Effects of Amphotericin B-Conjugated Functionalized Carbon Nanoparticles in the Treatment of Cutaneous Leishmaniasis.

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti-leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f-CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real-time PCR was used to quantify the parasite load post-infection. Levels of nitric oxide and cytokines IL-4 and IFN-γ were also determined. We found that f-CNT-AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti-leishmanial activity with an IC50 of 0.00494 ± 0.00095 mg/mL for promastigotes and EC50 of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post-infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f-CNT-AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN-γ significantly increased in the f-CNT-AmB treated groups. Also, our results showed that the level of IL-4 significantly decreased after f-CNT-AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f-CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response.

[Special lesion on back of the hand]. / Bijzondere huidafwijking op de handrug.

A 74-year-old man, previously healthy, presented at the Dermatology department with an asymptomatic hand lesion persisting for two months. The general practitioner initially treated the lesion with betamethasone and fusidic acid cream. Examination revealed a 3 cm livid plaque with central crusts. A biopsy confirmed cutaneous leishmaniasis tropica. The patient travelled to Greece, Spain, and Southern France before the lesion occurred, which is consistent with the endemicity of leishmaniasis in the Mediterranean. Treatment involved cryotherapy and antimony injections, resulting in lesion resolution after two sessions. This case underscores the importance of considering travel history and endemic diseases in diagnosing and managing dermatological conditions, especially in regions prone to specific infections.

First case of urban leishmaniasis in the Campeche State, Mexico.

Cutaneous leishmaniasis represents 99% of all reported leishmaniasis cases in Mexico and typically occurs in agricultural or sylvatic areas. Campeche State is endemic for leishmaniasis; however, there are no previous records of urban Leishmania transmission. This report presents a case of cutaneous leishmaniasis in a 75-year-old man residing in an urban area. The patient presented with a three-month-old lesion on the right ear following an initial misdiagnosis of a bacterial infection. Given the suspicion of leishmaniasis, a tissue imprint was collected, revealing the presence of Leishmania amastigotes. Subsequently, amplification and sequencing of the Alanine aminotransferase and Internal transcribed spacer subunit 1 genes confirmed the presence of Leishmania mexicana. The patient was then treated with intralesional meglumine antimoniate. This case is significant as it marks the first confirmed human transmission of L. mexicana in an urban environment in Campeche State, demonstrating the importance of considering this pathology in patients with skin lesions originating from non-endemic areas in Mexico.

Epoxy-a-lapachone in nanosystem: a prototype drug for leishmaniasis assessed in the binomial BALB/c - Leishmania (Leishmania) amazonensis.

This perspective presents and supports arguments for a new formulation of epoxy-α-lapachone loaded microemulsion (ELAP-ME), a nanosystem, as a prototype drug for the treatment of leishmaniasis. The benefits of ELAP as a multitarget compound, with properties that affect key physiological pathways of Leishmania spp. are discussed. ELAP-ME demonstrated efficacy in murine infection models, particularly with the binomial BALB/c-Leishmania (Leishmania) amazonensis. Furthermore, it is proposed that the technological maturity of ELAP-ME be classified as Technology Readiness Level 4 (TLR 4) within the context of innovative drugs for American Cutaneous Leishmaniasis (ACL).

Leishmania spp. genetic factors associated with cutaneous leishmaniasis antimony pentavalent drug resistance: a systematic review.

BACKGROUND: Leishmaniasis is a neglected zoonosis caused by parasites of Leishmania spp. The main drug used to treat cutaneous leishmaniasis (CL) is the antimoniate of meglumine. This drug, which has strong adverse and toxic effects, is usually administered intravenously, further complicating the difficult treatment. Factors such as Leishmania gene expression and genomic mutations appear to play a role in the development of drug resistance. OBJECTIVES: This systematic review summarises the results of the literature evaluating parasite genetic markers possibly associated with resistance to pentavalent antimony in CL. METHODS: This study followed PRISMA guidelines and included articles from PubMed, SciELO, and LILACS databases. Inclusion criteria were studies that (i) investigated mutations in the genome and/or changes in gene expression of Leishmania associated with treatment resistance; (ii) used antimony drugs in the therapy of CL; (iii) used naturally resistant strains isolated from patients. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess article quality and risk of bias. FINDINGS: A total of 23 articles were selected, of which 18 investigated gene expression and nine genomic mutations. Of these 23 articles, four examined gene expression and genomic mutations in the same samples. Regarding gene expression, genes from the ABC transporter protein family, AQP1, MRPA, TDR1 and TRYR were most frequently associated with drug resistance. In one of the articles in which mutations were investigated, a mutation was found in HSP70 (T579A) and in three articles mutations were found in AQP1 (A516C, G562A and G700A). A limitation of this review is that in most of the included studies, parasites were isolated from cultured lesion samples and drug resistance was assessed using in vitro drug susceptibility testing. These approaches may not be ideal for accurate genetic evaluation and detection of treatment failure. MAIN CONCLUSIONS: The development of further studies to evaluate the genetic resistance factors of Leishmania spp. is necessary to elucidate the mechanisms of the parasite and improve patient treatment and infection control.

A Targeted and Protease-Activated Genetically Encoded Melittin-Containing Particle for the Treatment of Cutaneous and Visceral Leishmaniasis.

Intracellular infections are difficult to treat, as pathogens can take advantage of intracellular hiding, evade the immune system, and persist and multiply in host cells. One such intracellular parasite, Leishmania, is the causative agent of leishmaniasis, a neglected tropical disease (NTD), which disproportionately affects the world's most economically disadvantaged. Existing treatments have relied mostly on chemotherapeutic compounds that are becoming increasingly ineffective due to drug resistance, while the development of new therapeutics has been challenging due to the variety of clinical manifestations caused by different Leishmania species. The antimicrobial peptide melittin has been shown to be effective in vitro against a broad spectrum of Leishmania, including species that cause the most common form, cutaneous leishmaniasis, and the most deadly, visceral leishmaniasis. However, melittin's high hemolytic and cytotoxic activity toward host cells has limited its potential for clinical translation. Herein, we report a design strategy for producing a melittin-containing antileishmanial agent that not only enhances melittin's leishmanicidal potency but also abrogates its hemolytic and cytotoxic activity. This therapeutic construct can be directly produced in bacteria, significantly reducing its production cost critical for a NTD therapeutic. The designed melittin-containing fusion crystal incorporates a bioresponsive cathepsin linker that enables it to specifically release melittin in the phagolysosome of infected macrophages. Significantly, this targeted approach has been demonstrated to be efficacious in treating macrophages infected with L. amazonensis and L. donovani in cell-based models and in the corresponding cutaneous and visceral mouse models.

Use of topical rSm29 in combination with intravenous meglumine antimoniate in the treatment of cutaneous leishmaniasis: A randomized controlled trial.

BACKGROUND: Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1ß play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases. The protein, rSm29 of Schistosoma mansoni, down-modulates pro-inflammatory cytokine production. We evaluate if the combination of topical rSm29 plus MA increases the cure rate of CL. METHODS: In this randomized clinical trial, 91 CL patients were allocated in 3 groups. All cases received MA (20 mg/kg/weight) for 20 days. Group 1 used topical rSm29 (10 µg), group 2 a placebo topically applied, and group 3 received only MA. RESULTS: The cure rate on day 90 was 71% in subjects treated with rSm29 plus MA, and 43% in patients who received MA plus placebo or MA alone (P < 0.05). There was a decrease in GzmB and an increase in IFN-γ (P < 0.05) in supernatants of skin biopsies of the lesions obtained on D7 of therapy (P < 0.05) in patients who received rSm29. CONCLUSION: rSm29 associated with MA reduces GzmB levels, is more effective than MA alone, and decreases CL healing time. CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov under NCT06000514.

Development of a Core Outcome Measure Instrument; "LeishCOM_LCL", for Localised Cutaneous Leishmaniasis.

BACKGROUND: Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease. A literature review identified inconsistencies in clinical trials. The aims of this study were to reach a consensus on the most important domains to measure when assessing LCL, agree on parameters to measure the domains, and develop a tool representing a Core Outcome Set (COS), for use in clinical assessment of LCL. METHODOLOGY & PRINCIPAL FINDINGS: A literature review was conducted to identify any existing COS for LCL embracing agreed Outcome Domains, i.e. what to measure and any Outcome Measurement Instruments (OMIs). As no COS was available, potential outcome domains for assessment of LCL were identified through an international collaborative approach using e-consultations and virtual discussions with expert stakeholders (n = 20) from geographically different LCL endemic countries. Subsequent judgmental validation process included a face-to-face multidisciplinary stakeholders' meeting adopting the Nominal Group Technique. A final consensual agreement on outcome domains and items required to measure these domains was established. "Clinical Cure" was defined as the ideal overall "General Concept". The five Core Outcome Domains included Signs capturing clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score, Treatment Efficacy assessing percentage change in size of the lesion and re-epithelialization compared to baseline, Treatment Impact which included an investigator and patient visual analogue score, and Clinical Sequelae rating pigment change, atrophic and hypertrophic/keloid scars. It was agreed that two open-ended questions should be included to capture some aspects of Health-Related Quality of Life as a means of capturing a patient-focused approach. CONCLUSION: LeishCOM_LCL was generated to reflect a COS for LCL. This captured demographic details, agreed outcome domains and measures to assess these domains. Validation of LeishCOM_LCL will be reported in a separate paper. Development of a Patient Reported Outcome Measure will be considered in the future.

Photodynamic therapy in management of cutaneous leishmaniasis: A systematic review.

This systematic review evaluated the efficacy and safety of photodynamic therapy (PDT) in the management of cutaneous leishmaniasis (CL). The electronic search for identification of relevant studies, adhered to the PICOS (Population, Intervention, Comparator, Outcomes and Study type) framework, was conducted through PubMed, Google scholar, Dimensions, X-mol, and Semantic Scholar till December 2023. All types of studies reporting PDT in the management of CL with no language restriction were included. Methodological quality appraised of the selected studies was performed using Jadad index. Of the 317 identified studies, 21 reported PDT for the treatment of CL lesions, consisting of two randomized controlled trials (RCTs), four single-center open study, one case series and 14 case reports. Collectively, these studies presented a total of 304 patients with ages ranging from 1 to 82 years, undergoing varying number of PDT sessions (3-28) and follow-up durations spanning 4 weeks to 24 months. The CL lesions predominantly manifested on the exposed body areas, such as face, limbs, neck, ear and nose, and characterized with the use of clinical variables, such as plaques, papules, erythema and ulceration. PDT protocols differed in the photosensitizer type, incubation time, light source characteristics (e.g., wavelength, output power, and energy density), duration of light illumination, number of PDT sessions and their respective frequencies. Treatment response was assessed through the clinical presentation (i.e., at the baseline and after PDT completion) or by the absence of Leishmania parasites. Adverse effects comprised of pain, burning and tingling sensation experienced during PDT, followed by erythema, pigmentation changes and edema post-treatment. This systematic review revealed that PDT is an efficacious and safe modality for the treatment of CL, with mild and transient side effects.

Semen Cannabis and Oleum Hyperici: Antileishmanial activity against Leishmania tropica promastigotes and intracellular amastigotes.

The exploration of alternative agents and novel drug candidates for the effective treatment of cutaneous leishmaniasis has garnered significant attention, driven by the high cost, toxic effects, and the emergence of drug resistance associated with current therapeutic options. Plant extracts derived from Semen Cannabis, the seeds of the Cannabis sativa L. (hemp) plant, and Oleum Hyperici, the oily macerate of Hypericum perforatum L. (St. John's Wort) plant, were prepared by using solvents of varying polarity (n-hexane, chloroform, ethanol, and 60% aqueous ethanol). The primary objective of this study was to research in vitro and ex vivo antileishmanial efficacy of Semen Cannabis and Oleum Hyperici plant extracts against Leishmania tropica promastigotes and intracellular amastigotes. The efficacy of plant extracts against promastigotes were assessed using the cell counting by hemocytometer and the CellTiter-Glo assay. Additionally, their impact on infected THP-1 macrophages and the quantity of intracelluler amastigotes were investigated. Cytotoxicity was evaluated in THP-1 macrophages. Among the tested plant extracts, chloroform extract of Oleum Hyperici demonstrated significant antileishmanial activity against promastigotes (SI: 12.6) and intracellular amastigotes (SI: 16.8) of L. tropica without inducing cytotoxic effects and hold promise for further investigation as potential antileishmanial agents.

Microemulsions strongly promoted the activity of α-bisabolol against different Leishmania species and its skin permeation.

This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.

Assessment of the antileishmanial activity of diallyl sulfide combined with meglumine antimoniate on Leishmania major: Molecular docking, in vitro, and animal model.

Currently, no safe vaccine against leishmaniasis is available. So far, different control strategies against numerous reservoir hosts and biological vectors have not been environment-friendly and feasible. Hence, employing medicinal components and conventional drugs could be a promising approach to developing novel therapeutic alternatives. This study aimed to explore diallyl sulfide (DAS), a dynamic constituent of garlic, alone and in a mixture with meglumine antimoniate (MAT as standard drug) using in vitro and animal model experiments against Leishmania major stages. The binding affinity of DAS and four major defense elements of the immune system (iNOS, IFN-É£, IL-12, and TNF-α) was used to predict the predominant binding mode for molecular docking configurations. Herein, we conducted a broad range of experiments to monitor and assess DAS and MAT potential treatment outcomes. DAS, combined with MAT, displayed no cytotoxicity and employed a powerful anti-leishmanial activity, notably against the clinical stage. The function mechanism involved immunomodulation through the induction of Th1 cytokine phenotypes, triggering a high apoptotic profile, reactive oxygen species (ROS) production, and antioxidant enzymes. This combination significantly decreased cutaneous lesion diameter and parasite load in BALB/c mice. The histopathological findings performed the infiltration of inflammatory cells associated with T-lymphocytes, particularly CD4+ phenotypes, as determined by biochemical markers in alleviating the amastigote stage and improving the pathological changes in L. major infected BALB/c mice. Therefore, DAS and MAT deserve further advanced therapeutic development and should be considered as possible candidates for treating volunteer cases with cutaneous leishmaniasis in designing an upcoming clinical trial.

Antileishmanial activity of a dillapiole derivative obtained from Piper aduncum L. (Piperaceae).

Cutaneous leishmaniasis (CL) is considered a public health problem. Current treatments have disadvantages because they are invasive and have serious side effects, and thus there is a need for research into new, more effective pharmacological alternatives. Plants are promising sources of bioactive substances, and new analogues can be obtained through chemical reactions. The present study aimed to evaluate the antileishmanial effects of the analog dillapiole n-butyl ether (DBE) extracted from Piper aduncum leaves. The cytotoxic potential of DBE was evaluated at concentrations of 15.62 to 500 µM in peritoneal macrophages for 48 h, and in RAW 264.7 macrophages for 72 h using a dose-response method. The antileishmanial activity in L. amazonensis promastigotes used concentrations of 0.2 to 4.5 µM for 24, 48 and 72 h and the quantification of the cellular infection rate used a concentration of 4.5 µM of DBE against the amastigote forms internalized in macrophages for 24 h and 48 h. Nitric oxide was quantified from macrophages previously treated with DBE for 24 h and 48 h. The dosage of reactive oxygen species used a concentration of 4.5 µM of DBE incubated together with dichlorofluorescein acetate for 1, 3, 6, and 24 h. For the molecular modeling of DBE, the Leishmania protein, available in the "Protein Data Bank" database, was used. The studied molecule was not toxic to cells and presented a CC50 of 413 µM in peritoneal macrophages and 373.5 µM in RAW 264.7. The analogue inhibited promastigote forms of L. amazonensis with an IC50 of 1.6 µM for 72 h. DBE presented an infection rate of 17% and 12%, dillapiole of 24% and 14% and Pentacarinat® of 10% and 9% over 48 h. DBE demonstrated a binding energy of -7.8 for the U53 enzyme. It is concluded that the analogue showed promising antileishmanial activity for future in vivo tests.

Demographic characteristics and clinical features of patients presenting with different forms of cutaneous leishmaniasis, in Lay Gayint, Northern Ethiopia.

Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by Leishmania parasites, that can cause long-term chronic disabilities. The clinical presentation of CL varies in both type and severity. CL presents as three main clinical forms: localised lesions (localised cutaneous leishmaniasis, LCL); mucocutaneous leishmaniasis (MCL) that affects the mucosa of the nose or the mouth; or as disseminated not ulcerating nodules (diffuse cutaneous leishmaniasis, DCL). Here we recruited a cohort of CL patients in a newly established leishmaniasis treatment centre (LTC) in Lay Gayint, Northwest Ethiopia, and collected detailed demographic and clinical data. The results of our study show that more males than females present to the LTC to seek diagnosis and treatment. 70.2% of CL patients presented with LCL and 20.8% with MCL. A small number of patients presented with DCL, recidivans CL (a rare form of CL where new lesions appear on the edges of CL scars) or with a combination of different clinical presentations. The duration of illness varied from 1 month to 180 months. Over a third of CL patients had additional suspected CL cases in their household. Despite the majority of CL patients having heard about CL, only a minority knew about its transmission or that it could be treated. Most CL patients lived in areas where environmental factors known to be associated with the transmission of CL were present. This work highlights that CL is an important public health problem in Lay Gayint and emphasises the urgent need for more CL awareness campaigns, better health education and better disease management practices.

Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome.

BACKGROUND: The host cellular immune response associated with two treatments for post-kala-azar dermal leishmaniasis (PKDL) - paromomycin plus miltefosine (Arm 1), and liposomal amphotericin B plus miltefosine (Arm 2) - was examined in Sudanese patients before treatment (D0), at the end of treatment (D42), and during the post-treatment period (D180). METHODS: Whole blood samples were stimulated with soluble Leishmania antigen for 24 h (whole blood assay [WBA]) and the concentrations of Th1/Th2/Th17-associated cytokines, IP-10, PDL-1 and granzyme B were determined. RESULTS: The Arm 1 treatment (98.2% cure rate) induced a Th1/Th2/Th17 response, while the Arm 2 treatment (80% cure rate) induced a Th1/Th2 response. Five Arm 2 patients relapsed and showed lower IFN-γ, TNF and IL-1ß concentrations at D0 than non-relapsers in this Arm. In patients with low-IFN-γ-production at D0, Arm 1 treatment led to a better host immune response and clinical outcome than Arm 2 treatment. CONCLUSIONS: A Th1/Th2/Th17 response was associated with a higher cure rate. Patients with low IFN-γ, TNF and IL-1ß before treatment are more likely to relapse if they undergo Arm 2-type treatment. Determining IFN-γ, TNF and IL-10 levels prior to treatment could help predict patients at higher risk of relapse/recovery from PKDL. TRIAL REGISTRATION: ClinicalTrials.gov NCT03399955, Registered 17 January 2018, https://clinicaltrials.gov/study/ NCT03399955.

Deciphering Molecular Mechanisms of Cutaneous Leishmaniasis, Pathogenesis and Drug Repurposing through Systems Biology

Background: Cutaneous leishmaniasis (CL) is a major health problem caused by an intracellular pathogen of the genus Leishmania. CL results in morphologically distinct skin injuries, ranging from nodules to plaques and ulcers, which persist as a recuperating incessant injury depending on the type of contaminating parasite. There is still no effective treatment to reduce the skin lesions in patients infected with CL. The aim of this study was to develop strategies to treat skin lesions in CL patients. Methods: We retrieved the transcriptomic data of skin lesions from patients with CL and normal skin from the gene Expression Omnibus (GEO) database. The protein-protein interaction network (PPIN) was constructed using the STRING database and Cytoscape v3.10.1 software. Critical genes were identified by topological network analysis and cluster detection. Finally, gene ontology and repurposing drugs for critical genes were determined. Results: CD8A, IFNG, IL-6, PTPRC, CCR7, TLR2, GSTA5, CYBB, IL-12RB2, ITGB2, FCGR3A, CTLA4, and IFNG were identified as the critical genes in PPIN and subnetworks. Enrichment analysis revealed that T-cell receptor signaling, toll-like receptor signaling, cytokine-cytokine receptor interaction, graft-versus-host disease, leishmaniasis, chemokine signaling, primary immunodeficiency, and Th17 cell differentiation were the major pathways associated with critical genes. The drug repurposing results identified cyclosporine, rituximab, infliximab, blinatumomab, and methylprednisolone as candidates for treatment of CL. Conclusion: After validating our model with available experimental data, we found that critical molecules and drug candidates play a crucial role in the treatment of skin lesions caused by Leishmania in prospective studies.

Case Report: Cutaneous Leishmaniasis: A Case Series with Intralesional Treatment in Northeast Brazil.

In 2022, the Pan American Health Organization recommended the intralesional application (IL) of pentavalent antimonials in adult patients with localized cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis. Other guidelines differ from that recommendation, considering that infections caused by a Leishmania species that can be associated with increased risk for mucosal leishmaniasis, in particular L. (V.) braziliensis, should not be eligible for intralesional treatment. This was a prospective interventional study carried out with eight patients diagnosed with CL residing in northeast Brazil during the period from 2019 to 2022. To our knowledge, this is the first prospective study on the subject conducted in the northeast region, which has the second-highest number of cases in the country. In our sample, clinical cure was achieved with the use of intralesional treatment in all cases, and there were no serious adverse events or mucosal involvement during the 1-year follow-up period. We emphasize the importance of using the right criteria for choosing this therapeutic modality and highlight the advantages of intralesional treatment due to the lower risk of adverse events and cost reduction to health services.

Severe Inflammatory and Disseminated Cutaneous Leishmaniasis in a Pregnant Woman: A Case Report from Portoviejo, Ecuador.

BACKGROUND Leishmaniasis is a zoonosis with worldwide prevalence that causes dermal lesions and can be serious in humans. This report presents a case of cutaneous leishmaniasis (CL) that was apparently associated with a zoonotic transmission in a peri-urban area of the city of Portoviejo, Ecuador, close to mountainous and forested sites. CASE REPORT For 37 years, we have studied transmission of leishmaniasis in Ecuador, and have seen a wide variety of clinical presentations of the disease caused by different strains of the parasite Leishmania in patients, including pregnant women, without marked difference among them. CL without complications causes painless lesions of different clinical aspect. The present study reports a case of a 25-year-old woman presenting with severely inflamed, disseminated, and painful lesions of CL. The patient was not given antimonial treatment; however, local cryotherapy was given, together with topical anti-inflammatory and antibiotic ointment. All the lesions were observed to heal, and no amastigotes were found in smear stains after clinical healing. Since there was no reactivation after 1.5 years of follow-up, conventional antileishmanial treatment with meglumine antimoniate was not given to the patient. CONCLUSIONS This report shows the importance of a properly done epidemiological and clinical presumtive diagnosis, followed by parasitological confirmation, and the benefit of using an alternative treatment for vulnerable patients, such as this pregnant woman, for whom the therapy with pentavalent antimonials is not indicated. All observed lesions healed and no amastigotes were found in the smears after clinical healing.