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https://www.arca.fiocruz.br/handle/icict/48376
CRYPTOCOCCAL MENINGITIS IN NON-HIV PATIENTS IN THE STATE OF AMAZONAS, NORTHERN BRAZIL
Case series
Cryptococcal meningitis
Cryptococcus gattii
HIV-negative
MLST
VGII genotype
Author
Pinheiro, Silviane Bezerra
Sousa, Ednaira Sullany
Cortez, Ana Claúdia Alves
Rocha, Diego Fernando da Silva
Menescal, Lizandra Stephany Fernandes
Chagas, Valéria Soares
Gómez, Aline Stephanie Pérez
Cruz, Kátia Santana
Santos, Lucilaide Oliveira
Alves, Marla Jalene
Matsuura, Ani Beatriz Jackisch
Wanke, Bodo
Trilles, Luciana
Frickmann, Hagen
Souza, João Vicente Braga de
Sousa, Ednaira Sullany
Cortez, Ana Claúdia Alves
Rocha, Diego Fernando da Silva
Menescal, Lizandra Stephany Fernandes
Chagas, Valéria Soares
Gómez, Aline Stephanie Pérez
Cruz, Kátia Santana
Santos, Lucilaide Oliveira
Alves, Marla Jalene
Matsuura, Ani Beatriz Jackisch
Wanke, Bodo
Trilles, Luciana
Frickmann, Hagen
Souza, João Vicente Braga de
Affilliation
Universidade Federal do Amazonas. Pós Graduação em Ciências Farmacêuticas. Manaus, AM, Brasil / Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Universidade Federal do Amazonas. Pós Graduação em Ciências Farmacêuticas. Manaus, AM, Brasil / Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas Maria Deane. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas Maria Deane. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Bundeswehr Hospital Hamburg. External site at the Bernhard Nocht Institute. Department of Microbiology and Hospital Hygiene. Hamburg, Germany / University Medicine Rostock. Institute for Medical Microbiology, Virology and Hygiene. Rostock, Germany.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Universidade Federal do Amazonas. Pós Graduação em Ciências Farmacêuticas. Manaus, AM, Brasil / Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas Maria Deane. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas Maria Deane. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Bundeswehr Hospital Hamburg. External site at the Bernhard Nocht Institute. Department of Microbiology and Hospital Hygiene. Hamburg, Germany / University Medicine Rostock. Institute for Medical Microbiology, Virology and Hygiene. Rostock, Germany.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Micologia. Manaus, AM, Brasil.
Abstract
Cryptococcosis is a life-threatening fungal infection caused by the Cryptococcus neoformans/Cryptococcus gattii species complex. Most cases are recorded in patients suffering from HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome). However, this infection also occurs in non-HIV patients with a proportion of 10-30% of all cases. The study aimed at the clinical and molecular characterization of non-HIV patients diagnosed with cryptococcosis at the Tropical Medicine Foundation (FMT-HVD) from July 2016 to June 2019. Medical records of respective patients were analyzed to describe the course of cryptococcosis in non-HIV patients. In addition, multi-locus sequence typing (MLST) was applied to identify the sequence types of the isolated Cryptococcus strains, to perform phylogenetic analysis, and to evaluate the isolates' genetic relationship to global reference strains. Antifungal susceptibility profiles to amphotericin B, fluconazole, and itraconazole were assessed by broth microdilution. From a total of 7 patients, 4 were female, the age range varied between 10 and 53 years (median of 36.3 years). Cryptococcal meningitis was the common clinical manifestation (100%). The period between onset of symptoms and confirmed diagnosis ranged from 15 to 730 days (mean value of 172.9 days), and the observed mortality was 57.1%. Of note, comorbidities of the assessed cryptococcosis patients comprised hypertension, diabetes mellitus, and intestinal tuberculosis. Genotyping applying PCR-RFLP of the URA5 gene identified all clinical isolates as C. gattii genotype VGII. Using MLST, it was possible to discriminate the sequence types ST20 (n = 4), ST5 (n = 3), and the newly identified sequence type ST560 (n = 1). The antifungals amphotericin B, fluconazole, and itraconazole showed satisfactory inhibitory activity (microdilution test) against all C. gattii VGII strains.
Keywords
AmazonCase series
Cryptococcal meningitis
Cryptococcus gattii
HIV-negative
MLST
VGII genotype
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