Tuberculosis

TUBERCULOSIS
By
Sriloy Mohanty
B.N.Y.S,4th year
S-VYASA

Contents…
• Introduction
• Problem statement
• Natural history of TB
• Modes Of Transmission
• Control of TB
• Chemotherapy
• Childhood TB
• BCG vaccination
• Chemoprophylaxis
• NTP
• Stop TB strategy
• TB and HIV
• Epidemiological impact
• Yoga
• Research

INTRODUCTION
 Specific infectious diseases
 Caused by-M. tuberculosis
 Primary effect on lungs-pulmonary tuberculosis
 Also affects intestine,meninges,bones,
joints,lymph nodes,etc.

Cont…
 It affects also animals like cattles
 Known as “Bovine tuberculosis”
 May communicated to man

Problem statement
 Distribution-worldwide
 WHO estimates that about 9.2 million new cases
of TB occurred in 2006
 Of these cases, 4.1 million were new smear
positive cases
 This includes 789,000 tuberculosis with HIV co-infected
cases
 There were 14.4 million prevalent cases
 An estimated 1.7 million people died from TB
which 231,000 were those co-infected with HIV

 31.8 million new and relapse cases and
15.5 million smear positive case were
notified by DOTS Programme between
1995-2006

India
 India is the first rank in incidence
 1/5th of global burden of TB
 1.8 million persons develop TB of which
0.8 million are new smear positive (highly
infectious)
 0.37 million people die every year
 DOTS program was launched in March
1997

TB estimates for India
Population 1151 million
Global rank (by estimated number of cases) 1
Incidence (all cases/1 lakh population/year) 168
Incidence (new smear +ve cases/lakh population/year) 75
Prevalence (smear +ve cases/lakh population) 299
TB mortality/1 lakh population/year 28
% of new TB cases HIV positive 1.2
% of new case multidrug resistance 2.8
Previously treated TB cases multidrug resistance (%) 17

 It is mainly a disease of the poor
 Majority of victims are migrant laborers, slum
dwellers, residents of backward areas and tribal
pockets

History of TB
 TB has affected humans
for millennia
 Historically known by a
variety of names,
including:
 Consumption
 Wasting disease
 White plague
 TB was a death sentence
for many
Vintage image circa 1919
Image credit: National Library of Medicine

History of TB
Scientific Discoveries in 1800s
 Until mid-1800s, many
believed TB was
hereditary
 1865 Jean Antoine-
Villemin proved TB was
contagious
 1882 Robert Koch
discovered M.
tuberculosis, the bacterium
that causes TB
Mycobacterium tuberculosis
Image credit: Janice Haney Carr

History of TB
 Before TB antibiotics,
many patients were sent to
sanatoriums
 Patients followed a
regimen of bed rest, open
air, and sunshine
 TB patients who could not
afford sanatoriums often
died at home
Sanatorium patients resting outside

Breakthrough in the Fight Against
TB
Drugs that could kill TB
bacteria were discovered
in 1940s and 1950s
 Streptomycin (SM) discovered
in 1943
 Isoniazid (INH) and
p-aminosalicylic acid (PAS)
discovered between 1943 and
1952

 M. tuberculosis causes most
TB
 Mycobacteria that cause TB:
 M. tuberculosis
 M. bovis
 M. africanum
 M. microti
 M. canetti
 Mycobacteria that do not
cause TB
 e.g., M. avium complex
M. tuberculosis
TB Transmission
Types of Mycobacteria

Natural history of TB
Agent factor
 M.tuberculosis is a intracellular parasite
 Ingested by phagocytes but resistant to
intracellular killing
 Indian tubercle bacillus is said to be less virulent
then the European bacillus

 Source of infection
 Two source of infection
 Human source-person whose sputum is
positive for tubercle bacilli
 Discharge of bacilli in their sputum
 Bovine source-infection is usually by milk
 Not a problem in India because of the practice of
boiling milk before consuption

Modes Of Transmission
 Mainly by droplate infection and droplate nuclei
generated by sputum positive patient
 Particle should be fresh enough to carry
 Coughing generates all size of droplates
 Notes-not transmitted by fomites

TB Transmission
Dots in air represent droplet nuclei containing
M. tuberculosis

Incubation period
 Ranges from 3-6 week

PATHOGENESIS
Susceptible
Or
Mycobacterium
Tuberculosis
Latent
Infection
Recovery
Reactivation
Active
tuberculosis
Miliary
tuberculosis
Extrapulmonary
Tuberculosis
PULMONARY
TUBERCULOSIS

Contribution of Mycobacterial Cellular
Envelope to Pathogenesis
Resistance to Drying and Other Environmental Factors
- Thick, waxy nature of cellular envelope protects M. tuberculosis
from drying, alkali conditions, and chemical disinfectants
- Hinders entrance of antimicrobial agents
Entry into Host Cells
- Lipoarabinomannan (LAM) binds to mannose
receptors on alveolar macropages leading to
entry into the cell
Interference of Host Immune Response
- Glycolipids and sulfolipids decrease the effects of oxidative
cytotoxic mechanism
- Inhibition of phagosome and lysosome fusion inside macrophage
- Waxy cellular envelope prevents acidification of the bacteria inside
the phagosome

Common Symptoms of TB Disease
 Cough (2-3 weeks or more)
 Coughing up blood
 Chest pains
 Fever
 Night sweats
 Feeling weak and tired
 Losing weight without trying
 Decreased or no appetite
 If you have TB outside the lungs, you may have
other symptoms

Host Factor
 AGE
 Affects all ages
 In India under 5 age group-1%
 At the age of 15years-30%

 SEX
 More prevalent in male then female
 HEREDITY
 It is not a hereditary disease

 NUTRITION
 Malnutrition is believed to predispose to TB
 Diet had no effect on the recovery of patient
 IMMUNITY
 No inherited immunity against TB
 Acquired after natural infection or BCG
vaccination

Social factor
 TB is a disease with both social and
medical aspects
 Social factors includes
 Poor quality of life
 Poor housing
 Population explosion
 Early marriages
 Lack of awareness of causes of disease

TB Infection vs. TB Disease
 There is a difference between TB “infection” and
TB “disease”
 TB infection: TB germs stay in your lungs, but
they do not multiply or make you sick
 You cannot pass TB germs to others
 TB disease: TB germs stay in your lungs or move
to other parts of your body, multiply, and make
you sick
 You can pass the TB germs to other people

LTBI vs. TB Disease
Latent TB Infection (LTBI) TB Disease (in the lungs)
Inactive, contained tubercle bacilli
Active, multiplying tubercle bacilli
in the body
in the body
TST or blood test results usually
positive
TST or blood test results usually
positive
Chest x-ray usually normal Chest x-ray usually abnormal
Sputum smears and cultures
negative
Sputum smears and cultures may
be positive
No symptoms Symptoms such as cough, fever,
weight loss
Not infectious Often infectious before treatment
Not a case of TB A case of TB

Progression to TB Disease
 Risk of developing TB disease is highest the first 2
years after infection
 People with LTBI can be given treatment to prevent
them from developing TB disease
 Detecting TB infection early and providing treatment
helps prevent new cases of TB disease

Some conditions increase probability of LTBI
progressing to TB disease
 Infection with HIV
 Chest x-ray findings suggestive
of previous TB
 Substance abuse
 Recent TB infection
 Prolonged therapy with
corticosteroids and other
immunosuppressive therapy,
such as prednisone and tumor
necrosis factor-alpha [TNF-α]
antagonists
 Organ transplant
 Silicosis
 Diabetes mellitus
 Severe kidney disease
 Certain types of cancer
 Certain intestinal conditions
 Low body weight

People Exposed to TB
Not
TB Infected
Latent TB
Infection (LTBI)
Not
Infectious
Positive TST or
QFT-G test result
Latent TB
Infection
May go on to
develop TB
disease
Not
Infectious
Negative TST or
QFT-G test result
No
TB Infection

TB Classification System
Based on pathogenesis of TB
Class Type Description
0 No TB exposure
Not infected
No history of TB exposure
Negative result to a TST or IGRA
1 TB exposure
No evidence of
infection
History of TB exposure
Negative result to a TST (given at least 8-
10 weeks after exposure) or IGRA
2 TB infection
No TB disease
Positive result to a TST or IGRA
Negative smears and cultures (if done)
No clinical or x-ray evidence of active
TB disease

TB Classification System
Based on pathogenesis of TB
Class Type Description
3 TB,
clinically
active
Positive culture (if done) for M. tuberculosis
Positive result to a TST or IGRA, and clinical,
bacteriological, or x-ray evidence of TB disease
4 Previous
TB disease
(not
clinically
active)
Medical history of TB disease
Abnormal but stable x-ray findings
Positive result to a TST or IGRA
Negative smears and cultures (if done)
No clinical or x-ray evidence of active TB
disease
5 TB
suspected
Signs and symptoms of TB disease, but
evaluation not complete

Sites of TB Disease
Bacilli may reach any part of the body, but common sites
include:
Brain
Lymph node
Pleura
Lung
Spine
Larynx
Bone
Kidney

Sites of TB Disease
Location Frequency
Pulmonary TB Lungs Most TB cases are
pulmonary
Extrapulmonary TB Places other than
lungs such as:
• Larynx
• Lymph nodes
• Pleura
• Brain
• Kidneys
• Bones and joints
Found more often in:
• HIV-infected or
other
immunosuppressed
persons
• Young children
Miliary TB Carried to all parts
of body, through
bloodstream
Rare

Diagnosis and Treatment for Latent & Active TB
Tools for Diagnosing TB Infection
 Mantoux skin test (PPD)
 Chest x-ray
 Sputum cultures

TUBERCULIN TEST
 Discovered by Von Pirquet(1907)
 Three main test are currently in use
 Mantoux intradermal test
 Heaf test
 Tine multiple puncture test

Chest X-Ray
 A chest x-ray is ordered when a
person presents a recent skin test
conversion and is suspected of
having TB.
 If a chest x-ray is normal, further
diagnostic testing may not be
necessary.

Sputum
 A sputum specimen is necessary to
confirm that the TB bacteria is present in
the lung.
 The sputum specimens should:
-come from deep within the lungs;
-be obtained from the first coughed up
sputum of the day, for 3 consecutive days
-may be obtained through special
respiratory therapy procedures.

Control of TB
 Reduction in prevalence and incidence
 WHO defines control as prevalance of natural
infection in the age 0-14yrs is of the order of 1%
 In india it is about 40%
 Control measure consists of
 Curative component-case finding and treatment
 Preventive component-BCG vaccination

 Case finding tools
 Sputum examination
 Sputum smear examination
Who also have problems like
 persistant cough of about 3-4weeks
 Continous fever
 Chest pain
 haemoptysis

Chemotherapy
 Indicated for every case of active TB
 Objectives are
 Elimination of both the fast and slow multiplying
bacilli
 Mainly elimination of bacilli from patients sputum
 Available for free of charge

Anti-tuberculosis drugs
 An anti-tuberculosis drug should follow some
criteria's like
 Free from side effects
 Highly effective
 Easy to administrate
 Reasonably cheap

Classification of drugs
 Currently used drugs are classified in to
 Bactericidal drugs-kills the bacteria
 Bacteriostatic drugs-inhibits the multiplication of the
bacilli and leads to destruction by the immune
mechanism of the host

Bactericidal drugs
 Rifampicin(RMP)
 Powerful Bactericidal drugs
 Permeates all tissue membrane
 Only Bactericidal drugs active against the dormant
bacilli
 Only oral drug
 10-12mg/kg body weight
 May feel nausea,gastritis,purpra

 INH
 Most powerful drug
 Can penitrate the cell membrane
 Active against intracellular and extracellular bacilli
 It can also pass BBB,present in CSF
 4-5gm/kg body weight

 Streptomycin
 Act on rapidly multiplying bacilli
 Less active on slow multiplying bacilli
 No action on persisters
 Non-permeate cell wall
 0.75-1gm in a single injection

 Pyrazinamide
 Active against slow-multiplying intracellular
bacilli
 Drug given orally
 Usual dose 30gm/kg body weight
 Recommended in tuberculous meningitis

Bacteriostatic drugs
 Ethambutol
 Used in combination to prevent the
emergence to the drugs
 Given orally
 Side-effect-retro-bulbar neuritis
 15mg/kg body weight given in 2-3 doses

 Thioacetazone
 Companion drug to INH
 Adult dose-2mg/kg body weight
 Side-effect includes gastrointestinal
disturbances, blurring of vision, haemolytic
anaemia

Two-phase chemotherapy
 Consist of two phase of effective treatment
 Short aggressive or intense phase
 Lasting 1-3months
 Three or more drugs are combined to kill initialy
 Continuation phase
 Aimed to sterilizing the smaller number of
dormant
 Not less then 18 months
 If rifampcin and pyrazinamide applied,then it can
reduced to 6-9 months

Treatment during pregnancy
 Streptomycin can cause permanent deafness in
the baby
 So ethambutol should be used instead of
streptomycin,
 Isoniazid, rifampicin, pyrazinamide and
ethambutol are safe to use
 Second line drugs should not be used because
these are teratogenic
(flouroquinolomes,ethionamide)

Childhood TB
 TB in children present between 10-20% of all TB
 Source is usually adult
 Frequency of childhood TB depends
 Number of infectious case
 Closeness of contact with an infectious case
 Age of the child when exposed to TB

 Childhood TB is mainly due to failure in control
of TB in adult
 Under 5 age group-20%
 The commonest age-1-4years

BCG vaccination
 Calmette and guerin in 1919 discovered bacille
Calmette guerin(BCG)
 Avirulent for man while retaining its capacity to
induce an immune response
 During 1921-1925-given orally
 After 1927-intradermal technique
 1948-it is accepted by TB workers

AIM
 Induce benign artificial primary infection
 By stimulating an acquired resistance

Vaccine
 Widely used live bacterial vaccination
 Derived from an attenuated bovine stain of
tubercle bacilli
 WHO has recommended the “Danish 1331” stain
for production of BCG vaccination

Types of vaccination
 Two types of BCG vaccination
 Liquid vaccination(fresh)
 Freeze-dried vaccination(stable)

 BCG is stable for several weeks in a tropical
climate and for up to 1 year if kept away from
direct light and stored in cool environment
preferably refrigerator at a temperature below 10
deg C
 Normal saline is recommended for diluent for
reconstituting the vaccine

Dosage
 For vaccination the usual strength is 0.1 g in 0.1
ml volume
 For new born (below 4 weeks) 0.5 ml, because
the skin of the new born is thin

Administration
 Inject the vaccine intradermally using a
tuberculin syringe (recommended by WHO)
 If injected subcutaneously an abscess is likely to
develop
 The site of injection should be above the insertion
of deltoid

Phenomena after vaccination
 After 2-3 weeks a papule develops at the site of
vaccination
 It increases slowly in the diameter about 4-8 mm
in 5 weeks
 Healing occurs within 6-12weeks
 Round scar is formed

 complication
 Prolonged severe ulceration
 Supractive lymphadenitis
 Osteomyelitis
 Death

Revaccination
Even 80 years after the development of the vaccine, it is
not known whether booster doses are indicated or
advisable
Contraindication
Generalized eczema, infective dermatosis,
hypogammaglobulinaemia, to those with a history of
deficient immunity
Patient under immunosuppresent treatment and in
pregnancy

 Direct BCG vaccination
 Vaccination without a prior tuberculin test has been
adopted as a National policy in many developing
countries including India
 No adverse effects have been reported even if
BCG is given to tuberculin – positive reactors

Impact
 BCG is less effective than the chemotherapy
BCG vaccination and HIV infection
 A single dose of BCG vaccine should be given to
all healthy infants as soon as possible after birth
unless the child presented with symptomatic HIV
infection

Combined vaccination
 BCG may be given at the same time as OPV.
DPT vaccine may also be given at the same time
as BCG, but in different arm without reducing the
immune responses or increasing the rate of
complication

Chemoprophylaxis
 The case against INH chemoprophylaxis rests on
3 points:
 It is a costly exercise
 It is not strikingly effective
 It can induce hepatitis
 According to WHO mass treatment is not feasible
 In this context, BCG gets priority over
chemoprophylaxis

 Drugs resistance
 All drugs used in TB produce resistance
 Resistance may be of two types
 Pretreatment resistance
 Acquired resistance

National Tuberculosis
Programme (NTP)
 NTP has been under operation since 1962
 The long term goal of NTP is “to reduce the
problem of tuberculosis in the community
sufficiently quickly to the level where it ceases to
be a public health problem”.

Revised NTP
 The Govt. of India, WHO and World Bank
together reviewed the NTP in the year 1992
 The main pillars of the revised strategy are;
 Achievement of not less than 85% cure rate amongst
infectious cases of TB, through short course
chemotherapy involving peripheral health
functionary

 Detecting 70% of the estimated cases – through quality
sputum microscopy
 Involvement of NGOs
 Direct Observed Therapy Short – term (DOTS) – a
community based TB treatment and care strategy

Stop TB strategy
 2006- WHO launched
 Core of the strategy – DOTS
 Indicators used to measure implementation and
impact of TB control:
 Case detection
 Treatment success
 Incidence
 Prevalence
 Deaths

Stop TB partnership target
 By 2005
 70% of people with sputum smear positive TB will
be diagnosed
 By 2015
 Global burden of TB will be reduced by 50% relative
to 1990 levels
 By 2050
 Global incidence of TB will be less then or equal to 1
case/million population/year

TB and HIV
 HIV virus damages the bodies natural defense
 Accelerates the speed at which TB progresses
from a harmful infection to life – threatening
condition

Epidemiological impact
 Reactivation of latent infection
 People who are infected with both TB and HIV are
25-30 times more likely to develop TB than the
people infected with only TB
 Recurring infection
 People having HIV who have been cured of TB may
be at more risk of developing TB again
 In the community
 Educate people that TB is curable and the people are
no longer infectious after the first few weeks of
treatment

Management and prevention
through IAYT

IAYT approach
ANNAMAYA
PRÁNAMAYA
MANÔMAYA
VIJÒÁNAMAYA
ÁNANDAMAYA

 There are 5 layers of existence
1 Annamaya kosha
2 Pranamaya kosha
3 Manomaya kosha
4 Vijanamaya kosha
5 Anadamaya kosha

Aims and objectives
 Improves immune system
 Reduce the infection
 Reduce the symptom scores
 Giving them a healthy life
 Reduce the resistance to the medicine

1 Annamaya kosha
 Diet
 Kriya
 Asana
 Cyclic meditation

DIET
•Mastery over mind
•Better mastery over appetite & satisfaction
APPETITE SATIETY

 Tuberculosis is said to be a diseases of
calcium deficiency
 Exclusive fresh fruit diet with milk
 Banana should be avoided
 Give more citrus fruits
 Custard apple – effective food

KRIYAS
 Laghusankha prakshalana
 Vamana dhauti
 Jala neti

ASANA
Mandukasana
Ardha matsyendrasna
sarvangasana
viparitakarani

Cyclic Meditation
Aim -Stimulation and deep rest
Reduces stress
improve immunity

2.Pranamaya kosha
 Disturbed prana balance in disease
 Nadi suddhi prnayama
 Bharamari
 Surya anuloma viloma pranayama

 Advance technique
 PET

Manomaya kosha
 Darana
 Dhayna
 Emotional culture ( bhajan , satsang )

 MSRT
 MIRT
 MEMT

4. Vijanamaya kosha
 Notional correction
 Happiness analysis
 Study
 counselling
 Adnance technique
 VISAK – vijana sadhana kausala

5 Anadamaya kosha
 Karma yoga (action with bliss)
 Yogic games
 ANAMS- ananda amruta sinchana

complementary role for yoga in the
management of pulmonary tuberculosis
 yoga group showed a significant reduction
in symptom scores(88.1%), and an increase
in weight (10.9%), FVC (64.7%) and
FEV(83.6%)
 breath awareness group also showed a
significant (paired t-test) reduction in
symptom scores (16.3%), and an increase
in weight (2.1%) and FEV(63.8%)

 Ten of 13 in the yoga group had negative
sputum culture after 60 days compared
with four of 19 in the breath awareness
group
 Improvement in the radiographic picture
occurred in 16/25 in the yoga group
compared to 3/22 in the breath awareness
group on day 60

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