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Cryptococcal meningitis in non-HIV patients in the State of Amazonas, Northern Brazil

  • Clinical Microbiology - Research Paper
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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.

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Acknowledgments

We thank the medical staff of the FMT-HVD and all participating patients for providing the clinical and epidemiological data. We thank the Mycology and Mycobacteriology laboratories of the National Research Institute of Amazonia (INPA) for assistance with equipment and reagents. In addition, we are also grateful to the Laboratory of Functional Genomics and Bioinformatics of Oswaldo Cruz Institute (Fiocruz, RJ) for the indispensable support regarding the DNA sequencing procedures and to Dr. Jaidson Nandi Becker for designing the map used in this publication.

Funding

We wish to thank the Coordination for the Improvement of Higher Education Personnel (CAPES) program for financial support and the Amazonas Research Foundation (FAPEAM) for funding this research: Public Notice N. 001/2017 – PPSUS.

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Authors and Affiliations

  1. Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus, Brazil

    Silviane Bezerra Pinheiro & Ednaira Sullany Sousa

  2. Laboratório de Micologia, Instituto Nacional de Pesquisas da Amazônia, Manaus, Brazil

    Silviane Bezerra Pinheiro, Ednaira Sullany Sousa, Ana Claúdia Alves Cortez, Diego Fernando da Silva Rocha & João Vicente Braga de Souza

  3. Fundação de Medicina Tropical Doutor Heitor Vieira Dourado – AM, Manaus, Brazil

    Lizandra Stephany Fernandes Menescal, Valéria Soares Chagas, Aline Stephanie Pérez Gómez, Kátia Santana Cruz & Lucilaide Oliveira Santos

  4. Instituto Leônidas Maria Deane, Fiocruz – AM, Manaus, Brazil

    Marla Jalene Alves & Ani Beatriz Jackisch Matsuura

  5. Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - RJ, Rio de Janeiro, Brazil

    Bodo Wanke & Luciana Trilles

  6. Department of Microbiology and Hospital Hygiene, External site at the Bernhard Nocht Institute, Bundeswehr Hospital Hamburg, Hamburg, Germany

    Hagen Frickmann

  7. Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Rostock, Germany

    Hagen Frickmann

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  1. Silviane Bezerra Pinheiro
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  2. Ednaira Sullany Sousa
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Correspondence to João Vicente Braga de Souza.

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Pinheiro, S.B., Sousa, E.S., Cortez, A.C.A. et al. Cryptococcal meningitis in non-HIV patients in the State of Amazonas, Northern Brazil. Braz J Microbiol 52, 279–288 (2021). https://doi.org/10.1007/s42770-020-00383-1

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