The Effectiveness of Topical Dimethicone Together with a One Health Approach for the Control of Tungiasis in the Sanumás Communities, Yanomami Territory, Amazon Rainforest: A Real-World Study.

BACKGROUND: The success of tungiasis treatment is highly dependent on adequate environmental control. METHODS: This is a real-world observational cohort study designed to monitor the effectiveness of topical dimethicone together with a One Health approach for the control of tungiasis in the Sanumás communities, Amazon rainforest, Brazil. We followed up on 562 indigenous people and 81 domestic dogs for 1.5 years in a 3-month interval. A new molecular method for large-scale soil evaluation was also tested. The control of tungiasis was independently conducted by the Brazilian Ministry of Health and comprised topical dimethicone application (NYDA®) for humans, single-dose oral afoxolaner for dogs, and in-house soil fumigation with fipronil. The main outcome was the occurrence of tungiasis after the use of topical dimethicone together with the One Health approach. RESULTS: A total of 49 of the 562 indigenous people had active tungiasis at enrollment (8.72%). Only three cases of tungiasis resulted in active lesions after the use of topical dimethicone together with the One Health approach, with two cases of recurrence. From the 6-month follow-up and after, soil infestation was not detected. CONCLUSIONS: We conclude that the use of NYDA® together with animal and environmental interventions are effective measures for the control of tungiasis.

Tungiasis in the Sanumás Amerindians in the Amazon Rainforest, Brazil: Prevalence, Intensity and Morbidity.

BACKGROUND: Tungiasis is a disease associated with extreme poverty. We aimed to evaluate the prevalence of tungiasis in six different settlements of the Sanumás indigenous community in a remote area in the Auaris region, Yanomami territory, Brazil. METHODS: We conducted an observational study to detect clinical and epidemiological factors associated with tungiasis using a cross-sectional strategy and multivariate logistic regression. Soil analysis was performed by visual and microscopic methods. RESULTS: We examined 555 persons, 45 of whom had active tungiasis; 18 cases were classified as mild, 16 as moderate and 11 as severe. The disease was significantly more prevalent in children than in adults (odds ratio (OR) 15.77; 95% confidence interval (CI) = 5.34-67.91; p < 0.001). Soil infestation was significantly related to the occurrence of human tungiasis (OR = 12.29; 95% CI = 3.75-45.88). The sex and GPS location of the houses were not related to the occurrence of tungiasis. CONCLUSIONS: We conclude that tungiasis is an important problem in the Sanumás community, especially for children. We suggest that interruption of the off-host transmission cycle, together with regular treatment [human and animal interventions], must be prioritized to achieve control of tungiasis in indigenous populations.

Automated Identification of Cutaneous Leishmaniasis Lesions Using Deep-Learning-Based Artificial Intelligence.

The polymorphism of cutaneous leishmaniasis (CL) complicates diagnosis in health care services because lesions may be confused with other dermatoses such as sporotrichosis, paracocidiocomycosis, and venous insufficiency. Automated identification of skin diseases based on deep learning (DL) has been applied to assist diagnosis. In this study, we evaluated the performance of AlexNet, a DL algorithm, to identify pictures of CL lesions in patients from Midwest Brazil. We used a set of 2458 pictures (up to 10 of each lesion) obtained from patients treated between 2015 and 2022 in the Leishmaniasis Clinic at the University Hospital of Brasilia. We divided the picture database into training (80%), internal validation (10%), and testing sets (10%), and trained and tested AlexNet to identify pictures of CL lesions. We performed three simulations and trained AlexNet to differentiate CL from 26 other dermatoses (e.g., chromomycosis, ecthyma, venous insufficiency). We obtained an average accuracy of 95.04% (Confidence Interval 95%: 93.81-96.04), indicating an excellent performance of AlexNet in identifying pictures of CL lesions. We conclude that automated CL identification using AlexNet has the potential to assist clinicians in diagnosing skin lesions. These results contribute to the development of a mobile application to assist in the diagnosis of CL in health care services.

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.

The Presence of Leishmania braziliensis DNA in the Nasal Mucosa of Cutaneous Leishmaniasis Patients and the Search for Possible Clinical and Immunological Patterns of Disease Progression: A Cross Sectional Study.

Leishmania braziliensis is the most important causal agent of American tegumentary leishmaniasis (ATL), and 3 to 5% of patients develop mucosal lesions. The mechanisms related to parasite and host immune interactions and the parasite life cycle that lead to dissemination to the mucosa are poorly understood. We aimed to detect L. braziliensis DNA in the nasal mucosa of cutaneous leishmaniasis (CL) patients with early mucous dissemination and to relate those findings to specific inflammatory responses. Nasal swabs were collected from patients with the cutaneous form of ATL. L. braziliensis DNA was investigated using TaqMan-based real-time PCR. The levels of serum cytokines (IL-12, IL-6, TNF-α, IL-10, IL-1ß and IL-8) were measured by a multiplex cytometric array. A Poisson regression model was used to test prevalence ratios (PRs) and multivariate interactions of clinical and laboratory characteristics. Of the 79 CL patients, 24 (30%) had L. braziliensis DNA in the nasal mucosa. In the multivariate model, parasite DNA presence in mucosa was associated with a reduction in IL-12 levels (PR = 0.440; p=0.034), increased IL-6 levels (PR = 1.001; p=0.002) and a higher number of affected body segments (PR = 1.65; p<0.001). In this study, we observed a higher rate of early dissemination to the nasal mucosa than what was previously described. We suggest that an enhanced Th1 profile characterized by higher IL-12 is important for preventing dissemination of L. braziliensis to the mucosa. Further evaluation of parasite-related interactions with the host immunological response is necessary to elucidate the dissemination mechanisms of Leishmania.

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study.

BACKGROUND: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. METHODOLOGY/PRINCIPAL FINDINGS: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19. CONCLUSIONS/SIGNIFICANCE: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.

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.

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

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

α1-Acid glycoprotein and seminal parameter in chronic hemodialysis patients.

INTRODUCTION: To find out the changes in seminal quality of hemodialysis chronic renal patients, we investigated the possible relationship between seminal parameter and seminal α1-acid glycoprotein levels in chronic hemodialysis patients. METHODS: Prospective study of prevalence realized in the Hemodialysis Sector of the University Hospital of the University of Brasília, between July 2016 and December 2016. Men aged 18-60 years grouped into case groups (n = 81) represented by chronic hemodialysis patients and control group (n = 20) of healthy men without clinical or laboratory signs of infection and eugonadic. We performed a spermogram, hormonal profile, and assessment of leukocytes and seminal α1-acid glycoprotein level in the semen. The most appropriate statistical test was applied to verify differences and correlations between the studied variables. RESULTS: The age in case and control is similar (49.47 ± 5.55 years vs 50.53 ± 4.24 years; p = 0.060). Mean level of α1-acid glycoprotein in human seminal plasma were not significantly different between case and control (48.52 ± 4.90 mg/L vs 46.33 ± 4.29 mg/L; p = 0.10) and between normosperm and oligosperm (47.76 ± 5.15 mg/L vs 49.48 ± 4.49 mg/L; p = 0.19). Mean level of α1-acid glycoprotein in human seminal plasma in the case group, which were classified into severe, moderate, mild, and normosperm, were similar to each other (p = 0.27) and did not correlate (p > 0.05) with the analyzed seminal parameters. All participants presented normal hormonal profile. CONCLUSION: Results of this study suggest that the seminal α1-acid glycoprotein levels do not help in the initial evaluation of patients with seminal parameter changes.

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

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

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

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

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

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

Aplicações do Deep Learning para diagnóstico de doenças e identificação de insetos vetores / Deep Learning applications for disease diagnosis and identification of insect vectors

RESUMO Deep Learning é uma técnica de aprendizado de máquina na qual o programa computacional aprende padrões diretamente a partir de imagens classificadas previamente. O presente ensaio objetivou apresentar essa técnica e algumas de suas aplicações para diagnóstico de doenças e identificação de insetos vetores para incentivar profissionais da saúde que não tenham conhecimento aprofundado em informática e que desejem utilizar a ferramenta para realizar análises automatizadas. Deep Learning tem sido aplicado para diagnóstico de câncer, fibrose cardíaca, tuberculose, detecção de parasitos como Plasmodium e Leishmania e ainda para identificação de insetos vetores. Na Universidade de Brasília, a técnica tem sido aplicada para desenvolver uma ferramenta para identificar lesões ulceradas de leishmaniose em diagnóstico diferencial e para detectar Leishmania em lâminas de estudos histopatológicos. Além disso, Deep Learning tem sido usado para identificar as espécies de vetores da doença de Chagas - o que é importante para auxiliar na vigilância epidemiológica. O uso da tecnologia envolve desafios éticos e procedimentais que são discutidos no presente ensaio. O ensaio aponta perspectivas de desenvolvimento de aplicativos que auxiliem os profissionais de saúde no diagnóstico de Leishmaniose e de vetores da doença de Chagas, o que vai ao encontro dos objetivos da pesquisa translacional.

ABSTRACT Deep Learning is a machine learning technique in which the computational algorithm learns patterns directly from images previously classified. The present essay aims to show some of its applications for clinical diagnosis and identification of insect vectors to encourage health professionals who do not have deep knowledge of computer science and who wish to use the tool to perform automated analyzes. Deep Learning has been applied to the diagnosis of cancer, cardiac fibrosis, tuberculosis, detection of parasites such as Plasmodium and Leishmania, and to identify insect vectors. At the University of Brasília, Deep Learning has been used to develop a tool to identify ulcers caused by leishmaniasis, as well as to detect Leishmania parasites. Moreover, Deep Learning was applied to identify the species of vectors of Chagas disease, an important contribution to the epidemiological surveillance of the disease. The use of Deep Learning involves some ethical and procedural issues that are discussed in this paper. Finally, the essay points out perspectives of development of apps that assist health professionals in the diagnosis of Leishmaniasis and Chagas disease vectors, which meets the goals of translational research.

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

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

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

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

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

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