1. IntroductionLeishmaniasis is a vector-borne zoonotic disease caused by several species of Leishmania parasites. Its transmission cycle involves several vertebrate mammals (primary reservoirs and secondary or accidental hosts) and vector sandfly species (Psychodidae: Phlebotominae) [1]. It is a significant health problem in many world areas and continues to spread to new areas in endemic and non-endemic countries. In 2020, 98 countries were considered endemic to leishmaniasis [2]. Its clinical expressions vary, but the most frequent are cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (ML) and visceral leishmaniasis (VL) [3].All clinical forms occur in Mexico, but localized cutaneous leishmaniasis (LCL) is the most frequently occurring since 99% of new annually reported cases belong to this clinical form [4]. The main causal agent of LCL in the country is Leishmania (Leishmania) mexicana. The recognized primary vector for this parasite species is the sandfly Bichromomyia olmeca olmeca. The rodents of the genera Heteromys, Nyctomys, Ototylomys, Sigmodon and Peromyscus are the reservoir hosts of Leishmania parasites in several active transmission areas [1,5,6].In 1912, Seidelin published the first description of the disease in latex (the raw material for chewing gum) collecting workers from the Yucatan Peninsula (comprised of the states of Quintana Roo, Campeche, and Yucatan). Ulcerative lesions developed predominantly in their ears and became known as “Chiclero’s ulcers” [7]. Latex harvest was one of the main activities in forested areas, covering 90% of Quintana Roo lands, two-thirds of Campeche’s and a small strip in the south of Yucatan state. Therefore, the disease prevailed in Campeche and Quintana Roo, and infection was related to sylvatic environments [7,8].Until today, the sylvatic regions of Campeche, Quintana Roo, Tabasco and Chiapas, all in south-southeast Mexico, continue to be the main endemic areas of transmission, where Leishmania parasites, vector sandflies and mammal reservoirs have been extensively studied [1,4,9,10,11].Historically, the northern area of the peninsula occupied by the state of Yucatan is not endemic for leishmaniasis although the state is classified as a vulnerable and receptive area for Leishmania transmission [1]. Therefore, recent autochthonous cases suggest new local transmission demanding an updated analysis of the epidemiological situation of the disease, including human cases, sandfly vectors, hosts/reservoirs and environmental factors that may favor the emergence of new transmission foci. In this review we analyze and describe relevant literature about human cases of cutaneous leishmaniasis, Leishmania parasite species, vector sandfly species, vertebrate hosts and environmental disturbances in Yucatan. Information was accessed through different databases, including PubMed, Scopus, Google and morbidity official databases from Yucatan and Mexico from the Mexican Health Ministry. 3. Vector Sandfly SpeciesThe vectors of Leishmania parasites are hematophagous dipterans of the family Psychodidae, subfamily Phlebotominae. In the Americas, several genera concentrate species exclusively distributed on the continent. However, the species of public health relevance are found in the genera Lutzomyia, Bichromomyia and Psychodopygus due to their demonstrated capacity as vectors involved in the transmission of the different Leishmania species [26].In Mexico, Bi. olmeca olmeca is recognized as the primary vector responsible for the transmission of Leishmania to humans. However, Lu. cruciata has also been incriminated as a potential vector, mainly due to its anthropophilic nature and abundance in endemic areas. Furthermore, other species, such as Psathyromyia (Psathyromyia) shannoni, Psychodopygus panamensis and Nyssomyia ylephiletor, have been recently found involving L. mexicana in the state of Campeche [1,6].In Yucatán, the presence of 15 Phlebotominae species has been documented: Brumptomyia hamata, Br. mesai, Dampfomyia (Coromyia) beltrani, Da. (Cor.) deleoni, Lutzomyia (Lutzomyia) longipalpis, Lu. (Tricholateralis) cruciata, Bi. olmeca olmeca, Pintomyia (Pifanomyia) serrana, Psathyromyia (Forattiniella) carpenteri, Pa (Psa.) cratifer, Pa. (Psa.) shannoni, Pa. (Psa.) undulata, Micropygomyia (Coquillettimyia) chiapanensis, Mi. (Micropygomia) cayennensis maciasi and Mi. (Sauromyia) trinidadensis [22,23,24].Current geographic records of Phlebotomines show a wide distribution into the Yucatan territory, where Phlebotominae vectors would not be expected to occur in northern municipalities with high population densities in urban settings like Mérida, Umán or high population affluence like Celestún (Figure 1); probably because the study of the Phlebotominae fauna in Yucatan has been historically sporadic due to the absence of leishmaniasis cases. To our knowledge, only the study of Pérez-Blas et al. has recorded molecular evidence of Lu. cruciata and Pa. shannoni carrying L. mexicana in a locality from Ticul municipality [25]. Formal studies on the abundance and distribution of these insects have been limited in the last 15 years, where a couple of studies focused on specific localities, which shows a noticeable need to study in greater detail the populations of species of medical importance and the changes in their distribution and abundance derived from anthropogenic transformation and environmental variation since these are factors that directly affect the establishment and maintenance of their populations [22,24,27]. 4. Vertebrate HostsIn the Americas, more than 80 species of several mammal orders have been reported infected with Leishmania parasites, such as opossums (Didelphimorphia), anteaters, sloths (Pilosa), armadillos (Cingulata), mice, squirrels (Rodentia), dogs, jaguars (Carnivora), bats (Quiroptera), horses (Perissodactyla), monkeys and humans (Primates) [28,29]. However, not all these hosts play the same role in the transmission of Leishmania. Most mammals may act as “dead-end hosts”, which means that they develop low levels of parasitaemia and cannot pass the parasites on to susceptible sand flies. In contrast, few mammalian species can act as reservoir hosts given that they can maintain sufficient values of parasitaemia and for longer periods to efficiently infect vectors [28].In Yucatan, the infection with Leishmania has been investigated in domestic dogs and cats. In Celestún, Longoni et al. found that the sera of 29 (52.7%) dogs were positive for Leishmania spp. [18]. Arjona-Jiménez et al. also found a similar frequency (50.5%, 110/218) of Leishmania-positive dogs in the city of Mérida [19]. Longoni et al. identified specific antibodies against Leishmania spp. in 6 (54.5%) and 18 (25%) cats from the cities of Umán and Mérida, respectively [20]. This serological evidence indicates an exposure of these animals to the parasites and the likelihood of vectorial transmission in these localities close to Kinchil (ca. 20–44 km), where a case of human leishmaniasis was reported. (Figure 1).There is scientific evidence in Campeche and other regions of Mexico and Latin America that highlight the role of rodents, bats, and opossums as reservoir hosts of Leishmania [29,30,31], suggesting potential participation in leishmaniasis foci on Yucatan. In Campeche, studies on the sylvatic cycle of Leishmania have reported six wild rodents (Heteromys gaumeri, Peromyscus yucatanicus, Oryzomys melanotis, Ototylomys phyllotis, Reithrodontomys gracilis and Sigmodon toltecus) infected with the Leishmania parasites [30,31]. Data on seasonality of infection suggest that H. gaumeri, P. yucatanicus and O. phyllotis may be the primary reservoir hosts of Leishmania in Campeche [32]. These rodent species are widely distributed in Yucatan. Occurring in tropical forests, grassland, and cornfields, however, their abundances vary in response to rain, food availability, conservation status of tropical forests, topography, and other factors [33]. Heteromys gaumeri is abundant in southern Yucatan, whereas P. yucatanicus and O. phyllotis predominate in north-central areas of the state [34,35,36]. Moreover, P. yucatanicus and S. toltecus may visit backyards of rural households associated with secondary forests [37,38]. The presence of Leishmania in wild rodents has only been investigated in Tinum, Yucatan where H. gaumeri and O. phyllotis were found infected by the parasites [21].Berzunza-Cruz et al. provided the first evidence of Leishmania infection in 13 bat species from the Chiapas–Tabasco ecoregion and Jalisco, Mexico [39]. Chiroptera is the most diverse order of mammals in Yucatan with an estimated 43 species belonging to seven families [40]. Eight species of bats (Pteronotus psilotis, Artibeus jamaicensis, A. lituratus, Dermanura phaeotis, Carollia sowelli, Desmodus rotundus, Glossophaga mutica and Sturnira parvidens) that were found naturally infected by Leishmania also exist in Yucatan [39]. Most of them belong to the family Phyllostomidae, except for P. psilotis, which belongs to the family Mormoopidae. Phyllostomidae is the most diverse family of bats in Yucatan [40]. Members of this family are frugivorous, insectivorous, nectarivorous, carnivorous and hematophagous (although some species have mixed diets) and inhabit a variety of natural sites, such as caves, rock crevices, foliage and hollow trees. They commonly occupy artificial sites like buildings and householding surroundings [41]. The evidence points out a noticeable research gap on Leishmania bat infection in the region.Leishmania infection in opossums of the genus Didelphis has been reported in several countries of Latin America in both sylvatic and domestic habitats [42,43,44,45]. In Yucatan, this genus is represented by two species, Didelphis virginiana and D. marsupialis. The first species abound in the northern area of the state, whereas the later species predominates in central-south areas of the state [46]. Opossums of the genus Didelphis can adapt to human-modified landscapes due to their ability to exploit a wide range of resources and environments [47]. Particularly, D. virginiana is a species that has been extensively studied in Yucatan and reported as a common visitor of the peridomicile of urban and rural areas where they find food (e.g., fruits, chicks, organic waste) and shelters (e.g., roofs of houses, hollow trees, and piles of rocks) [46], but surprisingly, an opossum infection with Leishmania has not been reported in Mexico. 6. Conclusions

Leishmaniasis is a neglected public health problem, mainly for tropical and subtropical areas of the world, despite current control initiatives. Environmental changes caused by anthropogenic activities that disturb natural ecosystems will continue influencing the emergence and reemergence of the disease, particularly in tropical areas. The evidence reviewed here highlights the occurrence of human leishmaniasis cases in several municipalities of Yucatan, where local transmission of the disease had not previously occurred.

Very likely, we are witnessing the spread of leishmaniasis from hyperendemic areas to vulnerable and receptive areas of the peninsula and the emergence of new transmission foci in the Yucatan state. Global environmental changes are occurring in Yucatan. Deforestation and urban expansion will reach areas projected to have medium to severe environmental changes in the following decades, driving vector and reservoirs ecology changes, raising the risk of disease emergence in unexpected localities.

Further research must look for the forecasting and evaluation of scenarios of environmental changes to be able to predict the effects on the emergence of leishmaniasis in the state. Given that control strategies are limited, prevention and action through the One Health approach could lead to sustainable acts against disease emergence and increasing risk.

The One Health approach proposes to address health problems from the different aspects involved in their occurrence. From this perspective, the emergence of leishmaniasis foci in Yucatan shows the need to strengthen a multisectoral approach, consisting primarily in the joint work of different sectors to address the health problem [62]. The information described in this review shows how the government sector, through the Mexican health authorities and the academic sector, has begun the task of jointly addressing the identification, documentation, and act on the emergence of new outbreaks, each from their areas of responsibility and capacities for action. There are new windows of opportunity for the integration of the environmental and food production sectors, seeking to expand the prevention and response capacity in a coordinated manner since the scenario favors the appearance of new outbreaks and the potential establishment of new transmission foci.