**1. Introduction**

Global human population is facing the impacts of centuries of constant changes in natural environments. Impacts in the dynamics of infectious diseases are not only expected, but can already be noticed. Vector-borne diseases are particularly susceptible to environmental changes, since their occurrence depends on the ecological balance between different species in complex transmission cycles [1-3]. Leishmaniases are among the vector-borne diseases most affected by this *ecological chaos* driven by human actions [4], and one of the expected impacts is the expansion of its geographical distribution [5-7].

Leishmaniases are among the world's six most neglected diseases, affecting indistinctively men, women and children. Usually they occur among the poorest of the poor, mainly in developing countries, contributing to establishment and maintenance of social inequities [7]. They can be divided in two main clinical forms: visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). Despite this simple classification, a wide clinical spectrum is observed, mostly because of the high diversity of parasites (Trypanosomatidae of *Leishmania* genus), vectors (Phlebotominae sand flies) and reservoir hosts (mammals of several orders) involved in its transmission cycles [7, 8].

The geographical distribution of leishmaniases includes 98 countries in American, European, Asiatic, African and Australian continents. The World Health Organization estimates the yearly occurrence of about 200,000 to 400,000 VL human cases and 700,000 to 1.2 million CL human cases. More than 90% of global VL cases are recorded in six countries: India, Bangla‐ desh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in tropical regions of the Americas, the

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Mediterranean basin, western and central Asia. In the American continent, Brazil is the country with the highest estimated incidences of both visceral and cutaneous leishmaniases [9].

The distribution of leishmaniases in the world can be partially explained by its widely distributed vectors. The sand flies are small insects (adults of about 3-5 mm) from order Diptera, family Psychodidae, subfamily Phlebotominae. Although occurring mainly in the tropical, hottest areas of the world (Latin America, South Europe, Africa, South Asia and Australia), their distribution stretches north and south to latitudes of over 40°, such as in Germany [10] and Argentinean Patagonia [11]. Sand flies have primarily crepuscular and nocturnal habits, but adults were captured during the day in dense forests [12], caves [13] and dark, humid animal shelters [14]. Only females are haematophagous and thus are related with *Leishmania* transmission. Their broad feeding habits contribute to the transmission of patho‐ gens between hosts in sylvatic and peridomestic areas [15, 16]. Of approximately 900 described sand fly species, no more than 70 have been implicated in leishmaniases transmission [17]. All New World vector species belong to *Lutzomyia* genus, while the Old World vectors are grouped in *Phlebotomus* genus [15, 18].

In Brazil, the concept of leishmaniases as a sylvatic zoonosis is restricted to the Amazon Forest, Atlantic Forest fragments and parts of Cerrado. A new transmission profile has emerged, driven mostly by human-made environmental changes. In past decades, human migration of different origins and purposes resulted in major deforestation and unplanned settlements. These changes favor the dispersion of sylvatic animals (some *Leishmania* reservoir hosts) and sand flies (especially those species with eclectic feeding habits) to peridomestic areas, where new transmission cycles may establish close to human dwellings [19-21].

This new transmission profile is especially evident for American Cutaneous Leishmaniasis (ACL), which is caused by a variety of *Leishmania* parasites. Although some clinical manifes‐ tations are more frequently associated with a particular *Leishmania* species or subgenus (*Viannia* or *Leishmania*), none is unique to a species. In addition, a substantial but variable proportion of infections are asymptomatic. Human cases have been occurring with different clinical forms, including localized, disseminated, diffuse and atypical cutaneous and mucosal lesions. Different species of sand flies and reservoirs interact in complex transmission cycles, with particular ecoepidemiological features on each disease focus [22, 23].

According to Brazilian Ministry of Health [23], ACL can be categorized in three epidemiolog‐ ical patterns:


**3.** Rural/periurban (colonization areas): ACL occurrence is related to human migration, occupation of slopes and aggregation in periurban areas associated with secondary and residual vegetation. Synanthropic and domestic animals such as dogs, horses and rodents are suggested reservoir hosts.

Mediterranean basin, western and central Asia. In the American continent, Brazil is the country with the highest estimated incidences of both visceral and cutaneous leishmaniases [9].

The distribution of leishmaniases in the world can be partially explained by its widely distributed vectors. The sand flies are small insects (adults of about 3-5 mm) from order Diptera, family Psychodidae, subfamily Phlebotominae. Although occurring mainly in the tropical, hottest areas of the world (Latin America, South Europe, Africa, South Asia and Australia), their distribution stretches north and south to latitudes of over 40°, such as in Germany [10] and Argentinean Patagonia [11]. Sand flies have primarily crepuscular and nocturnal habits, but adults were captured during the day in dense forests [12], caves [13] and dark, humid animal shelters [14]. Only females are haematophagous and thus are related with *Leishmania* transmission. Their broad feeding habits contribute to the transmission of patho‐ gens between hosts in sylvatic and peridomestic areas [15, 16]. Of approximately 900 described sand fly species, no more than 70 have been implicated in leishmaniases transmission [17]. All New World vector species belong to *Lutzomyia* genus, while the Old World vectors are grouped

In Brazil, the concept of leishmaniases as a sylvatic zoonosis is restricted to the Amazon Forest, Atlantic Forest fragments and parts of Cerrado. A new transmission profile has emerged, driven mostly by human-made environmental changes. In past decades, human migration of different origins and purposes resulted in major deforestation and unplanned settlements. These changes favor the dispersion of sylvatic animals (some *Leishmania* reservoir hosts) and sand flies (especially those species with eclectic feeding habits) to peridomestic areas, where

This new transmission profile is especially evident for American Cutaneous Leishmaniasis (ACL), which is caused by a variety of *Leishmania* parasites. Although some clinical manifes‐ tations are more frequently associated with a particular *Leishmania* species or subgenus (*Viannia* or *Leishmania*), none is unique to a species. In addition, a substantial but variable proportion of infections are asymptomatic. Human cases have been occurring with different clinical forms, including localized, disseminated, diffuse and atypical cutaneous and mucosal lesions. Different species of sand flies and reservoirs interact in complex transmission cycles,

According to Brazilian Ministry of Health [23], ACL can be categorized in three epidemiolog‐

**1.** Sylvatic: In this case, transmission occurs in primary vegetation areas, where the disease is characterized as a strictly sylvatic zoonosis. Humans get infected occasionally when

**2.** Sylvatic/occupational and impacted areas: This pattern is associated with exploitation of natural environments and deforestation, originated mostly from constructions of roads, hydroelectric power plants, human settlements, wood extraction, agricultural activities, military training and ecotourism. In this case, humans are more intensively exposed to

new transmission cycles may establish close to human dwellings [19-21].

with particular ecoepidemiological features on each disease focus [22, 23].

entering these areas, where the enzootic cycle is maintained;

in *Phlebotomus* genus [15, 18].

4 Leishmaniasis - Trends in Epidemiology, Diagnosis and Treatment

ical patterns:

vector contact;

Brazil is currently facing an increasing geographical expansion of ACL, with a shift from the classical predominant epidemiological pattern 1 to frequent observations of pattern 2. All of its states have records of the disease, with a growing number of municipalities affected each year (Figure 1).

**Figure 1.** Brazilian municipalities with records of American Cutaneous Leishmaniasis, 2001 to 2012. Each point on the map represents one municipality with ACL human case records

This expansion can probably be explained by the growing environmental changes, which in turn affect vector behavior. Some ACL vector species have been showing evidences of adaptation to man-modified environments, establishing in peridomestic areas, even in outskirts of large cities [22, 23]. In this case, two sand fly species are particularly good examples, in different ecoepidemiological situations: *Lutzomyia (Nyssomyia) whitmani* and *Lutzomyia (Nyssomyia) flaviscutellata*. On the following sections the geographical distribution in Brazil and relation with ACL transmission of these species are presented.
