Cryptococcal antigenemia and susceptibility of Cryptococcuss neoformans to antifungal agents in HIV infection

Abstract

Background: Cryptococcus neoformans is a ubiquitous, environmental encapsulated fungus commonly found in soil and pigeon faecal samples. Transmitted C. neoformans via aerosols threatens HIV patients’ survival with ‘subtle’ meningitis, particularly in patients whose CD4+ counts declines below 200 cells/mm3 and causes early mortality in HIV-infected cohorts in resource-limited countries in sub-Saharan Africa. Early detection of C. neoformans in HIV patients is very crucial to their survival. Hence, this study investigated strategic cultural and serological diagnostics favourable for early detection of Cryptococossis in HIV patients and susceptibility to antifungal agents on clinical and environmental isolates of C. neoformans. Case description: A total of 665 blood samples were obtained from 615 seropositive HIV-infected patients and 60 seronegative patients across three referral health facilities in Abeokuta, Ogun, Nigeria. Following ethical approval, voluntary and informed consents were obtained from the study population. Structured questionnaires were administered to obtain the demographic data of the patients. Lateral flow serological methods were employed to determine Cryptococcal antigen (CrAg) in the serum of the patients. The cerebrospinal fluid (CSF) samples of HIV patients and pigeon droppings in soil were aseptically collected and cultured on five different culture media in order to isolate and identify C. neoformans. Agar-well-dilution and micro-tube dilution methods were used to determine the susceptible isolates’ to ketoconazole and fluconazole antifungal agents. Discussion: The results showed HIV prevalence among ages 21–40 years and female to male ratio of 2:1. Lateral flow CrAg detected C. neoformans antigenemia in HIV seropositive patients whose CD4 counts were less than 200 cells/mm3. The detection capacity of the five different media used revealed no significant association between isolates obtained from CSF and soil contaminated with pigeon droppings (P > X2 = 1.27, P = 0.115). The clinical, environmental and control isolates showed similar susceptibility rate (P value > 0.05) to ketoconazole and fluconazole. Conclusion: Lateral flow assay offered early detection of sub-clinical cryptococcal infection in HIV patients, while prompt therapeutic intervention using ketoconazole and fluconazole were effective antifungal agents as combination therapy with anti-retroviral agents. Minimising exposure of HIV patients to contaminated soil could reduce associated risks of cryptococcosis in HIV seropositive people.