Cutaneous and Mucocutaneous Leishmaniasis | Actas Dermo-Sifiliográficas

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Ordiales, F. Vázquez-López, M. Pevida, B. Vázquez-Losada, L.M. Quirós, C. Martín" "autores" => array:7 [ 0 => array:2 [ "nombre" => "H." "apellidos" => "Ordiales" ] 1 => array:2 [ "nombre" => "F." "apellidos" => "Vázquez-López" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Pevida" ] 3 => array:2 [ "nombre" => "B." "apellidos" => "Vázquez-Losada" ] 4 => array:2 [ "nombre" => "F." "apellidos" => "Vázquez" ] 5 => array:2 [ "nombre" => "L.M." "apellidos" => "Quirós" ] 6 => array:2 [ "nombre" => "C." 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Parte 2: aplicaciones en psoriasis, dermatitis atópica y otras dermatosis" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1650 "Ancho" => 2917 "Tamanyo" => 276752 ] ] "descripcion" => array:1 [ "en" => "IL-4/IL-13/JAK/STAT signaling pathway and SYK pathway in atopic dermatitis. The figure shows various JAK inhibitors and dual JAK/SYK inhibitors in atopic dermatitis. The biological functions of IL-4 and IL-13 are mediated by their binding to the subunits IL-4Rα and IL-13Rα1 of the corresponding receptors. IL-4 binds to a type 1 receptor that includes IL-4Rα and the γ chain of the cytokine receptor or a type 2 receptor configured by IL-4Rα and IL-13R α1. The latter is the main IL-13 receptor. IL-5 produced as a result of polarization of type 2 helper T cells binds to the IL-5Rα subunit of its receptor to form a complex with a shared signaling subunit, the β chain, and induce phosphorylation of JAK1/JAK2 and activation of STAT1, STAT3, and STAT5. Via its SH2 domains, SYK binds to diphosphorylated immunoreceptor tyrosine-based activation motifs (ITAM) in the cytoplasm of various immune receptors, such as T-, B-, NK-cell receptors or the various receptors for the constant fraction of immunoglobulin (Fc) in neutrophils, mastocytes, macrophages dendritic cells, and other strains of the immune system. This interaction results in the activation of other proteins that transmit downstream signals. Figure generated with the assistance of Biorender.com." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Garcia-Melendo, X. Cubiró, L. Puig" "autores" => array:3 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Garcia-Melendo" ] 1 => array:2 [ "nombre" => "X." "apellidos" => "Cubiró" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Puig" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731021000065" "doi" => "10.1016/j.ad.2020.12.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731021000065?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219021001682?idApp=UINPBA000044" "url" => "/15782190/0000011200000007/v1_202107020822/S1578219021001682/v1_202107020822/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Cutaneous and Mucocutaneous Leishmaniasis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "601" "paginaFinal" => "618" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "I. Abadías-Granado, A. Diago, P.A. Cerro, A.M. Palma-Ruiz, Y. Gilaberte" "autores" => array:5 [ 0 => array:4 [ "nombre" => "I." "apellidos" => "Abadías-Granado" "email" => array:2 [ 0 => "isabel.abadiasg@gmail.com" 1 => "iabadias@salud.aragon.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Diago" ] 2 => array:2 [ "nombre" => "P.A." "apellidos" => "Cerro" ] 3 => array:2 [ "nombre" => "A.M." "apellidos" => "Palma-Ruiz" ] 4 => array:2 [ "nombre" => "Y." "apellidos" => "Gilaberte" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Miguel Servet, Zaragoza, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Leishmaniasis cutánea y mucocutánea" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1880 "Ancho" => 2512 "Tamanyo" => 451159 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A, Mucocutaneous leishmaniasis manifests as a chronic ulcer often affecting the nasal mucosa. B, Firm cutaneous leishmaniasis papules on the palm of a patient coinfected with visceral leishmaniasis and human immunodeficiency virus. C, Hyperpigmented macules in the neck area. D, Hypopigmented macules as a manifestation of post-kala-azar dermal leishmaniasis in a 7-year-old boy. The diagnosis was established by molecular techniques, as the biopsy was negative." ] ] ] "textoCompleto" => "IntroductionLeishmaniasis is a chronic disease caused by flagellate protozoa of the genus Leishmania, of which there are over 20 species. Leishmania parasites are obligate intracellular parasites transmitted by the bite of infected female sandflies of the Phlebotomus and Lutzomyia genera. Leishmaniasis is essentially a zoonotic disease. The main reservoirs are dogs and rodents, but there are 2 cases for which humans are the main reservoirs: Leishmania donovani and Leishmania tropica.EpidemiologyThe estimated incidence of leishmaniasis according to the World Health Organization is 700 000 to 1 million cases a year, of which 50 000 to 90 000 correspond to visceral leishmaniasis (VL).<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Approximately 95% of all cutaneous leishmaniasis (CL) cases occur in South America, the Mediterranean Basin, the Middle East, or Central Asia. LV, by contrast, is predominant in Brazil, East Africa, and India. In 2018, over 85% of new CL cases reported to the WHO were from Afghanistan, Algeria, Bolivia, Brazil, Colombia, Iran, Iraq, Pakistan, Syria, and Tunisia, while over 95% of new LV cases were from Brazil, China, Ethiopia, India, Iraq, Kenya, Nepal, Somalia, and Sudan.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Finally, over 90% of new mucocutaneous leishmaniasis (MCL) cases were reported in 4 countries: Brazil, Bolivia, Ethiopia, and Peru.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Leishmaniasis has traditionally been classified as Old World or New World depending on its geographic location. Old World leishmaniasis occurs in Asia, Africa, and Europe, and is mostly caused by L tropica, Leishmania major, Leishmania aethiopica, Leishmania infantum, or L donovani. New World leishmaniasis, in turn, occurs in America, and is mostly caused by Leishmania mexicana, Leishmania amazonensis, Leishmania braziliensis, Leishmania panamensis, or Leishmania infantum chagasi (a subspecies of L infantum in the New World, formerly known as Leishmania chagasi).2 The main epidemiological and clinical patterns for most common Leishmania species are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<a class="elsevierStyleCrossRefs" href="#bib0010">2–5</a><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the geographic distribution of the main species and their principal reservoirs.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>In Spain, leishmaniasis is a zoonotic disease endemic to the peninsula and the Balearic Islands. The main causative species in both CL and VL is L infantum, which is transmitted by Phlebotomus perniciosus and Phlebotomus ariasi.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Dogs are the main reservoir for L infantum, although other reservoirs such as hares<a class="elsevierStyleCrossRef" href="#bib0035">7</a> and rats<a class="elsevierStyleCrossRef" href="#bib0040">8</a> have been described. Apart from its endemic form, leishmaniasis can occur in patients with human immunodeficiency virus (HIV) infection<a class="elsevierStyleCrossRef" href="#bib0045">9</a> or a compromised immune system (e.g., patients being treated with tumor necrosis factor [TNF] inhibitors).<a class="elsevierStyleCrossRef" href="#bib0050">10</a> There have also been epidemic outbreaks, such as the Madrid outbreak that occurred between 2009 and 2013.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Finally, phenomena such as globalization, international travel, and migration have increased the prevalence of leishmaniasis in developed countries.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>PathogenesisLeishmania promastigotes are injected into human skin by infected female sandflies. Here, through phagocytosis by macrophages, they transform into amastigotes, multiplying inside the cells and infecting other mononuclear phagocytized cells. Sandflies becomes infected by ingesting infected cells while feeding on the host’s blood. Once in the intestine of the sandflies, the amastigotes transform into promastigotes.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> The incubation period of leishmaniasis varies according to the clinical form of disease, but is generally 2 weeks (or less) to 2 months for CL, 3 to 9 months for VL, and over 2 years for MCL.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>The clinical manifestations of leishmaniasis vary according to the species involved<a class="elsevierStyleCrossRef" href="#bib0070">14</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) and the host’s immune response.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> The spectrum of immune response ranges from a strong T-cell response that results in the production of interferon (IFN) γ to a humoral response that produces high antibody levels. Leishmania species are eliminated by IFN-γ-activated macrophages, but cannot be neutralized by antibodies. This is why individuals who mount a strong immune response have lesions with few parasites, while those with a humoral response are unable to control infection. Diffuse CL is caused by uncontrolled infection. It should also be noted that an exaggerated T helper type 1 response and increased expression of CD8+ T cells are associated with more severe forms of disease, such as MCL.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>Clinical ManifestationsCutaneous LeishmaniasisCL starts with the formation of a papule at the inoculation site, which is typically located in exposed areas of the body, such as the face or extremities. The papule typically develops into a plaque or a nodule (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A-E) with a tendency to ulcerate. Gum collectors (chicleros) in Mexico and Central America, for example, develop a characteristic ulcerated lesion on their ear following infection by L mexicana.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> CL lesions can be single or multiple and infection can spread through the lymphatic system, causing lymph node enlargement, satellite lesions, and even sporotrichoid lesions.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Atypical forms, such as eczematous, erysipeloid, lupoid, annular, and verrucous lesions, are more common in the New World.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> CL lesions can resolve spontaneously within several months leaving a scar. Some cases, however, become chronic or spread. Chronic recurrent forms are typical in L tropica infections and are characterized by the formation of papules at the periphery of previously healed ulcers.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Chronicity has been linked to numerous factors, including increased arginase activity in polymorphonuclear leukocytes.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Diffuse CL, which is caused by L aethiopica, L Mexicana, or L amazonensis, presents as multiple nonulcerated papules and/or nodules involving most of the skin.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> The lesions contain abundant parasites and can result in significant facial changes, causing a leonine-like appearance similar to that seen in lepromatous leprosy. Mucosal lesions are common.<a class="elsevierStyleCrossRef" href="#bib0105">21</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Mucocutaneous LeishmaniasisMucosal involvement can coincide with cutaneous involvement or occur after the clearance of cutaneous lesions, sometimes even year later. The infection can spread through the bloodstream or lymphatic system. In endemic areas, mucosal involvement may be seen in up to 20% of patients.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Most cases of MCL are caused by L braziliensis, but other species involved are L amazonensis, L guyanensis, and L panamensis. The nasal (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A) and oral mucosa are the most frequently affected areas. Lesions in the oral cavity can spread to the oropharynx and larynx, and may affect cartilage and vocal cords.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> MCL lesions are ulcerated and can cause disfigurement. Treatment is essential to control infection, as the condition can be fatal.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Visceral LeishmaniasisIn VL, infected macrophages spread through the reticuloendothelial system to the bone marrow, spleen, and liver. Clinical manifestations include fever, weight loss, hepatosplenomegaly, and lymph node enlargement. VL is mainly caused by L donovani in adults and L infantum or L chagasi in children and immunosuppressed individuals. Patients may also develop skin manifestations, which can be specific, such as papules (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>b), nodules, and ulcers, or nonspecific, such as purpura and hyperpigmentation (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>C). The presence of hyperpigmentation probably explains the origin of the term kala-azar, which means black fever in Hindu. Skin darkening has been described in 9.88% of patients with VL<a class="elsevierStyleCrossRef" href="#bib0120">24</a> and was recently linked to an increased production of cortisol.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Because hyperpigmented areas show amastigotes on histology, they could perhaps be considered a specific manifestation of leishmaniasis.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>Post Kala-Azar Dermal LeishmaniasisPost kala-azar dermal leishmaniasis (PKDL) occurs in patients with VL caused by L donovani or, on occasions, L infantum. It is particularly common in immunosuppressed patients<a class="elsevierStyleCrossRef" href="#bib0135">27</a> and can appear up to 20 years after treatment.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> In patients infected with HIV, however, PKDL can coincide with, or at times precede, VL.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> It is characterized by hypopigmented macules (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>D), flesh-colored nodules and/or verrucous papules that mainly affect the face, although they can spread to the rest of the body.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> PKDL mainly occurs in east Africa and India, although cases are occasionally seen in Spain.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> The clinical presentation varies depending on geographic location and the host’s immune response. In Asia, 90% of cases appear as macules, while in Africa, papules are predominant.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> PKDL is more common—and severe—in immunosuppressed patients, who may exhibit atypical forms such as nodules not necessarily involving the face and a higher abundance of parasites in lesions.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> The main entity in the differential diagnosis is leprosy, which is characterized by a loss of sensation. PKDL must be treated systemically, although African forms can resolve spontaneously within a year.HIV CoinfectionHIV infection has been linked to a 2000-fold increased risk of VL.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> This is because both infections share a immunopathogenic mechanism involving macrophages and dendritic cells that accelerates progression in both cases.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> HIV was responsible for the resurgence of VL in Europe during the 1990s that hit Spain, Portugal, Italy, and France particularly hard.<a class="elsevierStyleCrossRefs" href="#bib0165">33,35</a> Eighty percent of all cases of VL-HIV coinfection reported to the WHO during this period were from Spain.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> In addition, a retrospective analysis of all patients hospitalized for leishmaniasis in Spain between 1997 and 2008 found that 37% were HIV positive.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> Coinfection can result in atypical presentations of CL and VL,<a class="elsevierStyleCrossRefs" href="#bib0090">18,38,39</a> poor response to treatment, higher mortality rates, higher viral loads, and faster progression to AIDS. The introduction of highly active antiretroviral therapy in 1997 increased survival rates and also reduced the incidence and recurrence of leishmaniasis.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> It is important thus to rule out HIV in all patients with VL, even those living in endemic areas.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>Leishmaniasis and TNF InhibitorsTNF inhibitors are widely used to treat inflammatory diseases such as psoriasis and rheumatoid arthritis. TNF-α participates in cell-mediated immune response by activating CD4+ and CD8+ T cells. Together with other cytokines such as interleukin 12 and IFN-γ, it has a key role in early infection control. Parasite DNA has been detected in the blood of up to 58% of healthy individuals in the Mediterranean, an endemic area with high levels of exposure to Leishmania, but the actual numbers of people who develop the disease are low.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> It is therefore believed that most immunocompetent individuals are able to control infection before it manifests. Likewise, it has been suggested that TNF-α inhibitors could favor the reactivation of latent leishmaniasis,<a class="elsevierStyleCrossRef" href="#bib0050">10</a> and also modify clinical presentation, the natural course of disease, and response to treatment. Based on the cases published to date, the best approach to dealing with reactivation of a latent infection would appear to be to treat the infection with systemic therapy and interrupt TNF inhibitor treatment until the infection has cleared<a class="elsevierStyleCrossRef" href="#bib0050">10</a>; the treatment should then be reintroduced with close follow-up. Etanercept and certolizumab appear to be associated with a lower risk of reactivation than adalimumab or infliximab.<a class="elsevierStyleCrossRef" href="#bib0205">41</a>DiagnosisLeishmaniasis is diagnosed by demonstrating the presence of Leishmania amastigotes in clinical specimens using direct microscopic examination or molecular analysis based on nuclear or kinetoplast DNA amplification. Amastigotes are round and have a diameter of 1 to 4 μm and a characteristic rod-shaped structure known as a kinetoplast. The main sampling and diagnostic techniques are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<a class="elsevierStyleCrossRefs" href="#bib0210">42–45</a> Considering the limited sensitivity of some of the diagnostic techniques, it may be necessary to take several samples and/or use a combination of techniques to reach a diagnosis. In the case of biopsy specimens, for example, one part could be used for histology, another for touch imprint cytology, and another for culture. Diagnostic sensitivity in VL varies according to tissue type and can be as high as 90% for spleen tissue. Spleen aspiration is the procedure of choice for diagnosing VL, but it is associated with a high risk of intra-abdominal bleeding. Sensitivity rates ranging from 50% to 85% have been reported for bone marrow samples, and even lower rates have been described for lymph node and peripheral blood.<a class="elsevierStyleCrossRef" href="#bib0230">46</a> In PKDL, diagnostic sensitivity using smears or biopsy specimens is largely dependent on the type of lesion analyzed, with rates of up to 100% for nodular lesions contrasting with very low rates for macular lesions,<a class="elsevierStyleCrossRef" href="#bib0235">47</a> where more sensitive molecular methods are needed.<a class="elsevierStyleCrossRef" href="#bib0240">48</a> More information on sampling methods and diagnostic techniques can be consulted in the guidelines of the Centers for Disease Control and Prevention<a class="elsevierStyleCrossRef" href="#bib0245">49</a> and the Infectious Diseases Society of America.<a class="elsevierStyleCrossRef" href="#bib0250">50</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Histology can show nonspecific features such as ulceration, pseudoepitheliomatous hyperplasia, and a mixed inflammatory infiltrate, as well as specific features, such as amastigotes in dermal macrophages, seen in 50% to 70% of cases<a class="elsevierStyleCrossRef" href="#bib0215">43</a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). As lesions develop, there is an increase in the number of giant cells and a decrease in that of parasites. Other findings include tuberculoid granulomas,<a class="elsevierStyleCrossRef" href="#bib0255">51</a> and in advanced stages, dermal fibrosis and abundant plasma cells.<a class="elsevierStyleCrossRef" href="#bib0260">52</a> Four histologic patterns have been described for leishmaniasis: 1) abundant amastigotes (45%); 2) a mixture of macrophages, neutrophils, and plasma cells accompanied by necrosis (27.5%); 3) incipient granulomas with epithelioid cells, lymphocytes, and plasma cells (15%); and 4) fully formed epithelioid granulomas with Langhans-type giant cells.<a class="elsevierStyleCrossRef" href="#bib0265">53</a> Histologic findings are similar in CL and MCL. A diffuse infiltrate of macrophages containing large numbers of amastigotes is seen in diffuse CL.<a class="elsevierStyleCrossRef" href="#bib0260">52</a><elsevierMultimedia ident="fig0020"></elsevierMultimedia>Dermoscopy is another useful diagnostic aid.<a class="elsevierStyleCrossRef" href="#bib0270">54</a> The most frequently described dermoscopic structures are erythema (100%); vascular structures (90.6%), including polymorphous (40.2%), hairpin (39.4%), and arborizing vessels (38.6%); crusts (70.1%); and erosion/ulceration (44.1%). Less common but more characteristic structures are white-yellow teardrop-like structures (42.5%) and the white starburst pattern (8.6%)<a class="elsevierStyleCrossRef" href="#bib0275">55</a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>F).Other tests, which are less useful in the diagnosis of CL, are the Montenegro skin test and serological tests. The former consists of the intradermal injection of leishmanin, and its results are read and interpreted in a similar way to those of the tuberculin test. It is negative in diffuse CL, active VL, and PKDL,<a class="elsevierStyleCrossRef" href="#bib0280">56</a> and cannot differentiate between current and past infection. It is mainly useful for epidemiological purposes.Serological tests include the direct agglutination test, immunofluorescence, enzyme-linked immunoassay (ELISA), and Western blot analysis. These tests are highly sensitive in VL.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> Antibody titers, however, drop very slowly after cure and the test does not discriminate between active and past infection. Results can also be affected by cross-reactivity with other antibodies (e.g., Chagas disease).<a class="elsevierStyleCrossRef" href="#bib0290">58</a> In addition, asymptomatic individuals in endemic areas often have antibodies, meaning that results have to be carefully interpreted according to the clinical context. High levels of anti-α-galactosyl antibodies have been detected using ELISA in CL caused by L tropica and L major.<a class="elsevierStyleCrossRef" href="#bib0295">59</a> A number of rapid diagnostic tests, such as rK39, are also available. These have high sensitivity for VL,<a class="elsevierStyleCrossRef" href="#bib0300">60</a> but they have the same limitations as other serological tests. More recent antigen detection tests include the latex agglutination test<a class="elsevierStyleCrossRef" href="#bib0305">61</a> and ELISA<a class="elsevierStyleCrossRef" href="#bib0310">62</a> with urine samples in VL and an immunochromatographic strip that tests for peroxidoxin antigen<a class="elsevierStyleCrossRef" href="#bib0315">63</a> in CL.Differential DiagnosisThe main entities that should be considered in the differential diagnosis are other infections, such as ecthyma, sporotrichosis, skin tuberculosis, furuncular myasis, subcutaneous mycosis, tertiary syphilis, and lepromatous leprosy; malignancies, such as squamous cell carcinoma, basal cell carcinoma, and lymphoma; and other skin disorders, such as persistent arthropod bite reactions, sarcoidosis, and granulomatosis with polyangitis.<a class="elsevierStyleCrossRef" href="#bib0215">43</a>TreatmentMany cases of CL resolve spontaneously in under 2 years. Variations in resolution times are largely related to the species involved (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), with infections caused by L braziliensis and L panamensis most likely to persist.<a class="elsevierStyleCrossRef" href="#bib0320">64</a> Depending on this and other factors, such as anatomic location, infection severity, and the host’s immune response, CL can be classified as simple or complex. Simple infections can be treated conservatively or with local treatments, while complex infections require systemic therapies.<a class="elsevierStyleCrossRef" href="#bib0250">50</a> The characteristics of simple and complex CL are summarized in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. Multiple treatments exist for leishmaniasis, although the evidence supporting the options for CL is weak.<a class="elsevierStyleCrossRef" href="#bib0325">65</a> The main treatments are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>.<a class="elsevierStyleCrossRefs" href="#bib0330">66–97</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>After weighing up the risks and benefits, a watch-and-wait approach can be taken in patients who meet the criteria for simple CL. Local treatment can be used for lesions that do not resolve spontaneously or when the goal is to achieve a faster cure or reduce the risk of scarring. The most widely accepted local treatments are intralesional pentavalent antimonials<a class="elsevierStyleCrossRefs" href="#bib0330">66–69</a> and cryotherapy.<a class="elsevierStyleCrossRef" href="#bib0380">76</a> The combination of both produces better outcomes.<a class="elsevierStyleCrossRefs" href="#bib0350">70,71</a> Topical paromomycin is also used to treat CL, particularly in the New World.<a class="elsevierStyleCrossRefs" href="#bib0365">73–75</a>There have been reports of good responses to other local treatments,<a class="elsevierStyleCrossRef" href="#bib0490">98</a> such as carbon dioxide laser therapy,<a class="elsevierStyleCrossRef" href="#bib0495">99</a> which has shown efficacy rates of 93% and very few adverse effects (hyperpigmentation, persistent erythema, and hypertrophic scarring); photodynamic therapy<a class="elsevierStyleCrossRef" href="#bib0400">80</a>; and imiquimod.<a class="elsevierStyleCrossRef" href="#bib0500">100</a>Systemic therapies are recommended for patients who meet any of the criteria for complex CL. Liposomal amphotericin B is highly effective but carries a risk of nephrotoxicity.<a class="elsevierStyleCrossRefs" href="#bib0445">89–93</a> The traditional use of systemic pentavalent antimonials<a class="elsevierStyleCrossRefs" href="#bib0425">85–88</a> to treat complex CL and MCL has led to resistance in certain areas, limiting their use.<a class="elsevierStyleCrossRef" href="#bib0435">87</a> Other options include azoles,<a class="elsevierStyleCrossRef" href="#bib0405">81</a> miltefosine,<a class="elsevierStyleCrossRefs" href="#bib0410">82–84</a> and pentamidine.<a class="elsevierStyleCrossRefs" href="#bib0470">94–96</a>A clinical trial comparing twice-daily chloroquine 250 mg and once-daily doxycycline 200 mg for 3 months reported an efficacy of 100% and 92%, respectively.<a class="elsevierStyleCrossRef" href="#bib0505">101</a>Annual check-ups are recommended in patients with CL due to L braziliensis to enable early detection of progression to MCL. Signs of MCL include persistent nasal secretion or bleeding.PKDL from Africa is not normally treated as the vast majority of cases (85%) resolve spontaneously within a year. In India, however, systemic treatment with miltefosine or amphotericin B is generally needed.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>We have drawn up an algorithm for the management of CL and MCL based on current guidelines and expert recommendations (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).<elsevierMultimedia ident="fig0025"></elsevierMultimedia>Prevention and ControlProphylactic vaccines for leishmaniasis in humans are not yet available. The fact that most patients who recover from leishmaniasis do not become reinfected facilitates vaccine research efforts.<a class="elsevierStyleCrossRef" href="#bib0510">102</a> One of the main control strategies for CL and VL, apart from vector control, involves early detection and treatment, as infected patients are reservoirs. The WHO’s target for CL in the eastern Mediterranean region was to detect 70% of all cases and to treat at least 90% by 2020, an ambitious target considering the few treatment options available, the suboptimal diagnostic tools, and the low levels of awareness among the scientific community, particularly in relation to CL, which is not classified as an infection control priority.ConclusionsCL has become a relatively common condition in our setting due to international travel and migration. Its management, however, can be complicated due to low indices of suspicion among clinicians, the low sensitivity of some diagnostic tests, poor access to molecular testing, limited treatment options, and adverse treatment effects. HIV coinfection and use of TNF inhibitors are associated with atypical presentations and the need for systemic treatment.Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:17 [ 0 => array:3 [ "identificador" => "xres1542265" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1395150" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1542264" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1395151" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Pathogenesis" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Clinical Manifestations" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Cutaneous Leishmaniasis" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Mucocutaneous Leishmaniasis" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Visceral Leishmaniasis" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Post Kala-Azar Dermal Leishmaniasis" ] ] ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "HIV Coinfection" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Leishmaniasis and TNF Inhibitors" ] 10 => array:2 [ "identificador" => "sec0055" "titulo" => "Diagnosis" ] 11 => array:2 [ "identificador" => "sec0060" "titulo" => "Differential Diagnosis" ] 12 => array:2 [ "identificador" => "sec0065" "titulo" => "Treatment" ] 13 => array:2 [ "identificador" => "sec0070" "titulo" => "Prevention and Control" ] 14 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions" ] 15 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflicts of Interest" ] 16 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-12-29" "fechaAceptado" => "2021-02-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1395150" "palabras" => array:5 [ 0 => "Cutaneous leishmaniasis" 1 => "Mucocutaneous leishmaniasis" 2 => "Clinical manifestations" 3 => "Diagnosis" 4 => "Treatment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1395151" "palabras" => array:5 [ 0 => "Leishmaniasis cutánea" 1 => "Leishmaniasis mucocutánea" 2 => "Manifestaciones clínicas" 3 => "Diagnóstico" 4 => "Tratamiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Leishmaniasis is a chronic disease caused by flagellate protozoa of the genus Leishmania. It is a global disease, but most cases are seen in South America, the Mediterranean, and some areas of Asia and Africa. The 3 main types of leishmaniasis are cutaneous (the most common), mucocutaneous, and visceral (the most severe). Visceral leishmaniasis is also known as kala-azar. Leishmaniasis is diagnosed by demonstrating the presence of Leishmania amastigotes in clinical specimens using direct microscopic examination or molecular analysis. Various treatments exist, although the evidence supporting the options available for cutaneous leishmaniasis is weak. Both the classical presentation of leishmaniasis and our management of the disease have changed in recent decades because of acquired immune deficiency caused by conditions such as human immunodeficiency infection or the use of tumor necrosis factor inhibitors." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La leishmaniasis es una enfermedad crónica causada por un protozoo flagelado perteneciente al género Leishmania. Tiene distribución mundial, aunque la mayoría de casos se agrupan en América del Sur, la cuenca mediterránea y algunas zonas de Asia y África. Existen tres formas fundamentales de enfermedad: cutánea, la más frecuente; mucocutánea; y visceral, también denominada kala-azar, la forma más grave. El diagnóstico se establece con la demostración de la presencia de los amastigotes en muestras clínicas, mediante visión directa al microscopio o mediante técnicas moleculares. Existen múltiples opciones terapéuticas, aunque la evidencia en la que se basa el tratamiento de la leishmaniasis cutánea es débil. Actualmente, las alteraciones de la inmunidad producidas por factores como el VIH o el uso de fármacos anti-TNF han cambiado tanto la forma de presentación de las formas clínicas clásicas como sus tratamientos." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Abadías-Granado I, Diago A, Cerro PA Palma-Ruiz AM, Gilaberte Y. Leishmaniasis cutánea y mucocutánea. ACTAS Dermo-Sifiliogr. 2021;112:601–618." ] ] "multimedia" => array:9 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1156 "Ancho" => 2113 "Tamanyo" => 242967 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Geographic distribution of the main Leishmania species and their principal reservoirs." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2828 "Ancho" => 2508 "Tamanyo" => 667515 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A–C, The presence of an erythematous papule or nodule exhibiting progressive growth and a tendency to ulcerate in exposed areas, such as the face or extremities, is the most characteristic presentation of cutaneous leishmaniasis. D, Some patients have multiple lesions, or atypical presentations such as the verrucous lesion in this patient with New World cutaneous leishmaniasis. Clinical (E) and dermoscopic (F) image of a cutaneous leishmaniasis lesion on the forearm showing central ulceration surrounded by an erythematous area with peripheral polymorphous and hairpin vessels (asterisks) and white-yellow teardrop-like structures (arrows)(polarized light, original magnification ×10). Images courtesy of Dr. Morales Moya (2C), Dr. Galimberti (2D), and Dr Mayo Martínez (2E and F)." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1880 "Ancho" => 2512 "Tamanyo" => 451159 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A, Mucocutaneous leishmaniasis manifests as a chronic ulcer often affecting the nasal mucosa. B, Firm cutaneous leishmaniasis papules on the palm of a patient coinfected with visceral leishmaniasis and human immunodeficiency virus. C, Hyperpigmented macules in the neck area. D, Hypopigmented macules as a manifestation of post-kala-azar dermal leishmaniasis in a 7-year-old boy. The diagnosis was established by molecular techniques, as the biopsy was negative." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1880 "Ancho" => 2512 "Tamanyo" => 873405 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A, Panoramic punch biopsy of an erythematous nodule on the forearm (hematoxylin-eosin, original magnification ×5). B, Dense superficial dermal inflammatory infiltrate and pseudoepitheliomatous hyperplasia (hematoxylin-eosin, original magnification ×10). C, Detail of inflammatory infiltrate composed mainly of macrophages, lymphocytes, and some epithelioid cells (hematoxylin-eosin, original magnification ×20). D, Characteristic amastigotes in infected macrophages (hematoxylin-eosin, original magnification ×40)." ] ] 4 => array:8 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 2859 "Ancho" => 3333 "Tamanyo" => 739059 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Treatment algorithm for cutaneous and mucocutaneous leishmaniasis. IL indicates intralesional; IM, intramuscular; IV, intravenous; PDT, photodynamic therapy; VO, oral. * foreign medication." ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: CL, cutaneous leishmaniasis; MCL, mucocutaneous leishmaniasis; PKDL, post-kala-azar dermal leishmaniasis; VL, visceral leishmaniasis." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Complex \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main Species \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main Reservoir \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main Geographic Distribution \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Most Common Clinical Patterns and Their Main Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Natural Progression \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania donovani</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">L donovani</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Human</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">India, Bangladesh, Ethiopia, Sudan</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VL: fever, hepatosplenomegaly, weight loss, anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Without treatment, death within 2 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PKDL: macular, papular, or nodular lesions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Resolves spontaneously in up to 85% of cases in Africa, but rarely in Asia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania infantum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dog, hare \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mediterranean Basin, China \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CL: mildly inflammatory solitary nodulesVL: more common in children and immunosuppressed individuals</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tends to resolve spontaneously within a year, conferring immunity</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania infantum chagasi \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dog, fox \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Central and South America \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania tropica</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">L tropica \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Human \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eastern Mediterranean, Middle East, India \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CL: <3 dry ulcers, mostly on the head; chronic, recurrent course \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Most cases resolve spontaneously within 2 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania major \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rodents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Africa, Middle East, Central Asia, India, China \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LC: multiple moist inflammatory ulcers, most of which progress rapidly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70% of cases resolve in 4 mo but leave severe scarring \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania aethiopica \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyraxes (dassie) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ethiopia, Kenya \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LC: localized nodules or ulcers; may result in diffuse involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Usually resolves spontaneously with 2-5 years, except for diffuse forms \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania mexicana</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">L mexicana \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rodents, marsupials \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mexico, Central and South America, Texas \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LC: solitary or multiple ulcerated lesions, sometimes with diffuse involvement; responsible for characteristic ulcerated ulcer lesion in gum collectors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>80% of cases resolve spontaneously within 3–4 mo, although some lesions can last up to 20 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania amazonensis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rodents, possums \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">South America \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LC: ulcerated lesions, often with diffuse involvementCan progress to MCL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not well described \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania (Viannia) braziliensis</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">L braziliensis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rodents, dogs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Central and South America \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LC: ulcerated lesionsMCL: mainly caused by L braziliensis; ulcerated lesions in oral and nasal mucosa; can extend to oropharynx and larynx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Causes serious infections; often associated with satellite lesions, subcutaneous nodules, and enlarged locoregional lymph nodes; 6% of cases resolve spontaneously in 6 mo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania panamensis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sloths \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Panama, Costa Rica, Colombia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CL: superficial ulcers, often with lymphatic spreadMCL: nasopharyngeal involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Does not resolve spontaneously. Spreads through lymphatic vessels and can cause mucocutaneous lesions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania guyanensis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Possums, sloths, and anteaters \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">South America \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LC: multiple ulcers that can spread through the lymphatic system, resulting in a sporotrichoid distributionMCL: cutaneous involvement that can progress to mucocutaneous involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tends to need treatment and recurs frequently; at times, resolves spontaneously within 6 months \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2648064.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical and Epidemiological Characteristics of the Main Species of Leishmania." ] ] 6 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviation: PCR: polymerase chain reaction." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of Lesion \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sampling Method</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diagnostic Techniques \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Technique \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Considerations \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ulcer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Base \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Swab. To collect DNA. Rub ulcer several times. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PCR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Real-time PCRSamples can be stored in high concentrations of ethanol or in paraffin, although paraffin-embedded samples yield lower sensitivity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Advantages: highest sensitivity and specificity, relatively fast, and allows identification of speciesDisadvantages: not always availableSensitivity: 100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Touch print cytology. Remove the crust and take an imprint of the base of the ulcer on a slide. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SmearGiemsa staining and direct visualization using ×100 lens and oil immersionVisualization of amastigotes and their characteristic kinetoplast structure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Advantages: fast and cheap Disadvantages: does not allow identification of speciesSensitivity: 85% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Border \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fine-needle aspiration. Aspirate using a 1-mL syringe with a 20-25-G needle and 0.1 mL of sterile saline solution 0.9%. If no material is obtained, inject 0.05-0.1 mL of the saline solution and reaspirate. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smear, culture, PCR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CultureSterile sampleMedium: Novy-MacNeal-Nicolle \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Advantages: allows identification of species and definitive diagnosisDisadvantages: frequent contamination by skin flora and low sensitivitySensitivity: 40%Recent microculture techniques offer higher sensitivity (close to 100%), but do not allow identification of species \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Skin scrapings. Use a scalpel to obtain tissue scrapings from the upper dermis, via an incision or removal of necrotic tissue. Requires local anesthesia and bleeding control for better results. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smear, culture, PCR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biopsy. Shave or punch. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smear, culture, PCR, histology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HistologyHematoxylin-eosin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Advantages: can be used to rule out other possible causes, in particular, malignancyDisadvantages: invasive, does not allow identification of species, and has low sensitivitySensitivity: 60% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nodule/plaque \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fine-needle aspiration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smear, culture, PCR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smear, culture, PCR, histology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2648065.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Sampling Methods and Diagnostic Techniques for Cutaneous and Mucocutaneous Leishmaniasis." ] ] 7 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: HIV, human immunodeficiency virus; TNF, tumor necrosis factor." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Simple Cutaneous Leishmaniasis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Complex Cutaneous Leishmaniasis \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania species associated with low likelihood of mucosal involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leishmania species associated with high likelihood of mucosal involvement, particularly species from Leishmaniasis braziliensis complex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No notable mucosal involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mucosal involvement, subcutaneous nodules, and/or significantly enlarged regional lymph nodes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Single or few lesions < 1 cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥ 5 lesions measuring > 1 cm or single lesion measuring > 5 cm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Located in areas without significant cosmetic concerns and that are accessible for local treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Located on the face, ears, fingers or toes, and skin covering joints or genitals \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Immunocompetent host \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Immunosuppressed host (HIV, TNF inhibitors, etc.) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lesions showing signs of spontaneous resolution at diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">History of non-response to local treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No criteria for complex cutaneous leishmaniasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recurrent disease or diffuse presentation \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2648066.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of Simple and Complex Cutaneous Leishmaniasis." ] ] 8 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0045" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Abbreviations: ALA, aminolevulinic acid; IL, intralesional; MAL, methyl aminolevulinate; MBCL, methyl benzethonium chloride; MCL, mucocutaneous leishmaniasis; NWCL, New World cutaneous leishmaniasis; OWCL, Old World cutaneous leishmaniasis; PDT, photodynamic therapy; VL, visceral leishmaniasis." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug or Device \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indication \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose, Adverse Effects and Other Considerations \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Effectiveness<a class="elsevierStyleCrossRef" href="#bib0485">97</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Level of Evidence<a class="elsevierStyleCrossRef" href="#bib0005">1</a>,<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Local TreatmentIntralesional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pentavalent antimonials</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sodium stibogluconate<a class="elsevierStyleCrossRefs" href="#bib0330">66–68</a> (Pentostam 100 mg/mL, foreign medication) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OWCLConsider for NWCL if no risk of mucosal involvement</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intradermal injection 0.2-0.5 mL (0.1 mL/cm2 in up to 5 sites/lesion every 3-7 d for up to 5 sessions)May require local anesthesiaMore effective when combined with cryotherapy<a class="elsevierStyleCrossRefs" href="#bib0350">70,71</a>Intralesional administration does not usually cause adverse effects (except for local reactions), although QT interval prolongation has been reported in up to 25% of patients<a class="elsevierStyleCrossRef" href="#bib0360">72</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41%-98% (OWCL)77%-90% (NWCL)89%-91% (when combined with cryotherapy)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A (combined with cryotherapy, LCVM)B (NMCL)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Meglumine antimoniate<a class="elsevierStyleCrossRef" href="#bib0345">69</a>(Glucantime 1500 mg/5 mL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TopicalParomomycin<a class="elsevierStyleCrossRef" href="#bib0365">73</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Paromomycin ointment<a class="elsevierStyleCrossRef" href="#bib0370">74</a> (Leshcutan, paromomycin 15% + MBCL 12%, foreign medication) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ulcerated lesions due to Leishmania spp. in OWCL and NWCL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Twice daily for 10-20 d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Similar to intralesional pentavalent antimonials in OWCL, and inferior in NWCL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A (OWCL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Paromomycin 15% cream + gentamicin 0.5%<a class="elsevierStyleCrossRef" href="#bib0375">75</a> (not commercially available) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Better responses in Leishmania major and Leishmania panamensis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B (NWCL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Similar results for formulations with and without gentamicinCan cause intense inflammation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cryotherapy<a class="elsevierStyleCrossRef" href="#bib0380">76</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liquid nitrogen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recent-onset CL lesionsResidual lesions after systemic treatmentConsider in pregnant and breastfeeding women and patients with contraindications for systemic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 freeze-thaw cycles for 15-20 s, with halo of 1-2 mm; repeated every 3 wk until cureMore effective when combined with intralesional pentavalent antimonialsCan cause permanent hypopigmentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57%-75% (similar efficacy to intralesional pentavalent antimonials)89%-91% (if combined with intralesional pentavalent antimonials) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A (combined with IL APV, OWCL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thermoterapy<a class="elsevierStyleCrossRefs" href="#bib0385">77–79</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Application of superficial heat via radiofrequency (ThermoMed) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OWCL and NWCLConsider in pregnant and breastfeeding women and patients with contraindications for systemic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 °C for 30 s applied to lesion and up to 1-2 mm of surrounding skin; 1-2 sessionsBased on in vitro studies showing that Leishmania parasites do not multiply at > 39 °C Requires local anesthesiaProduces second-degree burns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48%-98% (OWCL)58%-90% (NWCL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A (OWCL, NWCL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PDT<a class="elsevierStyleCrossRef" href="#bib0400">80</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Conventional PDT with ALA or MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OWCL, especially that caused by L major or Leishmania tropicaConsider in CL resistant to other treatments or in aesthetically sensitive areasNot recommended in CL due to Leishmania braziliensis complex or Leishmania donovani complex</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1-7 sessions a week; ≥ 3 sessions more effective than ≤2Mechanism of action believed to involve immune system response as does not directly kill the parasiteConventional PTD with ALA (6 sessions) seems to be at least as effective as cryotherapy (5 sessions) and produces better aesthetic results, although is more poorly toleratedLocal adverse effects (burning, reddening, edema, pain)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96%-100% (conventional PDT)74%-82% (daylight PDT)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B (conventional PTD, OWCL)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Daylight PDT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intralesional PDT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systemic therapyOral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">[1,0]Azoles<a class="elsevierStyleCrossRef" href="#bib0405">81</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluconazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Off-label use for CL with lymphatic involvement and certain complex cases of CL; not indicated for cases due to L braziliensis</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">200-400 mg/d for 42 dAdverse effects include gastrointestinal disturbances and hepatotoxicity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44%-81% (OWCL)22% (NWCL)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A (OWCL, fluconazole 200 mg/d, 42 d, Lmajor)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Itraconazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">200 mg/d for 42-56 d \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Miltefosine<a class="elsevierStyleCrossRefs" href="#bib0410">82–84</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Miltefosine (Impavido 50 mg capsules, foreign medication) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LC due to L braziliensis complex; can also be used in LC due to L major, L tropica, or Leishmania mexicana \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.5 mg/kg/d (maximum 150 mg), administered orally in 3 doses for 28 dExpensiveTeratogenic and can cause gastrointestinal disturbances and hepatotoxicity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81% (OWCL)53%-91% (NWCL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B (NWCL)C (OWCL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parenteral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pentavalent antimonials<a class="elsevierStyleCrossRefs" href="#bib0425">85–88</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sodium stibogluconate (Pentostam, 100 mg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">[1,0]Complex OWCL and NWCL and MCL</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 mg/kg/d in a single daily dose administered orally (preferred) or intramuscularly (very painful) for 10-30 dTreatment failures have increased due to resistance<a class="elsevierStyleCrossRef" href="#bib0435">87</a>Usually associated with pentoxifylline 400 mg 3 times a day for 10-20 d, or allopurinol 20 mg/kg for 30 days in recurrent LC due to L tropicaCan cause cardiotoxicity (e.g., arrhythmias, QT interval prolongation), pancreatitis, and hepatotoxicity</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41%-85% (OWCL)77%-90% (NWCL)30%-90% (MCL)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A (OWCM, MCL)C (recurrent CL)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Meglumine antimoniate(Glucantime 1500 mg/5 mL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amphotericin B<a class="elsevierStyleCrossRefs" href="#bib0445">89–93</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liposomal (AmBisome 50 mg), treatment of choice due to its lower toxicity compared with conventional options \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Off-label use for complex CL and MCL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 mg/kg/d IV for 7 d (days 1-5, 14, and 21) up to a total dose of 21 mg/kg.Optimal dose for LC not well-defined; treatment regimens are based on the doses used for VL; higher doses and longer treatments are usually required in immunosuppressed patientsApproval of topical formulation of amphotericin 3% with similar efficacy to intralesional pentavalent antimonials in LC<a class="elsevierStyleCrossRef" href="#bib0460">92</a>Can cause nephrotoxicity, lower back pain, hypokalemia, chills \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">84%-100% (OWCL, NWCL)78%-100% (MCL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C (NWCL, MCL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pentamidine<a class="elsevierStyleCrossRefs" href="#bib0470">94–96</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pentamidine isethionate 300 mg (Pentacarinat) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alternative treatment for NWCL; good responses in Leishmania guyanensis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 mg/kg/d, intramuscular on alternating days for a weekCan also be administered intravenously (more effective).Intralesional administration recently approved; similar efficacy to pentavalent antimonialsCan cause severe toxicity: pancreatitis, QT interval prolongation, hyperpotassemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58%-95% (NWCL)91% (MCL, but 25% recurrence rate) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C (NWCL, MCL) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2648063.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Level of evidence (World Health Organization system): evidence supported by A, at least 1 well-designed clinical trial; B, well-designed nonrandomized clinical trials; C, descriptive studies, expert committees; D, expert opinions without conclusive studies." ] ] ] "descripcion" => array:1 [ "en" => "Main Treatments for Cutaneous and Mucocutaneous Leishmaniasis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:102 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leishmaniasis" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "WWW" => array:2 [ "link" => "http://www.who.int/mediacentre/factsheets/fs375/es/" "fecha" => "2020" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tropical dermatology: Tropical diseases caused by protozoa" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2009.03.004" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol." "fecha" => "2009" "volumen" => "60" "paginaInicial" => "897" "paginaFinal" => "928" "link" => array:1 [ …1] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leishmaniasis" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(18)31204-2" "Revista" => array:6 [ "tituloSerie" => "Lancet." "fecha" => "2018" "volumen" => "392" "paginaInicial" => "951" "paginaFinal" => "970" "link" => array:1 [ …1] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New World and Old World Leishmania Infections: A Practical Review" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.det.2015.03.018" "Revista" => array:6 [ "tituloSerie" => "Dermatol Clin." 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Review

Cutaneous and Mucocutaneous Leishmaniasis

Leishmaniasis cutánea y mucocutánea

I. Abadías-Granado

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isabel.abadiasg@gmail.com
iabadias@salud.aragon.es

Corresponding author.

, A. Diago, P.A. Cerro, A.M. Palma-Ruiz, Y. Gilaberte

Servicio de Dermatología, Hospital Universitario Miguel Servet, Zaragoza, Spain

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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A&#44; Mucocutaneous leishmaniasis manifests as a chronic ulcer often affecting the nasal mucosa&#46; B&#44; Firm cutaneous leishmaniasis papules on the palm of a patient coinfected with visceral leishmaniasis and human immunodeficiency virus&#46; C&#44; Hyperpigmented macules in the neck area&#46; D&#44; Hypopigmented macules as a manifestation of post-kala-azar dermal leishmaniasis in a 7-year-old boy&#46; The diagnosis was established by molecular techniques&#44; as the biopsy was negative&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Leishmaniasis is a chronic disease caused by flagellate protozoa of the genus <span class="elsevierStyleItalic">Leishmania&#44;</span> of which there are over 20 species&#46; <span class="elsevierStyleItalic">Leishmania</span> parasites are obligate intracellular parasites transmitted by the bite of infected female sandflies of the <span class="elsevierStyleItalic">Phlebotomus</span> and <span class="elsevierStyleItalic">Lutzomyia</span> genera&#46; Leishmaniasis is essentially a zoonotic disease&#46; The main reservoirs are dogs and rodents&#44; but there are 2 cases for which humans are the main reservoirs&#58; <span class="elsevierStyleItalic">Leishmania donovani</span> and <span class="elsevierStyleItalic">Leishmania tropica</span>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Epidemiology</span><p id="par0010" class="elsevierStylePara elsevierViewall">The estimated incidence of leishmaniasis according to the World Health Organization is 700 000 to 1 million cases a year&#44; of which 50 000 to 90 000 correspond to visceral leishmaniasis &#40;VL&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Approximately 95&#37; of all cutaneous leishmaniasis &#40;CL&#41; cases occur in South America&#44; the Mediterranean Basin&#44; the Middle East&#44; or Central Asia&#46; LV&#44; by contrast&#44; is predominant in Brazil&#44; East Africa&#44; and India&#46; In 2018&#44; over 85&#37; of new CL cases reported to the WHO were from Afghanistan&#44; Algeria&#44; Bolivia&#44; Brazil&#44; Colombia&#44; Iran&#44; Iraq&#44; Pakistan&#44; Syria&#44; and Tunisia&#44; while over 95&#37; of new LV cases were from Brazil&#44; China&#44; Ethiopia&#44; India&#44; Iraq&#44; Kenya&#44; Nepal&#44; Somalia&#44; and Sudan&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Finally&#44; over 90&#37; of new mucocutaneous leishmaniasis &#40;MCL&#41; cases were reported in 4 countries&#58; Brazil&#44; Bolivia&#44; Ethiopia&#44; and Peru&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Leishmaniasis has traditionally been classified as Old World or New World depending on its geographic location&#46; Old World leishmaniasis occurs in Asia&#44; Africa&#44; and Europe&#44; and is mostly caused by <span class="elsevierStyleItalic">L tropica&#44; Leishmania major&#44; Leishmania aethiopica&#44; Leishmania infantum&#44;</span> or <span class="elsevierStyleItalic">L donovani&#46;</span> New World leishmaniasis&#44; in turn&#44; occurs in America&#44; and is mostly caused by <span class="elsevierStyleItalic">Leishmania mexicana&#44; Leishmania amazonensis&#44; Leishmania braziliensis&#44; Leishmania panamensis</span>&#44; or <span class="elsevierStyleItalic">Leishmania infantum chagasi</span> &#40;a subspecies of <span class="elsevierStyleItalic">L infantum</span> in the New World&#44; formerly known as <span class="elsevierStyleItalic">Leishmania chagasi</span>&#41;&#46;<span class="elsevierStyleSup">2</span> The main epidemiological and clinical patterns for most common <span class="elsevierStyleItalic">Leishmania</span> species are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;5</span></a><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the geographic distribution of the main species and their principal reservoirs&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In Spain&#44; leishmaniasis is a zoonotic disease endemic to the peninsula and the Balearic Islands&#46; The main causative species in both CL and VL is <span class="elsevierStyleItalic">L infantum</span>&#44; which is transmitted by <span class="elsevierStyleItalic">Phlebotomus perniciosus</span> and <span class="elsevierStyleItalic">Phlebotomus ariasi</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Dogs are the main reservoir for <span class="elsevierStyleItalic">L infantum</span>&#44; although other reservoirs such as hares<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and rats<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> have been described&#46; Apart from its endemic form&#44; leishmaniasis can occur in patients with human immunodeficiency virus &#40;HIV&#41; infection<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> or a compromised immune system &#40;e&#46;g&#46;&#44; patients being treated with tumor necrosis factor &#91;TNF&#93; inhibitors&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> There have also been epidemic outbreaks&#44; such as the Madrid outbreak that occurred between 2009 and 2013&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Finally&#44; phenomena such as globalization&#44; international travel&#44; and migration have increased the prevalence of leishmaniasis in developed countries&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pathogenesis</span><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Leishmania</span> promastigotes are injected into human skin by infected female sandflies&#46; Here&#44; through phagocytosis by macrophages&#44; they transform into amastigotes&#44; multiplying inside the cells and infecting other mononuclear phagocytized cells&#46; Sandflies becomes infected by ingesting infected cells while feeding on the host&#8217;s blood&#46; Once in the intestine of the sandflies&#44; the amastigotes transform into promastigotes&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The incubation period of leishmaniasis varies according to the clinical form of disease&#44; but is generally 2 weeks &#40;or less&#41; to 2 months for CL&#44; 3 to 9 months for VL&#44; and over 2 years for MCL&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The clinical manifestations of leishmaniasis vary according to the species involved<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; and the host&#8217;s immune response&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The spectrum of immune response ranges from a strong T-cell response that results in the production of interferon &#40;IFN&#41; &#947; to a humoral response that produces high antibody levels&#46; <span class="elsevierStyleItalic">Leishmania</span> species are eliminated by IFN-&#947;-activated macrophages&#44; but cannot be neutralized by antibodies&#46; This is why individuals who mount a strong immune response have lesions with few parasites&#44; while those with a humoral response are unable to control infection&#46; Diffuse CL is caused by uncontrolled infection&#46; It should also be noted that an exaggerated T helper type 1 response and increased expression of CD8<span class="elsevierStyleSup">&#43;</span> T cells are associated with more severe forms of disease&#44; such as MCL&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical Manifestations</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Cutaneous Leishmaniasis</span><p id="par0035" class="elsevierStylePara elsevierViewall">CL starts with the formation of a papule at the inoculation site&#44; which is typically located in exposed areas of the body&#44; such as the face or extremities&#46; The papule typically develops into a plaque or a nodule &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A-E&#41; with a tendency to ulcerate&#46; Gum collectors &#40;<span class="elsevierStyleItalic">chicleros</span>&#41; in Mexico and Central America&#44; for example&#44; develop a characteristic ulcerated lesion on their ear following infection by <span class="elsevierStyleItalic">L mexicana</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> CL lesions can be single or multiple and infection can spread through the lymphatic system&#44; causing lymph node enlargement&#44; satellite lesions&#44; and even sporotrichoid lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Atypical forms&#44; such as eczematous&#44; erysipeloid&#44; lupoid&#44; annular&#44; and verrucous lesions&#44; are more common in the New World&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> CL lesions can resolve spontaneously within several months leaving a scar&#46; Some cases&#44; however&#44; become chronic or spread&#46; Chronic recurrent forms are typical in <span class="elsevierStyleItalic">L tropica</span> infections and are characterized by the formation of papules at the periphery of previously healed ulcers&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Chronicity has been linked to numerous factors&#44; including increased arginase activity in polymorphonuclear leukocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Diffuse CL&#44; which is caused by <span class="elsevierStyleItalic">L aethiopica</span>&#44; <span class="elsevierStyleItalic">L Mexicana</span>&#44; or <span class="elsevierStyleItalic">L amazonensis</span>&#44; presents as multiple nonulcerated papules and&#47;or nodules involving most of the skin&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The lesions contain abundant parasites and can result in significant facial changes&#44; causing a leonine-like appearance similar to that seen in lepromatous leprosy&#46; Mucosal lesions are common&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Mucocutaneous Leishmaniasis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Mucosal involvement can coincide with cutaneous involvement or occur after the clearance of cutaneous lesions&#44; sometimes even year later&#46; The infection can spread through the bloodstream or lymphatic system&#46; In endemic areas&#44; mucosal involvement may be seen in up to 20&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Most cases of MCL are caused by <span class="elsevierStyleItalic">L braziliensis</span>&#44; but other species involved are <span class="elsevierStyleItalic">L amazonensis&#44; L guyanensis</span>&#44; and <span class="elsevierStyleItalic">L panamensis</span>&#46; The nasal &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#41; and oral mucosa are the most frequently affected areas&#46; Lesions in the oral cavity can spread to the oropharynx and larynx&#44; and may affect cartilage and vocal cords&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> MCL lesions are ulcerated and can cause disfigurement&#46; Treatment is essential to control infection&#44; as the condition can be fatal&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Visceral Leishmaniasis</span><p id="par0045" class="elsevierStylePara elsevierViewall">In VL&#44; infected macrophages spread through the reticuloendothelial system to the bone marrow&#44; spleen&#44; and liver&#46; Clinical manifestations include fever&#44; weight loss&#44; hepatosplenomegaly&#44; and lymph node enlargement&#46; VL is mainly caused by <span class="elsevierStyleItalic">L donovani</span> in adults and <span class="elsevierStyleItalic">L infantum</span> or <span class="elsevierStyleItalic">L chagasi</span> in children and immunosuppressed individuals&#46; Patients may also develop skin manifestations&#44; which can be specific&#44; such as papules &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>b&#41;&#44; nodules&#44; and ulcers&#44; or nonspecific&#44; such as purpura and hyperpigmentation &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>C&#41;&#46; The presence of hyperpigmentation probably explains the origin of the term <span class="elsevierStyleItalic">kala-azar</span>&#44; which means <span class="elsevierStyleItalic">black fever</span> in Hindu&#46; Skin darkening has been described in 9&#46;88&#37; of patients with VL<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and was recently linked to an increased production of cortisol&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Because hyperpigmented areas show amastigotes on histology&#44; they could perhaps be considered a specific manifestation of leishmaniasis&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Post Kala-Azar Dermal Leishmaniasis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Post kala-azar dermal leishmaniasis &#40;PKDL&#41; occurs in patients with VL caused by <span class="elsevierStyleItalic">L donovani</span> or&#44; on occasions&#44; <span class="elsevierStyleItalic">L infantum</span>&#46; It is particularly common in immunosuppressed patients<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and can appear up to 20 years after treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> In patients infected with HIV&#44; however&#44; PKDL can coincide with&#44; or at times precede&#44; VL&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> It is characterized by hypopigmented macules &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>D&#41;&#44; flesh-colored nodules and&#47;or verrucous papules that mainly affect the face&#44; although they can spread to the rest of the body&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> PKDL mainly occurs in east Africa and India&#44; although cases are occasionally seen in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> The clinical presentation varies depending on geographic location and the host&#8217;s immune response&#46; In Asia&#44; 90&#37; of cases appear as macules&#44; while in Africa&#44; papules are predominant&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> PKDL is more common&#8212;and severe&#8212;in immunosuppressed patients&#44; who may exhibit atypical forms such as nodules not necessarily involving the face and a higher abundance of parasites in lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> The main entity in the differential diagnosis is leprosy&#44; which is characterized by a loss of sensation&#46; PKDL must be treated systemically&#44; although African forms can resolve spontaneously within a year&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">HIV Coinfection</span><p id="par0055" class="elsevierStylePara elsevierViewall">HIV infection has been linked to a 2000-fold increased risk of VL&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> This is because both infections share a immunopathogenic mechanism involving macrophages and dendritic cells that accelerates progression in both cases&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> HIV was responsible for the resurgence of VL in Europe during the 1990s that hit Spain&#44; Portugal&#44; Italy&#44; and France particularly hard&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#44;35</span></a> Eighty percent of all cases of VL-HIV coinfection reported to the WHO during this period were from Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In addition&#44; a retrospective analysis of all patients hospitalized for leishmaniasis in Spain between 1997 and 2008 found that 37&#37; were HIV positive&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> Coinfection can result in atypical presentations of CL and VL&#44;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;38&#44;39</span></a> poor response to treatment&#44; higher mortality rates&#44; higher viral loads&#44; and faster progression to AIDS&#46; The introduction of highly active antiretroviral therapy in 1997 increased survival rates and also reduced the incidence and recurrence of leishmaniasis&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> It is important thus to rule out HIV in all patients with VL&#44; even those living in endemic areas&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Leishmaniasis and TNF Inhibitors</span><p id="par0060" class="elsevierStylePara elsevierViewall">TNF inhibitors are widely used to treat inflammatory diseases such as psoriasis and rheumatoid arthritis&#46; TNF-&#945; participates in cell-mediated immune response by activating CD4<span class="elsevierStyleSup">&#43;</span> and CD8<span class="elsevierStyleSup">&#43;</span> T cells&#46; Together with other cytokines such as interleukin 12 and IFN-&#947;&#44; it has a key role in early infection control&#46; Parasite DNA has been detected in the blood of up to 58&#37; of healthy individuals in the Mediterranean&#44; an endemic area with high levels of exposure to <span class="elsevierStyleItalic">Leishmania</span>&#44; but the actual numbers of people who develop the disease are low&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> It is therefore believed that most immunocompetent individuals are able to control infection before it manifests&#46; Likewise&#44; it has been suggested that TNF-&#945; inhibitors could favor the reactivation of latent leishmaniasis&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and also modify clinical presentation&#44; the natural course of disease&#44; and response to treatment&#46; Based on the cases published to date&#44; the best approach to dealing with reactivation of a latent infection would appear to be to treat the infection with systemic therapy and interrupt TNF inhibitor treatment until the infection has cleared<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#59; the treatment should then be reintroduced with close follow-up&#46; Etanercept and certolizumab appear to be associated with a lower risk of reactivation than adalimumab or infliximab&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Diagnosis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Leishmaniasis is diagnosed by demonstrating the presence of <span class="elsevierStyleItalic">Leishmania</span> amastigotes in clinical specimens using direct microscopic examination or molecular analysis based on nuclear or kinetoplast DNA amplification&#46; Amastigotes are round and have a diameter of 1 to 4&#160;&#956;m and a characteristic rod-shaped structure known as a <span class="elsevierStyleItalic">kinetoplast</span>&#46; The main sampling and diagnostic techniques are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#8211;45</span></a> Considering the limited sensitivity of some of the diagnostic techniques&#44; it may be necessary to take several samples and&#47;or use a combination of techniques to reach a diagnosis&#46; In the case of biopsy specimens&#44; for example&#44; one part could be used for histology&#44; another for touch imprint cytology&#44; and another for culture&#46; Diagnostic sensitivity in VL varies according to tissue type and can be as high as 90&#37; for spleen tissue&#46; Spleen aspiration is the procedure of choice for diagnosing VL&#44; but it is associated with a high risk of intra-abdominal bleeding&#46; Sensitivity rates ranging from 50&#37; to 85&#37; have been reported for bone marrow samples&#44; and even lower rates have been described for lymph node and peripheral blood&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> In PKDL&#44; diagnostic sensitivity using smears or biopsy specimens is largely dependent on the type of lesion analyzed&#44; with rates of up to 100&#37; for nodular lesions contrasting with very low rates for macular lesions&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> where more sensitive molecular methods are needed&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> More information on sampling methods and diagnostic techniques can be consulted in the guidelines of the Centers for Disease Control and Prevention<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> and the Infectious Diseases Society of America&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Histology can show nonspecific features such as ulceration&#44; pseudoepitheliomatous hyperplasia&#44; and a mixed inflammatory infiltrate&#44; as well as specific features&#44; such as amastigotes in dermal macrophages&#44; seen in 50&#37; to 70&#37; of cases<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; As lesions develop&#44; there is an increase in the number of giant cells and a decrease in that of parasites&#46; Other findings include tuberculoid granulomas&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> and in advanced stages&#44; dermal fibrosis and abundant plasma cells&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> Four histologic patterns have been described for leishmaniasis&#58; <span class="elsevierStyleItalic">1</span>&#41; abundant amastigotes &#40;45&#37;&#41;&#59; <span class="elsevierStyleItalic">2</span>&#41; a mixture of macrophages&#44; neutrophils&#44; and plasma cells accompanied by necrosis &#40;27&#46;5&#37;&#41;&#59; <span class="elsevierStyleItalic">3</span>&#41; incipient granulomas with epithelioid cells&#44; lymphocytes&#44; and plasma cells &#40;15&#37;&#41;&#59; and <span class="elsevierStyleItalic">4</span>&#41; fully formed epithelioid granulomas with Langhans-type giant cells&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> Histologic findings are similar in CL and MCL&#46; A diffuse infiltrate of macrophages containing large numbers of amastigotes is seen in diffuse CL&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Dermoscopy is another useful diagnostic aid&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> The most frequently described dermoscopic structures are erythema &#40;100&#37;&#41;&#59; vascular structures &#40;90&#46;6&#37;&#41;&#44; including polymorphous &#40;40&#46;2&#37;&#41;&#44; hairpin &#40;39&#46;4&#37;&#41;&#44; and arborizing vessels &#40;38&#46;6&#37;&#41;&#59; crusts &#40;70&#46;1&#37;&#41;&#59; and erosion&#47;ulceration &#40;44&#46;1&#37;&#41;&#46; Less common but more characteristic structures are white-yellow teardrop-like structures &#40;42&#46;5&#37;&#41; and the white starburst pattern &#40;8&#46;6&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>F&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Other tests&#44; which are less useful in the diagnosis of CL&#44; are the Montenegro skin test and serological tests&#46; The former consists of the intradermal injection of leishmanin&#44; and its results are read and interpreted in a similar way to those of the tuberculin test&#46; It is negative in diffuse CL&#44; active VL&#44; and PKDL&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> and cannot differentiate between current and past infection&#46; It is mainly useful for epidemiological purposes&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Serological tests include the direct agglutination test&#44; immunofluorescence&#44; enzyme-linked immunoassay &#40;ELISA&#41;&#44; and Western blot analysis&#46; These tests are highly sensitive in VL&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> Antibody titers&#44; however&#44; drop very slowly after cure and the test does not discriminate between active and past infection&#46; Results can also be affected by cross-reactivity with other antibodies &#40;e&#46;g&#46;&#44; Chagas disease&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> In addition&#44; asymptomatic individuals in endemic areas often have antibodies&#44; meaning that results have to be carefully interpreted according to the clinical context&#46; High levels of anti-&#945;-galactosyl antibodies have been detected using ELISA in CL caused by <span class="elsevierStyleItalic">L tropica</span> and <span class="elsevierStyleItalic">L major</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> A number of rapid diagnostic tests&#44; such as rK39&#44; are also available&#46; These have high sensitivity for VL&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> but they have the same limitations as other serological tests&#46; More recent antigen detection tests include the latex agglutination test<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a> and ELISA<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> with urine samples in VL and an immunochromatographic strip that tests for peroxidoxin antigen<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> in CL&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Differential Diagnosis</span><p id="par0090" class="elsevierStylePara elsevierViewall">The main entities that should be considered in the differential diagnosis are other infections&#44; such as ecthyma&#44; sporotrichosis&#44; skin tuberculosis&#44; furuncular myasis&#44; subcutaneous mycosis&#44; tertiary syphilis&#44; and lepromatous leprosy&#59; malignancies&#44; such as squamous cell carcinoma&#44; basal cell carcinoma&#44; and lymphoma&#59; and other skin disorders&#44; such as persistent arthropod bite reactions&#44; sarcoidosis&#44; and granulomatosis with polyangitis&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Treatment</span><p id="par0095" class="elsevierStylePara elsevierViewall">Many cases of CL resolve spontaneously in under 2 years&#46; Variations in resolution times are largely related to the species involved &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; with infections caused by <span class="elsevierStyleItalic">L braziliensis</span> and <span class="elsevierStyleItalic">L panamensis</span> most likely to persist&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a> Depending on this and other factors&#44; such as anatomic location&#44; infection severity&#44; and the host&#8217;s immune response&#44; CL can be classified as simple or complex&#46; Simple infections can be treated conservatively or with local treatments&#44; while complex infections require systemic therapies&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> The characteristics of simple and complex CL are summarized in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Multiple treatments exist for leishmaniasis&#44; although the evidence supporting the options for CL is weak&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a> The main treatments are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">66&#8211;97</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">After weighing up the risks and benefits&#44; a watch-and-wait approach can be taken in patients who meet the criteria for simple CL&#46; Local treatment can be used for lesions that do not resolve spontaneously or when the goal is to achieve a faster cure or reduce the risk of scarring&#46; The most widely accepted local treatments are intralesional pentavalent antimonials<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">66&#8211;69</span></a> and cryotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a> The combination of both produces better outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">70&#44;71</span></a> Topical paromomycin is also used to treat CL&#44; particularly in the New World&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">73&#8211;75</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">There have been reports of good responses to other local treatments&#44;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">98</span></a> such as carbon dioxide laser therapy&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">99</span></a> which has shown efficacy rates of 93&#37; and very few adverse effects &#40;hyperpigmentation&#44; persistent erythema&#44; and hypertrophic scarring&#41;&#59; photodynamic therapy<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a>&#59; and imiquimod&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">100</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Systemic therapies are recommended for patients who meet any of the criteria for complex CL&#46; Liposomal amphotericin&#160;B is highly effective but carries a risk of nephrotoxicity&#46;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">89&#8211;93</span></a> The traditional use of systemic pentavalent antimonials<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">85&#8211;88</span></a> to treat complex CL and MCL has led to resistance in certain areas&#44; limiting their use&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">87</span></a> Other options include azoles&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> miltefosine&#44;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">82&#8211;84</span></a> and pentamidine&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">94&#8211;96</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">A clinical trial comparing twice-daily chloroquine 250&#160;mg and once-daily doxycycline 200&#160;mg for 3 months reported an efficacy of 100&#37; and 92&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">101</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Annual check-ups are recommended in patients with CL due to <span class="elsevierStyleItalic">L braziliensis</span> to enable early detection of progression to MCL&#46; Signs of MCL include persistent nasal secretion or bleeding&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">PKDL from Africa is not normally treated as the vast majority of cases &#40;85&#37;&#41; resolve spontaneously within a year&#46; In India&#44; however&#44; systemic treatment with miltefosine or amphotericin B is generally needed&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">We have drawn up an algorithm for the management of CL and MCL based on current guidelines and expert recommendations &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Prevention and Control</span><p id="par0135" class="elsevierStylePara elsevierViewall">Prophylactic vaccines for leishmaniasis in humans are not yet available&#46; The fact that most patients who recover from leishmaniasis do not become reinfected facilitates vaccine research efforts&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">102</span></a> One of the main control strategies for CL and VL&#44; apart from vector control&#44; involves early detection and treatment&#44; as infected patients are reservoirs&#46; The WHO&#8217;s target for CL in the eastern Mediterranean region was to detect 70&#37; of all cases and to treat at least 90&#37; by 2020&#44; an ambitious target considering the few treatment options available&#44; the suboptimal diagnostic tools&#44; and the low levels of awareness among the scientific community&#44; particularly in relation to CL&#44; which is not classified as an infection control priority&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">CL has become a relatively common condition in our setting due to international travel and migration&#46; Its management&#44; however&#44; can be complicated due to low indices of suspicion among clinicians&#44; the low sensitivity of some diagnostic tests&#44; poor access to molecular testing&#44; limited treatment options&#44; and adverse treatment effects&#46; HIV coinfection and use of TNF inhibitors are associated with atypical presentations and the need for systemic treatment&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of Interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Leishmaniasis is a chronic disease caused by flagellate protozoa of the genus <span class="elsevierStyleItalic">Leishmania</span>&#46; It is a global disease&#44; but most cases are seen in South America&#44; the Mediterranean&#44; and some areas of Asia and Africa&#46; The 3 main types of leishmaniasis are cutaneous &#40;the most common&#41;&#44; mucocutaneous&#44; and visceral &#40;the most severe&#41;&#46; Visceral leishmaniasis is also known as <span class="elsevierStyleItalic">kala-</span><span class="elsevierStyleItalic">azar</span>&#46; Leishmaniasis is diagnosed by demonstrating the presence of <span class="elsevierStyleItalic">Leishmania</span> amastigotes in clinical specimens using direct microscopic examination or molecular analysis&#46; Various treatments exist&#44; although the evidence supporting the options available for cutaneous leishmaniasis is weak&#46; Both the classical presentation of leishmaniasis and our management of the disease have changed in recent decades because of acquired immune deficiency caused by conditions such as human immunodeficiency infection or the use of tumor necrosis factor inhibitors&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La leishmaniasis es una enfermedad cr&#243;nica causada por un protozoo flagelado perteneciente al g&#233;nero <span class="elsevierStyleItalic">Leishmania</span>&#46; Tiene distribuci&#243;n mundial&#44; aunque la mayor&#237;a de casos se agrupan en Am&#233;rica del Sur&#44; la cuenca mediterr&#225;nea y algunas zonas de Asia y &#193;frica&#46; Existen tres formas fundamentales de enfermedad&#58; cut&#225;nea&#44; la m&#225;s frecuente&#59; mucocut&#225;nea&#59; y visceral&#44; tambi&#233;n denominada <span class="elsevierStyleItalic">kala-azar&#44;</span> la forma m&#225;s grave&#46; El diagn&#243;stico se establece con la demostraci&#243;n de la presencia de los amastigotes en muestras cl&#237;nicas&#44; mediante visi&#243;n directa al microscopio o mediante t&#233;cnicas moleculares&#46; Existen m&#250;ltiples opciones terap&#233;uticas&#44; aunque la evidencia en la que se basa el tratamiento de la leishmaniasis cut&#225;nea es d&#233;bil&#46; Actualmente&#44; las alteraciones de la inmunidad producidas por factores como el VIH o el uso de f&#225;rmacos anti-TNF han cambiado tanto la forma de presentaci&#243;n de las formas cl&#237;nicas cl&#225;sicas como sus tratamientos&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Abad&#237;as-Granado I&#44; Diago A&#44; Cerro PA Palma-Ruiz AM&#44; Gilaberte Y&#46; Leishmaniasis cut&#225;nea y mucocut&#225;nea&#46; ACTAS Dermo-Sifiliogr&#46; 2021&#59;112&#58;601&#8211;618&#46;</p>"
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        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2828
            "Ancho" => 2508
            "Tamanyo" => 667515
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Fig&#46; "
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        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A&#8211;C&#44; The presence of an erythematous papule or nodule exhibiting progressive growth and a tendency to ulcerate in exposed areas&#44; such as the face or extremities&#44; is the most characteristic presentation of cutaneous leishmaniasis&#46; D&#44; Some patients have multiple lesions&#44; or atypical presentations such as the verrucous lesion in this patient with New World cutaneous leishmaniasis&#46; Clinical &#40;E&#41; and dermoscopic &#40;F&#41; image of a cutaneous leishmaniasis lesion on the forearm showing central ulceration surrounded by an erythematous area with peripheral polymorphous and hairpin vessels &#40;asterisks&#41; and white-yellow teardrop-like structures &#40;arrows&#41;&#40;polarized light&#44; original magnification &#215;10&#41;&#46;</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Images courtesy of Dr&#46; Morales Moya &#40;2C&#41;&#44; Dr&#46; Galimberti &#40;2D&#41;&#44; and Dr Mayo Mart&#237;nez &#40;2E and F&#41;&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1880
            "Ancho" => 2512
            "Tamanyo" => 451159
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A&#44; Mucocutaneous leishmaniasis manifests as a chronic ulcer often affecting the nasal mucosa&#46; B&#44; Firm cutaneous leishmaniasis papules on the palm of a patient coinfected with visceral leishmaniasis and human immunodeficiency virus&#46; C&#44; Hyperpigmented macules in the neck area&#46; D&#44; Hypopigmented macules as a manifestation of post-kala-azar dermal leishmaniasis in a 7-year-old boy&#46; The diagnosis was established by molecular techniques&#44; as the biopsy was negative&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1880
            "Ancho" => 2512
            "Tamanyo" => 873405
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A&#44; Panoramic punch biopsy of an erythematous nodule on the forearm &#40;hematoxylin-eosin&#44; original magnification &#215;5&#41;&#46; B&#44; Dense superficial dermal inflammatory infiltrate and pseudoepitheliomatous hyperplasia &#40;hematoxylin-eosin&#44; original magnification &#215;10&#41;&#46; C&#44; Detail of inflammatory infiltrate composed mainly of macrophages&#44; lymphocytes&#44; and some epithelioid cells &#40;hematoxylin-eosin&#44; original magnification &#215;20&#41;&#46; D&#44; Characteristic amastigotes in infected macrophages &#40;hematoxylin-eosin&#44; original magnification &#215;40&#41;&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "fig0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 2859
            "Ancho" => 3333
            "Tamanyo" => 739059
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for cutaneous and mucocutaneous leishmaniasis&#46; IL indicates intralesional&#59; IM&#44; intramuscular&#59; IV&#44; intravenous&#59; PDT&#44; photodynamic therapy&#59; VO&#44; oral&#46; &#42; foreign medication&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0030"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; CL&#44; cutaneous leishmaniasis&#59; MCL&#44; mucocutaneous leishmaniasis&#59; PKDL&#44; post-kala-azar dermal leishmaniasis&#59; VL&#44; visceral leishmaniasis&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Complex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main Species&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main Reservoir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main Geographic Distribution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Most Common Clinical Patterns and Their Main Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Natural Progression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania donovani</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">L donovani</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Human</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">India&#44; Bangladesh&#44; Ethiopia&#44; Sudan</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VL&#58; fever&#44; hepatosplenomegaly&#44; weight loss&#44; anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Without treatment&#44; death within 2 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PKDL&#58; macular&#44; papular&#44; or nodular lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resolves spontaneously in up to 85&#37; of cases in Africa&#44; but rarely in Asia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania infantum</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dog&#44; hare&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mediterranean Basin&#44; China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CL&#58; mildly inflammatory solitary nodulesVL&#58; more common in children and immunosuppressed individuals</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tends to resolve spontaneously within a year&#44; conferring immunity</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania infantum chagasi</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dog&#44; fox&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Central and South America&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania tropica</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">L tropica</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Human&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eastern Mediterranean&#44; Middle East&#44; India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CL&#58; &#60;3 dry ulcers&#44; mostly on the head&#59; chronic&#44; recurrent course&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Most cases resolve spontaneously within 2 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania major</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rodents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Africa&#44; Middle East&#44; Central Asia&#44; India&#44; China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LC&#58; multiple moist inflammatory ulcers&#44; most of which progress rapidly&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#37; of cases resolve in 4 mo but leave severe scarring&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania aethiopica</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hyraxes &#40;dassie&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ethiopia&#44; Kenya&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LC&#58; localized nodules or ulcers&#59; may result in diffuse involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Usually resolves spontaneously with 2-5 years&#44; except for diffuse forms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania mexicana</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">L mexicana</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rodents&#44; marsupials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mexico&#44; Central and South America&#44; Texas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LC&#58; solitary or multiple ulcerated lesions&#44; sometimes with diffuse involvement&#59; responsible for characteristic ulcerated ulcer lesion in gum collectors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;80&#37; of cases resolve spontaneously within 3&#8211;4 mo&#44; although some lesions can last up to 20 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania amazonensis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rodents&#44; possums&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">South America&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LC&#58; ulcerated lesions&#44; often with diffuse involvementCan progress to MCL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not well described&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania &#40;Viannia&#41; braziliensis</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">L braziliensis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rodents&#44; dogs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Central and South America&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LC&#58; ulcerated lesionsMCL&#58; mainly caused by <span class="elsevierStyleItalic">L braziliensis&#59;</span> ulcerated lesions in oral and nasal mucosa&#59; can extend to oropharynx and larynx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Causes serious infections&#59; often associated with satellite lesions&#44; subcutaneous nodules&#44; and enlarged locoregional lymph nodes&#59; 6&#37; of cases resolve spontaneously in 6 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania panamensis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sloths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Panama&#44; Costa Rica&#44; Colombia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CL&#58; superficial ulcers&#44; often with lymphatic spreadMCL&#58; nasopharyngeal involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Does not resolve spontaneously&#46; Spreads through lymphatic vessels and can cause mucocutaneous lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania guyanensis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Possums&#44; sloths&#44; and anteaters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">South America&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LC&#58; multiple ulcers that can spread through the lymphatic system&#44; resulting in a sporotrichoid distributionMCL&#58; cutaneous involvement that can progress to mucocutaneous involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tends to need treatment and recurs frequently&#59; at times&#44; resolves spontaneously within 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Clinical and Epidemiological Characteristics of the Main Species of <span class="elsevierStyleItalic">Leishmania</span>&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0035"
            "detalle" => "Table "
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Abbreviation&#58; PCR&#58; polymerase chain reaction&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of Lesion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sampling Method</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diagnostic Techniques&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Technique&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Considerations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Base&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Swab</span>&#46; To collect DNA&#46; Rub ulcer several times&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PCR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Real-time PCR<span class="elsevierStyleHsp" style=""></span>Samples can be stored in high concentrations of ethanol or in paraffin&#44; although paraffin-embedded samples yield lower sensitivity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Advantages&#58;</span> highest sensitivity and specificity&#44; relatively fast&#44; and allows identification of species<span class="elsevierStyleItalic">Disadvantages&#58;</span> not always available<span class="elsevierStyleItalic">Sensitivity</span>&#58; 100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Touch print cytology&#46;</span> Remove the crust and take an imprint of the base of the ulcer on a slide&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smear&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smear<span class="elsevierStyleHsp" style=""></span>Giemsa staining and direct visualization using &#215;100 lens and oil immersion<span class="elsevierStyleHsp" style=""></span>Visualization of amastigotes and their characteristic kinetoplast structure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Advantages&#58;</span> fast and cheap <span class="elsevierStyleItalic">Disadvantages&#58;</span> does not allow identification of species<span class="elsevierStyleItalic">Sensitivity&#58;</span> 85&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Border&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fine-needle aspiration&#46;</span> Aspirate using a 1-mL syringe with a 20-25-G needle and 0&#46;1&#160;mL of sterile saline solution 0&#46;9&#37;&#46; If no material is obtained&#44; inject 0&#46;05-0&#46;1&#160;mL of the saline solution and reaspirate&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smear&#44; culture&#44; PCR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Culture<span class="elsevierStyleHsp" style=""></span>Sterile sample<span class="elsevierStyleHsp" style=""></span>Medium&#58; Novy-MacNeal-Nicolle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Advantages&#58;</span> allows identification of species and definitive diagnosis<span class="elsevierStyleItalic">Disadvantages&#58;</span> frequent contamination by skin flora and low sensitivity<span class="elsevierStyleItalic">Sensitivity&#58;</span> 40&#37;Recent microculture techniques offer higher sensitivity &#40;close to 100&#37;&#41;&#44; but do not allow identification of species&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Skin scrapings&#46;</span> Use a scalpel to obtain tissue scrapings from the upper dermis&#44; via an incision or removal of necrotic tissue&#46; Requires local anesthesia and bleeding control for better results&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smear&#44; culture&#44; PCR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Biopsy&#46;</span> Shave or punch&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smear&#44; culture&#44; PCR&#44; histology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HistologyHematoxylin-eosin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Advantages&#58;</span> can be used to rule out other possible causes&#44; in particular&#44; malignancy<span class="elsevierStyleItalic">Disadvantages&#58;</span> invasive&#44; does not allow identification of species&#44; and has low sensitivity<span class="elsevierStyleItalic">Sensitivity&#58;</span> 60&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nodule&#47;plaque&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fine-needle aspiration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smear&#44; culture&#44; PCR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smear&#44; culture&#44; PCR&#44; histology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Sampling Methods and Diagnostic Techniques for Cutaneous and Mucocutaneous Leishmaniasis&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0040"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; HIV&#44; human immunodeficiency virus&#59; TNF&#44; tumor necrosis factor&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Simple Cutaneous Leishmaniasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Complex Cutaneous Leishmaniasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania</span> species associated with low likelihood of mucosal involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Leishmania</span> species associated with high likelihood of mucosal involvement&#44; particularly species from <span class="elsevierStyleItalic">Leishmaniasis braziliensis</span> complex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No notable mucosal involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mucosal involvement&#44; subcutaneous nodules&#44; and&#47;or significantly enlarged regional lymph nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Single or few lesions &#60; 1&#160;cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805; 5 lesions measuring &#62; 1&#160;cm or single lesion measuring &#62; 5&#160;cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Located in areas without significant cosmetic concerns and that are accessible for local treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Located on the face&#44; ears&#44; fingers or toes&#44; and skin covering joints or genitals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immunocompetent host&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immunosuppressed host &#40;HIV&#44; TNF inhibitors&#44; etc&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lesions showing signs of spontaneous resolution at diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">History of non-response to local treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No criteria for complex cutaneous leishmaniasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recurrent disease or diffuse presentation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2648066.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Characteristics of Simple and Complex Cutaneous Leishmaniasis&#46;</p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0045"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ALA&#44; aminolevulinic acid&#59; IL&#44; intralesional&#59; MAL&#44; methyl aminolevulinate&#59; MBCL&#44; methyl benzethonium chloride&#59; MCL&#44; mucocutaneous leishmaniasis&#59; NWCL&#44; New World cutaneous leishmaniasis&#59; OWCL&#44; Old World cutaneous leishmaniasis&#59; PDT&#44; photodynamic therapy&#59; VL&#44; visceral leishmaniasis&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug or Device&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose&#44; Adverse Effects and Other Considerations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Effectiveness<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">97</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Level of Evidence<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Local Treatment</span><span class="elsevierStyleItalic">Intralesional</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pentavalent antimonials</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sodium stibogluconate<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">66&#8211;68</span></a> &#40;Pentostam 100&#160;mg&#47;mL&#44; foreign medication&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OWCLConsider for NWCL if no risk of mucosal involvement</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intradermal injection 0&#46;2-0&#46;5&#160;mL &#40;0&#46;1&#160;mL&#47;cm<span class="elsevierStyleSup">2</span> in up to 5 sites&#47;lesion every 3-7 d for up to 5 sessions&#41;May require local anesthesiaMore effective when combined with cryotherapy<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">70&#44;71</span></a>Intralesional administration does not usually cause adverse effects &#40;except for local reactions&#41;&#44; although QT interval prolongation has been reported in up to 25&#37; of patients<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#37;-98&#37; &#40;OWCL&#41;77&#37;-90&#37; &#40;NWCL&#41;89&#37;-91&#37; &#40;when combined with cryotherapy&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A &#40;combined with cryotherapy&#44; LCVM&#41;B &#40;NMCL&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Meglumine antimoniate<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a>&#40;Glucantime 1500&#160;mg&#47;5&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Topical</span>Paromomycin<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paromomycin ointment<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a> &#40;Leshcutan&#44; paromomycin 15&#37;&#160;&#43;&#160;MBCL 12&#37;&#44; foreign medication&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ulcerated lesions due to <span class="elsevierStyleItalic">Leishmania</span> spp&#46; in OWCL and NWCL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Twice daily for 10-20 d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Similar to intralesional pentavalent antimonials in OWCL&#44; and inferior in NWCL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A &#40;OWCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paromomycin 15&#37; cream&#160;&#43;&#160;gentamicin 0&#46;5&#37;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a> &#40;not commercially available&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Better responses in <span class="elsevierStyleItalic">Leishmania major</span> and <span class="elsevierStyleItalic">Leishmania panamensis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B &#40;NWCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Similar results for formulations with and without gentamicinCan cause intense inflammation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cryotherapy<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liquid nitrogen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recent-onset CL lesionsResidual lesions after systemic treatmentConsider in pregnant and breastfeeding women and patients with contraindications for systemic treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 freeze-thaw cycles for 15-20&#160;s&#44; with halo of 1-2&#160;mm&#59; repeated every 3 wk until cureMore effective when combined with intralesional pentavalent antimonialsCan cause permanent hypopigmentation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#37;-75&#37; &#40;similar efficacy to intralesional pentavalent antimonials&#41;89&#37;-91&#37; &#40;if combined with intralesional pentavalent antimonials&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A &#40;combined with IL APV&#44; OWCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thermoterapy<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">77&#8211;79</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Application of superficial heat via radiofrequency &#40;ThermoMed&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OWCL and NWCLConsider in pregnant and breastfeeding women and patients with contraindications for systemic treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#160;&#176;C for 30&#160;s applied to lesion and up to 1-2&#160;mm of surrounding skin&#59; 1-2 sessionsBased on in vitro studies showing that <span class="elsevierStyleItalic">Leishmania</span> parasites do not multiply at &#62;&#160;39&#160;&#176;C Requires local anesthesiaProduces second-degree burns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#37;-98&#37; &#40;OWCL&#41;58&#37;-90&#37; &#40;NWCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A &#40;OWCL&#44; NWCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDT<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Conventional PDT with ALA or MAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OWCL&#44; especially that caused by <span class="elsevierStyleItalic">L major</span> or <span class="elsevierStyleItalic">Leishmania tropica</span>Consider in CL resistant to other treatments or in aesthetically sensitive areasNot recommended in CL due to <span class="elsevierStyleItalic">Leishmania braziliensis</span> complex or <span class="elsevierStyleItalic">Leishmania donovani</span> complex</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1-7 sessions a week&#59; &#8805;&#160;3 sessions more effective than &#8804;2Mechanism of action believed to involve immune system response as does not directly kill the parasiteConventional PTD with ALA &#40;6 sessions&#41; seems to be at least as effective as cryotherapy &#40;5 sessions&#41; and produces better aesthetic results&#44; although is more poorly toleratedLocal adverse effects &#40;burning&#44; reddening&#44; edema&#44; pain&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&#37;-100&#37; &#40;conventional PDT&#41;74&#37;-82&#37; &#40;daylight PDT&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B &#40;conventional PTD&#44; OWCL&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Daylight PDT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intralesional PDT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Systemic therapy</span><span class="elsevierStyleItalic">Oral</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;1&#44;0&#93;Azoles<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fluconazole&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Off-label use for CL with lymphatic involvement and certain complex cases of CL&#59; not indicated for cases due to <span class="elsevierStyleItalic">L braziliensis</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">200-400&#160;mg&#47;d for 42 dAdverse effects include gastrointestinal disturbances and hepatotoxicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#37;-81&#37; &#40;OWCL&#41;22&#37; &#40;NWCL&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A &#40;OWCL&#44; fluconazole 200&#160;mg&#47;d&#44; 42 d&#44; <span class="elsevierStyleItalic">L</span><span class="elsevierStyleItalic">major</span>&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Itraconazole&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">200&#160;mg&#47;d for 42-56 d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Miltefosine<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">82&#8211;84</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Miltefosine &#40;Impavido 50&#160;mg capsules&#44; foreign medication&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LC due to <span class="elsevierStyleItalic">L braziliensis</span> complex&#59; can also be used in LC due to <span class="elsevierStyleItalic">L major&#44; L tropica&#44;</span> or <span class="elsevierStyleItalic">Leishmania mexicana</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;5&#160;mg&#47;kg&#47;d &#40;maximum 150&#160;mg&#41;&#44; administered orally in 3 doses for 28 dExpensiveTeratogenic and can cause gastrointestinal disturbances and hepatotoxicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&#37; &#40;OWCL&#41;53&#37;-91&#37; &#40;NWCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B &#40;NWCL&#41;C &#40;OWCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Parenteral</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pentavalent antimonials<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">85&#8211;88</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sodium stibogluconate &#40;Pentostam&#44; 100&#160;mg&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#91;1&#44;0&#93;Complex OWCL and NWCL and MCL</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#160;mg&#47;kg&#47;d in a single daily dose administered orally &#40;preferred&#41; or intramuscularly &#40;very painful&#41; for 10-30 dTreatment failures have increased due to resistance<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">87</span></a>Usually associated with pentoxifylline 400&#160;mg 3 times a day for 10-20 d&#44; or allopurinol 20&#160;mg&#47;kg for 30 days in recurrent LC due to <span class="elsevierStyleItalic">L tropica</span>Can cause cardiotoxicity &#40;e&#46;g&#46;&#44; arrhythmias&#44; QT interval prolongation&#41;&#44; pancreatitis&#44; and hepatotoxicity</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#37;-85&#37; &#40;OWCL&#41;77&#37;-90&#37; &#40;NWCL&#41;30&#37;-90&#37; &#40;MCL&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A &#40;OWCM&#44; MCL&#41;C &#40;recurrent CL&#41;</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Meglumine antimoniate&#40;Glucantime 1500&#160;mg&#47;5&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amphotericin B<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">89&#8211;93</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liposomal &#40;AmBisome 50&#160;mg&#41;&#44; treatment of choice due to its lower toxicity compared with conventional options&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Off-label use for complex CL and MCL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#160;mg&#47;kg&#47;d IV for 7 d &#40;days 1-5&#44; 14&#44; and 21&#41; up to a total dose of 21&#160;mg&#47;kg&#46;Optimal dose for LC not well-defined&#59; treatment regimens are based on the doses used for VL&#59; higher doses and longer treatments are usually required in immunosuppressed patientsApproval of topical formulation of amphotericin 3&#37; with similar efficacy to intralesional pentavalent antimonials in LC<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">92</span></a>Can cause nephrotoxicity&#44; lower back pain&#44; hypokalemia&#44; chills&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&#37;-100&#37; &#40;OWCL&#44; NWCL&#41;78&#37;-100&#37; &#40;MCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C &#40;NWCL&#44; MCL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pentamidine<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">94&#8211;96</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pentamidine isethionate 300&#160;mg &#40;Pentacarinat&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alternative treatment for NWCL&#59; good responses in <span class="elsevierStyleItalic">Leishmania guyanensis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t">C &#40;NWCL&#44; MCL&#41;&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2021.05.011

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