Novel detection of Leishmania RNA virus-1 (LRV-1) in clinical isolates of Leishmania Viannia panamensis.

American tegumentary leishmaniasis comprises a discrete set of clinical presentations endemic to Latin America. Leishmania RNA virus-1 (LRV-1) is a double-stranded RNA virus identified in 20­25% of the Leishmania Viannia braziliensis and L. V. guyanensis, however not in L. V. panamensis. This is the first report of LRV-1 in L. V. panamensis and its associations with clinical phenotypes of ATL. Unique surplus discard clinical isolates of L. V. panamensis were identified from the Public Health Ontario Laboratory (PHOL) and the Leishmania Clinic of the Instituto de Medicina Tropical 'Alexander von Humboldt' between 2012 and 2019 and screened for LRV-1 by real-time polymerase chain reaction. Patient isolates were stratified according to clinical phenotype. Of 30 patients with L. V. panamensis, 14 (47%) and 16 (53%) patients had severe and non-severe ATL, respectively. Five (36%) of 14 severe cases and 2 (12%) of 16 non-severe cases were positive for LRV-1, respectively. No differences in sex were observed for clinical phenotype and LRV-1 status. Although an association between LRV-1 status and clinical phenotype was not demonstrated, this is the first description of the novel detection of LRV-1 in L. V. panamensis, a species that has been documented predominantly in Central America.

Nasal Leishmaniasis Misdiagnosed With Intranasal Polyp in a Patient Candidate for Rhinoplasty.

Mucosal leishmaniasis (ML) is a chronic and rare form of leishmaniasis that causes malignant lesions in the mucosa of the nasal, pharyngeal, and laryngeal regions. We describe a 29-year-old woman who had been suffering from an intranasal polyp for 3 years. The polyp recurred annually after surgical removal, and was diagnosed as nasal leishmaniasis.

Accuracy of serological tests in diagnosing mucosal leishmaniasis.

In this serum panel-based study, we evaluated the accuracy of serological tests originally developed for visceral leishmaniasis (VL), for diagnosis of mucosal leishmaniasis (ML). A total of five tests were evaluated, four of which are registered at the National Agency of Sanitary Surveillance (Agência Nacional de Vigilância Sanitária-ANVISA) (RIDASCREEN® Leishmania Ab from R-Biopharm AG., Leishmania ELISA IgG + IgM from Vircell S.L., IFI Leishmaniose Humana-BioManguinhos, and IT-LEISH® from Bio-Rad Laboratories, Inc.), and the other a direct agglutination test (DAT-LPC) prototype kit developed at Fiocruz. The panel was composed of 40 serum samples from patients with confirmed ML and 20 from patients with mucosal involvement and negative parasitological/molecular tests for leishmaniasis and confirmation of another etiology. All cases were treated from 2009 to 2016 in a referral center for leishmaniasis in Belo Horizonte, Minas Gerais, Brazil (Instituto René Rachou, Fiocruz). Diagnostic accuracy, based on the cut-off point for VL diagnosis, was 86.2% with RIDASCREEN® Leishmania Ab, 73.3% with Leishmania ELISA IgG + IgM, and 66.7% with IFI Leishmaniose Humana, while IT-LEISH® and DAT-LPC had the lowest accuracy (38.3%), despite high specificity (100% and 95%, respectively). New cut-off points defined with sera from ML patients improved accuracy from 86.2 to 89% (p = 0.64) and 73.3 to 88% (p = 0.04) for RIDASCREEN® Leishmania Ab and Leishmania ELISA IgG + IgM, respectively. Moreover, these tests presented greater sensitivity and immunoreactivity in patients with moderate/severe clinical ML forms. The data of this study suggest that ELISA assays can contribute to laboratory diagnosis, especially for patients with moderate or severe mucosal involvement.

Factors associated with mucosal involvement in tegumentary leishmaniasis: a nation-based study using surveillance data from Brazil

ABSTRACT This study aimed to assess the factors associated with mucosal leishmaniasis (ML) within the scope of tegumentary leishmaniasis (TL) cases reported in Brazil. Surveillance data were assessed, and comparisons were made between ML and cutaneous leishmaniasis (CL) cases. Additionally, ML incidence rates for municipalities were depicted through a geographic information system. From 2007 to 2017, 235,489 TL cases were reported, of which 235,232 were classified as follows: 14,204 (6%) were ML cases and 221,028 (94%) were CL cases. Multivariate analysis showed that the proportion of ML cases reached 16.8% among individuals >75 years (adjusted OR = 2.77; 95% CI = 2.41-3.19; p < 0.001), and ML was also more frequent among males (aOR = 1.28; 95% CI = 1.20-1.38; p < 0.001), HIV-positive patients (aOR = 2.15; 95% CI = 1.80-2.56; p < 0.001), patients residing in urban areas (aOR = 1.52; 95% CI = 1.43-1.62; p < 0.001), and imported cases (with respect to county) when compared to autochthonous cases (aOR = 1.84; 95% CI = 1.71-1.98; p < 0.001). A lower proportion of positive results in direct parasitological examinations was observed in ML cases (32.6% vs. 60.8%; p < 0.001). The leishmanin skin test results were more often positive in ML cases (41.7% vs. 25.9%; p < 0.001). In ML, compatible changes in histopathology were more frequent (14.6% vs. 3.9%; p < 0.001). A greater proportion of ML cases were treated with amphotericin B (6.9% vs. 0.9%; p < 0.001). The case-fatality rate was higher in ML (0.6% vs. 0.1%; p < 0.001). A higher incidence of ML was observed in a geographical band extending across the Amazon region from the southern Para State to the Acre State. ML exhibited varying frequencies within specific populations. The definition of predictable factors predisposing Leishmania-infected subjects to develop ML is important for defining strategies to mitigate the mucosal damage caused by leishmaniasis.

Tegumentary Leishmaniasis in Northeastern Italy from 2017 to 2020: A Neglected Public Health Issue.

Tegumentary leishmaniasis (TL) includes cutaneous (CL) and mucosal (ML) leishmaniasis; despite being endemic in southern Europe, it is often underdiagnosed and underreported. This study aimed to retrospectively examine data collected from patients with TL in a selected area of northeastern Italy (Emilia-Romagna region, RER). A network of 10 diagnostic units within RER was established, and TL cases diagnosed in RER from 2017 to 2020 were evaluated. A total of 135 TL cases were collected (62% male, 38% female); patients ranged from 1 to 84 years, with a median age of 57. Among these cases, 113 (84%) were notified to the public health authorities. The average annual incidence of TL was 0.76 cases per 100,000 inhabitants. Infections were acquired within the RER in 84% of cases; the 113 autochthonous cases were distributed in the foothills areas of the region. We provide evidence of a defined spatial distribution of TL cases in a selected area of northeastern Italy, as well as a relevant number of ML cases. Our observations suggest the need to raise awareness about TL among clinicians and pathologists, promote the molecular confirmation of cases by reference laboratories, and encourage the establishment of surveillance networks for this neglected disease.

Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline.

Mucosal leishmaniasis (ML) is a severe form of tegumentary leishmaniasis associated with a persistent inflammatory response. High levels of TNF, IFN-γ, CXCL9 and CXCL10 are found in ML patients, and the association of pentoxifylline with antimony is more effective in decreasing the healing time in ML patients when compared to antimony alone. The present study aimed to investigate the existence of a correlation between cytokine and chemokine production and ML severity and evaluate the potential value of cytokine and chemokine production as marker of therapeutic response in ML patients. This prospective study included 86 subjects in an area of endemic Leishmania braziliensis transmission. Patients diagnosed with ML were classified into clinical stages ranging from I to V according to disease severity. TNF, IFN-γ, CXCL9 and CXCL10 levels were quantified in the supernatant of the mononuclear cell cultures by ELISA before and after treatment with antimony alone or antimony plus pentoxifylline. The median TNF level in the group with mild disease (Stages I-II) was 1064 pg/mL (142-3738 pg/mL), while, in the group with moderate or severe disease (Stages III-V), it was 1941 pg/mL (529-5294 pg/mL) (p = 0.008). A direct correlation was observed between ML clinical severity and levels of TNF production (r = 0.44, p = 0.007). Patients who were treated with antimony and pentoxifylline healed significantly faster than those treated with antimony alone (52 vs. 77 days, hazard ratio = 0.60; 95% confidence interval = 0.38-0.95, p = 0.013). Therapeutic failure was higher in the group that received antimony alone (25% vs. 7%; p = 0.041). There was a significant decrease in CXCL9 after therapy of ML in both groups (p = 0.013; p = 0.043). TNF levels are associated with the severity of mucosal diseases, and pentoxifylline associated with antimony should be the recommended therapy for ML in countries where liposomal amphotericin B is not available.

Clinical Diagnosis and Management of Mucosal Leishmaniasis in the Context of a Global Pandemic: A Case Report.

Mucosal leishmaniasis (ML) is a rare metastatic complication of Leishmania infection. It has a high potential for destructive and disfiguring complications, namely destruction of nasal architecture and airway compromise. ML is difficult to treat for a variety of reasons, including variable antimicrobial resistance rates between species, as well as between endemic areas geographically. There are several treatment options available, which are discussed here. In the majority of cases, a nuanced approach to treatment is required based on speciation and geography. Importantly, the treatment of ML requires a multi-disciplinary approach. We present a patient with a history of cutaneous leishmaniasis who presented with signs and symptoms concerning ML, but due to the COVID-19 global pandemic diagnostic testing was not possible, was treated empirically under clinical suspicion of ML with good results.

Meglumine antimoniate was associated with a higher cure rate than liposomal amphotericin B in the treatment of American tegumentary leishmaniasis: A retrospective cohort study from a Leishmania braziliensis-endemic area.

Background: Pentavalent antimonials (PAs) are the primary therapeutic option for American tegumentary leishmaniasis (ATL). However, the use of these drugs is complicated by adverse events (AEs), resistance and contraindications. Alternative therapies relative effectiveness is not well established. Objective: This study compared the effectiveness of liposomal amphotericin B (LAB) with intravenous meglumine antimoniate (NMG) in the treatment of ATL. We also analysed and compared associated AEs and treatment interruption rates. Methods: This was a retrospective cohort study from Brazil. The potential risk factors for the primary outcome were age, sex, total cutaneous lesion area, presence of mucosal lesions, AEs and treatment interruption. The primary outcome was lesion healing within 6 months of treatment. AEs and treatment interruption were also analysed. Multiple analytic strategies were employed to evaluate the reliability of the results. Results: Before propensity score (PS) matching, patients in the LAB group were older and had a higher frequency of mucosal lesions. The NMG group had a higher cure rate than the LAB group (cure rate 88% versus 55% respectively) in the adjusted analysis (relative risk (RR)=1.55 95% CI: 1.19 - 2.02) and after PS matching (RR=1.63 95% CI: 1.20 - 2.21). NMG group had a higher AE rate (event rate 52% versus 44%) in the adjusted analysis (RR= 1.61, 95% CI: 1.06 - 2.43, p=0.02), but this result was not observed after PS matching (RR= 0.87, 95% CI: 0.49 -1.52, p= 0.61). Conclusions: We observed that the NMG group had a higher cure rate than the LAB group, with an equivocally higher EV rate in the adjusted analysis.

Severe mucosal leishmaniasis with torpid and fatal evolution.

Mucosal leishmaniasis is a clinical condition that is difficult to diagnose and treat and usually precedes a cutaneous leishmaniasis condition with a long latency period as observed in our study of a patient who experienced a torpid evolution in 9 months, caused by having had cutaneous leishmaniasis on the neck without therapeutic treatment, although with ulcer closure 18 years earlier, incomplete treatment with antimonials and amphotericin B, with the destruction of the eyeball, a large area of necrosis on the face and nasal bone exposure. Additionally, the patient had chronic anemia (9.4 g/dl), lymphopenia and neutrophilia (lymphocytes 13.1%, neutrophils 84.4%), and co-infections by fungi (yeasts and hyphae) and Gram-negative bacteria (multidrug-resistant Proteus mirabilis and Escherichia coli) leading to sepsis and subsequent death of the patient.

Mucocutaneous Leishmaniasis in a Pregnant Immigrant.

Cutaneous leishmaniasis is a parasitic infection that causes significant maternal morbidity, and even fetal mortality, during pregnancy, yet there are limited therapeutic options. Here, we report a case of leishmaniasis in a pregnant immigrant with exuberant mucocutaneous lesions with favorable response to liposomal amphotericin B.

Painful and swollen tongue: mucosal leishmaniasis due to Leishmania infantum.

BACKGROUND: Leishmaniasis is a parasitic disease caused by different Leishmania species. L. infantum is found in the Mediterranean area. It usually causes visceral or cutaneous leishmaniasis, but rarely mucosal leishmaniasis (ML). METHODS: A 62-year-old man with metastatic non-small-cell lung carcinoma visited the outpatient clinic because of a painful and swollen tongue. Initially, oral candidiasis was suspected and patient was unsuccessfully treated accordingly. Subsequently, a biopsy from the tongue was taken. RESULTS: Histology of the tongue biopsy showed an inflammation with histiocytes and Leishmania amastigotes. Molecular analysis determined these parasites as L. donovani complex. Based on the patient's travel history, ML caused by L. infantum was diagnosed. CONCLUSION: ML is an unusual presentation of L. infantum. ML is not only caused by Leishmania species endemic in Latin America, but also should be considered in the differential diagnosis for European patients. A biopsy of the affected location is needed to confirm the diagnosis.

Overcoming the Negligence in Laboratory Diagnosis of Mucosal Leishmaniasis.

The northern region of Brazil, which has the largest number of cases of tegumentary leishmaniasis (TL) in the country, is also the region that has the highest diversity of species of vectors and Leishmania parasites. In this region, cases of mucosal leishmaniasis (ML), a clinical form of TL, exceed the national average of cases, reaching up to 12% of the total annual TL notifications. ML is associated with multiple factors, such as the parasite species and the viral endosymbiont Leishmania RNA virus 1 (LRV1). Being a chronic parasitological disease, laboratory diagnosis of ML poses a challenge for health services. Here, we evaluated more than 700 clinical samples from patients with clinical suspicion of TL, including patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis, comparing the results of parasitological tests-direct parasitological examination by microscopy (DP) and conventional PCR (cPCR) targeting of both kDNA and hsp70. The DP was performed by collecting material from lesions through biopsies (mucosal lesions) or scarification (cutaneous lesions); for PCR, a cervical brush was used for sample collection. Blood samples were tested employing standardized real-time PCR (qPCR) protocol targeting the HSP70 gene. PCR tests showed higher sensitivity than DP for both CL and ML samples. Considering ML samples only (N = 89), DP showed a sensitivity of 49.4% (N = 44) against 98.8% (N = 88) for kDNA PCR. The qPCR hsp70 for blood samples from patients with ML (N = 14) resulted in superior sensitivity (50%; N = 7) compared to DP (21.4%; N = 3) for samples from the same patients. Our results reinforced the need to implement a molecular test for the diagnosis of ML, in addition to proposing methods less invasive for collecting material from TL patients. Sample collection using a cervical brush in lesions observed in CL and ML patients is easy to perform and less invasive, compared to scarification and biopsies. Blood samples could be a good source for qPCR diagnosis for ML patients. Thus, we propose here a standardized method for collection and for performing of molecular diagnosis of clinical samples from suspicious ML patients that can be applied in reference services for improving ML diagnosis.

Wegener's granulomatosis and differential diagnosis of mucosal leishmaniasis.

Granulomatosis with polyangiitis with nasal septal perforation can be confused with infectious diseases such as mucosal leishmaniasis, so these cases warrant an in-depth study in order to provide the correct treatment. Among the main characteristics to consider to define a Wegener's granulomatosis as opposed to an infectious disease are vasculitis, lymphadenopathy, and sinusopathy.

A Pilot Randomized Clinical Trial: Oral Miltefosine and Pentavalent Antimonials Associated With Pentoxifylline for the Treatment of American Tegumentary Leishmaniasis.

Introduction: American tegumentary leishmaniasis (ATL), which can present as either cutaneous (CL) or mucosal leishmaniasis (ML), is endemic in South America, and first-line antimonial treatments are known for their wide range of adverse effects (AEs). Growing reports of drug resistance increase the urgency of the need for better treatment options. The objective of this pilot clinical trial was to assess the efficacy of and AEs associated with the oral combination of miltefosine and pentoxifylline based on a post hoc analysis. Methods: A pilot, randomized, open-label clinical trial was performed. The experimental group (M+P) received 50 mg twice a day (BID) miltefosine and 400 mg three times a day (TID) pentoxifylline, and the control group (A+P) received 20 mg Sb+V/kg/day intravenously and 400 mg TID pentoxifylline. Patients with ML received treatment for 28 days, and patients with CL received treatment for 20 days. Results: Forty-three patients were included: 25 with ML and 18 with CL caused by L.(V.) braziliensis. AEs were more frequent in the A+P group (p=0.322), and there was a need for treatment interruption due to severe AEs (p=0.027). Patients with CL had a higher chance of achieving a cure (p=0.042) and a higher risk of AEs (p=0.033). There was no difference in the chance of a cure based on the treatment (p=0.058). Conclusion: In this pilot randomized clinical trial, M+P treatment and A+P treatment yielded similar cure rates, and the former was associated with a lower risk of AEs. Future studies with more patients and longer follow-up are recommended.

High Anti-Leishmania IgG Antibody Levels Are Associated With Severity of Mucosal Leishmaniasis.

Background: Mucosal leishmaniasis (ML), the most inflammatory form of tegumentary leishmaniasis, is predominantly caused by Leishmania braziliensis. The disease is characterized by the development of lesions, mainly in the nasal mucosa. An exacerbated inflammatory response has been associated with the presence of destructive and disfiguring lesions, with stages of severity ranging from small nodulations to the complete destruction of the nasal pyramid architecture. As Leishmania is an intracellular parasite, most immunological studies have emphasized the cell-mediated immune response, while relatively few studies aimed to investigate the role antibodies in protection against, or the pathology of ML. Methods: Patients with a confirmed diagnosis of ML were classified according to clinical staging criteria. Serum levels of Leishmania-specific IgG, IgG1 and IgG2 antibodies were determined by ELISA before and after treatment with antimony or antimony plus pentoxifylline. Results: Patients in stages IV and V produced higher concentrations of IgG and IgG1 antibodies when compared to those in stage I and II. Significant reductions were seen in the concentrations of IgG and IgG2 antibodies in most patients who responded well to treatment. Conclusions: Our data demonstrate an association between IgG antibody titers and the severity of mucosal disease. The observed reduction in antibody production after successful treatment in most patients preliminarily indicates that these tests can be used to aid in the assessment of therapeutic response.

Efficacy and safety of pentamidine isethionate for tegumentary and visceral human leishmaniasis: a systematic review.

RATIONALE FOR REVIEW: We performed a systematic review of the literature to investigate the efficacy and safety of pentamidine isethionate for the treatment of human tegumentary and visceral leishmaniasis. KEY FINDINGS: A total of 616 papers were evaluated, and 88 studies reporting data on 3108 cases of leishmaniasis (2082 patients with tegumentary leishmaniasis and 1026 with visceral leishmaniasis) were finally included. The majority of available studies were on New World cutaneous leishmaniasis and visceral leishmaniasis caused by Leishmania donovani. At the same time, few data are available for Old World cutaneous leishmaniasis, mucosal leishmaniasis, and visceral leishmaniasis caused by L. infantum. Pooled cure rate for tegumentary leishmaniasis was 78.8% (CI 95%, 76.9-80.6%) and 92.7% (CI 95%, 88.3-97.1%) according to controlled randomized trial and observational studies and case report and case series respectively. Pooled cure rate for visceral leishmaniasis was 84.8% (CI 95%, 82.6-87.1%) and 90.7% (CI 95%, 84.1-97.3%) according to controlled randomized trial and observational studies and case report and case series, respectively. Comparable cure rate was observed in recurrent and refractory cases of visceral leishmaniasis. Concerning the safety profile, among about 2000 treated subjects with some available information, the most relevant side effects were six cases of arrhythmia (including four cases of fatal ventricular fibrillation), 20 cases of irreversible diabetes, 26 cases of muscular aseptic abscess following intramuscular administration. CONCLUSIONS/RECOMMENDATIONS: Pentamidine isethionate is associated with a similar cure rate of the first-line anti-leishmanial drugs. Severe and irreversible adverse effect appear to be rare. The drug may still have a role in the treatment of any form of human leishmaniasis when the first-line option has failed or in patients who cannot tolerate other drugs also in the setting of travel medicine. In difficult cases, the drug can also be considered as a component of a combination treatment regimen.

El tratamiento intralesional de Leishmaniasis cutánea es seguro frente al riesgo de complicaciones mucosas? / Is the intralesional treatment of cutaneous Leishmaniasis safe against the risk of mucosal complications?

OBJETIVO: evaluar la seguridad a largo plazo frente al riesgo de complicaciones mucosas del uso intralesional de antimoniales pentavalentes en pacientes con leishmaniasis cutánea comparado con el uso sistémico de los mismos. MÉTODOS: estudio observacional, cuantitativo de tipo longitudinal retrospectivo. Se analizó un total de 66 registros clínicos de pacientes, con diagnóstico de Leishmaniasis cutánea del parque Isiboro Secure durante el periodo 2012 a 2016. Se evaluó un total de 46 tratamientos sistémicos y 20 intralesionales. RESULTADOS: la evaluación clínica realizada entre 4 y 7 años posteriores a la cicatrización de las lesiones cutáneas de Leishmaniasis mostró la ausencia de desarrollo de lesiones mucosas. Así mismo no se reportó fallas terapéuticas, recidivas ni efectos adversos a corto plazo. CONCLUSIONES: el tratamiento intralesional fue seguro y eficaz a largo plazo y es una opción confiable para el tratamiento de leishmaniasis cutánea evitando las complicaciones futuras de la enfermedad.

OBJECTIVE: to assess the long-term safety against the risk of mucosal complications of intralesional pentavalent antimonials (PA) in patients with cutaneous Leishmaniasis compared to the systemic use of PA. METHODS: retrospective longitudinal quantitative observational study. A total of 66 clinical records of patients diagnosed with cutaneous Leishmaniasis in Isiboro Secure Park were analyzed between 2012 and 2016. A total of 46 systemic and 20 intralesional treatments were evaluated. RESULTS: clinical evaluation 4-7 years after healing of Leishmaniasis skin lesions showed no development of mucosal lesions. Likewise, no therapeutic failures, relapses or short-term adverse effects were reported. CONCLUSIONS: intralesional treatment was safe and effective in the long term and is a reliable option for the treatment of cutaneous Leishmaniasis avoiding the future complications of the disease.

Pharmaceutical agents for treatment of leishmaniasis: a patent landscape.

INTRODUCTION: Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. Worldwide, approximately 1.5-2 million new cases of leishmaniasis and 20,000-30,000 deaths occurs each year. Effective treatment for all forms of leishmaniasis have numerous adverse effects contributing to poor adherence and/or treatment interruption by the patient. Development of novel therapies, as multitarget drugs, for example, can contribute to accelerate discover safer, more active, and patient-compliant drugs for leishmaniasis treatment. AREAS COVERED: In this review, authors summarize pharmaceutical agents for treatment of leishmaniasis developed between 2014 and 2019, which includes synthetic and natural drugs for specific treatments, as well as considering new approaches and strategies using drug delivery system. EXPERT OPINION: Universities or public research institutes produced most of the patents related to pharmaceutical agents for treatment of leishmaniasis in this review, and the majority of the inventions disclosed did not conduct clinical trials. In other words, there is still a lot of investment to be done for the identification of new drugs.

Effects of Meglumine Antimoniate Treatment on Cytokine Production in a Patient with Mucosal Leishmaniasis and Chagas Diseases Co-Infection.

The influence of antimoniate treatment on specific anti-protozoan T-cell responses was evaluated in a 48-year-old male patient diagnosed with mucosal leishmaniasis and Chagas disease infection. Before and after treatment, PBMC (peripheral blood mononuclear cells) were cultured in the absence or presence of Leishmania braziliensis or Trypanosoma cruzi live parasites, their soluble antigens, or PHA (phytohaemagglutinin). Cytokines were measured and Treg (T regulatory) cell percentages were quantified. Before treatment, PBMC were able to produce higher amounts of TNF-α, IL-6 (Interleukin-6), and IL-10 (Interleukin-10) but lower amounts of IL-12 (Interleukin-12) in response to culture stimulation. However, after treatment, there was a down-modulation of TNF-α, IL-6, and IL-10 cytokines but an up-modulation in IL-12 production. PBMC had the ability to produce TNF-α only against live parasites or PHA. There was an overall decrease of circulating Treg cells after treatment. In mixed Leishmaniasis and Chagas disease infection, treatment with antimoniate could modulate immune responses toward a more protective profile to both diseases.