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
Feb 23, 2016
Elizabeth A. Talbot MDAssociate Professor, Deputy State EpiInfectious Disease & International HealthGeisel School of Medicine at Dartmouth
Latent TB Infection onWorld TB Day 2014
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
GEISELMED.DARTMOUTH.EDU
• 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
GEISELMED.DARTMOUTH.EDU
• 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
GEISELMED.DARTMOUTH.EDU
2013 US Epi Snapshot
*MDR=resistance to H+R**XDR=MDR with resistanceTo FQ and injectable agent
GEISELMED.DARTMOUTH.EDU
GEISELMED.DARTMOUTH.EDU
PRIORITIZE LTBI TESTING FOR THOSE WITH RISK FACTORSFOR DEVELOPMENT OF TB
To control TB (and solve many of our testing dilemmas):
7
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
UNDERSTAND KEY FEATURES OF LTBI TESTING METHODS AND INTERPRETATION
For best (and credible) patient care:
GEISELMED.DARTMOUTH.EDU
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!
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
UPDATES REGARDING LTBI TREATMENT
The goal is treating LTBI to control TB:
17
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
RPT+INH clearly non-inferior to INH monotherapyMore pronounced in intention to treat analysis
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
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
GEISELMED.DARTMOUTH.EDU
GEISELMED.DARTMOUTH.EDU
• 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
GEISELMED.DARTMOUTH.EDU
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
THANK YOU!!And thanks to my trusted colleagues at NH DHHS for their encouragement and expertise