An update on the occurrence of Paracoccidioides species in the Midwest region, Brazil: Molecular epidemiology, clinical aspects and serological profile of patients from Mato Grosso do Sul State

Background Paracoccidioidomycosis (PCM) is a systemic and endemic fungal infection in Latin American, mainly in Brazil. The majority of PCM cases occur in large areas in Brazil, comprising the South, Southeast and Midwest regions, with the latter demonstrating a higher incidence of the species Paracoccidioides lutzii. Methodology and main findings This study presents clinical, molecular and serological data of thirteen new PCM cases during 2016 to 2019 from the state of Mato Grosso do Sul, located in the Midwest region, Brazil. From these thirteen cases, sixteen clinical isolates were obtained and their genomic DNAs were subjected to genotyping by tub1 -PCR-RFLP. Results showed Paracoccidioides brasiliensis sensu stricto (S1) (11/16; 68.8%), Paracoccidioides restrepiensis (PS3) (4/16; 25.0%) and P. lutzii (1/16; 6.2%) as Paracoccidiodes species. Therefore, in order to understand whether the type of phylogenetic species that are circulating in the state influence the reactivity profile of serological tests, we performed double agar gel immunodiffusion (DID), using exoantigens from genotyped strains found in this series of PCM cases. Overall, our DID tests have been false negative in about 30% of confirmed PCM cases. All patients were male, most with current or previous rural activity, with ages ranging from 17 to 59 years, with 11 patients (84.6%) over 40 years of age. No clinical or epidemiological differences were found between Paracoccidioides species. However, it is important to note that the only case of P. lutzii died as an outcome. Conclusions This study suggests P. brasiliensis sensu stricto (S1) as the predominant species, showing its wide geographic distribution in Brazil. Furthermore, our findings revealed, for the first time, the occurrence of P. restrepiensis (PS3) in the state of Mato Grosso do Sul, Brazil. Despite our setbacks, it would be interesting to provide the complete sequencing of these clinical isolates to complement the molecular information presented. Author summary Paracoccidioides spp. complex and P. lutzii are etiological agents of paracoccidioidomycosis (PCM), one of the most important systemic mycosis of Latin America. This study aimed to describe the molecular epidemiology associated with clinical and serological data of Paracoccidiodes spp. in the Mato Grosso do Sul, located in the Midwest region, Brazil. Thus, for the first time in this state, the clinical Paracoccidioides species were molecularly identified. Previous findings have frequently been misinterpreted as proving that P. lutzii predominates in this region. In fact, we observed that this state differs from others in the Midwest, presenting a higher proportion of PCM cases due to P. brasiliensis sensu stricto (S1). In addition, we described the first report of P. restrepiensis (PS3) occurrence in the Brazilian Midwest region. Then, we presented an update on the occurrence of Paracoccidioides species in the Midwest region from Brazil. On the other hand, our results do not demonstrate clinical and epidemiological differences between Paracoccidioides spp. Nevertheless, this study reinforces that other researches should be carried out in order to evaluate an association of clinical manifestations and epidemiology with Paracoccidioides species.