2. Tuberculosis, its epidemiology & current situation

3. Causal Agent - Mycobacterium tuberculosis complex - Mycobacterium tuberculosis complex - M. tuberculosis - M. tuberculosis - M. bovis - M. bovis - M. africanum - M. africanum - M. microti - M. microti - M. caneti - M. caneti - M. pinnipedii - M. pinnipedii - M. caprae - M. caprae

4. - Slow and Little Alarmant Clinical Presentation - Excessive Delay to Consult the HC - Very Late Diagnosis Long time to be contagious when the Cases are Diagnosed Long time to be contagious when the Cases are Diagnosed - M. tuberculosis delay 16-24 h. to be divided (60 < Estafiloc.) - M. tuberculosis delay 16-24 h. to be divided (60 < Estafiloc.) Very Slow Division Capacity provided by Caminero

5. Causal Agent - Mycobacterium tuberculosis complex - Mycobacterium tuberculosis complex Polyvalent Polyvalent behaviour behaviour depending depending on medium. on medium.

6. In a tuberculosis patient, there are different bacillary populations formed of bacilli in different situations ■ In a tuberculosis patient, there are different bacillary populations formed of bacilli in different situations - Location - pH - Replication rate, susceptibility to drugs, … Bacillary populations provided by Caminero

7. Bacillary populations 1. Rapidly multiplying bacilli - Optimum medium: Extracellular. PH 6.5-7, maximum oxygenation (cavern wall) - Large number of bacilli → High probability of spontaneous natural mutations Many Millions Natural Resistant Mutants Failure

8. Relapses 2. Slow multiplication Bacilli - Intramacrophagic location. Acid pH. Population<10 5 No Naturally Resistant Mutants Bacillary populations

9. 3. Intermittently growing bacilli - Unfavourable conditions. Solid caseum. Extracellular - Population <10 5- Relapse capacity No Naturally Resistant Mutants Relapses

10. Bacillary populations 1. Rapidly multiplying bacilliINH 1. Rapidly multiplying bacilli → INH - Optimum medium: Extracellular. PH 6.5-7, maximum oxygenation (cavern wall) - Large number of bacilli → High probability of spontaneous mutations 2. Slowly multiplying bacilliPZ 2. Slowly multiplying bacilli → PZ - Intramacrophagic location. Acid pH. Population<10 5 3. Intermittently growing bacilliRIF 3. Intermittently growing bacilli → RIF - Unfavourable conditions. Solid caseum. Extracellular - Population <10 5. Relapse capacity 4. Bacilli in latent state: 4. Bacilli in latent state: Not susceptible to drugs - Reactivations and relapses provided by Caminero

11. 2. Reservoir. Source of Infection provided by Caminero

12. ReservoirReservoir - MAN: - MAN: * Infected, healthy * Infected, healthy World Population: 6.100 Millions M. TB Infection: 2.000 Millions ¡¡ Possible Reservoir MDR-TB: 50 Millions !! provided by Caminero

13. Source of Infection - MAN: - MAN: * Active disease * Active disease TB Cases: 16 million MDR-TB Cases:+ 500.000 provided by Caminero

14. Mechanism of Transmission - Fundamentally AEROGEN - Fundamentally AEROGEN - Very Uncommon: - Very Uncommon: - Cutaneous-Mucosal - Cutaneous-Mucosal - Urogenital - Urogenital - Inoculation - Inoculation - Tran placental, etc - Tran placental, etc provided by Caminero

15. TB Transmission. Contagious aerosol (droplets < 5 micras)

16. Greatest TB Transmitters 1.- Persons with bad Coughs 2.- Sputum Sm+ Patients 3.- Untreated patients 4.- Patients who have just commenced treatment 5.- Cases with poor response to treatment

17. Pulmonary TB (85%) Exposure to Source of disease Sputum Smear + Infection Active TB Extra Pulmonary (15%) 10-15 persons / year 5 – 10% Sputum Smear Negative (35%) 50% TB Epidemiologic Cycle

18. TB Risk Groups Relative Risk of developing TB (compared with control population, regardless of PPD) - HIV/AIDS150 -Silicosis 30 -Diabetes2 – 4.1 -Chronic renal failure / Haemodial.10 – 25.3 -Gastrectomy2-5 -Jejunoileal by-pass 27 - 63 -Kidney transplant37 -Heart “ 20 - 74 -Head or neck carcinoma 16 ATS/CDC. Am J Respir Crit Care Med 2000; 161 (part 2)

19. M. tuberculosis Resistance Natural Resistant Mutants according to Bacillary Population INH1 x 10 5 -10 6 Bacilli RIF1 x 10 7 -10 8 Bacilli SM 1 x 10 5 -10 6 Bacilli EMB1 x 10 5 -10 6 Bacilli PZ1 x 10 2 -10 4 Bacilli ? Quinolones 1 x 10 5 -10 6 Bacilli ? Others 1 x 10 5 -10 6 Bacilli ?

20. M. tuberculosis Resistance Bacillary Population in different TB Lesions TB Sm+ 10 7 -10 9 Bacilli Cavitary10 7 -10 9 Bacilli Infiltrated10 4 -10 7 Bacilli Nodules10 4 -10 6 Bacilli Adenopathies10 4 -10 6 Bacilli Renal TB 10 7 -10 9 Bacilli Extrapul. TB10 4 -10 6 Bacilli

21. Bacteriological Fundaments of TB Treatment 1. Drug combinations The combination of drugs prevents the appearance of resistance, because it avoids the selection of naturally resistant mutants

22. Selection of Natural Resistance, Acquired and Initial Resistance SUSCEPTIBLE to Drugs RESISTANT Latent Contagious Latent Contagious Develop into DR TB transmission acquire DR-TB acquire (M)DR-TB transmission Develop into TB

23. Basic Concepts in TB Resistance M.D.R.

24. M. Tuberculosis Resistance Multidrug-resistance (MDR) Defined as resistance at a minimum to “INH+RIF” It is extremely dangerous, as this TB is very difficult to cure MDR may be: –Primary or Initial –Acquired Will it determine the future of TB?

25. موارد مقاوم به چند داروموارد حساس به دارو بین 25 تا 250 میلیون تومان کمتر از 000,200 تومان هزينه 40 تا 60 درصدبیش از 95%اميد بهبودي 18 تا 24 ماه6 ماهطول دوره درمان 100% موارد 4 تا 6 ماه کمتر از 10% موارد به مدت کوتاه نیاز به بستری غالبا نارسایی تنفسی برای تمام عمر نداردمعلوليت حفظ يك منبع آلودگي از نوع مقاوم حذف یک منبع انتشاراپيدميولوژي مقايسه هزينه ، طول مدت درمان و اثر بخشي رژيم هاي درماني موجود ميان يك بيمار مبتلا به سل حساس به دارو و يك بيمار به سل مقاوم به چند دارو

26. LOSS OF HEALTHY LIFE DUE TO TB

27. Estimated numbers of new cases, 2006 No estimate 0–999 10 000–99 999 100 000–999 999 1 000 000 or more 1000–9999 Estimated number of new TB cases (all forms) 9m cases annually >1/3 in India and China

28. Estimated TB incidence rate, 2006 Estimated new TB cases (all forms) per 100 000 population No estimate 0-24 50-99 300 or more 25-49 100-299 World : 139/100,000 Highest TB rates per capita are in Africa linked to HIV/AIDS

29. Tuberculosis notification rates, 2006 No report 0–24 25–49 50–99 100 or more Notified TB cases (new and relapse) per 100 000 population World : 82/100,000 82*100/139 = 57% Smear+ CDR= 61%

30. World Health Assembly 1991 "…attain a global target of cure of 85% sputum-positive patients under treatment and detection of 70% of cases by the year 2000"

31. MILLENNIUM DEVELOPMENT GOALS (2015) 1.Eradicate poverty and hunger 2.Universal primary education 3.Empower women 4.Reduce child mortality 5.Improve maternal health 6.Combat HIV/AIDS, malaria and other diseases 7.Environmental sustainability 8.Global partnership for development Stop TB Department

32. Targets for global TB control MILLENNIUM DEVELOPMENT GOALS "to have halted and begun to reverse incidence... by 2015" Implementation (DOTS) Target Year Case detection 70%2005 Treatment success 85%2004/5 Impact Prevalence 50% 2015 Death 50% 2015 Incidence <1 per million 2050

33. Estimated TB Burden I.R.IRAN – 2006GlobalEMROIran Prevalence Rate 219/100,000152/100,000 28/100,000 Mortality Rate 25/100,00020/100,000 3/100,000 Incidence Rate All forms 139/100,000105/100,000 22/100,000 SS+62/100,00047/100,000 10/100,000 HIV prev. in new TB cases 7.7 % 1.1 % 1.7

34. Estimated HIV prevalence in new TB cases, 2006 No estimate 0–4 20–49 50 or more 5–19 HIV prevalence in TB cases, (%) World= 7.7%

35. MDR-TB Prevalence Rate among new cases 2006 World: 3.1% EMRO: 2.9%

36. MDR-TB Prevalence Rate among Previously Treated Cases 2006 World: 19.3% EMRO: 28.9%

37. XDR-TB Extensively drug-resistant TB (XDR TB) defined as: MDR TB with further resistance to: A fluoroquinolone One or more of the following injectable drugs: kanamycin, amikacin, capreomycin Source: Global XDR-TB Task Force, 7-8 October, 2006

38. Czech Republic The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.  WHO 2005. All rights reserved Ecuador Georgia Argentina Bangladesh Germany Republic of Korea Armenia Russian Federation South Africa Portugal Latvia Mexico Peru USA Brazil UK Sweden Thailand Chile Spain Islamic Republic of Iran China, Hong Kong SAR France Japan Norway Canada Countries with confirmed XDR-TB cases as of February 2007

39. Estimated number of cases Estimated number of deaths 1.6 million 8.8 million 116,000*424,000 All forms of TB Multidrug -resistant TB (MDR-TB) Extensively drug-resistant TB (XDR-TB) 27,000*16,000* * Calculated based on several available estimates Latest Global TB Estimates - 2005

40. Drug susceptible TB* *or limited resistance Manageable with 4 drug regimen - DOTS Resistanc e to H&R Treatable with 2 nd line drugs MDR- TB 1990 XDR-TB 2006 Resistance to 2 nd line drugs Treatment options seriously restricted Total DR ? Resistance to all available drugs No treatment options Evolution of drug-resistant TB

41. وضعيت فعلي بيماري سل در جمهوري اسلامي ايران

42. بيست و دو كشور داراي بيشترين بار بيماري

43. فراواني و ميزان بروز گزارش شده سل در كشور ( 1387 ) ميزان بروز گزارش شده ( /100,000 ) تعداد 13.49742 كل اشكال سل 6.74885 اسمير خلط مثبت سل ريوي 2.7 1936 اسمير خلط منفي 3.62606 سل خارج ريوي

44. وضعيت ميزان بيماريابي سل در كشور ( 1387 ) CDR ميزان بروز ( /100,000 ) تعداد مورد انتظار گزارش شده 61 %22 13.49742 كل اشكال سل 67%10 6.74885 اسمير خلط مثبت سل ريوي 2.7 1936 اسمير خلط منفي 3.62606 سل خارج ريوي

45. 67% موارد موجود شناسايي و گزارش شده اند. موارد شناسايي نشده (گم شده): 33% بيماران اين موارد شناسايي نشده، كجا گم شده اند؟

46. روند فراواني موارد سل اسمير مثبت گزارش شده در كشور به تفكيك مليت 1387

47. ميزان بروز سل ريوي اسمير خلط مثبت برحسب دانشگاههاي علوم پزشكي كشور – سال 1387

48. توزيع جنسي بروز سل ريوي اسمير مثبت در كشور در سال 1387

49. نتيجه درمان بيماران مبتلا به سل ريوي اسمير مثبت جمهوری اسلامی ایران – سال 85 1385 83 ميزان موفقيت درمان