A look at medical factors that increase the risk for TB disease

Transcription

1 A look at medical factors that increase the risk for TB disease Mark Lobato, MD New England TB Consultant Division of Tuberculosis Elimination CDC Overview The spectrum of M. tuberculosis infection Immune regulation Three medical risks Diabetes mellitus Rheumatologic and inflammatory diseases Bladder cancer Recommendations Spectrum of M. tuberculosis Infection LTBI { Clinical presentation Clinical disease Subclinical bacterial replication Controlled infection with non replication Infection eliminated with T cell priming Immune response Disease Active infection Quiescent infection Acquired immunity Infection eliminated without specific T cells Innate immunity 1

2 T cell Immune Response wwhat Do We Know About Medical Risk Factors? Latent TB Infection (LTBI) M. tuberculosis can replicate in latency Immunosuppressed states are potent activators for progression to TB disease To control TB infection, immune cells release immune regulatory substances called cytokines Interferon γ is released by T cells Activates macrophages for eliminating M. tb Tissue necrosis factor α is released by macrophages Helps in the formation and stabilization of granuloma Granuloma 2

3 Relative Risk for Developing TB Disease, by Selected Clinical Conditions Silicosis, 30 Diabetes mellitus, Chronic renal failure/hemodialysis, Gastrectomy, 2 5 Jejunoileal bypass, Solid organ transplantation Renal, 37 Cardiac, Carcinoma of head or neck, 16 Source: CDC 2000 Development of TB among contacts Risk factors for developing tuberculosis: a 12 year follow up of TB contacts INT J TUBERC LUNG DIS 14: Morán Mendoza O, Marion SA, Elwood K, Patrick D, FitzGerald JM Table 1. Risk factors, TB incidence and hazard ratios (Cox s analysis) in contacts Risk factor Subjects TB cases TB rate/ Hazard ratio (95%CI) P value Diabetes 641 (1.9) 4 (1.8) ( ) Table 3. Final model. Cox multivariate analysis with robust variance estimation Risk factor Hazard ratio (95%CI)* P value Diabetes mellitus 1.76 ( ) Case S.G. is a 54 y/o Peruvian who has poorly controlled diabetes mellitus Recently diagnosed with rheumatoid arthritis Questions What are his TB risk factors? What do you want to know? What would you do first? What do you want to tell his specialty providers? 3

4 Three Conditions You May Encounter Diabetes mellitus Rheumatologic and immune mediated inflammatory diseases Bladder cancer Diabetes mellitus Almost 24 million people affected in the US Rapidly increasing along with obesity Affects different populations and geographic areas Native Americans Southeast May have other TB risks ESRD County level Estimates of Diagnosed Diabetes for Adults aged 20 years: United States

5 The Increasing Diabetes Epidemic, by age Rate of New Cases of Type 1 and Type 2 Diabetes among Youth aged <20 years, by race/ethnicity, ,000 per year) Rate (per Type 1 Type 2 0 ALL NHW AA H API AI ALL NHW AA H API AI <10 years years CDC. National Diabetes Fact Sheet, 2007 Source: SEARCH for Diabetes in Youth Study NHW=Non-Hispanic whites; AA=African Americans; H=Hispanics; API=Asians/Pacific Islanders; AI=American Indians Old Truths Tuberculosis is contagious phthisis (TB) frequently complicates diabetes Avicenna, 11 th century Abū Alī al Husayn ibn Abd Allāh ibn Sīnā' 5

6 TB and Diabetes Diabetes involving chronic high blood sugar is associated with altered immune responses Found to have lower IFN γ levels (Eur J Clin Microbiol Infec Dis 2008) Take longer to respond to anti TB treatment May be more likely to have MDR TB Glucose control may be more difficult TB disease Drugs (rifampin, INH, ethionamide) Testing for M. tuberculosis TST: sensitivity reduced owing to anergy QFT G Sensitivity Role of QuantiFERON TB Gold, Interferon Gamma Inducible Protein 10 and Tb Tuberculin Skin Test in Active Tuberculosis Diagnosis i PLoS ONE (2) () 11% (20/177) of patients with pulmonary TB had DM DM did not influence the sensitivity of the QFT G Indeterminate Results Clinical evaluation of QuantiFERON TB 2G test for immunocompromised patients Eur Respir J 2007; 30:945 Among 52 persons with diabetes and suspected LTBI, 3.8% (2) had an indeterminate QFT G result Diabetes and Pulmonary TB More likely to have atypical CXR Lower lobe only (24% vs. 2%) Cavitary lesion (51% vs. 39%) Shaikh Saudi Med J 2007 Left lower lobe TB 6

7 Effect of Type 2 Diabetes on the Treatment Response of Pulmonary TB DM + TB: associated with older age and greater body weight On presentation, diabetic patients had more symptoms but no evidence of more severe TB After 2 months (on DOT), sputum microscopic exam was more often positive in diabetics (18% vs. 10%) After 6 months, 22% of cultured sputum were positive for M. tb (odds ratio, 7.65) Alisjahbana B, et al. Clin Infect Dis 2007;45: Impact of Diabetes Mellitus on Treatment Outcomes of Patients with TB Disease In Maryland, of 297 TB patients 14% had DM After adjustments, the odds of death were 6.5 times higher in patients with diabetes Time to sputum culture conversion was longer in diabetes (median 49 vs. 39 days) Treatment failure occurred more often in patients with diabetes (6.7% vs. 4.1%) Dooley KE,e t al. Am J Trop Med Hyg, 2009;80:634 9 Lower rifampin concentrations in DM [rifampin] peak may be ~1/2 of non diabetics in the continuation phase TB + DM: AUC = 12.3 TB only: AUC = 25.9 (p=0.003) Associated with higher body weight and poor glucose control Nijland HM, et al. Clin Infect Dis 2006;43: No difference in AUC, C max, C max (T max ) during intensive phase for RIF, PZA, EMB Ruslami R. Antimicrob Agents Chemother 2010;54:

8 TB and DM on the Texas Mexico Border Research by the Nuevo Santander TB Trackers 5094 TB patients in S. Texas and N.E. Mexico High rates of DM (28% in Texan, 18% Mexican) Patients with ih diabetes were Older More likely to have hemoptysis, cavitations on CXR Smear positive at diagnosis Remain smear positive at the end of the 1 st (Texas) or 2 nd (Mexico) month of treatment Recommendations: Diabetes and TB WHO: none CDC/ATS/IDSA LTBI: give pyridoxine (B6) TB disease: none Indian Health Service, USPHS* (TST) should be done within 1 year of diabetes diagnosis Patients should be treated if they have LTBI Standards needed * Standards of Care for Adults With Type 2 Diabetes, March 2009 Rheumatologic and Inflammatory Diseases Rheumatoid arthritis Inflammatory bowel disease (Chron s) Psoriatic arthritis Anklylosing spondylitis Juvenile idiopathic arthritis 8

9 TNF α Antagonists Tissue necrosis factor (TNF) α inhibitors etanercept (Enbrel ), binds to TNF α infliximad (Remicade ), mouse/human monocloncal antibody adalimumab (Humira ), human monoclonal antibody The relative risk for TB increased up to 25 times TB Associated with TNF α Antagonists TB risk using TNF α antagonists Time to tuberculosis onset after starting infliximab or eternacept Lancet Infect Dis 2008;8:

10 Guidance when treating with TNF α Antagonists Screen patients for TB risk factors Test prior to starting immunotherapy Treat for LTBI those with a positive test (If TNF α started, use 5 mm TST cutoff) Consider delaying start of TNF α antagonist if possible to optimize treatment for LTBI Educate patients about TB symptoms Bladder Cancer BCG is used as immunotherapy to treat superficial bladder cancer Limited adverse events with BCG including fever Complications of BCG Therapy Local and systemic adverse events Localized bladder infection from BCG Disseminated BCG with or without shock 10

11 Management of persons with LTBI May result in local infection with BCG Contact precautions Treatment with 2 3 drugs (not PZA) Reports of disseminated BCG Pulmonary disease is infectious requiring isolation Treatment with 3 4 drugs (not PZA) for 9 months? Shock: add corticosteroid What Can the TB Program Do? Should TB patients be tested for diabetes? Partner with professional organizations Reach out and educate providers Case presentations Educational materials Guidelines Thank you! Discussion 11