TB

1. TROPICAL MEDICINE
Major Tropical Diseases
TUBERCULOSIS

2. Major Tropical Diseases
TUBERCULOSIS -Definition-1
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*

3. Major Tropical Diseases
TUBERCULOSIS- Aetiology- 2
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 *

4. Major Tropical Diseases
TUBERCULOSIS - Epidemiology- 3
• 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

5. Major Tropical Diseases
TUBERCULOSIS - Epidemiology- 4
• 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

6. Major Tropical Diseases
TUBERCULOSIS -Transmission- 5
• 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

7. Major Tropical Diseases
TUBERCULOSIS -Transmission- 6
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)

8. Major Tropical Diseases
TUBERCULOSIS - Risk Factors - 7
(a) Host Factors:
1. Age: higher in infants and adolescents
2. Compromised immunity as in: *
• HIV infection
• Malnutrition
• Measles infection
• Malignancies (e.g. lymphomas)
• Cytotoxics/Corticosteroid therapy
• Diabetes mellitus (3X increase)
• Alcoholism
3. Silicosis: increases TB risk by about 30-fold
4. Cigarette Smoking: Nearly doubles risk of TB

9. Major Tropical Diseases
TUBERCULOSIS - Risk Factors - 8
(b) Mycobacterium-associated Factors
1. Virulence of mycobacterium
2. Dose of mycobacterium
3. Environmental factors:
• Overcrowding
• Presence of open cases
• Poor ventilation
• Poor socioeconomic status

10. Major Tropical Diseases
TUBERCULOSIS – Pathogenesis - 9
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

11. Major Tropical Diseases
TUBERCULOSIS – Pathogenesis - 10
• 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

12. Major Tropical Diseases
TUBERCULOSIS – Pathology - 11
• 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)**

13. Major Tropical Diseases
TUBERCULOSIS – Clinical Features - 12
(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

14. Major Tropical Diseases
TUBERCULOSIS – Clinical Features - 13
(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

15. Major Tropical Diseases
TUBERCULOSIS – Clinical Features - 14
(C) CLINICAL FEATURES OF EXTRA-PULMONARY TB: *
• Extra-pulmonary TB occurs in 15-20% (> 50% in HIV) cases;
Common among immunosuppressed children
• R/S: Miliary TB, Pleurisy/Pleural effusion (Pleural
involvement)
• CVS: Progressive anaemia; Pericardial effusion; Cardiac
temponade (compression)
• CNS: TBM; TB spine (Kyphosis (Gibus; Pott’s disease ); /bones
(osteomyelitis) /joints; Paraplegia (Vertebral involvement)
• G.I.T: TB Peritonitis (ascites; recurrent intestinal obstruction);
Diarrhoea; malabsorption
• Skin: Lupus vulgaris (TB skin ulcer)
• GUT: Urogenital TB

16. Major Tropical Diseases
TUBERCULOSIS – Complications - 15
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

17. TUBERCULOSIS –Childhood Diagnosis- 16
(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

18. TUBERCULOSIS –Childhood Diagnosis- 17
(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

19. TUBERCULOSIS –Childhood Diagnosis- 18
(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

21. Major Tropical Diseases
(A) ACTIVE TB-Diagnosis - 20
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, Adenosine deaminase tests; others)

22. Major Tropical Diseases
(B) LATENT TB –Diagnosis - 21
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

23. Major Tropical Diseases
Multi-Drug Resistant (MDR)TB - 22
• 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

24. Major Tropical Diseases
Extensively -Drug Resistant (XDR)TB - 23
• 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

25. Major Tropical Diseases
ADVANCED TUBERCULOSIS –Diagnosis - 24
•Infection in both lungs marked by white arrows
•Formation of a cavity in lungs marked by black arrows

26. Tropical Diseases
TUBERCULOSIS –Diagnosis – 25
M. tuberculosis (stained red) in sputum

27. Major Tropical Diseases
TUBERCULOSIS –Diagnosis - 26

28. Major Tropical Diseases
TUBERCULOSIS –Diagnosis- 27
Mantoux tuberculin skin test

29. Major Tropical Diseases
TUBERCULOSIS – Management - 28
• 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?

30. Major Tropical Diseases
TUBERCULOSIS –Prevention - 29
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****

31. Major Tropical Diseases
TUBERCULOSIS – Prognosis*- 30
• 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

32. 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