Prospective cohort of AIDS patients screened for cryptococcal antigenaemia, pre-emptively treated and followed in Brazil

Abstract

Background Cryptococcal 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. Methods Prospective 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. Results Of 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. Conclusions CrAg 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.

Epidemiology and Mortality of Cryptococcal Disease in Guatemala: Two-Year Results of a Cryptococcal Antigen Screening Program

“…For more information about the reporting criteria in each country, see Supplementary Data (Supplementary Material) . Considering all regional publications, four reported the frequency of CrAg in patients with ≤100 cells/mm 3 [ 9 , 10 , 11 , 12 ] and three in patients with <200 cells/mm 3 [ 9 , 13 , 14 ]. Using these results and ours, the estimated overall CrAg frequency in the region for PLWHIV with <100 CD4 cells/mm 3 was 9.2% (IC95% 7.9–10.7%) and 8.1% in those with AHD (IC95% 7.9–10.7%).…”

“…Among Latin American people with HIV, we estimated that CrAg positivity is 9.2% (IC95% 7.9–10.7%) in patients with <100 CD4/mm 3 [ 9 , 10 , 11 , 12 , 13 , 14 ]. This number is 3.2% higher than the global estimation by Rajasingham et al in asymptomatic patients [ 2 ], which is an uncertain denomination considering the deep immunosuppressed status of such HIV patients.…”

Prevalence of Cryptococcal Antigen and Outcomes in People With Human Immunodeficiency Virus in Honduras: A Cohort Study

“…Our findings suggest that cryptococcal antigenemia prevalence is potentially higher than most of the studies in South America [ 8 , 9 , 18 ]. However, testing among these cohorts was performed on individuals with CD4 <200 cell/mm 3 [ 7 , 8 ], and thus this could explain potential differences of cryptococcal antigenemia prevalence with our study. Moreover, a Brazilian cohort also showed a prevalence of CrAg in CSF of 8.9% [ 8 ], comparable to our findings where prevalence in CSF was almost 8%.…”

“…Although recent evidence suggests high burden of CM in Latin America, Central America was not represented, because no studies exist from this region [ 1 ]. Efforts to address this gap have been mostly undertaken in South American countries [ 7–9 ] rather than in Central America or the Caribbean, where the burden of human immunodeficiency virus (HIV) is high [ 10 ] and the epidemic is worsening [ 11 ]. Honduras has recently reported high mortality rates associated with CM in individuals with HIV [ 12 ].…”

False-negative result of serum cryptococcal antigen lateral flow assay in an HIV-infected patient with culture-proven cryptococcaemia

“…More than one month later (T1, Day +47), during outpatient follow-up he complained solely of asthenia, without other systemic or neurological symptoms. A blood sample was collected for LFA cryptococcal antigenemia, blood culture and biochemical examinations as part of a study recruitment [9]. The serum CrAg LFA was negative, and the patient was advised to maintain clinical follow-up and adherence to ART.…”