Coccidioidomycosis Emergence in South America: Exploring Northeastern Brazil's Epidemiological, Clinical, and Genomic Landscape

Coccidioidomycosis is an invasive mycosis included in WHOs priority list. It is endemic and notifiable in the United States but neglected in Central and South America. We used a multi-institutional approach to assess whether disease characteristics, genetic variation in the pathogen or environmental factors affects the epidemiology of coccidioidomycosis and disease outcomes throughout the American continent. We identified 292 patients with coccidioidomycosis between 1978 and 2021 in the Piaui and Maranhao states of Brazil; the largest cases series reported outside the US/Mexico epidemic range. The male-to-female ratio was 57.4:1 and the main risk factor was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Forty-two outbreaks involving two to six patients were observed. Most patients (92.8%) presented typical acute pulmonary disease, followed by disseminated (3.4%), chronic pulmonary (2.4%) and regressive pulmonary (1.4%). The most frequent clinical symptoms were cough (93%), fever (90%) and chest pain (77%). Mortality was observed in 8% of the patients. In 2004, and between 2015 and 2017, we observed a spike in coccidioidomycosis in Brazil, particularly in the state of Piaui. Unlike other main hotspots, the soil is acidic in this region and precipitation (p=0.015) and precipitation one-year prior (p=0.001) were predictors of higher coccidioidomycosis rates. The Brazilian strains are genotypically divergent from other described C. posadasii within the Texas/Mexico/South America clade. Coccidioidomycosis in Northeastern Brazil has a specific infection profile and armadillo hunters are at higher risk. Low pluviosity and extensive drought appear key to increasing the number of cases in Brazil. A unique C. posadasii lineage exists in Brazil; therefore, environmental, virulence, and/or pathogenesis traits may differ from other Coccidioides genotypes.