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  1. 1. TROPICAL MEDICINE Major Tropical Diseases TUBERCULOSIS
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
  20. 20. 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)
  21. 21. 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
  22. 22. 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
  23. 23. 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
  24. 24. 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
  25. 25. Tropical Diseases TUBERCULOSIS –Diagnosis – 25 M. tuberculosis (stained red) in sputum
  26. 26. Major Tropical Diseases TUBERCULOSIS –Diagnosis - 26
  27. 27. Major Tropical Diseases TUBERCULOSIS –Diagnosis- 27 Mantoux tuberculin skin test
  28. 28. 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?
  29. 29. 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****
  30. 30. 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
  31. 31. 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

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