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Cryptococcal Antigen Screening in Uganda. David R Boulware MD MPH Radha Rajasingham MD David B Meya MMed. Infectious Disease Institute Makerere University. Etiologies of Meningitis in Africa. Cape Town, South Africa. Kampala, Uganda. Jarvis J et al. AIDS 2009. Unpublished 2006-2011 data.
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Cryptococcal Antigen Screening in Uganda David R Boulware MD MPH Radha Rajasingham MD David B Meya MMed Infectious Disease Institute Makerere University
Etiologies of Meningitis in Africa Cape Town, South Africa Kampala, Uganda Jarvis J et al. AIDS 2009 Unpublished 2006-2011 data
Cryptococcal Antigen (CrAg) Prevalence 0% 5% 10% 15% 20% 25% Cambodia, CD4<100 Kumasi, Ghana, CD4 <100 Tororo, Uganda, CD4<100 Masaka, Uganda, CD4<200 Mbarara, Uganda, HIV clinic pop. Thailand (Rural), HIV+ pneumonia Benin City, Nigeria, CD4<200 Bangkok, Thailand, CD4<100 Cape Town, South Africa, CD4<100 Kisumu, Kenya, CD4<100 Kampala, Uganda, CD4<100 hospitalized Kampala, Uganda, CD4<100, HIV clinic Kinshasa, DRC, HIV clinic pop. Rhein J. Neurobehavioiral HIV Med 2012
Long Term Survival in Kampala Butler E. et al. Submitted
Cost Effectiveness No CrAg Screening CrAg Latex Agglutination CrAg Lateral Flow Assay Rajasingham MOAB0102
Cost per Life Saved by CrAg LFA Screening vs. Prevalence Cambodia, CD4<100 Kumasi, Ghana, CD4 <100 Tororo, Uganda, CD4<100 Masaka, Uganda, CD4<200 Mbarara, Uganda, HIV clinic pop. Thailand (Rural), HIV+ pneumonia Benin City, Nigeria, CD4<200 Bangkok, Thailand, CD4<100 Cape Town, South Africa, CD4<100 Kisumu, Kenya, CD4<100 Kampala, Uganda, CD4<100 hospitalized Kampala, Uganda, CD4<100, HIV clinic Kinshasa, DRC, HIV clinic pop. $2.50 CrAg LFA total test cost Rhein J. Neurobehavioiral HIV Med 2012
CRAG Screening is Cost Saving • Conversely, the cost of hospitalization and 14 days of amphotericin for treatment of cryptococcal meningitis is: • $425 per episode in Uganda [WEPE028] • $2883 per episode in South Africa • Thus for the treatment costs of 1 cryptococcal meningitis episode, one could perform CRAG LFA screening on: • 170 persons in Uganda • 1153 persons in South Africa. • Above a CRAG+ prevalence of 1%, pre-ART CRAG screening is Cost Savingcompared to the cost of any Cryptococcal Meningitis treatment Rajasingham MOAB0102
CrAg Screening concept is great, but will it work in the real world?
ORCAS Trial • Operational Research in CrAg Screening • Multisite CrAg Screening Project in Uganda • Implementation Science • Stepped Wedge Design, RCT • Roll out over 2 years
CrAg Roll Out IDI
Design Lab-reflex test +POC CD4 Clinician-based
ORCAS Endpoints • Primary: 6-month Survival • Secondary: • Cryptococcal meningitis free survival time • Uptake of screening & pre-emptive treatment • Cost Effectiveness • Concordance between LFA & latex, other body fluids
Multiple ORCAS Partners • Infectious Disease Institute • David Meya, Radha Rajasingham, Yuka Manabe • University of Minnesota • David Boulware, Melissa Rolfes, Josh Rhein • CDC and CDC-Uganda • Jonathan Kaplan, Emmy Bangizi Muramuzi, Anthony Mukasa Mubiru, Ben Park, et al.