Abstract

BackgroundCryptococcal meningitis has a high morbidity and mortality among AIDS population. Cryptococcal antigen (CrAg) detection is considered an independent predictor for meningitis and death. Since 2011, the World Health Organization recommends CrAg screening for people living with HIV/AIDS (PLHAs) with CD4 counts <100–200 cells/μl. Its implementation is still limited in low-middle-income countries. We aimed to estimate the prevalence and predictors of CrAg positivity in PLHAs. We also evaluated outcomes among those who were CrAg-positive.MethodsProspective cohort conducted at an infectious diseases hospital, in Brazil. Adults with CD4 <200 cells/μl, without previous cryptococcal disease and regardless of symptoms, were enrolled from 2015 to 2018. CrAg tests were performed by LFA. Lumbar puncture was done in CrAg+ individuals and pre-emptive therapy was offered for those without meningitis.ResultsOf 214 individuals recruited, 88% were antiretroviral experienced, of which only 11.6% with viral suppression. Overall, CrAg prevalence was 7.9% (95% CI, 4.7–12.4). In CD4 ≤100 cells/μl group it was 7.5% (95% CI, 4.1–12.6) and 9.1% (95% CI, 3.4–19.0) in the group with CD4 101 to 199 cells/μl (p = 0.17). Prevalence in asymptomatic subjects was 5.3% (95% CI, 1.4–13.1). One among 17 CrAg+ participants had documented meningoencephalitis and no subclinical meningitis was detected. Adherence to pre-emptive treatment was 68.7% (11/16). There were no statistically significant differences in sociodemographic, clinical or laboratory characteristics to predict CrAg positivity. No case of cryptococcal disease was diagnosed among CrAg + subjects, followed by a median of 12 months.ConclusionsCrAg screening for severely immunosuppressed PLHAs in Brazil yielded a prevalence of 7.9%. No difference was found in the prevalence of CrAg stratified by CD4 values (CD4 <100 versus CD4 101–199 cells/μl). No clinical nor laboratory factors predicted CrAg positivity, corroborating the need for the implementation of universal CrAg screening for PLHAs with CD4 <200 cells/μl in similar settings.

Highlights

  • Cryptococcal meningoencephalitis accounts for 70% to 90% of cases of cryptococcal disease in patients with HIV; it is a life-threatening infection and the second leading cause of death in this population [1, 2]

  • Cryptococcal antigen (CrAg) screening for severely immunosuppressed people living with HIV/AIDS (PLHAs) in Brazil yielded a prevalence of 7.9%

  • No clinical nor laboratory factors predicted CrAg positivity, corroborating the need for the implementation of universal CrAg screening for PLHAs with CD4

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Summary

Introduction

Cryptococcal meningoencephalitis accounts for 70% to 90% of cases of cryptococcal disease in patients with HIV; it is a life-threatening infection and the second leading cause of death in this population [1, 2]. In Brazil in 2017, around 860,000 (630,000–1,100,000) people were living with HIV, 84% of whom were aware of their status; 64% received ART and 59% had an undetectable viral load [5]. Latin America has the third highest rate of HIV/AIDS-related cryptococcal meningitis in the world, with an estimated 7,000 (3,600–11,100) people with positive antigenaemia, 5,300 (2,600–8,900) with cryptococcal meningitis and 2,400 (1,100–4,400) deaths annually [1]. The mortality rate of cryptococcosis as the primary cause of death among people living with HIV/AIDS (PLHAs) in Brazil was found to be 0.47/million inhabitants [7], reaching 30% to 62% of fatality in cryptococcal meningitis [8,9,10]. Since 2011, the World Health Organization recommends CrAg screening for people living with HIV/AIDS (PLHAs) with CD4 counts

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