Risk factors for cryptococcal infection among people with HIV receiving care at a referral hospital in Uganda: a nested case–control study
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Date
2026-04-27
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Nature
Abstract
Background
Cryptococcal infection is a major cause of morbidity and mortality among people with HIV (PWH), particularly those with advanced immunosuppression. Cryptococcal infection, detected by a laboratory-confirmed positive serum cryptococcal antigen (CrAg) test (cryptococcal antigenemia), typically precedes cryptococcal meningitis and provides a critical window for prevention. However, recent data on its risk factors in Uganda are limited. We assessed the risk factors for cryptococcal infection among PWH with non-suppressed viral load and severe immunosuppression receiving care at a referral hospital in midwestern Uganda.
Methods
We conducted a facility-based nested case-control study among PWH with non-suppressed viral load (viral load ≥ 1,000 copies/mL) and severe immunosuppression (CD4 < 200 cells/µL) at the Fort Portal Regional Referral Hospital in midwestern Uganda. Cases were PWH with a positive serum CrAg test, and controls were those with a negative serum CrAg test in a 1:2 case-to-control ratio, respectively. Socio-demographic and clinical data were retrospectively extracted from routine records. Multivariable binary logistic regression analysis was used to identify factors independently associated with cryptococcal infection. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported.
Results
We included 89 cases and 178 controls, with comparable mean age between the groups: 40.3 ± 12.4 years vs. 40.4 ± 11.7 years, respectively; p = 0.952. In the multivariable analysis, PWH with advanced World Health Organization (WHO) clinical stages III/IV compared to WHO clinical stages I/II (aOR 3.45, 95% CI 1.28–9.97), and those with missed clinic visits within three months before the serum CrAg testing compared to those without any missed clinic visits (aOR 2.39, 95% CI 1.14–5.02) had higher odds of cryptococcal infection.
Conclusion
This study showed that among PWH with non-suppressed viral load and severe immunosuppression, cryptococcal infection is strongly associated with markers of advanced HIV disease and gaps in care engagement. Strengthening retention in care, improving clinic appointment tracking, and ensuring timely serum CrAg screening among PWH with non-suppressed viral load may reduce cryptococcal disease burden through early diagnosis and treatment.
Description
This study advances Sustainable Development Goal (SDG) 3 (Good Health and Well-being), Target 3.4, by enhancing health literacy and informed health decision-making among young people. It further supports SDG 4 (Quality Education), Target 4.7, by promoting critical thinking, evidence-based learning, and lifelong learning skills, as well as SDG 16 (Peace, Justice and Strong Institutions), Target 16.7, by encouraging informed and inclusive decision-making. In alignment with Uganda’s National Development Plan IV (NDP IV), the research supports the Human Capital Development Programme, particularly initiatives aimed at improving education quality, learner competencies, and health awareness. By investigating the potential adverse effects of critical thinking interventions, such as anxiety, inequity, conflict, and cognitive dissonance, this study offers evidence to inform the design of more effective and learner-centered educational programmes. The results inform the development of policies and teaching strategies that foster critical thinking while protecting learner wellbeing, thereby contributing to human capital development, evidence-based decision-making, and the cultivation of informed, resilient citizens equipped to address complex health and societal challenges.
Keywords
Cryptococcal antigenemia, Cryptococcal infection, People with HIV, Uganda
Citation
Namuyanja, S., Appeli, S., & Izudi, J. (2026). Risk factors for cryptococcal infection among people with HIV receiving care at a referral hospital in Uganda: a nested case–control study. BMC Infectious Diseases,