Neurocriptococosis en el contexto de la infección con el VIH en Guayaquil, Ecuador / Neurocryptococcosis in the context of HIV infection in Guayaquil, Ecuador

Introducción: la neurocriptococosis resulta de la inhalación de levaduras del complejo de especies Cryptococcus neoformans y afecta principalmente a pacientes inmunocomprometidos, provocando altas tasas de mortalidad. Objetivo: describir la infección por Cryptococcus spp. en pacientes con VIH/sida de Guayaquil, Ecuador. Métodos: estudio descriptivo, transversal y prospectivo, entre diciembre/2013-enero/2015. Se recopilaron 82 muestras de líquido cefalorraquídeo así como los datos demográficos, clínicos y de laboratorio de igual cantidad de pacientes seropositivos al VIH ingresados en el Hospital de Infectología Dr. José Daniel Rodríguez Maridueña. La infección criptococósica se confirmó mediante examen microscópico directo del líquido cefalorraquídeo con tinta china, cultivo en agar Sabouraud y pruebas bioquímicas convencionales. El estudio cumplió con los requerimientos éticos establecidos. Resultados: el 89,02 por ciento de los pacientes incluidos en el estudio fueron de género masculino y el 45,12 por ciento del grupo etario de 20-30 años. El 33 por ciento de los pacientes presentaron la infección por C. neoformans, y sus características clínicas más frecuentes fueron: impresión diagnóstica de neuroinfección (41 por ciento), cefalea (78 por ciento; 21/27), vómitos (85 por ciento; 23/27) y pérdida de peso (89 por ciento; 24/27); niveles de CD4 < 200/uL (26 por ciento; 7/27), leucocitos 5 000-10 000 cél/mm3 (63 por ciento; 17/27), hemoglobina 11-15 g/dL (44 por ciento; 12/27) y hematócrito < 35 por ciento (78 por ciento; 21/27). Se demostró además, la existencia de una asociación entre la infección y la presencia de vómitos, pérdida de peso y adenopatías (razón de prevalencias > 1). Conclusiones: La infección criptococósica es una importante micosis oportunista en pacientes VIH-SIDA, que puede ser asociada a determinadas características, lo que permite definir mecanismos de control y prevención(AU)

Introduction: neurocryptococcosis results from inhalation of yeasts from the Cryptococcus neoformans species complex. The disease mainly affects immunocompromised patients, causing high mortality rates. Objective: describe infection due to Cryptococcus spp. in patients with HIV/AIDS from Guayaquil, Ecuador. Methods: a descriptive cross-sectional prospective study was conducted from December 2013 to January 2015. Eighty-two cerebrospinal fluid samples were collected, as well as the demographic, clinical and laboratory data of an equal number of HIV seropositive inpatients from Dr. José Daniel Rodríguez Maridueña infectious diseases hospital. Cryptococcal infection was confirmed by India ink direct microscopic examination of cerebrospinal fluid, Sabouraud agar culture and conventional biochemical tests. The study met the ethical requirements established. Results: 89.02 percent of the patients included in the study were male and 45.12 percent were in the 20-30 years age group. 33 percent had infection with C. neoformans, and their most common clinical features were diagnostic impression of neuroinfection (41 percent), headache (78 percent; 21/27), vomiting (85 percent; 23/27), weight loss (89 percent; 24/27); CD4 counts < 200/uL (26 percent; 7/27), leucocytes 5 000-10 000 cells/mm3 (63 percent; 17/27), hemoglobin 11-15 g/dL (44 percent; 12/27) and hematocrit < 35 percent (78 percent; 21/27). An association was also found between infection and the presence of vomiting, weight loss and adenopathies (prevalence ratio >1). Conclusions: cryptococcal infection is an important opportunistic mycosis in HIV/AIDS patients. It may be associated with certain features, which makes it possible to define control and prevention mechanisms(AU)

Cryptococcus and cryptococcosis in Cuba. A minireview.

Cryptococcosis has emerged as an important public health problem in Africa, Asia and the Americas due to the increasing numbers of persons at risk of this infection and the adaptation of its aetiological agents to new environments. The proper management requires early recognition of Cryptococcus neoformans/C. gattii species complex infection, familiarity with the use and limitations of diagnostic tests and knowledge of the available treatment options. This review will address these issues with the goal of providing sufficient information to suspect, diagnose and treat patients with cryptococcosis based on Cuban data and review of the literature.

Fatal Cryptococcus gattii genotype AFLP5 infection in an immunocompetent Cuban patient.

We describe the first clinical case of cryptococcosis due C. gattii in a Cuban immunocompetent patient who had a traveling history two years before to Central America. Molecular characterization of the isolate showed it to be genotype AFLP5 of which MLST sequences clustered with clinical and environmental strains from Colombia. The patient died one year after the diagnosis despite a prolonged treatment with (liposomal) amphotericin B, fluconazole, voriconazole and gamma interferon.

Microsatellite typing and susceptibilities of serial Cryptococcus neoformans isolates from Cuban patients with recurrent cryptococcal meningitis.

BACKGROUND: Cryptococcus neoformans is commonly associated with meningoencephalitis in immunocompromised patients and occasionally in apparently healthy individuals. Recurrence of infection after initial treatment is not uncommon. We studied C. neoformans isolates from 7 Cuban patients with recurrent cryptococcal meningitis. Antifungal susceptibility and genotyping with microsatellite molecular typing were carried out. METHODS: Isolates (n = 19) were recovered from cerebrospinal fluid, blood, urine and semen. Antifungal susceptibilities for amphotericin B, fluconazole, flucytosine, itraconazole, voriconazole, posaconazole and isavuconazole were tested by CLSI M27A3 broth microdilution method. Genotyping was done using a panel of 9 microsatellite (STR) markers: (CT)n, (TG)n, (TA)n, (CTA)n, (TCT)n, (CCA)n, (TTAT)n, (ATCC)n and (TATT)n. RESULTS: The average number of isolates/patient was 2.71. The mean time interval between the collection of any two isolates was 52.5 days. All strains were identified as C. neoformans var. grubii (serotype Aα). Although none of the strains were resistant to the studied drugs, in serial isolates from two patients, MICs values of triazoles increased 4-5 log2 dilutions over time. STR patterns showed 14 distinctive profiles. In three patients the recurrent infection was associated with genotypically identical isolates. The four other patients had relapse isolates which were genotypically different from the initial infecting strain. CONCLUSION: Recurrences of cryptococcal meningitis in our series of patients was not associated with development of drug resistance of the original strain but by an initial infection with different strains or a reinfection with a new strain.

Microsatellite typing of clinical and environmental Cryptococcus neoformans var. grubii isolates from Cuba shows multiple genetic lineages.

BACKGROUND: Human cryptococcal infections have been associated with bird droppings as a likely source of infection. Studies toward the local and global epidemiology of Cryptococcus spp. have been hampered by the lack of rapid, discriminatory, and exchangeable molecular typing methods. METHODOLOGY/PRINCIPAL FINDINGS: We selected nine microsatellite markers for high-resolution fingerprinting from the genome of C. neoformans var. grubii. This panel of markers was applied to a collection of clinical (n = 122) and environmental (n = 68; from pigeon guano) C. neoformans var. grubii isolates from Cuba. All markers proved to be polymorphic. The average number of alleles per marker was 9 (range 5-51). A total of 104 genotypes could be distinguished. The discriminatory power of this panel of markers was 0.993. Multiple clusters of related genotypes could be discriminated that differed in only one or two microsatellite markers. These clusters were assigned as microsatellite complexes. The majority of environmental isolates (>70%) fell into 1 microsatellite complex containing only few clinical isolates (49 environmental versus 2 clinical). Clinical isolates were segregated over multiple microsatellite complexes. CONCLUSIONS/SIGNIFICANCE: A large genotypic variation exists in C. neoformans var. grubii. The genotypic segregation between clinical and environmental isolates from pigeon guano suggests additional source(s) of human cryptococcal infections. The selected panel of microsatellite markers is an excellent tool to study the epidemiology of C. neoformans var. grubii.