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TB chemoprophylaxis Graham Bothamley Clinical Director, NE London TB Network.

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Presentation on theme: "TB chemoprophylaxis Graham Bothamley Clinical Director, NE London TB Network."— Presentation transcript:

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2 TB chemoprophylaxis Graham Bothamley Clinical Director, NE London TB Network

3 Questions 1.Do we know who will develop TB? 2.Who should take treatment? 3.How many will receive unnecessary treatment? 4.How many actually take treatment? 5.Is it cost-effective? 6.Is isoniazid the right treatment?

4 Latent TB infection or long-lasting TB immunity? Cochrane review: 1.68% over 5 years HIV+ PPD+ cohort: 4% over 22 months (7.9 cases per 100 person years) Human macrophages cannot kill Mtb 1-3 tubercle bacilli required for disease Selwyn et al NEJM 320: 545

5 Children: tuberculin responses, risk of TB over first 9 years and timing of exposure Horsburgh. NEJM 2004; 350:2060 US data:

6 Adults: tuberculin responses, risk of TB over first 9 years and timing of exposure Horsburgh. NEJM 2004; 350:2060 US data:

7 Progression to TB Immigrant contacts of S+ve cases >16 yrs in Holland CriterionTB cases/ positives % (95% CI) Sensitivity (%) PPD  10 mm 9/ ( )100 PPD  15 mm 7/ ( )88 QFT-GIT5/ ( )63 T-SPOT.TB6/ ( )75 All IGRA patients had PPD>10 mm; 1/8 patients missed if 15 mm Kaplan Meier for progression, pos vs. neg: even PPD >15 mm P= contacts from 380 index cases Kik et al. Eur Respir J 2010; (in press)

8 Predictive values of IGRA Subjects (n) Tests (n) False results Mean % Range % NPV PPV / PPV-HIV / TBNET review: Diel et al (ECDC)

9 PPD+: NNT to prevent 1 case TB ConditionNNTConditionNNT Transplant5Diabetes53.5 HIV+13.5Silicosis61 Gastrectomy23.5Unexplained WL66.5 Child contact24.5CRF on dialysis67 PPD conversion24.5Leukaemia91 IVDU30.5Immigrants93 Steroids98.5 No risk123.5 Rose. Arch Intern Med 2000; 160:1513

10 Treatment and harm Treat 72 to prevent one case of TB Treat 333 to cause isoniazid induced hepatitis (varies with age)

11 Hepatotoxicity of isoniazid Comstock & Edwards. Am Rev Respir Dis 1795; 111: 573

12 Adherence Horsburgh et al. Chest 2010; 137: clinics 123/720 declined (17.1%: %) 1045/1994 (52.4%) failed to complete IJTLD 2008; 12: 1235 & seen 8 had TB (0.2%) PPD+ = refused and only 40% eligible (>35 yrs) 320 (8.9% total; 67% who started) completed

13 Isoniazid Active against rapidly dividing population Course longer than TB treatment Most hepatotoxic of TB drugs Cheap

14 Chemoprophylaxis? 3 year old Mother has smear-positive pulmonary tuberculosis BCG vaccinated PPD 5 mm response

15 Chemoprophylaxis? 16 year old Somali Mother had LN TB BCG vaccinated PPD 12 mm response

16 Chemoprophylaxis? 34 year old Russian Screened as a new entrant to EU Chest x-ray normal PPD 35 mm response

17 Chemoprophylaxis? 45 year old health care worker Occupational health screening To work with HIV+ Born in UK Visited relatives in India for 3m last year Chest x-ray normal PPD 16 mm response

18 Chemoprophylaxis? 37 year old from Guinea-Bissau HIV+ BCG vaccinated PPD 15 mm response

19 Chemoprophylaxis? 45 year old from Turkey Screened as new entrant BCG vaccinated Chest x-ray: one calcified granuloma PPD 12 mm response Quantiferon: 0.52 IU/ml (>0.35 IU/ml)


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