**3.2. Clinical features**

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

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

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

VL is recognized by the World Health Organization (WHO) as one of the most important zoonoses, due to its high incidence and mortality. Every year about 500,000 new cases of VL are reported, with 40,000–50,000 deaths worldwide [20]. The disease is endemic in 65 countries, including Bangladesh, India, Brazil, Nepal, Ethiopia and Sudan. In Latin America, VL is pres‐ ent in 12 countries and is caused by the protozoan *Leishmania (L.) infantum chagasi*, with 90% of the cases being reported in Brazil, especially in the Northeast and Southeast regions, rep‐ resenting a significant public health concern [3, 21]. In Brazil, the average number of cases of VL increased from 2866 in 1990–2000 to 3353 in 2001–2014 [22], with a fatality rate of about

The disease has shown significant changes in the pattern of transmission, initially with a predominantly rural distribution, which fly has expanded to peri‐urban and large urban areas [20, 24]. Although the main route of transmission is associated to hematophagous sand‐ fly vectors, there are other routes which are important to be reported, including sexual, verti‐

Although the infection can affect people of all ages, in endemic areas, most reported cases are children below 10 years old. This is probably due to their immunological immaturity aggravated by malnutrition, which is common in these areas [3, 20]. Over 60% of the affected

forms: cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL) [17].

patients infected with human immunodeficiency virus (HIV) [18, 19].

systemic and chronic disease, and it is highly fatal if not treated [1].

**3. Visceral leishmaniasis**

62 The Epidemiology and Ecology of Leishmaniasis

**3.1. Epidemiology**

7% in 2014 [23].

cal and hematogenic [16].

people are males [21, 25].

VL is also known as kala‐azar or "black fever/disease", which is a reference to the skin hyper‐ pigmentation by melanocyte stimulation during infection. In addition, other terms are used to describe VL, such as Dumdum fever, Assam fever and infantile splenomegaly. It is the most severe leishmaniasis form and generally affects the spleen, liver, bone marrow or other lymphoid tissues. The syndrome is characterized by fever, weight loss, hepatosplenomegaly, pancytopenia and hypergammaglobulinemia. The fever can be continuous or remittent, and also characteristically described as periods with and without pyrexia, becoming intermittent at a later stage. Patients may also report night sudoresis, weakness, diarrhea, malaise and anorexia [26].

The onset of VL can be insidious or sudden, and the incubation period varies from 3 to 6 months, depending on the patient's age and immune status, as well as the species of *Leishmania*. If untreated, it is frequently fatal within 2 years. Death may be related to hem‐ orrhage, severe anemia, immunosuppression and/or secondary infections. Interestingly, some successfully treated VL cases may develop maculopapular or nodular rashes, named post‐kala‐azar dermal leishmaniasis [17, 19] and classified into three types: depigmented macules, erythematous patches, and yellowish pink nodules [27]. Complications of VL include amyloidosis, glomerulonephritis [28] and cirrhosis [29]. In HIV patients coinfected with VL, atypical symptoms include gastrointestinal ulcerations, pleural effusion and ody‐ nophagia [30].
