Prevalence and factors associated with cryptoccocal antigenemia among patients with advanced HIV in Mbale regional referral hospital.

Abstract

Background Cryptococcal infection is an opportunistic infection caused by a fungal infection with Cryptococcus neoformans. It is found majorly among severely immunocompromised people, especially those living with advanced HIV. It is associated with a high rate of morbidity and mortality. A positive serum test for cryptococcal antigen (CrAg) is the current clinical practice gold standard for diagnosis of cryptococcal infection. This antigen-based test is the basis for categorizing patient’s antigenemia status. Cryptococcal infection is an independent predictor for cryptococcal meningitis which is the most severe form of Cryptococcal infection and the second commonest cause of morbidity and death among People Living with HIV (PLHIV) with Advanced HIV disease (AHD). AHD is defined as having a CD4 cell count of less than 200cells/mm World Health Organization (WHO) clinical stage 3 or 4 event at presentation in adults. In Uganda, Cryptococcal antigenemia and AHD have been described specially in central Uganda, but there are no formal studies describing the condition in Eastern Uganda. This study, therefore, assessed the prevalence and the factors associated with cryptococcal antigenemia among PLHIV with advanced HIV disease in Mbale Regional Referral Hospital (Mbale RRH).

Aims/Rationale The main objective of this study was to determine the prevalence and factors associated with cryptococcal antigenemia among PLHIV with advanced HIV disease.

Materials and Methods In this cross-sectional study, we recruited participants of 18 years of age and above who were HIV positive with advanced disease in Mbale RRH medical ward. Eligible participants were; all patients with AHD aged 18 years and above, voluntarily willing to participate in the study and able to give informed consent. They were recruited consecutively until a sample size of 228 was achieved. We collected data on social, demographic and clinical characteristics using a pre-tested customized data collection tool administered to study participants. Cryptococcal antigenemia was determined using Lateral flow assay (Immuno-Mycologics IMMYR) test. Besides the consent to participate in this study, additional mandatory clinical care consent was obtained as part of the hospital protocol from all CrAg positive patients to do a lumbar puncture (LP) and obtained Cerebral spinal fluid (CSF). The CSF was tested using the Lateral flow assay and if found positive was cultured using Sabouraud Dextrose agar culture media. All the positive cultures were subjected with a drug sensitivity testing (DST) for fluconazole and Amphotericin B sensitivity. The collected data were entered into an excel based databased, exported and were analyzed using STATA version 14.0. proportions of socio demographic factors were reported and prevalence of cryptococcal antigenemia was reported as proportion of those patients with positive serum CrAg compared to the total number of patients enrolled in the study. Factors associated with cryptococcal antigenemia were reported first as proportion and further analyses to determine the associations were conducted using multiple logistic regression models.

Results Between May to June 2019, we enrolled 228 participants, 152 (66.7%) females, mean age (SD) 42 (12.4) years and median CD4 count of 194 cells/mm3 (IQR 129-370). Of the total 228 patients, only 10/228 (4.4%; 95% CI, 0.024 - 0.080) had cryptococcal antigenemia. Although the factors associated with cryptococcal antigenemia were significant at bivariate analysis, they were found to lack significance at multivariate analysis, these factors included; CD4 cell count of less than 100cells/mm3 (AOR=3.70), keeping poultry at home, taking ART was protective (AOR=0.240). Clinical features associated with a positive serum CrAg; headaches (AOR=1), neck and back pains (AOR=8.817), altered vision (18.061), recent confusion (AOR=6.323) and neck stiffness (AOR=676.217). 30% of those with positive serum CrAg had a suppressed viral load.

Conclusions Cryptococcal antigenemia is common among the people living with AHD with a CD4 of <100cells/mm3, independent predictors associated with were CD4cell count <100cells/mm clinical symptoms & signs of meningeal irritation and poultry keeping. We recommend regular screening for CD4 counts, prophylaxis for those found with CD4 counts <100cells/mm prophylaxis for those who have AHD and also keep poultry at home, early & effective ART initiation and education of people living with HIV/AIDS (PLWHA) as a means of early detection of patients at risk, prevention and reduction of risks respectively.