Laboratory-reflex cryptococcal antigen screening is associated with a survival benefit in Tanzania.

Abstract

BACKGROUND

Cryptococcal antigen (CrAg) screening in persons with advanced HIV/AIDS is recommended to prevent death. Implementing CrAg screening only in outpatients may underestimate the true CrAg prevalence and decrease its potential impact. Our previous 12-month survival/retention in CrAg-positive persons not treated with fluconazole was 0%.

METHODS

HIV testing was offered to all ART-naive outpatients and hospitalized patients in Ifakara, Tanzania, followed by laboratory-reflex CrAg screening for CD4<150 cells/μL. CrAg-positive individuals were offered lumbar punctures, and antifungals were tailored to the presence/absence of meningitis. We assessed the impact on survival and retention-in-care using multivariate Cox regression models.

RESULTS

We screened 560 individuals for CrAg. The median CD4 count was 61 cells/μL (IQR 26-103). CrAg prevalence was 6.1% (34/560) among individuals with CD4 ≤150 and 7.5% among ≤100 cells/μL. CrAg prevalence was 2.3-fold higher among hospitalized participants than in outpatients (12% vs. 5.3%, p=0.02). We performed lumbar punctures in 94% (32/34), and 31% (10/34) had cryptococcal meningitis. Mortality did not differ significantly between treated CrAg-positive without meningitis and CrAg-negative individuals (7.3 vs 5.4 deaths per 100 persons-year, respectively, p=0.25). Independent predictors of 6-month death/lost to follow-up were low CD4, cryptococcal meningitis (adjusted hazard ratio (aHR) 2.76, 95% CI 1.31-5.82)), and no ART initiation (aHR 3.12, 95%CI 2.16-4.50).

CONCLUSIONS

Implementing laboratory-reflex CrAg screening among outpatients and hospitalized-individuals resulted in a rapid detection of cryptococcosis and a survival benefit. These results provide a model of a feasible, effective and scalable CrAg screening and treatment strategy integrated into routine care in sub-Saharan Africa.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.