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Double Trouble: Diabetes and Tuberculosis

Double Trouble: Diabetes and Tuberculosis. Kris Ernst, BSN, RN, CDE Division of Diabetes Translation Centers for Disease Control and Prevention. Disclaimer. This presentation represents the opinion of the author and is not the official opinion of CDC . Tuberculosis and Diabetes: Old Foes.

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Double Trouble: Diabetes and Tuberculosis

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  1. Double Trouble:Diabetes and Tuberculosis Kris Ernst, BSN, RN, CDE Division of Diabetes Translation Centers for Disease Control and Prevention

  2. Disclaimer • This presentation represents the opinion of the author and is not the official opinion of CDC

  3. Tuberculosis and Diabetes:Old Foes • Indian physician Susruta, in 600 A.D. “phthisis frequently complicated diabetes” • Autopsy of diabetics in 1883 showed presence of TB granuloma I 50% of diabetics • Prior to the insulin era: Diagnosis of DM was a death sentence • Leading cause of death was: Tuberculosis

  4. Definitions • Latent Tuberculosis Infection (LTBI) • Persons are infected with M. tuberculosis, but do not have active TB disease. • Active TB Disease • Persons infected with M tuberculosis bacteria that progress from latent TB infection.

  5. Background • Diabetes increases risk for progression from latent TB infection (LTBI) to active TB disease and complicates treatment of active TB • Delays in diagnosis for both diabetes and TB • Globally, the number of people with diabetes is increasing

  6. Number (in Millions) of Persons with Diagnosed Diabetes, United States, 1980–2007

  7. Background • Pathophysiology – diabetes,especially when poorly-controlled, causes relative immunocompromise and increases likelihood of reactivation of TB • Epidemiology – dramatic increase of diabetes • Demographics – diabetes disproportionately affects lower socioeconomic groups and ethnic minorities that also have higher prevalence of TB

  8. Background Treatment considerations – hard to treat TB in the face of poor glucose control Hidden epidemic – estimated that ¼ of people with diabetes don’t know they have it

  9. TB Case Rates,* United States, 2008 D.C. < 3.5 (year 2000 target) 3.6–4.2 > 4.2 (national average) *Cases per 100,000.

  10. Reported TB Cases by Age Group, United States, 2008 <15 yrs (6%) >65 yrs (19%) 15–24 yrs (11%) 25–44 yrs (33%) 45–64 yrs (30%)

  11. Asian/Pacific Islander American Indian/Alaska Native Black or African-American White Hispanic TB Case Rates by Race/Ethnicity* United States, 1993–2008** Cases per 100,000 *All races are non-Hispanic. In 2003, Asian/Pacific Islander category includes persons who reported race as Asian only and/or Native Hawaiian or Other Pacific Islander only.**Updated as of May 20, 2009.

  12. Reported TB Cases by Race/Ethnicity* United States, 2008 American Indian or Alaska Native (1%) White (17%) Asian (26%) Native Hawaiian or Other Pacific Islander (<1%) Hispanic or Latino (29%) Black or African-American (25%) *All races are non-Hispanic. Persons reporting two or more races accounted for less than 1% of all cases.

  13. Reported TB Cases* United States, 1982–2008 No. of Cases Year *Updated as of May 20, 2009.

  14. TB MorbidityUnited States, 2003–2008 Year No. Rate* • 2003 14,836 5.1 • 2004 14,500 4.9 • 2005 14,067 4.7 • 13,727 4.6 • 13,288 4.4 • 12,904 4.2 *Cases per 100,000, updated as of May 20, 2009.

  15. Transmission of M. tuberculosis • Spread by airborne route; droplet nuclei • Transmission affected by • Infectiousness of patient • Environmental conditions • Duration of exposure • Most exposed persons do not become infected

  16. TB Pathogenesis (1)Latent TB Infection • Once inhaled, bacteria travel to lung alveoli and establish infection • 2–12 wks after infection, immune response limits activity; infection is detectable • Some bacteria survive and remain dormant but viable for years (latent TB infection, or LTBI)

  17. TB Pathogenesis (2)Latent TB Infection • Persons with LTBI are • Asymptomatic • Not infectious • LTBI formerly diagnosed only with TST • Now QFT-G can be used

  18. Anergy Anergy is the immune system’s failure to respond to injected reagents or antigens Persons with compromised immunity may not react to tuberculin A few persons with normal immunity also do not react Thus, absence of TST reaction does not rule out LTBI or TB disease Anergy testing not recommended as adjunct to TST, because TST results alone cannot guide clinical decision making

  19. What’s New • QuantiFERON-TB Gold test (QFT-G) • QFT-G is a type of blood assay for M. tuberculosis (BAMT) • Measures the patient’s immune system reaction to M. tuberculosis • Blood samples must be processed within 12 hours • Interpretation of QFT-G results is influenced by the patient’s risk for infection with M. tuberculosis • An alternative to TST

  20. Clinical Diagnosis Obtain medical history and physical exam Place patients with suspected or known infectious TB disease under AII precautions until determined to be noninfectious Evaluate persons with extrapulmonary TB for concurrent pulmonary TB disease Although normally not infectious, children should be evaluated for infectiousness

  21. Diagnosis of Latent TB Infection • Persons with LTBI • Are asymptomatic • Do not feel sick • Cannot spread TB to others • Diagnostic procedures • Positive TST with medical evaluation to exclude TB • Evaluation includes assessing symptoms and signs, x-ray, and sputum tests • Blood assay for M. tuberculosis (BAMT) now available

  22. Treatment for LTBI • Treating LTBI reduces the risk that M. tuberculosis infection will develop into TB disease • Certain groups have higher risk for developing TB disease after infection; should be treated • Before beginning treatment for LTBI • Exclude diagnosis of TB • Ensure patient has no history of adverse reactions resulting from prior LTBI treatment

  23. Candidates for Treatment for LTBI The frequency of TB testing for HCWs will be determined by the risk classification for the setting.

  24. TB Patient Characteristics That Increase Risk for Infectiousness (1) • Coughing • Undergoing cough-inducing or aerosol-generating procedure • Failing to cover cough • Having cavitation on chest radiograph

  25. TB Patient Characteristics That Increase Risk for Infectiousness (2) • Positive acid-fast bacilli (AFB) sputum smear result • Disease of respiratory tract and larynx • Disease of respiratory tract and lung or pleura • Inadequate TB treatment

  26. Characteristics of Infectiousness Infectiousness related to • Cough >3 weeks • Cavitation on chest radiograph • Positive sputum smear results

  27. Characteristics of Infectiousness • Respiratory tract disease involving lung, airway, or larynx • Failure to cover mouth and nose when coughing • Inadequate treatment • Undergoing cough- or aerosol-producing procedures

  28. Isoniazid Rifampin Pyrazinamide Ethambutol Rifabutin* Rifapentine Streptomycin Cycloserine p-Aminosalicylic acid Ethionamide Amikacin or kanamycin* Capreomycin Levofloxacin* Moxifloxacin* Gatifloxacin* Antituberculosis Drugs First-Line Drugs Second-LineDrugs *Not approved by the U.S. Food and Drug Administration for use in the treatment of TB

  29. Ethambutol EMB Isoniazid INH Pyrazinamide PZA Rifampin RIF Rifapentine RPT Streptomycin SM Drug Abbreviations

  30. Treatment Regiments for LTBI

  31. Treatment for TB Disease • TB treatment regimens must contain multiple drugs to which M. tuberculosis is susceptible • Treating TB disease with a single drug can lead to resistance • Also, adding a single drug to a failing regimen can lead to drug resistance

  32. Treatment for TB Disease • Preferred regimen • Initial phase: 2 months isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol • Continuation phase: 4 months INH and RIF • In patients with cavitary pulmonary TB and positive culture results at end of initiation phase, continuation phase should be 7 months • TB patients with HIV who are taking anti-retrovirals (ARVs) should be managed by TB/HIV disease experts • TB treatment regimens might need to be altered

  33. Epidemiologic information Clinical, pathological, chest x-ray findings Microscopic examination of acid-fast bacilli (AFB) in sputum smears Nucleic acid amplification test (when performed) Factors Guiding Treatment Initiation

  34. Persons at Higher Risk for Exposure to and Infection with M. tuberculosis HCWs unknowingly exposed to TB patient Low-income, medically underserved groups Locally defined high-risk groups Young persons exposed to high-risk adults

  35. When to Consider Treatment Initiation • Positive AFB smear • Treatment should not be delayed because of negative AFB smears if high clinical suspicion: • History of cough and weight loss • Characteristic findings on chest x-ray • Emmigration from a high-incidence country

  36. Other Examinations to Conduct When TB Treatment Is Initiated • Counseling and testing for HIV infection • CD4+ T-lymphocyte count for HIV-positive persons • Hepatitis B and C serologic tests, if risks present

  37. Other Examinations to Conduct When TB Treatment Is Initiated • Measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, alkaline phosphatase, serum creatinine, and platelet count • Visual acuity and color vision tests (when EMB used)

  38. Algorithm to Guide Treatment of Culture-Negative TB Isinitial culture positive? NO YES Wastheresymptomaticor chest x-ray improvement after 2 months of treatment? Continue treatment for culture-positive TB NO YES • Discontinue treatment • Patient presumed to have LTBI • Treatment completed Give continuation- phase treatment of INH/RIF dailyor twice weekly for2 months

  39. Role of New Drugs Rifabutin: For patients receiving medications having unacceptable interactions with rifampin (e.g., persons with HIV/AIDS) Rifapentine: Used in once-weekly continuation phase for HIV-negative adults with drug-susceptible noncavitary TB and negative AFB smears at completion of initial phase of treatment

  40. Role of New Drugs • Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin): Used when -first-line drugs not tolerated; -strains resistant to RIF, INH, or EMB; or -evidence of other resistance patterns with fluoroquinolone susceptibility

  41. Common Adverse Reactions to Drug Treatment

  42. Common Adverse Reactions to Drug Treatment

  43. Common Adverse Reactions to Drug Treatment

  44. Drug Interactions • Relatively few drug interactions substantially change concentrations of antituberculosis drugs • Antituberculosis drugs sometimes change concentrations of other drugs -Rifamycins can decrease serum concentrations of many drugs, (e.g., most of the HIV-1 protease inhibitors), to subtherapeutic levels -Isoniazid increases concentrations of some drugs (e.g., phenytoin) to toxic levels

  45. Prevention of TB in persons with DM • Persons with diabetes mellitus (DM) who are at increased risk of tuberculosis (TB) should be screened for latent TB infection (LTBI) • TST or IGRA should be done at time of DM diagnosis • Patients with DM who are found to have LTBI should be encouraged to take INH for 9 months • Patients with DM on INH should receive vitamin B6 to prevent INH induced neuropathy

  46. Screening for DM in persons with TB • Every patient with TB over the age of 18 should be screened for DM • A fasting plasma glucose > 125 mg/dl = DM • A random plasma glucose > 200 mg/dl = DM • A Hemoglobin A1c > 6.5% = DM • Abnormal glucose values should be repeated in patients who have no symptoms of DM

  47. Screening for DM in persons with TB • Glucose should be repeated after 2-4 weeks of TB Rx or if symptoms of hyperglycemia develop • Rifampin and INH can markedly elevate glucose levels • Use the same criteria to diagnose DM as at initial evaluation • Ask about polyuria/polydipsia at TB clinic visits

  48. Management of DM in patients receiving TB treatment • Use the frequent contact with the patient during TB treatment to help manage his/her DM in the TB clinic • There should be a glucose meter in every TB clinic and blood glucose should be frequently checked in the clinic for those with DM • All clinical staff should reinforce lifestyle changes at TB clinic visits • If available, refer persons with diabetes to a diabetes specialty clinic or clinician comfortable with treating DM

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