Genotypic diversity and clinical outcome of cryptococcosis in renal transplant recipients in Brazil

Vinicius Ponzio,Yuan Chen,Anderson Messias Rodrigues,Jennifer L Tenor,Dena L Toffaletti,José Osmar Medina-Pestana,Arnaldo Lopes Colombo,John R Perfect

doi:10.1080/22221751.2018.1562849

Abstract

ABSTRACT Genotypic diversity and fluconazole susceptibility of 82 Cryptococcus neoformans and Cryptococcus gattii isolates from 60 renal transplant recipients in Brazil were characterized. Clinical characteristics of the patients and prognostic factors were analysed. Seventy-two (87.8%) isolates were C. neoformans and 10 (12.2%) were C. gattii. VNI was the most common molecular type (40 cases; 66.7%), followed by VNII (9 cases; 15%), VGII (6 cases; 10%), VNB (4 cases; 6.7%) and VNI/II (1 case; 1.7%). The isolates showed a high genetic diversity in the haplotype network and six new sequence types were described, most of them for VNB. There was a bias towards skin involvement in the non-VNI population (P = .012). VGII isolates exhibited higher fluconazole minimum inhibitory concentrations compared to C. neoformans isolates (P = 0.008). The 30-day mortality rate was 38.3%, and it was significantly associated with fungemia and absence of headache. Patients infected with VGII had a high mortality rate at 90 days (66.7%). A variety of molecular types produce disease in renal transplant recipients in Brazil and highlighted by VGII and VNB. We report the clinical appearance and impact of the molecular type, fluconazole susceptibility of the isolates, and clinical characteristics on patient outcome in this population.

Highlights

Cryptococcosis is a life-threatening invasive fungal disease caused by the encapsulated yeasts, Cryptococcus neoformans and Cryptococcus gattii [1]
Our retrospective analysis describes 60 cases of cryptococcosis among renal transplant recipients documented during a period of 26 years
These data are comparable to some prior studies evaluating cryptococcosis in renal transplant recipients [3,5,6,7,8,26,27]

Summary

Introduction

Cryptococcosis is a life-threatening invasive fungal disease caused by the encapsulated yeasts, Cryptococcus neoformans and Cryptococcus gattii [1]. As a starting point, cryptococcosis is caused primarily by two species C. neoformans and C. gattii and currently these species can be further divided into ten molecular siblings known as VNI, VNII, VNB, VNIII, VNIV, VGI, VGII, VGIII and VGIV [12] with a possible new molecular type designated VGV. The most widely utilized sequence-based genotyping method for the molecular identification of these complexes has been multilocus sequence typing (MLST). This method is robust and portable between laboratories [14,15]

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