1. Treatment of latent TB in tuberculosis control Turkish Thoracic Society Antalya, 27 April 2007

2. Objectives of the session By the end of the session, participants will be able to: Describe the mechanism of preventive chemotherapy List the benefits Explain where it is indicated Outline its drawbacks

3. Susceptible Exposed Infected Diseased Diagnosed Treated Cured Each transition has a measurable probability Probability varies with the situation Transitions in Tuberculosis Mechanism of transmission of tuberculosis Adapted from: Respiratory Epidemiology in Europe 2000: 67-91

4. Infected Diseased Transitions in Tuberculosis Mechanism of preventive chemotherapy Preventive therapy

5. Criteria for preventive treatment Characteristics of disease  Important frequency / severity  Natural history known with latency  Test characteristics good  Safe and effective treatment available

6. Frequency / severity of disease Rate per 100 000 person years  1 000 plus  100 to 999  10 to 99  1 to 10  0.2 to 1  0.1 Epidemic High risk Medium risk Low risk Elimination phase Eliminated Bull IUATLD 1990;65:71

7. Who to treat: Risk of disease Rate per 100 000 person-years Risk: 7 900 900 800 500 400 250 200 Group: PLWHA Contacts Silicosis Fibrotic lesions Gastrectomy Urban poor Cancer chemotherapy Dialysis Can J Pub Health 1987;78:305; Epidemiol Rev 1989;11:79

8. Natural history of tuberculosis Disease after infection, Aboriginals 10+ mm < 10 mm Int J Tuberc Lung Dis 1998;2:S16

9. Test characteristics of tuberculin Experimental conditions, Djibouti 1994 Excluding ‘0’

10. Test characteristics of tuberculin Real conditions, Aboriginals Int J Tuberc Lung Dis 1998;2:S16 Excluding ‘0’

11. Test characteristics of tuberculin Ability to predict disease risk, Aboriginals Int J Tuberc Lung Dis 1998;2:S16

12. Criteria for treatment  Better prognosis than usual  Facilities / resources available  Acceptable to patients

13. Tuberculosis in contacts Impact of preventive therapy Adv Tuberc Res 1969:17

14. Tuberculosis in contacts Risk reduction from preventive therapy Am Rev Respir Dis 1963;88:161 Size of tuberculinRisk reduction 5-9 mm94.2% 10 mm87.3%

15. Preventive therapy in contacts Trend in risk reduction Am Rev Respir Dis 1963;88:161

16. Preventive therapy Fibrotic lesions, by weeks of treatment Bull WHO 1982;60:555

17. Preventive therapy in contacts Reduction in risk of disease CountryTreatmentRisk reduction PhilippinesDuring30% After0% KenyaDuring70% After20% NetherlandsDuring85% After100% Adv Tuberc Res 1969;17

18. (Re) Infected Diseased Transitions in Tuberculosis Lack of action of preventive chemotherapy

19. Preventive therapy of fibrotic lesions Estimated risk reduction Bull WHO 1982;60:555 Size of lesion

20. Tuberculosis in communities Risk reduction from preventive therapy Adv Tuberc Res 1969; 17 LocationRisk reduction Tunisia16.7% Greenland27.8% Alaska66.0%

21. Tuberculosis in PLWHA Risk reduction from preventive therapy Lancet 1993;342:268 AIDS 1997;11:875 LocationRisk reduction Haiti70.7% Kenya0.0%

22. -Susceptible- -Exposed- -Infected- -Diseased- Transitions in Tuberculosis Distribution of the population over lifetime High burden 100,000 80,000 50,000 5,000 Low burden 100,000 5,000 500 50

23. Adherence to treatment in contacts Experimental conditions: clinical trial

24. Adherence to treatment in contacts Real conditions: British Columbia 1988-92

25. Adherence to treatment in contacts Real conditions: Alberta 1990-91

26. Return on investment Number treated to prevent a case GroupNumber to treat Active disease1.2 Infected contacts10.0 Fibrotic lesions10.8 PLWHA12.5 Cancer treatment42.0 Dialysis50.0 Urban poor60.5 Young infected adults99.3

27. Preventive therapy Medications stopped for toxicity Am Rev Respir Dis 1963;88:161

28. Placebo effects of treatment Drugs stopped for toxicity Am Rev Respir Dis 1963;88:161

29. Placebo effects of treatment Drugs stopped for toxicity Am Rev Respir Dis 1963;88:161

30. Placebo effects of treatment Drugs stopped for toxicity Am Rev Respir Dis 1963;88:161

31. Preventive therapy Risk of hepatitis Bull WHO 1982;60:555

32. Treatment of latent TB infection Conclusions  First priority is cure of patients  Treatment of TB infection only if latent  Treatment of latent infection does not help if Transmission risk remains high Individuals remain immune suppressed  Policies for routine treatment should be determined according to risk  To be effective, adherence must be high  Once started, be cautious about stopping