19 louie ltbi - ucsfcme.com · tb-4 (radiographic evidence of old tb disease) •inh + rifampin x 4...
TRANSCRIPT
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Latent Tuberculosis Infection (LTBI) 101
Janice Louie, MD, MPHMedical Director
San Francisco Tuberculosis Prevention and Control Program
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§ Background§ Screening (Who to Test)§Testing§ LTBI Treatment
Outline
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TB Epidemiology-U.S. (2017)
• US: 9,105 active TB cases* (2.8 per 100,000 population)
• California is a hotspot (5.3 per 100,000)
• San Francisco is super hot (13.1 per 100,000)
*Centers for Disease Control and Prevention TB Data and Statistics: https://w w w.cdc.gov/tb/statistics/default.htm
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San Francisco TB Cases: 2018
• Incidence rate of 13.1 per 100,000 (n=118)• Non-US Born: 86%• Most common countries of origin outside
of the US: China, Philippines, Vietnam• Median age: 64 years (range 3-95)• 49% were ≥65 years of age• The median age of TB cases in San
Francisco is increasing.• Most of these cases are preventable!
50.352.751.356.4
52.454.550.1
57.258.1 59 59.6 6064
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Age
(Yea
rs)
TB Case Age Trend Over Time
M ed ia n Age
2018 TB Cases by Country of Origin
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Health disparity in TB: API San Franciscans
The TB case-rate in Asian-Americans is 10.8X that in Non-Hispanic White populations
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~2.4 million Californians with latent TB infection-most are unaware and untreated
1.8M
20% 12%0.0
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1.0
1.5
2.0
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LTBI preva lence Aware of LTBI Treat ed f or LTBI
Mill
ions
of p
erso
ns
U.S. -bornForeign-born
NHANES 2011-2012 applied to California population 6
Estimated 65,111 San Franciscans with LTBI
(2017, CDPH TBCB Report)
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TB Disease vs. (Latent) Tuberculosis Infection (LTBI)
Active TB disease Latent TB infection
Cough, fever, weight loss, night sweats
No symptoms
Abnormal chest x-ray Normal chest x-ray
Infectious Not infectious
May progress to active TB disease
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Natural History of TB
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Latent TB (LTBI)(Dormant or “sleeping”)
Active TB disease
Exposure to infectious
TB
Rapidly developactive TB disease (~1-5%)
- Children <5 years- Im m unocom prom ised/HIV
- Recent converters
years
Not infected
5-10% over lifetime, depending on risk factors
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• Background• Screening (Who To Test)• Testing• LTBI Treatment
Outline
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Risk of false positives is high in a low incidence population
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86% of TB cases in SF are non-US born. Countries of origin for most cases outside of US include: China, Philippines and Vietnam.
HIV patients have exceptionally high rate of reactivation (7-10% per year); screen annually
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Routine testing of persons without risk factors is not recommended and may result in unnecessary evaluation and treatment because of false positive results
Note: Age not considered in this assessment, however younger adults have more years of expected life. Some clinicians may choose to prioritize younger non-US born persons
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Watch out! Patients with abnormal CXR and report that says “lesions consistent with old TB, no evidence of active TB”
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• Risk of developing active TB is up to 19-fold higher
• TST or IGRA may be negative• Check sputa and await culture
results before starting LTBI treatment
• Data still unclear on what are best regimenso At SFDPH we use INH+ RIF x
4 months or INH x 9 months
Radiographic lesions “consistent with inactive TB”
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LTBI with abnormal chest X-ray: 3 casesA
B
C
• Non- US born• Asymptomatic• QFT+• CXR report: “BUL nodules, calcified,
consistent with old granulomatous disease. No active disease.”
What do you do?
Check sputa!Sputa preliminary results: • Smear neg x 3, geneXp neg x 1• Await cultures (8 weeks)
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Culture resultsA
B
C
Å Yes, Active TB, pan-sensitive
Å No, TB 4 (old granulomatous disease, LTBI treatment with INH and rifampin)
Å Yes, Active TB, pan-sensitive
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Pathophysiology of TB lesions: a dynamic state
A radiographic interpretation of “old” TB on chest X-ray does NOT rule out active disease
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Risk Factors for Developing Active TB
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• Children <5 years at high risk of disseminated TB/TB meningitis
• Active TB in children is usually pauci-bacillary:- Asymptomatic or atypical
symptoms- CXR abnormalities non-
specific: look for infiltrate in lower lobes, mediastinal lymphadenopathy
- Sputum typically non-diagnostic, need gastric aspirates x 3 (geneXp often not available)
- Exposure history important- Infants and children <5 yrs
are “sentinels of transmission”
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§ Background§ Screening (Who to Test)§Testing§ LTBI Treatment
Outline
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Tuberculin Skin Testing
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> 5 mm of induration > 10 mm of induration*
Considered positive in: • Persons with HIV or immunosuppression • Recent contacts to an active case of
pulmonary or laryngeal TB • Persons with fibrotic changes on chest X-ray
consistent with old TB
Considered positive in all other persons recommended for TB screening
California TST interpretation guidelines
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History of BCG vaccination
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ESAT-6, CFP-10, and proprietary CD8 antigens (absent from all BCG strains and from most nontuberculous mycobacteria with the exception of M. kansasii, M. szulgai, and M. marinum)
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Repeat testing provided valid result (positive or negative) in 68% (Banach Int Jl TB Lung Dis 2011)
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73% false positive rate
12% false positive rate
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§ Background§ Screening (Who to Test)§Testing§ LTBI Treatment
Outline
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LTBI Treatment OptionsNormal CXR• Rifampin x 4 months• INH + rifapentine x 3 months• INH x 6 months• INH x 9 months (gold standard)- immunocompromised/HIV
TB-4 (Radiographic evidence of old TB disease)• INH + Rifampin x 4 months*
*Jasmer et al. Twelve months of isoniazid compared with four months of isoniazid and rifampin for persons with radiographic evidence of previous tuberculosis: an outcome and cost-effectiveness analysis. Am J Respir Crit Care Med 2000 Nov;162(5):1648-52.
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First Line: RifampinMulti-center Phase 3 RCT: N= 3443
Rifampin x 4 months vs INH x 9 months
Study sites: Australia, Canada, Benin, Brazil, Ghana, Guinea, Indonesia, Korea, Saudi Arabia
Findings:
• Rifampin x 4 months was non-inferior to INH x 9 months for the prevention of active TB at 28 months of follow-up
• Higher rate of treatment completion
• Lower rate of adverse events and hepatotoxicity
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First Line: 3-HP by Directly Observed Therapy
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Multi-center RCT (n=8053)
3HP DOT x 12 weeks vs INH x 9 months
Study Sites: U.S., Canada, Brazil and Spain
• 3HP was non-inferior to INH x 9 months for the prevention of active TB at 33 months of follow-up
• Higher rate of treatment completion
• Lower rate of hepatotoxicity
Prevent TB Study
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Self Administered-3HP• Recommended by CDC June 2018*• Based on study of 1000+ adults in Denver, median age 36 years• SFDPH protocol:
Inclusion criteria: o All adults, who upon mutual assessment by MD and nursing, can be complianto Children <18 years who are able to swallow pills (without crushing) and can be monitored by
a parentExclusion criteria: o Any patient who requires DOPT
o Any adult where noncompliance is a concerno Children who need crushed pills or liquid formulationso Children (including adolescents and teenagers) where parents do not agree or are unable to
monitor compliance
*M M W R Weekly / June 29, 2018 / 67(25);723–726
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“52 weeks of INH prevented the most tuberculosis, but 24 weeks prevented the most tuberculosis per case of hepatitis caused.”
Second line- Isoniazid x 6 months(Use when rifamycin is not tolerated or contra-indicated)
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*But increased hepatoxicity as duration of INH increases
Second line- Isoniazid x 9 monthsRecommended for immunocompromised/HIV
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Isoniazid Adverse Events• Hepatitis
• Uncommon in age <20 years• Increased risk with older age: ~2% in ages 50-64 years• Increased risk with ETOH abuse or chronic liver disease
• Asymptomatic transaminitis (20%)• Peripheral neuropathy (<0.2%); supplement with B6 50 mg• Rash• Mild CNS effects• Note drug interactions: increase Dilantin, carbamazepine and
Antabuse levels
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Monthly Monitoring• Adherence• Symptoms:
o Fatigue, anorexia, nausea/vomiting, abdominal paino Icterus, jaundice, dark urineo Rash, itchinesso Peripheral numbness
• LFTS:o History of liver disease or ETOH useo HIVo Pregnancy/post-partum (<3 months)o Other hepatotoxic meds (e.g. statins)o Age> 50
ATS/CDC LTBI Guidelines 2000
Hold medications if:• Symptomatic and LFTS >3X ULN• Asymptomatic and LFTS >5X ULN
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Dosing recommendations in children vary:https://www.cdc.gov/tb/topic/treatment/ltbi.htm
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Take-Home MessagesTargeted Testing takes into account differing risks in populations. Do test:
• Foreign-born, especially those with medical risk factors for progression to active TB• Immunocompromised• Contacts• Converters• Residents of congregate settings• Abnormal CXR concerning for old or active TB
Diagnosis• IGRA is more specific; preferred in non-US born• TST is cheaper, reasonable to use in US born (but beware misinterpretation)
Treatment Options: Short courses are now the standard of care• Rifampin x 4 months• 3-HP x 3 months• INH x 6 months (9 months if immunocompromised)• INH x 9 or RIF/INH x 4 months if CXR suggests old TB (rule out active TB first)
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SFDPH TB Prevention and Control Program Resources
Physician/RN questions• Phone: 628 206-8524• E-consult• E-mail: [email protected] or [email protected]
Felix Crespin, Surveillance• Questions about possible active case or hospitalization discharge
approvalo628 206-3398
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Questions?
Questions?
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