Cutaneous Leishmania mexicana infections in the United States: definingstrains through endemic human pediatric cases in northern Texas

Over a 6-month span, three patients under 5 years old with cutaneous leishmaniasis presented to the Pediatric Infectious Diseases Clinic at the University of Texas Southwestern Medical Center/Children's Health Dallas. None had traveled outside of northern Texas/southern Oklahoma; all had Leishmania mexicana infections confirmedby PCR. We provide case descriptions and images to increase the awareness of this disease among United States (US) physicians and scientists. Two patients responded to fluconazole,but the youngest required topical paromomycin. Combining these cases with guidelines and our literature review, we suggest that (i) higher doses (10-12 mg/kg/day) of fluconazoleshould be considered in young children to maximize likelihood and rapidity of response and (ii) patients should transition to alternate agents if they do not respond to high-dose fluconazolewithin 6 weeks. Furthermore, and of particular interest to the broad microbiology community, we used samples from these cases as a proof of concept to propose a mechanism to strain-type US-endemic L. mexicana. For our analysis, we sequenced three housekeeping genes and the internal transcribed sequence 2 of the ribosomal RNA gene. We identifiedgenetic changes that not only allow us to distinguish US-based L. mexicana strains from strains found in other areas of the Americas but also establish polymorphisms that differbetween US isolates. These techniques will allow documentation of genetic changes in this parasite as its range expands. Hence, our cases of cutaneous leishmaniasis provide significantevolutionary, treatment, and public health implications as climate change increases exposure to formerly tropical diseases in previously non-endemic areas.