Cryptococcal Meningitis: A Retrospective Cohort of a Brazilian Reference Hospital in the Post-HAART Era of Universal Access

Abstract

Objective Cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome worldwide. However, limited data exist for HIV-infected patients in the post-HAART (highly active antiretroviral therapy) era in Brazil. The aim of this study was to describe the clinical characteristics and outcomes of cryptococcosis in a cohort of patients attending a teaching tertiary care hospital in southern Brazil after the introduction of HAART in Brazil. Patients and Methods A retrospective study was conducted in tertiary care hospital in southern Brazil. Detailed data on risk factors, clinical manifestations, diagnosis methods, treatment, and prognosis of patients with meningeal cryptococcosis were evaluated from January 2009 to December 2016. Results Seventy-nine cases of cryptococcal meningitis were identified. Most of the patients presented positive CSF (cerebrospinal fluid) cultures for Cryptococcus neoformans (96%). The prevalence of males and females with meningeal cryptococcosis was similar. The age of the patients ranged from 5 to 67 years. The median time of hospitalization was 28 days. The most common underlying disease was HIV (82%), followed by solid transplant (10%). Fever, nausea, vomiting, headache, and altered mental status were the most common clinical manifestations. Initial opening intracranial pressures varied from 30 to 130 cm H2O. CNS imaging abnormalities include hydrocephalus and hypodensities. Widened Virchow–Robin spaces were described in only 2 patients (2.5%). Induction treatment of the majority of the patients consisted of amphotericin B and flucytosine (67%) followed by amphotericin B and fluconazole (19%). Multivariate analysis of Cox regression identified headache at presentation, mechanical ventilation, CSF glucose <20 mg/dL, and CSF cryptococcal antigen ≥1 : 1000 for independent risk factors for death. All-cause 30-day and 60-day mortalities were 19% and 24%, respectively. Conclusions Meningeal cryptococcosis mostly caused by C. neoformans continues to occur predominantly in HIV-infected adults despite HAART being widely distributed in Brazil. Cryptococcosis remains a significant opportunistic infection in solid organ transplant recipients. Despite adequate antifungal treatment and management of intracranial hypertension in a reference tertiary care hospital, mortality was high. Identification of risk factors and additional treatment modalities, especially for intracranial hypertension, are necessary to improve care for patients with cryptococcal meningitis.

Neuro-meningeal cryptococcal infection revealing a multiple myeloma

“…A likely conjecture supposes that our patient was exposed to the fungus through the pigeons he raises in his garden. The organism usually enters through the lungs, spreads via the blood stream, and seeds within the central nervous system causing meningoencephalitis [ 6 , 7 ]. The etiologic diagnosis of IgA type myeloma was based upon an elevated serum level of IgA together with hypogammaglobulinemia associated with decreased serum levels of non-myeloma immunoglobulins.…”

Infecciones fúngicas en un hospital público de referencia para la atención de personas con VIH/SIDA, Medellín 2013-2017

“…Se debe tener presente que en Estados Unidos se han descrito casos de infección por Cryptococcus gattii 16 , lo que evidencia retos para el correcto diagnóstico y orientación terapéutica adecuada. Este agente toma mayor importancia al considerar que el seguimiento de algunas cohortes evidencia que la criptococosis meníngea sigue presentándose en adultos infectados por el VIH pese a la introducción del tratamiento antirretroviral, al tiempo que la criptococosis sigue siendo una infección importante en trasplantes de órganos sólidos 17 .…”

Social, environmental and microbiologic aspects of endemic mycoses in Brazil

“…In Brazil, mortality rate ranged from 32% to 60% in HIV-infected population. Meningeal cryptococcosis mostly caused by C. neoformans occurs predominantly in these patients despite highly active antiretroviral therapy being widely distributed in Brazil [58] , [59] , [60] .…”

“…and Epidermophyton floccosum Cosmopolitan diseasePeople with dry skin, school-age children, rural workers and athletes. People with diabetes, HIV/AIDS infection, immunosuppressed and obeseSubcutaneousSporotrichosis [29], [31] Sporothrix spp.Higher incidence occurs in Rio de Janeiro and São PauloChildren or housewives with frequent contact with domestic and stray catsChromoblastomycosis [23], [25], [26], [27] Fonsecaea, Cladophialophora and Rhinocladiella Higher incidence occurs in Maranhão and ParáRural workers, mainly babassu extractorsSystemic (primary pathogens)Paracoccidioidomycosis [37], [38], [39], [41], [42], [44] Paracoccidioides spp.Several endemic areas with higher incidence: São Paulo, Paraná, Rio Grande do Sul, Goiás; and also regions with progressive devastation of tropical forestsWorking-age men and farmers in contact with soilHistoplasmosis [47], [48] Histoplasma capsulatum Higher incidence occurs in regions with caves and/or with progressive devastation of tropical forestsHIV/AIDS patients, rural workers, speleologists, tourists in contact with bat guano and soilCoccidioidomycosis [49], [50], [52], [53] Coccidioides immitis Endemic areas with dry climates, mainly Piauí, Ceará, Bahia and Maranhão; also regions with progressive devastation of tropical forestsRural workers, armadillo hunters and constructors in contact with soilOpportunistic yeasts and mouldsCandidiasis [12], [13], [69], [70], [71] (dermatitis, mucocutaneous, bloodstream) Candida spp.Cosmopolitan diseaseImmunocompromised hosts, HIV/AIDS patients, patients with haematologic cancer and stem-cell transplant recipientsCryptococcosis [57], [58], [59] Cryptococcus spp.Cosmopolitan diseaseImmunocompromised male hosts, HIV/AIDS patients, transplant recipientsAspergillosis and fusariosis [72], [73], [74], [75] Aspergillus spp., Fusarium spp.Cosmopolitan diseaseHospitalized and immunocompromised hosts, patients with HIV/AIDS, haematologic cancer and st...…”

“… Several endemic areas with higher incidence: São Paulo, Paraná, Rio Grande do Sul, Goiás; and also regions with progressive devastation of tropical forests Working-age men and farmers in contact with soil Histoplasmosis [47] , [48] Histoplasma capsulatum Higher incidence occurs in regions with caves and/or with progressive devastation of tropical forests HIV/AIDS patients, rural workers, speleologists, tourists in contact with bat guano and soil Coccidioidomycosis [49] , [50] , [52] , [53] Coccidioides immitis Endemic areas with dry climates, mainly Piauí, Ceará, Bahia and Maranhão; also regions with progressive devastation of tropical forests Rural workers, armadillo hunters and constructors in contact with soil Opportunistic yeasts and moulds Candidiasis [12] , [13] , [69] , [70] , [71] (dermatitis, mucocutaneous, bloodstream) Candida spp. Cosmopolitan disease Immunocompromised hosts, HIV/AIDS patients, patients with haematologic cancer and stem-cell transplant recipients Cryptococcosis [57] , [58] , [59] Cryptococcus spp. Cosmopolitan disease Immunocompromised male hosts, HIV/AIDS patients, transplant recipients Aspergillosis and fusariosis [72] , [73] , [74] , [75] Aspergillus spp., Fusarium spp.…”