Cutaneous Leishmaniasis Caused by an Unknown Strain

In This Article

Abstract and Introduction

Abstract

We investigated an autochthonous case of cutaneous leishmaniasis caused by a genetically different Leishmania sp. in a patient in Arizona, USA. This parasite was classified into the subgenus Leishmania on the basis of multilocus DNA sequence and phylogenetic analyses of the rRNA locus and 11 reference genes.

Introduction

Human leishmaniasis is a vectorborne disease occurring mostly in Central and South America, the Europe/Africa Mediterranean area, the Middle East, and the Indian subcontinent. This disease is caused by parasites in the Leishmania subgenera Viannia and Leishmania, affects ≈2.5 million persons, and causes 60,000 deaths yearly worldwide.^[1] The disease has 3 main clinical forms: cutaneous leishmaniasis (CL), the most prevalent form and caused by species in both Viannia and Leishmania subgenera; mucocutaneous leishmaniasis, caused by species in the subgenus Viannia; and visceral leishmaniasis, caused by L. (L.) donovani and L. (L.) infantum. These syndromes might lead to social stigma because of permanent scars, skin disfigurement, and partial/total destruction of oral/nasopharyngeal mucosa and can result in systemic symptoms including splenomegaly, wasting, and even death.^[2]

Species-specific Leishmania identification is critical in clinical management and epidemiologic investigations.^[2] Detection and identification of Leishmania parasites were traditionally done through microscopic and multilocus enzyme electrophoresis analysis. Currently, PCR-based methods and multilocus DNA sequence analyses (MLSA) combined with next-generation sequencing, have improved phylogenetic resolution and provided insights into parasite identification, classification, genetic polymorphism, virulence, and drug resistance.^[3,4]

Leishmania parasites are emerging in previously nonendemic areas;^[5] traditional and exotic Leishmania species/strains have been reported in focal areas of the Americas, Europe, Africa, Asia, and the Western Pacific.^[6] In the United States, leishmaniasis is mostly nonreportable and historically considered a travel-associated disease. However, the activity of natural vectors of Leishmania and occurrence of autochthonous zoonotic cases of CL and visceral leishmaniasis caused by L. (L.) mexicana or L. (L.) infantum have been reported in several states, including Alabama, Arizona, Arkansas, Delaware, Georgia, Kentucky, Louisiana, Maryland, Mississippi, Ohio, Oklahoma, South Carolina, and Texas.^[7–10] Those reports suggest the possibility of local transmission of leishmaniasis, especially in the southwestern US region. We report an autochthonous case of CL from Arizona, USA, caused by an unknown parasite in the subgenus Leishmania.

Table. Comparative analysis of sequences of 13 genes showing percent sequence identity between a *Leishmania* isolate from a patient in Arizona, USA, and other *Leishmania* species*
Gene ORF†	Arizona isolate vs. L. (L.) donovani		Arizona isolate vs. L. (L.) infantum		Arizona isolate vs. L. (L.) mexicana		Arizona isolate vs. L. (M.) enrietti		Arizona isolate vs. L. (M.) martiniquensis		MiSeq fragment length, bp†
Gene ORF†	Accession no.	ID, %	Accession no.	ID, %	Accession no.	ID, %	Accession no.	ID, %	Accession no.	ID, %	MiSeq fragment length, bp†
ACT	AY079087	97.26	GQ246778	96.86	GQ246777	97.29	ATAF02000030	88.95	NA	–	1,145

*Accession numbers are for GenBank. ID, % indicates percent identity between sequences. ACT, β-actin; ASAT, aspartate aminotransferase; GAPDH, glyceraldeyde-3-phosphate dehydrogenase; GPI, glucose-6-phosphate isomerase; G6PDH, glucose-6-phosphate dehydrogenase; HSP70, heat-shock protein 70; ICD, isocitrate dehydrogenase; ID, identity; ITS, internal transcribed spacer; ME, malic enzyme; MPI, mannose-6-phosphate isomerase; NA, not available; NADP, nicotinamide adenine dinucleotide phosphate; ORF, open reading frame; PGD, PGM, 6-phosphogluconate dehydrogenase; PGM, phosphoglucomutase; –, not applicable. †GenBank accession numbers for the Arizona isolate were MT786532 (ACT), MT786533 (ASAT), MT786534 (G6PDH), MT786535 (GAPDH), MT786536 (GPI), MT786537 (ICD), MT786538 (ME), MT786539 (MPI), MT786540 (PGD), MT786541 (PGM), MT813027 (HSP70), MT776522 (18S rRNA) and ITS-1 rRNA region MT791386 (rRNA-ITS region). Sequences for ME and HSP70 were shorter by 206 and 20–30 bp, respectively, when compared with sequences in GenBank. ‡Only a 37-bp partial sequence of ITS rRNA of L. (M.) martiniquensis is available for comparison.