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Immunosuppression is an important risk factor for leishmaniasis. We assessed the clinical profile, geographic distribution and prevalence of leishmaniasis in patients undergoing immunosuppressive therapy for dermatological, rheumatological or gastroenterological autoimmune diseases. We identified relevant studies in PubMed, EMBASE, Scopus, Web of Science and LILACS on July 3rd, 2018. We included articles that reported at least one case of leishmaniasis in patients undergoing immunosuppressive treatment for dermatological, rheumatological or gastroenterological diseases. Our protocol was registered in PROSPERO (CRD42018103050). We assessed the quality of the included studies with the Joanna Briggs Institute Critical Appraisal Tool. After the removal of duplicates, 5,431 articles were collected and screened. We included 138 articles; the prevalence of leishmaniasis in six methodologically similar studies varied from three to 1,282 cases per 100,000 patients using anti-TNFα drugs, but the results were significantly heterogeneous . Leishmaniasis in patients treated with immunosuppressive drugs is a health problem mostly reported in European countries bordering the Mediterranean Sea; sporadic activities, such as travelling, seem not to be associated with a significant risk of leishmaniasis, although effective control measures must always be observed.

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-1β 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]