Screening for Cryptococcal Antigenemia in Patients Accessing an Antiretroviral Treatment Program in South Africa

Abstract

Background Cryptococcal meningitis is a leading cause of death in AIDS patients and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. Screening for cryptococcal antigen (CRAG) in patients enrolling in ART programs may identify those at risk of cryptococcal meningitis and permit targeted use of pre-emptive therapy. Methods In this retrospective study, CRAG was measured in stored plasma samples obtained from patients as they enrolled in a well characterised ART cohort in South Africa. The predictive value of screening for CRAG prior to ART for development of microbiologically confirmed cryptococcal meningitis or death during the first year of follow-up was determined. Results Of 707 participants with a baseline median CD4 count of 97 (IQR 46-157) cells/μL, 46 (7%) had a positive CRAG. Antigenaemia was 100% sensitive for predicting development of cryptococcal meningitis during the first year of ART and in multivariate analysis was an independent predictor of mortality (AHR 3.2, 95%CI 1.5-6.6). Most (92%) cases of cryptococcal meningitis developed in patients with a CD4 count ≤100 cells/μL. In this sub-set of patients, a CRAG titre ≥1 in 8 was 100% sensitive and 96% specific for predicting incident cryptococcal meningitis during the first year of ART in those with no previous history of the disease. Conclusions CRAG screening prior to commencing ART in patients with a CD4 count ≤100 cells/μL is highly effective at identifying those at risk of cryptococcal meningitis and death and might permit implementation of a targeted pre-emptive treatment strategy.

Phased implementation of screening for cryptococcal disease in South Africa

“…10 In two South African ART cohorts, the prevalence of incident antigenaemia among patients with a CD4+ T-lymphocyte count <100 cells/µl was 4% and 7% respectively. 11,12 This is greater than the breakpoint above which screening was found to be potentially cost-saving in a Ugandan study. 13,14 To reduce disability and deaths associated with HIV infection, it has been suggested that laboratory-based screening and preemptive antifungal treatment of cryptococcal disease be routinely implemented as part of the South African National Strategic Plan for HIV, STIs and TB, 2012-2016.…”

Cryptococcal neorformans Antigenemia among HIV-Infected Patients in North Eastern Nigeria

“…The high prevalence in our study warrants the need to screen for and diagnose cryptococcal infection among patients with severe immunosuppression prior to initiation of ART. This may prevent unmasking of sub-clinical infection, especially in patients who are asymptomatic due to immune reconstitution [32].…”

Cryptococcosis in apparently immune-competent patients: taxonomy, epidemiology, pathophysiology and treatment

“…Although CD4 + T-cell function is clearly of key importance (as demonstrated by the emergence of cryptococcosis alongside the HIV/AIDS epidemic), only 4%-11% of patients with CD4 + T-cell counts of less than 100 cells/μl in sub-Saharan Africa have cryptococcal antigen detectable in blood. [25][26][27][28][29][30][31][32][33][34] This indicates that additional or underlying factors, in addition to CD4 + T-cell deficiency, may lead to increased susceptibility in a subset of individuals. A greater understanding of host immunity to cryptococcosis has been achieved though recent studies in animal models as well as humans, both with and without immune-compromise.…”