Cryptococcal Antigenemia in South African Children Living With HIV

Alison Gifford; Rudzani Mashau; Ruth Mpembe; David Khanyile; Thabo Maota; Mbali Dube; Boitumelo Kgoale; Adilia Warris; Nelesh P Govender

doi:10.1097/INF.0000000000005154

Cryptococcal Antigenemia in South African Children Living With HIV

Pediatr Infect Dis J. 2026 Jan 28:10.1097/INF.0000000000005154. doi: 10.1097/INF.0000000000005154. Online ahead of print.

Authors

Alison Gifford¹, Rudzani Mashau^{2

3}, Ruth Mpembe², David Khanyile⁴, Thabo Maota⁴, Mbali Dube², Boitumelo Kgoale², Adilia Warris¹, Nelesh P Govender^{1

2

3}

Affiliations

¹ Department of Biosciences, Faculty of Life and Health Sciences, MRC Centre for Medical Mycology, University of Exeter, Exeter, UK.
² Division of the National Health Laboratory Service, National Institute for Communicable Diseases, Johannesburg, South Africa.
³ Wits Mycology Division, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Epicentre Health Research, Johannesburg, South Africa.

Abstract

Background: Cryptococcal meningitis (CM) is associated with high mortality and neurodevelopmental sequelae and predominantly affects people living with HIV. Screening and pre-emptive treatment for cryptococcal antigen (CrAg) in blood in adults with CD4 <200 cells/µL reduces mortality. The World Health Organization does not recommend screening children <10 years due to a presumed low prevalence of CM. Nevertheless, CrAg testing is performed for all ages in South Africa in those with CD4 <100 cells/µL.

Methods: Children (<18 years) with CD4 <100 cells/µL and a CrAg screening result were identified from National Health Laboratory Service records from 2017 to 2022 in South Africa. Fifteen healthcare facilities in Gauteng province were chosen for a convenience sample of CrAg-positive and matched CrAg-negative children to collect detailed clinical information.

Results: Prevalence of cryptococcal antigenemia in South African children <18 years was 4.7% (1352/28,839) with a median age of 14 years (IQR 11-16). CrAg-positive prevalence in children <10 years was 3.5% (261/7440). Fifty-one CrAg-positive children were included for in-depth chart review. Twenty-four (24/49; 49%) CrAg-positive children had documented symptoms of meningitis at testing; 33% were diagnosed with CM. Forty-seven percent (8/17) of CrAg-positive children without documented symptoms developed their first CM episode in the subsequent 12 months. Five percent (1/19) of CrAg-positive children pre-emptively treated with fluconazole were subsequently diagnosed with CM, compared with 58% (7/12) of those without a documented prescription (P = 0.002). The 6-month mortality for CrAg-positive children was 19% (7/36). No CrAg-negative children developed CM.

Conclusions: CrAg prevalence in children with CD4 <100 cells/µL is comparable to adults (4.7% and 5.8%, respectively). CrAg screening guidelines should be extended to include all children to improve outcomes.

Keywords: Cross-sectional study; Cryptococcus; HIV; cryptococcal antigen; cryptococcal meningitis.

Grants and funding

MR/ W502649/1/Medical Research Council Centre Doctoral Training Grant