Primary Care Management of Latent Tuberculosis Infection in the Foreign-Born: Primary Care Management of Latent Tuberculosis Infection in the Foreign-Born Investigators
Carey Jackson MD, MPH University of Washington
Jenny Pang MD, MPH, Seattle-King County Department of Public Health
Nick DeLuca PhD, Centers for Disease Control and Prevention (CDC)
Stacey Bryant RN, Research Coordinator Public Health Seattle & King County
Slide2: Contents
Definitions
Epidemiology
Latent TB Infection Testing (LTBI)
Treatment for Latent TB Infection (LTBI)
Summary
Local Information
Definitions: Definitions
Active TB Disease: Active TB Disease Tubercle bacilli in the body
Usually positive skin test
Infectious (before treatment)
Symptoms of TB
Chest x-ray usually abnormal
Sputum smears and cultures usually positive
An active “case” of TB
Granuloma breaks down and tubercle escape and multiply
Symptoms of Active TB Disease: Symptoms of Active TB Disease
Latent TB Infection (LTBI): Latent TB Infection (LTBI) LTBI is the presence of M. tuberculosis organisms (tubercle bacilli) without symptoms or radiographic evidence of active TB disease
Slide7: Latent TB Infection (LTBI) Tubercle bacilli in the body
Usually positive skin test
NOT infectious
No symptoms
Normal chest X-ray
Sputum smears and cultures are negative
Not a “case” of TB
Epidemiology : Epidemiology
Slide9: 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!
TB Case Rates,* United States, 2006: 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!
Trends in TB Cases in Foreign-born Persons, United States, 1986–2006*: Trends in TB Cases in Foreign-born Persons, United States, 1986–2006* No. of Cases Percentage *Updated as of April 6, 2007. 57% of cases in 2006 were foreign-born
Percentage of TB Cases Among Foreign-born Persons, United States*: Percentage of TB Cases Among Foreign-born Persons, United States* >50% 25%–49% <25% 1996 2006 DC *Updated as of April 6, 2007.
TB Rates in Countries of Birth 2005: TB Rates in Countries of Birth 2005 Per 100,000 Source: World Health Organization
TB Case Rates by Age Group and Sex, United States, 2006: TB Case Rates by Age Group and Sex, United States, 2006 Cases per 100,000
Highest Incidence is in 65+
Percent of Foreign-born with TB by Time of Residence in U.S. Prior to Diagnosis,* 2006: 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!
Countries of Birth of Foreign-born Persons Reported with TB United States, 2006: 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%)
Latent TB Infection Testing: Latent TB Infection Testing
Flow Chart for Latent TB Infection (LTBI) in Primary Care: 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
Who Should Be Tested: Who Should Be Tested Know the TB status of your at risk patients.
Other Groups At High Risk for TB: Other Groups At High Risk for TB
Medical Conditions that Put People at High Risk for TB: Medical Conditions that Put People at High Risk for TB
Who needs repeat LTBI testing?: Who needs repeat LTBI testing? Healthcare workers
Close contacts to infectious TB cases
Frequent travelers to abroad
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.
Reading the Tuberculin Skin Test (TST): Reading the Tuberculin Skin Test (TST) Measure reaction in 48 to 72 hours
Measure induration, not erythema (redness)
Record reaction in millimeters, not “negative” or “positive”
Ensure trained health care professional measures and interprets the TST (PPD)
Interpreting the TST (PPD): Interpreting the TST (PPD) A positive TST (PPD) is determined by
The size of the induration
The patient’s risk factors
Slide25: (Note: the CDC discourages testing of people at low risk for infection.) Interpreting Tuberculin Skin Test Reactions
TB screening for those coming to US: TB screening for those coming to US Refugees and Immigrants
In Country of Origin
Evaluated for active TB ONLY
In the US
Those applying for an adjustment of status are evaluated for LTBI but treatment is NOT mandated
Visitors, students, temporary workers, undocumented
Not evaluated The Immigration Process does not take care of Latent TB Infection (LTBI) for you!
BCG: 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
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 Source: CDC TB Fact Sheet “BCG Vaccine” 2006.
Literature Review on BCG 2006: Literature Review on BCG 2006 1500 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 countries
The effect of the BCG vaccine on TST (PPD) reaction decreases with increasing time since vaccination.
Literature Review on BCG 2006 (cont.): 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.” 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.)
Treatment for Latent Tuberculosis Infection (LTBI): Treatment for Latent Tuberculosis Infection (LTBI)
Who Should be Treated for Latent TB Infection (LTBI)?: 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 therapy
Available to be monitored during the full course of treatment
No 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.)
Risk Factors for Progression from Latent TB Infection (LTBI) to Active TB Disease: Risk Factors for Progression from Latent TB Infection (LTBI) to Active TB Disease Immunosuppression
Lymphoma, leukemia
Diabetes
Renal dialysis
Malnutrition
Silicosis
Gastrectomy/ jejunoileal bypass
Head and neck cancer
HIV + Medical Conditions Your patient’s TB infection may be latent now, but many factors could increase the risk of progression
Slide33: Immunosuppressive agents
Steroids (not inhaled) (prednisone >15 mg/day for 1 month or more)
Cancer chemotherapy
Cyclosporine
Anti-Rheumatics*
Etanercept (Enbrel)
Infliximab (Remicade)
Adalimumab (Humira TM)
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
Case Example of Progression from LTBI to Active TB: Case Example of Progression from LTBI to Active TB Case #1:
68 yo Chinese man with latent TB untreated
Hx of Hepatitis B with low level activity
Family history of colon cancer
Developed adenocarcinoma of the colon and was receiving chemotherapy
Developed hemoptysis and was thought to have a lung metastasis
Bronchoscopy aspirate grew TB
Slide35: Case #2
66 yo Vietnamese female with latent TB (untreated), diabetes inflammatory arthritis, and depression/ PTSD
Developed idiopathic thrombocytopenic purpura and began to have bleeding
Treated with systemic high dose steroids in the hospital and developed milliary TB
Died 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
Current Treatment for LTBI Preferred Regimen: Current Treatment for LTBI Preferred Regimen A minimum of 270 doses must be administered
within 12 months
Alternative Regimens for LTBI: Alternative Regimens for LTBI
No Longer Recommended Regimen for LTBI: 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.
Monitoring of Patients on Treatment for LTBI: Monitoring of Patients on Treatment for LTBI Baseline and monthly laboratory testing not needed except for patients with
HIV infection
Pregnancy or within 3 months post-partum
History of liver disease/heavy alcohol use
Patient on chemotherapy
Evaluate patients monthly for
Adherence to treatment
Symptoms of hepatitis (fatigue, weight loss, nausea, vomiting, jaundice)
Treatment of Patients 35 Years of Age and Older: 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 groups
Use 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
Hepatic Adverse Drug Effects of Isoniazid (INH): Hepatic Adverse Drug Effects of Isoniazid (INH) Frequent (~5%): Liver Enzyme Elevations
Infrequent (~0.1%): Hepatitis
Large Scale Study:
11,141 treated with INH from 1989-1995
11 had hepatitis, no deaths
Overall rate was 1 per 1000 (or 0.1%)
(Nolan CM, Goldberg SV, Buskin SE. JAMA. 1999 Mar 17;281(11):1014-8.)
Patients with Chronic Hepatitis B But No Active Liver Disease: Patients with Chronic Hepatitis B But No Active Liver Disease Yes, they can receive treatment for LTBI
Baseline liver function tests and at 1 month
If 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 abnormal
If any one of the liver function tests exceeds 3-5 times the upper limit of normal at any time, strongly consider stopping therapy
Counseling a Patient with LTBI: Counseling a Patient with LTBI Don’t Say:
“You’ve been “exposed” to TB so you need to be treated.”
Say Instead:
“You have been exposed AND infected with the TB bacteria. But don’t worry…”
Counseling a Patient with LTBI (cont.): Good news:
“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 don’t treat it now it can wake up later and make you very ill and contagious to others.” Counseling a Patient with LTBI (cont.)
Counseling a Patient with LTBI (cont.): Why get treated?
“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.”
“ TB germs are ‘TOUGH bugs’ … so take your medicine correctly and completely.” Counseling a Patient with LTBI (cont.)
Summary : Summary
Meeting the Challenge of LTBI: Meeting the Challenge of LTBI For every patient
Assess TB risk factors
If risk is present, perform TST (PPD)
If TST (PPD) is positive, rule out active TB disease
If active TB disease is ruled out, evaluate as candidate for LTBI treatment
If good candidate, initiate treatment for LTBI
If treatment is initiated, ensure completion
Meeting the Challenge of LTBI (cont.): Latent 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 infection
While the condition in itself is asymptomatic, the risks assumed by ignoring it are substantial Meeting the Challenge of LTBI (cont.)
Slide49: Always include TB in the DDX
“THINK TB” and “TB RISK” Physicians Caring for
At Risk Populations
Acknowledgements: Acknowledgements The following individuals provided consultation and review of this presentation:
Masa Narita MD, TB Controller for Seattle-King County Public Health
John Bernardo, MD – Tuberculosis Control Officer, Massachusetts Department of Public Health
L. 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, Texas
Slide51: Without the help of the following individuals, this project would not have been possible:
Lan Nguyen
Ed Chow
Jessie Wing
Ximena Urrutia-Rojas
Jeff Caballero
Sharon Sharnprapai
References: References 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
DSHS/Public Health Service/CDC. 2006. “TB 101 for Healthcare Providers.” PPT.
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
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/default.htm
References (cont.): Hong, SW. 2001. “Preventing Nosocomial Mycobacterium tuberculosis Transmission in International Settings”. Emerging Infectious Diseases. Vol. 7, No. 2, March-April 2001
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.
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.)
References (cont.): World Health Organization. 2005. Global Health Atlas. Accessed 10-2-06 from: www.who.int/globalatlas/dataQuery/default.asp
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/mm5231a4.htm References (cont.)