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Primary Care Management of Latent Tuberculosis Infection in the Foreign-Born Investigators Carey Jackson MD, MPH University of WashingtonCarey Jackson.

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Presentation on theme: "Primary Care Management of Latent Tuberculosis Infection in the Foreign-Born Investigators Carey Jackson MD, MPH University of WashingtonCarey Jackson."— Presentation transcript:

1 Primary Care Management of Latent Tuberculosis Infection in the Foreign-Born Investigators Carey Jackson MD, MPH University of WashingtonCarey Jackson MD, MPH University of Washington Jenny Pang MD, MPH, Seattle-King County Department of Public HealthJenny Pang MD, MPH, Seattle-King County Department of Public Health Nick DeLuca PhD, Centers for Disease Control and Prevention (CDC)Nick DeLuca PhD, Centers for Disease Control and Prevention (CDC) Stacey Bryant RN, Research CoordinatorStacey Bryant RN, Research Coordinator Public Health Seattle & King County

2 Contents 1.Definitions 2.Epidemiology 3.Latent TB Infection Testing (LTBI) 4.Treatment for Latent TB Infection (LTBI) 5.Summary 6.Local Information

3 Active TB Disease Tubercle bacilli in the bodyTubercle bacilli in the body Usually positive skin testUsually positive skin test Infectious (before treatment)Infectious (before treatment) Symptoms of TBSymptoms of TB Chest x-ray usually abnormalChest x-ray usually abnormal Sputum smears and cultures usually positiveSputum smears and cultures usually positive An active case of TBAn active case of TB Granuloma breaks down and tubercle escape and multiply

4 Symptoms of Active TB Disease Systemic Symptoms Pulmonary Symptoms Weight lossWeight loss FatigueFatigue FeverFever Night sweatsNight sweats ChillsChills Coughing (duration of 3 weeks)Coughing (duration of 3 weeks) Chest pain (when breathing or coughing)Chest pain (when breathing or coughing) HemoptysisHemoptysis

5 Latent TB Infection (LTBI) LTBI is the presence of M. tuberculosis organisms (tubercle bacilli) without symptoms or radiographic evidence of active TB disease

6 Latent TB Infection (LTBI) Tubercle bacilli in the bodyTubercle bacilli in the body Usually positive skin testUsually positive skin test NOT infectiousNOT infectious No symptomsNo symptoms Normal chest X-rayNormal chest X-ray Sputum smears and cultures are negativeSputum smears and cultures are negative Not a case of TBNot a case of TB

7 Epidemiology

8 Source: WHO Stop TB Department, website: http://www.who.int/globalatlas/interactiveMapping/MainFrame2.asp (Active TB all forms [per 100,000 population per year]) Active TB Incidence Worldwide, 2005 2 billion infected with LTBI!

9 TB Case Rates,* United States, 2006 < 3.5 (year 2000 target) 3.6–4.6 > 4.6 (national average) D.C. *Cases per 100,000. 15 million infected with LTBI!

10 Trends in TB Cases in Foreign-born Persons, United States, 1986–2006* No. of CasesPercentage *Updated as of April 6, 2007. 57% of cases in 2006 were foreign-born

11 Percentage of TB Cases Among Foreign- born Persons, United States* >50% 25%–49% <25% 19962006 DC *Updated as of April 6, 2007.

12 TB Rates in Countries of Birth 2005 Per 100,000 Source: World Health Organization

13 TB Case Rates by Age Group and Sex, United States, 2006 Cases per 100,000 Highest Incidence is in 65+

14 Percent of Foreign-born with TB by Time of Residence in U.S. Prior to Diagnosis,* 2006 *Data exclude foreign-born TB patients for when length of residence in the U.S. prior to diagnosis was unknown. Over HALF of active TB cases in the Foreign-Born have been in the US more than 5 years!

15 Countries of Birth of Foreign-born Persons Reported with TB United States, 2006 Mexico (25%) Philippines (11%) Viet Nam (8%) India (7%) China (5%) Haiti (3%) Guatemala (3%) Other Countries (38%)

16 Latent TB Infection Testing

17 Flow Chart for Latent TB Infection (LTBI) in Primary Care Patient with risk factors for LTBI Negative No treatment; Document status in medical record Candidate for LTBI Treatment Treatment of active TB by TB clinic Refer to TB clinic for evaluation of active TB Abnormal Positive Negative Positive Normal TST (PPD ) History/HIV risk, physical exam, chest x-ray Note: Evaluate patient for LTBI testing and treatment regardless of BCG status Rule out active TB disease before treatment for LTBI is started

18 Who Should Be Tested Know the TB status of your at risk patients. Who is considered at risk? What countries are considered TB endemic? Foreign born patients from TB endemic countries, where prior TB exposure is almost certain All of Asia except JapanAll of Asia except Japan All of Central and South AmericaAll of Central and South America All of AfricaAll of Africa All of Eastern EuropeAll of Eastern Europe (Yes, that is practically the whole world)

19 Other Groups At High Risk for TB Groups Close contacts of Active TB casesClose contacts of Active TB cases Usually taken care of by TB clinicUsually taken care of by TB clinic Healthcare workers who serve high risk clientsHealthcare workers who serve high risk clients Residents & employees of congregate settingsResidents & employees of congregate settings Medically underserved/low-income groups:Medically underserved/low-income groups: HomelessHomeless Migrant workersMigrant workers Street drug usersStreet drug users Children with parents who have risk factorsChildren with parents who have risk factors

20 Medical Conditions that Put People at High Risk for TB Medical Conditions HIV + Renal dialysis Immunocompromised (>15 mg prednisone qd for 1 month or more) Diabetes mellitus Silicosis Cancer of the head and neck Hematologic and reticuloendothelial diseases Intestinal bypass or gastrectomy Chronic malabsorption syndromes Low body weight Organ Transplant

21 Who needs repeat LTBI testing? 1)Healthcare workers 2)Close contacts to infectious TB cases 3)Frequent travelers to abroad If baseline TST is negative, consider retesting your patients that have extended travel to high risk areas.If baseline TST is negative, consider retesting your patients that have extended travel to high risk areas. Do symptom review upon return and possibly retesting 8-10 week after return.Do symptom review upon return and possibly retesting 8-10 week after return.

22 Reading the Tuberculin Skin Test (TST) Measure reaction in 48 to 72 hoursMeasure reaction in 48 to 72 hours Measure induration, not erythema (redness)Measure induration, not erythema (redness) Record reaction in millimeters, not negative or positiveRecord reaction in millimeters, not negative or positive Ensure trained health care professional measures and interprets the TST (PPD)Ensure trained health care professional measures and interprets the TST (PPD)

23 Interpreting the TST (PPD) A positive TST (PPD) is determined by The size of the indurationThe size of the induration The patients risk factorsThe patients risk factors

24 (Note: the CDC discourages testing of people at low risk for infection.) Interpreting Tuberculin Skin Test Reactions 5 mm or greater 10 mm or greater 15 mm or greater HIV positive personsHIV positive persons Recent contacts of persons with active tuberculosisRecent contacts of persons with active tuberculosis Fibrotic changes on chest radiograph, consistent with tuberculosisFibrotic changes on chest radiograph, consistent with tuberculosis Patients with organ transplants and other immunosuppressed patientsPatients with organ transplants and other immunosuppressed patients Immigrants from high- prevalence areasImmigrants from high- prevalence areas Injection drug usersInjection drug users Residents and employees* of high-risk congregate settingsResidents and employees* of high-risk congregate settings Personnel in mycobacteriology laboratoriesPersonnel in mycobacteriology laboratories Persons with clinical conditions that place them at high riskPersons with clinical conditions that place them at high risk Children: <4 years of age; all exposed to adults at high-riskChildren: <4 years of age; all exposed to adults at high-risk No known risk factors

25 Interpreting IGRAs 1) Not entirely sensitive to detect TB-- about 70% sensitive and >90% specific1) Not entirely sensitive to detect TB-- about 70% sensitive and >90% specific 2) Cannot distinguish latent TB from active TB2) Cannot distinguish latent TB from active TB 3)For LTBI---Useful because of specificity of assay to distinguish a false positive TST from a true positive in testing a foreign-born population where BCG vaccination is routinely used.3)For LTBI---Useful because of specificity of assay to distinguish a false positive TST from a true positive in testing a foreign-born population where BCG vaccination is routinely used.

26 Interpreting IGRAs 4)In low prevalence LTBI populations, such has health care workers born in the US--the jury is still out to whether using these assay is feasible and cost effective4)In low prevalence LTBI populations, such has health care workers born in the US--the jury is still out to whether using these assay is feasible and cost effective a) CDC is studying this question currently through TBESC b) preliminary data shows that there could be a reversion from QFN positive to QFN negative and vice versa with serial testing over time a) CDC is studying this question currently through TBESC b) preliminary data shows that there could be a reversion from QFN positive to QFN negative and vice versa with serial testing over time

27 Interpreting IGRAs 5) ? MAI distinction--maybe, but not well studied. 5) ? MAI distinction--maybe, but not well studied. 6) Discordance in testing someone for LTBI---- TST negative and QFN positive-- No one knows what will happen to these patients. A long term follow-up study needs to see if TB develops in these patients. 6) Discordance in testing someone for LTBI---- TST negative and QFN positive-- No one knows what will happen to these patients. A long term follow-up study needs to see if TB develops in these patients. 7) Elispot is labor intensive and require processing the same day. Current QuantiFERON -TB In Tube does not. It requires an incubator, if specimen is not processed the same day.7) Elispot is labor intensive and require processing the same day. Current QuantiFERON -TB In Tube does not. It requires an incubator, if specimen is not processed the same day.

28 TB screening for those coming to US 1)Refugees and Immigrants In Country of Origin Evaluated for active TB ONLYEvaluated for active TB ONLY In the US Those applying for an adjustment of status are evaluated for LTBI but treatment is NOT mandatedThose applying for an adjustment of status are evaluated for LTBI but treatment is NOT mandated 2)Visitors, students, temporary workers, undocumented Not evaluated The Immigration Process does not take care of Latent TB Infection (LTBI) for you!

29 BCG Should persons who have been vaccinated with BCG (Bacille Calmette-Guerin) be tested for LTBI According to CDC guidelines, persons who have received BCG should be tested for LTBI as otherwise indicated According to CDC guidelines, persons who have received BCG should be tested for LTBI as otherwise indicated How should the results be interpreted? Positive TST should be assumed to be due to TB infection, not BCG, and treatment should be recommended, unless contraindicated Positive TST should be assumed to be due to TB infection, not BCG, and treatment should be recommended, unless contraindicated Source: CDC TB Fact Sheet BCG Vaccine 2006.

30 Literature Review on BCG 2006 1500 papers reviewed from 1980-20051500 papers reviewed from 1980-2005 Data demonstrate that the TST (PPD) performs well on BCG vaccinated adult (15+) patients and on patients from high and intermediate incidence countriesData demonstrate that the TST (PPD) performs well on BCG vaccinated adult (15+) patients and on patients from high and intermediate incidence countries The effect of the BCG vaccine on TST (PPD) reaction decreases with increasing time since vaccination.The effect of the BCG vaccine on TST (PPD) reaction decreases with increasing time since vaccination.

31 Conclusion: Adults (15+) from intermediate and high-incidence countries are at high risk for LTBI and the results of tuberculin testing can be interpreted in the same manner, regardless of vaccination status.Adults (15+) from intermediate and high-incidence countries are at high risk for LTBI and the results of tuberculin testing can be interpreted in the same manner, regardless of vaccination status. Source: Joos, TJ et al. 2006. Tuberculin reactivity in bacille Calmette-Guerin vaccinated populations: a compilation of international data. The International Journal of Tuberculosis and Lung Disease, Volume 10, Number 8, August 2006. Literature Review on BCG 2006 (cont.)

32 Treatment for Latent Tuberculosis Infection (LTBI)

33 Who Should be Treated for Latent TB Infection (LTBI)? Anyone who has been diagnosed with latent TB infection is a candidate for treatment, if they also fulfill the following criteria: Willing and able to complete a full course of therapyWilling and able to complete a full course of therapy Available to be monitored during the full course of treatmentAvailable to be monitored during the full course of treatment No medical contraindications such as active liver diseaseNo medical contraindications such as active liver disease (Note: careful assessment to rule out the possibility of active TB disease is always necessary before treatment for LTBI is started.)

34 Risk Factors for Progression from Latent TB Infection (LTBI) to Active TB Disease ImmunosuppressionImmunosuppression Lymphoma, leukemiaLymphoma, leukemia DiabetesDiabetes Renal dialysisRenal dialysis MalnutritionMalnutrition SilicosisSilicosis Gastrectomy/ jejunoileal bypassGastrectomy/ jejunoileal bypass Head and neck cancerHead and neck cancer HIV +HIV + Medical Conditions Your patients TB infection may be latent now, but many factors could increase the risk of progression

35 Immunosuppressive agents Steroids (not inhaled) (prednisone >15 mg/day for 1 month or more)Steroids (not inhaled) (prednisone >15 mg/day for 1 month or more) Cancer chemotherapyCancer chemotherapy CyclosporineCyclosporine Anti-Rheumatics*Anti-Rheumatics* Etanercept (Enbrel)Etanercept (Enbrel) Infliximab (Remicade)Infliximab (Remicade) Adalimumab (Humira TM)Adalimumab (Humira TM) Anakinra (Kineret)Anakinra (Kineret) Risk Factors for Progression from Latent TB Infection (LTBI) to Active TB Disease (cont.) * Brassard, P. 2006. Antirheumatics Drugs and the Risk of Tuberculosis. CID 2006:43 (15 September). Drugs

36 Case Example of Progression from LTBI to Active TB Case #1: 68 yo Chinese man with latent TB untreated68 yo Chinese man with latent TB untreated Hx of Hepatitis B with low level activityHx of Hepatitis B with low level activity Family history of colon cancerFamily history of colon cancer Developed adenocarcinoma of the colon and was receiving chemotherapyDeveloped adenocarcinoma of the colon and was receiving chemotherapy Developed hemoptysis and was thought to have a lung metastasisDeveloped hemoptysis and was thought to have a lung metastasis Bronchoscopy aspirate grew TBBronchoscopy aspirate grew TB

37 Case #2 66 yo Vietnamese female with latent TB (untreated), diabetes inflammatory arthritis, and depression/ PTSD66 yo Vietnamese female with latent TB (untreated), diabetes inflammatory arthritis, and depression/ PTSD Developed idiopathic thrombocytopenic purpura and began to have bleedingDeveloped idiopathic thrombocytopenic purpura and began to have bleeding Treated with systemic high dose steroids in the hospital and developed milliary TBTreated with systemic high dose steroids in the hospital and developed milliary TB Died of complicationsDied of complications Source: from practice of PI, Carey Jackson, MD. Internal Medicine. International Clinic, Harborview Medical Center, Seattle, Washington. Case Example of Progression from LTBI to Active TB

38 Current Treatment for LTBI Preferred Regimen DrugDoseFrequencyDuration Isoniazid (INH) 300 mg Daily 9 months A minimum of 270 doses must be administered within 12 months

39 Alternative Regimens for LTBI DrugDoseFrequencyDurationOther Isoniazid 900 mg Twice weekly 9 months DOT Isoniazid 300 mg Daily 6 months Isoniazid 900 mg Twice weekly 6 months DOT Rifampin 600 mg Daily 4 months

40 No Longer Recommended Regimen for LTBI Rifampin plus pyrazinamide x 2 months This regimen has been associated with increased risk of severe hepatic injury and death Source: Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection---United States, 2003; MMWR, August 8, 2003 / 52(31);735-739.

41 Monitoring of Patients on Treatment for LTBI Baseline and monthly laboratory testing not needed except for patients withBaseline and monthly laboratory testing not needed except for patients with HIV infectionHIV infection Pregnancy or within 3 months post-partumPregnancy or within 3 months post-partum History of liver disease/heavy alcohol useHistory of liver disease/heavy alcohol use Patient on chemotherapyPatient on chemotherapy Evaluate patients monthly forEvaluate patients monthly for Adherence to treatmentAdherence to treatment Symptoms of hepatitis (fatigue, weight loss, nausea, vomiting, jaundice)Symptoms of hepatitis (fatigue, weight loss, nausea, vomiting, jaundice)

42 Treatment of Patients 35 Years of Age and Older The CDC changed its guideline in 2000 and now encourages treatment of LTBI in all age groupsThe CDC changed its guideline in 2000 and now encourages treatment of LTBI in all age groups Use clinical judgment in treating older patientsUse clinical judgment in treating older patients * CDC/ATS Guidelines: Morbidity and Mortality Weekly Report (MMWR), Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection. June 9, 2000

43 Hepatic Adverse Drug Effects of Isoniazid (INH) Frequent (~5%): Liver Enzyme ElevationsFrequent (~5%): Liver Enzyme Elevations Infrequent (~0.1%): HepatitisInfrequent (~0.1%): Hepatitis Large Scale Study: 11,141 treated with INH from 1989-199511,141 treated with INH from 1989-1995 11 had hepatitis, no deaths11 had hepatitis, no deaths Overall rate was 1 per 1000 (or 0.1%)Overall rate was 1 per 1000 (or 0.1%) (Nolan CM, Goldberg SV, Buskin SE. JAMA. 1999 Mar 17;281(11):1014-8.)

44 Patients with Chronic Hepatitis B But No Active Liver Disease Yes, they can receive treatment for LTBI Baseline liver function tests and at 1 monthBaseline liver function tests and at 1 month If the tests are normal at 1 month, no further testing is necessary unless symptoms developIf the tests are normal at 1 month, no further testing is necessary unless symptoms develop If the tests are elevated at 1 month, continue monthly testing as long as levels are abnormalIf the tests are elevated at 1 month, continue monthly testing as long as levels are abnormal If any one of the liver function tests exceeds 3-5 times the upper limit of normal at any time, strongly consider stopping therapyIf any one of the liver function tests exceeds 3-5 times the upper limit of normal at any time, strongly consider stopping therapy

45 Counseling a Patient with LTBI Dont Say: Youve been exposed to TB so you need to be treated.Youve been exposed to TB so you need to be treated. Say Instead: You have been exposed AND infected with the TB bacteria. But dont worry…You have been exposed AND infected with the TB bacteria. But dont worry…

46 Good news: You do not have the disease and you are not contagious to anyone.You do not have the disease and you are not contagious to anyone. Bad news: However, it is sleeping in your body and if you dont treat it now it can wake up later and make you very ill and contagious to others.However, it is sleeping in your body and if you dont treat it now it can wake up later and make you very ill and contagious to others. Counseling a Patient with LTBI (cont.)

47 Why get treated? Treatment will prevent future disease and protect you and those close to you.Treatment will prevent future disease and protect you and those close to you.Warning Taking medication for 9 months is a long time but it takes that long to kill all the TB germs.Taking medication for 9 months is a long time but it takes that long to kill all the TB germs. TB germs are TOUGH bugs … so take your medicine correctly and completely. TB germs are TOUGH bugs … so take your medicine correctly and completely. Counseling a Patient with LTBI (cont.)

48 Summary

49 Meeting the Challenge of LTBI For every patient Assess TB risk factorsAssess TB risk factors If risk is present, perform TST (PPD)If risk is present, perform TST (PPD) If TST (PPD) is positive, rule out active TB diseaseIf TST (PPD) is positive, rule out active TB disease If active TB disease is ruled out, evaluate as candidate for LTBI treatmentIf active TB disease is ruled out, evaluate as candidate for LTBI treatment If good candidate, initiate treatment for LTBIIf good candidate, initiate treatment for LTBI If treatment is initiated, ensure completionIf treatment is initiated, ensure completion

50 Latent TB Infection should be treated as a condition in itself which is a precursor to a serious and potentially fatal diseaseLatent TB Infection should be treated as a condition in itself which is a precursor to a serious and potentially fatal disease Much the same way we treat hypertension as a condition in itself because it significantly heightens risk of heart disease, renal failure, and stroke or place infants in car seats because of the significant risk of injury without them, so should we approach latent TB infectionMuch the same way we treat hypertension as a condition in itself because it significantly heightens risk of heart disease, renal failure, and stroke or place infants in car seats because of the significant risk of injury without them, so should we approach latent TB infection While the condition in itself is asymptomatic, the risks assumed by ignoring it are substantialWhile the condition in itself is asymptomatic, the risks assumed by ignoring it are substantial Meeting the Challenge of LTBI (cont.)

51 Always include TB in the DDXAlways include TB in the DDX THINK TB and TB RISKTHINK TB and TB RISK Physicians Caring for At Risk Populations

52 Acknowledgements The following individuals provided consultation and review of this presentation: Masa Narita MD, TB Controller for Seattle-King County Public HealthMasa Narita MD, TB Controller for Seattle-King County Public Health John Bernardo, MD – Tuberculosis Control Officer, Massachusetts Department of Public HealthJohn Bernardo, MD – Tuberculosis Control Officer, Massachusetts Department of Public Health L. Masae Kawamura - MD, Director TB Control Section, San Francisco Department of Public HealthL. Masae Kawamura - MD, Director TB Control Section, San Francisco Department of Public Health Stephen Weis, DO –Director of Tuberculosis and Refugee Services for Tarrant County Health Department, TexasStephen Weis, DO –Director of Tuberculosis and Refugee Services for Tarrant County Health Department, Texas

53 Without the help of the following individuals, this project would not have been possible: Lan NguyenLan Nguyen Ed ChowEd Chow Jessie WingJessie Wing Ximena Urrutia-RojasXimena Urrutia-Rojas Jeff CaballeroJeff Caballero Sharon SharnprapaiSharon Sharnprapai

54 References 1.CDC Fact Sheet. BCG Vaccine. 2006. In Division of TB Elimination Fact Sheets. Retrieved 11-22-06 from: www.cdc.gov/nchstp/tb/pubs/tbfactsheets/250120.htm 2.DSHS/Public Health Service/CDC. 2006. TB 101 for Healthcare Providers. PPT. 3.DTBE/CDC. 2005. Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection. In Division of Tuberculosis Elimination. Retrieved 9-16-06 from: www.cdc.gov/nchstp/tb/pubs/slidesets/slides.htm 4.DTBE/CDC. 2005. Tuberculosis in the United States: National Surveillance System Highlights from 2004. In Division of Tuberculosis Elimination. Retrieved 9-16-06 from: www.cdc.gov/nchstp/tb/pubs/slidesets/surv/surv2004/d efault.htm

55 5.Hong, SW. 2001. Preventing Nosocomial Mycobacterium tuberculosis Transmission in International Settings. Emerging Infectious Diseases. Vol. 7, No. 2, March-April 2001 6.Joos, TJ; Miller WC; Murdoch, DM. 2006. Tuberculin reactivity in bacille Calmette-Guerin vaccinated populations: a compilation of international data. The International Journal of Tuberculosis and Lung Disease, Volume 10, Number 8, August 2006, pp. 883-891. 7.Kawamura, L. Masae. 2006. Targeted Testing and Treatment of Tuberculosis. In Francis J. Curry National Tuberculosis Center. Retrieved 9-16-06 from: www.nationaltbcenter.edu/testing_ltbi/presentation.cfm References (cont.)

56 8.World Health Organization. 2005. Global Health Atlas. Accessed 10-2-06 from: www.who.int/globalatlas/dataQuery/default.asp 9.Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection---United States, 2003 MMWR, August 8, 2003 / 52(31);735-739. Assessed 2-2-07 from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5 231a4.htm References (cont.)


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