Meglumine Antimoniate Treatment Research Articles

Owners' experiences of administering meglumine antimoniate injections to dogs with leishmaniosis: An online questionnaire study.

This study examined the experiences of owners of dogs with leishmaniosis who treated their dogs with daily subcutaneous meglumine antimoniate injections. The owners' perceived ease of administering the injections, the occurrence of problems and the effects on the owners and on the dog‒owner bond were evaluated. Dogs prescribed meglumine antimoniate as a treatment for leishmaniosis were identified using the database of the veterinary pharmacy of the Faculty of Veterinary Medicine, Utrecht University. An online questionnaire was sent to the owners of these dogs to evaluate the perceived ease of administering the injections, the occurrence of problems and the effects on the owner and the dog-owner bond. Responses were received from 64 dog owners. Most respondents (78%) reported that administering the injections was not difficult. Pain or the development of nodules at the injection site was reported in 50% and 40% of the dogs, respectively. Polyuria was reported in 44% of the dogs. Some owners reported that administering the injections had a negative impact on their psychological wellbeing (20%), and some would have liked more veterinary support (11%). Some questions were answered by a limited number of people, and their responses may not be representative. Dog owners remain highly motivated to persevere with meglumine antimoniate treatment and are willing to administer the injections themselves. The availability of active support when needed during the therapy cycle may further improve their acceptance of and confidence in giving the injections.

Geriatric cutaneous leishmaniasis: a retrospective analysis of 622 cases.

Cutaneous leishmaniasis (CL) is most common in childhood because children are exposed to the parasite early and, unlike adults, do not have immunity to CL. Since CL is less common in geriatric patients, clinical and epidemiological data in this age group are limited. This study aims to compare the clinical and demographic characteristics of geriatric patients diagnosed with CL with young patients. In this retrospective study, 622 patients aged 65 and over and 6350 patients aged 19-64, who applied to Şanlıurfa Oriental Boil Diagnosis and Treatment Center between January 2013 and February 2024 and were diagnosed with CL by parasitological examination, were included. Clinical and demographic characteristics of patients diagnosed with CL, such as age, gender, location of the lesion, lesion size, duration of the lesion, and treatments applied due to the diagnosis of CL, were recorded. Clinical and demographic characteristics of geriatric and young patients were compared. The mean age of elderly CL cases was 72.95 ± 6.54years, and 65.2% were female. The most common clinical forms were ulcers (51.9%) and plaques (41%), respectively, in young and elderly patients. The most common locations of the lesions were upper limbs (54.8%) in all patients. The most preferred treatment method was intralesional (IL) meglumine antimoniate (MA) treatment (98.3%) in all patients. There were no difference between young and elderly CL cases in terms of mean number of lesions, average lesion duration, average lesion size, lesion location, clinical forms of lesions, and treatments options (P > 0.05). Based on the results of our study, it can be said that the clinical and demographic characteristics of CL are similar in young and old patients and systemic MA treatment shows similar clinical benefit in both age groups. In addition, it can be said that systemic MA therapy can be used safely in young patients and elderly patients without contraindications. IL MA therapy can be used in elderly patients where systemic MA therapy is contraindicated.

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.

Phylogenetic analysis and antimony resistance of Leishmania major isolated from humans and rodents.

Cutaneous Leishmaniasis (CL) is one of the world's neglected diseases which is caused by Leishmania spp. The aim of this study was to assess molecular profile and antimony resistance of Leishmania isolated from human and rodent hosts. Samples were collected from suspected CL patients referred tohealth centres and wild rodent's traps in Gonbad-e-Qabus region, north-eastern Iran. Smears weresubjected to PCR-RFLP to identify Leishmania species. In addition, ITS1-PCR products weresequenced for phylogenetic analysis. Clinical isolates and rodent samples were subjected to MTTassay to determine IC50 values and in vitro susceptibilities. Expression levels of antimony resistance-related genes were determined in CL isolates. Out of 1,949 suspected patients with CL and 148rodents, 1,704 (87.4%) and 6 (4.05%) were positive with direct smear, respectively. Digestion patterns of BusRI (HaeIII) endonuclease enzyme were similar to what expected for Leishmania major. Phylogenetic analysis revealed that the highest interspecies similarity was found between current L.major sequences with L. major obtained from Russia and Uzbekistan. Out of 20 L. major samples tested, 13 (65%) were resistant to meglumine antimoniate (MA) treatment, with an activity index (AI) exceeding 4. The remaining 7 samples (35%) responded to MA treatment and were classified as sensitive isolates, with a confirmed sensitive phenotype based on their AI values. The comparison expression analysis of three major antimony resistance-associated genes in unresponsive clinical isolates demonstrated significant fold changes for TDR1 (4.78-fold), AQP1 (1.3-fold), and γ-GCS (1.17-fold) genes (P < 0.05). Herein, we demonstrate genetic diversity and antimony resistance of L.major isolated from human and reservoir hosts in north-eastern Iran, which could be the basis forplanning future control strategies.

Clinical Risk Factors of Systemic Antimony Treatment Failure in Patients with Acute Cutaneous leishmaniasis referred to the Dermatology Clinics of Mashhad University of Medical Sciences, Iran

Background: Systemic or topical forms of pentavalent antimony compounds such as meglumine antimoniate (MA) are used as standard treatment for cutaneous leishmaniasis (CL). However, an increasing number of studies demonstrate evidence of treatment failure with these drugs. The objective of this study was to determine the factors associated with systemic MA treatment failure in patients with acute CL. Methods: In this case-control study, patients with urban cutaneous referred to leishmaniasis clinics in Mashhad from 2017 to 2018 were followed up 12 months after the start of treatment and were evaluated for improvement or failure according to the national leishmaniasis protocol. Results: A total of 112 cases of CL (59 men and 53 women) with a mean age of 23.3±21.11 years were studied. The number of patients with clinical improvement was significantly higher in women (P=0.005). Age, body mass index (BMI), occupation and education, the possible infection and living location, past medical, drug and leishmaniasis recurrence history, lesion’s characteristics and ulceration were also significantly different between the two groups of improved and unhealed patients. Conclusion: The results of this study showed that the male sex, age less than 18 years, receiving pentostam, previous treatment history, lymphadenopathy, urban leishmaniasis, duration of illness more than 4 months, having a single lesion especially on the face, BMI less than 18 kg/m2 and a lesion size of more than 3 cm is more common in patients with treatment failure.

Treatment of leishmaniasis with chemotherapy and vaccine: a mathematical model

Leishmaniasis, an infectious disease, manifests itself mostly in two forms, cutaneous leishmaniasis (CL) and, a more severe and potentially deadly form, visceral leishmaniasis (VL). The current control strategy for leishmaniasis relies on chemotherapy drugs such as sodium antimony gluconate (SAG) and meglumine antimoniate (MA). However, all these chemotherapy compounds have poor efficacy, and they are associated with toxicity and other adverse effects, as well as drug resistance. While research in vaccine development for leishmaniasis is continuously progressing, no vaccine is currently available. However, some experimental vaccines such as LEISH-F1+MPL-SE (V) have demonstrated some efficacy when used as drugs for CL patients. In this paper we use a mathematical model to address the following question: To what extent vaccine shots can enhance the efficacy of standard chemotherapy treatment of leishmaniasis? Starting with standard MA treatment of leishmaniasis and combining it with three injections of V , we find, by Day 84, that efficacy increased from 29% to 65–91% depending on the amount of the vaccine. With two or just one injection of V , efficacy is still very high, but there is a definite resurgence of the disease by end-time.

Is There Any Difference in the In Situ Immune Response in Active Localized Cutaneous Leishmaniasis That Respond Well or Poorly to Meglumine Antimoniate Treatment or Spontaneously Heal?

Localized cutaneous leishmaniasis caused by Leishmania braziliensis can either respond well or poorly to the treatment or heal spontaneously; It seems to be dependent on the parasite and/or host factors, but the mechanisms are not fully understood. We evaluated the in situ immune response in eighty-two active lesions from fifty-eight patients prior to treatment classified as early spontaneous regression (SRL-n = 14); treatment responders (GRL-n = 20); and non-responders (before first treatment/relapse, PRL1/PRL2-n = 24 each). Immunohistochemistry was used to identify cell/functional markers which were correlated with the clinical characteristics. PRL showed significant differences in lesion number/size, clinical evolution, and positive parasitological examinations when compared with the other groups. SRL presented a more efficient immune response than GRL and PRL, with higher IFN-γ/NOS2 and a lower percentage of macrophages, neutrophils, NK, B cells, and Ki-67+ cells. Compared to SRL, PRL had fewer CD4+ Tcells and more CD163+ macrophages. PRL1 had more CD68+ macrophages and Ki-67+ cells but less IFN-γ than GRL. PRL present a less efficient immune profile, which could explain the poor treatment response, while SRL had a more balanced immune response profile for lesion healing. Altogether, these evaluations suggest a differentiated profile of the organization of the inflammatory process for lesions of different tegumentary leishmaniasis evolution.

Pentoxifylline in the Treatment of Cutaneous Leishmaniasis: A Randomized Clinical Trial in Colombia.

Addition of the immunomodulator pentoxifylline (PTX) to antimonial treatment of mucosal leishmaniasis has shown increased efficacy. This randomized, double-blind, placebo-controlled trial evaluated whether addition of pentoxifylline to meglumine antimoniate (MA) treatment improves therapeutic response in cutaneous leishmaniasis (CL) patients. Seventy-three patients aged 18–65 years, having multiple lesions or a single lesion ≥ 3 cm were randomized to receive: intramuscular MA (20 mg/kg/day × 20 days) plus oral PTX 400 mg thrice daily (intervention arm, n = 36) or MA plus placebo (control arm, n = 37), between 2012 and 2015. Inflammatory gene expression was evaluated by RT-qPCR in peripheral blood mononuclear cells from trial patients, before and after treatment. Intention-to-treat failure rate was 35% for intervention vs. 25% for control (OR: 0.61, 95% CI: 0.21–1.71). Per-protocol failure rate was 32% for PTX, and 24% for placebo (OR: 0.50, 95% CI: 0.13–1.97). No differences in frequency or severity of adverse events were found (PTX = 142 vs. placebo = 140). Expression of inflammatory mediators was unaltered by addition of PTX to MA. However, therapeutic failure was associated with significant overexpression of il1β and ptgs2 (p < 0.05), irrespective of study group. No clinical benefit of addition of PTX to standard treatment was detected in early mild to moderate CL caused by Leishmania (V.) panamensis.

Therapeutic effect of Prosopis strombulifera (LAM) BENTH aqueous extract on a murine model of cutaneous leishmaniasis

Background and aimProsopis strombulifera (Lam.) Benth is a rhizomatous shrub native from different zones of Argentine Republic. P. strombulifera aqueous extract (PsAE) has different effects and several biological activities have been reported. The goal of this study was to analyze the activity of PsAE on a murine model of cutaneous leishmaniasis caused by Leishmania amazonensis. Experimental procedurePsAE was orally administered at 150 mg/animal/day on BALB/c mice infected in the right footpad (RFP) with 1 × 105 promastigotes of L. amazonensis. As a chemotherapeutic control of treatment, animals receive a commercial form of meglumine antimoniate (MA) (Glucantime®, Aventis, Paris, France). Results and conclusionWe observe that the size of RFP lesions of infected mice without treatment showed a grade of inflammation, ulceration and necrosis at the site of infection much greater than that observed with PsAE or MA treatment. Moreover, PsAE was capable of decreasing parasite burden and splenic index. Furthermore, PsAE treated mice showed a significant decrease in O.D. of total anti-Leishmania IgG antibody responses against L. amazonensis. This decrease was similar to those observed when the reference drug, MA, was used. This would indicate that PsAE treatment inhibits or delays disease progression in mice. In conclusion, our findings suggest that PsAE could be a potential candidate to be used, as a new therapeutic strategy, to treat cutaneous leishmaniasis caused by L. amazonensis.

In vivo efficacy of meglumine antimoniate-loaded nanoparticles for cutaneous leishmaniasis: a systematic review.

Background: Nanotechnology is a promising strategy to improve existing antileishmanial agents. Objective: To explore the evidence of encapsulated meglumine antimoniatefor cutaneous leishmaniasis treatment in animal models. Materials & methods: The studies were recovered from PubMed, Scopus, EMBASE, LILACS, WoS and Google according to eligibility criteria following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Population, Intervention, Comparison, Outcomes and Study design (PICOS) strategy. Study appraisal was assessed using the Animal Research Reporting of In Vivo Experiments, SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) and Grading of Recommendations Assessment, Development and Evaluation(GRADE) recommendations. Results: Five studies were included. Liposomes, metallic and polymeric nanoparticles were tested in BALB/c mice against Leishmania major, L. tropica or L. amazonensis. Limitations: Few studies were found to meet the eligibility criteria. Conclusion: All formulations had a significant efficacy, similar to the meglumine antimoniate reference treatment concerning the lesion size and parasite burden. The studies had a high and moderate risk of bias, and the confidence in cumulative evidence was considered low. Therefore, we encourage the development of high-quality preclinical studies. Registration: PROSPERO register CRD42020170191.

Determinants of Unresponsiveness to Treatment in Cutaneous Leishmaniasis: A Focus on Anthroponotic Form Due to Leishmania tropica

Cutaneous leishmaniasis (CL) is a curable disease; however, due to various risk factors, unresponsiveness to CL treatments is inevitable. The treatment of CL has been firmly correlated with multiple determinants, such as demographical, clinical, and environmental factors, the host’s immune response, poor treatment adherence, the parasite’s genetic make-up, and Leishmania RNA virus. This study primarily focuses on the risk factors associated with different therapeutic outcomes following meglumine antimoniate (MA; Glucantime®) treatment and policy approaches to prevent unresponsiveness in CL patients with a focus on anthroponotic form (ACL). Findings suggest that effective preventive and therapeutic measures should be more vigorously implemented, particularly in endemic areas. Accordingly, extensive training is essential to monitor drug unresponsiveness regularly, especially in tropical regions where the disease is prevalent. Since humans are the fundamental reservoir host of ACL due to L. tropica, prompt detection, early diagnosis, and timely and effective treatment could help control this disease. Furthermore, major challenges and gaps remain: efficacious vaccine, new tools, and expert staff are crucial before CL can be definitively controlled.

Risk factors for antimony treatment failure in American Cutaneous Leishmaniasis in Northwestern-Argentina.

Background. To date, there is no specific literature available on the determinants for therapeutic failure (TF) with meglumine antimoniate (MA) in Northwestern-Argentina. This study aimed to identify epidemiological, clinical, and treatment-related factors that could be involved in TF. Methodology/Principal Findings. We performed a case-control study. Cases were represented by patients who showed TF after administration of the first course of MA treatment, whereas, controls were determined as patients who evolved towards healing after the first MA cycle received. Crude Odds Ratios and their corresponding 90% confidence intervals (CI) were calculated, and risk factors were then tested by multivariate analysis using logistic binary regression. Three hundred and eighty-four patients with a presumptive diagnosis of ACL were recruited, and 153 with a positive diagnosis were selected. We included in the study 71 patients, who underwent specific treatment with MA, presented complete data on response to treatment, and had a minimum post-treatment follow-up of 6 months in cutaneous leishmaniasis, and 12 months in mucosal leishmaniasis. Of these, 34 (47.9%) presented TF. In the initial analysis, TF was significantly associated with the geographical area of disease acquisition (p = 0.036), the presence of mucosal lesions (p = 0.042), the presence of concomitant skin and mucosal lesions (p = 0.002), and lesion age ≥ 6 months (p = 0.018). Risk factors influencing TF in the final multivariate model included the geographical area where the disease was acquired (adjusted Odd Ratio 8.062; 95% CI 1.914–33.959; p = 0.004), and lesion age ≥ 6 months (adjusted Odd Ratio 10.037; 95% CI 1.383–72.843; p = 0.023). Conclusions/Significance. The results of the present study suggest the existence of some risk factors linked to TF in Northwestern-Argentina, which deserve further investigation. Herein we recorded a high percentage of TF and we described clinical and epidemiological characteristics associated with TF that could be taken into account improving the clinical management of patients.

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.

Immunomodulatory effects of topical diphencyprone for the treatment of acute urban cutaneous leishmaniasis

Background and objective Efficacious and safe treatments are lacking for cutaneous leishmaniasis (CL). This study investigates the efficacy of adding diphencyprone immunotherapy to conventional meglumine antimoniate (MA) treatment for acute urban CL. Methods This randomized controlled pilot study included 46 patients with acute CL. They were randomly allocated to receive either combination of diphencyprone immunotherapy with intralesional MA (intervention; N = 23) or intralesional MA alone (control; N = 23) weekly. The size and duration of lesions were measured at the baseline and after that at 4th, 8th, 12th, and 24th weeks. Data were analyzed in SPSS and p < .05 was considered significant. Results The groups showed no significant difference in duration of lesions, but number of injections was significantly higher in the control group compared with the intervention group (p < .001). Size and induration of lesions was significantly reduced in both groups during the course of study (p < .001). The intervention group showed significantly lower induration of lesions in 4th, 8th, and 12th week compared with controls (p < .05). Conclusion Combination of diphencyprone with MA resulted in earlier resolution of acute CL lesions with a relatively acceptable rate of adverse effects, compared with intralesional MA alone.

Treatment for human visceral leishmaniasis: a cost-effectiveness analysis for Brazil.

To estimate the cost-effectiveness of strategies for the treatment of VL in Brazil. Cost-effectiveness study comparing three therapeutic options: meglumine antimoniate (MA), liposomal amphotericin B (LAMB) and a combination of LAMB plus MA (LAMB plus MA), from public health system and societal perspectives. An analytical decision-making model was used to compare strategies for the following outcomes: early therapeutic failure avoided at 30days, days of hospitalisation avoided and VL cure at 180days. The efficacy and safety parameters of the drugs came from a randomised, open-label trial and the cost data came from a cost-of-illness study, both carried out in Brazil. For all outcomes analysed, the LAMB strategy was more effective. The MA strategy was inferior to the LAMB plus MA strategy for the outcomes early therapeutic failure avoided and cure. When only LAMB and MA were compared from a societal perspective, a cost of US$ 278.56 was estimated for each additional early therapeutic failure avoided, a cost of US$ 26.88 for each additional day of hospitalisation avoided and a cost of US$ 89.88 for each additional case of cured VL, for the LAMB strategy vs. MA. In Brazil, the LAMB strategy proved to be cost-effective for treating VL, considering a GDP per capita as the willingness-to-pay threshold, for all of the outcomes analysed in comparison to MA.

Embryonic toxico-pathological effects of meglumine antimoniate using a chick embryo model.

Leishmaniasis is one of the diverse and neglected tropical diseases. Embryo-toxicity of drugs has always been a major concern. Chick embryo is a preclinical model relevant in the assessment of adverse effects of drugs. The current study aimed to assess embryonic histopathological disorders and amniotic fluid biochemical changes following meglumine antimoniate treatment. The alteration of vascular branching pattern in the chick’s extra-embryonic membrane and exploration of molecular cues to early embryonic vasculogenesis and angiogenesis were also quantified. Embryonated chicken eggs were treated with 75 or 150 mg/kg of meglumine antimoniate. Embryo malformations, growth retardation and haemorrhages on the external body surfaces were accompanied by histopathological lesions in the brain, kidney, liver and heart in a dose-dependent manner. Significant rise occurred in the biochemical indices of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and amylase in the amniotic fluid. Quantification of the extra-embryonic membrane vasculature showed that the anti-angiogenic and anti-vasculogenic effects of the drug were revealed by a significant decrease in fractal dimension value and mean capillary area. The relative expression levels of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 mRNA also significantly reduced. Concerns of a probable teratogenicity of meglumine antimoniate were established by data presented in this study. It is concluded that tissue lesions, amniotic fluid disturbance, altered early extra-embryonic vascular development and gene expression as well as the consecutive cascade of events, might eventually lead to developmental defects in embryo following meglumine antimoniate treatment. Therefore, the use of meglumine antimoniate during pregnancy should be considered as potentially embryo-toxic. Hence, physicians should be aware of such teratogenic effects and limit the use of this drug during the growing period of the fetus, particularly in rural communities. Further pharmaceutical investigations are crucial for planning future strategies.

Depot Subcutaneous Injection with Chalcone CH8-Loaded Poly(Lactic-Co-Glycolic Acid) Microspheres as a Single-Dose Treatment of Cutaneous Leishmaniasis.

Conventional chemotherapy of cutaneous leishmaniasis (CL) is based on multiple parenteral or intralesional injections with systemically toxic drugs. Aiming at a single-dose localized therapy, biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with 7.8% of an antileishmanial nitrochalcone named CH8 (CH8/PLGA) were constructed to promote sustained subcutaneous release. In vitro, murine macrophages avidly phagocytosed CH8/PLGA smaller than 6 μm without triggering oxidative mechanisms. Upon 48 h of incubation, both CH8 and CH8/PLGA were 40 times more toxic to intracellular Leishmania amazonensis than to macrophages. In vivo, BALB/c were given one or three subcutaneous injections in the infected ear with 1.2 mg/kg of CH8 in free or CH8/PLGA forms, whereas controls received three CH8-equivalent doses of naked PLGA microparticles or meglumine antimoniate (Glucantime; Sanofi-Aventis). Although a single injection with CH8/PLGA reduced the parasite loads by 91%, triple injections with free CH8 or CH8/PLGA caused 80 and 97% reductions, respectively, in relation to saline controls. Meglumine antimoniate treatment was the least effective (only 36% reduction) and the most toxic, as indicated by elevated alanine aminotransferase serum levels. Together, these findings show that CH8/PLGA microparticles can be effectively and safely used for single-dose treatment of CL.

Low dose systemic or intralesional meglumine antimoniate treatment for American tegumentary leishmaniasis results in low lethality, low incidence of relapse, and low late mucosal involvement in a referral centre in Rio de Janeiro, Brazil (2001-2013).

BACKGROUNDAmerican tegumentary leishmaniasis (ATL) is a non-lethal parasitic disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL treatment aims at healing the lesions and preventing the development of the late mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg Sb5+/kg/day is the first choice of treatment. However, alternative therapies using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil.OBJECTIVESTo evaluate lethality and the incidence of relapse and development of late ML in CL patients treated at NIID from 2001 until 2013.METHODSData were recovered from records of all ATL patients diagnosed during that period.FINDINGSOut of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1% received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some patients required 1-3 additional courses of treatment, thus making a total of 997 courses; 85.2% of them were subjected to alternative therapies. Lethality was 0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow-up.MAIN CONCLUSIONSAlternative MA schedules resulted in low lethality without increase of relapse or late ML incidence.

Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum.

Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which meglumine antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with meglumine antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that meglumine antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both meglumine antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a meglumine antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.

Standardization of intralesional meglumine antimoniate treatment for cutaneous leishmaniasis

Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. The technique is described in detail sufficient to enable replication. The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.