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1Public Health Seattle & King County Primary Care Management of Latent Tuberculosis Infection in the Foreign-BornInvestigatorsCarey Jackson MD, MPH University of WashingtonJenny Pang MD, MPH, Seattle-King County Department of Public HealthNick DeLuca PhD, Centers for Disease Control and Prevention (CDC)Stacey Bryant RN, Research CoordinatorMain Points of Presentation:TB is a global problem and TB is endemic in your patients’ countries of origin.More and more, TB in the US is a disease of the foreign bornTB is a problem locally for your patient populationIn immigrants here > 5 yearsIn 65+ populationWhether from China or from Hong KongLTBI testing and treatment is part of primary careYou should know the TB status of your FB patients from endemic areas andTreat your patient’s LTBI if patient is a good candidate for treatment completionImmigration and Public Health are not able to take care of LTBI for you and your patients.Many factors that go along with aging can increase your patient’s risk for progression from latent to active TB; treat now to prevent progression later.Serious side effects with INH treatment, such as hepatitis, are rare and most patients do not require baseline LFTs but should be evaluated monthly.Make sure they know what Public Health offers in their area: LTBI testing and treatment (HI, TX, Boston) or not (CA, WA).Public Health Seattle & King County
2Contents Definitions Epidemiology Latent TB Infection Testing (LTBI) Treatment for Latent TB Infection (LTBI)SummaryLocal InformationThis talk focuses on Latent TB and we will cover the following topics: basic definitions, national and local epidemiology, testing and treatment issues and then some local TB clinic information.
3Active TB Disease Tubercle bacilli in the body Usually positive skin testInfectious (before treatment)Symptoms of TBChest x-ray usually abnormalSputum smears and cultures usually positiveAn active “case” of TBMain Point: slides 1-2 present a quick overview of the definition and symptoms of active disease. Go over quickly as focus of presentation is LTBI.#1Granuloma breaks down and tubercle escape and multiply
4Symptoms of Active TB Disease Systemic SymptomsPulmonary SymptomsWeight lossFatigueFeverNight sweatsChillsCoughing (duration of ≥ 3 weeks)Chest pain (when breathing or coughing)Hemoptysis
5Latent TB Infection (LTBI) LTBI is the presence of M. tuberculosis organisms (tubercle bacilli) without symptoms or radiographic evidence of active TB disease#3
6Latent TB Infection (LTBI) Tubercle bacilli in the bodyUsually positive skin testNOT infectiousNo symptomsNormal chest X-raySputum smears and cultures are negativeNot a “case” of TBMain Point: quick review of differences between latent and active TB.#1
8Active TB Incidence Worldwide, 2005 2 billion infected with LTBI! Main Point: TB is endemic over most of the world including your foreign born patients’ countries of origin.Supplement: You can see that with the exception of North America, Western Europe, Australia and Japan, it is a global problem.This is the reason it is relevant (in this clinic or for this group or for your population), is that …(point out area where clinic population comes from)#4(Active TB all forms [per 100,000 population per year])Source: WHO Stop TB Department,website:
9TB Case Rates,* United States, 2006 D.C.TB Case Rates, United States, This map shows TB rates for Twenty-six states had a rate of less than or equal to 3.5 TB cases per 100,000, the interim goal for the year 2000 established by the Advisory Council for the Elimination of Tuberculosis. This group of states has remained fairly constant over the last decade; five states (CT, MI, NM, OR, and PA) joined the group in 2000, one state (MO) joined the group in 2001 (also in 1998 for one year only), and one state (KY) joined the group in Twelve states and the District of Columbia (DC) reported a rate above the 2006 national average of 4.6 cases per 100,000: AK, AZ, CA, FL, GA, HI, LA, NJ, NY, SC, TN and TX. These 12 states and DC accounted for 65% of the national total and experienced substantial overall decreases in cases and rates from 1992 through 2006.< 3.5 (year 2000 target)15 million infected with LTBI!3.6–4.6> 4.6 (national average)*Cases per 100,000.
10Trends in TB Cases in Foreign-born Persons, United States, 1986–2006* No. of CasesPercentageTrends in TB Cases in Foreign-born Persons, United States, 1986– This slide shows trends in TB cases in foreign-born persons in the United States from 1986, when information on country of birth was first reported by all areas submitting reports to CDC, through The number of TB cases in foreign-born persons increased from nearly 5,000 in 1986 to 7,000–8,000 each year since The percentage of TB cases accounted for by foreign-born persons increased from 22% in 1986 to 57% in 2006.57% of cases in 2006 were foreign-born*Updated as of April 6, 2007.
11Percentage of TB Cases Among Foreign-born Persons, United States* 19962006DCDCPercentage of TB Cases Among Foreign-born Persons, United States, 1996 and The percentage range of the total number of TB cases that occurred in foreign-born persons in each state is highlighted for 1996 and 2006 in these side-by-side maps. The number of states with at least 50% of cases in the foreign-born increased from nine in 1996 to 27 in The number of states with at least 70% of cases in the foreign-born increased from two (HI and VT) in 1996 to eleven (CA, HI, IA, MA, MN, NE, NH, NJ, NY, RI and WA) in 2006 (not shown on slide).>50%25%–49%<25%*Updated as of April 6, 2007.
12TB Rates in Countries of Birth 2005 Per 100,000Source: World Health Organization
13TB Case Rates by Age Group and Sex, United States, 2006 Cases per 100,000TB Case Rates by Age Group and Sex, United States, This slide graphs the TB rates in 2006 by age group and sex. It shows that rates tended to increase with age, ranging from a low of less than 2 per 100,000 in children to a high of approximately 10 per 100,000 in men 65 years and older. The rates in men 45 years and older were more than twice those in same-age women.Highest Incidence is in 65+
14Percent of Foreign-born with TB by Time of Residence in U. S Percent of Foreign-born with TB by Time of Residence in U.S. Prior to Diagnosis,* 2006Over HALF of active TB cases in the Foreign-Born have been in the US more than 5 years!Percent of Foreign-born with TB by Time of Residence in U.S. Prior to Diagnosis, The length of U.S. residence among foreign-born persons prior to their TB diagnosis in 2006 is shown in these stacked bars. Overall, 21% had been in the United States for less than 1 year, 23% between 1 and 4 years, and 56% for at least 5 years. The distribution is also shown for the top three countries of birth: Mexico, the Philippines, and Viet Nam. Among persons born in Mexico, 17% had been in the United States for less than 1 year, 22% between 1 and 4 years, and 61% for at least 5 years. Among persons born in the Philippines, 26% had been in the United States for less than 1 year, 18% between 1 and 4 years, and 56% for at least 5 years. Among persons born in Viet Nam, 24% had been in the United States for less than 1 year, 14% between 1 and 4 years, and 62% for at least 5 years.*Data exclude foreign-born TB patients for when length of residence in the U.S. prior to diagnosis was unknown.
15Countries of Birth of Foreign-born Persons Reported with TB United States, 2006 Mexico(25%)OtherCountries(38%)Countries of Birth of Foreign-born Persons Reported with TB, United States, This slide shows the overall distribution of the countries of birth of foreign-born persons reported with TB in 2006, with the top seven highlighted. The list of countries has remained relatively constant since 1986, when information on country of birth was first reported by all areas submitting reports to CDC. However, for 2006, Guatemala replaced South Korea in the list of countries contributing the highest percentages of foreign-born patients. The seven top countries accounted for 62% of the total, with Mexico accounting for 25%; the Philippines, 11%; Viet Nam, 8%; India, 7%; China, 5%; Haiti, 3%; and Guatemala, 3%. Persons from more than 135 other countries each accounted for 2% or less of the total, but altogether accounted for 38% of foreign-born persons reported with TB.Philippines(11%)Guatemala(3%)Viet Nam(8%)Haiti(3%)India(7%)China(5%)
17Flow Chart for Latent TB Infection (LTBI) in Primary Care Patient with risk factors for LTBINote: Evaluate patient for LTBI testing and treatment regardless of BCG statusRule out active TB disease before treatment for LTBI is startedTST (PPD)NegativePositiveNo treatment; Document status in medical recordHistory/HIV risk, physical exam, chest x-rayNormalAbnormalRefer to TB clinic for evaluation of active TBPositiveTreatment of active TB by TB clinicCandidate forLTBI TreatmentNegative
18Who 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 fromTB endemic countries, where prior TB exposure is almost certainAll of Asia except JapanAll of Central and South AmericaAll of AfricaAll of Eastern Europe(Yes, that is practically the whole world)Main Point: If your patient was born in a TB endemic country, his/her TB status should be known and documented in a designated place in their medical record. Your patients were born in __________, a TB endemic country.#15
19Other Groups At High Risk for TB Close contacts of Active TB casesUsually taken care of by TB clinicHealthcare workers who serve high risk clientsResidents & employees of congregate settingsMedically underserved/low-income groups:HomelessMigrant workersStreet drug usersChildren with parents who have risk factors
20Medical Conditions that Put People at High Risk for TB HIV +Renal dialysisImmunocompromised (>15 mg prednisone qd for 1 month or more)Diabetes mellitusSilicosisCancer of the head and neckHematologic and reticuloendothelial diseasesIntestinal bypass or gastrectomyChronic malabsorption syndromesLow body weightOrgan Transplant
21Who needs repeat LTBI testing? Healthcare workersClose contacts to infectious TB casesFrequent travelers to abroadIf 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.Main point: retesting is a judgment call, but extended travel to high risk areas should prompt retesting.Discuss that it is subjective and a judgment call on their part; 2 weeks to a village with TB patients should prompt retesting; 2 months in a tourist area of Hong Kong may not.If they are negative and they say “I’m going to make the Hajj, or I’m going to Cambodia”, when they come back and have had a significant risk of exposure, they need to be retested about 3 months or so after they come back to see if they have now have positive status.
22Reading the Tuberculin Skin Test (TST) Measure reaction in 48 to 72 hoursMeasure induration, not erythema (redness)Record reaction in millimeters, not “negative” or “positive”Ensure trained health care professional measures and interprets the TST (PPD)Main Point: quick basic review on reading TST. Induration vs. redness. Document in mm not just negative or positive.#16
23Interpreting the TST (PPD) A positive TST (PPD) is determined byThe size of the indurationThe patient’s risk factors#16
24Interpreting Tuberculin Skin Test Reactions 5 mm or greater10 mm or greater15 mm or greaterHIV positive personsRecent contacts of persons with active tuberculosisFibrotic changes on chest radiograph, consistent with tuberculosisPatients with organ transplants and other immunosuppressed patientsImmigrants from high-prevalence areasInjection drug usersResidents and employees* of high-risk congregate settingsPersonnel in mycobacteriology laboratoriesPersons with clinical conditions that place them at high riskChildren: <4 years of age; all exposed to adults at high-riskNo known risk factorsMain Point: quick review with emphasis on 10 mm result for foreign born from high prevalence areas.#17(Note: the CDC discourages testing of people at low risk for infection.)
25Interpreting IGRA’s1) Not entirely sensitive to detect TB--about 70% sensitive and >90% specific2) Cannot distinguish latent TB from active TB3)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. #16
26Interpreting IGRA’s4)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#16
27Interpreting IGRA’s 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.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.#16
28TB screening for those coming to US Refugees and ImmigrantsIn Country of OriginEvaluated for active TB ONLYIn the USThose applying for an adjustment of status are evaluated for LTBI but treatment is NOT mandatedVisitors, students, temporary workers, undocumentedNot evaluatedMain point: Many think that the immigration process takes care (or should take care) of LTBI but this is not the case.#18,19The Immigration Process does not take care of Latent TB Infection (LTBI) for you!
29BCGShould persons who have been vaccinated with BCG (Bacille Calmette-Guerin) be tested for LTBIAccording to CDC guidelines, persons who have received BCG should be tested for LTBI as otherwise indicatedHow should the results be interpreted?Positive TST should be assumed to be due to TB infection, not BCG, and treatment should be recommended, unless contraindicatedMain Point: CDC guideline regarding BCG.#20-21Source: CDC TB Fact Sheet “BCG Vaccine” 2006.
30Literature Review on BCG 2006 1500 papers reviewed fromData demonstrate that the TST (PPD) performs well on BCG vaccinated adult (15+) patients and on patients from high and intermediate incidence countriesThe effect of the BCG vaccine on TST (PPD) reaction decreases with increasing time since vaccination.
31Literature 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.”Main Point: studies support CDC guideline of discarding BCG as a factor in foreign born patients from intermediate and high incidence countries.Supplemental: way to approach with your patients: requires a certain amount of diplomacy explaining why you are discarding BCG: “wanes over time and if I test you today and you got BCG when you are 5, and you’re 50 and you have a 21 mm reaction it is not likely it is BCG, and I’m pretty sure of that.” Patients may say, I’ve gotten this, you don’t understand how medicine is practiced in our part of the world, we don’t really need this.” And then you have to be really really clear: possibly explain economics and politics of TB management in their country vs. here and why it makes sense to treat LTBI here.We did not include a slide on QFT-Gold the new blood test that is not affected by BCG because it is not widely available yet but this would be a good place to touch on it quickly, especially if your area is more likely to have it generally available to providers in the next year.Source: Joos, TJ et al “Tuberculin reactivity in bacille Calmette-Guerin vaccinated populations: a compilationof international data.” The International Journal of Tuberculosis and Lung Disease, Volume 10, Number 8, August 2006.
32Treatment for Latent Tuberculosis Infection (LTBI)
33Who 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 therapyAvailable to be monitored during the full course of treatmentNo 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.)Main Point: what makes a good candidate for LTBI treatment.Supplement: If patient if presenting with multiple and more urgent problems, approach as one of the problems on a patient’s problem list: after more urgent problems are stabilized can make LTBI treatment a priority.#22
34Risk Factors for Progression from Latent TB Infection (LTBI) to Active TB Disease Medical ConditionsYour patient’s TB infection may be latent now, but many factors could increase the risk of progressionImmunosuppressionLymphoma, leukemiaDiabetesRenal dialysisMalnutritionSilicosisGastrectomy/ jejunoileal bypassHead and neck cancerHIV +Main Point: many common medical conditions that your patients may develop as they age or drugs that they may need increase the likelihood of progression from LTBI to active disease. (treat sooner rather than later!)#23
35Risk Factors for Progression from Latent TB Infection (LTBI) to Active TB Disease (cont.) DrugsImmunosuppressive agentsSteroids (not inhaled) (prednisone >15 mg/day for 1 month or more)Cancer chemotherapyCyclosporineAnti-Rheumatics*Etanercept (Enbrel)Infliximab (Remicade)Adalimumab (Humira TM)Anakinra (Kineret)#24* Brassard, P Antirheumatics Drugs and the Risk of Tuberculosis. CID 2006:43 (15 September).
36Case Example of Progression from LTBI to Active TB 68 yo Chinese man with latent TB untreatedHx of Hepatitis B with low level activityFamily history of colon cancerDeveloped adenocarcinoma of the colon and was receiving chemotherapyDeveloped hemoptysis and was thought to have a lung metastasisBronchoscopy aspirate grew TBPlease insert case examples from your own practice of patients:with long standing LTBIDid not get treatment for LTBI for whatever reasonProgressed to active TB when older and sickerIf want to use these examples:#1: 68 year old Chinese male, with untreated LTBI. Hx of hepatitis B with low level activity, Hx of family colon cancer, developed cancer of the colon, was receiving chemotherapy. He started coming in with hemoptysis. Physician thought that he had lung lesion that was metastatic cancer. Sputum was taken and it turn out that he had active TB.
37Case Example of Progression from LTBI to Active TB 66 yo Vietnamese female with latent TB (untreated), diabetes inflammatory arthritis, and depression/ PTSDDeveloped idiopathic thrombocytopenic purpura and began to have bleedingTreated with systemic high dose steroids in the hospital and developed milliary TBDied of complicationsSource: from practice of PI, Carey Jackson, MD. Internal Medicine. International Clinic, Harborview Medical Center, Seattle, Washington.#2: 66 year old Vietnamese female, untreated LTBI, diabetes, several years previously had been offered treatment, but had she turned it down. LTBI was forgotten about. She had inflammatory arthritis, depression, PTSD and she was very noncompliant. She presented in the ER with lots of bruising , bleeding, showed up in the ER, and was then admitted because of her thrombocytopenia; she was actively bleeding, they brought her in, they put her on high dose steroids and next thing they knew, they had millary TB. She was in the unit and died.
38Current Treatment for LTBI Preferred Regimen DrugDoseFrequencyDurationIsoniazid (INH)300 mgDaily9 monthsA minimum of 270 doses must be administeredwithin 12 monthsMain Point: quick review of treatment regimens for LTBI.#25
39Alternative Regimens for LTBI DrugDoseFrequencyDurationOtherIsoniazid900 mgTwice weekly9 monthsDOT300 mgDaily6 monthsRifampin600 mg4 monthsMain Point: quick review of treatment regimens for LTBI.#25
40No Longer Recommended Regimen for LTBI Rifampin plus pyrazinamide x 2 monthsThis regimen has been associated with increased risk of severe hepatic injury and death#26Source: “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);
41Monitoring of Patients on Treatment for LTBI Baseline and monthly laboratory testing not needed except for patients withHIV infectionPregnancy or within 3 months post-partumHistory of liver disease/heavy alcohol usePatient on chemotherapyEvaluate patients monthly forAdherence to treatmentSymptoms of hepatitis (fatigue, weight loss, nausea, vomiting, jaundice)Main Point: monthly evaluations encouraged. Baseline LFTs not needed except under certain circumstances.Discussion Point for patients without insurance or others where monthly visits are a problem. Have nursing staff make monthly call to patient for symptom and adherence check or have patient call in monthly.#27
42Treatment of Patients 35 Years of Age and Older The CDC changed its guideline in 2000 and now encourages treatment of LTBI in all age groupsUse 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, 2000Main Point: Guideline changed; there is no cutoff for treatment for LTBI at 35 any longer.Supplemental: For older patients, it is a judgment call. Example: a 70 year old who has LTBI and who is on a host of other meds, many will lean to the decision not to treat. On the other hand, a 55 year old who is has LTBI with a PPD result of 21 mm, with HTN, diabetes and worsening asthma is an easier decision to treat.#28,29
43Hepatic Adverse Drug Effects of Isoniazid (INH) Frequent (~5%): Liver Enzyme ElevationsInfrequent (~0.1%): HepatitisLarge Scale Study:11,141 treated with INH from11 had hepatitis, no deathsOverall rate was 1 per 1000 (or 0.1%)(Nolan CM, Goldberg SV, Buskin SE. JAMA Mar 17;281(11): )Main Point: Hepatitis in reaction to INH infrequent.#30
44Patients with Chronic Hepatitis B But No Active Liver Disease Yes, they can receive treatment for LTBIBaseline liver function tests and at 1 monthIf the tests are normal at 1 month, no further testing is necessary unless symptoms developIf the tests are elevated at 1 month, continue monthly testing as long as levels are abnormalIf any one of the liver function tests exceeds 3-5 times the upper limit of normal at any time, strongly consider stopping therapyMain Point: Patients with chronic, non active hepatitis are able to be treated with monitoring.#31
45Counseling 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…”Main Point: discussion of how to talk to a patient about LTBI.
46Counseling 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.”Main Point sleeping in your body and can wake up. Some use agricultural analogy of seed waiting to sprout.Supplement: “I’m worried about those days 20 years from now when you don’t have the health reserve you have now and you might have chronic medical problems I have to deal with that put you at even higher risk for disease; I want to take care of this now.”
47Counseling 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.”
49Meeting the Challenge of LTBI For every patientAssess TB risk factorsIf risk is present, perform TST (PPD)If TST (PPD) is positive, rule out active TB diseaseIf active TB disease is ruled out, evaluate as candidate for LTBI treatmentIf good candidate, initiate treatment for LTBIIf treatment is initiated, ensure completionMain Point: review of primary care management of LTBI.
50Meeting 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 diseaseMuch 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 infectionWhile the condition in itself is asymptomatic, the risks assumed by ignoring it are substantialMain Point: Take LTBI seriously and as a risk for a serious disease for your patients.Supplement: “Often we treat latent TB as though it is not a real problem; it’s really active disease we worry about. It is helpful to think of latent TB as its own unique infection because it changes the way you address it. To make an analogy, low level HTN is not such an issue, it’s what it can do that has us managing it because it is a risk factor for other things. And so we get excited about HTN and it’s the same way we need to see latent TB. It requires that same kind of attention.”
51Physicians Caring for At Risk Populations Main Point: for your at risk patients, think TB.Always include TB in the DDX“THINK TB” and “TB RISK”
52AcknowledgementsThe following individuals provided consultation and review of this presentation:Masa Narita MD, TB Controller for Seattle-King County Public HealthJohn Bernardo, MD – Tuberculosis Control Officer, Massachusetts Department of Public HealthL. Masae Kawamura - MD, Director TB Control Section, San Francisco Department of Public HealthStephen Weis, DO –Director of Tuberculosis and Refugee Services for Tarrant County Health Department, Texas
53Without the help of the following individuals, this project would not have been possible: Lan NguyenEd ChowJessie WingXimena Urrutia-RojasJeff CaballeroSharon Sharnprapai
54ReferencesCDC Fact Sheet. “BCG Vaccine” In Division of TB Elimination Fact Sheets. Retrieved from:DSHS/Public Health Service/CDC “TB 101 for Healthcare Providers.” PPT.DTBE/CDC “Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection”. In Division of Tuberculosis Elimination. Retrieved from:DTBE/CDC “Tuberculosis in the United States: National Surveillance System Highlights from 2004”. In Division of Tuberculosis Elimination. Retrieved from:
55References (cont.)Hong, SW “Preventing Nosocomial Mycobacterium tuberculosis Transmission in International Settings”. Emerging Infectious Diseases. Vol. 7, No. 2, March-April 2001Joos, TJ; Miller WC; Murdoch, DM “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, ppKawamura, L. Masae “Targeted Testing and Treatment of Tuberculosis”. In Francis J. Curry National Tuberculosis Center. Retrieved from:
56References (cont.)World Health Organization Global Health Atlas. Accessed from: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); Assessed from