Topical application of ozonated sunflower oil accelerates the healing of lesions of cutaneous leishmaniasis in mice under meglumine antimoniate treatment.

Besides being scarce, the drugs available for treating cutaneous leishmaniasis have many adverse effects. Ozone is an option to enhance the standard treatment due to the wound-healing activity reported in the literature. In this study, we evaluated the efficiency of ozonated sunflower oil as an adjuvant in treating cutaneous lesions caused by Leishmania amazonensis. BALB/c mice were infected with L. amazonensis, and after the lesions appeared, they were treated in four different schedules using the drug treatment with meglumine antimoniate (Glucantime®), with or without ozonated oil. After thirty days of treatment, the lesions' thickness and their parasitic burden, blood leukocytes, production of NO and cytokines from peritoneal macrophages and lymph node cells were analyzed. The group treated with ozonated oil plus meglumine antimoniate showed the best performance, improving the lesion significantly. The parasitic burden showed that ozonated oil enhanced the leishmanicidal activity of the treatment, eliminating the parasites in the lesion. Besides, a decrease in the TNF levels from peritoneal macrophages and blood leukocytes demonstrated an immunomodulatory action of ozone in the ozonated oil-treated animals compared to the untreated group. Thus, ozonated sunflower oil therapy has been shown as an adjuvant in treating Leishmania lesions since this treatment enhanced the leishmanicidal and wound healing effects of meglumine antimoniate.

Comparison of Meglumine Antimoniate and Miltefosine in Cutaneous Leishmaniasis.

OBJECTIVE: To compare the efficacy and safety of meglumine antimoniate and miltefosine in the treatment of cutaneous leishmaniasis in Pakistan. STUDY DESIGN: Randomised-controlled trial. Place and Duration of the Study: Department of Dermatology, Combined Military Hospital, Lahore and Peshawar, from January to December 2021. METHODOLOGY: Smear positive and/or skin biopsy-confirmed cases of cutaneous leishmaniasis in adult males aged between 18-60 years were enrolled after receiving informed consent. Patients were randomly divided into Group A and Group B by lottery method. Group A received intramuscular meglumine antimoniate 15-20mg/kg/day, and Group B received oral miltefosine 50 mg thrice a day for a duration of 28 days. Data were analysed by SPSS 22. Effectiveness and safety of therapeutic agents were calculated by Independent t-test and p-value of 0.05 or less was taken as significant. RESULTS: Sixty-six patients, 33 in each group, participated in the study. Total number of cutaneous leishmaniasis lesions were 77 in Group A and 76 in Group B. The duration of lesions was 3.5 months in Group A and 3.2 months in Group B. Treatment response, in terms of complete or near complete resolution of lesions, was significantly higher in Group A as compared to Group B (p = 0.011). Both therapeutic agents had considerable side-effects with more patients withdrawn from Group A as compared to Group B (p = 0.010). CONCLUSION: Intra-muscular meglumine antimoniate was more effective in comparison to oral miltefosine in the treatment of cutaneous leishmaniasis. However, efficacy of meglumine antimoniate is mired by its side-effect profile. KEY WORDS: Cutaneous leishmaniasis, Meglumine antimoniate, Miltefosine, Efficacy, Side-effects, Adverse effects, Safety, Treatment, Old world cutaneous leishmaniasis.

Immunosuppressants alter the immune response associated with Glucantime® treatment for Leishmania infantum infection in a mouse model.

Background: Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop. Objectives: To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses. Results: Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment. Conclusion: The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.

Survival time and prognostic factors in canine leishmaniosis in a non-endemic country treated with a two-phase protocol including initial allopurinol monotherapy.

BACKGROUND: Leishmania infantum is an intracellular protozoan parasite which is endemic in countries of the Mediterranean Basin. Leishmaniosis is increasingly diagnosed in non-endemic areas due to the relocation of dogs from endemic areas and the travel of dogs to and from these areas. The prognosis of leishmaniosis in these dogs may differ from that of those in endemic areas. The aims of this study were (1) to determine the Kaplan-Meier estimated survival time for dogs with leishmaniosis in the Netherlands (a non-endemic country), (2) to determine if clinicopathological variables at the time of diagnosis predicted the survival of these dogs, and (3) to evaluate the effect of a two-phase therapy protocol of allopurinol monotherapy followed by meglumine antimoniate and/or miltefosine in the case of incomplete remission or relapse. METHODS: The database of the Department of Clinical Sciences of Companion Animals of the Faculty of Veterinary Medicine, Utrecht University was investigated for leishmaniosis patients. Patient records were reviewed for signalment and clinicopathological data at the time of diagnosis. Only treatment-naive patients were included. Follow-up was performed during the study by phone contact and included treatment received and date and cause of death. Univariate analysis was performed using the Cox proportional hazards regression model. RESULTS: The estimated median Kaplan-Meier survival time was 6.4 years. In the univariate analysis, increases in monocyte, plasma urea and creatinine concentrations, and urine protein to creatinine ratio were all significantly associated with decreased survival time. The majority of patients only received allopurinol monotherapy. CONCLUSIONS: Canine leishmaniosis patients in our study population in the Netherlands, which is non-endemic for the disease, had an estimated Kaplan-Meier median survival time of 6.4 years, which is comparable to the outcome of other reported therapy protocols. Increased plasma urea and creatinine concentrations and monocyte concentration were statistically associated with an increased risk of death. We conclude that initial allopurinol monotherapy for 3 months should be effective in more than half of canine leishmaniosis cases, provided there is adequate follow-up, and that meglumine antimoniate or miltefosine therapy should be started as the second phase of the protocol in cases where remission is incomplete or there is a relapse.

Clinicopathological characteristics of cutaneous and mucocutaneous leishmaniasis in patients treated with TNF-α inhibitors.

BACKGROUND AND OBJECTIVES: The increasing use of biologics in the treatment of inflammatory diseases has led to more cases of leishmaniasis in patients subjected to iatrogenic immunosuppression. The main objective was to describe the characteristics of the patients with cutaneous (CL) or mucocutaneous (MCL) leishmaniasis who were receiving a biological therapy at the time of diagnosis. PATIENTS AND METHODS: A multicenter retrospective study was design based on a cohort of patients diagnosed with CL or MCL. All patients who were being treated with biologicals were included. For each case, two matched non-exposed patients were included for comparison. RESULTS: 38 patients were diagnosed with CL or MCL while being treated with tumor necrosis factor alpha (TNF-α) inhibitors. Leishmaniasis presented more frequently as a plaque (58.3%) with a larger median lesion size (2.5 cm), ulceration (92.1%), and required a greater median number of intralesional meglumine antimoniate infiltrations (3 doses) (P < 0.05) than in non-exposed patients. We found no systemic involvement in patients being treated with anti-TNF-α. We did not find differences regarding the treatment characteristics whether biologic therapy was modified or not. CONCLUSIONS: Although management should be individualized, maintenance of biologic therapy does not seem to interfere with treatment of CL or MCL.

Treatment of Cutaneous Leishmaniasis with Allopurinol Plus Itraconazole in Iran.

Cutaneous leishmaniasis (CL) is a serious tropical disease and a neglected health challenge in Iran. Although limited data are available regarding anthroponotic CL, cases resistant to meglumine antimoniate (Glucantime) are increasingly being reported. Via an open-label noncontrolled case series, allopurinol (10 mg/kg/day) plus itraconazole (3-4 mg/kg/day) were orally administered for 1 month to 27 patients (56 lesions) with anthroponotic CL, most of whom were resistant to Glucantime. A mean lesion size of 3.5 ± 1.9 cm at baseline was reduced to 0.6 ± 1.0 after 1 month of treatment. Excellent treatment response was observed in 85.7% of lesions after 1 month. Recurrence only occurred in one patient in the 3-month follow-up session. This study presents preliminary evidence that oral allopurinol plus itraconazole could be an effective treatment in patients with anthroponotic CL.

Low doses of 3-phenyl-lawsone or meglumine antimoniate delivery by tattooing route are successful in reducing parasite load in cutaneous lesions of Leishmania (Viannia) braziliensis-infected hamsters.

Current therapeutic ways adopted for the treatment of leishmaniasis are toxic and expensive including parasite resistance is a growing problem. Given this scenario, it is urgent to explore treatment alternatives for leishmaniasis. The aim of this study was to evaluate the effect of 3-phenyl-lawsone (3-PL) naphthoquinone on Leishmania (Viannia) braziliensis infection, both in vitro and in vivo, using two local routes of administration: subcutaneous (higher dose) and tattoo (lower dose). In vitro 3-PL showed low toxicity for macrophages (CC50 >3200 µM/48h) and activity against intracellular amastigotes (IC50 = 193 ± 19 µM/48h) and promastigotes (IC50 = 116 ± 26 µM/72h), in which induced increased ROS generation. Additionally, 3-PL up-regulated the production of cytokines such as tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-10 in infected macrophages. However, the anti-amastigote action was independent of nitric oxide production. Treatment of hamsters infected with L. (V.) braziliensis from one week after infection with 3-PL by subcutaneous (25 µg/Kg) or tattooing (2.5 µg/Kg) route, during 3 weeks (3 times/week) or 2 weeks (2 times/week) significantly decreased the parasite load (p<0.001) in the lesion. The reduction of parasite load by 3-PL treatment was comparable to reference drug meglumine antimoniate administered by the same routes (subcutaneous 1mg/Kg and tattoo 0.1mg/Kg). In addition, treatment started from five weeks after infection with 3-PL per tattoo also decreased the parasite load. These results show the anti-leishmanial effect of 3-PL against L. (V.) braziliensis and its efficacy by subcutaneous (higher dose) and tattoo (lower dose) routes. In addition, this study shows that drug delivery by tattooing the lesion allows the use of lower doses than the conventional subcutaneous route, which may support the development of a new therapeutic strategy that can be adopted for leishmaniasis.

Mucosal Leishmaniasis of the lip: Report of an Exuberant case in a Young man.

BACKGROUND: Leishmaniasis is a tropical disease caused by protozoan parasites of the genus Leishmania. Mucosal leishmaniasis has been described as secondary to the cutaneous form; however, isolated mucosal involvement can also occur. Specifically, mucosal leishmaniasis of the lip is poorly described and its diagnosis challenges clinicians. METHODS: We herein report a case of mucosal leishmaniasis affecting the lower lip without cutaneous involvement in a 20-year-old Venezuelan man. The patient had no relevant past medical history. Clinically, a mass-like lesion with ulcerations and crusts was observed. RESULTS: Microscopically, the lesion was composed of granulomatous inflammation along with macrophages containing intracytoplasmic inclusions similar to round-shaped Leishmania. The species Leishmania (Viannia) braziliensis was confirmed. Treatment with meglumine antimonate was effective. The lesion healed satisfactorily, and no side effects or recurrences were observed. CONCLUSION: Clinicians should be aware of isolated forms of mucosal leishmaniasis of the lip, even in cases where the cutaneous lesion is undetected or clinically manifests as self-limiting. Knowing the endemic areas in the scenario of the dynamics of the ecoepidemiology of leishmaniasis is also essential for surveillance and counselling of the population.

Comparison Of Oral Dapsone With Intramuscular Meglumine Antimoniate In Cutaneous Leishmaniasis.

BACKGROUND: Many drugs are effective are used as second line treatment for cutaneous leishmaniasis. Dapsone therapy is tolerated well and cost effective. The aim of present study is to determine the efficacy of oral dapsone in comparison with intramuscular meglumine antimoniate in patients with cutaneous leishmaniasis and thus find out an effective second line treatment agent. METHODS: This randomized controlled trial was carried out at dermatology department, of tertiary care centre Rawalpindi, Pakistan from November 2017 to June 2018. Hundred biopsy proven patients of cutaneous leishmaniasis completed the study with 50 patients in two group. Group A received intramuscular meglumine antimoniate (15 mg/kg/day). Group B received oral dapsone2.5 mg /kg/body weight /day (200 mg per day). Efficacy of therapeutic response was noted at the end of treatment. Data was analyzed with statistical analysis program (IBM-SPSS V22). Chi-square test was applied to compare efficacy, p value of ≤0.05 was significant. Stratification of data with respect to age, gender, duration of disease, number of lesions and weight was done to see their effect on treatment efficacy. Post stratification chi-square test for both groups was applied (p≤0.05 considered significant). RESULTS: A total of 100 participants took part in the study. Duration of treatment (p-value <0.001) and the efficacy of the drugs (p-value=0.020) were significant. Meglumine antimoniate therapy group displayed a comparatively fast-paced recovery in (21- 40 days) whereas Dapsone group showed better recovery in (41-60 days) in their lesions. CONCLUSIONS: Dapsone is an effective treatment for cutaneous Leishmaniasis.

Chronic diarrhea secondary to canine leishmaniosis: Case series.

Chronic diarrhea is a clinical sign associated with canine leishmaniosis, varying from 3 % to 30 % of prevalence. However, its occurrence in dogs has been mostly associated with chronic kidney or liver disease. Leishmania organisms can cause inflammation of the digestive tract with chronic diarrhea as the only clinical manifestation, although it has been poorly documented in dogs. The aim of this retrospective observational study was to describe dogs with chronic diarrhea as the main clinical sign associated with leishmaniosis. All cases had a complete blood count, biochemistry, urinalyses, and diagnostic tests for leishmaniosis. Exclusion criteria included renal or hepatic disease and/or previous diagnosis of gastrointestinal disease. Twenty-three dogs were included. Small bowel diarrhea was present in 7/23 (30.4 %), large bowel diarrhea in 9/23 (39.2 %) and mixed diarrhea in 7/23 (30.4 %). Gastrointestinal biopsies were performed in 8/23 dogs and Leishmania amastigotes were found in all of them. In the others, leishmaniosis was diagnosed by serology in 10/15 dogs (66.7 %), serology plus blood PCR in 3/15 (20.0 %), lymph node cytology in 1/15 (6.7 %), and blood PCR in 1/15 (6.7 %). All dogs treated had a complete resolution of diarrhea with specific treatment for leishmaniosis alone, based on meglumine antimoniate (75-100 mg/kg SID SC for 1 month) plus allopurinol (10 mg/kg BID PO ≥ 6 months). This study suggests that leishmaniosis should be also included in the differential diagnosis of dogs from endemic areas presenting with the primary problem of large-bowel, small-bowel, or mixed-bowel chronic diarrhea.

Increased Leishmania infantum resistance to miltefosine and amphotericin B after treatment of a dog with miltefosine and allopurinol.

BACKGROUND: Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate. METHODS: In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated. RESULTS: The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. CONCLUSION: The data indicates an increased L. infantum resistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number of L. infantum strains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated.

ASSESSMENT OF THE OXIDATIVE AND NITROSATIVE STRESS IN THE SERUM OF SAUDI PATIENTS WITH CUTANEOUS LEISHMANIASIS BEFORE AND AFTER TREATMENT.

Macrophages, within which Leishmania species replicate, generate large amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS) to kill these parasites. The present study assessed the oxidative and nitrosative stress, and specific immune enzymes in the serum of patients with cutaneous leishmaniasis (Cl) before and after treatment and in the control individuals. Serum activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), L-arginase, myeloperoxidase (MPO), and adenosine deaminase (ADA) and the levels of reduced glutathione, malondialdehyde (MDA), and nitric oxide (NO) were studied. The activities of L-arginase, MPO, and ADA and the levels of MDA and NO were significantly elevated (P < 0.001), while the activities of SOD, CAT, and GSH-Px, and the levels of reduced glutathione (GSH) were significantly (P < 0.001) reduced in untreated patients as compared with values of patients after treatment and of control individuals. The treatment, which included intramuscular injection of sodium stibogluconate and meglumine antimoniate, ameliorated these factors in comparison to the untreated group. These results suggest that oxidative and nitrosative stress may play an important role in the pathogenesis of untreated cutaneous leishmaniasis. Furthermore, the reduction in oxidative and nitrosative stress in the treated Cl patients may be due to the drug decreasing energy production by the parasite, which eventually leads to its death.

AgNP-PVP-meglumine antimoniate nanocomposite reduces Leishmania amazonensis infection in macrophages.

BACKGROUND: Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and presents different clinical manifestations. The adverse effects, immunosuppression and resistant strains associated with this disease necessitate the development of new drugs. Nanoparticles have shown potential as alternative antileishmanial drugs. We showed in a previous study the biosynthesis, characterization and ideal concentration of a nanocomposite that promoted leishmanicidal activity. In the present study, we conducted a specific analysis to show the mechanism of action of AgNP-PVP-MA (silver nanoparticle-polyvinylpyrrolidone-[meglumine antimoniate (Glucantime®)]) nanocomposite during Leishmania amazonensis infection in vitro. RESULTS: Through ultrastructural analysis, we observed significant alterations, such as the presence of small vesicles in the flagellar pocket and in the extracellular membrane, myelin-like structure formation in the Golgi complex and mitochondria, flagellum and plasma membrane rupture, and electrodense material deposition at the edges of the parasite nucleus in both evolutive forms. Furthermore, the Leishmania parasite infection index in macrophages decreased significantly after treatment, and nitric oxide and reactive oxygen species production levels were determined. Additionally, inflammatory, and pro-inflammatory cytokine and chemokine production levels were evaluated. The IL-4, TNF-α and MIP-1α levels increased significantly, while the IL-17 A level decreased significantly after treatment. CONCLUSIONS: Thus, we demonstrate in this study that the AgNP-PVP-MA nanocomposite has leishmanial potential, and the mechanism of action was demonstrated for the first time, showing that this bioproduct seems to be a potential alternative treatment for leishmaniasis.

[Generalized old world leishmaniasis: first Moroccan case in an immunocompetent adult?] / Leishmaniose généralisée de l'Ancien monde : Premier cas marocain chez un adulte immunocompétent ?

Background: Post-kala-azar dermal Leishmaniasis (PKDL) is a rare skin syndrome observed after treatment of visceral Leishmaniasis (VL) with pentavalent antimonial organic salts, never described in Morocco before. Here we report a case in an immunocompetent adult. Case: A 36-year-old-man from Tata in southern Morocco, with a history of visceral Leishmaniasis 2 years before and treated with meglumine antimoniate and amphotericin B with good clinical course, was hospitalized in dermatology for an erythematous papulo-nodular closet of the face. Six months ago, he presented oral mucosa involvement, then 3 months later, cutaneous lesions appeared on the face. The dermatological examination revealed a papulo-nodular erythematous closet extending to the nose and both cheeks, crusty and lupoid lesions on the forehead, around the eyes and chin, associated with an ulcerative and painless lesion on the heeL. The examination of the oral mucosa revealed an ulceration of the posterior third of the tongue and a papillomatous aspect of the soft palate. The skin biopsy and smear found some amastigote forms of Leishmania bodies. ITS1 PCR was positive (genus Leishmania). The HIV serology was negative. The diagnosis of PKDL was then evoked. The patient received intra-muscular injections of meglumine antimoniate with good progress. Conclusion: To our knowledge, this is the first case of generalised leishmaniasis suggesting PKDL reported in a Moroccan immunocompetent adult.

Association of miltefosine with granulocyte and macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis in the Amazon region: A randomized and controlled trial.

OBJECTIVES: To compare topical granulocyte and macrophage colony-stimulating factor (GM-CSF) and miltefosine (G + M) versus placebo and miltefosine (P + M) or parenteral meglumine antimoniate (MA) in the treatment of 150 patients with cutaneous leishmaniasis (CL) caused by Leishmania guyanensis in the Amazon. DESIGN: A randomized and double-blinded clinical trial. RESULTS: At 90 days after the initiation of therapy, the cure rates were 66%, 58%, and 52% for the groups P + M, G + M, and MA, respectively (p > 0.05). Cure rates at 180 days did not differ. Healing time was similar in the 3 groups, but faster in the MA group as compared to the G + M group (p = 0.04). Mild and transitory systemic adverse events were frequent in all groups (above 85%). Nausea (85%) and vomiting (39%) predominated in the miltefosine groups and arthralgia (51%) and myalgia (48%) in the MA group. One patient (group MA) stopped treatment after presenting with fever, exanthema, and severe arthralgia. CONCLUSIONS: Miltefosine did not present a higher cure rate than MA, and the association of GM-CSF did not improve the therapeutic response. Nevertheless, because of its less toxicity, easier administration, and a similar cure rate when compared with MA, miltefosine should remain as one of the main drugs for treating CL due to L. guyanensis. (Clinicaltrials.gov Identifier NCT03023111).

Estimating direct costs of the treatment for mucosal leishmaniasis in Brazil

Abstract INTRODUCTION: The objective of this study was to estimate the direct medical costs of the treatment for mucosal leishmaniasis (ML) using three therapeutic approaches in the Brazilian context. METHODS: We performed this economic assessment from the perspective of the Brazilian public healthcare system. The following therapeutic approaches were evaluated: meglumine antimoniate, liposomal amphotericin B, and miltefosine. Direct medical costs were estimated considering four treatment components: a) drug, b) combined medical products, c) procedures, and d) complementary tests. RESULTS: Treatment with meglumine antimoniate had the lowest average cost per patient (US$ 167.66), followed by miltefosine (US$ 259.92) in the outpatient treatment regimen. The average cost of treatment with liposomal amphotericin B was US$ 715.35 both in inpatient regimen. In all estimates, the drugs accounted for more than 60% of the total cost for each treatment approach. CONCLUSIONS: These results demonstrate the marked differences in costs between the therapeutic alternatives for ML. In addition to efficacy rates and costs related to adverse events, our data have the potential to support a complete cost-effectiveness study in the future. Complete analyses comparing costs and benefits for interventions will assist health managers in choosing drugs for ML treatment in Brazil as well as in establishing effective public health policies.

Unusual manifestation of genital cutaneous leishmaniasis in an immunocompetent patient from São Paulo, Brazil: A case report

Abstract A 31-year-old male patient developed an ulcer on the glans penis that evolved for three months without healing. We diagnosed it as leishmaniasis using polymerase chain reaction. No immunosuppression or associated diseases were observed. The patient was treated with meglumine antimoniate that cured the lesion in a month post-treatment. Here, we report this case of cutaneous leishmaniasis lesion at the unusual location of glans penis in an immunocompetent individual. The lesion likely developed due to the bite of a vector, highlighting the need for considering cutaneous leishmaniasis among differential diagnosis of sexually transmitted diseases in areas endemic for leishmaniasis.

Potential of Artesunate in the treatment of visceral leishmaniasis in dogs naturally infected by Leishmania infantum: Efficacy evidence from a randomized field trial.

Leishmaniasis is among the world's most neglected diseases. Dogs are the main reservoirs/hosts of Leishmania infantum, causative agent of both canine and human visceral leishmaniosis. Canine leishmaniasis (CanL) represents a public health problem as one of the most prevalent zoonotic diseases worldwide. Current therapeutics present drawbacks; thus, there is a need for more effective, safer, and cheaper drugs. The aim of this study was to evaluate and to compare the efficacy of oral administration of artesunate or meglumine antimoniate/allopurinol in dogs with clinical leishmaniasis. Forty-two dogs with naturally occurring clinical leishmaniasis were included in this open-label, simple randomized positive-control clinical field trial with 6 months of follow-up. Dogs received meglumine antimoniate 100 mg/kg/day and allopurinol 30 mg/kg/day for 28 days (control group, n = 26) or artesunate 25 mg/kg/day for 6 days (test group, n = 16). The animals were evaluated for their clinical evolution, parasite load (by qPCR) and humoral response at different time points: 0, 30, 90, and 180 days after treatment. Data analyses showed a significant improvement in both groups in clinical scores, parasitemia and antibody titers after treatment. Compared to the control group, the artesunate group showed significantly lower clinical score (P = 0.0001), lower parasitemia (P = 0.0001) and antibody titers after 6 months of follow-up. Compared to baseline values, a rapid, significant reduction (P < 0.012) in antibody levels, 2.28- versus 3.04-fold for the control versus artesunate groups, respectively, was observed 30 days after treatment. Antibody levels continued to decrease further in the artesunate group, where 58% of cases became seronegative at the 6-month follow-up. All qPCR-positive dogs were negative after treatment with artesunate, while 14.3% remained positive with the appearance of two new cases in the control group. Artesunate was well tolerated, and no side effects were recorded. Treatment failures were similar in both groups with 27.27% (6/22), including 18.18% (4/22) mortality in the control group, versus 26.66% (4/15), including 13.33% (2/15) mortality in the artesunate group. This is the first report showing the potential of artesunate in the treatment of dogs with clinical leishmaniasis. Artesunate showed higher efficacy than the current first-line treatment for CanL without any adverse effects. It could be a good alternative chemotherapy for CanL, and may be considered for further studies in human leishmaniases. Further clinical trials are needed to confirm these findings, to determine if there are relapses after treatment and if dogs remain infective to sandflies, to define the ideal therapeutic dosage and duration of treatment with artesunate.

Case Report: Unusual Presentation of Pharyngeal Mucosal Leishmaniasis due to Leishmania (Viannia) braziliensis.

Mucosal leishmaniasis (ML) affects predominantly the nose and occurs usually weeks or months after the cure of the primary cutaneous lesion. The pathology of ML is characterized by an exaggerated inflammatory reaction with infiltration of lymphocytes, macrophages, and plasma cells. There is also a paucity of parasites and a strong delayed-type hypersensitivity reaction. Herein, we report a case of a young man who had a large ulcer in his left leg and complained of dysphagia. In nasofibrolaryngoscopy, there were nodular lesions in the oropharynx and rhinopharynx. The skin lesion biopsy showed a chronic inflammation with amastigotes inside macrophages, and DNA of Leishmania braziliensis confirmed the diagnosis of ML in tissue biopsied from the pharynx. The leishmaniasis skin test was negative. Cytokine evaluation showed lack of production of interferon (IFN)-γ, interleukin (IL)-1ß, and IL-17 with enhancement of these cytokine levels after cure.

A natural cell-penetrating nanopeptide combined with pentavalent antimonial as experimental therapy against cutaneous leishmaniasis.

The inadequacy of available treatments for leishmaniasis has presented up to 40% therapeutic failure. This fact suggests an urgency in the discovery of new drugs or alternative approaches for treating this disease. The objective of this study was to evaluate the antileishmanial activity of combined therapy between crotamine (CTA) from Crotalus durissus terrificus and the pentavalent antimonial Glucantime® (GLU). The assays were in vitro performed measuring the inhibition of Leishmania amazonensis amastigotes, followed by the evaluation of cellular production of cytokines and nitrites. After that, analytical methods were performed in order to characterize the molecules involved in the study by Mass Spectrometry, molecular affinity through an in silico assay and Surface Plasmon Resonance. In vivo experiments with BALB/c mice were performed by analyzing parasitemia, lesion size and immunological mediators. In the in vitro experiments, the pharmacological association improved the inhibition of the amastigotes, modulated the production of cytokines and nitric oxide. The therapy improved the effectiveness of the GLU, demonstrating a decreased parasitemia in the infected tissues. Altogether, the results suggest that the combined approach with CTA and GLU may be a promising alternative for the treatment of cutaneous leishmaniasis.