Microbiology and clinical aspects of tuberculosis and leprosy

Microbiology and clinical aspects of tuberculosis and leprosy have been discussed

1. Tuberculosis Mycobacterium tuberculosis 2

2. Mycobacterium tuberculosis Acid fast rod Obligate aerobe 60% of the cell wall is mycolic acid; major virulence factor Wax D (cord factor) inhibits macrophage migration; elicits granuloma formation sulfatides inhibit secondary lysosomal fusion Transmission; aerosolization of contaminated respiratory secretions Risk factors – DM, poverty, HL, CRF,malnutrition

3. Primary tuberculosis is the form of disease that develops in a previously unexposed, and therefore unsensitized , person. Secondary tuberculosis occurs due to reinfection / reactivation of latent disease- i.e occurs in a person who has already been infected once.

4. Primary Tuberculosis Delayed hypersensitivity will develop at least 3 weeks (sometimes 30-50 days) following exposure Inhalation of organisms  phagocytosis by alveolar macrophages  systemic dissemination  macrophage activation & kill bacteria Macrophages present processed antigen to helper T-cells & secrete interleukin 12  induces helper T-cells to differentiate into sensitized T H 1cells (have memory)

5. Primary Tuberculosis Ghon focus) granuloma (tubercle) in the upper part of lower lobes of lung or lower part of upper lobes Ghon complex Ghon focus+ enlarged hilar LNs, draining lymphatics

6. Primary Tuberculosis Ghon focus 8

7. Primary Tuberculosis Clinical symptoms: cough (initially dry becomes productive ) variable hemoptysis , fever, night sweats, weight loss Fate of primary tuberculosis Healing by scar formation. Latent TB Progressive primary tuberculosis Tuberculous pneumonia Miliary TB Disseminated TB

8. Latent TB organisms disseminate in macrophages high oxygen areas; lung other & organs  dormant immunosupression  reactivate  secondary (reactive) TB

9. Tuberculosis Progressive primary TB infants, children, immunosuppressed adults primary tuberculosis resembles an acute bacterial pneumonia, with lower and middle lobe consolidation, hilar adenopathy , and pleural effusion Lymphohematogenous dissemination may result in the development of tuberculous meningitis and miliary tuberculosis 12

10. Miliary Tuberculosis Numerous small (millimeters) tubercles Symptoms are nonspecific Miliary TB occurs when organisms draining thro’ lymphatics enter venous blood and circulate back to the lung. Liver, spleen, bone marrow, adrenals, meninges, kidneys, fallopian tubes and epididymis are involved biopsies of these sites usually are diagnostic 13

11. Pulmonary Tuberculosis 14 most cases immunosuppression Ghon focus

12. Secondary or Reactivation TB Reactivation occurs in the oxygen rich apex of the lungs Factors that predispose for reactivation immunosuppression, malnutrition, alcoholism, diabetes mellitus, old age, stress, AIDS Localized Secondary TB granuloma; initially at apices lung, hilar LNs local dissemination (parenchyma, LN) via airways, lymphatics cavitary lesion +/- massive hemoptysis, bronchiectasis, reactive amyloidosis

13. Secondary or Reactivation TB Progressive Secondary TB organisms  lymphatics, alveolar capillaries  blood  systemic dissemination multiple organs  miliary TB most common, bone marrow, liver, spleen, retina, kidney adrenals skin rare (lupus vulgaris) 16

14. Miliary Tuberculosis

15. Miliary Tuberculosis 18

16. Gross Tuberculosis Tubercles; mm (miliary TB)  3-4 cm white-yellow/gray caseated +/- cavitated (drain into airways) fibrous capsule enlarged LN  fibrotic, calcified, caseous necrosis Miliary TB, -numerous small tubercles +/- pleuritis, empyema 19

17. Microscopy - Tuberculosis Central areas caseous necrosis variable (abundant- none) Surr by granuolmatous inflammation epitheloid macrophages, Langhans giant cells, lymphs Surr fct Healed lesions; fct +/- calcification no inflammation Early lesion; organisms are present 20

18. Microscopy Pulmonary Tuberculosis 21

19. MicroscopyPulmonary Tuberculosis 22 N N

20. Microscopy Pulmonary Tuberculosis 23 Auromine fluorescent stain Acid fast stain

21. Tuberculosis Diagnosis Chest X-ray Sputum for culture and acid fast bacteria stains (gold standard) Ziehl-Neelsen & Kinyoun stains fluorochrome techniques Skin tests-PPD PCR

22. Extrapulmonary TB and Other Facts Most common extrapulmonary site is kidney Scrofula: Chronic TB lymphadenitis of the cervical lymph nodes Increasing incidence in HIV 30 times more likely to have reactivation In developing countries, TB is the most common opportunistic infection in AIDS patients TB is the MOST COMMON infectious cause of death worldwide

23. Extrapulmonary TB and Other Facts Pott’s disease: TB of the vertebral column CNS: meningitis, granulomatous abscesses, intracerebral granulomas Skin; lupus vulgaris which predisposes to squamous cell carcinoma TB is the most common cause of constrictive pericarditis world wide 26

24. Multiple granulomas in the CNS

25. Pott’s Disease

26. Tuberculosis of the Kidney

27. Leprosy 30

28. Mycobacterium leprae Hansen’s disease Low infectivity and long incubation period (2-5 years) Cannot be cultured Contracted by direct contact or droplet Three clinical forms Tuberculoid Indeterminate Lepromatous

29. Leprosy Tuberculoid Form Usually non-contagious Intact cellular immunity (+) lepromin skin test Granulomas; dermis, trunk, extremities & face hypopigmented to erythromatous macules, sharply demarcated and anesthetic very few organisms Peripheral nerves surr by granulomas epitheloid macrophages, giant cells, lymphocytes few organisms 32

30. 33

31. Leprosy Lepromatous Form Lack of cellular immunity negative lepromin test Skin; macules, papules Nerve involvement  anesthesias, muscle atrophy, and autoamputation more generalized involvement than tuberculoid numerous organisms variable sized aggreg. foamy macrophages no granulomas organisms within peripheral nerves & Schwann cells

32. Lepromatous leprosy “Leonine facies”

33. Lepromatous leprosy

34. Leprosy Lepromatous Form Grenz zone Lepromatous form only Dermis is filled with foamy macrophages (Virchow- Lepra cells) which are filled with masses of AFB [ globi ] Clear zone demarcating the epidermis from the infiltrated dermis. Grentz zone 37

35. Lepromatous leprosy 38

36. Mycobacterium leprae Leprosy Indeterminate Form mild form primarily in children 39

37. Leprosy Clinical Tuberculoid leprosy - Skin; large irregular, red hyperpigmented macules with pale centres asymmetric hypoesthesia Contractures, paralysis, autoamputation fingers & toes Paralysis eyelids; keratitis, corneal ulcers 40

38. Leprosy Lepromatous leprosy – skin, peripheral nerves, anterior chamber of the eye, upper airways, testes, hands,and feet. Macular, papular or nodular lesions on the face, ears, wrists . Nodules coalesce to form leonine facies. Symmetric skin thickening and nerve involvement

39. Leprosy Most prevalent Asia & Africa > Central & South America USA; endemic areas; Texas, Louisiana, Florida, California, & Hawaii Tx Dapsone excellent prognosis w/ tx 42

40. Erythema Nodosum Seen in lepromatous leprosy in > 30% of cases being treated in the 1 st year Immune-mediated response to soluble antigens of bacteria liberated from cells Diffuse painful erythematous nodules  +/- necrosis and suppuration Fever, malaise +/- glomerulonephritis 43

41. Leprosy 44

42. Leprosy 45

43. Lepromatous leprosy 46

44. Lepromatous leprosy Grentz zone 47