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

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

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

Infected Diseased Transitions in Tuberculosis Mechanism of preventive chemotherapy Preventive therapy

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

Frequency / severity of disease Rate per person years  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

Who to treat: Risk of disease Rate per person-years Risk: Group: PLWHA Contacts Silicosis Fibrotic lesions Gastrectomy Urban poor Cancer chemotherapy Dialysis Can J Pub Health 1987;78:305; Epidemiol Rev 1989;11:79

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

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

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

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

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

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

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%

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

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

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

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

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

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

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

-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,

Adherence to treatment in contacts Experimental conditions: clinical trial

Adherence to treatment in contacts Real conditions: British Columbia

Adherence to treatment in contacts Real conditions: Alberta

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

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

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

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

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

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

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