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Tuberculosis

Tuberculosis. Scott Lindquist MD MPH Washington State Communicable Disease Epidemiologist. Estimated TB Global Incidence 2012. A Brief History of Tuberculosis (TB). Tuberculosis (phthisis) described since the time of Hippocrates (460 BC - 370 BC)

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Tuberculosis

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  1. Tuberculosis Scott Lindquist MD MPH Washington State Communicable Disease Epidemiologist

  2. Estimated TB Global Incidence 2012

  3. A Brief History of Tuberculosis (TB) • Tuberculosis (phthisis) described since the time of Hippocrates (460 BC - 370 BC) • 1689: Doctor Richard Morton used the term “consumption” to denote TB. • Second half of the 17th century: high death rates from TB in Europe. • 1722: Doctor Benjamin Marten proposed that TB could be transmitted in the air and described TB as being caused by “wonderfully minute living creatures” • End of 19th century to the start of 20th century: Principal cause of death in Europe was TB. • The romantic Era of TB “Queen Guinevere” painted by William Morris

  4. A Brief History of Tuberculosis (TB) • 1865 Jean-Antoine Villemin: confirmed that • TB is contagious. • Robert Koch: • 1882: Isolated and cultured M. tuberculosis. • 1890: Announced the discovery of tuberculin. • Developed staining methods used to identify the bacteria. • 1905: Received the Nobel Prize • Bacteriologist Paul Ehrlich developed Ziehl- • Neelsen staining. • Late 1800’s: Edward Livingston Trudeau • established “Adirondack Cottage • Sanatorium”, first TB sanatorium in the US. Visualization of M. tuberculosis using the Ziehl-Neelsen stain

  5. Tuberculosis • 1882 – Robert Koch – “one seventh of all human beings die of tuberculosis and… if one considers only the productive middle-age groups, tuberculosis carries away one-third and often more of these…”

  6. A Brief History of Tuberculosis (TB) • 1896 Theobald Smith demonstrated that bovine TB is caused by M. bovis. • 1908 Albert Calmette and Camille Guérin isolated M. bovis and grew it in ox bile. • Identified a morphological variant of M. bovisfound to be avirulent, conferred immunity against M. tuberculosis. • Lead to the BCG vaccine (bacilli Calmette-Guérin). • Development of antibiotics to combat infection: • 1947: streptomycin, 1952: isoniazid • The majority of drugs used to combat infection were identified between 1945 and 1967. • No new drugs developed since the 1980’s • Reoccurrence of TB for two main reasons: 1)HIV/AIDS pandemic 2)Development of drug resistance M. bovis

  7. Reported TB Cases United States, 1982–2012* No. of Cases Year *Updated as of June 10, 2013.

  8. TB MorbidityUnited States, 2007–2012 *Cases per 100,000. Updated as of June 10, 2013.

  9. TB Case Rates,* United States, 2012 D.C. <3.2 (2012 national average) >3.2 *Cases per 100,000.

  10. Map of U.S.-Affiliated Pacific Islands by TB Case Rates,* 2012 Northern Mariana Islands • Guam • Marshall Islands • Palau • Federated States of Micronesia • American Samoa ≤9.9 10–49.9 ≥50 *Cases per 100,000

  11. TB Case Rates,* U.S.-Affiliated Pacific Islands, 2012 *Cases per 100,000

  12. TB Case Rates* by Age Group United States, 1993–2012 Cases per 100,000 Age Group (years) * Updated as of June 10, 2013.

  13. TB Case Rates by Age Group and Race/Ethnicity,*United States, 2012 Cases per 100,000 *All races are non-Hispanic. Persons reporting two or more races accounted for less than 1% of all cases.

  14. Number of TB Cases inU.S.-born vs. Foreign-born Persons, United States, 1993–2012* No. of Cases *Updated as of June 10, 2013

  15. Trends in TB Cases in Foreign-born Persons,United States, 1992 – 2012* No. of Cases Percentage *Updated as of June 10, 2013

  16. Reported TB Cases by Origin and Race/Ethnicity,* United States, 2012 Foreign-born** U.S.-born *All races are non-Hispanic. Persons reporting two or more races accounted for less than 1% of all cases. ** American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander accounted for less than 1% of foreign-born cases and are not shown.

  17. TB Case Rates in U.S.-born vs. Foreign-born Persons, United States, 1993 – 2012* Cases per 100,000 *Updated as of June 10, 2013.

  18. Estimated HIV Coinfection in Persons Reported with TB, United States, 1993 – 2012* % Coinfection *Updated as of June 10, 2013 Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group

  19. Percent of Foreign-born with TB by Time of Residence in U.S. Prior to Diagnosis, 2012 *Foreign-born TB patients for whom information on length of residence in the U.S. prior to diagnosis is unknown or missing

  20. TB Cases by Residence in Correctional Facilities, Age ≥15, United States, 1993-2012* *Updated as of June 10, 2013 Note: Resident of correctional facility at time of TB diagnosis

  21. TB Cases Reported as Homeless in the 12 Months Prior to Diagnosis, Age ≥15, United States, 1993-2012* *Updated as of June 10, 2013 Note: Homeless within past 12 months of TB diagnosis

  22. Transmission of M. tuberculosis • M. tb spread via airborneparticles called dropletnuclei • Expelled when person withinfectious TB coughs, sneezes, shouts, or sings • Transmission occurs when droplet nuclei inhaled and reach the alveoli of the lungs, via nasal passages, respiratory tract, and bronchi

  23. Pathogenesis of TB Infection

  24. Pathogenesis of TB Infection

  25. TB – A Multi-system Infection

  26. Probability TB Will Be Transmitted • Susceptibility of the exposed person • Infectiousness of person with TB (i.e., number of bacilli TB patient expels into the air) • Environmental factors that affect the concentration of M. tb organisms • Proximity, frequency, and duration of exposure (e.g., close contacts) • Can be transmitted from children, though less likely

  27. Latent TB Infection (LTBI) or TB Infection • Granulomas may persist (LTBI), or may break down to produce TB disease • 2 to 8 weeks after infection, LTBI can be detected via TST or interferon-gamma release assay (IGRA) • The immune system is usually able to stop the multiplication of bacilli • Persons with LTBI are not infectious and do not spread organisms to others

  28. Natural History of TB Infection Exposure to TB No infection (70-90%) Infection (10-30%) Latent TB (90%) Active TB (10%) Never develop Active disease Untreated Treated Die within 2 years Survive Die Cured

  29. LTBI Progression to Active TB Disease • LTBI • 10% lifetime risk of active TB disease • 90% lifetime risk of no active TB • 30% lifetime risk if diabetic • 10% risk per year if HIV +

  30. TB Disease • In some, the granulomas break down, bacilli escape and multiply, resulting in TB disease • Can occur soon after infection, or years later • Persons with TB disease are usually infectious and can spread bacteria to others • Positive M. tb culture confirms TB diagnosis

  31. Latent TB vs. Active TB Latent TB (LTBI) (Goal = prevent future active disease) = TB Infection = No Disease = NOT SICK = NOT INFECTIOUS Active TB (Goal = treat to cure, prevent transmission) = TB Infection which has progressed to TB Disease = SICK (usually) = INFECTIOUS if PULMONARY (usually) = NOT INFECTIOUS if not PULMONARY (usually)

  32. LTBI vs. TB Disease

  33. Identifying Who Is At Risk For Infection or Disease • Infection • Foreign Born • Age greater than 65 y/o (usually LTBI) • Homeless • Alcohol use • Disease • Age (very young) • Anything that lowers the immune system

  34. Initial TB Testing • Two methods for detecting M. tb infection: TST and IGRAs • TST and IGRAs help differentiate persons with M. tb infection from those not infected • Negative reaction to either does not exclude diagnosis of TB or LTBI

  35. TST versus IGRA

  36. Initial TB Testing Pro’s and Con’s Cheap 2 visits Human error/bias Variable sensitivity and specificity Reacts with BCG and MOTTS Shortage of supplies Pro’s and Con’s Initial expense higher Single visit Positive and negative control Better sensitivity and specificity Does not react with BCG and most other MOTTS Tuberculin Skin Test (TST) Interferon Gamma Release Assay (IGRA)

  37. Sorting Out TB Infection/Disease • Epidemiology profile • develop a high index of suspicion • TB Test (IGRA or TST) is least helpful • Radiograph • Sputum for AFB smear and culture • Hi Tech diagnostics have a role but only after the above have been considered

  38. Targeting High Risk Patients with High Tech Tools • This is the partnership between the lab and clinician • Clinician has a high index of suspicion for TB • Laboratorian makes sure tools are available and proficiency is assured • Automated NAA testing • Molecular Drug Susceptibility Testing • Interferon Gamma Release Assays

  39. Automated NAA TestGeneXpert (Cepheid) • New platform for TB NAAT • Platform used for other diseases • Technically simple • Performance is excellent • very high specificity • very high sensitivity for smear positive • Provides rapid rifampin susceptibility

  40. GeneXpert

  41. Xpert MTB/RIF assay & GeneXpert instrument

  42. Xpert MTB/RIF assay & GeneXpert

  43. Xpert MTB/RIF assay & GeneXpert Sensitivity and specificity Compared to culture • Sensitivity for AFB+/culture+ 98.2% • Sensitivity for AFB-/culture+ 72.5% • Specificity 99.2% Rifampin resistance detection • Sensitivity – 98% • Specificity – 99%

  44. Universal Genotyping • All TB cultures are now sent to CDC sponsored labs for “fingerprinting” from each state • Goal is to detect clusters

  45. Number and Percent of Unique* andCounty-GENType Clustered** Cases,United States, 2010–2012 *Unique case is a case with a spoligotype and 24-locus locus MIRU-VNTR (GENType) that does not match any other case in that county during the specified 3-year time period ** Two or more cases with matching spoligotype and 24-locus locus MIRU-VNTR (GENType) within a county during the specified 3-year time period

  46. Molecular Detection of Drug Resistance • CDC offers a semi-automated rapid detection of drug resistance in isolates • Using conventional PCR and DNA sequencing • Looks for common mutations associated with drug resistance • The resistance testing will define MDR and XDR

  47. Molecular Detection of Drug Resistance • Drug Resistance Testing • INH • Rifampin • FQ • KAN • AMK • CAP

  48. Primary Anti-TB Drug Resistance,United States, 1993 – 2012* % Resistant *Updated as of June 10, 2013. Note: Based on initial isolates from persons with no prior history of TB. Multidrug resistant TB (MDR TB) is defined as resistance to at least isoniazid and rifampin

  49. Primary Isoniazid Resistance in U.S.-born vs. Foreign-born Persons,United States, 1993 – 2012* % Resistant *Updated as of June 10, 2013. Note: Based on initial isolates from persons with no prior history of TB.

  50. Primary MDR TB in U.S.-born vs. Foreign-born PersonsUnited States, 1993 – 2012* % Resistant *Updated as of June 10, 2013. Note: Based on initial isolates from persons with no prior history of TB. MDR TB defined as resistance to at least isoniazid and rifampin.

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