**1. Introduction**

The vectors of leishmaniasis are dipterans belonging to the Psychodidae family, belonging to the genera Phlebotomus (Old World), and Lutzomyia (New World), with wide distribution in warm and temperate climates [1]. Only female sandflies are hematophagous and when infected become vectors [2], they can contaminate, in addition to humans, other mammals such as domestic dogs and cats, making them important reservoirs of the protozoan [3]. These vectors have been more active in the twilight and post-dusk, sheltering during the day in humid, shaded places and well protected from the winds, for example, wild animal burrows, wood holes, bamboo cavities [4].

Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a group of neglected tropical diseases whose clinical manifestations vary depending on the infectious species of Leishmania and weakness of the host [5]. Leishmaniasis presents an unstable epidemiological pattern, presenting unpredictable fluctuations in the number of cases in each region. In the Old World, it was

initially described as a dermal condition known as Rish-e-Balkhi (Balkh Wound) as well as "kala-azar". In the New World, leishmaniasis parasites were first described in 1909 by Adolpho Carlos Lindenberg, Antonio Carini, and Ulysses de Freitas Paranhos in skin lesions of patients with 'Bauru's ulcers' in the state of São Paulo, Brazil [6]. Currently, there are three groups of parasites of the genus Leishmania classified into different subgenera and these vary depending on which parts of the vector's gut are colonized by the parasites [7].

It is now known that leishmaniasis can present different characteristics that vary from skin lesions (such as erythematous or hypopigmented macules, papules, nodules, and patches) to visceralization, depending on the species of infecting parasite and the immune response developed by the host (**Figure 1**). However, it is known that cultural, environmental, and socioeconomic factors play an important role. Furthermore, due to the outbreak of tegumentary leishmaniasis in conflict zones in the Middle East, it reveals that war, ecological disasters, and forced migration are other factors associated with leishmaniasis risk factors [6]. Leishmaniasis-causing protozoa have two main life cycle morphologies: the amastigote phase [without apparent flagellum], which is intracellular in the mammalian host, and the promastigote phase [presence of flagellum in the anterior position of the cell] in the fly. The promastigote phase presents five main forms: procyclic, nectomonad, leptomonad, haptomonad, and metacyclic [7]. The growth of the flagellum in the promastigote occurs in several cell cycles. There are clear implications for the mechanisms of regulation of flagellum length, life cycle stage differentiation, and trypanosomatid division in general, and post-genomic analyzes of Leishmania cell biology have contributed to a better understanding of these mechanisms, not only regarding cell differentiation but also to the molecular mechanisms behind the protozoan infection, both in the vector and in the hosts [8].

Studies indicate that leishmaniasis parasites have adaptation mechanisms that allow the optimal activity of each life stage at its corresponding environmental pH [9]. For example, at pH 7.0 it produces morphologically mixed populations of promastigotes in the stationary phase, but it also includes a subpopulation with similar morphology to the metacyclic (**Figure 2**) [18, 19].

#### **Figure 1.**

*Representative scheme of the genus Leishmania classification illustrating three subgenres. The species presented include some of the more investigated that are the focus of biomedical research. They were colored by occurrences in the old world (blue boxes) and new world (red boxes), and the without colors occur in both regions. Parasites of the Leishmania and Viannia subgenus infect mammals, while Sauroleishmania infects reptiles as vertebrate hosts. Adapted from [1, 7].*

*Leishmaniasis: Molecular Aspects of Parasite Dimorphic Forms Life Cycle DOI: http://dx.doi.org/10.5772/intechopen.102370*

#### **Figure 2.**

*Representative scheme of Leishmania differentiation process inside the sand fly vector. AM = amastigote form, the decrease in temperature and an increase in pH is detected by the cell and stimulate cell differentiation [10, 11], through modulation of the expression of genes linked to cell functions [12]. PP = pro-cyclic promastigote form, the secretion of chitinol enzymes aids in the escape from peritrophic membrane allowing the fixation on the vector intestine wall [13], the decrease in pH linked to the increase in glucose in the medium stimulates differentiation and migration according to the gradient of glucose concentration [14] by modulating the expression of genes linked to different cellular functions [12]. NP = Nectomonad Promatigote form, migrate to the thoracic portion of the midgut and begin to secrete PSG [15], as well as a decrease in the expression of several genes [12]. LP = Leptomonad Promatigote form, PSG secretion and detection of decreased oxygenation and pH actives signals for cell differentiation [16] into HP = Haptomonad Promatigote which attaches to the thoracic midgut wall and produces the PSG gel [17], or differentiates into MP = Metacyclic Promatigote form, the infecting phase, which migrates to the anterior portion of the sand fly intestine and infects the host during the next meal [14]. The increase is represented as blue arrows and the decrease is represented as red arrows.*
