An old drug and different ways to treat cutaneous leishmaniasis: Intralesional and intramuscular meglumine antimoniate in a reference center, Rio de Janeiro, Brazil.

BACKGROUND: Treatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil. METHODOLOGY: A historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10-20 mg Sb5+/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb5+/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests. RESULTS: SR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity. CONCLUSIONS/SIGNIFICANCE: AR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs.

Leishmanicidal potentials of Gossypium hirsutum extract and its fractions on Leishmania major in a murine model: parasite burden, gene expression, and histopathological profile.

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species.Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development.Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action.Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure.Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major.Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.

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).

Tratamiento de la leishmaniasis localizada mediante el antimoniato demeglumina intralesional y la terapia fotodinámica / Treatment of localized cutaneous leishmaniasis with intralesional meglumine antimoniateand photodynamic therapy

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Comparison of Three Different Therapies for Cutaneous Leishmaniasis and Identification of the Etiologic Isolates in Isfahan, Iran.

BACKGROUND: In Iran, zoonotic and anthroponotic cutaneous leishmaniasis (CL) are caused by Leishmania major and L. tropica respectively. Despite extensive studies, no effective therapies have ever been reported for CL. The main objective of this research was to determine and compare the three different protocols for treatment of CL patients referring to Skin Diseases and Leishmaniasis Research Center (SDLRC), affiliated to Isfahan University of Medical Sciences, Isfahan, Iran from September 2017 to October 2018. METHODS: In a randomized controlled parallel groups clinical trial, 150 selected CL patients who met our inclusion criteria were randomly assigned to one of the three therapy groups: A, intra-lesional glucantime plus 50% trichloroacetic acid (TCA), B, intralesional glucantime and C, systemic glucantime. All patients in the three groups received the complete course of treatment and were followed for 6 months. To identify the etiologic agents, smears from their lesions were prepared and PCR-RFLP was used after parasite culture. Also, clinical characteristics, history of previous involvement, endemic emigration and demographic data were collected. RESULTS: The results showed that the mean value of healing period was 53.12 ± 25.88 (median: 45, IQR: Q1 = 30-Q3 = 77) days in group A, 57.22 ± 44.02 (median: 42.5, IQR: Q1 = 30-Q3 = 60) days in group B, and 73.56 ± 41.08 (median: 71, IQR: Q1 = 45-Q3 = 90) days in group C; the observed differences were statistically significant (P=0.024). There was a significant difference between group A and group C (P = 0.049), and between group B and group C (P = 0.047) in terms of mean healing period. Finally, complete recovery rates of 80%, 62% and 42% were shown in the three medicinal groups of A, B and C, respectively (P = 0.022). CONCLUSION: In this study, the average duration of lesion healing among the three groups was the shortest in patients with IL glucantime plus 50% TCA treatment regimen. Also, the use of 50% TCA in patients suffering from CL was associated with a significant improvement in the depth of scars, the time and the percentage of recovery, and the low cost of this agent in the treatment of CL.

Treatment and follow-up of a domestic ferret (Mustela putorius furo) with clinical leishmaniosis caused by Leishmania infantum.

Leishmania infantum infection including treatment and follow up in domestic animals other than dogs and cats has not been described at this moment. This article describes the anti-Leishmania treatment and follow-up of a ferret (Mustela putorius furo) with leishmaniosis. A combined therapeutic protocol established for the patient, not yet approved for ferrets, was a combination of meglumine antimoniate plus allopurinol. A follow-up was established monthly during the first year in order to monitor the health condition of the patient. Six months after commencing allopurinol therapy, xanthine crystalluria was observed in urine sediment with no other urine alterations detected by urine analysis. The ferret worsened progressively with diarrhoea and weight loss after cohabiting with another ferret diagnosed with cryptosporidiosis. Cryptosporidium parvum was isolated in faecal samples from the patient detected by three different methods including Ziehl-Neelsen staining, a qualitative test to detection of C. parvum antigens and finally a specific molecular analysis to characterize the species. To the best of the authors´ knowledge, this is the first report providing information about anti-Leishmania protocol therapy used and follow-up in a domestic ferret with clinical leishmaniosis. Veterinarians practicing in endemic areas should be aware of this infection in ferrets at risk and their susceptibility especially when immunosuppressive conditions are present.

Sporotrichoid Abscesses: A Rare Form of Recurrent Cutaneous Leishmaniasis in an Infant's Face.

An 8-month-old infant presented with a 3-month history of two swellings on her left cheek. Past history revealed cutaneous leishmaniasis (CL) of the same site 8 months earlier; the patient was treated with intralesional infiltrations of meglumine antimoniate over 4 months, leaving behind an atrophic scar. The current lesions started 1 month after the healing of the initial ones and gradually increased in size and later became fluctuant. She had been treated with several antimicrobial agents, without any improvement. Her examination revealed two subcutaneous inflammatory and renitent nodules of 2-3 cm in diameter on the left cheek, associated with a cribriform scar under the external angle of the left eye, corresponding with the CL. The abscesses were aspirated, revealing yellowish pus. Culture was negative for bacterial growth. Smears for Leishmania bodies performed, using Leishman and Giemsa stains and taken from both the subcutaneous abscesses and the dystrophic scar; were positive. The diagnosis of a lymphatic dissemination was established based on the previous history of CL treated with local therapy. The patient was started on intramuscular injections of meglumine antimoniate (60 mg/kg/day) for 21 days, and she responded well to the treatment, with complete disappearance of the lesions. Repeat skin smears were negative for Leishmania bodies.

Interventions for American cutaneous and mucocutaneous leishmaniasis.

BACKGROUND: On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009. OBJECTIVES: To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML). SEARCH METHODS: We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome. MAIN RESULTS: We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.

Mucocutaneous leishmaniasis in a cocaine user: diagnostic and therapeutic knowledge.

Mucocutaneous leishmaniasis (MCL) is a chronic infection that can affect the skin and mucous membranes. We report a case of oral, nasopharyngeal, and penile lesions in a 35-year-old cocaine user. The patient presented with ulcerated lesions in 2014. Histopathologic analysis revealed amastigotes, and serological test results were positive for leishmaniasis. Systemic therapy with meglumine antimoniate was administered; however, the patient failed to present for follow-up. In 2018, he returned with nasal collapse, and another histopathologic test confirmed MCL. This case illustrates the importance of careful differential diagnosis of skin and mucous ulcers to identify the particular pathology.

Refractory mucocutaneous leishmaniasis resolved with combination treatment based on intravenous pentamidine, oral azole, aerosolized liposomal amphotericin B, and intralesional meglumine antimoniate.

INTRODUCTION: Mucocutaneous leishmaniasis (MCL) is a complication of tegumentary leishmaniasis, causing potentially life-threatening lesions in the ear, nose, and throat (ENT) region, and most commonly due to Leishmania (Viannia) braziliensis. We report a case of relapsing MCL in an Italian traveler returning from Argentina. CASE DESCRIPTION: A 65-year-old Italian male patient with chronic kidney disease, arterial hypertension, prostatic hypertrophy, and type-2 diabetes mellitus was referred for severe relapsing MCL acquired in Argentina. ENT examination showed severe diffuse pharyngolaryngeal edema and erythema, partially obstructing the airways. A nasopharyngeal biopsy revealed a lymphoplasmacytic inflammation and presence of Leishmania amastigotes, subsequently identified as L. (V.) braziliensis by hsp70 PCR-RFLP analysis and sequencing. Despite receiving four courses of liposomal amphotericine B (L-AmB) and two courses of miltefosine over a 2-year period, the patient presented recurrence of symptoms a few months after the end of each course. After the patient was referred to us, a combined treatment was started with intravenous pentamidine 4 mg/kg on alternate days for 10 doses, followed by one dose per week for an additional seven doses, intralesional meglumine antimoniate on the nasal lesion once per week for six doses, oral azoles for three months, and aerosolized L-AmB on alternate days for three months. The treatment led to regression of mucosal lesions and respiratory symptoms. Renal function temporarily worsened, and the addition of insulin was required to maintain glycemic compensation after pentamidine discontinuation. CONCLUSIONS: This case highlights the difficulties in managing a life-threatening refractory case of MCL in an Italian traveler with multiple comorbidities. Even though parenteral antimonial derivatives are traditionally considered the treatment of choice for MCL, they are relatively contraindicated in cases of chronic kidney disease.The required dose adjustment in cases of impaired renal function is unknown, therefore the use of alternative drugs is recommended. This case was resolved with combination treatment, including aerosolized L-AmB, which had never been used before for MCL.

Case Report: Coinfection by Leishmania amazonensis and HIV in a Brazilian Diffuse Cutaneous Leishmaniasis Patient.

Diffuse cutaneous leishmaniasis (DCL) is a rare type of leishmaniasis characterized by diffuse skin lesions. In Brazil, Leishmania (L.) amazonensis is the main etiological agent of this clinical form. The state of Maranhão has the highest prevalence of this disease in the country, as well as a high rate of HIV infection. Here, we report the first case of DCL/HIV of Brazil. A 46-year-old man from the Amazonian area of Maranhão state presented atypical lesion in the left upper limb and dissemination of diffuse erythematous nodules over his entire body. Histopathological examination confirmed the presence of intracellular amastigotes of Leishmania, and a polymerase chain reaction and molecular identification by restriction fragment profile identified L. (L.) amazonensis as the causative agent of the disease. The patient was also diagnosed with HIV virus after the leishmaniasis diagnosis. The initial treatments for leishmaniasis were liposomal amphotericin B (AmB-L) (4 mg/kg) for 10 days and prophylactic use of Glucantime® (10 mg/Sb+5/kg) for 2 months. After unsuccessful initial treatments, he was treated with a combination of AmB-L (4 mg/kg) alternated with pentamidine (4 mg/kg) for 10 days but failed in the first therapeutic cycle. Subsequently, he had a good response to treatment with pentamidine (4 mg/kg).

Sugar-based colloidal nanocarriers for topical meglumine antimoniate application to cutaneous leishmaniasis treatment: Ex vivo cutaneous retention and in vivo evaluation.

The leishmaniases are a group of diseases caused by protozoan parasites from Leishmania species. Effectiveness therapies for cutaneous leishmaniasis (CL), the most common form, are still needed to be developed since the available drugs such as meglumine antimoniate (MA) present severe adverse reactions. Here, we develop and characterize maltodextrin polymeric colloidal nanocarriers containing MA (PCN-MA) for topical CL treatment. PCN-MA is composed of 5 to 8% maltodextrin, 0.3% NaCl, 1% MA in 21% of water as aqueous-internal phase, containing or no 3% Kolliphor® P-188, and 10% SF1540 dispersed in a silicone-based external phase. It formed a colloidal system dispersed in silicone with high encapsulation efficiency (87% to 92%) and composite spherical-shaped particles with the smooth and regular surface within the nanosized scale, which was confirmed by scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. Ex vivo cutaneous retention studies using pig ears skin on Franz diffusion cells revealed that the MA cutaneous retention is improved when delivered by PCN. Topical PCN-MA evaluation in murine leishmaniasis model showed similar efficacy than the intraperitoneal injection of the reference medicine (Glucantime®) regarding parasite titer reduction and superior healing activity in terms of collagen area deposition. Our results suggest that this sugar-based PCN is a promising agent for topical delivery of meglumine antimoniate.

Safety profile of meglumine antimoniate intralesional infiltration for cutaneous leishmaniasis.

Objectives: Cutaneous leishmaniasis is a neglected disease, associated with high morbidity, which is partially due to the toxicity of available therapies. The pentavalent antimonial derivatives intralesional infiltration has proven to be as effective as the intravenous drug-based therapy, however, there is a lack of robust safety data.Methods: Phase II, uncontrolled, unicenter clinical trial to assess the safety profile of a standardized meglumine antimionate intralesional therapy, based on weekly infiltrations.Results: Fifty-three patients were studied, predominantly men (60%) and young adults (43.7 ± 17.1 years). Overall, 86.9% of the patients had at least one clinical adverse event. Local events were the most frequent (83%), followed by systemic ones (47.3%). Fourteen participants (26%) presented biochemical abnormalities. In all cases, laboratorial alterations were classified as mild and treatment discontinuation was not required. Differently, the two hypersensitivity (3.8%) reactions observed led to permanent treatment interruption. QTc interval prolongation was recorded in 14 patients (25.5%). The following risk associations to adverse events were identified in the multiple analysis: hypertension with systemic clinical events and smoking with QT interval prolongation.Expert commentary: In general, MA-IL was well tolerated and although associated with local and systemic adverse events, there was a low risk of high intensity or severe complications.

Cutaneous and mucocutaneous leishmaniasis: experience of a Mediterranean hospital.

BACKGROUND: Leishmaniasis, considered by the World Health Organization as one of the most important tropical diseases, is endemic in the Mediterranean Basin. The aim of this study was to evaluate epidemiological and clinical characteristics of cutaneous (CL) and mucocutaneous leishmaniasis (MCL) in La Fe University Hospital, Valencia, Spain. The particular focus was on diagnosis techniques and clinical differences according to the immunological status of the patients. METHODS: An eleven-year retrospective observational study of CL and MCL episodes at the hospital was performed. Epidemiological, clinical and therapeutic variables of each case, together with the microbiological and anatomopathological diagnosis, were analyzed. RESULTS: A total of 42 patients were included, 30 of them were male and 28 were immunocompetent. Most of the cases (36/42) were diagnosed in the last 5 years (2013-2017). The incidence of CL and MCL increased from 3.6/100,000 (2006-2012) to 13.58/100,000 (2013-2017). The majority of the patients (37/42) exhibited CL, in 30 cases as single lesions (30/37). Ulcerative lesions were more common in immunosuppressed patients (13/14) than in immunocompetent patients (20/28), (P = 0.2302). The length of lesion presence before diagnosis was 7.36 ± 6.72 months in immunocompetent patients and 8.79 ± 6.9 months in immunosuppressed patients (P = 0.1863). Leishmania DNA detection (92.3%) was the most sensitive diagnostic technique followed by Giemsa stain (65%) and histopathological examination (53.8%). Twelve patients (12/42) had close contact with dogs or were living near to kennels, and 10 of them did not present underlying conditions. Intralesional glucantime (21/42) and liposomal amphotericin B (7/42) were the most common treatments administered in monotherapy. All patients evolved successfully and no relapse was reported. CONCLUSIONS: Some interesting clinical and epidemiological differences were found in our series between immunocompetent and immunosuppressed patients. Future studies can take these results further especially by studying patients with biological therapy. Skin biopsies combining NAAT with histological techniques are the most productive techniques for CL or MCL diagnosis.

Case Report: Combination Therapy with Liposomal Amphotericin B, N-Methyl Meglumine Antimoniate, and Pentamidine Isethionate for Disseminated Visceral Leishmaniasis in a Splenectomized Adult Patient.

In immunocompromised patients, visceral leishmaniasis (VL) can present with atypical clinical symptoms that include poor response to treatment. No optimal therapeutic regimen is available for such cases. In a splenectomized male patient, we observed a disseminated form of the disease in the liver, bone marrow, lymph nodes, and gastrointestinal tract. There was an apparent clinical improvement when he was initially treated with liposomal amphotericin B (L-AmB), but this was followed by a relapse involving severe clinical symptoms. He was finally treated successfully with a combination of L-AmB, meglumine antimoniate, and pentamidine isethionate. It is important to include asplenia as an immunosuppressive condition that induces exotic VL pathologies. In such cases, combination anti-Leishmania drug therapy should be considered.

Mucocutaneous leishmaniasis in a cocaine user: diagnostic and therapeutic knowledge

Abstract Mucocutaneous leishmaniasis (MCL) is a chronic infection that can affect the skin and mucous membranes. We report a case of oral, nasopharyngeal, and penile lesions in a 35-year-old cocaine user. The patient presented with ulcerated lesions in 2014. Histopathologic analysis revealed amastigotes, and serological test results were positive for leishmaniasis. Systemic therapy with meglumine antimoniate was administered; however, the patient failed to present for follow-up. In 2018, he returned with nasal collapse, and another histopathologic test confirmed MCL. This case illustrates the importance of careful differential diagnosis of skin and mucous ulcers to identify the particular pathology.

Intralesional infiltration versus parenteral use of meglumine antimoniate for treatment of cutaneous leishmaniasis: A cost-effectiveness analysis.

Cutaneous leishmaniasis (LC) is a complex and variable disease in terms of epidemiology, aetiology, pathology and clinical characteristics. The mainstay of treatment is still pentavalent antimony (Sbv) compounds administered systemically, despite their recognized toxicity. The advantages of antimony intralesional (IL) infiltration are the use of lower doses of Sbv and, therefore, less toxic effects. The objective of this study was to estimate the cost-effectiveness ratio of intralesional meglumine antimoniate therapy (IL-MA) compared with endovenous meglumine antimoniate therapy (EV-MA) for the treatment of CL in the context of the Brazilian National Health System (SUS). An analytical decision model (decision tree) was developed using TreeAge Pro 2018 software. Data from the open-label, uncontrolled phase II clinical trial evaluating IL-MA were used as a reference for posology, efficacy, and adverse event rates (AE). The same premises for the intravenous approach (EV-MA) were extracted from systematic literature reviews. Macro and micro calculations of spending were included in the analysis. The IL-MA and EV-MA strategies had a total cost per patient cured of US$330.81 and US$494.16, respectively. The intralesional approach was dominant, meaning it was more economic and effective than was endovenous therapy. The incremental cost-effectiveness ratio showed that IL-MA could result in savings of US$864.37 for each additional patient cured, confirming that the IL-MA strategy is cost effective in the context of the Brazilian public health scenario.

Short term impacts of meglumine antimoniate treatment on kidney function in dogs with clinical leishmaniosis.

This study examines correlations among serum proteins, clinical score, body weight and kidney function biomarkers after a standard treatment course (meglumine antimoniate plus allopurinol) in twelve Canine leishmaniosis (CanL) patients at the three times points pre treatment, after treatment and after the end of treatment. The laboratory variables measured were those used for the follow-up of sick dogs along with biomarkers of kidney function: glomerular filtration rate (GFR), creatinine (Cr), urea, calcium, inorganic phosphorus, urine specific gravity (USG) and urine protein to creatinine ratio (UPC). Arterial blood pressure (systolic blood pressure, SBP), clinical score (CS) and weight were also monitored over the study period. At Tp0, GFR was within the normal range in most dogs. Hyperfiltration was detected in three patients and hypofiltration in one. In dogs showing hyperfiltration, this factor remained in the non-azotemic range over the whole study period. After treatment normal filtration values were recovered. Meglumine antimoniate did not modify GFR or USG. A significant reduction in UPC was recorded. In all dogs, clinical scores improved. Negative correlation was found between GFR and Cr, UPC and albumin (Alb) and CS and Alb, while positive correlation was detected between UPC and total globulins (GlobT), CS and GlobT, UPC and total solids (TS), SBP and CS and SBP and UPC. Our findings indicate no impacts on kidney function of the treatment of CanL with meglumine antimoniate, as no effects were produced on GFR or USG. Treatment was effective and found to reduce UPC which could suggest improved glomerular injury.