Cutaneous Leishmania mexicana Infections in the United States: Defining Strains Through Endemic Human Pediatric Cases in Northern Texas

Over a six-month span, three patients under five years old with cutaneous leishmaniasis presented to the Pediatric Infectious Diseases Clinic at the University of Texas Southwestern Medical Center/Childrens Health Dallas. None had traveled outside of the United States (US); all had confirmed L. mexicana infections by PCR. We provide case descriptions and images to increase the awareness of this disease among US physicians and scientists. Two patients responded to fluconazole, but one required topical paromomycin. Combining these cases with guidelines and our literature review, we suggest that: 1) higher doses (ten-twelve mg/kg/day) of fluconazole should be considered in young children to maximize likelihood and rapidity of response and 2) patients should transition to alternate agents if they do not respond to high-dose fluconazole within six 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 identified genetic 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 differ between US isolates. These techniques will allow documentation of genetic changes in this parasite as its range expands. Hence, our cases of cutaneous leishmaniasis provide significant evolutionary, treatment and public health implications as climate change increases exposure to formerly tropical diseases in previously non-endemic areas. IMPORTANCELeishmaniasis is a parasitic disease that typically affects tropical regions worldwide. However, the vector that carries Leishmania is spreading northward into the United States (US). Within a six-month period, three young cutaneous leishmaniasis patients were seen at the Pediatric Infectious Diseases Clinic at The University of Texas Southwestern/Childrens Health Dallas. None had traveled outside of north Texas. We document their presentations, treatments, and outcomes and compare their management to clinical practice guidelines for leishmaniasis. We also analyzed the sequences of three critical genes in Leishmania mexicana isolated from these patients. We found changes that not only distinguish US-based strains from strains found elsewhere, but also differ between US isolates. Monitoring these sequences will allow tracking of genetic changes in parasites over time. Our findings have significant US public health implications as people are increasingly likely to be exposed to what were once tropical diseases.