Lecture 35 & 36 [MICRO & PATH]:

Tuberculosis: Immunopathogenesis, pathology and

laboratory diagnosis

Dr MM Khan
Unit of Pathology
Lecture 35 & 36 [MICRO & PATH]: Tuberculosis: Immunopathogenesis, pathology and
laboratory diagnosis
Objectives
The objective of this lecture is to discuss the etiology, clinical course, types, pathogenesis,
morphology, and complications of tuberculosis.

Topic Outcomes
At the end of the lecture, students should be able to:
35-36.1 Describe the morphology of Mycobacterium tuberculosis.
35-36.2 Explain the immunopathogenesis of pulmonary infection by Mycobacterium
tuberculosis.
35-36.3 Describe the natural history and clinical spectrum of tuberculosis.
35-36.4 Describe the gross and microscopic morphology of primary and secondary tuberculosis.
35-36.5 Construct a flowchart to explain the principles of the laboratory diagnosis of
Mycobacterium tuberculosis with emphasis on pulmonary TB-AFB staining, routine and special
culture methods and molecular methods.
35-36.6 Recall and adapt further reading strategy on the relevant immunological aspects-
BCG/Tuberculin testing/Serological testing/Candidate vaccines.
Estimated tuberculosis incidence (per 100,000 population)
Estimated Numbers of Tuberculosis-related Deaths
 Tuberculosis (TB) in Malaysia

The number of tuberculosis (TB) cases in Malaysia increased by 3,664 cases

or 17% in 2022 compared to 2021.

Malaysia recorded a total of 25,391 TB cases in 2022 (a rate of 77.8 cases

per 100,000 people) compared to 2021 which only saw 21,727 cases (a rate of
63.5 cases per 100,000 people).

Malaysia also recorded 2,572 TB deaths in 2022, an increase of 284 deaths

(12%) from 2021 which only saw 2,288 deaths.

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New TB Cases in Malaysia
New TB cases in Malaysia 2005-2011: State wide
 Transmission of TB

• Caused by Mycobacterium tuberculosis (M. tuberculosis)

• Spread person to person through airborne particles that contain
M. tuberculosis, called droplet nuclei
• Transmission occurs when an infectious person coughs, sneezes,
laughs, or sings
• Prolonged contact needed for transmission
• 10% of infected persons will develop TB disease at some point in
their lives

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 Who Becomes Infected to TB?
• Probability of transmission depends on:
– Infectiousness
– Type of environment
– Length of exposure
• 10% of infected persons will develop
TB disease at some point in their lives
– 5% within 1-2 years
– 5% at some point in their lives

• Persons at high risk for developing TB

• Those who have been recently infected
• Those with clinical conditions that increase their risk of progressing
from LTBI to TB disease
 Primary Tuberculosis
The infection of an individual who has not been previously infected or immunised
is called primary tuberculosis or Ghon’s complex or childhood tuberculosis

Consist of primary complex involving

1. Pulmonary component is the primary focus or Ghon’s

focus. It is 1-2 cm solitary area located peripherally in
any part of the lung.
2. Lymphatic vessel component The lymphatics draining
the lung lesion contain phagocytes containing bacilli and
may.
3. Lymph node component This consists of enlarged
hilar and tracheo-bronchial lymph nodes in the area
drained. The affected lymph nodes are matted and show
caseation necrosis.
 Fate of Primary Tuberculosis

1. primary tuberculosis commonly do not progress but instead heal by fibrosis, and in
time undergo calcification and even ossification.
2. In some cases, it may create caseous material which is disseminated to other
parts of lung. This is called progressive primary tuberculosis.
3. At times, bacilli may spread by haematogenous route to other tissues and organs
causing miliary tuberculosis
4. Due to lowered host resistance and increased hypersensitivity, the healed lesions
of primary tuberculosis may get reactivated.
 Secondary Tuberculosis
The infection of an individual who has been previously infected or sensitized is
called secondary, or post-primary or reinfection, or chronic tuberculosis.

Secondary tuberculosis

1. Reactivation of a previous primary

tuberculosis site
2. Involves one or both apices in upper lobes.
Massive cavitation may occur.
3. Release of cytokines from memory T cells
results in a cavitation
4. Reactivation is more common in
low-prevalence areas, while reinfection plays
an importantrole in regions of high contagion.
Difference Between Primary and Secondary TB
Natural History of Tuberculosis
 Pathogenesis
of Tuberculosis
 Pathogenesis
of Tuberculosis
 Clinical Features of Tuberculosis
The clinical manifestations in tuberculosis may be variable depending upon the
location, extent and type of lesions.

1. Lungs Features: productive cough (may be with haemoptysis),

pleural effusion, dyspnoea, orthopnoea
Chest X-ray may show typical apical changes like pleural effusion, nodularity, and
miliary or diffuse infiltrates in the lung parenchyma.
2. Systemic features: fever, night sweats, fatigue, loss of appetite and weight.
 Diagnosis of Tuberculosis
The diagnosis is made by the following tests:

i) AFB microscopy of diagnostic specimen such as

sputum, aspirated material.
ii) Mycobacterial culture (on LJ medium for 4-8 weeks,
newer method by HPLC of mycolic acid with result in 2-3
weeks).
iii) Molecular methods such as PCR.
iv) Complete haemogram (lymphocytosis and raised ESR).
v) Radiographic procedures e.g. chest X-ray showing
hilar nodules and other parenchymal changes.
vi) Mantoux skin test .
vii) Serologic tests based on detection of antibodies.
viii) Fine needle aspiration cytology of an enlarged
peripheral lymph node
 Diagnosis
of Tuberculosis
 Lab Diagnosis of Tuberculosis: Malaysia Guideline

Line Probe Assay (LPA)