Symptomatic Cryptococcal Meningitis with Negative Serum and Cerebrospinal Fluid Cryptococcal Antigen Tests

• Published in: HIV/AIDS (Auckland) 2021-09, Vol.13, p.861-865
• Main Authors: Nanfuka, Vivien, Mkhoi, Mkhoi L, Gakuru, Jane, Kwizera, Richard, Baluku, Joseph Baruch, Bongomin, Felix, Meya, David B
• Format: Article
• Language: English
• Subjects: Amphotericin B; Antifungal agents; Antigens; Antiparasitic agents; Antiretroviral drugs; Antiretroviral therapy; Asymptomatic; Case Report; Case reports; CD4 antigen; Cell culture; Cerebrospinal fluid; cryptococcal antigen test; Cryptococcal meningitis; Cryptococcus; Drug therapy; Efavirenz; Fluconazole; Flucytosine; Fluid flow; Health aspects; Highly active antiretroviral therapy; HIV; HIV (Viruses); Human immunodeficiency virus; India; india ink; Infectious diseases; Intravenous administration; Lymphocytes; Lymphocytes T; Medical tests; Meningitis; Mortality; Patients; Printing-ink; Seroconversion; T cells; Uganda
• ISSN: 1179-1373; 1179-1373
• DOI: 10.2147/HIV.S328084

Cryptococcal meningitis is a leading cause of mortality in advanced HIV disease. A positive cerebrospinal fluid cryptococcal antigen (CrAg) test defines cryptococcal meningitis. Herein, we present a patient with serum and cerebrospinal fluid CrAg negative cryptococcal meningitis, despite a positive cerebrospinal fluid India ink examination and quantitative culture. A 56-year-old HIV-positive Ugandan woman, with an undetectable HIV RNA viral load and CD4+ T-cell count of 766 cells per microlitre presented with signs and symptoms consistent with cryptococcal meningitis. Her serum and cerebrospinal fluid CrAg tests were negative despite having a positive cerebrospinal fluid India ink and quantitative culture. On day 1, she was commenced on intravenous amphotericin B deoxycholate (1mg/kg) for 3 days (considering 10 CFU growth of spp) in combination with oral flucytosine (100mg/kg) for 7 days and then fluconazole 1200mg once daily for the next 11 days. By day 7, she was symptom free and quantitative cerebrospinal fluid culture was negative for spp. She was discharged on day 9. At 10 weeks (day +40) and 18 weeks (day +72), she was well and adherent to her antiretroviral therapy and on maintenance phase of cryptococcal meningitis on fluconazole at a dose of 400mg once daily. This report alerts clinicians managing patients with HIV-associated cryptococcal meningitis to four uncommon clinical scenarios; first, the possibility of negative serum and cerebrospinal fluid CrAg lateral flow assay results in the context of low cerebrospinal fluid fungal burden in a symptomatic patient. Second, possible occurrence of cryptococcal meningitis in a patient with high CD4 T-cell lymphocyte counts. Third, an early seroconversion of cryptococcal antigenaemia following effective fluconazole therapy. Fourth, an early symptomatic relapse of cryptococcal meningitis albeit negative serum CrAg.