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Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients hospitalized for suspected tuberculosis in Uganda.

ABSTRACT: BACKGROUND:Cryptococcal infection occurs in HIV-seropositive patients and is associated with high mortality. However, limited information is available on the prevalence and outcomes of cryptococcal antigenemia among hospitalized HIV-seropositive patients in sub-Saharan Africa. OBJECTIVES:To determine the prevalence of and risk factors for cryptococcal antigenemia among HIV-seropositive patients presenting to Mulago Hospital (Kampala, Uganda) with unexplained cough ?2 weeks and suspected tuberculosis (TB) and also to determine if antigenemia is associated with an increased mortality. METHODS:Between September 2009 and September 2010, we enrolled consecutive HIV-seropositive adults hospitalized at Mulago Hospital with cough ?2 weeks and suspected TB. Banked serum was tested for cryptococcal antigen. We compared demographic and clinical characteristics, and 2-month mortality in patients with and without cryptococcal antigenemia. RESULTS:Of 563 HIV-seropositive patients, 32 (5.7%) were cryptococcal antigen (CrAg) positive. None had Cryptococcus neoformans detected on fungal culture of bronchoalveolar lavage fluid (n = 116). CrAg-positive patients had a lower median CD4 count compared with CrAg-negative patients (25 vs. 55 cells/?L, P = 0.02), and a substantial proportion of CrAg-positive patients also had concurrent TB (31%). A positive CrAg test was not associated with increased mortality during the 2-month follow-up period (hazard ratio: 0.99, 95% confidence interval: 0.63 to 1.54, P = 0.95) after adjusting for CD4 count and antiretroviral therapy use at enrollment and/or follow-up. CONCLUSIONS:Occult cryptococcal antigenemia occurs commonly among hospitalized HIV-seropositive patients with suspected TB. CrAg testing should be considered in hospitalized HIV-seropositive patients with CD4 count <50 cells/?L, coupled with longer follow-up to evaluate the diagnostic value of CrAg and therapeutic interventions in patients with asymptomatic cryptococcal antigenemia.

SUBMITTER: Andama AO

PROVIDER: S-EPMC3779784 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients hospitalized for suspected tuberculosis in Uganda.

Andama Alfred O AO den Boon Saskia S Meya David D Cattamanchi Adithya A Worodria William W Davis J Lucian JL Walter Nicholas D ND Yoo Samuel D SD Kalema Nelson N Haller Barbara B Huang Laurence L

Journal of acquired immune deficiency syndromes (1999) 20130601 2

<h4>Background</h4>Cryptococcal infection occurs in HIV-seropositive patients and is associated with high mortality. However, limited information is available on the prevalence and outcomes of cryptococcal antigenemia among hospitalized HIV-seropositive patients in sub-Saharan Africa.<h4>Objectives</h4>To determine the prevalence of and risk factors for cryptococcal antigenemia among HIV-seropositive patients presenting to Mulago Hospital (Kampala, Uganda) with unexplained cough ≥2 weeks and sus ...[more]

PMID: 23542636

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Project description:BACKGROUND:Management of co-infections including cryptococcal meningitis, tuberculosis and other opportunistic infections in persons living with HIV can lead to complex polypharmacotherapy and increased susceptibility to drug-drug interactions (DDIs). Here we characterize the frequency and types of potential DDIs (pDDIs) in hospitalized HIV patients presenting with suspected cryptococcal or tuberculous meningitis. METHODS:In a retrospective review of three cryptococcal meningitis trials between 2010 and 2017 in Kampala, Uganda, medications received over hospitalization were documented and pDDI events were assessed. IBM Micromedex DRUGDEX® online drug reference system was used to identify and describe potential interactions as either contraindicated, major, moderate or minor. For antiretroviral DDIs, the Liverpool Drug Interactions Checker from the University of Liverpool was also used to further describe interactions observed. RESULTS:In 1074 patients with suspected meningitis, pDDIs were present in 959 (overall prevalence?=?89.3%) during the analyzed 30?day window. In total, 278 unique interacting drug pairs were identified resulting in 4582 pDDI events. Of all patients included in this study there was a mean frequency of 4.27 pDDIs per patient. Of the 4582 pDDI events, 11.3% contraindicated, 66.4% major, 17.4% moderate and 5% minor pDDIs were observed. Among all pDDIs identified, the most prevalent drugs implicated were fluconazole (58.4%), co-trimoxazole (25.7%), efavirenz (15.6%) and rifampin (10.2%). Twenty-one percent of the contraindicated pDDIs and 27% of the major ones involved an antiretroviral drug. Increased likelihood of QT interval prolongation was the most frequent potential clinical outcome. Dissonance in drug interaction checkers was noted requiring clinicians to consult more than one database in making clinical decisions about drug combinations. CONCLUSIONS:The overall prevalence of pDDIs in this population is high. An understanding of drug combinations likely to result in undesired clinical outcomes, such as QT interval prolongation, is paramount. This is especially important in resource limited settings where availability of therapeutic drug monitoring and laboratory follow-up are inconsistent. Adequate quantification of the increased likelihood of adverse clinical outcomes from multiple drug-drug interactions of the same kind in a single patient is needed to aid clinical decisions in this setting.

Project description:INTRODUCTION:Cryptococcus causes 15% of AIDS-related deaths and in South Africa, with its high HIV burden, is the dominant cause of adult meningitis. Cryptococcal meningitis (CM) mortality is high, partly because patients enter care with advanced HIV disease and because of failure of integrated care following CM diagnosis. We evaluated pathways to hospital care, missed opportunities for HIV testing and initiation of care. METHODS:We performed a cross-sectional study at five public-sector urban hospitals. We enrolled adults admitted with a first or recurrent episode of cryptococcal meningitis. Study nurses conducted interviews, supplemented by a prospective review of medical charts and laboratory records. RESULTS:From May to October 2015, 102 participants were enrolled; median age was 40 years (interquartile range [IQR] 33.9-46.7) and 56 (55%) were male. In the six weeks prior to admission, 2/102 participants were asymptomatic, 72/100 participants sought care at a public-sector facility, 16/100 paid for private health care. The median time from seeking care to admission was 4 days (IQR, 0-27 days). Of 94 HIV-seropositive participants, only 62 (66%) knew their status and 41/62 (66%) had ever taken antiretroviral treatment. Among 13 participants with a known previous CM episode, none were taking fluconazole maintenance therapy. In-hospital management was mostly amphotericin B; in-hospital mortality was high (28/92, 30%). Sixty-four participants were discharged, 92% (59/64) on maintenance fluconazole, 4% (3/64) not on fluconazole and 3% (2/64) unknown. Twelve weeks post-discharge, 31/64 (48%) participants were lost to follow up. By 12 weeks post discharge 7/33 (21%) had died. Interviewed patients were asked if they were still on fluconazole, 11% (2/18) were not. CONCLUSIONS:Among hospitalised participants with CM, there were many missed opportunities for HIV care and linkage to ART prior to admission. Universal reflex CrAg screening may prompt earlier diagnosis of cryptococcal meningitis but there is a wider problem of timely linkage to care for HIV-seropositive people.

Project description:Background:Cryptococcus neoformans is a frequent opportunistic infection in patients with the acquired immunode?ciency syndrome. While the advent of ART reduces the occurrence of cryptococcal meningitis in HIV patients, cryptococcal disease remains a leading cause of morbidity and mortality in the developing world especially in sub-Saharan Africa which is the epicenter of HIV. This study aimed to assess the cryptococcal antigenemia, CD4+ Th cell counts, HIV RNA viral load, and clinical presentations among HIV-positive patients in Northwest Ethiopia. Method:A total of two hundred (200) HIV-positive patients were recruited for this study. Cryptococcus antigenemia prevalence in plasma samples of HIV-positive patients was determined by using Antigen lateral ?ow assay (CrAg-LFA) also, and CD4+ Th cell counts and HIV-RNA levels were quantified from blood specimen. Patients' demographic data, clinical manifestation, and concurrent opportunistic infection were recorded. Result:The sex distributions of study participants were 105(52.5%) male and 94(47.5%) female with an age range of 15-65 (mean 39.42?±?9) years. All patients had a CD4+ T-cell count <100?cells/µl with the median 54?cells/?l and median HIV-RNA viral load 2.16?×?105 RNA copies/ml (50-3.66?×?105 RNA copies/ml); the prevalence of cryptococcal antigenemia was found to be 4% in HIV-positive patients. More than half and two third of CrAg-positive patients had a CD4 count <25?cells/?l and HIV viral load >10,000 copies/ml, respectively, as well; Tuberculosis, Candidiasis, and herpes zoster are the most often observed concurrent infections while cryptococcal antigenemia is significantly associated with oral candidiasis (p < 0.001). Conclusion:Although the advent of ART, early diagnosis of cryptococcosis, and application of antifungal interventions, HIV-induced cryptococcal antigenemia positivity in HIV infected individuals is still the countries' big challenge. Thus, stringent follow-up and case management should be considered.

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.

Dataset Information

Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients hospitalized for suspected tuberculosis in Uganda.

Publications

Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients hospitalized for suspected tuberculosis in Uganda.

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