Primary Care Management of Primary Care Management of Latent Tuberculosis Infection Latent Tuberculosis Infection in the Foreign in the Foreign - - Born Born Investigators Investigators • • Carey Jackson MD, MPH University of Washington Carey Jackson MD, MPH University of Washington • • Jenny Pang MD, MPH, Seattle Jenny Pang MD, MPH, Seattle - - King County King County Department of Public Health Department of Public Health • • Nick DeLuca PhD, Centers for Disease Control and Nick DeLuca PhD, Centers for Disease Control and Prevention (CDC) Prevention (CDC) • • Stacey Bryant RN, Research Coordinator Stacey Bryant RN, Research Coordinator Public Health Seattle & King County
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Primary Care Management of Primary Care Management of Latent Tuberculosis InfectionLatent Tuberculosis Infection
in the Foreignin the Foreign--BornBornInvestigatorsInvestigators
•• Carey Jackson MD, MPH University of WashingtonCarey Jackson MD, MPH University of Washington•• Jenny Pang MD, MPH, SeattleJenny Pang MD, MPH, Seattle--King County King County
Department of Public HealthDepartment of Public Health•• Nick DeLuca PhD, Centers for Disease Control and Nick DeLuca PhD, Centers for Disease Control and
Prevention (CDC)Prevention (CDC)•• Stacey Bryant RN, Research CoordinatorStacey Bryant RN, Research Coordinator
(LTBI)(LTBI)5.5. SummarySummary6.6. Local InformationLocal Information
DefinitionsDefinitions
Active TB DiseaseActive TB Disease•• Tubercle bacilli in the bodyTubercle bacilli in the body•• Usually positive skin testUsually positive skin test•• Infectious (before Infectious (before
treatment)treatment)•• Symptoms of TBSymptoms of TB•• Chest xChest x--ray usually ray usually
abnormalabnormal•• Sputum smears and Sputum smears and
cultures usually positivecultures usually positive•• An active An active ““casecase”” of TBof TBGranuloma breaks
down and tubercle escape and multiply
Symptoms of Active TB DiseaseSymptoms of Active TB Disease
Systemic Systemic SymptomsSymptoms
PulmonaryPulmonarySymptomsSymptoms
•• Weight lossWeight loss•• FatigueFatigue•• FeverFever•• Night sweatsNight sweats•• ChillsChills
•• Coughing (duration of Coughing (duration of ≥≥ 3 weeks)3 weeks)
•• Chest pain (when Chest pain (when breathing or coughing)breathing or coughing)
LTBI is the presence of LTBI is the presence of M. tuberculosisM. tuberculosis organisms organisms (tubercle bacilli) (tubercle bacilli) without symptoms or without symptoms or radiographic evidence of radiographic evidence of active TB diseaseactive TB disease
Latent TB Infection (LTBI)Latent TB Infection (LTBI)•• Tubercle bacilli in the Tubercle bacilli in the
bodybody•• Usually positive skin testUsually positive skin test•• NOT infectiousNOT infectious•• No symptomsNo symptoms•• Normal chest XNormal chest X--rayray•• Sputum smears and Sputum smears and
cultures are negativecultures are negative•• Not a Not a ““casecase”” of TBof TB
EpidemiologyEpidemiology
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, 2006TB Case Rates,* United States, 2006
Percentage of TB Cases Among ForeignPercentage of TB Cases Among Foreign--born Persons, United States*born Persons, United States*
>50%25%–49%<25%
1996 2006
DC DC
*Updated as of April 6, 2007.
TB Rates in Countries of BirthTB Rates in Countries of Birth20052005
4.6 23100
168 175
291 305 344
506
119
0
100
200
300
400
500
600
USAMex
icoChinaRuss
iaIndia
Vietna
mPhilip
pinesHait
iEthiop
iaCam
bodia
Per 1
00,0
00
Source: World Health Organization
TB Case Rates by Age Group TB Case Rates by Age Group and Sex, United States, 2006and Sex, United States, 2006
02468
1012
<15 yrs 15–24 yrs 25–44 yrs 45–64 yrs >65 yrs
Male Female
Cases per 100,000
Highest Incidence is in 65+Highest Incidence is in 65+
Percent of ForeignPercent of Foreign--born with TB by Time of born with TB by Time of Residence in U.S. Prior to Diagnosis,* 2006Residence in U.S. Prior to Diagnosis,* 2006
0%
20%
40%
60%
80%
100%
All Mexico Philippines Viet Nam
<1 yr 1–4 yrs >5 yrs*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 ForeignOver HALF of active TB cases in the Foreign--Born Born have been in the US have been in the US moremore than 5 years!than 5 years!
Countries of Birth of ForeignCountries of Birth of Foreign--born born Persons Reported with TB Persons Reported with TB
Flow Chart for Latent TB Infection (LTBI) in Primary CareFlow Chart for Latent TB Infection (LTBI) in Primary CarePatient with risk factors
for LTBI
Negative
No treatment; Document status in
medical record
Candidate for LTBI Treatment
Treatment ofactive 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 TestedWho Should Be TestedKnowKnow the TB status of your the TB status of your at riskat risk patients.patients.
Who is considered Who is considered at risk?at risk?
What countries are What countries are considered TB endemic?considered TB endemic?
Foreign born Foreign born patients from patients from TB endemicTB endemiccountries, countries, where prior TB where prior TB exposure is exposure is almost certainalmost certain
•• All All of Asia except Japanof Asia except Japan•• AllAll of Central and South of Central and South
AmericaAmerica•• AllAll of Africa of Africa •• AllAll of Eastern Europeof Eastern Europe
(Yes, that is practically (Yes, that is practically the whole world)the whole world)
Other Groups At High Risk for TBOther Groups At High Risk for TBGroupsGroups
•• 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 Healthcare workers who serve high risk clientsclients
•• Residents & employees of congregate Residents & employees of congregate settingssettings
•• Medically underserved/lowMedically underserved/low--income groups:income groups:•• HomelessHomeless•• Migrant workersMigrant workers•• Street drug usersStreet drug users•• Children with parents who have risk factorsChildren with parents who have risk factors
Medical Conditions that Medical Conditions that Put People at High Risk for TBPut People at High Risk for TB
Medical ConditionsMedical 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
Who needs repeat LTBI testing?Who needs repeat LTBI testing?
1)1) Healthcare workersHealthcare workers2)2) Close contacts to infectious TB casesClose contacts to infectious TB cases3)3) Frequent travelers to abroadFrequent travelers to abroad
•• If baseline TST is negative, consider If baseline TST is negative, consider rretestetestinging your patients that have your patients that have extended travel to high risk areasextended travel to high risk areas..
•• Do symptom review upon return and Do symptom review upon return and possibly retesting 8possibly retesting 8--10 week after 10 week after return.return.
Reading the Tuberculin Skin Test Reading the Tuberculin Skin Test (TST)(TST)
•• Measure reaction in 48 to 72 Measure reaction in 48 to 72 hourshours
•• Measure induration, Measure induration, not erythema (redness)not erythema (redness)
•• Record reaction in Record reaction in millimeters, not millimeters, not ““negativenegative””or or ““positivepositive””
•• Ensure trained health care Ensure trained health care professional measures and professional measures and interprets the TST (PPD)interprets the TST (PPD)
Interpreting the TST (PPD)Interpreting the TST (PPD)
A positive TST (PPD) is determined byA positive TST (PPD) is determined by•• The size of the indurationThe size of the induration•• The patientThe patient’’s risk factorss risk factors
(Note: the CDC discourages testing of people at low risk for inf(Note: the CDC discourages testing of people at low risk for infection.)ection.)
Interpreting Tuberculin Skin Test ReactionsInterpreting Tuberculin Skin Test Reactions5 mm 5 mm
or greateror greater10 mm 10 mm
or greateror greater15 mm 15 mm
or greateror greater•• HIV positive persons HIV positive persons •• Recent contacts of Recent contacts of
persons with active persons with active tuberculosis tuberculosis
•• Fibrotic changes on Fibrotic changes on chest radiograph, chest radiograph, consistent with consistent with tuberculosis tuberculosis
•• Patients with organ Patients with organ transplants and other transplants and other immunosuppressed immunosuppressed patientspatients
•• Immigrants from highImmigrants from high--prevalence areasprevalence areas
•• Injection drug users Injection drug users •• Residents and employees* of Residents and employees* of
highhigh--risk congregate settingsrisk congregate settings•• Personnel in Personnel in
mycobacteriologymycobacteriology laboratories laboratories •• Persons with clinical Persons with clinical
conditions that place them at conditions that place them at high riskhigh risk
•• Children: <4 years of age; all Children: <4 years of age; all exposed to adults at highexposed to adults at high--riskrisk
No known No known risk factorsrisk factors
TB screening for those coming to USTB screening for those coming to US
1)1) Refugees and ImmigrantsRefugees and ImmigrantsIn Country of OriginIn Country of Origin
•• Evaluated for Evaluated for active TB ONLYactive TB ONLYIn the USIn the US
•• Those applying for anThose applying for an aadjustment of status are djustment of status are evaluated for LTBI butevaluated for LTBI but treatment is NOT mandatedtreatment is NOT mandated
The Immigration Process does not take care of The Immigration Process does not take care of Latent TB Infection (LTBI) for you!Latent TB Infection (LTBI) for you!
BCGBCG
Should persons who have been vaccinatedShould persons who have been vaccinated with BCG with BCG ((BacilleBacille CalmetteCalmette--Guerin) Guerin) be tested for LTBIbe tested for LTBI
•• According to CDC guidelines, persons who have According to CDC guidelines, persons who have received BCG should be tested for LTBI as received BCG should be tested for LTBI as otherwise indicatedotherwise indicated
How How should the results be interpreted?should the results be interpreted?•• Positive TSTPositive TST should be assumed to be due to TB should be assumed to be due to TB
infection, not BCG, and treatment should be infection, not BCG, and treatment should be recommended, unless contraindicatedrecommended, unless contraindicated
Literature Review on BCGLiterature Review on BCG20062006
•• 1500 papers reviewed from 19801500 papers reviewed from 1980--20052005•• Data demonstrate that the TST (PPD) Data demonstrate that the TST (PPD)
performs well on BCG vaccinated adult performs well on BCG vaccinated adult (15+) patients and on patients from (15+) patients and on patients from high and intermediate incidence high and intermediate incidence countriescountries
•• The effect of the BCG vaccine on TST The effect of the BCG vaccine on TST (PPD) reaction decreases with (PPD) reaction decreases with increasing time since vaccinationincreasing time since vaccination..
Conclusion:Conclusion:
•• ““Adults (15+) from intermediate and Adults (15+) from intermediate and highhigh--incidence countries are at high incidence countries are at high risk for LTBI and the results of risk for LTBI and the results of tuberculin testing can be interpreted in tuberculin testing can be interpreted in the same manner, regardless of the same manner, regardless of vaccination status.vaccination status.””
Source: Joos, TJ et al. 2006. “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.
Literature Review on BCGLiterature Review on BCG2006 (cont.)2006 (cont.)
Treatment for Treatment for Latent Tuberculosis Latent Tuberculosis
Infection (LTBI)Infection (LTBI)
Who Should be Treated for Who Should be Treated for Latent TB Infection (LTBI)?Latent TB Infection (LTBI)?
Anyone who has been diagnosed with latent Anyone who has been diagnosed with latent TB infection is a candidate for treatment, if TB infection is a candidate for treatment, if they also fulfill the following criteria:they also fulfill the following criteria:
•• Willing and able to complete a full course of Willing and able to complete a full course of therapytherapy
•• Available to be monitored during the full Available to be monitored during the full course of treatmentcourse of treatment
•• No medical contraindications such as active No medical contraindications such as active liver diseaseliver disease
(Note: careful assessment to rule out the possibility of (Note: careful assessment to rule out the possibility of active TB disease is active TB disease is always always necessary before necessary before treatment for LTBI is started.)treatment for LTBI is started.)
Risk Factors for Progression from Latent Risk Factors for Progression from Latent TB Infection (LTBI) to Active TB DiseaseTB Infection (LTBI) to Active TB Disease
>15 mg/day for 1 month or more)>15 mg/day for 1 month or more)•• Cancer chemotherapyCancer chemotherapy•• CyclosporineCyclosporine•• AntiAnti--Rheumatics*Rheumatics*
Risk Factors for Progression from Latent TB Risk Factors for Progression from Latent TB Infection (LTBI) to Active TB Disease (cont.)Infection (LTBI) to Active TB Disease (cont.)
Drugs
* * Brassard, P. 2006. Brassard, P. 2006. AntirheumaticsAntirheumatics Drugs and the Risk of TuberculosisDrugs and the Risk of Tuberculosis. CID 2006:43 (15 . CID 2006:43 (15 September).September).
Case Example of Progression from Case Example of Progression from LTBI to Active TBLTBI to Active TB
Case #1:Case #1:•• 68 yo Chinese man with latent 68 yo Chinese man with latent
TB untreatedTB untreated•• Hx of Hepatitis B with low level Hx of Hepatitis B with low level
activity activity •• Family history of colon cancerFamily history of colon cancer•• Developed adenocarcinoma Developed adenocarcinoma
of the colon and was receiving of the colon and was receiving chemotherapy chemotherapy
•• Developed hemoptysis and was thought Developed hemoptysis and was thought to have a lung metastasisto have a lung metastasis
Case #2Case #2•• 66 66 yoyo Vietnamese female Vietnamese female
with latent TB (untreated), with latent TB (untreated), diabetes inflammatory diabetes inflammatory arthritis, and depression/arthritis, and depression/PTSD PTSD
•• Developed idiopathic thrombocytopenic Developed idiopathic thrombocytopenic purpurapurpuraand began to have bleedingand began to have bleeding
•• Treated with systemic high dose steroids in the Treated with systemic high dose steroids in the hospital and developed hospital and developed milliarymilliary TB TB
•• Died of complicationsDied of complicationsSource: from practice of PI, Carey Jackson, MD. Internal MedicinSource: from practice of PI, Carey Jackson, MD. Internal Medicine. International Clinic, e. International Clinic,
Harborview Medical Center, Seattle, Washington.Harborview Medical Center, Seattle, Washington.
Case Example of Progression from LTBI to Active TB
Current Treatment for LTBICurrent Treatment for LTBIPreferred RegimenPreferred Regimen
No Longer Recommended No Longer Recommended Regimen for LTBIRegimen for LTBI
Rifampin plus pyrazinamide x 2 Rifampin plus pyrazinamide x 2 monthsmonths
This regimen has been associated with This regimen has been associated with increased risk of severe hepatic injuryincreased risk of severe hepatic injury
and deathand death
Source: Source: ““Update: Adverse Event Data and Revised American Thoracic SocietyUpdate: Adverse Event Data and Revised American Thoracic Society/CDC /CDC Recommendations Against the Use of Rifampin and Pyrazinamide forRecommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Treatment of Latent Tuberculosis InfectionTuberculosis Infection------United States, 2003United States, 2003””; MMWR, August 8, 2003 / 52(31);735; MMWR, August 8, 2003 / 52(31);735--739.739.
Monitoring of Patients on Monitoring of Patients on Treatment for LTBITreatment for LTBI
•• Baseline and monthly laboratory testing Baseline and monthly laboratory testing not not neededneeded except for patients withexcept for patients with•• HIV infectionHIV infection•• Pregnancy or within 3 months postPregnancy or within 3 months post--partumpartum•• 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, Symptoms of hepatitis (fatigue, weight loss,
Treatment of PatientsTreatment of Patients35 Years of Age and Older35 Years of Age and Older
•• The CDC changed its guideline in 2000 The CDC changed its guideline in 2000 and now encourages treatment of LTBI and now encourages treatment of LTBI in all age groupsin all age groups
•• Use clinical judgment in treating older Use clinical judgment in treating older patientspatients
**CDC/ATS Guidelines: Morbidity and Mortality Weekly Report CDC/ATS Guidelines: Morbidity and Mortality Weekly Report (MMWR),(MMWR), ““Targeted Tuberculin Testing and Treatment of Latent Targeted Tuberculin Testing and Treatment of Latent Tuberculosis InfectionTuberculosis Infection..”” June 9, 2000June 9, 2000
Hepatic Adverse Drug Effects of Hepatic Adverse Drug Effects of Isoniazid (INH)Isoniazid (INH)
Large Scale Study:Large Scale Study:•• 11,141 treated with INH from 198911,141 treated with INH from 1989--19951995•• 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. Nolan CM, Goldberg SV, Buskin SE. JAMA.JAMA. 1999 Mar 17;281(11):10141999 Mar 17;281(11):1014--8.) 8.)
Patients with Chronic Hepatitis B Patients with Chronic Hepatitis B But No Active Liver DiseaseBut No Active Liver Disease
Yes, they can receive treatment for LTBIYes, they can receive treatment for LTBI
•• Baseline liver function tests and at 1 month Baseline liver function tests and at 1 month •• If the tests are normal at 1 month, no further If the tests are normal at 1 month, no further
testing is necessary unless symptoms testing is necessary unless symptoms developdevelop
•• If the tests are elevated at 1 month, continue If the tests are elevated at 1 month, continue monthly testing as long as levels are monthly testing as long as levels are abnormalabnormal
•• If any one of the liver function tests exceeds If any one of the liver function tests exceeds 33--5 times the upper limit of normal at any 5 times the upper limit of normal at any time, strongly consider stopping therapytime, strongly consider stopping therapy
Counseling a Patient with LTBICounseling a Patient with LTBI
DonDon’’t Say:t Say:•• ““YouYou’’ve been ve been
““exposedexposed”” to TB to TB so you need to beso you need to betreated.treated.””
Say Instead:Say Instead:•• ““You have been exposed AND infected You have been exposed AND infected
with the TB bacteria. But donwith the TB bacteria. But don’’t worryt worry…”…”
Good news:Good news:•• ““You do not have You do not have
the disease and youthe disease and youare not contagious are not contagious to anyone.to anyone.””
Bad news:Bad news:•• ““However, it is sleeping in your body and if However, it is sleeping in your body and if
you donyou don’’t treat it now it can wake up later t treat it now it can wake up later and make you very ill and contagious to and make you very ill and contagious to others.others.””
Counseling a Patient with LTBI (cont.)Counseling a Patient with LTBI (cont.)
Why get treated?Why get treated?•• ““Treatment will prevent Treatment will prevent
future disease and future disease and protect you and those protect you and those close to you.close to you.””
WarningWarning•• ““Taking medication for 9 months is a long Taking medication for 9 months is a long
time but it takes that long to kill all the TB time but it takes that long to kill all the TB germs.germs.””
•• ““ TB germs are TB germs are ‘‘TOUGH bugsTOUGH bugs’’ …… so take so take your medicine correctly and completely.your medicine correctly and completely.””
Counseling a Patient with LTBI (cont.)Counseling a Patient with LTBI (cont.)
SummarySummary
Meeting the Challenge of LTBIMeeting the Challenge of LTBIFor every patientFor 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 If TST (PPD) is positive, rule out active TB
diseasedisease•• If active TB disease is ruled out, evaluate If active TB disease is ruled out, evaluate
as candidate for LTBI treatmentas candidate for LTBI treatment•• If good candidate, initiate treatment for If good candidate, initiate treatment for
LTBILTBI•• If treatment is initiated, ensure completionIf treatment is initiated, ensure completion
•• Latent TB Infection should be treated as a condition Latent TB Infection should be treated as a condition in itself which is a precursor to a serious and in itself which is a precursor to a serious and potentially fatal disease potentially fatal disease
•• Much the same way we treat hypertension as a Much the same way we treat hypertension as a condition in itself because it significantly heightens condition in itself because it significantly heightens risk of heart disease, renal failure, and stroke or risk of heart disease, renal failure, and stroke or place infants in car seats because of the significant place infants in car seats because of the significant risk of injury without them, so should we approach risk of injury without them, so should we approach latent TB infectionlatent TB infection
•• While the condition in itself is asymptomatic, the While the condition in itself is asymptomatic, the risks assumed by ignoring it are substantialrisks assumed by ignoring it are substantial
Meeting the Challenge of LTBI (cont.)Meeting the Challenge of LTBI (cont.)
•• Always include TB in the DDXAlways include TB in the DDX•• ““THINK TBTHINK TB”” and and ““TB RISKTB RISK””
Physicians Caring for Physicians Caring for At Risk PopulationsAt Risk Populations
AcknowledgementsAcknowledgements
The following individuals provided consultation and The following individuals provided consultation and review of this presentation:review of this presentation:
•• Masa Narita MD, TB Controller for SeattleMasa Narita MD, TB Controller for Seattle--King King County Public HealthCounty Public Health
•• John Bernardo, MD John Bernardo, MD –– Tuberculosis Control Officer, Tuberculosis Control Officer, Massachusetts Department of Public HealthMassachusetts Department of Public Health
•• L. Masae Kawamura L. Masae Kawamura -- MD, Director TB Control MD, Director TB Control Section, San Francisco Department of Public HealthSection, San Francisco Department of Public Health
•• Stephen Weis, DO Stephen Weis, DO ––Director of Tuberculosis and Director of Tuberculosis and Refugee Services for Tarrant County Health Refugee Services for Tarrant County Health Department, TexasDepartment, Texas
Without the help of the following Without the help of the following individuals, this project would not have individuals, this project would not have been possible:been possible:
•• LanLan NguyenNguyen•• Ed ChowEd Chow•• Jessie WingJessie Wing•• XimenaXimena UrrutiaUrrutia--RojasRojas•• Jeff CaballeroJeff Caballero•• Sharon Sharon SharnprapaiSharnprapai
ReferencesReferences1.1. CDC Fact Sheet. CDC Fact Sheet. ““BCG VaccineBCG Vaccine””. 2006. In . 2006. In Division of Division of
2.2. DSHS/Public Health Service/CDC. 2006. DSHS/Public Health Service/CDC. 2006. ““TB 101 for TB 101 for Healthcare Providers.Healthcare Providers.”” PPT.PPT.
3.3. DTBE/CDC. 2005. DTBE/CDC. 2005. ““Targeted Tuberculin Testing Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infectionand Treatment of Latent Tuberculosis Infection””. In . In Division of Tuberculosis Elimination.Division of Tuberculosis Elimination. Retrieved 9Retrieved 9--1616--06 06 from: from: www.cdc.gov/nchstp/tb/pubs/slidesets/slides.htmwww.cdc.gov/nchstp/tb/pubs/slidesets/slides.htm
4.4. DTBE/CDC. 2005. DTBE/CDC. 2005. ““Tuberculosis in the United States: Tuberculosis in the United States: National Surveillance System Highlights from 2004National Surveillance System Highlights from 2004””. In . In Division of Tuberculosis Elimination.Division of Tuberculosis Elimination. Retrieved 9Retrieved 9--1616--06 06 from: from: www.cdc.gov/nchstp/tb/pubs/slidesets/surv/surv2004/dwww.cdc.gov/nchstp/tb/pubs/slidesets/surv/surv2004/default.htmefault.htm
6.6. Joos, TJ; Miller WC; Murdoch, DM. 2006. Joos, TJ; Miller WC; Murdoch, DM. 2006. ““Tuberculin reactivity in bacille CalmetteTuberculin reactivity in bacille Calmette--Guerin Guerin vaccinated populations: a compilation of vaccinated populations: a compilation of international data.international data.”” The International Journal of The International Journal of Tuberculosis and Lung Disease, Volume 10, Tuberculosis and Lung Disease, Volume 10, Number 8, August 2006, pp. 883Number 8, August 2006, pp. 883--891.891.
7.7. Kawamura, L. Masae. 2006. Kawamura, L. Masae. 2006. ““Targeted Testing and Targeted Testing and Treatment of TuberculosisTreatment of Tuberculosis””. In . In Francis J. Curry Francis J. Curry National Tuberculosis Center.National Tuberculosis Center. Retrieved 9Retrieved 9--1616--06 06 from: from: www.nationaltbcenter.edu/testing_ltbi/presentationwww.nationaltbcenter.edu/testing_ltbi/presentation.cfm.cfm
References (cont.)References (cont.)
8.8. World Health Organization. 2005. Global Health World Health Organization. 2005. Global Health Atlas. Accessed 10Atlas. Accessed 10--22--06 from: 06 from: www.who.int/globalatlas/dataQuery/default.aspwww.who.int/globalatlas/dataQuery/default.asp
9.9. Update: Adverse Event Data and Revised Update: Adverse Event Data and Revised American Thoracic Society/CDC American Thoracic Society/CDC Recommendations Against the Use of Rifampin Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent and Pyrazinamide for Treatment of Latent Tuberculosis InfectionTuberculosis Infection------United States, 2003 United States, 2003 MMWR, August 8, 2003 / 52(31);735MMWR, August 8, 2003 / 52(31);735--739. Assessed 739. Assessed 22--22--07 from 07 from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm231a4.htm