What you need to know about diagnosing and treating TB: a preventable, fatal disease Bob Belknap M.D. Denver Public Health November 2014
The Critical First Step Consider TB in the Differential 1. Risks for infection 2. Risks for progression 3. Concerning symptoms
Global TB Incidence WHO Global TB Report 2013
1.5 million deaths annually WHO Global TB Report 2013
Risk Factors for Progression HIV Fibrotic CXR c/w prior TB Immunosuppression (transplants, TNFalpha inhibitors) Recent close contact to active TB Diabetes Chronic renal failure Silicosis Leukemia / lymphoma Head/neck cancer Wt loss > 10% gastric bypass surgery
TB Symptoms Typical Cough > 3 weeks Weight loss Night sweats Fever Hemoptysis Atypical Recurrent pneumonia or UTIs (cx neg) Pleuritic chest pain Swollen lymph nodes Headache or altered mental status Pathologic fractures Unexplained anemia Infertility
TB Symptoms and HIV Symptom/sign HIV positive (%) HIV negative (%) Dyspnea Fever Sweats Weight loss Diarrhea Hepatomegaly Splenomegaly Lymphadenopathy 97 79 83 89 23 41 40 35 81 62 64 83 4 21 15 13 Chest 1994;106:1471-6
Why hasn t TB been eliminated? Transmitted from person to person Most people who get infected don t get sick Diagnostic test > 100 years Effective treatment for > 50 years
Transmission of M. tuberculosis In approaching the consumptive one breathes pernicious air. One takes the disease because there is in this air something diseaseproducing. Aristotle 384-322 BC
Brief history of TB diagnostics 400 BC Hippocrates had clinical deduction 1761 Auenbrugger describes auscultation 1816 Laennec invents the stethoscope 1882 Koch identifies TB using smears 1895 Roentgen discovers x-rays 1907 von Pirquet describes hypersensitivity to PPD 1910 Mantoux describes intradermal injection
Tuberculin Skin Test (TST) and Interferon-gamma Release Assays (IGRAs) Meta-analysis Data presented for the commercially available assays (QFT-GIT and T-SPOT) Results: % (95% CI) TST 70( 67-72) QFT-GIT 84 (81-87) T-SPOT 88 (85-90) Diel, Chest April 2010 137(4): 952 12
All BAL (+) patients were diagnosed by induced sputa BAL missed 2 patients No difference in yield between sputa collected over 3 days vs. 1 day
Molecular Diagnosis - GeneXpert Sputum Smear 50-70 % sensitive GeneXpert Sensitivity Smear (+) 98% Smear (-) 73% Next Generation Xpert MTB/Rif Ultra being developed to increase the sensitivity NEJM Sept 2010; 363: 1005 / CID April 2012; 54: 1071
Empirical TB treatment without a positive smear or culture Clinical reasons at risk for life-threatening TB, including ones often never confirmed (e.g. < 50% of TB meningitis is culture positive) Public health reasons return to work/school while cultures are pending, children at home, staying in a congregate setting (nursing home or homeless shelter)
First-line TB Therapy Medication Rifampin (Rif) Isoniazid (INH) Pyrazinamide (PZA) Ethambutol (EMB) Side Effects P450 inducer,hepatitis, rash, flu-like symptoms, hypersensitivity Fatigue, peripheral neuropathy, hepatitis GI upset, rash, hepatitis, uric acid elevation (rare gout attack) Rare optic neuritis
Standard Treatment of Tuberculosis 1. Intensive Phase INH, Rifampin, Pyrazinamide and Ethambutol x 2 months First 2 to 3 weeks are spent in home isolation can t work, go to school or be out in public places 2. Continuation Phase INH and Rifampin x 4 months
Drug Resistant Tuberculosis Multi-drug Resistant (MDR) Resistant to at least INH and Rifampin Extensively Drug Resistant (XDR) Resistant to INH and Rifampin plus Fluoroquinolones Second-line injectable agent (amikacin, kanamycin, or capreomycin)
WHO Global Report 2013 Estimated 450,000 MDR TB patients in 2012
Treatment of Suspected Drug-resistant TB Consider when a patient has a prior history of TB treatment and appears to have relapsed Never add a single drug to a failing regimen (eg. fluoroquinolones) Treat with 4-6 drugs known or likely to be effective, daily therapy directly observed for 18-24 months
Before Initiating Treatment for LTBI Rule out active TB CXR on everyone sputum collection if the CXR is abnormal or the person is symptomatic Determine prior history of treatment for LTBI or TB disease Assess risks of toxicity Determine current and previous drug therapy