Changes in the epidemiological behavior of American Tegumentary Leishmaniasis caused by Leishmania Panamensis in Colombia (1986 - 2018) and variations in the number of copies of genes associated with virulence.

Abstract

Introduction. Molecular changes occurring in Leishmania spp. may reflect variations not only in the pathogenicity of the parasite but also in the epidemiology of the disease. Objective. This study aimed to describe the epidemiological characteristics of cutaneous leishmaniasis cases diagnosed between 1986 and 2018 and to identify the changes that occurred over these years, as well as variations in the copy number (CNV) of virulence-associated genes GP63, HSP83, HISH4, and H2B, BTUB, ATG8, PHOSP, SERP, and PTR1 in Leishmania panamensis strains isolated from these cases. Methods. A database was constructed with the clinical histories of cases attended between 1986 and 2018 in which sociodemographic, clinical, and pharmacological variables were included. Changes in disease behavior over time were identified, grouping cases by 10-year periods. CNVs were determined in 9.3% (n = 125) of the clinical isolates of L. panamensis. Finally, CNVs were suggested between CNVs and observed changes in clinical variables such as lesion size, the occurrence of relapses/reactivations, and response to treatment. The retrospective study included information obtained from 1351 cases from 26 departments of Colombia. Seventy-seven percent were men and the average age was 23 years old. Ninety-seven percent of the cases presented LC with 72% of ulcers, and 7% had a history of leishmaniasis. Thirty-two percent had one lesion and 68% had two or three lesions; 50% with an evolution time < 2 months; size < 4 cm2 and 16% > 4 cm2. No correlation was found between the type of occupation and the appearance of reinfection, nor between age, type of lesion, number of lesions, size of lesions, time of evolution, the occurrence of reactivation or reinfection, or additional treatment cycles. However, changes in the variables were observed between Period 3 compared to the other two Periods studied, with a greater number of cases in patients with indoor activities, mucosal involvement and disseminated infection, relapses and reactivations, and larger lesion size. When comparing the changes in the copy number (CNV) of genes associated with virulence among L. panamensis isolates from the three study periods, an increase in the number of copies of the genes evaluated was observed in Periods 2 and 3 compared to Period 1, with the PHOSP gene showing the greatest variation. Results. These results suggest that L. panamensis has undergone virulence-associated genomic changes over time that could be increasing its pathogenic potential, causing larger lesions and more complex forms of LC, including relapses, reactivations, and reinfections. However, further studies are needed to expand information on the genetic variability of L. panamensis and its association with virulence, resistance, and pathogenicity mechanisms.