Cryptococcosis in the Democratic Republic of Congo from 1953 to 2021: A systematic review and meta-analysis.

Cryptococcosis is a common opportunistic infection associated with HIV/AIDS. The present review systematically describes the clinical and biological aspects of cryptococcosis in the Democratic Republic of Congo (DRC) and estimates its 2020 burden in people living with HIV (PLHIV). Following PRISMA guidelines, we searched online databases for records of cryptococcosis/Cryptococcus spp. in the DRC. Meta-analysis was then performed to estimate summary statistics and the corresponding 95% confidence intervals (CI). A total of 30 studies were included. These included 1,018 cryptococcosis patients, including 80.8% with neuromeningeal cryptococcosis (NMC) and predominantly immunocompromised due to HIV/AIDS (97.6%). The NMC mean prevalence was estimated at 9.63% (95% CI: 5.99-14.07). More than one in two patients (52.7%) under treatment died. Monotherapy with fluconazole was the main treatment administered (80.6%). Furthermore, we estimate that about 9,265 (95% CI: 5,763-13,537) PLHIV had cryptococcosis in 2020, in DRC; of which about 4,883 (95% CI: 3,037-7,134) would have died in the same year. Among isolates in all included studies, 74 strains have been characterised. Of these, 82.4% concerned Cryptococcus neoformans sensu lato (s.l) (exclusively of serotype A and mostly of molecular types VNI and VNII) and 17.6% concerned Cryptotoccus gattii s.l (belonging to serotype B/molecular type VGI). Cryptococcosis remains common with an unacceptably high mortality rate. A large number of PLHIV affected by and dying from cryptococcosis in 2020 demonstrates its heavy burden among the Congolese PLHIV. To mitigate this burden, it is important to improve the quality and accessibility of care for all PLHIV.

Comparison of clinical and biological characteristics of HIV-infected patients presenting Cryptococcus neoformans versus C. curvatus/C. laurentii meningitis.

BACKGROUND: Cryptococcal meningitis is mainly caused by Cryptococcus neoformans/C. gattii complex. We compared the clinical, biological, and antifungal susceptibility profiles of isolates from HIV-Infected Patients (HIVIP) with C. neoformans (Cn) versus C. curvatus/C. laurentii (Cc/Cl) meningitis. METHODS: Comparative analytical study were conducted. Apart from patients' clinical data, the following analysis were performed and the results were compared in both groups: biochemical examination, cryptococcal antigen test, India ink staining, and culture on Cerebral Spinal Fluid (CSF), strains identification by mass spectrometry, ITS sequencing, PCR serotyping and antifungal susceptibility. The main outcome variable was the "species of Cryptococcus identified", which was compared to other variables of the same type using the Pearson Chi-square test or the Fisher exact test. RESULTS: A total of 23 (79.3%) Cn meningitis cases versus 6 (20.7%) Cc/Cl meningitis were retained. Cn meningitis was more frequently associated with headache (100% vs 50%, p = 0.005) than Cc/Cl meningitis and meningeal signs were more frequent in Cn infected patients. Biologically, hypoglycorrhachia and low CD4 count were more observed in Cn group (90% vs 20% of patients, p = 0.01; 45.6 vs 129.8 cells/µL, p = 0.02, respectively). A higher proportion of Cn strains (91.3%) showed a low Minimum Inhibitory Concentration (MIC) (< 8 mg/L) for fluconazole compared to Cc/Cl strains (66.7%). Also, Cc/Cl strains resistant to 5-flucytosine and amphotericin B were found in 16.7% of cases for each of the two antifungal agents. Cryptococcus detection by routine analysis (India ink, culture, and antigens) was better for Cn samples than Cc/Cl. Except ITS sequencing, which identified all strains of both groups, mass spectrometry and serotyping PCR identified Cn strains better than Cc/Cl (100% vs 80%, p = 0.1; 100% vs 0%, p < 0.0001, respectively). After treatment with amphotericin B, 5-flucytosine, and fluconazole in both groups, the outcome was similar. CONCLUSIONS: Clinical presentation of Cn meningitis is certainly more severe than that of Cc/Cl meningitis, but Cc/Cl infection should be considered in the management of HIVIP with meningeal syndrome because of the diagnostic difficulty and the high MICs of antifungal agents required for the treatment of meningitis due to these cryptococcal species.

Epidemiological, clinical and biological profile of neuromeningeal cryptococcosis among people living with HIV in Kinshasa, Democratic Republic of Congo.

Neuromeningeal cryptococcosis (NMC) is one of the most frequent opportunistic infections (OI) in Human Immunodeficiency Virus (HIV) infection. In Kinshasa, the latest data on cryptococcosis were published in 1996. The objective was to describe the epidemiological, clinical and biological profiles of NMC in HIV-infected people living in Kinshasa. This is a descriptive study based on the medical records of patients who attended three clinics in Kinshasa between January 1 s t 2011 and December 31st 2014. Only the medical records of HIV-infected people presenting the NMC were reviewed. During the 4 year-period of the study, 261 HIV-positive patients presented to the clinics for neuromeningeal syndrome, including 23 with NMC. The global prevalence of NMC was 8.8% for the three clinics. The mean age was 42.8 ± 9.5 years, with male predominance (65.2%). The main symptoms were headache (73.9%), neck stiffness (60.9%), fever (47.8%), and coma (47.8%). Biological records were as follows: median CD4 cell count was 79 cells/mm3; cerebrospinal fluid (CSF) was clear for 56.5% of the cases with predominance of neutrophils in 73.9%. The outcome was fatal in 34.8% of cases. The prevalence and therapeutic outcome of NMC show that it constitutes a non-negligible OI in Kinshasa, especially in HIV-infected people at the AIDS stage. As HIV-infected people with severe immunosuppression are the most affected by NMC, active preventive measures should benefit this vulnerable category of people.