Epidemiological, clinical, and genomic landscape of coccidioidomycosis in northeastern Brazil

Abstract

Coccidioidomycosis, listed as a priority mycosis by the WHO, is endemic in the United States but often overlooked in Central and South America. Employing a multi-institutional approach, we investigate how disease characteristics, pathogen genetic variation, and environmental factors impact coccidioidomycosis epidemiology and outcomes in South America. We identified 292 cases (1978-2021) and 42 outbreaks in Piauí and Maranhão states, Brazil, the largest series outside the US/Mexico epidemic zone. The male-to-female ratio was 57.4:1 and the most common activity was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Most patients (92.8%) exhibited typical acute pulmonary disease, with cough (93%), fever (90%), and chest pain (77%) as predominant symptoms. The case fatality rate was 8%. Our negative binomial regression model indicates that reduced precipitation levels in the current (p = 0.015) and preceding year (p = 0.001) predict heightened incidence. Unlike other hotspots, acidic soil characterizes this region. Brazilian strains differ genomically from other C. posadasii lineages. Northeastern Brazil presents a distinctive coccidioidomycosis profile, with armadillo hunters facing elevated risks. Low annual rainfall emerges as a key factor in increasing cases. A unique C. posadasii lineage in Brazil suggests potential differences in environmental, virulence, and/or pathogenesis traits compared to other Coccidioides genotypes.

Fig. 1. Distribution of coccidioidomycosis cases in Northeastern Brazil.

The 292 coccidioidomycosis cases in Brazil were georeferenced and assigned to each municipality in Piauí and Maranhão states; the scale transitions from pale, the lowest number of cases, to dark red, the highest number of cases. Micro-epidemics are represented by circles within each municipality; the higher the number of episodes, the greater the size of the circles. The main biomes are also represented by map layers delimited by different color scales: Blue shades represent the Caatinga biome, Green shades represent the Cerrado biome, and purple shades represent the Amazon Rainforest Biome.

Fig. 2. Descriptive epidemiology and climatic predictors of coccidioidomycosis in Northeastern Brazil.

A Time series analysis unveils the evolving distribution of coccidioidomycosis cases in Piauí and Maranhão states over the years. The year intervals are displayed on the x-axis, and case counts are displayed on the y-axis. Loess curves of precipitation (B) and precipitation one year prior (C) show a correlation with the increase of coccidioidomycosis cases in Northeastern Brazil. The volume of precipitation is displayed on the x-axis in millimeters (mm), and case counts are displayed on the y-axis. Error bars represent the 95% confidence intervals.

Fig. 3. Average precipitation maps and coccidioidomycosis prevalence density in Northeastern Brazil.

A Mean annual precipitation (1978–2021) based on 30 rain gauges in the states of Maranhão and Piauí and B prevalence density of coccidioidomycosis by the municipality from the states of Maranhão and Piauí between 1978 and 2021.

Fig. 4. Species distribution modeling of Coccidioides sp. in Northeastern Brazil.

Species distribution modeling was conducted using environmental and ecological data to estimate the potential geographic range of Coccidioides sp. occurrence. The distribution map is based on a combination of climatic factors, data from field surveys, laboratory analysis, and previous records of Coccidioides spp. occurrences and considered in the modeling process. The color gradient on the map represents the probability of Coccidioides sp. presence, with lighter shades indicating higher likelihood. The Northeastern states and the main biomes in Brazil are also delimited.

Fig. 5. Evolutionary analysis of Coccidioides posadasii isolated in Northeastern Brazil.

A The Maximum-likelihood phylogenomic tree shows that clinical isolates from Brazil are nested within C. posadasii species in a unique cluster with the Texas/Mexico/South America population. The branches are proportional to the number of mutations and 1000 ultrafast bootstraps and SH-aLRT were used to test branch support and added to the Brazil clade. The nodes in the tree represent common ancestors, and the branching points indicate the divergence of lineages. The tree was rooted with C. immitis. B Principal coordinate analysis (PCA) shows the genetic distribution of Coccidioides, a fungal pathogen. These coordinates are derived from a matrix of whole-genome polymorphisms or dissimilarities between the isolates from diverse geographical locations The PCA plot depicts the distribution of the isolates along the first two principal coordinates; PC1 axis indicates the degree of genetic dissimilarity or similarity between C. immitis and C. posadasii while PC2 captures a smaller proportion of the total variation of C. posadasii clusters.