CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

screening may accelerate appropriate treatment, serum-based testing may be preferred where resources are available.

787 SYMPTOMATIC CRYPTOCOCCAL ANTIGENEMIA PRESENTING AS EARLY CRYPTOCOCCAL MENINGITIS Kenneth Ssebambulidde 1 , Mahsa Abassi 2 , Joshua Rhein 2 , Ananta Bangdiwala 2 , Darlisha A. Williams 2 , Edward Mpoza 1 , Lillian Tugume 1 , Richard Kwizera 1 , Abdu Musubire 3 , Fiona Cresswell 4 , Sarah Lofgren 2 , Kathy Huppler Hullsiek 2 , David R. Boulware 2 , David Meya 1 1 Infectious Disease Institute, Kampala, Uganda, 2 University of Minnesota, Minneapolis, MN, USA, 3 Makerere University College of Health Sciences, Kampala, Uganda, 4 London School of Hygiene & Tropical Medicine, London, UK Background: Individuals with cryptococcal antigenemia are at high risk for developing cryptococcal meningitis (CM) if left untreated. It is unknown if meningitis may precede the detection of cryptococcal antigen (CrAg) in cerebrospinal fluid (CSF). We present a sub-population of individuals with symptomatic cryptococcal antigenemia, but negative CSF CrAg. Methods: We evaluated serum and CSF CrAg among 1,236 HIV-seropositive individuals presenting with suspected meningitis in Kampala and Mbarara, Uganda between August 2013 and May 2017. Baseline characteristics and clinical outcomes of individuals with symptomatic cryptococcal antigenemia with negative CSF CrAg were compared to individuals with confirmed CM, (positive CSF CrAg). Wilcoxon rank sum tests were used to compare continuous variables and chi-square or Fisher’s exact tests were used to compare categorical variables. Results: We found 44% (547/1,236) of individuals screened had CM and 4.3% (53/1,236; 95% CI 3.2%-5.4%) had symptomatic cryptococcal antigenemia with negative CSF CrAg. The median CD4 count was higher for individuals with negative CSF CrAg compared to those with CM (29 (IQR 7, 86) versus 16 (IQR 6, 48) cells/µL; p=0.09), and headache was a less common symptom (81% vs 97%; p<0.01) (table). More individuals with negative CSF CrAg presented with normal CSF WBC (<5 cells/µL) (78% vs 60%; p<0.01) and normal OP (<20cmH20) (87% vs 39%; p<0.01). Of those presenting with negative CSF CrAg, 26% (14/53) were diagnosed with tuberculous meningitis (TBM) and 5.6% (3/53) subsequently grew Cryptococcus on CSF culture. Of those with TBM, 7 were detected by CSF Gene-Xpert, 2 by MTB culture, and 1 by AFB smears; 6 were purely empirical diagnoses. We had no cases of bacterial or viral meningitis on CSF PCR or culture, and 68% (36/53) had no known etiology. Among those with known in-hospital outcome, mortality was similar in those with symptomatic antigenemia with negative CSF CrAg and those with cryptococcal meningitis (39% (16/41) vs 32% (168/522); p=0.37); 23% of those with negative CSF CrAg had unknown outcome. Conclusion: Symptomatic cryptococcal antigenemia with a negative CSF CrAg is a relatively common presentation. We hypothesize this represents early cryptococcal CNS infection. We observed a similar high in-hospital mortality in individuals with CrAg antigenemia regardless of CSF CrAg positivity. Further studies to better understand the clinical course and optimal management of this subset of individuals are warranted.

788 POSTMORTEM CRYPTOCOCCAL MENINGITIS FOLLOWING TREATMENT FOR CRYPTOCOCCAL ANTIGENAEMIA Rachel M. Wake 1 , Tanvier Omar 2 , Aaron S. Karat 3 , Joseph N. Jarvis 4 , Nelesh P. Govender 5 , Thomas S. Harrison 1 1 St. George’s University of London, London, UK, 2 University of the Witwatersrand, Johannesburg, South Africa, 3 London School of Hygiene & Tropical Medicine, London, UK, 4 University of Pennsylvania in Botswana, Gaborone, Botswana, 5 National Institute for Communicable Diseases, Johannesburg, South Africa Background: Cryptococcal antigen (CrAg) screening and treatment with pre- emptive fluconazole reduces the incidence of evident cryptococcal meningitis and death among adults with advanced HIV. However, mortality remains higher in CrAg-positive than in CrAg-negative patients with similar CD4+ T-lymphocyte counts. Causes of this residual high mortality remain unclear. Methods: Minimally-invasive autopsies (MIA) were performed on patients enrolled in a prospective cohort study in Johannesburg, who died following CrAg screening. Samples obtained by needle biopsy or aspiration, included lung, liver, spleen, kidney, and skin tissue, and blood, pericardial and cerebrospinal fluid (CSF). Samples underwent microbiological testing at the National Institute for Communicable Disease, and histological analysis at the University of the Witwatersrand. Investigators performing analyses were not aware of the patients’ ante mortem CrAg test status. Results: Death within 6 months occurred in 15/68 (22%) CrAg-positive and 12/129 (9%) CrAg-negative patients (adjusted HR 2.6, 95% CI 1.1 – 6.1, p=0.036). MIA was performed on four CrAg-positive and two CrAg-negative patients, none of whom had symptoms or signs of meningitis at the time of CrAg screening. Two patients were on antiretroviral therapy (ART) at enrolment, two commenced after 14 and 22 days, and two never received ART prior to death. CrAg-positive patients started antifungal therapy (fluconazole 800mg daily for two weeks, followed by 400mg for two months, then 200mg daily) in accordance with national CrAg screen-and-treat guidelines. All CrAg positive patients had lumbar punctures; one was diagnosed with subclinical cryptococcal meningitis and started on amphotericin B and fluconazole. Death occurred at median 35 days (IQR 34 – 38) after CrAg screening. Post-mortem cryptococcal meningitis was diagnosed in all four CrAg-positive patients by CSF CrAg test (n=4) and culture (n=1). Cryptococcosis was also identified histologically in lung tissue (n=1). Although other pathogens that likely contributed to death were identified in autopsy samples, there was no evidence of cryptococcal disease in either CrAg-negative patient. Conclusion: Undiagnosed cryptococcal meningitis may contribute to mortality among CrAg-positive patients despite the currently recommended pre-emptive fluconazole regimen. More aggressive antifungal therapy, for example combination therapy with flucytosine, may prevent death among asymptomatic CrAg-positive patients identified through screening.

Poster Abstracts

CROI 2018 296