Molecular types of Cryptococcus species isolated from patients with cryptococcal meningitis in a Brazilian tertiary care hospital

ABSTRACT There are limited data on the molecular epidemiology of cryptococcosis in Brazil. Here, we report on the identification of the molecular pattern of the Cryptococcus species that caused meningitis in patients admitted in a Brazilian reference tertiary care hospital, and review the published studies addressing the molecular epidemiology of Cryptococcus in Brazil. Our study has shown the predominance of molecular type VNII in HIV-infected patients with cryptococcal meningoencephalitis. Molecular types VNII and VGII were occasionally detected in HIV-infected and non-infected patients with meningoencephalitis. In contrast, previous studies have shown that several regions exhibited a high prevalence of the VNI molecular type and sporadic cases of the VNII and VGII molecular types in patients with cryptococcosis in Brazil. Additional studies including VNII isolates will contribute to understanding the epidemiology and phylogenetic relationship of these genotype compared to the other ones. So far, no clear correlation has been established between genotypes, antifungal susceptibility for Cryptococcus and clinical outcome in cryptococcosis.

Clinicopathologic characteristics and prognosis of medullary breast carcinoma / 中华普通外科杂志

Objective To investigate the clinicopathologic characteristics and prognosis of medullary breast carcinoma.Methods We conducted a retrospective analysis on clinical and pathologic data of 166 patients with medullary breast cancer.Results All the patients were female with a median age of 52 years old.The proportion of patients with stage Ⅰ,Ⅱ and Ⅲ disease was 16.9％,68.1％,15.0％,respectively.The Luminal,HER-2 overexpressing and triple-negative subtypes constituted 31.3％,8.4％,and 60.3％,respectively.There was significant difference in regional lymph node status of medullary breast cancer patients with different molecular types (x2 =18.248,P =0.003),but not in tumor size,TNM stage,histological grade,and expression of Ki67 (all P ＞ 0.05).Multivariate survival analysis indicated that TNM stage was an independent predictor in the prognosis of medullary breast cancer (HR =5.664,P =0.001).All the patients were followed up from 15 months to 145 months with a median follow-up time of 108 months.The 5-year survival rate was 91.5％ and the 10-year survival rate was 87.2％.Conclusions The prognosis of medullary breast cancer is favorable.Personalized treatment according to the TNM stage and histopathologic characteristics achieve a favorable prognosis.

Identificación molecular de los complejos cryptococcus neoformans y gattii por PCR fingerprinting y PCR-RFLP / Molecular identification of cryptococcus neoformans and gattii complexes by PCR fingerprinting and PCR-RFLP

La criptococosis es una micosis de curso subagudo o crónico causada por levaduras oportunistas del género Cryptococcus, principalmente por las especies de los Complejos C. neoformans y C. gattii. La criptococosis pasó de ser considerada una micosis de aparición esporádica, a posicionarse como una de las primeras afecciones oportunistas asociadas al SIDA con una tasa de infección elevada en estos pacientes quienes con frecuencia desarrollan una meningoencefalitis. En Venezuela poco se conoce sobre los serotipos, susceptibilidad y virulencia de las cepas circulantes. El propósito de este trabajo fue realizar la caracterización molecular de los Complejos Cryptococcus neoformans y gattii, se empleó la PCR-RFLP siguiendo el protocolo descrito por Escandon y col. Se utilizaron 80 cepas, 67 del complejo C.neoformans y 13 del complejo C.gattii, conservadas en la micoteca del INHRR. Se encontró que el tipo molecular más prevalente es el VNI con un 77,2% similar a lo reportado a nivel mundial, en segundo lugar se encuentra el tipo molecular VGII (12,7%), que concuerda con lo reportado para Latinoamérica. Este estudio aporta información epidemiológica sobre los tipos moleculares circulantes y permite de esta manera profundizar en el conocimiento de esta micosis oportunista en Venezuela.

Cryptococcosis is a fungal infection of subacute or chronic course caused by opportunistic yeast genus Cryptococcus, mainly species of Complex C neoformans and C. gattii. Cryptococcosis went from being considered a fungal infection of sporadic occurrence, to position itself as one of the first opportunistic diseases associated with AIDS with a high rate of infection in these patients who often develop meningoencephalitis. In Venezuela little is known about the serotypes, susceptibility and virulence of circulating strains. The purpose of this study was to perform the molecular characterization of the complexes Cryptococcus neoformans and gattii, PCR-RFLP was used following the protocol described by Escandon et al. 80 strains were used, 67 of C. neoformans and 13 of C.gattii complex, preserved in mycology library of INHRR. It was found that the most prevalent molecular type is the VNI with 77.2% similar to that reported worldwide, in second place is the molecular type VGII (12.7%), consistent with that reported for Latin America. This study provides epidemiological information on circulating molecular types and allows deeper understanding of this opportunistic fungal infections in Venezuela.

Regional pattern of the molecular types of Cryptococcus neoformans and Cryptococcus gattii in Brazil

The molecular types of 443 Brazilian isolates of Cryptococcus neoformans and Cryptococcus gattii were analyzed to determine their geographic distribution within Brazil and their underlying host conditions. The following data, imported from previous epidemiological studies as well as two culture collections, were analyzed for: place of isolation, source (clinical or environmental), host risk factors, species, serotype, mating type, and molecular type. Molecular typing by PCR-fingerprinting using primers for the minisatellite-specific core sequence of the wild-type phage M13 or microsatellites [(GACA)4, (GTG)5], restriction fragment length polymorphism of URA5 gene analysis, and/or amplified fragment length polymorphism (AFLP) identified eight major genotypes: VNI/AFLP1, VNII/AFLP1A, VNIII/AFLP2, and VNIV/AFLP3 for C. neoformans, and VGI/AFLP4, VGII/AFLP6, VGIII/AFLP5, and VGIV/AFLP7 for C. gattii. The most common molecular type found in Brazil was VNI (64 percent), followed by VGII (21 percent), VNII (5 percent), VGIII (4 percent), VGI and VNIV (3 percent each), and VNIII (< 1 percent). Primary cryptococcosis caused by the molecular type VGII (serotype B, MAT) prevails in immunocompetent hosts in the North and Northeast regions, disclosing an endemic regional pattern for this specific molecular type in the Northern Brazil.