Tuberculosis is a widespread infectious disease caused by the bacterium Mycobacterium tuberculosis. It infects one third of humanity and causes over 1.6 million deaths per year, making it one of the leading causes of death from infectious disease worldwide. The highest case rates are found in Asia, with India, China, and Indonesia having the most cases. Tuberculosis is often found concurrently with HIV infection and about half of those coinfected will develop active TB. Treatment involves a combination of antibiotics over several months, but drug resistance is a major problem, especially in Asia.

1. Tuberculosis – an overview Presented by: Dave Jay S. Manriquez RN. February 1, 2009

2. TB - Prevalence 1/3 rd of humanity (2 billion people) infected One new infection every second 8.8 million new cases per year 1.6 million deaths/year Kills more humans per year than any other infectious disease

3. TB – worldwide distribution

4. Estimated Tuberculosis Case Rates, 1997 India 1,799,000 China: 1,402,000 Indonesia: 583,000 Bangladesh: 300,000 Pakistan: 261,000 Nigeria 253,000 Philippines 222,000 South Africa 170,000 Russian Federation 156,000 Ethiopia 156,000 Vietnam 145,000 Democratic Republic of Congo 129,000 Adapted from Dye C, Scheele S, Dolin P, et al. Consensus statement. Global burden of tuberculosis : Estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA. 1999;282:677–686.

5. TB global stats 1/3 rd of all new incident cases in Asia ½ of all deaths from tb occur in Asia In Africa, grew rapidly over last two decades due to HIV Period of decline, altered by worldwide epidemic of HIV

6. Bach Christian Hospital TB stats (2002) 141 new cases of tuberculosis (over 11 new cases per month) 840 total TB patients under treatment 100 patients discharged having completed treatment

7. TB and HIV

8. Tuberculosis and HIV - over 8 million coinfected - reactivation rates 20 times higher than in non HIV-infected persons - 50% with dual infection develop active tb

9. Tuberculosis - resistance ½ of all new cases have some resistance Worst in 6 Asian countries of Bangladesh, China, India, Indonesia, Pakistan and Philippines Every country has resistance to at least one single drug

10. MDR Tuberculosis Defined as resistance to at least INH and rifampicin 450,000 cases per year XDR – extensive drug resistance Generally where there is also HIV

11. Tuberculosis MDR distribution Highest in former USSR and China

12. Mycobacterium others, generally opportunistic and assoc. with HIV M. Avium Intracellulare M. Asiaticum M. Flavenscens M. fortuitum complex M. Heamophilum M. Kanasasii M. Malmoense M. Marinum M. Scrofulaceum M. Simiae M. Genavense M. xenopi

13. Mycobacterium tuberculosis- the pathogen – AFB staining

14. Mycobacterium tuberculosis – immune response Principle response is formation of a granuloma – monocyte and t cells are with multi-nucleated giant cells on the edge of an area of caseation Caseous necrosis and calcium deposition

15. Tuberculosis - pathology Caseous necrosis in kidney

16. Tuberculosis – clinical presentation Primary tb in childhood Inhalation of organisms Formation of hilar LAD Only 5% develop symptomatic disease 30% develop established infection 3-5% chance of reactivation 1/3 rd of adult presentations due to new infection

17. Primary Tuberculosis -hilar adenopathy and infiltrate

18. Pulmonary Tuberculosis Most cases reactivation of disease acquired years earlier Predominant symptoms of cough (78%), weight loss (74%), fatigue (68%), fever (60%), night sweats (55%), hemoptysis (33%)

19. Pulmonary Tuberculosis – CXR findings Apical lesions – mod. and severe w/cavity

20. Chest X-Ray findings, atypical Pneumonic consolidation

21. Pulmonary Tuberculosis – pleural effusion Usually appear 3-6 months after primary disease With or without lung infection Usually unilateral Predominance of lymphs Exudative w/protein >3 gms/dl Often AFB neg, cx positive

22. Miliary tuberculosis In immune-suppressed Follows blood-borne dissemination May present as FUO High mortality rate

23. Miliary Tuberculosis - choroidal

24. Extra-pulmonary TB Scrofula (lymphadenitis) most frequent extrapulmonary manifestation 80% cervical Nearly always PPD positive Granulomas on biopsy Persistent nodes after tx common

25. Extrapulmonary tb - GI Anywhere from mouth to anus 70% w/advanced pulmonary get GI Small bowell- ileocecal valve Perforations common Responds well to tx

26. tapeworms roundworms

27. Extrapulmonary TB - peritonitis Ascites, pain, +/- fever, wt. loss Ascitic fluid seldom AFB positive Culture positive in only 25% Need tissue biopsy Diagnosis often delayed

28. Extrapulmonary TB - meningitis In early childhood, post-primary May present with subtle symptoms 3/4ths with miliary pattern on CXR AFB positive in 37% initially, 90% after 4 th spinal tap

29. Extrapulmonary TB – osteomyelitis Pott’s most common – 50% of all osteo Low thoracic most common Anterior destruction

30. Extrapulmonary TB - arthritis Chronic, progressive, monoarticular Usually hip or knee AFB positive in only 1/4 th Ideally, synovial biopsy

31. Extrapulmonary TB – cold abscesses

32. Extrapulmonary TB - urogenital Often asymptomatic, but kidney most commonly affected May present with cystitis symptoms, sterile pyuria Cultures 90% sensitive Males – scrotal mass, oligospermia Female – infertility with hematogenous focus in endosalpinx

33. Tuberculosis – laboratory investigations AFB – inexpensive Cultures – expensive, sensitivities helpful in MDR PCR – out of reach in poorer countries ESR – inexpensive and helpful, decreases with treatment Anemia of chronic disease

34. Tuberculosis - PPD 10mm – 90% infected >15mm – virtually all 5-10mm – may be result of BCG Unless recent BCG administration, if >10mm, then not from BCG

35. BCG vaccine Routinely administered in much of the world Efficacy 60-80%, though not uniformly

36. Tuberculosis - treatment INH (isoniazid) – bactericidal Most common side effect hepatotoxicity Check LFTs (20% of patients) If occurs, may reintroduce one med at a time Other side effect – peripheral neuritis, prevented by coadministration of piridoxine

37. Tuberculosis - treatment Rifampin Bactericidal Many interactions with other drugs Hepatotoxicity

39. Tuberculosis - treatment Pyrizinimide GI intolerance Hepatotoxicity – from elevated transaminases to liver failure

40. Tuberculosis - treatment Ethambutol -bactericidal -side effect – retrobulbar neuritis, presenting initially with blurred vision

41. Tuberculosis – treatment Streptomycin First antituberculous med Side effects of ototoxicity, nephrotoxicity Given IM

42. Tuberculosis – treatment Second line drugs Ethionamide Ciprofloxacin Capreomycin Kanamycin Amikacin Cycloserine Thiacetazone

43. Tuberculosis – treatment Bacteria killed over 6-mo period, but patient clinically improves in a few weeks Can do a 1-3 month interval AFB or culture evaluation Can follow ESR/weights

44. Tuberculosis - treatment Variety of regimens BCH regimen - for first 2 months, four drugs (INH/rifampin, pyrizinamide, ethambutal - next four months, only INH/rifampin - CNS – 12 months - depending on clinical scenario DOTS Use of steroids

45. Leprosy Organism – mycobacterium leprae Infection of skin and nerves

46. Leprosy Prevalence - 10-15 million in 1950s - 600,000 in 2000 Countries affected (>1/10,000) 122 in 1985 15 in 2000 83% in India, Brazil, Myanmar, Madagascar, Nepal, Mozambique

47. Leprosy - transmission Generally nasal secretions, particularly in lepromatous Importance of proximity, but most cases sporadic

48. Leprosy - presentation Subclinical more common than clinical, as incubation 4-10 years Clinical – tuberculoid vs. lepromatous

50. Leprosy – clinical presentation Tuberculoid – limited by vigorous cell-mediated response Lepromatous – proliferation of bacteria with extensive skin and nerve involvement

51. Leprosy - tuberculoid

52. Leprosy - lepromatous

53. Leprosy - lepromatous

55. Leprosy – borderline tuberculoid

56. Leprosy – mid borderline

58. Leprosy – clinical presentation Reversal reactions Occur in all forms except polar tuberculoid Sometimes after initiation of treatment Inflammation of existing lesions or new skin lesions, may present with acutely swollen nerves Respond to steroids

59. Leprosy – reversal reactions

60. Leprosy - treatment Combination therapy with dapsone, rifampin, clofazimine, quinolones, minocycline, azithromycin Multibacillary vs. paucibacillary High dose steroids for reversal reactions