Associate Professor Deputy State Epi Infectious Disease amp International Health Geisel School of Medicine at Dartmouth Latent TB Infection on World TB Day 2014 World TB Day 2014 Relevant global and US epidemiology ID: 380513
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Elizabeth A. Talbot MDAssociate Professor, Deputy State EpiInfectious Disease & International HealthGeisel School of Medicine at Dartmouth
Latent TB Infection on
World TB Day 2014Slide2
World TB Day 2014Relevant global and US epidemiologyTop issues re: latent TB infection (LTBI)Testing: Interferon gamma release assays (IGRAs) and tuberculin skin test (TST)Treatment optionsOperational tidbitsOutlineSlide3
Number of new TB cases decreased to ~9MIndia+China 40%, Africa 24%13% co-infected with HIV1.4 million people died from TBMulti-drug resistant (MDR*) TB3.7% among new cases20% among previously treated
9% of MDR is XDRTB**2013 Global Epi Snapshot*MDR=resistance to H+R
**XDR=MDR with resistance to FQ and injectableSlide4
One-third of TB cases missed50% of ~1.1 million new cases of HIV-related TB missed75% with MDR-TB missed“Missed” = gap between estimated number who became ill with TB and the number notified to national TB programsSlide5
2013 US Epi Snapshot*MDR=resistance to H+R**XDR=MDR with resistanceTo FQ and injectable agentSlide6Slide7
Prioritize LTBI Testing for Those with Risk Factorsfor Development of TBTo control TB (and solve many of our testing dilemmas):6Slide8
Most US TB is Reactivated LTBI>80% of US TB is result of reactivated LTBIData from representative survey of US pop showed 4.2% of persons screened 1999-2000 had LTBITwo risk categories for reactivation TB LTBI prevalence is increased: e.g., foreign-born personsRate of reactivation during LTBI is increased: e.g., HIV Both risks are present: e.g., recent contact with caseNearly all these cases can be prevented by treatment of LTBI
Horsburgh & Rubin, NEJM 2011; 364 (154): 1441-8Slide9
Targeted TestingIdentify, evaluate, and treat persons at high risk for LTBI or Progression LTBI to TBIf you test for LTBI, have strategy to evaluate and treat those found to be infectedLocal health department is a resource
CDC Core CurriculumSlide10
High Risk for TB ExposureClose contacts to TBHCWs who serve people at high risk for TBPersons who were born in or visit TB endemic areas
>40/100,000 populationPersons who work or reside in high-risk congregate settingsPrisons, LTCFs, sheltersLocal populations at high risk for infection or diseaseDrug users
Horsburgh
& Rubin, NEJM 2011; 364 (154): 1441-8Slide11
High Risk for Progression from LTBI to Active TB
Plus, persons with certain other medical conditions:
SilicosisCarcinoma of head or neck
Gastrectomy
or
jejunoilial
bypass
Horsburgh
&
Rubin,
NEJM 2011; 364 (154): 1441-8Slide12
Understand key features of LTBI Testing methods and interpretationFor best (and credible) patient care:Slide13
Tuberculin Skin Test Do’s and Don’t’s Do TSTPrior to immunosuppression
8–10 weeks after prior negative TST for contact investigationHealth department does contact investigations Don’t testIf previous positive resultEspecially severe reaction<6 weeks after live virus vaccine
Can be done at same time as vaccineWhat if patient has history of BCG* vaccination?IGRA is preferred because no cross reactionBut . . .
*BCG: TB vaccine derived from
M.
bovis
, most commonly given vaccine worldwide!Slide14
Effect of BCG on TST reactionBCG given in infancy (age <2)23 studies with 78,846 vaccinees6.3% positive TST
1% positive TST after >10yBCG given to older (age >2)11 studies with 4,026 vaccinees
40% positive TST due to BCG20% positive TST after >10y
Farhat, Menzies. Int J Tuberc Lung Dis 2006;10:1192-204Slide15
False Positive LTBI Testing ResultsMany 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 resultsQuantitative test results can helpTST induration
IGRA valuesPatient considerationsCosts/risks/benefits of treating or not treating?Help patient weigh, be honest about uncertainties, adviseSlide16
Do Which When?One is PreferredIGRAsHistory of BCG vaccinationFor those with low rates of return for TST readingHomeless, IVDA
TSTChildren <5When other unavailableBoth is Justifiable*
When 1
st
test is
neg
, but risk for progression is high
When 1
st
test is
pos
, but more evidence is needed to encourage compliance
When IGRA is indeterminate, borderline or invalid
If suspect 1
st
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 TSTSlide17
Updates regarding LTBI TreatmentThe goal is treating LTBI to control TB:16Slide18
LTBI Treatment RegimensDrugs
Months of DurationInterval
Minimum
Doses
INH
9*
Daily
270
2x wkly**
76
INH
6
Daily
180
2x wkly**
52
RIF***
4
Daily
120
*Preferred; **Intermittent treatment only with DOT; ***
Rifabutin
can be substituted Slide19
Rifapentine (Priftin)Rifamycin derivative developed in 1950s, marketed 1998Similar spectrum as rifampin, but with longer half-life for weekly dosingFor active TB treatment
Higher relapse ratesDifficulty complying with asynchronous regimenDrug-drug interactions HIV protease inhibitorsNew clinical trials underway for TBSlide20
PREVENT TB: INH & Rifapentine for 12wksINH for 9m vs. INH + RPT weekly for 12wks with DOTStudy population: 8,000 patientsTST+ 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 diseaseCompletion rate higher 82 v 69%Cost higher $160 v $6, but may be cost-effectiveSlide21
RPT+INH clearly non-inferior to INH monotherapyMore pronounced in intention to treat analysisSlide22
RecommendationsEqual alternative to 9m INH in ≥12y plus high risk for TB diseaseClose contactConverterFibrotic changes on CXRHIV not on ART, otherwise healthyConsider other patients on an individual basisChildren 2-11y can be considered, especially if unlikely to complete 9m plus high risk to progress to TB diseaseSlide23
INH-RPT NOT RecommendedChildren < 2 years oldHIV on ARTPregnancy, or likely to become pregnant during treatmentPresumed INH or RIF resistancePrior adverse reaction with INH or
rifamycinSlide24
Current LTBI Treatment RegimensDrugs
Months of DurationInterval
Minimum
Doses
INH
9*
Daily
270
2x wkly**
76
INH
6
Daily
180
2x wkly**
52
RIF***
4
Daily
120
INH-RPT
3
Weekly**
12
*Preferred; **Intermittent treatment only with DOT; ***
Rifabutin
can be substituted Slide25Slide26
65/90 contacts chose INH+RPTDOT at school, calls/texts/visitsTreatment completion similar94%-100% for 3 regimens4 did not complete HP; 1 eachHA+nauseaRash+dizziness
F+achesUnknown“CDC collaborating with health departments and institutions for more data nationally”Programmatic Use of INH+RPTSlide27
SummaryTB remains a global threatIn US, treatment of LTBI is key TB control strategyDiagnosis of LTBI should
Target risk populationsIncorporate updated approaches using TST and IGRAsTreatment options for LTBI now include 12 dose rifapentine-INH regimenState and local health departments offer up to date epidemiology and medical consultationSlide28
THANK YOU!!And thanks to my trusted colleagues at NH DHHS for their encouragement and expertise