Molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii in Latin America

Objective: To combine and analyse data reported from Latin America that has contributed to the identification, genotyping, molecular epidemiology, geographical distribution, ecological niche identification, and population genetics of the aetiological agents of cryptococcosis, a life-threatening mycosis acquired from the environment, that is caused by the encapsulated yeasts Cryptococcus neoformans and C. gattii. In Latin America, the study of cryptococcosis and its aetiological agents has become increasingly important
as this mycosis has significant morbimortality, with more than 5000 individuals affected with cryptococcal meningitis yearly and 2400 attributable annual deaths. Additionally, the number of immunocompromised patients in the region constantly increases, with about 100000 new HIV infections annually, which is the main condition predisposing to cryptococcosis. Methods: Search on the studies on the molecular epidemiology of Cryptococcus and cryptococcosis was performed in English and Spanish in PubMed and Google databases using the keywords “cryptococcus” or “cryptococcosis” combined with each name of the 20 Latin American countries. Results: Analysis of the combined molecular data of 2110 clinical and 1029 environmental cryptococcal isolates from Latin America showed that, as worldwide, C. neoformans molecular type VNI is the most common cause of cryptococcosis (69.6%), affecting predominantly HIV patients, followed by C. gattii molecular type VGII (16.1%), which generally affects otherwise healthy individuals. Interestingly, in the environment these two molecular types also predominate with slightly different proportions (55.1% for VNI and 26.7% for VGII). However, whilst the environmental reservoir of C. neoformans is mainly avian guano, decaying organic matter and soil, the C. gattii niche is associated with several tree species. In Brazil and Colombia, the countries with the largest number of isolates, VNI and VGII are the most common molecular types, although in Colombia, the prevalence of VGIII is very similar to that of VGII. In Mexico and Argentina, however, after VNI, the molecular types VGIII and VGI are the most common among C. gattii isolates, respectively. By multi-locus sequence typing and whole genome sequencing, further advance to understand C. gattii populations has been also achieved in Latin America. Firstly, the global study of C. gattii VGII isolates provided evidence on the evolution of this pathogen in North America and gave support to the extensive evolution in, and dispersal from, South America, most likely from the Amazonia and the Northeast of Brazil, where VGII strains have shown to be the most variable genetically compared to worldwide isolates. Additionally, Mexico and Colombia have been proposed to be the likely origin of the VGIII population, as isolates from these countries are the basal group of isolates recovered worldwide. Conclusion: This work summarizes the significant progress that has been made in the recent years towards the molecular epidemiology of cryptococcal isolates in Latin America, that contribute to understand how these pathogenic yeasts have spread around the world and what is their population structure, and to better define some disease aspects of cryptococcosis, an important mycosis in the region.