Tuberculosis research study. Going in medical detail

1. Tuberculosis
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Introduction

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• A major global public health problem,
• Until the coronavirus (COVID-19) pandemic, TB was the
leading cause of death from a single infectious agent,
ranking above HIV/AIDS.
• A curable and preventable common communicable disease
• About a quarter of the world’s population has been infected
with M. Tuberculosis.

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History of tuberculosis
• 1882 - Robert Koch discovered M.tuberculosis on 24th
March.
• 1921 - Calmette & Guerin discovered BCG
• 1944 – Selman S Waksman discovered streptomycin
• 1946 – INH and PAS were introduced
• 1960- National Tuberculosis Institute established at Banglore
• 1962 – GOI launched National Tuberculosis Control Programme
• 1972 – Short course chemotherapy introduced. Wallae Fox etal
showed addition of R & Z to INH can reduce duration of regimen
from 1.5yr to 6 months
• 1993 – WHO declared TB a “Global Emergency”
- RNTCP introduced

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Epidemiology
 WHO has established three categories (first category for TB, second
for HIV-associated TB and third for MDR/rifampicin-resistant TB) of
global High Burden Countries for 2021–2025, unfortunately India is
among all these three lists.
 India
 reports more than 5000 TB cases daily (new & relapse);
 total 19,33,381 TB patients were notified during 2021
 TB is accountable for more than 200 deaths daily
 total number of reported deaths among DS-TB patients notified in
2020 was 76002 (4.3% of the total notifications of 2020).

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 India has huge burden of drug resistant TB also
 estimated number of 4 MDR cases per 100,000 population
and
 1 XDR-TB cases per 100,000 population have been put on
treatment yearly as per the global TB report 2021.

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Epidemiological determinants
• The epidemiology of TB in a community is the resultant of
the interplay between
• environmental conditions or social factors
• host factors
• agent factors

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Host Factors
• Age – prevalence increases with age
• 0-15yr pravelence = 5%
• 15-24 yr pravalence = 20.9%
• Sex – more common in males
• Nutrition
• Incubation period – variable. Infection to tuberculin
positivity in 3-6 wks
• Period of communicability – as long as bacilli excreted in
sputum. Effective ATT reduces infectivityby 90% within 48hrs

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Social Factors
• Poor quality of life
• Poor housing / overcrowding
• Malnutrition
• Lack of education
• Lack of awareness
• Social stigma

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Agent Factors
• Organism – mycobacterium tuberculosis
• Rod-shaped, non spore forming, thin, aerobic bacterium
• Mycobacterial cell wall contains
• Lipids (e.g. Mycolic acids) which leads to very low
permeability of the cell wall, thus reducing
effectiveness of most antibiotics.
• Lipoarabinomannan is involved in the pathogen-host
interaction and facilitates the survival of m.
Tuberculosis within macrophages.

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Transmission
• M. tuberculosis is most commonly transmitted from a person
with infectious pulmonary TB by droplet nuclei, which are
aerosolized by coughing, sneezing, or speaking.
• The tiny droplets dry rapidly; the smallest (<5- 10 μm in
diameter) may remain suspended in the air for several hours
and may reach the terminal air passages when inhaled.
• Likelihood of transmission depends on:-
• Probability of contact with infectious person
• Duration and intimacy of contact
• Degree of infectiousness of case
• Shared environment (crowding in poorly ventilated rooms being
most important factor)

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Risk factors for Active TB in persons who
have been infected with tubercle bacilli

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Classification of tubercular disease
• On the basis of events following first exposure
oPrimary TB – disease in person with no previous exposure
oProgressive Prmary TB – Primary disease progress to give rise to
larger lesions
oPost-primary TB – disease as a result of endogenous reactivation
or exogenous reinfection
• Based on location
oPulmonary
oExtra-pulmonary
oDisseminated

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Pulmonary Tuberculosis
A. Clinical Features
B. Systemic Examination
C. Respiratory System Examination

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A. Clinical Features of PTB
CONSTITUTIONAL SYMPTOMS
• Anorexia/ weight loss
• Low grade fever/Evening rise
of temp
• Night sweats
• Fatigue/ tiredness
• Weight loss: >10% in last 6
months / >5% in last 1 month:
Unintentional
PULMONARY SYMPTOMS
• Cough lasting > 2 weeks and
not responding to usual
antibiotics
• Mucoid/ Purulent/
Mucopurulent sputum with /
without haemoptysis
• Dyspnoea
• Chest pain

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B. Systemic Examination
• General Physical Examination
• Signs of PEM/ Low BMI- Cachexia
• Pallor
• Tachycardia, Tachypnoea
• Digital Clubbing
• Lymphadenopathy (Cervical, axillary etc)

19. C. Respiratory System Examination
• Inspection :
• Trachea
• Shape of chest can be
symmetrical/asymmetrical
(retraction/ fibrosis /collapse,
etc)
• Spine
• Movements
• Palpation
• Trachea - Mediastinum
• Asymmetrical Chest
Movements
• Tactile vocal fremitus-
increased in consolidation
/cavity
• Crowding of ribs
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• Auscultation
• Normal vesicular breath sounds
• Bronchial breathing sound
• High-pitched [tubular] - TB pneumonia
• low-pitched [cavernous] - an underlying cavity in the lung or an open
pneumothorax
• high-pitched [amphoric] with “echo-like” quality - large cavity with smooth
walls or a pneumothorax communicating with a bronchus
• Vocal resonance–
• Increased- consolidation/cavity
• Diminished - obstructed bronchus
• Absent - pleural effusion or thickening
C. Respiratory System Examination

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Extra-pulmonary TB
1. Lymph node
2. Pleural
3. Skeletal
4. Gastro-intestinal
5. CNS
6. Upper Airway
7. Cutaneous
8. Ocular
9. Urogenital
10.Pericardial

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Extrapulmonary TB = 15–20% of all TB cases
1. Lymph node TB (35%)
2. Pleural TB (30%)
3. Skeletal TB (10%)
4. Genitourinary TB (4%)
5. Pericardial TB (1-2%)
6. Gastrointestinal TB(3%)
7. Tuberculous Meningitis (1%)rways
8. TB of upper airways
9. Less common forms
Extra pulmonary TB :
Any Microbiologically confirmed or clinically diagnosed case of TB
involving organ other then lung

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Methods of Diagnosis of
Tuberculosis
**All efforts should be undertaken for microbiologically confirming
the diagnosis in presumptive TB patients.
1. DIRECT METHODS - Detects mycobacteria and its products
2. INDIRECT METHODS :
1. Cytology and HPE
2. Biochemistry – ADA
3. Antigen and Antibody Detection- TST , IGRA
3. RADIO-DIAGNOSIS - CXR, CT

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TB Diagnostic Algorithm
All notified TB patients
Presumptive TB
R resistance
detected
R resistance not
detected
H resistance not
detected
H resistance
detected
• PLHIV
• EPTB
• Smear -ve/NA with
X-ray suggestive of
TB including
paediatric patients
• Vulnerable
populations
• Contacts of DR TB
patient
Non responder to
treatment
FL – LPA,
SL – LPA and
LC DST for Mfx,
Lzd, Cfz, Z, Bdq,
Dlm
NAAT
FL LPA
SL LPA+LC DST for
Mfx, Z, Lzd, Cfz
• DS TB
• H mono/poly

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TB Diagnostic Algorithm

26. Treatment

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Goals of Tuberculosis
Treatment
• To decrease case fatality and morbidity by
ensuring relapse free cure.
• To minimize and prevent development of
drug resistance.
• To render patient non-infectious , break
the chain of transmission and to decrease
the pool of infection.

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Treatment of drug sensitive tuberculosis
• In recent years, the country has made far-reaching progress in
the management of TB. For example, an injection free
treatment regimen for Drug-sensitive TB (DS-TB) was
implemented across the country.
• Up till 2016, ATT was administered intermittently thrice daily
but later considering high relapse rate and poor compliance,
daily regimen with drugs in Fixed Dose Combination (FDC)
was implemented.

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Fixed drug combination (FDC) was incorporated:
• to simplify treatment,
• increase patient acceptance,
• lower emergence of drug resistance.
• Failure to follow uniform standard treatment along with poor follow
up has led to emergence of drug resistance.
Long term follow up for all TB patients is a visionary step to pick relapse
early and prevent further transmission.

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Evolution of drugs available for
treatment

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• The four first line drugs are:
1. Isoniazid (H)
2. Rifampicin (R)
3. Pyrazinamide (Z)
4. Ethambutol (E)
• DS TB treatment comprises of two phases:
• HRZE are given for 2 months in IP
• HRE in CP for 4 months

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DRTB regimens
• H- mono/poly resistant
• 6 or 9) Lfx R E Z
• Shorter all oral
• IP - (4-6) Bdq (6m), Lfx, Cfz, Z, E, Hh
, Eto
• CP - (5) Lfx, Cfz, Z, E
• All Oral Longer regimen
• (18-20) Bdq (6m or longer) Lfx Lzd# Cfz Cs
# Reduce Lzd to 300 mg/day after 6 to 8 months

34. Pediatric TB: Introduction
• TB in children accounts for ~10% of global TB cases.
• Often represents recent transmission from adults.
• High risk of progression from infection to disease.
• Challenges in diagnosis and treatment due to age-specific
factors.

35. Pediatric TB: Clinical Features
• • Symptoms: Fever, weight loss, poor growth, lethargy.
• • Often lacks classic pulmonary TB features like productive
cough.
• • Higher likelihood of extrapulmonary disease (e.g., TB
meningitis, miliary TB).
• • Diagnosis often based on clinical suspicion and history.

36. Pediatric TB: Diagnosis
• Diagnosis:
- Clinical criteria
- Chest X-ray (hilar lymphadenopathy common)
- GeneXpert on gastric aspirates or induced sputum

37. Pediatric vs. Adult TB: Clinical &
Diagnostic Differences
• Adults: More pulmonary TB, cavitary lesions, productive
cough.
• Children: More extrapulmonary TB, less specific symptoms.
• Adults: Diagnosis via sputum microscopy, GeneXpert.
• Children: Diagnosis harder; often clinical + imaging.

38. Pediatric vs. Adult TB: Management
Differences
• • Pediatric regimens are weight-adjusted and require close
monitoring.
• Children need nutritional support and monitoring for
growth.
• Adults tolerate standard fixed-dose combinations better.
Prevention: BCG vaccination and contact screening critical in
children.
Should be started on Tb Preventive Therapy if Contact is
positive and age less than 5 years

39. Diagnostic Modalities: Pediatric vs.
Adult TB
Feature Pediatric TB Adult TB
Sputum availability Difficult to obtain Easily available
GeneXpert Used on gastric
aspirate or induced
sputum
Routine use on sputum
Chest X-ray Hilar
lymphadenopathy,
non-specific
Cavitary lesions
common
Tuberculin Skin Test Useful adjunct, variable
sensitivity
Often used but less
reliable in BCG-
vaccinated
Clinical diagnosis Frequently relied upon Less common,
microbiological
confirmation preferred

40. Summary of Key Differences
Aspect Pediatric TB Adult TB
Transmission From close contact,
often adults
Environment or latent
reactivation
Type Primary TB common Reactivation TB
common
Common forms Extrapulmonary (e.g.,
TBM, miliary)
Pulmonary
predominant
Diagnosis Often clinical, imaging Microbiological
confirmation
Treatment Weight-based, careful
monitoring
Standard fixed-dose
regimen

41. Thanks