the air. A person needs to inhale only a few of these germs to become infected. About one-quarter of the world's population has latent TB, which means people have been infected by TB bacteria but are not (yet) ill with the disease and cannot transmit the disease. People infected with TB bacteria have a 5–15% lifetime risk of falling ill with TB. Persons with compromised immune systems, such as people living with HIV, malnutrition or diabetes, or people who use tobacco, have a higher risk of falling ill.

1. TUBERCULOSIS - INTERNATIONAL
PERSPECTIVES ON EPIDEMIOLOGY, DIAGNOSIS
AND CONTROL
RANJINI MANUEL
18-MVP-19
DEPARTMENT OF VETERINARY
EPIDEMIOLOGY AND
PREVENTIVE MEDICINE

3. ADVISORY COMMITTEE
Dr Deepa P M
Assistant Professor &
HOD (i/c)
Department Of
Veterinary Epidemiology
And Preventive Medicine
Pookode
Dr K.Vijayakumar
Professor & Head
Department of
Veterinary
Epidemiology and
Preventive Medicine
Mannuthy
Dr Janus. A
Assistant Professor
Department of
Veterinary
Epidemiology and
Preventive Medicine
Pookode
Dr Rajeshkumar
Assistant Professor
Department of
Veterinary physiology
Pookode

5. OUTLINE
INTRODUCTION EPIDEMIOLOGY
DIAGNOSIS CONTROL

6. INTRODUCTION

7. Biblical
reference
500,000BC
Egyptian illustrations
on TB
1834, Johann Schonlein- coined
the term Tuberculosis
1865, Jean Antoine
Villemin- TB contagious
1882, Robert Koch
discovered M.tuberculosis
1884, First Sanatorium
1943, discovery of
streptomycin
1946, new
drugs INH, PAS
1990’s TB decline due
to control measures

8. EPIDEMIOLOGY

9. TB IN HUMANS

10. TB INCIDENCE
(WHO- 2018)

12. 20%
10%
7%
5%
Tuberculosis Mortality
500,000 /year
2 Million new cases a year and
accounts for nearly 1/3rd of
prevalent cases globally
(Banerji et al., 2017)
INDIA

13. • In India TB incidence is estimated - 250 per 1 lakh
population whereas in Kerala it is 67 cases per 1
lakh population (2017 RNTCP )
• RNTCP has found just 352 new cases of TB all over
the state in a population of 3.4 crore
• Idukki and Wayanad have shown the maximum
decline in the number of TB cases, with a
notification rate of just 51 cases and 44 cases,
respectively, per 100,000 population (Kerala TB
Elimination Mission strategy document, 2017)
51 Cases
44 Cases
Population – 34,208129
Public sector – 20,199 private sector – 3567 Pediatric 1530
KERALA

14. TB IN ANIMALS
(World Organisation For Animal Health -2019)

15. 2%
1%
8%
37%
15%
6%
5%
20%
3%
7%
• 10-25% loss in productivity (Verma et al., 2014)
• 302 million Bovines
(Basic Animal Husbandry and Fisheries Statistics,
Government of India 2019)
• 21.8 million bovines are estimated to be bTB
positive in India, exceeding the total number of
dairy cattle in the United States (USDA, 2016)
• bTB prevalence is 7.2 % (Srinivasan, 2018)

16. • 1817 – first canine TB report, 2- 6%
• 1883- first feline TB report, 2-12%
• TB in dogs from a high-risk setting was 1%
• The prevalence of immunological sensitization to M. tuberculosis antigens in dogs
living in contact with sputum smear-positive TB patients was 50%
(Parsons, 2011)
England (William, 1970)

17. TYPES RESISTANCE
RR-TB (Rifampicin Resistant) RIF
MDR-TB (Multidrug Resistant) RF, INH, with or without resistance to
FLD
XDR-TB (Extensively Resistant) RF, INH to any fluoroquinolone, any 3
second line injectables (AMK, CAP,
and KAN)
TDR-TB (Total Drug Resistant ) FLD, SLD
XXDR-TB (Extremely Drug Resistant) FLD, SLD + Rifabutin, clofazimine,
dapsone, claritromycin, thiacetazone
First Line Drugs (FLD) – Isoniazid (INH),
Rifampicin (RIF), Ethambutol (EMB),
Pyrazinamide (PZA) & Streptomycin (SM)
Second Line Drugs(SLD) – Ofloxacin (OFX),
Prothionamide (PTH), Amikacin (AMK),
Kanamycin (KAN), Ethionamide (ETH), P-
aminosalicylic acid (PAS), and Capreomycin
(CAP)
DRUG RESISTANT TB
(Velayati, 2009)

18. 558 000 people
(RR-TB)
82% - MDR-
TB India
24%
China
13%Russian
Federation
10%
others
53%
MDR-TB 2017
India China
Russian Federation others
8.5 % - XDR-
TB
(WHO-2018)

19. DIAGNOSIS

20. o Volatile organic compounds (VOCs) detection
DIAGNOSIS
DIRECTLY DETECT THE ACTIVELY GROWING BACILLI
o Microscopy
o Culture
o Antigen detection
o Nucleic acid detection
INDIRECTLY DETECT THE IMMUNE RESPONSE AGAINST THE BACILLI
o Detection of immune response by tuberculin skin testing (TST)
o Interferon-gamma release assays (IGRAs)
NEW TECHNIQUE

21. DIRECT DETECTION METHODS
MICROSCOPY
Sputum smear
microscopy
Front-loaded microscopy
Sodium hypochlorite (bleach)
microscopy

22. SPUTUM MICROSCOPY
• Both Ziehl-Neelsen & Auramine staining are
highly specific.
• Rapid and reliable identification
• 2 sputum sample are collected, spot and
morning spot
• Sensitivity vary from 20-80%, needs >5000
bacilli/ml
• Hard to differentiate between
Mycobacterium tuberculosis and other non
tuberculosis bacteria

23. FLUORESCENT STAINING
• On comparison with ZN AO and culture ,
Sensitivity
False negative
• Using culture as the reference method, the sensitivity of
direct staining was
ZN-
44.1%,
AO-
71.6%
culture-
70%
AO
2.78%
ZN
40.27%
ZN-
55.5%
AO-
71.8%
(Singh, 2010) (Hooja et al., 2011)

24. • Automated microscopic technology
• Cell Scope
Portable digital FM that provides enlarged digitalised
images
• Vital fluorescent staining
Use fluorescein diacetate (FDA), in combination with
smear microscopy and it stains only living, cultivable
bacteria.
NEWER MICROSCOPIC
TECHNOLOGIES
(Seema and Nandita, 2019)

25. CULTURE
• Gold standard test
• Culture allows diagnostic confirmation of TB and is more
sensitive than microscopy
• 10-100 bacilli/ml are required to obtain a positive result
• Use of culture increases the number of TB cases found by
30–50% over smear
• Culture used for species identification, drug susceptibility
testing (DST), and genotyping
• Culture also used to monitor patient response to
treatment
(Seema and Nandita, 2019)

26. MEDIA
Solid Liquid
Eg; LJ medium Eg; Middlebrook 7H10, 7H11
• Increased recovery &
decreased detection
time
TAT 3-6 weeks
TAT- 4-8 weeks (Gaby et al., 2012)

27. AUTOMATED SYSTEM
Colorimetric sensor Fluorescence Pressure
• Monitor change in CO2
• In response to CO2, colour
change from grey to
green/yellow
• Eg- BacT/ALERT 3D
• Measures the consumption of
oxygen by growing organisms
• Eg- BACTEC MGIT
• Changes in headspace
pressure due to O2
consumption
• Eg- Versa TREKCapacity up to 960 cultures at a time
Benefit labs with high work load

28. ANTIGEN DETECTION
• Lipoarabinomannan (LAM) - 17.5-kD heat-stable glycolipid found in the cell wall of
Mycobacterium tuberculosis.
• LAM - 15% of the total bacterial weight and serves as an immunogenic virulence factor
that is released from metabolically active or degrading bacterial cells during TB infection
• LAM sensitivity - 70% and specificity - 92%
(Elsawy, 2012)

29. NUCLEIC ACID AMPLIFICATION TESTS (NAATs)
• Test that directly detects the genetic material of the infecting organism
• As few as 100 organisms/ mL may give a positive result with NAAT
• Detect the nucleic acid (DNA) of both live and dead bacilli – Initial diagnostic purpose
Types of NAAT are :
Polymerase chain reaction (PCR)
• PCR - sensitivity of 95% in smear positive TB and 50-60% in smear negative TB
• The specificity of PCR is around 98%
• PCR is more sensitive than microscopy but less sensitive than culture
MOLECULAR DETECTION
(Sarkar, 2017)

30. LINE PROBE ASSAY
• This strip test detects TB DNA and
genetic mutations associated with
drug resistance
• Two commercially available
products are
InnoLiPA
assay-Innogenetics,
Belgium
Hain Lifescience
GenoType® MTBDR plus.
(Seema and Nandita, 2019)

31. DNA Extraction
Amplification Hybridization
Result
OVER VIEW

32. • CBNAAT is a totally automated test and
can be used as POCT
• Rapid diagnosis of TB where results
obtained within a day
• The sensitivity and specificity are 95 and
98% respectively
• Samples – Sputum, biopsy of Lymph
nodes, cerebro-spinal fluid, synovial fluid,
pleural fluid
CARTRIDGE-BASED NAAT (CB-NAAT)
(Seema and Nandita, 2019)

33. • Identify M. tuberculosis and rifampicin (RIF)
resistance within 2 hours
• Requires only minimal training, and minimal
biosafety facilities
• In a systemic review and meta-analysis- the
sensitivity and specificity were 83 and 94
percent respectively
• The Xpert MTB/RIF can be done in all EP-TB
specimens except stool, urine and blood.
XPERT MTB/RIF ASSAY (GENE XPERT)
(Desikan, 2017)

34. Xpert MTB/RIF Ultra
• 10 fold more analytical sensitivity
• Cartridge detects Mycobacterium tuberculosis in
specimens with low numbers of bacilli
• South Africa is the only high TB burden country
currently using Ultra as the initial TB diagnostic test
• Two cartridge-based technologies being developed
in China and India which are under development

35. DETECTION OF VOLATILE COMPOUNDS
• Mycobacteria - unique volatile organic compounds (VOCs) as metabolites with
distinctive odors when cultured in vitro
• VOCs - Cyclohexane, benzene, decane and heptane derivatives
• Sample – urine , breath and sputum
URINE
• Identified 5 VOCs - significantly altered and together form a molecular signature
• VOCs - TB disease marker
BREATH
• Breath collection apparatus (BCA) that collects and concentrates breath VOCs
and analysis done by gas chromatography and mass spectroscopy (GC/MS)
• Breath test - approximately 70% sensitive and specific
(Banday et al., 2011)
(Phillips et al 2010)

36. CONTROL

37. United to End TB
WHO

38. CURRENT SCENARIO
• Highlights the need for immediate
action to accelerate progress towards
the goal of ending the TB epidemic by
2030
10
300
500
0
100
200
300
400
500
600
TB cases
New TB CASES- 2017
High income countries 30 high burden countries few countries
Latent
TB
Active
TB

39. 23
%
16
%
TB mortality
2% drop in
incidence
rate per year
European
region 5 %
decline
African
region 4 %
decline
TREATMENT
SUCCUESS
RATE
55%
YEAR-
2000
YEAR-
2017
PROGRESS

40. PROGRESS
BCG
VACCINATION
158 Countries
BCG vaccine
120 Countries –
90% coverage

41. 20 TB drugs
in clinical
trials
12 Vaccine
in clinical
trials
Treatment
regimens

43. RNTCP
• Revised National TB control programme
(RNTCP) and National AIDS Control Organisation
works together to scale up the global response
towards TB prevention and control
• FIND.TREAT.ALL is the initiative – focuses on
strengthening the surveys
ACTIONS
MONITORING
REPORTING
REVIEW

44. DIRECTLY OBSERVED TREATMENT- SHORT
COURSE (DOTS)
• DOTS program is the fastest-expanding and the largest program in the world in
terms of patients initiated on treatment & population coverage
• Management strategy of public health system
(Sadhu, 2011)

45. GOAL - Annual
decline rate
accelerated to
17% per year
New vaccine
New drugs and
treatment
Rapid diagnosis
Monitoring &
survey
FUTURE PERSPECTIVE

46. CONCLUSION
• Tuberculosis is a very challenging disease which is difficult to
eradicate mainly due to the drug resistance and its easy transmission
• Integrated approach towards TB, combined with long years of
perseverance we have succeeded to reduce the TB burden
• To achieve the goal of ending the epidemic by 2030, we need to
accelerate the progress to another level.

47. REFERENCES
• Daniel, T.M., 2000. Pioneers of medicine and their impact on tuberculosis. University Rochester Press
• Morse, D., Brothwell, D.R. and Ucko, P.J., 1964. Tuberculosis in ancient Egypt. American Review of
Respiratory Disease, 90(4), pp.524-541
• Daniel, V.S. and Daniel, T.M., 1999. Old Testament biblical references to tuberculosis. Clinical infectious
diseases, 29(6), pp.1557-1558
• Rothschild, B.M., Martin, L.D., Lev, G., Bercovier, H., Bar-Gal, G.K., Greenblatt, C., Donoghue, H.,
Spigelman, M. and Brittain, D., 2001. Mycobacterium tuberculosis complex DNA from an extinct bison
dated 17,000 years before the present. Clinical Infectious Diseases, 33(3), pp.305-311
• Daniel, T.M., 2006. The history of tuberculosis. Respiratory medicine, 100(11), pp.1862-1870
• Murray, J.F., Schraufnagel, D.E. and Hopewell, P.C., 2015. Treatment of tuberculosis. A historical
perspective. Annals of the American Thoracic Society, 12(12), pp.1749-1759
• Schatz, A., Bugle, E. and Waksman, S.A., 1944. Streptomycin, a Substance Exhibiting Antibiotic Activity
Against Gram-Positive and Gram-Negative Bacteria.∗. Proceedings of the Society for Experimental Biology
and Medicine, 55(1), pp.66-69
• Daniel, T.M. and Janicki, B.W., 1978. Mycobacterial antigens: a review of their isolation, chemistry, and
immunological properties. Microbiological reviews, 42(1), p.84

48. REFERENCES
• Kappelman, J., Alçiçek, M.C., Kazancı, N., Schultz, M., Özkul, M. and Şen, Ş., 2008. First Homo
erectus from Turkey and implications for migrations into temperate Eurasia. American Journal of
Physical Anthropology, 135(1), pp.110-116.
• Zysk, K.G., 1996. Medicine in the Veda: Religious Healing in the Veda: with Translations and
Annotations of Medical Hymns from the Ṛgveda and the Atharvaveda and Renderings from the
Corresponding Ritual Texts (Vol. 1). Motilal Banarsidass Publ.
• Banerji D, Andersen S. A sociological study of awareness of symptoms among persons with
pulmonary tuberculosis. Bull World Health Organ 1963;29:665-683)
• Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Global burden of tuberculosis: estimated
incidence, prevalence, and mortality by country. JAMA 1999;282:677-686)
• Shah NP, Singhal A, Jain A, Kumar P, Uppal SS, Srivatsava P, et al. Occurrence of overlooked
zoonotic tuberculosis : detection of Mycobacterium bovis in human cerebrospinal fluid
occurrence of overlooked zoonotic tuberculosis : detection of Mycobacterium bovis in human
cerebrospinal fluid. J Clin Microbiol. 2006;44(4):1352–8
• Verma R. Zoonotic tuberculosis in India. Zoonotic Tuberc Mycobacterium bovis Other Pathog
Mycobact 3rd Ed. 2014;197–201.

49. REFERENCES
• Srinivasan S, Easterling L, Rimal B, Niu XM, Conlan AJK, Dudas P, et al. Prevalence of Bovine
Tuberculosis in India: A systematic review and metaanalysis. Transbound Emerg Dis. 2018;65:1627–
40.
• (LoBue, P.A., Enarson, D.A. and Thoen, C.O., 2010. Tuberculosis in humans and animals: an overview
[Serialised article. Tuberculosis: a re-emerging disease in animals and humans. Number 1 in the
series]. The International Journal of Tuberculosis and Lung Disease, 14(9), pp.1075-1078.)
• Siddiqi K, Lambert M-L, Walley J. Clinical diagnosis of smear-negative pulmonary tuberculosis in
low-income countries: the current evidence. Lancet Infect Dis. 2005 Mar.21;3(5):288–96.
• Steingart KR, Henry M, Ng V, Hopewell PC. Fluorescence versus conventional sputum smear
microscopy for tuberculosis: a systematic review. Lancet Infect Dis. 2006;6:570–81.
• Toman's Tuberculosis: Case Detection Treatment, and Monitoring: Questions and Answers. 2nd ed.
Frieden TR, editor. World Health Organization, Geneva; 2004
• Mase SR, Ramsay A, Ng V, Henry M, Hopewell PC, Cunningham J, et al. Yield of serial sputum
specimen examination in the diagnosis of pulmonary tuberculosis: a systemic review. Int J Tuberc
Lung Dis. 2007May;11(5):485-95.
• (Hooja, S., Pal, N., Malhotra, B., Goyal, S., Kumar, V. and Vyas, L., 2011. Comparison of Ziehl Neelsen
& Auramine O staining methods on direct and concentrated smears in clinical specimens. The
Indian journal of tuberculosis, 58(2), pp.72-76.).