latent tb infection on world tb day 2014
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Elizabeth A. Talbot MD Associate Professor, Deputy State Epi Infectious Disease & International Health Geisel School of Medicine at Dartmouth. Latent TB Infection on World TB Day 2014. Outline. World TB Day 2014 Relevant global and US epidemiology - PowerPoint PPT PresentationTRANSCRIPT
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Elizabeth A. Talbot MDAssociate Professor, Deputy State EpiInfectious Disease & International HealthGeisel School of Medicine at Dartmouth
Latent TB Infection onWorld TB Day 2014
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GEISELMED.DARTMOUTH.EDU
• World TB Day 2014– Relevant global and US
epidemiology• Top issues re: latent TB
infection (LTBI)– Testing: Interferon gamma
release assays (IGRAs) and tuberculin skin test (TST)
– Treatment options– Operational tidbits
Outline
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• Number of new TB cases decreased to ~9M
– India+China 40%, Africa 24%– 13% co-infected with HIV
• 1.4 million people died from TB• Multi-drug resistant (MDR*) TB
– 3.7% among new cases– 20% among previously treated– 9% of MDR is XDRTB**
2013 Global Epi Snapshot
*MDR=resistance to H+R**XDR=MDR with resistance to FQ and injectable
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• One-third of TB cases missed
• 50% of ~1.1 million new cases of HIV-related TB missed
• 75% with MDR-TB missed
“Missed” = gap between
estimated number who
became ill with TB and the
number notified to national TB
programs
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2013 US Epi Snapshot
*MDR=resistance to H+R**XDR=MDR with resistanceTo FQ and injectable agent
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PRIORITIZE LTBI TESTING FOR THOSE WITH RISK FACTORSFOR DEVELOPMENT OF TB
To control TB (and solve many of our testing dilemmas):
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Most US TB is Reactivated LTBI• >80% of US TB is result of reactivated LTBI• Data from representative survey of US pop
showed 4.2% of persons screened 1999-2000 had LTBI
• Two risk categories for reactivation TB – LTBI prevalence is increased: e.g., foreign-born
persons– Rate of reactivation during LTBI is increased: e.g., HIV – Both risks are present: e.g., recent contact with case
• Nearly all these cases can be prevented by treatment of LTBI
Horsburgh & Rubin, NEJM 2011; 364 (154): 1441-8
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Targeted Testing
• Identify, evaluate, and treat persons at high risk for – LTBI or – Progression LTBI to TB
• If you test for LTBI, have strategy to evaluate and treat those found to be infected– Local health
department is a resourceCDC Core Curriculum
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High Risk for TB Exposure• Close contacts to TB
– HCWs who serve people at high risk for TB
• Persons who were born in or visit TB endemic areas– >40/100,000 population
• Persons who work or reside in high-risk congregate settings– Prisons, LTCFs, shelters
• Local populations at high risk for infection or disease– Drug users
Horsburgh & Rubin, NEJM 2011; 364 (154): 1441-8
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High Risk for Progression from LTBI to Active TB
Plus, persons with certain other medical conditions:• Silicosis• Carcinoma of head or
neck• Gastrectomy or jejunoilial
bypassHorsburgh & Rubin, NEJM 2011; 364 (154): 1441-8
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UNDERSTAND KEY FEATURES OF LTBI TESTING METHODS AND INTERPRETATION
For best (and credible) patient care:
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Tuberculin Skin Test Do’s and Don’t’s
• Do TST– Prior to immunosuppression– 8–10 weeks after prior negative
TST for contact investigation• Health department does contact
investigations• Don’t test
– If previous positive result• Especially severe reaction
– <6 weeks after live virus vaccine• Can be done at same time as
vaccine• What if patient has history of
BCG* vaccination?– IGRA is preferred because no cross
reaction– But . . .
*BCG: TB vaccine derived from M. bovis, most commonly given vaccine worldwide!
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Effect of BCG on TST reaction
• BCG given in infancy (age <2)– 23 studies with 78,846
vaccinees• 6.3% positive TST• 1% positive TST after
>10y• BCG given to older (age
>2)– 11 studies with 4,026
vaccinees• 40% positive TST due to
BCG• 20% positive TST after
>10y
Farhat, Menzies. Int J Tuberc Lung Dis 2006;10:1192-204
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False Positive LTBI Testing Results
• Many persons who have positive screening result are at low risk for reactivation, and even the best screening test would identify many more false positive results than true positive results
• Quantitative test results can help– TST induration– IGRA values
• Patient considerations– Costs/risks/benefits of treating or not treating?
• Help patient weigh, be honest about uncertainties, advise
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Do Which When?One is
Preferred• IGRAs
– History of BCG vaccination
– For those with low rates of return for TST reading
• Homeless, IVDA
• TST– Children <5
• When other unavailable
Both is Justifiable*
• When 1st test is neg, but risk for progression is high
• When 1st test is pos, but more evidence is needed to encourage compliance
• When IGRA is indeterminate, borderline or invalid
• If suspect 1st test is wrong
Neither is Preferred
• Recent contact to case– IGRA should be
repeated at 8-10 weeks (like TST)
– Data on timing of IGRA conversion not available
– IGRA may be more sensitive than TST
• Periodic screening (e.g., HCW)
*PPD may “boost” IGRA response. If you do TST then IGRA, do it within 7d of TST
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UPDATES REGARDING LTBI TREATMENT
The goal is treating LTBI to control TB:
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LTBI Treatment Regimens
Drugs Months of Duration Interval
Minimum
Doses
INH 9*Daily 270
2x wkly** 76
INH 6Daily 180
2x wkly** 52RIF*** 4 Daily 120
*Preferred; **Intermittent treatment only with DOT; ***Rifabutin can be substituted
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Rifapentine (Priftin)
• Rifamycin derivative developed in 1950s, marketed 1998• Similar spectrum as rifampin, but with
longer half-life for weekly dosing• For active TB treatment
– Higher relapse rates• Difficulty complying with asynchronous regimen
– Drug-drug interactions HIV protease inhibitors
– New clinical trials underway for TB
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PREVENT TB: INH & Rifapentine for 12wks
• INH for 9m vs. INH + RPT weekly for 12wks with DOT
• Study population: 8,000 patients– TST+ close contacts 70%– Converters 25%– TST+ HIV or HIV with close contact 2%– TST+ with fibrotic changes 2%
• Efficacy was similar – 0.19 v 0.43% developed TB disease
• Completion rate higher – 82 v 69%
• Cost higher $160 v $6, but may be cost-effective
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RPT+INH clearly non-inferior to INH monotherapyMore pronounced in intention to treat analysis
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Recommendations
• Equal alternative to 9m INH in ≥12y plus high risk for TB disease
– Close contact– Converter– Fibrotic changes on CXR– HIV not on ART, otherwise healthy
• Consider other patients on an individual basis
• Children 2-11y can be considered, especially if unlikely to complete 9m plus high risk to progress to TB disease
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INH-RPT NOT Recommended
• Children < 2 years old• HIV on ART• Pregnancy, or likely to become
pregnant during treatment• Presumed INH or RIF resistance• Prior adverse reaction with INH or
rifamycin
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Current LTBI Treatment Regimens
Drugs Months of Duration Interval
Minimum
Doses
INH 9*Daily 270
2x wkly** 76
INH 6Daily 180
2x wkly** 52RIF*** 4 Daily 120
INH-RPT 3 Weekly** 12
*Preferred; **Intermittent treatment only with DOT; ***Rifabutin can be substituted
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• 65/90 contacts chose INH+RPT• DOT at school, calls/texts/visits• Treatment completion similar
– 94%-100% for 3 regimens• 4 did not complete HP; 1 each
– HA+nausea– Rash+dizziness– F+aches– Unknown
• “CDC collaborating with health departments and institutions for more data nationally”
Programmatic Use of INH+RPT
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Summary
• TB remains a global threat• In US, treatment of LTBI is key TB control strategy• Diagnosis of LTBI should
– Target risk populations– Incorporate updated approaches using TST and
IGRAs• Treatment options for LTBI now include 12
dose rifapentine-INH regimen• State and local health departments offer up to
date epidemiology and medical consultation
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THANK YOU!!And thanks to my trusted colleagues at NH DHHS for their encouragement and expertise