3. Tuberculosis
Introduction *- 1a
• TB is a multi-systemic disease with myriad
presentations and manifestations
• is the most common cause of infectious
disease–related mortality worldwide
• It’s becoming more common in many parts of
the world
• In addition, the prevalence of drug-resistant
TB is increasing worldwide
4. Tuberculosis
Definition-1b
Definition:
Tuberculosis, MTB, or TB (short for tubercle
bacillus), in the past also called phthisis,
phthisis pulmonalis, or consumption, is a
widespread, and in many cases fatal,
infectious disease caused by various strains of
mycobacteria, usually Mycobacterium
tuberculosis*
5. Tuberculosis
Introduction *- 2
• Co-infection with the human immunodeficiency
virus (HIV) has been an important factor in the
emergence and spread of resistance*
• Mycobacterium tuberculosis, a tubercle bacillus,
is the causative agent of TB
• It belongs to a group of closely related
organisms—including M africanum, M bovis, and
M microti —in the M tuberculosis complex
6. Tuberculosis
Epidemiology - 3a
• World Health Organization (WHO) has
estimated that 2 billion people have latent TB
• In 2009, the disease killed 1.7 million people
globally
• Globally, more than 1 in 3 individuals is
infected with TB
• The 5 countries with the highest number of
incident cases in 2010 were India, China,
South Africa, Indonesia, and Pakistan*
7. Tuberculosis
Epidemiology- 3b
• One-third of the world's population is thought to
have M. tuberculosis
• New infections occur in about 1% of the population
each year
• In 2007, an estimated 13.7 million chronic cases
were active globally, while in 2010, about 8.8 million
new cases and 1.5 million associated deaths
occurred, mostly in developing countries
8. Tuberculosis
Epidemiology - 3c
• The absolute number of tuberculosis cases has
been decreasing since 2006
• New cases have decreased since 2002
• About 80% of the population in many Asian and
African countries have TB
• More people in the developing world contract
tuberculosis because of a poor immune system,
largely due to high rates of HIV infection and the
corresponding development of AIDS
10. Tuberculosis
Aetiology - 4b
Mycobacterium tuberculosis: *
• Acid-fast/Alcohol-fast bacillus (AAFB)
• Resistant to drying over long periods of time
• Very sensitive to light and heat
• Grows very slowly, multiplying over a period
of 20-24 hours
• Long treatment duration is needed for the
dormant tubercle bacillus *
11. Tuberculosis
Transmission/Risk Factors - 5a
• Transmission*
• Risk Factors*
• Pathophysiology
*
• TB in children*
• Genetic factors*
Activity 3.1:
1. Enumerate the
mode(s) of TB
transmission.
2. What are the risk
factors of TB and why?
12. Tuberculosis
Transmission- 5b
• Tuberculosis typically attacks the lungs, but can also affect
other parts of the body (except hair, nails and teeth -
enamel).
• It is spread through the air when people who have an
active TB infection cough, sneeze, or otherwise transmit
respiratory fluids through the air
• Most infections do not have symptoms, known as latent
tuberculosis
• About one in ten latent infections eventually progresses to
active disease which, if left untreated, kills more than 50%
of those so infected
13. Tuberculosis
Transmission - 5c
TB Transmission (Summary): *
1. Inhalation of infected droplets; main route; the smaller
the infected droplets, the higher the chances of infection
2. Ingestion of infected milk/food: in case of M. bovis
3. Traumatic inoculation: Broken skin/mucous membranes
Rare routes of TB transmission include:
4. Congenital TB : Transplacental/Aspiration of infected
amniotic fluid )
5. Contaminated formites (e.g. clothing, bronchoscopes,
syringes)
14. Tuberculosis
Pathogenesis - 6a
Stage Duration Features
1 3-8 weeks Primary complex develops; Conversion to tuberculin positivity
2 About
3months
Life-threatening forms occur due to haematogenous
dissemination (esp. TB meningitis and miliary TB)
3 3-4 months Tuberculous pleurisy from haematogenous or enlarging
primary focus
4 Up to 3
years
Lasts until primary complex resolves; Slower developing
extrapulmonary TB in bones and joints may appear
5 Up to 12
years
Genitourinary TB may occur as a late manifestation of
primary TB
Adapted from Wallgren and Ustvedt
15. Tuberculosis
Pathogenesis - 6b
• Blood-borne phagocytic cells, both macrophages and
polymorphonuclear leucocytes, aggregate around the focus
of infection, forming a foreign body granuloma termed
primary focus (formerly known as Ghon focus)
• Some bacilli are transported to the regional lymph nodes
(mediastinal, paratracheal and occasionally, the
supraclavicular nodes when the primary focus is in the
lungs), where secondary lesions develop
• Combination of the primary focus and the local lymphatic
component- lymphangitis and lymphadenopathy- is termed
the primary complex
16. Tuberculosis
Pathology - 6c
• Initial host response is acute inflammatory
reaction with an influx of PMNL
• It the acute inflammatory response is unable to
limit infectious process, a progressive infiltration
with macrophages occurs *
• Chronic inflammation then occurs with
granuloma formation, characteristic of chronic
infection (although granuloma restricts spread of
infection, it is a tissue-destroying SOL)**
17. Tuberculosis
Pathology - 6d
Tuberculosis:
• Aetiology
• Pathogenesis
• Pathology
• Clinical manifestations: PTB;
Extra-pulmonary TB
• Complications
• Diagnosis; Differentials
• Management
• Relationship of HIV and TB
Assignment 3.1:
1. Outline the pathogenesis,
pathology, clinical types,
clinical features and
complications of TB.
2. Discuss the current
approach to diagnosis and
management of TB.
3. Discuss relationship of TB
and HIV.
18. Tuberculosis
Pathology - 6e
• Inflammation occurs
at sites of infection;
• Phagocytosis begins
in macrophages
• Macrophages ingest
the TB bacterium;
• Macrophages produce
cytokines and
proteolytic enzymes as
bacteria multiply in
them;
• consequently, body
wasting, fever and
night sweats result.
19. Tuberculosis
Pathology - 6f
• Ghon focus occurs in
lungs, and this may
remain dormant for
long time
• Once active, it forms
areas of caseous
necrosis and granuloma
formation as exudate
accumulates in alveoli.
• Ghon focus plus
involvement of hilar
lymph nodes (hilar
lymphadenopathy)
forms the primary
complex.
20. Tuberculosis
Pathology - 6g
• Liquefaction occurs in
lesions formed as
macrophages burst to
release more TB bacilli to
surrounding tissues;
• Drainage of liquefaction
fluid into bronchi irritate
the bronchi to cause
coughing with
haemoptysis;
• Drainage into areas
outside the lungs
causes extrapulmonary
TB
• Calcification and
fibrosis also occur in
areas with TB lesions
21. Tuberculosis
Pathology - 6h
• Erosion of spinal
vertebrae may cause
gibus deformity;
paralysis
• Spread to brain may
cause TB meningitis
• Spread to all parts of the
lungs causes miliary TB
• Spread to other parts of
the body causes
extrapulmonary TB
• TB ffects all parts except
nails, hair and enamel
23. Tuberculosis
Clinical Features - 7b
(A) CLINICAL FEATURES OF CHILDHOOD TB:
1. Pulmonary (PTB) form: is commonest childhood form
2. Extra-pulmonary form: frequently seen; mainly:
• TB adenitis (commonly with cervical lymphadenopathy),
• TB Meningitis (TBM),
• TB bone & spine,
• Miliary TB;
• Cough (usually > 2 wks),
• Fever (irregular, recurrent),
• Weight loss,
• Anorexia,
• Night sweats
24. Tuberculosis
Clinical Features - 7c
(B) CLINICAL FEATURES OF PULMONARY TB (PTB) *
• Lung involvement (in 90% of cases) causes:
1. Chest pain
2. Prolonged cough (with mild haemoptysis); however
3. Massive bleeding (haemoptysis) may occur if pulmonary
artery is ruptured; this is termed Rasmussen's aneurysm)
4. Pleural effusion (presenting as pleural pain)
5. Pneumothorax
6. Chronic Lung fibrosis (due to scarring) may occur, especially
in upper lobes
7. Pneumonia (due to Pneumocystis carinii) may occur
26. Tuberculosis
Complications - 7e
Complications of Post-Primary (Extra-pulmonary) TB :
• Those due to broncho-pleural fistula formation:
Pleural effusion, Empyema(cold abscess formed if ruptured),
Pneumothorax, Pyopneumothorax;
• Those due to implantation of TB bacilli in swallowed
sputum: TB laryngitis/adenitis, indurated intestinal ulcers
• Those due to late secondary pulmonary fibrosis: Chronic
Obstructive Pulmonary Disease, Corpulmonale
• Others (late/rare):
Aspergillomas; Healed Cavitations, Amyloidosis
29. Tuberculosis
(A) ACTIVE TB-Diagnosis - 8b
1. Suggestive history: (High index of suspicion; Constitutional S&S > 2
wks: cough, night sweats, weight loss/wasting, ?HIV cases)
2. Suggestive Imaging features: CXR, (CT, US, MRI or radioisotope)
scans
3. Bacteriological examinations: [Multiple sputum (AAFB), tissue
biopsy, blood , pus, CSF, bronchial, pleural, pericardial, gastric,
peritoneal aspirates ] for microscopy and cultures
4. Immunological Tests: These include:
i. Tuberculin skin (Mantoux) Test : useless in HIV cases
ii. Interferon-γ release assays (IGRA) : little use in the developing
world and in HIV cases
5. Haematological/Biochemical: CBC, ESR, LFTs (Ltd diagnostic roles)
6. Molecular Techniques: (PCR/DNA-based rapid TB tests):
Nucleic acid amplification tests (e.g. GenExpert Test); Adenosine
deaminase tests; others
30. Tuberculosis
(B) LATENT TB –Diagnosis - 8c
Based on Immunological (Tuberculin) skin Tests, including:
1. MANTOUX TEST:
• Screening high-risk people
• False positive in previously immunized
• False negative in Sarcoidosis, Hodgkins lymphoma and Malnourished
patients
2. INTERFERON GAMMA RELEASE ASSAYS (IGRAs):
• Recommended for Mantoux positive patients
• Generate fewer false positive results but
• Adversely affected by other Mycobacterium spp.**
• may increase sensitivity when used in addition to the skin test, but
• may be less sensitive than the skin test when used alone
31. Tuberculosis
(B) LATENT TB –Diagnosis - 8d1
• GenExpert Test (CB-NAAT):
A molecular test for TB
Detects DNA in TB bacilli
Also tests for TB resistance to rifampicin (MDR/XDR
TB detection)
Also known (in India) as CB-NAAT - Cartridge Based
Nucleic Acid Amplification Test.
Assay now available in GenExpert platform, to test
COVID-19.
33. Tuberculosis
Diagnosis – 8e
• Axial noncontrast enhanced
computed tomography with
pulmonary window shows a
cavity with an irregular wall in
the right apex of a 37-year-old
man who presented with
cough and fever ((upper
picture.
• Coronal reconstructed
computed tomography image
shows the consolidated,
partially collapsed right upper
lobe with a cavity that is
directly connected to a
bronchus in a 43-year-old man
who presented with cough
and fever (same patient (lower
picture)
34. Tuberculosis
Diagnosis – 8f
• Axial chest computed tomography
without intravenous contrast with
pulmonary window setting through
the mid-chest shows a large,
irregular-walled cavity with nodules
and air-fluid level and two smaller
cavities in a 43-year-old man who
presented with cough and
hemoptysis (same patient as above).
Small, patchy peripheral opacities are
also present in the left lower lobe. In
the right mid-lung, nodular opacities
are in a tree-in-bud distribution,
suggestive of endobronchial spread.
(Upper picture)
• Coronal reconstructed computed
tomography image shows the lingular
cavity with irregular nodules and
right mid-lung nodular opacities in a
43-year-old man who presented with
cough and hemoptysis (same patient
as above) (Lower picture).
35. Tuberculosis
Diagnosis – 8g
• This radiograph shows a patient
with typical radiographic findings
of tuberculosis. (Upper picture)
• Anteroposterior chest radiograph
of a young patient who presented
to the emergency department (ED)
with cough and malaise. The
radiograph shows a classic
posterior segment right upper lobe
density consistent with active
tuberculosis. This woman was
admitted to isolation and started
empirically on a 4-drug regimen in
the ED. Tuberculosis was
confirmed on sputum testing.
Image courtesy of Remote
Medicine (remotemedicine.org).
(Lower picture)
36. Tuberculosis
Diagnosis – 8h
• Lateral chest radiograph of a
patient with posterior segment
right upper lobe density consistent
with active tuberculosis. Image
courtesy of Remote Medicine
(remotemedicine.org). (Upper
picture)
• This chest radiograph shows
asymmetry in the first
costochondral junctions of a 37-
year-old man who presented with
cough and fever. Further
clarification with computed
tomography is needed. (Upper
picture)
37. Tuberculosis
Diagnosis – 8i
• This posteroanterior chest
radiograph shows right upper lobe
consolidation with minimal volume
loss (elevated horizontal fissure)
and a cavity in a 43-year-old man
who presented with cough and
fever. (Upper picture)
• The posteroanterior chest
radiograph shows a large cavity
with surrounding consolidation in
the lingular portion of the left
upper lobe in a 43-year-old man
who presented with cough and
hemoptysis. There are also a few
nodular opacities in the right mid-
lung zone. (Lower picture)
38. Tuberculosis
Advanced TB Diagnosis - 8j
•Infection in both lungs marked by
white arrows
•Formation of a cavity in lungs marked
by black arrows
42. TUBERCULOSIS –Childhood Diagnosis - 8m
(Kenneth Jones Criteria , 1968)
Scoring System Points
Acid Fast Bacilli (Sputum microscopy) +5
Tubercle in biopsy (histology) +5
Tuberculin (Mantoux) or preferably Diagnostic BCG Test:
Positive (> 10mm)
+3
Tuberculin (Mantoux) or preferably Diagnostic BCG Test:
Borderline (5-9mm)
+2
Tuberculin (Mantoux) or preferably Diagnostic BCG Test:
Conversion from negative to positive
+2
Suggestive radiology +3
43. TUBERCULOSIS –Childhood Diagnosis - 8n
(Kenneth Jones Point System Criteria , 1968)*
Scoring System Points
Known contact with positive sputum (house hold contact) +2
Known contact with positive sputum (non-house hold contact) +1
Non-specific signs and symptoms of TB +1
Non-specific X-Ray (CXR , etc) findings +1
Non-specific granuloma +1
Less than 2 years of age +1
Response to specific anti-TB therapy +3
BCG vaccination given -1
44. TUBERCULOSIS –Childhood Diagnosis - 8p
(Kenneth Jones Point System Criteria ,1968)*
POINTS INTERPRETATION
1-2 TB diagnosis unlikely
3-4 TB possible; further investigations
required
5-6 TB probable, therapy may be justified
≥ 7 TB unquestionable
45. Tuberculosis
Clinical Features - 8q
Assignment 3.1:
1. Discuss/summarize the
clinical manifestations
and complications of
tuberculosis.
2. Outline the diagnosis and
management of
tuberculosis.
3. How is multi-drug
resistant (MDR)
tuberculosis and
extremely resistant (XDR)
Symptoms of Tuberculosis
•
47. Tuberculosis
Management – 9b
• Effective TB treatment is difficult *
• Directly Observed Therapy (DOT) recommended by WHO
• Commonly used drugs include:
1. Rifampicin
2. Isoniazid
3. Ethambutol
4. Streptomycin
• Students to study pharmacology of specific drugs used in
first and second line TB therapy: Duration, Dose, side effects
• What supportive and other treatment measures are given to
TB patients?
48. Tuberculosis
Multi-Drug Resistant (MDR)TB - 9c
• Multidrug-resistant TB (MDR TB) is caused by an organism
that is resistant to at least isoniazid and rifampicin (most
potent TB drugs) *
MDR TB is the same way (air borne) as ordinary TB but more
common among people who:
• Do not take their TB drugs regularly
• Do not take all of their TB drugs
• Develop TB disease again, after being treated for TB disease
in the past
• Come from areas of the world where drug-resistant TB is
common
• Have spent time with someone known to have drug-
resistant TB disease
49. Tuberculosis
Prevention – 9d
1. Immunization/Vaccination: **
• BCG given at birth/first contact with non-vaccinated persons
(especially infants)
• Other vaccines currently being developed by researchers**
2. Health education: Early diagnosis and treatment of cases:
• Active/Passive Case finding : Detecting infected cases thro’
clinical, radiological and laboratory evaluation ***
• High index of suspicion: e.g. investigate
HIV/immunosuppressed cases for TB
• Educate on need to overcome social stigma****
50. Tuberculosis
Extensively -Drug Resistant (XDR)TB - 9e
• Extensively drug-resistant TB (XDR TB) is a rare type of MDR
• TB that is resistant to isoniazid and rifampicin, plus any
fluoroquinolone and at least one of three injectable second-
line drugs (i.e., amikacin, kanamycin, or capreomycin) **
• Because XDR TB is resistant to the most potent TB drugs,
patients are left with treatment options that are much less
effective
• People with weaker immune system more susceptible to XDR
TB and related fatalities than others
51. Tuberculosis
Prevention - 9f
1. Immunization/Vaccination: **
• BCG given at birth/first contact with non-vaccinated persons
(especially infants)
• Other vaccines currently being developed by researchers**
2. Health education: Early diagnosis and treatment of cases:
• Active/Passive Case finding : Detecting infected cases thro’
clinical, radiological and laboratory evaluation ***
• High index of suspicion: e.g. investigate
HIV/immunosuppressed cases for TB
• Educate on need to overcome social stigma****
52. Tuberculosis
Prognosis*- 9g
• Progression from TB infection to overt TB disease occurs
some 1–5% of cases, soon after the initial infection
• Dormant bacilli produce active tuberculosis in 5–10% of
latent cases, often many years after infection
• The risk of reactivation increases with
immunosuppression (e.g. in people coinfected with M.
tuberculosis and HIV, the risk of reactivation increases to
10% per year
• The chance of death from a case of tuberculosis is about
4% as of 2008, down from 8% in 1995
53. Assignment 3.2:
Maina, a 35-year old man who has been separated from his wife for
five years and currently living with a mistress with whom they have
two children, presents with hotness of the body, sweating at night and
cough for three months. He has been getting herbal medicine for the
last two months without improvement. His mistress and the two
children also look wasted and generally unwell and malnourished,
according to one informer who accompanied them to hospital.
(a) Enumerate at least three differential diagnoses of Maina's ailment
and those of his children and mistress.
(b) What is the likely diagnosis (and why?)
(c) How will you go about the confirmation of diagnosis?
(d) Outline, giving reasons, the management of Maina, his mistress
and children.
54. References
• Geoff, G & Nick, B. 2004. Lecture notes: Tropical Medicine.
6th edition
• Gordon, C. C & Alimuddin, I . Z. 2009. Manson’s Tropical
Diseases. 22nd Edition. Saunders Elsevier Publishers.
• Mandal, B.K., Wilkins E.G.L., Dunbar, E.M., Mayon-White, R.T.
2004. Infectious Diseases. 6th Edition. Blackwell Publishing.
• McPhee, S.J., Papadakis, M.A. 2011. Current Medical
Diagnosis and Treatment. McGraw Hill Lange Publishers.
• Rubenstein, D & Wayne, D. Lecture notes on Clinical
Medicine. 3rd edition. Blackwell Scientific Publications.
• http://www.answers.com/topic/tropical-
medicine#ixzz3DudykneO
• http:// www. wikipedia website: the free encyclopedia
