Successful treatment of diffuse cutaneous leishmaniasis caused by Leishmania amazonensis

Abstract Diffuse cutaneous leishmaniasis is a rare universal disease associated with an inadequate host cell immune response, caused by different species: infantum, aethiopica, major, mexicana, and others, which presents the challenge of a poor therapeutic response. In Brazil, it is caused by L. amazonensis. A case confirmed by histopathology with an abundance of vacuolated macrophages full of amastigotes and lymphocyte scarcity, identified by RFLP-ITS1PCR and in vitro decrease and exhaustion of the host cell immune response to L. amazonensis antigen, was treated early (3 months after the onset) with Glucantime (2 months) and allopurinol (29 months) with clinical cure, after a follow-up for 30 months after treatment.

Leprosy detection rate in patients under immunosuppression for the treatment of dermatological, rheumatological, and gastroenterological diseases: a systematic review of the literature and meta-analysis.

BACKGROUND: Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases. METHODS: We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression. RESULTS: The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000-0.00266; I2 = 0%, p = 0.55). CONCLUSION: Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions. TRIAL REGISTRATION: This review is registered in PROSPERO with the registry number CRD42018116275 .

A retrospective cohort study of the effectiveness and adverse events of intralesional pentavalent antimonials in the treatment of cutaneous leishmaniasis.

INTRODUCTION: The standard therapy for American cutaneous leishmaniasis (ACL) is intravenous meglumine antimoniate (IV-MA). However, treatment interruptions due to adverse events (AEs) and non-adherence are frequent. Consequently, intralesional MA (IL-MA) was proposed. OBJECTIVE: This study examined the effectiveness of and AEs associated with IL-MA. METHODS: We performed a retrospective cohort study of 240 patients with ACL. We excluded patients with mucous lesions and disseminated leishmaniasis and those who received treatment in the previous 6 months. We considered protocol treatments as the main risk factors. IL-MA was performed using a subcutaneous injection of MA in a volume sufficient to elevate the lesion base (approximately 1 mL/cm2 of lesion area) once weekly for 1-8 weeks. IV-MA was performed via intravenous injections of MA at a dosage of 10-20 mg Sb5+/kg/day for 20 days. The primary outcome was defined as a lesion cure 3 months after treatment, and AEs were secondary outcomes. RESULTS: Seventy-three patients were included. The IL-MA group consisted of 21 patients, and the IV-MA group consisted of 52 patients. The IL-MA group was older, had more comorbidities and more previous unsuccessful treatment of ACL. The antimonial dose was significantly lower in this group. The cure rate for IL-MA was 66.7%, which was lower than that in the IV-MA group (relative risk (RR) = 0.68, 95% CI: 0.50-0.92, p < 0.001), while the rate of AEs was similar. Female sex (RR = 1.16, 95% CI: 1.02-1.33), lesion diameter ≤1 cm (RR = 1.25, 95% CI: 1.00-1.56) and treatment with IV-MA (RR = 1.43, 95% CI: 1.06-1.93) were independently associated with achieving a cure. Comorbidities (RR = 1.7, 95% CI: 1.06-2.98) were independently associated with AEs. CONCLUSIONS: Patients of IL-MA group were older, had more comorbidities and more previous unsuccessful treatment of ACL. Nevertheless, IL-MA had a cure rate of 66.7%, and it was useful in this context. A prospective randomized trial is recommended.

The interference of polypharmacy and the importance of clinical pharmacy advice in the treatment of leprosy: a case-control study.

INTRODUCTION: Although supervised doses are essential for reducing leprosy treatment failure, the impact of specific drug interactions has rarely been assessed. This study aimed to estimate the risk of leprosy treatment suspension in patients receiving polypharmacy. METHODS We performed this case-control study in which the primary outcome was defined as the need to discontinue multibacillary leprosy treatment for at least one supervised dose, and the main risk factor was the detection of polypharmacy. Multivariate analysis by logistic regression was used for calculating odds ratio (OR). RESULTS: This study included 103 patients, of whom 43 needed to discontinue leprosy treatment (hemolysis = 26, hepatitis = 2, hemolysis associated with hepatitis = 6, and suspected treatment resistance = 9) and the rest did not. The severity of drug interactions had no effect on treatment discontinuation. Patients who used five or more drugs in addition to leprosy treatment had almost a 4-fold greater risk of treatment suspension (OR, 3.88; 95% confidence interval: 1.79-9.12; p < 0.001). The number of drugs used also positively influenced the occurrence of hemolysis (p < 0.001). No patient presented evidence of molecular resistance to rifampicin, dapsone, or ofloxacin treatment, as evidenced by genetic sequencing detection of rpoB, folp1, and gyrA mutations. CONCLUSIONS: Polypharmacy has deleterious effects on the already difficult-to-adhere-to treatment of leprosy and polypharmacy induces hemolysis. Additional measures must be taken to avoid the undesirable effects of inadequate polypharmacy.

The accuracy of the Montenegro skin test for leishmaniasis in PCR-negative patients

Abstract INTRODUCTION: As highly specific molecular biology-based techniques may not be sensitive enough for the diagnosis of American tegumentary leishmaniasis (ATL), clinicians frequently rely on immunological tests before treatment initiation. Hence, the correct combination of diagnostic tests is imperative for ATL diagnosis. We aimed to evaluate the accuracy of the Montenegro (Leishmanin) skin test (MST) in polymerase chain reaction (PCR)-negative patients to accurately detect ATL. METHODS: Patients with a clinical picture compatible with ATL were divided into ATL (confirmed by lesion smear, culture indirect immunofluorescence, and/or histopathology) and no-ATL (diseases that can mimic leishmaniasis) groups. Conventional PCR for the minicircle kDNA of Leishmania was performed, and the MST was carried out for PCR-negative patients. RESULTS: Ninety-nine patients were included in this study, including 79 diagnosed with ATL (6 with mucocutaneous leishmaniasis) and 20 without ATL (no-ATL group). The MST showed a high sensitivity of 90.0% (95% confidence interval [CI] = 69.90-97.21) in PCR-negative patients that was 10% higher than the sensitivity reported in PCR-positive population (79.66%; 95% CI = 67.73-87.96). CONCLUSIONS: One of the most important reasons for PCR negativity among patients with active ATL is the presence of a strong cellular immunological response, especially in chronic and mucocutaneous leishmaniasis. This reinforces the considerable utility of the tests that detect cellular responses against Leishmania antigens such as the MST in PCR-negative patients when the performance in screening situations is questionable.

The interference of polypharmacy and the importance of clinical pharmacy advice in the treatment of leprosy: a case-control study

Abstract INTRODUCTION: Although supervised doses are essential for reducing leprosy treatment failure, the impact of specific drug interactions has rarely been assessed. This study aimed to estimate the risk of leprosy treatment suspension in patients receiving polypharmacy. METHODS We performed this case-control study in which the primary outcome was defined as the need to discontinue multibacillary leprosy treatment for at least one supervised dose, and the main risk factor was the detection of polypharmacy. Multivariate analysis by logistic regression was used for calculating odds ratio (OR). RESULTS: This study included 103 patients, of whom 43 needed to discontinue leprosy treatment (hemolysis = 26, hepatitis = 2, hemolysis associated with hepatitis = 6, and suspected treatment resistance = 9) and the rest did not. The severity of drug interactions had no effect on treatment discontinuation. Patients who used five or more drugs in addition to leprosy treatment had almost a 4-fold greater risk of treatment suspension (OR, 3.88; 95% confidence interval: 1.79-9.12; p < 0.001). The number of drugs used also positively influenced the occurrence of hemolysis (p < 0.001). No patient presented evidence of molecular resistance to rifampicin, dapsone, or ofloxacin treatment, as evidenced by genetic sequencing detection of rpoB, folp1, and gyrA mutations. CONCLUSIONS: Polypharmacy has deleterious effects on the already difficult-to-adhere-to treatment of leprosy and polypharmacy induces hemolysis. Additional measures must be taken to avoid the undesirable effects of inadequate polypharmacy.

A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis

Abstract INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

PD-L1 May Mediate T-Cell Exhaustion in a Case of Early Diffuse Leishmaniasis Caused by Leishmania (L.) amazonensis.

Introduction: Diffuse cutaneous leishmaniasis (DCL) is a rare disease form associated with Leishmania (L.) amazonensis in South America. It represents the "anergic" pole of American Tegumentary Leishmaniasis, and the explanation for its resistance to treatment remains elusive. We aimed to study some possible immunological mechanisms involved in the poor DCL treatment response by evaluating some cell surface molecules obtained from a patient with DCL by flow cytometry. Case presentation: A 65-year-old DCL patient who initially failed to respond to the standard treatment for the disease showed vacuolated macrophages filled with amastigotes in lesion biopsy, and L. (L.) amazonensis was identified through ITS1PCR amplification. The Leishmania skin test and indirect immunofluorescence analysis revealed negative results. Peripheral blood from the patient was collected after a few months of treatment, when the patient presented with no lesion. Peripheral blood mononuclear cells were analyzed ex vivo and in vitro after 48 h of stimulation with soluble L. (L.) amazonensis antigen (SLA). Cell death, surface molecules, and intracellular molecules, such as IFN-γ and granzyme B, were analyzed in the cells using flow cytometry. Analysis of the surface markers showed an increased expression of the inhibitory molecule programmed death ligand 1 (PD-L1) in the monocytes restimulated with SLA (approximately 65%), whereas the negative controls were 35% positive for PD-L1. Conversely, compared with the negative controls, we observed a decrease in CD4+IFN-γ+ T cells (8.32 versus 1.7%) and CD8+IFN-γ+ T cells (14% versus 1%). We also observed a relevant decrease in the granzyme B levels in the CD8+ T cells, from 31% in the negative controls to 5% after SLA restimulation. Conclusion: The dysfunctional activation of PD-L1 inhibitory pathway after Leishmania antigen stimulation and reduced levels of IFN-gamma and granzyme B-producing cells could be closely related to unresponssiveness to standard drug treatment of DCL patient.

American cutaneous leishmaniasis triggered by electrocoagulation.

Cutaneous leishmaniasis is usually transmitted by infected phlebotomine sand fly bites that initiate local cutaneous lesions. Few reports in the literature describe other modes of transmission. We report a case of a previously healthy 59-year-old woman who underwent electrocoagulation to remove seborrheic keratosis confirmed by dermatoscopy. Three months later, a skin fragment tested positive for Leishmania culture; the parasite was identified as L. (V.) braziliensis. Trauma may generate inflammatory cascades that favor Leishmania growth and lesion formation in previously infected patients. American cutaneous leishmaniasis is a dynamic disease with unclear pathophysiology because of continually changing environments, demographics, and human behaviors.

American cutaneous leishmaniasis triggered by electrocoagulation

Abstract Cutaneous leishmaniasis is usually transmitted by infected phlebotomine sand fly bites that initiate local cutaneous lesions. Few reports in the literature describe other modes of transmission. We report a case of a previously healthy 59-year-old woman who underwent electrocoagulation to remove seborrheic keratosis confirmed by dermatoscopy. Three months later, a skin fragment tested positive for Leishmania culture; the parasite was identified as L. (V.) braziliensis. Trauma may generate inflammatory cascades that favor Leishmania growth and lesion formation in previously infected patients. American cutaneous leishmaniasis is a dynamic disease with unclear pathophysiology because of continually changing environments, demographics, and human behaviors.

Field Validation of SYBR Green- and TaqMan-Based Real-Time PCR Using Biopsy and Swab Samples To Diagnose American Tegumentary Leishmaniasis in an Area Where Leishmania (Viannia) braziliensis Is Endemic.

The precise diagnosis of American tegumentary leishmaniasis (ATL) is an essential task due to the disease's associated morbidity. A noninvasive, extremely sensitive, and highly specific exam is critical, particularly for mucosal leishmaniasis (ML), in which a low parasite quantity is expected. We aimed to compare the diagnostic accuracy of swab and biopsy sample analysis using SYBR Green- and TaqMan-based real-time PCR (qPCR) assays with that of a composite reference standard consisting of the Montenegro skin test, serology, histopathology, smears, culture, and conventional PCR. In total, 55 patients with ATL (ML, 18 patients; cutaneous leishmaniasis [CL], 37 patients) and 36 patients without ATL were studied. qPCR analysis of swabs was more accurate when using SYBR Green (87.88%; 95% confidence interval [CI], 77.86 to 93.73 patients) than when using TaqMan (78.79%; 95% CI, 67.49 to 86.92%) (P = 0.031). SYBR Green (84.72%; 95% CI, 74.68 to 91.25%) was also more accurate than TaqMan (73.61%; 95% CI, 62.42 to 82.41%) for biopsy samples (P = 0.008). All qPCR methods were 100% specific. Swabs and biopsy specimens had similar sensitivity when using the same chemistry (P = 0.125 for SYBR Green and P = 0.625 for TaqMan). Moreover, qPCR achieved better performance than most existing techniques used for the diagnosis of ATL and also detected the Leishmania parasite in a greater proportion of patients than the associated histopathology, smear, culture, and conventional PCR techniques did. Swabs therefore represent a useful diagnostic tool because they not only are noninvasive but also can achieve an accuracy similar to that of biopsy samples. The high accuracy of SYBR Green-based qPCR may also reduce the requirement for associated parasitological tests for ATL diagnosis.

Field validation of a Leishmania (Leishmania) mexicana exo-antigens ELISA for diagnosing tegumentary leishmaniasis in regions of Leishmania (Viannia) predominance

Background: Several tests are performed to obtain better accuracy when diagnosing American tegumentary leishmaniasis (ATL). It is believed that antigens released via secretion, excretion and metabolism are more specific than are antigens released by the lysis of Leishmania parasites. Such antigens are known as exo-antigens (exo-Ag) and are formed from products released by cultured parasites in a way that is similar to that in which they cause infections in hosts. Objective: We attempted to validate a Leishmania mexicana ELISA exo-Ag for ATL diagnosis in Midwestern Brazil. Methods: A total of 281 patients were included in the study. We analysed pre-treatment blood from 98 ATL patients; out of those, 85.7% and 14.3% had cutaneous and mucosal forms, respectively. Results: The exo-Ag accuracy was 83.99% (95% CI = 79.24-87.81) with a sensitivity value of 90.82% (95% CI = 83.46-95.09) and an overall specificity value of 80.33% (95% CI = 73.97-85.44). The positive predictive value and negative predictive value were 71.20% (95% CI = 62.72-78.41) and 94.23% (95% CI = 89.40-96.94), respectively. Among healthy controls, exo-Ag had a specificity of 91.25% (95% CI = 83.02-95.70); additionally, the test had specificity rates of 66.67% (95% CI = 46.71-82.03) in Chagas disease patients, 60.61% (95% CI = 43.68-75.32) in patients with rheumatic diseases, 76.92% (95% CI = 49.74-91.82) in pemphigus foliaceus patients, 87.50% (95% CI = 52.91-97.76) in leprosy patients, 87.50% (95% CI = 63.98-96.50) in VRDL-positive patients, and 77.78 (95% CI = 45.26-93.68) in deep mycosis patients. Conclusion: Based on the indicators of validity, we conclude that the results obtained in this study enable the recommendation of the exo-Ag ELISA for ATL diagnosis once it presented a reasonable accuracy compared to classical methods. Cost evaluations are necessary to completely define the role of this technique in large scale. .

Accuracy of mucocutaneous leishmaniasis diagnosis using polymerase chain reaction: systematic literature review and meta-analysis.

The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of a gold standard. An accurate diagnosis is essential because of the high toxicity of the medications for the disease. This study aimed to assess the ability of polymerase chain reaction (PCR) to identify MCL and to compare these results with clinical research recently published by the authors. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement was performed using comprehensive search criteria and communication with the authors. A meta-analysis considering the estimates of the univariate and bivariate models was performed. Specificity near 100% was common among the papers. The primary reason for accuracy differences was sensitivity. The meta-analysis, which was only possible for PCR samples of lesion fragments, revealed a sensitivity of 71% [95% confidence interval (CI) = 0.59; 0.81] and a specificity of 93% (95% CI = 0.83; 0.98) in the bivariate model. The search for measures that could increase the sensitivity of PCR should be encouraged. The quality of the collected material and the optimisation of the amplification of genetic material should be prioritised.

Accuracy of mucocutaneous leishmaniasis diagnosis using polymerase chain reaction: systematic literature review and meta-analysis

The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of a gold standard. An accurate diagnosis is essential because of the high toxicity of the medications for the disease. This study aimed to assess the ability of polymerase chain reaction (PCR) to identify MCL and to compare these results with clinical research recently published by the authors. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement was performed using comprehensive search criteria and communication with the authors. A meta-analysis considering the estimates of the univariate and bivariate models was performed. Specificity near 100% was common among the papers. The primary reason for accuracy differences was sensitivity. The meta-analysis, which was only possible for PCR samples of lesion fragments, revealed a sensitivity of 71% [95% confidence interval (CI) = 0.59; 0.81] and a specificity of 93% (95% CI = 0.83; 0.98) in the bivariate model. The search for measures that could increase the sensitivity of PCR should be encouraged. The quality of the collected material and the optimisation of the amplification of genetic material should be prioritised.

Complementary exams in the diagnosis of american tegumentary leishmaniasis

The diagnosis of American Tegumentary Leishmaniasis is a difficult but essential task when considering the high toxicity profile of the drugs available. Since the discovery of its etiologic agent, numerous diagnostic tests have been developed. None of the tests available today can be considered as the gold standard, since they do not add enough accuracy for the disease detection. Good epidemiological and clinical knowledge of the disease are fundamental precepts of the dermatology practice and precede the rational use of existing diagnostic tests. In this article we aim, through extensive literature review, to recall fundamental concepts of any diagnostic test. Subsequently, based on this information, we will weave important comments about the characteristics of existing diagnostic tests, including immunological tests such as Montenegro's skin test, serology and detection of parasites by direct examination, culture or histopathology. Finally we will discuss the new technologies and options for the diagnosis of Cutaneous Leishmaniasis. The molecular biology technique is considered a promising tool, promoting the rapid identification of the species involved. We also aim to educate dermatologists about a disease with high morbidity and assist in its difficult recognition.

Avaliação do eletrocardiograma de pacientes com leishmaniose tegumentar americana tratados com antimonial pentavalente (glucantime) / Electrocardiographic assessment of patients with american cutaneous leihmaniasis treated with pentavalent antimonial (glucantime)

Os antimoniais pentavalentes (Antimoniato de N-metilglumina – Glucantime®) são fármacosde primeira escolha no tratamento da leishmaniose tegumentar americana (LTA). Apresentama cardiotoxicidade como importante efeito adverso e é evidenciada por alterações noeletrocardiograma de repouso (ECG). O alargamento do intervalo QT corrigido (QTc) é a principale potencialmente mais grave delas. O presente estudo teve como objetivo avaliar as alteraçõesno ECG e sua frequência nos pacientes com LTA tratados com Glucantime® no Serviço deDermatologia de nossa instituição. Para isso, um cardiologista avaliou os ECGs de 15 pacientes entre 18 e 59 anos de idade diagnosticados com LTA. Os exames foram realizados imediatamenteantes, no 7º, 14º e 21º dias do tratamento. Desses pacientes, cinco (33 por cento) desenvolveram algumdistúrbio no eletrocardiograma, cuja frequência foi diretamente proporcional ao tempo de uso dofármaco. Bradicardia sinusal nova foi o mais comum (5/15 pacientes), seguida por alargamento dointervalo QTc (2/15 pacientes, os quais também apresentaram bradicardia). Não houve registro decomplicações graves e nenhum paciente desenvolveu sintomatologia cardiovascular. Em apenasum caso foi necessária a interrupção do tratamento. A frequência de alterações no ECG observada écompatível com a relatada por estudos anteriores sobre o tema. Concluímos que a cardiotoxicidadedos antimoniais pentavalentes se manifestou de forma insidiosa, cumulativa, em proporçãocompatível com os relatos da literatura e sem repercussões clínicas.

The pentavalent antimonial compounds (Meglumine Antimoniate – Glucantime®) are thecornerstone for the treatment of American Cutaneous Leishmaniasis (ACL). Cardiotoxicity is theirprincipal adverse effect, which becomes evident as abnormalities in the resting Electrocardiogram(ECG), the prolongation of the corrected QT interval (QTc) being the most important and potentiallyhazardous of them. The purpose of this study was to evaluate the disturbances on ECG and theirfrequency in patients diagnosed with ACL and treated with Glucantime® at our Institution. Fifteenpatients between 18 and 59 years had their ECGs assessed by a senior cardiologist. The tests wereperformed prior to treatment, as well as on its 7th, 14th and 21st day. Five patients (33 percent) developed anabnormality not previously observed, and frequency correlated with the duration of the treatment.The most common was sinus bradycardia (5 of 15 patients), followed by prolongation of the QTcinterval (2 of 15 patients; both also had sinus bradycardia). No major cardiovascular symptomsor complications were reported. Only one patient had to interrupt the treatment. This proportionof ECG disturbances is consistent with previous studies on the subject. We conclude that thecardiotoxicity of the pentavalent antimonial drugs occurred insidiously in a percentage of patientscompatible with the literature, and was not associated with major clinical complications.

Leishmanicidal activity of amphotericin B encapsulated in PLGA-DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice.

The major goal of this work was to design a new nanoparticle drug delivery system for desoxycholate amphotericin B (D-AMB), based on controlled particle size, looking for the most successful release of the active agents in order to achieve the best site-specific action of the drug at the therapeutically optimal rate and dose regimen. For this, AMB nanoencapsulated in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles (Nano-D-AMB) has been developed, and its efficacy was evaluated in the treatment of experimental cutaneous leishmaniasis in C57BL/6 mice, to test if our nano-drug delivery system could favor the reduction of the dose frequency required to achieve the same therapeutic level of free D-AMB, and so, an extended dosing interval. Magnetic citrate-coated maghemite nanoparticles were added to this nanosystem (Nano-D-AMB-MG) aiming to increase controlled release of AMB by magnetohyperthermia. Female mice (N=6/group) were infected intradermally in the right footpad with promastigotes of Leishmania amazonensis in the metacyclic phase, receiving the following intraperitoneal treatments: 1% PBS for 10 consecutive days; D-AMB at 2 mg/kg/day for 10 days (totalizing 20 mg/kg/animal); Nano-D-AMB and Nano-D-AMB-MG at 6 mg/kg on the 1st, 4th and 7th days and at 2 mg/kg on the 10th day, also totalizing 20 mg/kg/animal by treatment end. The Nano-D-AMB-MG group was submitted to an AC magnetic field, allowing the induction of magnetohyperthermia. The evaluations were through paw diameter measurements; parasite number and cell viability were investigated by limiting dilution assay. D-AMB-coated PLGA-DMSA nanoparticles showed the same efficacy as free D-AMB to reduce paw diameter; however, the Nano-D-AMB treatment also promoted a significantly greater reduction in parasite number and cell viability compared with free D-AMB. The nano-drug AMB delivery system appeared more effective than free D-AMB therapy to reduce the dose frequency required to achieve the same therapeutic level. It thus favors a longer interval between doses, as expected with development of a new nano drug delivery system, and may be useful in the treatment of many different pathologies, from cancer to neurodegenerative diseases.

Recurrent cutaneous leishmaniasis / Leishmaniose recidiva cútis

We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because of the challenges imposed by treatment.

Paciente do sexo masculino, 18 anos. Dois anos após tratamento insuficiente para leishmaniose tegumentar americana, apresentou, na mesma localização, lesão formada por cicatriz atrófica central e nódulos verrucosos na periferia. Era imunocompetente, hígido e negava qualquer trauma local. O diagnóstico de leishmaniose recidiva cutis foi feito através de cultura do aspirado da lesão. Realizou tratamento com N-metilglucamina (20mgSbV/kg/dia) associado à pentoxifilina (1200mg/dia) durante 30 dias alcançando cura clínica. Os casos semelhantes requerem atenção diferenciada pela dificuldade ao tratamento.