The document provides an overview of tuberculosis (TB) including: - Causative agent, symptoms, and modes of transmission - Disease burden globally and in India - Diagnostic methods under India's National Tuberculosis Elimination Programme (NTEP) including sputum smear microscopy, culture-based tests, and molecular tests - Evolution of TB control in India from early programs to NTEP, which aims to eliminate TB in India by 2025

1. Presented by-
Harshita-19041
Himanshu-19042
Himanshu Sharma-19043
Hrishit-19044
Ishani Gautam-19045

2. • CONTENTS
• Tuberculosis & Epidemiology – Harshita (19041)
• Definitions & Indices -Himanshu (19042)
• NTEP --Himanshu Sharma( 19043)
• Diagnostic Methods
& Algorithm under - Hrishit jamwal (19044)
NTEP Ishani Gautam (19045)

3. Tuberculosis
• Chronic ??? infectious disease caused by
Mycobacterium tuberculosis
• Primarily affects lungs: Pulmonary Tuberculosis
• Can also affect intestine , meninges, bones and
joints ,lymph nodes, skin and other tissues

4. HISTORY OF TB
• Can be traced back to 9,000 years
• Earliest mention in India- 3,300 years ago
• Phthisis , White Plaque, Kshaya
• Term Tuberculosis: Johann Schonlein (1834)

5. *Robert Koch discovered that TB is caused by a bacteria
Mycobacterium tuberculosis on 24 March 1882
World TB day : 24th March
* Theme (2022) : “ Invest to end TB, save lives”

8. NATURAL HISTORY OF TUBERCULOSIS

9. AGENT FACTORS
• M. Tuberculosis: facultative intracellular parasite
• Two strains – Human and bovine
Human strain is responsible for majority of cases
• Bovine – affects mainly animals .

10. • SOURCE OF INFECTION
• Two sources of infection – human and bovine.
• Human source – whose sputum is positive for tubercle
bacilli and who has either received no treatment or has not
treated fully.
* Annually 10 -15 persons contract infection from one case of
infectious pulmonary TB.
• * Bovine source – Infected milk.
• Effective anti – microbial treatment reduces infectivity by
90 percent within 48 hours .

11. HOST FACTORS
A .AGE
• Affects all ages
• In India the infection rate is 2 per cent in 0 to 14 years age
group and 20 percent in 15 to 24 years .
B.SEX
More prevalent in males than females.

12. • C .NUTRITION
• Malnutrition is a predisposing factor of TB.
• D .IMMUNITY
• Acquired by natural infection or BCG vaccination.

13. SOCIAL FACTORS
It includes:
:Poor quality of life
:Poor housing
: Overcrowding
: Population explosion
: Undernutrition
: Smoking
: Alcohol abuse
:Large families
:Lack of awareness of causes of illness.

14. MODE OF TRANSMISSION
• Droplet transmission (1-5 micron)
• Not transmitted by fomites such as dishes and other articles.

15. INCUBATION PERIOD
-Weeks to years.
-The time between the infection and the development of
positive tuberculin skin test – 3 to 6 weeks.
-Disease development depends upon-
1.Closeness of contact.
2.Extent of disease.
3.Sputum positivity of source case.

16. SYMPTOMS
• Persistent cough
• Fever
• Coughing up blood
• Fatigue
• Loss of appetite
• Unintentional weight loss
• Night sweats
• Chest pain.

17. DISEASE BURDEN OF TB
• 13th leading cause of death worldwide
• 2nd leading cause of death of infectious diseases after covid in 2020
• 1/3rd of the global population: infected asymptomatically
• 10 billion people fall ill every year
• 1.5 million people die due to TB every year

18. • India contributes largest to the TB cases amoung all countries.
• The total no. Of incidence TB patients notified During 2021
was 19,33,381 which was 19% higher than that of 2020
(16,28,161).
• Rate of 188 per 1,00,000 population.
• In India Uttar Pradesh has the maximum number of TB cases.

19. SYSTEMS
EPIDEMIOLOGY
SYSTEMS BIOLOGY
Socio-Economic
Condition
Housing
TB control measures
Evolution
Mycobacterium
Tuberculosis
Host
HIV Epidemic
Urbanisation
Evolution
Environment

20. • Causitive agent-Mycobacterium tuberculosis.
• Host-usually human beings which harbors the disease.
• Environment-Tobacco smoke,indoor air pollution,overcrowding
living condition.
• The mission of an epidemiologist is to break at least one of side
of the triangle,disrupting the connection between the
environment the host and the agent and stopping the
continuation of the disease.

21. Epidemiological indices
• Need : to measure the problem in community as well as
planning and for evaluation
1. Incidence : No. of new and recurrent (relapsed) episodes of TB
occurring in a given year

22. 2.Prevalance: no of TB cases (all forms) present at a given
point of time or period of time.
Later being period prevalence and former being point
prevalance.
3.Mortality:no of deaths purely from TB (HIV – people)
4.Case fatality rate : risk of death from TB among people
with active disease.

24. 5. Case Notification Rate: New and recurrent episodes of
TB for a given year expressed per 1 lakh population.
Important in estimation of TB incidence.
6. Case Detection Rate: No. Of notification of new and
relapse cases in year divided by estimated incidence of such
cases.

25. Prevalence of drug resistant cases
It is prevalence of patient excreting bacilli resisted to anti TB
drugs.
A. Prevalence of infection. : %of individuals showing positive
reaction to tuberculin test .
Problems : BCG vaccination and cross senstivity.
B. Incidence of infection :% of population under study who will
be newly infected by TB.

26. • Newer definetions :(2014)
Presumptive case:(TB suspect) presents with symptoms and
signs.
A. CASE DEFINETIONS
1.Bacteriologically confirmed case:
one from whom biological specimen is positive by microscopy
, culture or rapid tests.
2.Clinically diagnosed case: one who is not
bacteriologically confirmed but diagnosed by clinician.

27. • These cases include diagnosis on basis of x ray
abnormalities or histology.
CASES ARE FURTHER CLASSIFIED ON :
1.Anatomical site of disease.
2.History of previous treatment.
3. Drug resistance.
4. HIV status.

28. 1. ANATOMICAL SITE OF DISEASE
PULMONARY TB
• Confirmed case of lung
parenchyma &
tracheobronchial tree.
• Miliary ,hilar ,mediastinal are
not included.
EXTRAPULMONARY TB
• Any confirmed case of TB
involving organs other than
TB .
• Eg :lung, lymph node,bones
e.t.c

29. • Based on history of previous treatment
NEW PATIENTS: Patients who have never been treated for TB
or have taken anti TB drugs for less than 1 month
PREVIOUSLY TREATED PAT. : Received 1 month or more anti
TB drugs.

30. • They are further classified as:
A. Relapse patients : Previously treated , cured, completed
treatment and are diagnosed now with recurrent episode of
TB
B.Treatment after failure patients:
Previously treated but treatment failed at end of most
recent treatment course

31. 3.Treatment after loss to follow up patients: Previously been
treated for TB , declared lost to follow up at end of their recent
treatment.
4.Other previously treated patients:
Previously treated but outcome unknown or undocumented

32. Based on drug resistance-
A. Mono resistance: Resistant to 1 first line anti TB drugs
B. Poly drug resistance :Resistant to more than 1 first line anti TB
drugs (except H&R)

33. c. Multidrug resistance: Resistance to at least both rifampicin
or isoniazid known as MDR TB.
D. Extensive drug resistance: In addition to MDR resistance to
FQs or at least one of three 2nd line injectable drug

34. 4. Based on HIV status:
HIV + TB PATIENT : Confirmed case of TB which have + result from HIV
TEST conducted
HIV – TB PATIENT: Confirmed case of TB who has – result from HIV
test conducted

35. Treatment outcome definitions:
They make clear distinctions b/w
1.Patient treated for drug susceptible TB
2.Patient treated for drug resistant TB .

36. TREATMENT OUTCOMES FOR TB PATIENTS (EXCLUDING MDR
&RR TB)
CURED : Pulmonary TB patient, bacteriologically confirmed at the
beginning of treatment who was smear negative in last month of
treatment.
TREATMENT COMPLETED: Patient who completed treatment without
failure but with no record to show that.

37. Smear results in last month of treatment and on at least one
previous occasions were negative.
TREATMENT FAILED:
TB patient whose smear is + at month five or later during
treatment.

38. Died: Patient who dies before or during course of treatment.
Lost to follow up: Patient who did not start treatment or
whose treatment was interrupted for 2 consecutive months or
more.
Not evaluated: Patient for whom no treatment outcome is
assigned.

39. Treatment success: Sum of cured and treatment
completed.
COHORT: Patients in whom TB has been diagnosed and
registered for treatment for a specific period .

40. OUTCOMES FOR RR TB/ XDR TB :
CURED: Treatment completed without evidence of failure
AND 3 or more + cultures taken at least 30 days apart are – after the
intensive phase .

41. TREATMENT COMPLETED: Without evidence of failure but no
record that 3 or more consecutive cultures taken 30 days
apart are – after intensive phase .
TREATMENT FAILED :Treatment terminated or need for permanent
regimen change of at least 2 anti TB drugs

42. DIED: Patient died during treatment
LOST TO FOLLOW UP: A patient whose treatment was interrupted
for 2 consecutive months or more .
NOT EVALUATED : No treatment outcome is assigned.

43. Cohort : a group of patients where RR TB has been
diagnosed & who were started 2nd line MDR TB drug
regimen during a specified time period .

44. EVOLUTION OF TB CONTROL IN INDIA
• 1950-60 - Important TB reasearch at TRC and NTI
• 1962 - National TB Programme
• 1992-Programme review.
• 1997-RNTCP.
• 2006-Stop TB Strategy.
• 2014-End TB Strategy.
• 2020- renamed as NTEP

45. Historical Aspect-
NTP1962
DOTS(Directly Observed Treatment Short Course)
consumption.
RNTCP 1997
NTEP 2020

46. Components of DOTS
• 1.Accountability.
• 2.Good quality sputum microscopy.
• 3.Political commitment.
• 4.Uninterrupted supply of good quality drugs.
• 5.Direct observation therapy

47. NTEP
• Adopted on janurary2020.
• Comprises of 5 levels.
- National level.
-State level.
-District level.
-Sub District level.(Tuberculosis unit level).
- Peripheral Health institutions.

48. Central TB Division
State TB Office
District TB Centre
Tuberculosis Unit
Designated Microscopy Centre
DOT Centre
State TB Officer
DTO, MO-DTC, LT, Driver
MO-TC
STS,STLS
MO, LT
DOT, Provider-MPW, NGO,
PP,Com Vol
State TB Training
and
Demonstration
Centre
• IRL :
Intermediate Ref
Lab
• State Drug Store

49. NTEP
• Goals NTEP ---
• Eliminate TB by 2025 in place of 2030
• Targets NTEP –
• --Decrease incidence by 80%
• --Decrease mortality by 90%

50. • National Level-
-Central TB division (CTB) manages NTEP programme in india.
- supported by NTI( national TB institute), NRL (national
reference laboratories)
• STATE LEVEL –
- comes under NHM of the state.
-resided by state tuberculosis officer(STO), state TB cell (STC)
-supported by STDC (TRAINING , SUPERVISION, MONITORING)
Intermediate refrence labortary (IRL)
IRL lab in himachal -- dharampur

51. • DISTRICT LEVEL -
-Managed by CMO
-Has DTC and resided by full time district TB officer (DTO).and
assisted by other technical and secretarial staff.
• SUB DISTRICT LEVEL(Tuberculosis unit level)-
-Intergrates TB contol Programme with health system.
-Tuberculosis unit (TU) are nodal point for TB control in sub
district with aim of optimum resource utilisation and monitoring
at block levelfo
-Managed by MO(usually BMO),Senior treatment
supervisor,Senior laboratory supervisor

52. - CMO undertake supervisory visits for 7 days in a month
- TU has also 1 microscopy centre.
-
• PERIPHERAL HEALTH INSTITUTIONS(PHI)-
-at least headed by MO
-PHCs, CHCs,FRUs.TB hospitals , Private and NGOs facilities fall
under this level.
-emphasis on case finding and treatment.
- There is 1 TBHV per 1lakh population.

53. Diagnostic test under NTEP
• Sputum smear microscopy –(a) ZN staining
-- (b) LED FM
• Culture medium ---(a) LJ medium
---(b)ALC
• Drug senstivity test
• Molecular diagnostic test –(a) LPA
--(b) NAAT

54. • CHEST X – ray
• Tuberculin skin test (TST)
• TB in HIV – (a) LF-LAM
• Skin test for TB (a) C -TB

55. Peripheral
Laboratories
State level
laboratories
CB NAAT
sites
DRTB
Centres
Laboratory Services

56. NIKSHAY (2012)
TB surveillance using case based, web based system.
NI +KSHAY = eradication of TB.

57. Management
& Details
Patient
Registration
Mobile
Application
SMS
Alerts
Periodic
Reports

59. 99 DOTS
• Low cost mobile phone based technology enabling monitoring
of daily intake of treatment.
• Calls are made on toll free number after taking specified dose
and drug taken is recorded.

60. TB notification
• For proper diagnosis, management and reducing transmission.
• Includes notifying every TB case to CMO via Health Care
Providers.
Ban on TB serology
• Serological tests are highly variable and may reflect remote
infection rather than active disease.
• Poor sensitivity and specificity

61. Direct Benefit Transfer Schemes
• Nikshay Poshan Yojana: Financial Incentive of Rs 500 per
month for each notified TB Patient
• Incentive of complete duration of treatment by linking patients
to Nikshay with AADHAR and PEMS via direct benefit transfer

62. Diagnostic Techniques For
Detecting Tuberculosis

63. 2 Types of Tools in Diagnosis
• Tools for microbiological confirmation of TB
• Supportive tools for clinical diagnosis of TB

64. Tools for Microbiological Conformation of TB
These include:
• Sputum smear microscopy
A) Zeihl-Neelsen staining
B)Fluorescence staining
• Culture:
A)Solid- Lowenstein Jensen medium
B)Automated liquid culture systems –BACTEC MGIT 960, BacT
Alert or Versatrek etc.

65. • Drug Sensitivity Testing
A)Modified proportionate sensitivity testing (PST) for MGIT 960
system
B)Economic variant of PST using LJ medium
• Rapid Molecular Diagnostic Tests
A)Line probe assay (LPA)
B)Nucleic acid amplification test (NAAT) including CBNAAT and
Truenat

66. Supportive Tools for Clinical Diagnosis of TB
• Radiological test like chest X-ray
• Tuberculin Skin Test (TST)
• Interferon Gamma Release Assay (IGRA)
• Histopathologic tests

67. Sputum Microscopy
• Most commonly used test.
• Number one case finding method all over the world.
• Advantage: It is rapid and economical.
• Disadvantage: It has limited sensitivity in children and PLHIV.
• It is of 2 types further:
Zeihl-Neelsen staining Fluoresent microscopy

68. Collection of Sputum Samples
• The patients should submit 2 sputum samples for microscopy
as the chances of finding TB bacilli are greater with two
samples than with one.
• In practice, the patient provides sputum sample as follows:
DAY 1 sample 1: On the spot sample.
DAY 2 sample 2: Morning sample.

69. • But if patient is,
A) coming from a long distance
B) having likelihood of defaulting to give a second sample
Then 2 spot specimens are collected with a gap of one hour.

70. ZN Staining Procedure

71. ACID-FAST-BACILLI

72. Slide Reporting
No. Of Bacilli Bacilli Per Slide Result Reported
NO AFB present per 100
slides
0
1-9 AFB present per 100
slides
Scanty/ Number of AFB
seen
10-99 AFB present per 100
slides
+ (+1)
1-10 AFB present per slide ++ (+2)
>10 AFB present per slide +++ (+3)

73. Some Important Points
• Lab technician should observe both slides.
• Smear examined by one microbiologist should not exceed
20/day as visual fatigue leads to deterioration of reading
quality.
• Sputum smear microscopy is positive when there are at least
10,000 organisms present per ml of sputum.

74. False Results in Sputum Microscopy
1) False Negative results may be due to:
A)Collecting Errors
• Inappropriate sputum container
• Inadequate sample
• Sample stored too long
B)Processing Errors
• Faulty sampling of sputum for smear
• Faulty smear preparation and staining

75. C)Interpreting Sputum Smears
• Inadequate time spent examining smear
• Inadequate attention to smear examination
D)Administrative Errors
• Misidentification of patient
• Incorrect labelling of sample
• Mistakes in documentation

76. 2) False Positive results may be due to:
• Red stain retained by scratches on the slide.
• Accidental transfer of AFBs from a positive slide to a negative
slide.
• Contamination of smear or slide by environmental
mycobacteria.
• Presence of various acid fast particles like food particles,
precipitates, other microorganisms.

77. Fluorescence Microscopy
• It is mainly used in developed countries.
• It is performed with auramine stain.
Now, Why is Fluorescent microscopy preferred over ZN staining?
• Field of view is 5-10 times bigger
• Higher speed of examination as scanning of one length
requires only 1-2 minutes.

79. Culturing Methods
• Culturing for isolation of mycobacterium continues to be very
useful in developing countries.
• It requires only 10-100 bacilli/ml of sputum.
• It is done in:
A) Solid media (LJ Media)
B) Automated liquid culture systems (BACTEC MGIT 960, BacT
Alert, Versatrek)

80. LJ Medium
BACTEC MGIT

81. Advantages of Culturing
• Useful in HIV infected patients with TB who are severely
immuno-compromised.
• Useful in patients presenting with respiratory symptoms and X-
rays suggestive ,but smear negative.
• Even few bacilli can be grown in spite of smear negativity.
• They can identify treatment failures.

82. Reasons for Fall of Culturing
• Specificity is lost due to contamination.
• Can yield false positive results in 1-4% of the cases.
• Even cultures may be negative in spite of X-rays being
suggestive of TB.

83. Emerging Methods of Culturing
• MGIT- Mycobacterium growth incubator tube method.
• BacT Alert is an automated microbial detection method based
on colorimetric detection of CO2 produced by growing
mycobacteria.
• Versatrek monitors bacterial growth by detecting pressure
changes in headspace of blood culture bottle.

84. Rapid Diagnostic Tools
• These include:
LPA NAAT
Both of these work on PCR in which:
a)TB bacilli are concentrated from sputum sample.
b)Genomic material is isolated from the sample and
subsequently amplified.

85. Line Probe Assay (LPA)
• These detect DNA sequences specific for TB complex as well as
mutations conferring drug resistance.
• Procedure:
a) Sputum samples are decontaminated.
b) Subjected to smear microscopy.
c) DNA is extracted from all smear positive samples.
d) Extracted DNA is subjected to PCR.

86. e) PCR amplified products are reverse hybridized on
nitrocellulose strips containing probes specific for detection of
MTB and mutations associated with drug resistance.
Resistances detected are:
A) First Line
•Rifampicin (rpoB)
•Isoniazid (katG,inhA)
A) Second Line
•Fluoroquinolone class resistance (gyrA, gyrB)
•Second line injectable class resistance (rrs, eis)

87. NAAT
• It also works on the principle of PCR.
• Provides accurate and rapid diagnosis of Mycobacterium
tuberculosis and Rifampicin (Rif) resistance.
• TB bacilli are detected in pulmonary as well as extra-pulmonary
sites.
• Under NTEP, its use is recommended for:
a) DR-TB
b) Children
c) PLHIV
d) Extra Pulmonary TB
e) Smear Negative TB

88. Advantages of NAAT
• Large number of samples can be processed at the same time.
• Results are obtained from unprocessed sputum samples in just
90 minutes.
• Drug resistance can be detected along with determining the
changed drug regimen’s effect on the patient.
Currently, CB-NAAT is the most widely employed method of TB
diagnosis in India.

89. Radiography
• Useful for diagnosis of smear negative pulmonary TB and TB in
children.
• Not routinely indicated in smear positive cases.
• These are valuable tools for the diagnosis of pleural and
pericardial effusion in early stages when clinical signs are
minimal.
• Essential in diagnosis of miliary tuberclosis.

92. Paeditric tuberculosis
• TB in children represent between 6-8% of all TB in age group of
under 15 years .
• SOURCE : Usually an adult often a family member with sputum
smear positive tuberculosis.
• FREQUENCY in a population depends upon-
1. Number of infectious cases
2. Closeness of contact with an infectious case
3. Age of child when exposed to TB

93. TUBERCULIN TEST
• Discovered by Von Pirquet in 1907
• POSITIVE REACTION : evidence of
past or present infection by
M. tuberculosis
• Only means of estimating
prevalence of infection in a
population

94. MANTOUX TEST
• 1 TU of PPD
• 0.1ml - intradermally
•
• On flexor surface of left forearm
(midway between elbow and wrist)
• Injection made with tuberculin
syringe (with needle bevel facing
upwards)

95. .
Mantoux test
Result read after 48- 96 hrs;
72 hrs (3rd day) ideal
>10 mm
POSITIVE
6-9mm
DOUBTFUL
<6mm
NEGATIVE
ERYTHEMA
AND
INDURATION
NO INDURATION – TEST
REGARDED AS ZERO

96. .

97. TB Interferon gamma release assays(IGRA)
• Blood tests that measure a
person’s immune response to
bacteria that cause TB .
• Work by detecting cytokine
called interferon gamma
cytokine.

98. .
• ADVANTAGES:
1. Only requires a single patient visit to carry out the TB test.
2. Results can be available within 24 hrs
3. Prior BCG vaccination does not cause false positive result.
• DISADVANTAGE:
1. Blood sample must be processed quickly
2. Test only for latent TB

99. Diagnostic algorithm for pulmonary TB
.

100. .
.
Presumptive TB patient
PLHIV
Smear examination CXR
SMEAR
+VE
SMEAR
+VE
SMEAR
-VE
SMEAR
-VE
CXR -VE
CXR
+VE
CXR
-VE
CXR +VE
CLINICAL
SUSPICION
HIGH
CBNAAT
PMDT criteria, high
MDR settings
Microbiologically confirmed TB

101. .
.
CBNAAT
MTB detected
MTB not detected
/result unavailable
Consider
alternate
diagnosis
and refer
to
specialist
Clinically
diagnosed
TB
Alternate
diagnosis
Rif
sensitive
Rif
indeterminate
Rif resistant
Refer to
mgt of Rif
resistance
Repeat
CBNAAT on
2nd sample
Microbiologically
confirmed TB
Indeterminate on 2nd sample ,
collect fresh sample for liquid
culture

102. Pediatric tuberculosis
• TB in children represent between 6-8% of all TB in age group of under
15 years .
• SOURCE : Usually an adult often a family member with sputum smear
positive tuberculosis.
• FREQUENCY in a population depends upon-
1. Number of infectious cases
2. Closeness of contact with an infectious case
3. Age of child when exposed to TB

103. .
TB diagnosis is based upon:
• Clinical features
• Smear examination of sputum
• Positive family history
• Tuberculin skin testing
• Chest radiography
• Histopathological examination

104. Diagnostic algorithm
for
paediatric pulmonary TB.
.

105. .
.
• Persistent fever >2 weeks , without a known cause and /or
• Unremitting cough for >2 weeks and /or
• Wt loss of 5% in 3 months or no wt gain in past 3 months
CBNAAT/ Smear ,if CBNAAT
not available
MTB detected
MTB not
detected
/sputum not
available
X-ray and TST
Microbiologically
confirmed TB case

106. .
.
X –ray and tuberculin skin
test
CXR highly
suggestive
CXR NS shadows
TST –VE
CXR Normal
TST +VE
CXR normal
TST -VE
Gastric
aspirate/induced
sputum for CBNAAT
+VE -VE
Microbiologically
confirmed TB
No other diagnosis ~clinically
diagnosed TB
Evaluate for EPTB.
Refer to expert
Look for
alternate cause

107. CXR NS shadows
TST –VE
Give course of
antibiotics
Persistent shadow
and symptoms
Gastric
aspirate/induced
sputum for CBNAAT
-VE
+VE
Refer to
expert for
workup of
persistent
pneumonia
Microbiologically
confirmed TB