TB and immunosuppression 80k WW1 The disease Depression Clinical + immune K WW2 U defences s n o Isoniazid, BCG i t a c i f i t o N The cure Public health 1900 1915 1930 1945 1960 1975 1990 Incidence of Tb - UK TB 33% of the world is infected TB 3 million deaths per annum Impacts on western world - Ease of travel Clinical aspects - HIV (TB resurgence - 30% infected in Africa) - Multidrug resistance • Cough - haemoptysis Mr MD - breathless for 2 weeks. Smoker, wt loss, haemoptysis • Weight loss 1
Tb granuloma Caseation Tb - Ghon focus • Multinucleated cells (fused macrophages) • T-cells. Tuberculous pleural effusion Miliary Tb Thoracoplasty - old treatment making a comeback? Tb abscess 2
Sputum Tb - 1. Z-N stain Mantoux 2. Culture testing 3. Sensitivity 4. PCR Mycobacteria 1. TB (M.Tb, M Bovis) 2. Leprae 3. Non-tuberculous (eg. MAC) 4. Non-pathogenic 7 Mr MD - breathless for 2 weeks. - Smoker - wt loss, haemoptysis Treatment R ifampicin I soniazid P yrazinamide E thambutol DOTS Directly Observed Treament, Short course. • Multinucleated cells (fused macrophages) • T-cells. 5 μ 3
Lymph node APC “look what I lung found” CD4 CD4 IFN γ “bang blood CD4 bang” CD4 Low O 2 High O 2 “watch out - I’m coming Lung - TB Heart after you. ” Skin - Mantoux Spleen CD4 IFN γ IL- 4,5 ‘Th1’ response ‘Th2’ response CD4 CD4 CD4 Impaired immunity Protective immunity NB. Pregnancy! 600 HIV Viral RNA load 400 M Tb 400 CD4 count 200 CD4 MAC 50 0 1 4 12 2 4 6 8 10 12 weeks years Primary Asymptomatic AIDS infection 4
TB What to do about it. You are put in charge of the tuberculosis program of a rural subsaharan african region. There are 3 small hospitals, 10 doctors and 100 trained health workers in the whole area. You have one year to do something to help control Tb. Your budget is $1m only and you have to pay for staff, diagnosis and treatment of TB. Population 1 million Incidence of Tb probably 300/100,000 - ? how many are ‘open’ Costs Health worker $2/day Chest X-ray $20 Doctor $10/day ZN stain $ 2 Mantoux test $ 2 Anti TB drug course $20 BCG vaccination $ 2 What are you going to do? Operation $50 1. Detect open Tb cases Staff ZN sputum stain Health workers 50 x 365 x $2 $36k (100/day) ? CXR Doctors 3 x 365 x $10 $10k ? mantoux ZN stains 100,000 x $2 $200k 2. Treat open cases (NB. CXRs for all would be 1m x $20 = $20m) 3. check contacts Therapy (assuming 300/100,000) mantoux Open cases 3,000 x $20 $60k +ve = CXR & treat Screening contacts 10 per case = 30,000ZNs $120k - ve = watch ?BCG ?isoniazid Treat +ves = 6,000 $120k (CXR if HIV +ve) Treat HIV? HIV +ve contacts = CXR needed $400k HIV treatment? $ 0 4. HIV – TB joint strategies (30% of HIV have TB) Total $946k 5
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