1. Cryptococcal Antigen Screening in Uganda David R Boulware MD MPH Radha Rajasingham MD David B Meya MMed Infectious Disease Institute Makerere University

2. Cape Town, South AfricaKampala, Uganda Jarvis J et al. AIDS 2009 Etiologies of Meningitis in Africa Unpublished 2006-2011 data

3. 0% 5% 10% 15% 20% 25% Masaka, Uganda, CD4<200 Thailand (Rural), HIV+ pneumonia Benin City, Nigeria, CD4<200 Bangkok, Thailand, CD4<100 Cape Town, South Africa, CD4<100 Cambodia, CD4<100 Kampala, Uganda, CD4<100, HIV clinic Mbarara, Uganda, HIV clinic pop. Tororo, Uganda, CD4<100 Kumasi, Ghana, CD4 <100 Kinshasa, DRC, HIV clinic pop. Kisumu, Kenya, CD4<100 Kampala, Uganda, CD4<100 hospitalized Cryptococcal Antigen (CrAg) Prevalence Rhein J. Neurobehavioiral HIV Med 2012

4. Meya D. Clin Infect Dis 2010

5. Long Term Survival in Kampala Butler E. et al. Submitted

6. CrAg Latex Agglutination CrAg Lateral Flow Assay No CrAg Screening Cost Effectiveness Rajasingham MOAB0102

7. Masaka, Uganda, CD4<200 Thailand (Rural), HIV+ pneumonia Benin City, Nigeria, CD4<200 Bangkok, Thailand, CD4<100 Cape Town, South Africa, CD4<100 Cambodia, CD4<100 Kampala, Uganda, CD4<100, HIV clinic Mbarara, Uganda, HIV clinic pop. Tororo, Uganda, CD4<100 Kumasi, Ghana, CD4 <100 Kinshasa, DRC, HIV clinic pop. Kisumu, Kenya, CD4<100 Kampala, Uganda, CD4<100 hospitalized Cost per Life Saved by CrAg LFA Screening vs. Prevalence Rhein J. Neurobehavioiral HIV Med 2012 $2.50 CrAg LFA total test cost

8. 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 C OST S AVING compared to the cost of any Cryptococcal Meningitis treatment CRAG Screening is Cost Saving Rajasingham MOAB0102

9. CrAg Screening concept is great, but will it work in the real world?

10. ORCAS Trial Operational Research in CrAg Screening Multisite CrAg Screening Project in Uganda Implementation Science Stepped Wedge Design, RCT Roll out over 2 years

12. IDI CrAg Roll Out

13. Design Lab-reflex test +POC CD4 Clinician-based

14. 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

15. 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.