3. What is Mycobacteria?
3
• Facultative intracellular pathogens usually infecting
mononuclear phagocytes (e.g. macrophages).
• Slow-growing
• Hydrophobic with a high lipid content in the cell wall.
Because the cells are hydrophobic and tend to clump
together, they are impermeable to the usual stains, e.g.
Gram's stain
• Known as “Acid-fast bacilli" because of their lipid-rich cell walls,
which are relatively impermeable to various basic dyes unless
the dyes are combined with phenol.
4. Tuberculosis highly Communicable Disease.
• Someone in the world is newly infected with TB
bacilli every second.
• Overall, one-third of the world's population is
currently infected with the TB bacillus.
• DOTS strategy = mid 1990-2005
• Stop TB Strategy = 2006-2015
• Ending TB epidemics by 2030 – SDGs
• WHO target for 2035 – 95% reduction in death &
90% decline in TB incidence
• 1/3rd female infertility in India – due to TB
5. H o w t u b e r c u l o s i s S p r e a d s
• Tuberculosis (TB) is a contagious disease. Like the common
cold, it spreads through the air.
• Only people who are sick with TB in their lungs are
infectious.
• When infectious people cough, sneeze, talk or spit, they
propel TB germs, known as bacilli, into the air.
• A person needs only to inhale a small number of these to
be infected.
7. Generation of Droplet Nuclei
• One cough produces
500 droplets.
• The average TB patient
generates 75,000 droplets
per day before therapy.
• This falls to 25 infectious
droplets per day within
two weeks of effective
therapy.
9. Pathology and Pathogenesis of
Tuberculosis
• Source of Infection – Open case of Pulmonary Tuberculosis.
• Every open case has potential to infect 10 – 15 healthy persons
in a year.
• (1% annual risk of infection – correspond to 50 new cases of
smear+ve pulmonary TB/year/100,000 general population.
• Coughing , Sneezing, or Talking - Each act can spill 3000 infective
nuclei in the air.
• Infective particles are engulfed by Alveolar Macrophages.
10. Mechanisms of
Infection
• Mycobacterium do not produce toxins.
• Allergy and Immunity plays the major role.
• Cell Mediated Immunity plays a crucial role.
• Humoral Immunity – not Important.
• CD4 Cell plays role in Immune Mechanisms.
12. Primary
Tuberculosis
• Events of Primary complex
1. Bacilli are engulfed by Alveolar Macrophages
2. Multiply and give rise to Sub pleural focus of
Tuberculosis, Pneumonia, involve lower lobes and
lower part of upper lobes Called as Ghon’s focus. The
Hilar Lymph nodes are also involved.
13. Primary
complex• This is known as the primary complex or primary infection.
The patient will heal and a scar will appear in the infected
loci.
• There will also be a few viable bacilli/spores may remain in
these areas (particularly in the lung).
• The bacteria at this time goes into a dormant state, as long
as the person's immune system remains active and functions
normally this person isn't bothered by the dormant bacillus.
14. Contd..
• Ghon’s focus with Enlarged lymph nodes appear
after 3- 8 weeks after infection.
• Heals in 2 – 6 months and calcified.
• Some bacteria remain alive and produce latent
infections.
• Infection activated in Immunosuppressed conditions
Eg. HIV infections and AIDS
• Can produce Meningitis, Miliary tuberculosis, other
disseminated Tuberculosis.
15. Reactivation of
Tuberculosis
• When a person's immune
system is depressed, a
secondary reactivation occurs.
• 85-90% of the cases seen
which are of secondary
reactivation type occurs in the
lungs.
Dr.T.V.Rao MD 66
16. Post Primary
Tuberculosis
• Mainly occurs due to Reactivation of Latent infection.
• May also due to Exogenous reinfection.
• Differs from Primary Infection.
• Leads to – Cavitations' of Lungs, Enlargement of Lymph
nodes, Expectoration of Bacteria laden sputum
Dissemination into Lungs and other extra
pulmonary areas.
22. Extra pulmonary
Tuberculosis
• Bacteria on circulation leads to bacteremia
leads to involvement of Genito urinary
system, Meninges, Gastro Intestinal system,
skin, Lymph nodes, Bone marrow, Pott's
spine
24. Revised Definition
(presumptive case/ “TB suspect”
Case
Definition
Bacteriolo
gically
confirmed
TB Case
Clinicall
y
diagnos
ed TB
Case
Classification
based on
anatomical
site disease
PTB
EPTB
Classification based
on previous TB
treatment
New patient
Previously
treated patients
Relapse
Treatment after
failure
Treatment after
loss to follow up
Other previously
treated
Unknown prev.
TB treatment
history
30. MTB : Cultural
characters
• Grow slowly. Generation time 14-15 hrs
• Colonies appear after 2 weeks or at 6-8
weeks
31. Laboratory Diagnosis
1 Sputum smears stained by Z-N stain
Advantage: - cheap – rapid
- Easy to perform
- High predictive value > 90%
-Specificity of 98%
Disadvantages:
- sputum ( need to contain atleast10000 AFB/ml.)
-Young children, elderly & HIV infected persons may
not produce cavities & sputum containingAFB.
32. 2- Detecting AFB by fluorochrome stain using
fluorescence microscopy
The smear may be stained by auramine-O dye. In this
method the TB bacilli are stained yellow against dark
background & easily visualized using florescent microscope.
Advantages:
More sensitive & field view is 5-10 times bigger
Rapid
Disadvantages:
- Hazards of dye toxicity
- more expensive
33. 3- Cultures on L J media
Lowenstein –Jensen medium is an egg based media
with addition of salts, 5 % glycerol, Malachite
green & penicillin.
Advantages:
Specificity about 99 %
More sensitive (need lower no. of bacilli 10-100 /ml)
Can differentiate between TB complex & NTM using biochemical
reactions
Sensitivity tests for antituberculous drugs ( St, INH, Rif., E)
Disadvantages: Slowly growing ( up to 4 weeks )
34. Recent Methods for Diagnosis
BACTEC 460 ( rapid radiometric culture system )
Specimens are cultured in a liquid medium (7H12 medium)
containing C – labeled palmitic acid.
Growing mycobacteria utilize the acid, releasing radioactive CO2
which is measured as growth index (GI) in the BACTEC instrument.
The daily increase in GI output is directly proportional to the rate &
amount of growth in the medium.
MGIT 960 – (o2 utilization based)
MB/BaCT System – nonradiometric (co2)
35. Polymerase Chain Reaction (PCR & Gene Probe)
Nucleic acid probes & nucleic acid amplification tests in
which polymerase enzymes are used to amplify ( make
many copies of specific DNA or RNA sequences
extracted from mycobacterial cells.
Advantages:
Rapid procedure (within a day)
High sensitivity (10-1000 bacilli/ml sputum)
TMA & NAA (within few hours)
CBNAAT (current gold standard for TB diagnosis)
GeneXpert (MTB/RIF)…90 minutes
36. Immuno-prophylaxis
• Intradermal injection of live attenuated vaccine
Bacille Calmette-Guerin (BCG).
• The strain causes self limited lesion and induces
hypersensitivity & immunity.
• Converts tuberculin negative person to positive reactor.
Immunity lasts for 10-15 years. (60- 80%).
• Protects against TB, the disease runs milder course in
protected, prevents skeletal, meningeal & miliary forms.
• Also found useful in leprosy, leukaemias and other
malignancies by non-specific stimulation of RE system.
93
37. Treatmen
t
Drugs used :
1- First line drugs :
- Isoniazid - Rifampicin - Pyrazinamide
- Ethambutol - Streptomycin
2- Second line drugs (more toxic and less effective):
- Kanamycin - capreomycin - Amikacin
- ethionamide -fluoroquinolone - Cycloserine
Newer drugs - Bedaquiline
Delamanid
38. Revised national tuberculosis control programme
(RNTCP)
Launched in 1993 based on WHO DOTS Strategy
◦ Entire country covered in March’06 through an
unprecedented rapid expansion of DOTS
Implemented as 100% centrally sponsored program
◦ Govt. of India is committed to continue the support till
TB ceases to be a public health problem in the country
39. Objectives
Achievement of at least 85% cure rate of infectious
cases; through DOTS involving peripheral health
functionaries.
Augmentation of case finding activities through
quality sputum microscopy to detect at least 70%
of estimated cases.
40. Directly Observed Treatment Short
Course, comprises five components
1. Sustained political and financial commitment. TB can be cured & the
epidemic reversed if adequate resources and administrative support for
control are provided
2. Diagnosis by quality ensured sputum-smear microscopy.
3. Standardized short-course anti-TB treatment (SCC) given under direct
and supportive observation (DOT).Helps to ensure the right drugs are taken
at the right time for the full duration of treatment.
4. A regular, uninterrupted supply of high quality anti-TB drugs.
Ensures that a credible national TB programme does not have to turn
anyone away.
5. Standardized recording and reporting. Helps to keep track of each
individual patient and to monitor overall programme performance
41.
42. NSP (2017-2025)
OBJECTIVES:
Find all drug sensitive and drug resistant TB
cases with an emphasis on reaching TB patients
seeking care from private providers, and
undiagnosed TB in high risk population
Initiate and sustain all patients on anti-TB
treatment wherever they seek care
Prevent emergence of TB in susceptible
populations
Build & strengthen enabling policies, empowered
institutions, additional human resources, provide
43. NSP
Aim:
To achieve elimination of TB by 2025.
80% reduction in TB incidence (211/lakh to 43/lakh)
90% reduction in TB mortality (32/lakh to 3/lakh)
0% patient having catastrophic expenditure due to
TB.
47. Indication for TB in steroid
TB meningitis (2mg/kg/day prednisolone or 0.4
mg/kg/day dexa for 4 weeks and taper over next 4
weeks)
Pericardial TB
Miliary TB
Tuberculoma with increased ICT
Massive & bilateral TB pleural effusion with
respiratory compromise
48. Daily dose regimen (drug sensitive
TB)
TYPE OF TB CASE REGIMEN (IP) REGIMEN(CP)
New (2)HRZE (4)HRE
Previously treated (2)HRZES +(1)HRZE (5)HRE
Weight
category
No. of tablets Inj.
StreptomycinIP (HRZE) CP(HRE)
75/150/400/275 75/150/275
25-39 kg 2 2 0.5
40-54 kg 3 3 0.75
55-69 kg 4 4 1
≥70 kg 5 5 1
49. Second line drugs (for drug resistant TB)
Group Drugs
A. Fluoroquinolones Levofloxaci (Lfx)
Moxifloxacin (Mfx)
Gatifloxacin (Gfx)
B. Second line injectable
agents (SLI)
Amikacin (Am)
Capreomycin (Cm)
Kanamycin (Km)
C. Other core second line
agents
Ethionamide/Prothionamide (Eto/Pto)
Cycloserine/Terizidone (Cs/Trd)
Linezolid (Lzd)
Clofazimine (Cfx)
D. Add-on agents(not part
of core MDR-TB regimen)
D1. Pyrazinamide (Z)
Ethambutol (E)
High dose Isoniazid (H)
D2. Bedaquiline (Bdq)
Delamanid (Dlm)
D3. PAS
Cilastin/Mpm
Amx-Clv
Thiocetazone (T)
50. RR/MDR-TB regimen –
atleast 5 effective TB medicine (IP)
Z +4 core 2nd line drug ( one from group A, one from
group B, atleast two from group C)
(if for any reason above regimen can not composed,
then an agent from group D2 & other from group D3
can be taken)
51. Standard regimen for initiating Tr. at District DR-TBC
based on CBNAAT/FL-LPA
Regimen (H mono/poly DR-TB)
R
susceptible
H resistant
(3-6) Lfx
Km R E Z
(6) Lfx R E
Z
REZ + augment with 1 GpA
+ 1 GpB drug
Shorter MDR-TB regimen
R resistant
+ H
sensitive
/unknown or
MDR-TB
(4-6) Mfx
Km Eto Cfz
Z H E
(5) Mfx Cfz
Z E
As per WHO
reccomendation
Regimen for MDR/RR-TB
R resistant
+ H
sensitive/un
known or
MDR-TB
(6-9) Lfx
Km Eto Cs
Z E
(18) Lfx Eto
Cs E
1 GpA + 1 GpB +2 GpC + Z
+ add on 1GpD1
52. XDR TB case
An MDR TB case whose recovered M. tuberculosis isolate is
resistant to at least isoniazid, rifampicin, a fluoroquinolone
(ofloxacin, levofloxacin, or moxifloxacin) and a second-line
injectable antiTB drug (kanamycin, amikacin, or capreomycin)
at a RNTCP-certified Culture & DST Laboratory.
o Liquid Culture & DST
o Solid Culture & DST
53. DST guided regimen for XDR-TB initiating treatment at
NDR-TBC based on SL-LPA
Regimen for XDR-TB (without new drug)
XDR-TB (resistance to
both FQ & SLI)
(6-12) Mfx Cm Eto
Cs Z Lzd Cfz E
(18) Mfx Eto Cs Lzd
Cfz E
Regimen for XDR-TB (with newer drug)
XDR-TB (resistance to
both FQ & SLI)
(6-12) Cm Eto Cs Z
Lzd Cfz E + (6) Bdq
(18) Eto Cs Lzd Cfz
E
54. TB in Pregnancy & Lactating Women
Duration of Pregnancy
<20 weeks
Advised MTP
MTP done
Start/
Continue
shorter
MDR-TB
regimen
Patient unwilling for
MTP
Start/Continue modified
conventional regimen
<12 weeks: omit Km &
Eto; add PAS
>12 weeks: omit Km only;
add PAS
Replace PAS with Km
after delivery & continue
till end of IP
>20 weeks
Start/Continue
modified conventional
MDR-TB regimen
Omit Km; add PAS till
delivery
Replace PAS with Km
after delivery and
continue till end of IP
55. Tuberculosis and HIV
10% activation of dormant TB infection over the life
span of an infected person increased to 10%
activation in one year if HIV infection is
superimposed.
IRIS – temporary exacerbation of symptoms & sign of
radiographic manifestation of TB after beginning of TB
treatment.
Isoniazid preventive therapy for PLHIV –
All children living with HIV - 6 month of IPT (10mg/kg/day)
Start antiTB
drug first
When TB
treatment
is
tolerated
(between
2 weeks-2
months)
Start
ART/
HAART
56. .
Tuberculosi
s and
Diabetes
•Diabetes accounts for 20% of all TB and
10% for smear positive TB
•Risk is 2-3 times higher than people
without diabetes
•Activities to improve the diagnosis &
management of diabetes among TB
patients
•Activities to improve diagnosis and
management of TB among diabetes
•Joint monitoring and evaluation
Tuberculosis
and Tobacco
38% of TB death associated with use of
tobacco
prevalence = 3 times higher
Mortality = 3-4 times higher
5’R’ – Relevance, Risk, Reward, Roadblock,
Repeat
57. WHO Global TB Strategies
1994 – DOTS STRATEGY
• Government commitment
• Case detection through passive case finding
• Standardized SCC
• Establishment of system for regular drug supply
• Establishment & maintenance of monitoring system
2006 – STOP TB STRATEGY
• 1. Pursue high-quality DOTS expansion andenhancement.
• 2. Address TB-HIV, MDR-TB, and other challenges
• 3. Contribute to health systemstrengthening
• 4.Engage all care providers
• 5. Empower people with TB and communities
• Enable and promote research
2015 – END TB STRATEGY
• Integrated, patient-centered care and prevention
• Bold policies and supportive systems
• Intensified research and innovation
58. Vision A world free of TB-zero deaths; disease &
suffering due to TB
Goal End the global TB epidemic
Indicators Milestones Targets
2020 2025 SDG 2030 END TB
2035
Reduction in no. of TB death
compared with 2015 (%)
35% 75% 90% 95%
Reduction in TB incidence
rate compared with 2015 (%)
20% 50% 80% 90%
TB affected families facing
catastrophic costs due to TB (%)
zero zero zero Zero
Principles •Government stewardship, accountability,
monitoring
•Strong coalition with society, communities
•Protection & promotion of human right, ethics,
equity
•Adaptation of strategies & targets a/c to global
collaboration
59. Global Plan’s targets – 90-90-90
targets
Reach at least 90%
of all people with TB
As a part of this approach,
reach at least 90% of the
key population i.e.
vulnerable, at risk
Achieve at least 90%
treatment success
60.
61. Case-based web-based reporting system
(NIKSHAY)
The database of RNTCP was conventionally on
Epiinfo based software for reporting with electronic
data transmission from district level upwards.
CTD in collaboration with National Informatics Centre
(NIC) developed a case based web-based online
(Cloud) application - ‘Nikshay’, launched in May 2012,
which has been now scaled up nationally.
62. NIKSHAY
It has following components –
• Master management
• User details
•TB patient registration & detail of
diagnosis, DOT provider, HIV status,
follow up, contact tracing, outcome
•Details of Solid and liquid culture &
Drug Sensitivity Testing (DST), Luciferin
Probe Assay (LPA), CBNAAT
• DRTB patient registration with details
• Referral & transfer of
patients
• Private health facility
registration and notification
• Automated periodic report
(case finding, sputum
conversion and outcome).
63. Programmatic management of drug resistant TB
(PMDT) services
The term “Programmatic Management of Drug
Resistant TB” (PMDT) (erstwhile DOTS Plus), refers to
programme based MDR TB diagnosis, management and
treatment.
RNTCP introduced the PMDT services since 2007 to address
the MDR TB issue in the country.
64. References..
Park’s Text book of Preventive & Social Medicine 25th ed.
Community medicine with Recent advances by
A.H.Suryakantha
Textbook of Community Medicine by Sunder Lal, Adarsh,
Pankaj.
www.tbcindia.gov.in