jason andrews, md, sm, dtm&h division of infectious diseases massachusetts general hospital
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Intensified case finding in the era of new diagnostics: what is the impact? . Jason Andrews, MD, SM, DTM&H Division of Infectious Diseases Massachusetts General Hospital Harvard Medical School International AIDS Society July 2, 2013. Introduction: Active Case Finding (ACF). - PowerPoint PPT PresentationTRANSCRIPT
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Jason Andrews, MD, SM, DTM&HDivision of Infectious Diseases Massachusetts General Hospital
Harvard Medical School
International AIDS SocietyJuly 2, 2013
Intensified case finding in the era of new diagnostics: what is the impact?
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Introduction: Active Case Finding (ACF)
• There are good data on yield of ACF for TB via community-based case finding or household contact investigations
• Meta-analysis of 27 studies: 4.5% HH contacts had active TB
• Shapiro et al. found at least one TB case in 19% of HHs where an index case had been found and 1% of random households visited in South Africa
• Fewer data on the individual level clinical benefits of early case detection.
• Even more limited evidence base (DETECTB, ZAMSTAR) on population level epidemiologic impact of ACF interventions Morrison et al., Lancet Infect Dis 2008
Shapiro et al., AJRCCM 2012
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What can mathematical models tell us about the benefits of active case finding for TB?
Not much… in quantitative terms.
Limitations in understanding of:1.Infectiousness over time2.Duration of subclinical tuberculosis3.Role of social contact structure
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Overview
1. Explain critical assumptions and limitations of TB diagnostic models
2. How these assumptions impact projections for community-based ACF and household contact investigations
3. What we need to make better projections
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Examining these assumptions:impact on ACF
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Dowdy DW, Basu S, Andrews JR. Am J Resp Crit Care Med, 2012
Passive CFActive CF
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Model and Results
• If individuals are asymptomatic (“subclinical”, and only 0.25x as infectious) for half of their duration of TB:- 20% increase in passive diagnosis would reduce TB incidence by 11% over 10 years- ACF targeted at 5% of population would reduce TB incidence by 16% over 10 years
• As duration/infectiousness subclinical period increases, efficacy of passive case detection decreases
• ACF needed if much of transmission occurs during a subclinical period
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Dowdy DW, Basu S, Andrews JR. Am J Resp Crit Care Med, 2012
?
?
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Examining these assumptions:household contact investigations
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Household
InfectiousExposedSusceptible
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Household
InfectiousExposedSusceptible
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Household
InfectiousExposedSusceptible
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Household
InfectiousExposedSusceptible
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Household
InfectiousExposedSusceptible
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Household Contacts
• Created a simple model, governed by ordinary differential equations, with two levels of transmission: within and between households
• Calibrated it to TB prevalence of 170/100,000• Varied proportion of TB transmitted within the
household versus within the community**• Projected the impact of:
1) HH contact investigations for active TB; 2) HH contact investigations + LTBI treatment
Assumed 100% coverage of intervention and “perfect” sensitivity of diagnostic testing
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0%
10%
20%
30%
40%
50%Reduction in TB Prevalence over 10 years
Screening Contacts Screening + LTBI Treatment
Percentage of all TB transmitted within Household
Redu
ction
in T
B Pr
eval
ence
20% 40%0%
Cape Town
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Conclusions
• We have poor data on role of subclinical TB in transmission, which is critical to projecting the impact of passive and active case finding approaches
• Epidemiologic impact of household contact investigations is somewhat attenuated due to mutual contacts between the index and secondary case
• Data on within-household versus between- household transmission could improve quantitative projections on contact investigation interventions
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Acknowledgements
Robin Wood, FCP(SA), DSc – University of Cape Town
Rochelle Walensky, MD, MPH – MGH/HarvardDavid Dowdy, MD, PhD – Johns HopkinsSanjay Basu, MD, PhD – StanfordMegan Murray, MD, ScD - Harvard