Chemokines and chemokine receptor-mediated effects are important mediators of the immunological response and cure in human leishmaniasis. However, in addition to their signalling properties for leukocytes, many chemokines have also been shown to act directly as antimicrobial peptides on bacteria and fungi. We screened ten human chemokines (CXCL2, CXCL6, CXCL8, CXCL9, CXCL10, CCL2, CCL3, CCL20, CCL27, CCL28) for antimicrobial effects on the promastigote form of the protozoan parasite Leishmania mexicana, and observed direct parasiticidal effects of several, CCL28 being the most potent. Damage to the plasma membrane integrity could be visualised by entrance of propidium iodide, as measured with flow cytometry, and by scanning electron microscopy, which showed morphological changes and aggregation of cells. The findings were in concordance with parasiticidal activity, measured by decreased mitochondrial activity in an MTT-assay. This is the first report of direct antimicrobial activity by chemokines on parasites. This component of immunity against Leishmania parasites identified here warrants further investigation that might lead to new insight in the mechanisms of human infection and/or new therapeutic approaches.
Background Cutaneous leishmaniasis (CL) is frequent in travellers and can involve oro-nasal mucosae. Clinical presentation impacts therapeutic management. Methodology Demographic and clinical data from 459 travellers infected in 47 different countries were collected by members of the European LeishMan consortium. The infecting Leishmania species was identified in 198 patients. Principal findings Compared to Old World CL, New World CL was more frequently ulcerative (75% vs 47%), larger (3 vs 2cm), less frequently facial (17% vs 38%) and less frequently associated with mucosal involvement (2.7% vs 5.3%). Patients with mucosal lesions were older (58 vs 30 years) and more frequently immunocompromised (37% vs 3.5%) compared to patients with only skin lesions. Young adults infected in Latin America with L. braziliensis or L. guyanensis complex typically had an ulcer of the lower limbs with mucosal involvement in 5.8% of cases. Typically, infections with L. major and L. tropica acquired in Africa or the Middle East were not associated with mucosal lesions, while infections with L. infantum, acquired in Southern Europe resulted in slowly evolving facial lesions with mucosal involvement in 22% of cases. Local or systemic treatments were used in patients with different clinical presentations but resulted in similarly high cure rates (89% vs 86%). Conclusion/Significance CL acquired in L. infantum-endemic European and Mediterranean areas displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised patients. When used as per recommendations, local therapy is associated with high cure rates.
Many endocarditis pathogens activate human platelets and this has been proposed to contribute to virulence. Here we report for the first time that many clinical isolates of Enterococcus faecalis, a common pathogen in infective endocarditis, aggregate human platelets. 84 isolates from human blood and urine were screened for their ability to aggregate platelets from four different donors. Platelet aggregation occurred for between 11 and 65 % of isolates depending on the donor. In one donor, a significantly larger proportion of isolates from blood than from urine caused platelet aggregation. Median time to aggregation was 11 minutes and had a tendency to be shorter for blood isolates as compared to urine isolates.Immunoglobulin G (IgG) was shown to be essential in mediating activation and aggregation. Platelet aggregation could be abolished by an IgG-specific proteinase (IdeS), by an antibody blocking FcRIIa on platelets, or by preabsorption of plasma with an E. faecalis isolate. Fibrinogen binding to bacteria or platelets does not contribute to platelet activation or aggregation under our experimental conditions. These results indicate that platelet activation and aggregation by E. faecalis is dependent on both host and bacterial factors and that it may be involved in the pathogenesis of invasive disease with this organism.
In Sweden, leishmaniasis is an imported disease and its epidemiology and incidence were not known until now. We conducted a retrospective, nationwide, epidemiological study from 1993 to 2016. Probable cases were patients with leishmaniasis diagnoses reported to the Swedish Patient registry, collecting data on admitted patients in Swedish healthcare since 1993 and out-patient visits since 2001. Confirmed cases were those with a laboratory test positive for leishmaniasis during 1993-2016. 299 probable cases and 182 confirmed cases were identified. Annual incidence ranged from 0.023 to 0.35 per 100 000 with a rapid increase in the last 4 years. Of 182 laboratory-verified cases, 96 were diagnosed from 2013 to 2016, and in this group, almost half of the patients were children under 18 years. Patients presented in different healthcare settings in all regions of Sweden. Cutaneous leishmaniasis was the most common clinical manifestation and the majority of infections were acquired in Asia including the Middle East, specifically Syria and Afghanistan. Leishmania tropica was responsible for the majority of cases (42%). A combination of laboratory methods increased the sensitivity of diagnosis among confirmed cases. In 2016, one-tenth of the Swedish population were born in Leishmania-endemic countries and many Swedes travel to these countries for work or vacation. Swedish residents who have spent time in Leishmania-endemic areas, could be at risk of developing disease some time during their lives. Increased awareness and knowledge are needed for correct diagnosis and management of leishmaniasis in Sweden.
BackgroundLeishmaniasis is a neglected and poorly reported parasitic infection transmitted by sand flies in tropical and subtropical regions. Knowledge about leishmaniasis has become important in non-endemic countries due to increased migration and travel. Few studies of the clinical management of cutaneous, mucocutaneous and visceral leishmaniasis in non-endemic regions have been published to date. In this study, we aimed to evaluate patient characteristics, clinical manifestations and treatments of leishmaniasis in Sweden, over a 20-year period.MethodsA retrospective observational nationwide study was performed using medical records of patients diagnosed with leishmaniasis in Sweden from 1996 to 2016. Cases with culture and polymerase chain reaction verified leishmaniasis were identified at the Public Health Agency of Sweden.ResultsIn total, 165 cases of leishmaniasis were diagnosed from 1996 to 2016. Medical records from 156 patients (95%) were available for review and included in the study. Cutaneous leishmaniasis was the dominant manifestation (n = 149, 96%), and in 66 patients (44%) cutaneous leishmaniasis was due to Leishmania tropica. Other manifestations were mucocutaneous (n = 4, 3%), visceral (n = 2, 1%) and post-kala-azar dermal leishmaniasis (n = 1, 1%). During this time period, the number of cases increased, especially after 2013. Most patients (n = 81, 52%) were migrants who were infected in their countries of origin (from 2013 to 2016, mainly Syria or Afghanistan). Other groups were Swedish tourists (25%) and returning workers (13%). The time from collection of the diagnostic sample to the start of treatment was less than one month in 81 (66%) patients and under three months in 124 patients (96%). Among the 149 patients with cutaneous leishmaniasis, 125 patients received antileishmanial treatment, and in 88 of these patients (70%) cure was achieved, regardless of treatment.ConclusionsThe number of leishmaniasis cases diagnosed in Sweden increased between 1996 and 2016, mainly in migrants from endemic countries. Although leishmaniasis is a rare disease in Sweden, patients appear to be diagnosed early and treated according to current European guidelines, resulting in an overall high cure rate.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3539-1) contains supplementary material, which is available to authorized users.
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