Autochthonous and imported tegumentary leishmaniasis in Catalonia (Spain): Aetiological evolution in the last four decades and usefulness of different typing approaches based on biochemical, molecular and proteomic markers

Abstract

Leishmaniasis is a transmissible disease caused by Leishmania protozoa. Spain is endemic for both visceral and cutaneous leishmaniasis, the autochthonous aetiological agent being Leishmania infantum. Around the world, the L. donovani complex is associated with visceral symptoms, while any species of the Leishmania or Viannia subgenera affecting human can produce tegumentary forms. In a context of growing numbers of imported cases, associated with globalisation, the aim of this study was to analyse the aetiological evolution of human tegumentary leishmaniasis in a region of Spain (Catalonia). Fifty‐six Leishmania strains, isolated from 1981 to 2018, were analysed using MLEE, gene sequencing (hsp70, rpoIILS, fh and ITS2) and MALDI‐TOF. The utility of these different analytical methods was compared. The results showed an increase in leishmaniasis over the two last decades, particularly imported cases, which represented 39% of all cases studied. Leishmania infantum, L. major, L. tropica, L. braziliensis, L. guyanensis and L. panamensis were identified. The combination of molecular and enzymatic methods allowed the identification of 29 different strain types (A to AC). Strain diversity was higher in L. (Viannia), whilst the different L. major types were relatable with geo‐temporal data. Among the autochthonous cases, type C prevailed throughout the studied period (39%). Minor types generally appeared within a short time interval. While all the techniques provided identical identification at the species complex level, MALDI‐TOF and rpoIILS or fh sequencing would be the most suitable identification tools for clinical practice, and the tandem hsp70‐ITS2 could substitute MLEE in the epidemiological field.

Usefulness of Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry in the Characterization of Leishmania Strains Causing Tegumentary Leishmaniasis in Bolivia versus hsp70 Gene Sequencing

“…Of the 13 strains identified by confidence index B, a correct identification was found for L. braziliensis ( n = 7), L. guyanensis ( n = 1), and L. amazonensis ( n = 1). In contrast, other studies have failed to correctly distinguish L. guyanensis from other species of the complex ( 23 , 36 ). Misidentifications with confidence index B may be due to sample quality, parasite concentration, and the type of culture media used ( 35 ).…”

“…To our knowledge, two studies assessed its performance in routine practice, but they analyzed a small number of strains: a study carried out in France with 20 strains isolated from travelers with CL ( n = 19) and VL ( n = 1) ( 35 ) and another in Turkey, including 2 strains isolated from 2 patients with CL ( 22 ). Another comparative study of analytical methods, including MALDI-TOF MS, analyzed 53 strains isolated from autochthonous and imported cases of TL in Spain ( 36 ).…”

“…Once the entire plate was dried, it was placed on the equipment support for reading. The mass spectra were acquired using an Autoflex II TOF-TOF instrument (Bruker Daltonics) with the Flex Control program, version 3.4 (Bruker Daltonics), using the default parameters ( 36 ).…”

Non-Endemic Leishmaniases Reported Globally in Humans between 2000 and 2021—A Comprehensive Review

“…Infection in these cases occurred in 22 different countries, with approximately half of MCL/ML cases (when country of infection was known) reported from Bolivia (n = 25|5, [30,77,82,107,108,173,180,228] and Spain (n = 6|12, [11,69,109,130,132,135,153,155,158,245]. Other countries (1 to 7 cases) were: Greece [11,69], Italy [69], France [20,69], Croatia [111], Peru [11,20,80,177], Ecuador [8,11], Brazil [9,102], Colombia [82], Venezuela [95,281], Suriname [12,64], French Guiana [66,69], Argentina [179], Belize [82,223], Nicaragua [69], Panama [154], Costa Rica [14,69,74], Cameroon [11], India…”

“…Reporting policies and practices in endemic countries are inconsistent, with a lack of systematic reporting of all human clinical forms of leishmaniases, leading to an un-derestimation of the local and global burden of leishmaniasis [5]. On the other hand, the available information shows an increase in the number of imported cases in endemic and non-endemic countries [6][7][8][9][10][11][12], which can be explained by a combination of factors, such as increased human traveling, migration, or population displacement from or to endemic areas and an increase in the number of susceptible populations due to immunosuppressive factors, co-morbidities, and aging. Altogether, increased human mobility and globalization have expanded the at-risk population for leishmaniasis and, simultaneously, pose a risk of geographic expansion of Leishmania species.…”