Project Overview
Project title: Cryptococcal Antigenaemia Screening and Treatment – Observations From the Field in South Africa.
Cryptococcus, a fungal pathogen, causes a meningitis that is the second leading cause of death among people with advanced HIV disease (AHD, defined as CD4 count<200 cells/μL). The lower a patient’s CD4 count, the greater their risk of developing cryptococcal meningitis. Cryptococcal antigen can be detected in the blood of asymptomatic patients before they develop symptomatic cryptococcal meningitis. In South Africa, a lumbar puncture is recommended for anybody with a positive serum cryptococcal antigen test, whether asymptomatic or symptomatic, to determine whether they have cryptococcal antigenaemia without cerebrospinal fluid involvement (treated with oral fluconazole) or cryptococcal meningitis (treated intravenous liposomal amphotericin B and flucytosine followed by oral fluconazole).
It is important to screen and treat cryptococcal infection as early as possible to prevent progression to meningitis and death among people with AHD.. A reflex screening programme initiated in 2016 in South Africa at all CD4 testing laboratories tests plasma/serum samples of all patients with a CD4 count<100 cells/μL for cryptococcal antigen (<200 cells/μL in the Western Cape), regardless of symptoms. Since 2016, the programme has achieved a high screening coverage of 92.4% of eligible patients.
However, follow-up and appropriate management of patients remain limited: only 11% of patients receive a lumbar puncture following a positive cryptococcal antigen result and fluconazole therapy is often delayed, incorrectly prescribed or not administered.
Study Design
CAST OFF-SA is a sub-study of the EFFECT trial which is an ongoing phase 3 randomised controlled trial comparing the impact of combining flucytosine with fluconazole versus fluconazole alone on all-cause 6-month mortality in adults with asymptomatic HIV-associated cryptococcal antigenaemia without cerebrospinal fluid involvement in South Africa and Tanzania.
Using questionnaires and focus group discussions with staff from clinics linked to EFFECT trial sites and in-depth interviews with EFFECT trial investigators in South Africa, CAST OFF-SA is exploring barriers to care for patients following a positive cryptococcal antigen result and potential solutions to these barriers. Furthermore, National Health Laboratory Service data will be used to compare system metrics before and after trial implementation.


