**2. Leishmaniasis**

Leishmaniasis is one of the most neglected diseases, present in at least 88 countries across the tropical and subtropical regions of Africa, Asia, Mediterranean, South Europe as well as South and Central Americas, with a global distribution of about two million new cases yearly worldwide [4]. The disease poses a great impact in public health contributing to 3.3 million disability adjusted life years [5]. It is a parasitic disease caused by the biphasic protozoan of the family Trypanosomatidae, order Kinetoplastida and genus *Leishmania*, which includes 35 species, being at least 13 of them considered human pathogens [6] (**Figure 1**).

**Figure 1.** Main species of the *Leishmania* genus. Those causing visceral leishmaniasis (VL): *Leishmania (L.) donovani* in Asia, *Leishmania (L.) chagasi* in the Americas and *Leishmania (L.) infantum* in Asia, Europe and Africa. Note: *Leishmania (L.) infantum chagasi* nomenclature was proposed by Marcili et al. [7] using phylogenetic analysis of *Leishmania* species occurring in Latin America.

*Leishmania* is transmitted by the bite of infected female sandflies of the Phlebotominea subfamily of the genus *Phebotomus* in the Old World and the genus *Lutzomyia* in the New World [8]. Sandflies become infected during blood meals by ingesting leishmanial amas‐ tigotes of infected cells. Amastigotes differentiated into dividing promastigotes (flagellate forms) to establish the parasite life cycle and multiplying in the gut of sandfly vector (in the hindgut and in the midgut for *Viannia* and *Leishmania* subgenus, respectively) [9, 10]. After digestion of the blood meal, successful infection in a sandfly vector results in the development of several promastigotes forms, named according to their morphology as pro‐ cyclic, haptomonad, nectomonad, paramastigote and metacyclic forms. Only metacyclic forms transmitted through sandfly bites are able to begin an infection in vertebrate hosts, and thereby the transmission cycle completes [11, 12]. Thus, during blood meals, the vector injects the infective promastigotes in the host, which induce chemotaxis of neutrophils and macrophages. The parasites are then engulfed by macrophages and other types of mono‐ nuclear and polymorphonuclear phagocytic cells, becoming amastigotes, which is the tissue stage. Inside the cell, the amastigotes reproduce by binary fission, breakup the cell and are released to extracellular environment, being again engulfed by phagocytic cells and repeat‐ ing the cycle [13–16] (**Figure 2**).

domestic dogs the principal reservoir in urban areas [1]. The introduction in urban settings is due to multiple conditions such as migrations, inadequate living conditions, high population

The disease presents itself in different clinical forms including cutaneous (CL), mucocuta‐ neous (MCL) and visceral leishmaniasis (VL), depending on the species of *Leishmania* and the parasite‐host relationship. In Latin America, VL is caused by the protozoan *Leishmania (Leishmania) infantum chagasi* and is the most severe form, characterized by intermittent fever,

Since VL is no longer being characterized as a rural disease (1980s), [3] the main strategy to limit the expansion of the disease, besides the treatment of human cases, is the control of the vector *Lutzomyia longipalpis* and the parasite's reservoirs. In addition, molecular epidemiologi‐ cal studies of natural infection with species of *Leishmania*, especially in relation to its endemic distribution, may indicate the infection rate of parasites in sandflies in order to assess the populations at risk and to direct public health control strategies. In this context, we aimed in this chapter to review the main features of VL with regard the distribution of disease cases

Leishmaniasis is one of the most neglected diseases, present in at least 88 countries across the tropical and subtropical regions of Africa, Asia, Mediterranean, South Europe as well as South and Central Americas, with a global distribution of about two million new cases yearly worldwide [4]. The disease poses a great impact in public health contributing to 3.3 million disability adjusted life years [5]. It is a parasitic disease caused by the biphasic protozoan of the family Trypanosomatidae, order Kinetoplastida and genus *Leishmania*, which includes

**Figure 1.** Main species of the *Leishmania* genus. Those causing visceral leishmaniasis (VL): *Leishmania (L.) donovani* in Asia, *Leishmania (L.) chagasi* in the Americas and *Leishmania (L.) infantum* in Asia, Europe and Africa. Note: *Leishmania (L.) infantum chagasi* nomenclature was proposed by Marcili et al. [7] using phylogenetic analysis of *Leishmania* species

and natural infection rates of *Leishmania* in phlebotomine females in Latin America.

35 species, being at least 13 of them considered human pathogens [6] (**Figure 1**).

density and environment changes [2].

60 The Epidemiology and Ecology of Leishmaniasis

**2. Leishmaniasis**

occurring in Latin America.

weight loss, hepatosplenomegaly and pancytopenia [3].

**Figure 2.** Life cycle of *Leishmania* spp. *Leishmania* parasites are transmitted by the bites of infected female sandflies during their blood meals. The vector injects the metacyclic promastigote forms, which are engulfed by phagocytic cells at the bite site. Inside the cells, promastigotes transform into amastigotes, the tissue stage of the parasite, which will then reproduce by binary fission and progress to infect other mononuclear phagocytic cells. Interactions between parasite, host and other factors will determine whether the infection progress to cutaneous or visceral leishmaniasis. Sandflies become infected by ingesting infected cells during blood meals. In the digestive tract of the vector, amastigotes differentiate into promastigotes and migrate to the proboscis, from where they are injected into the hosts during the bite.

Leishmaniasis in humans presents a wide diversity of clinical manifestations depending on the complex interactions between the parasite and the host immune responses, ranging from asymptomatic to severe and potentially lethal disease. The disease is classified into three main forms: cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL) [17].

CL is the most frequent clinical form, representing 75% of leishmaniasis total cases, and has an estimated yearly incidence of 0.7–1.2 million cases, being distributed in Afghanistan, Colombia, Brazil, Algeria, Peru, Costa Rica, Iran, Syria, Ethiopia and Sudan [4, 5]. CL is char‐ acterized by localized cutaneous nodules or lesions at the site of the sandfly bite (localized form). It has an incubation time of weeks to months, and initially has the appearance of an erythematous papule, which can evolve into a plaque or ulcer or can spontaneously heal in 2–10 months. These lesions are usually painless and without evident systemic symptoms or pruritus. Parasites can disseminate through the skin and form multiple non‐ulcerative nodules (diffuse form), which is associated to an ineffective immune response, especially in patients infected with human immunodeficiency virus (HIV) [18, 19].

Moreover, *Leishmania* spp*.* can propagate through the lymphatic system, resulting in naso‐ bronchial and oral mucosal tissue destruction (MCL form) [18, 19]. The MCL form affects both nasal and oral mucous membranes, leading to partial or total destruction. The VL is a systemic and chronic disease, and it is highly fatal if not treated [1].
