Cryptococcal Antigen Screening in Uganda

Cryptococcal Antigen Screening in Uganda

David R Boulware MD MPHRadha Rajasingham MD

David B Meya MMed

Infectious Disease Institute Makerere University

CryptococcusTBBacterialAseptic/Viral

Cape Town, South Africa Kampala, Uganda

CryptococcusTBBacterialAseptic/Viral

Jarvis J et al. AIDS 2009

Etiologies of Meningitis in Africa

Unpublished 2006-2011 data

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

Meya D. Clin Infect Dis 2010

Long Term Survival in Kampala

Butler E. et al. Submitted

CrAg Latex Agglutination

CrAg Lateral Flow Assay

No CrA

g Scre

ening

Cost Effectiveness

Rajasingham MOAB0102

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

• 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 SAVING compared to the cost of any Cryptococcal Meningitis treatment

CRAG Screening is Cost Saving

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

IDI

CrAg Roll Out

Design Lab-reflex test +POC CD4Clinician-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.