Abstract
Background: The prevalence of different underlying cryptococcal diseases in human immunodeficiency virus (HIV)-infected patients screened positive for cryptococcal antigenemia and the association between cryptococcal diseases and serum cryptococcal antigen (CrAg) titers were understudied.Methods: HIV-infected patients with CD4 < 200 cells/ul, admitted to the second hospital of Nanjing, Nanjing, China, from January 2016 to September 2019, were retrospectively analyzed. Integrated into routine HIV care, all these patients were screened for cryptococcal antigenemia with CrAg lateral flow assay. Positive patients received extensive laboratory and radiological studies to evaluate underlying cryptococcal diseases.Results: A total of 872 HIV inpatients were screened for serum CrAg. The prevalence of cryptococcal antigenemia in the study population was 10.3% (95% CI, 8.3–12.3%), 87.6% of which with cryptococcal antigenemia had clinically cryptococcal diseases. The prevalence of cryptococcal meningitis (CM), cryptococcemia and pulmonary cryptococcosis (PC) in patients with cryptococcal antigenemia were 58.4% (95% CI, 48.0–68.9%), 50.7% (95% CI, 39.1–62.2%), and 68.5% (95% CI, 58.7–78.4%), respectively. The median (range) serum CrAg titers in severe cryptococcal diseases (CM or cryptococcemia), localized PC (without co-existing CM or cryptococcemia) and isolated cryptococcal antigenemia were 1:2560 (1:10–1:2560), 1:20 (1:2–1:320), and 1:5 (1:2–1:320), respectively. Serum CrAg titers ≥1:320 were independently associated with CM (adjusted OR 26.88; 95%CI, 8.36–86.42). Severe cryptococcal diseases were found in all patients with serum CrAg titers ≥1:640. None of the patients with serum CrAg titers ≤ 1:5 had CM.Conclusion: The prevalence of cryptococcal antigenemia was high in HIV inpatients, supporting routine CrAg screening. Clinical cryptococcal diseases, most commonly the PC, existed in the majority of the patients with cryptococcal antigenemia. Since serum CrAg titer is correlated with cryptococcal disease severity, it may possibly guide anti-fungal treatment.
Highlights
The prevalence of different underlying cryptococcal diseases in human immunodeficiency virus (HIV)-infected patients screened positive for cryptococcal antigenemia and the association between cryptococcal diseases and serum cryptococcal antigen (CrAg) titers were understudied
The reported deaths of cryptococcal diseases are generally related to cryptococcal meningitis (CM) which had around 0.22 million incident cases leading to about 0.18 million deaths each year (Rajasingham et al, 2017)
A total of 872 hospitalized HIV-infected patients were screened for serum CrAg, 21% of whom were on antiretroviral therapy (ART) with median ART duration of 6 (Pac et al, 2015; Rajasingham et al, 2017) months
Summary
The prevalence of different underlying cryptococcal diseases in human immunodeficiency virus (HIV)-infected patients screened positive for cryptococcal antigenemia and the association between cryptococcal diseases and serum cryptococcal antigen (CrAg) titers were understudied. Cryptococcal antigenemia precedes symptoms of CM by a median of 22 days (French et al, 2002), suggesting that cryptococcal antigenemia screening may identify early cryptococcal diseases before progressing to CM. This screening strategy has been advocated in routine HIV care and may reduce mortality of HIV-infected patients (Rajasingham et al, 2012; Kaplan et al, 2015; Mfinanga et al, 2015). The prevalence of cryptococcal antigenemia was higher among inpatients 9.8%, with region-related variations (95% CI, 4.0–15.5%) (Ford et al, 2018)
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