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Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence.

ABSTRACT: Background. ?Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods. ?Sera were collected from 214 consenting HIV-infected participants with CD4(+) counts <250 cells/mm(3), irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results. ?Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4(+) cell count was 160 cells/mm(3) (interquartile range, 90-210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4(+) cell counts <100 cells/mm(3), 4 of 80 (5.0%) in the 100-200 group, and 9 of 73 (12.3%) in 200-250 cells/mm(3) group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm(3), which was unrelated to CrAg positivity (P = .018). Conclusions. ?We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We recommend CrAg screening for HIV-infected patients, even for patients on ART.

SUBMITTER: Oladele RO

PROVIDER: S-EPMC4866571 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence.

Oladele Rita O RO Akanmu Alani S AS Nwosu Augustina O AO Ogunsola Folasade T FT Richardson Malcolm D MD Denning David W DW

Open forum infectious diseases 20160315 2

Background. Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods. Sera were collected from 214 consenting HIV-infected participants with CD4(+) counts <250 cells/mm(3), irr ...[more]

PMID: 27186581

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Project description:Background. ?Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/µL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Methods. ?We conducted a retrospective study including all ART-naive adults with CD4 <150 cells/µL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen was assessed in cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of death or loss to follow-up (LFU) by CRAG status and fluconazole use. Results. ?Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/µL. Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG-negative patients were dead or LFU (P<.001), with no differences across CD4 strata. Cryptococcal antigen positivity was an independent predictor of death or LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions. ?Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150 cells/µL, and fluconazole increased survival or retention-in-care, suggesting that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG screening threshold of CD4 <100 cells/µL missed 18% of CRAG-positive patients, suggesting guidelines should consider a higher threshold.

Project description:BACKGROUND:Cryptococcosis is a global public health important infectious disease. HIV infection is the main risk factor estimated to account for 95% of cases in the middle- and low-income countries and 80% of the cases in high-income countries. OBJECTIVE:The main aim of the study was to determine the prevalence and associated risk factors of Cryptococcal antigenemia (CrAg) among HIV/AIDS Patients on second-line ART Therapy at Ambo General Hospital and Nekemte Referral Hospital, Western Oromia, Ethiopia. MATERIALS AND METHODS:Hospital-based cross-sectional study was employed from September 1, 2017, to October 30, 2017. Whole blood was tested for CrAg using Cryptococcal lateral flow assay (Immuno-Mycologics, Norman, OK, USA) according to the manufacturer's instructions. The collected data were analyzed using SPSS version 20 software. Binary logistic regression models were applied to assess the association between predictors and outcome variables at 95% CI. RESULT:Among the study participants, 115(62.8%) were females and the median age of the participants was 35 (IQR: 14) years. Majority, 169(92.3%), have been living with HIV for ? 5.6 years and 124 (67.8%) stayed on 2nd line ART for an average of 2.5 years. The overall prevalence of Cryptococcal antigenemia in the study participants was 7.7% (14/183). Being male [AOR, 95% CI: 4.78(1.14, 20.1)], poor adherence to ART [AOR, 95% CI: 0.12(0.03, 0.4)], occupational exposures to contaminated soil [AOR, 95% CI: 6.81(1.38, 33.4)], having non-separated house from chickens [AOR, 95% CI: 0.06(0.01, 0.51)], CD4 T+ cell levels ? 100 cell/?L [AOR, 95% CI: 6.57(1.9, 23.3)] and viral load >1000 copies/mL [AOR, 95% CI: 11.7(2.4, 57.8)] were significant predictors of Cryptococcal antigenemia (P? 0.05). CONCLUSION:The prevalence of Cryptococcal Antigenemia was significantly high in this study. Being male, occupational exposure to contaminated soil with avian droppings, CD4+ T cell levels <100 cell/?L and viral load >1000 copies/mL were significant predictors of Cryptococcal antigenemia. Therefore, public health measures, adherence to ART and early treatment are recommended.

Project description:BACKGROUND:Individuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies. METHODS:We evaluated 1201 human immunodeficiency virus-seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic-symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif. RESULTS:We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ?5 white cells/?L) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P = .91). CONCLUSIONS:Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity. CLINICAL TRIALS REGISTRATION:NCT01802385.

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Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence.

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Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence.

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