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. 2020 Apr 10;70(8):1683-1690.
doi: 10.1093/cid/ciz485.

Cryptococcal-related Mortality Despite Fluconazole Preemptive Treatment in a Cryptococcal Antigen Screen-and-Treat Program

Rachel M Wake  1   2 , Nelesh P Govender  1   3   4 , Tanvier Omar  5   6 , Carolina Nel  5   6 , Ahmad Haeri Mazanderani  7   8 , Aaron S Karat  9 , Nazir A Ismail  10 , Caroline T Tiemessen  7   11 , Joseph N Jarvis  12   13   14 , Thomas S Harrison  2
Affiliations

Cryptococcal-related Mortality Despite Fluconazole Preemptive Treatment in a Cryptococcal Antigen Screen-and-Treat Program

Rachel M Wake et al. Clin Infect Dis. .

Erratum in

Abstract

Background: Cryptococcal antigen (CrAg) screening and treatment with preemptive fluconazole reduces the incidence of clinically evident cryptococcal meningitis in individuals living with advanced human immunodeficiency virus (HIV) disease. However, mortality remains higher in CrAg-positive than in CrAg-negative patients with similar CD4+ T-lymphocyte counts.

Methods: We conducted a cohort study to investigate causes of morbidity and mortality during 6 months of follow-up among asymptomatic CrAg-positive and CrAg-negative (ratio of 1:2) patients living with HIV with CD4 counts <100 cells/µL attending 2 hospitals in Johannesburg, South Africa. When possible, minimally invasive autopsy (MIA) was performed on participants who died.

Results: Sixty-seven CrAg-positive and 134 CrAg-negative patients were enrolled. Death occurred in 17/67 (25%) CrAg-positive and 12/134 (9%) CrAg-negative participants (hazard ratio for death, adjusted for CD4 count, 3.0; 95% confidence interval, 1.4-6.7; P = .006). Cryptococcal disease was an immediate or contributing cause of death in 12/17 (71%) CrAg-positive participants. Postmortem cryptococcal meningitis and pulmonary cryptococcosis were identified at MIA in all 4 CrAg-positive participants, 3 of whom had negative cerebrospinal fluid CrAg tests from lumbar punctures (LPs) at the time of CrAg screening.

Conclusions: Cryptococcal disease was an important cause of mortality among asymptomatic CrAg-positive participants despite LPs to identify and treat those with subclinical cryptococcal meningitis and preemptive fluconazole for those without meningitis. Thorough investigation for cryptococcal disease with LPs and blood cultures, prompt ART initiation, and more intensive antifungals may reduce mortality among asymptomatic CrAg-positive patients identified through screening.

Keywords: AIDS-related opportunistic infections; acquired immunodeficiency syndrome; autopsy; cryptococcus; meningitis.

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Figures

Figure 1.
Figure 1.
Flow diagram showing patients included and excluded in the prospective cohort study. Abbreviations: CD4, CD4 T-lymphocyte count; CM, cryptococcal meningitis; CrAg, cryptococcal antigen; HIV, human immunodeficiency virus; MIA, minimally invasive autopsy.
Figure 2.
Figure 2.
Kaplan–Meier curve showing mortality estimates in CrAg-positive and CrAg-negative patients within 6 months, adjusted for baseline CD4 T-lymphocyte count. Abbreviations: CI, confidence interval; CrAg, cryptococcal antigen.
See this image and copyright information in PMC

Comment in

References

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