A Phylogeographic Description of Histoplasma capsulatum in the United States

Abstract

Histoplasmosis is one of the most under-diagnosed and under-reported endemic mycoses in the United States. Histoplasma capsulatum is the causative agent of this disease. To date, molecular epidemiologic studies detailing the phylogeographic structure of H. capsulatum in the United States have been limited. We conducted genomic sequencing using isolates from histoplasmosis cases reported in the United States. We identified North American Clade 2 (NAm2) as the most prevalent clade in the country. Despite high intra-clade diversity, isolates from Minnesota and Michigan cases were predominately clustered by state. Future work incorporating environmental sampling and veterinary surveillance may further elucidate the molecular epidemiology of H. capsulatum in the United States and how genomic sequencing can be applied to the surveillance and outbreak investigation of histoplasmosis.

Keywords: Histoplasma capsulatum; clades; epidemiology; genome; genomic; histoplasmosis.

Figure 1

Phylogenetic analysis of H. capsulatum isolates from eight U.S. states. The ML tree includes 54 isolates. Node color is based on the associated U.S. states where the patient resided. The following are the eight states: Indiana (IN), Kentucky (KY), Michigan (MI), Minnesota (MN), Nebraska (NE), Pennsylvania (PA), Wisconsin (WI), Louisiana (LA). Not available (NA).

Figure 2

Multi−dimensional (MDS) plot of H. capsulatum isolates. (A) MDS plot of the patristic distance with x axis being dimension 1 and y axis dimension 2. The plot which includes all isolates revealed four distinct clades. Most (92%) of the samples clustered with the NAm 2 clade, three with the LAm A clade, one with the NAm 1 clade, and none clustered with the Panama control sample. (B) MDS plot of isolates from the NAm 2 clade. Two separate clusters of isolates belonging to MI and MN were observed. The following are the eight states: Indiana (IN), Kentucky (KY), Michigan (MI), Minnesota (MN), Nebraska (NE), Pennsylvania (PA), Wisconsin (WI), Louisiana (LA). Not available (NA).