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Artikel ; Online: Leishmaniasis: A new method for confirming cure and detecting asymptomatic infection in patients receiving immunosuppressive treatment for autoimmune disease.

Botana, Laura / Ibarra-Meneses, Ana Victoria / Sanchez, Carmen / Matia, Belen / San Martin, Juan Victor / Moreno, Javier / Carrillo, Eugenia

PLoS neglected tropical diseases

2021 Band 15, Heft 8, Seite(n) e0009662

Abstract: Visceral leishmaniasis (VL) in patients receiving immunosuppressant drugs for autoimmune disease has been on the rise. It is important-but difficult-to know when cure has been achieved in these patients since the withdrawal of immunosuppressants during ... ...

Abstract	Visceral leishmaniasis (VL) in patients receiving immunosuppressant drugs for autoimmune disease has been on the rise. It is important-but difficult-to know when cure has been achieved in these patients since the withdrawal of immunosuppressants during antileishmania treatment is commonly required, and there is a risk of relapse when immunosuppression is restored. The prevalence of asymptomatic infection among those immunosuppressed for autoimmune disease is also uncertain. The present work describes how cytokine release assays can be used to confirm the cure of VL, and to determine the prevalence of asymptomatic infection, in such patients. After collection of blood from volunteers (n = 108), SLA-stimulation of peripheral blood mononuclear cell cultures and of whole blood was found to induce the production of different combinations of cytokines that served to confirm recovery from VL, and asymptomatic Leishmania infection. Indeed, cure was confirmed in 14 patients, all of whom showed a specific Th1 immune response against Leishmania, and the prevalence of asymptomatic infection was determined as 21.27%. Cytokine profiles could be used to manage VL in patients with autoimmune disease, and to identify and better protect those with asymptomatic infection who are at risk of developing this disease.
Mesh-Begriff(e)	Adult ; Aged ; Antibodies, Protozoan/blood ; Asymptomatic Infections ; Autoimmune Diseases/drug therapy ; Clinical Laboratory Techniques/methods ; Cytokines/metabolism ; Drug Monitoring/methods ; Humans ; Immunosuppressive Agents/therapeutic use ; Leishmaniasis/diagnosis ; Leishmaniasis/epidemiology ; Leukocytes, Mononuclear/immunology ; Middle Aged
Chemische Substanzen	Antibodies, Protozoan ; Cytokines ; Immunosuppressive Agents
Sprache	Englisch
Erscheinungsdatum	2021-08-02
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0009662
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Role of asymptomatic and symptomatic humans as reservoirs of visceral leishmaniasis in a Mediterranean context.

Molina, Ricardo / Jiménez, Maribel / García-Martínez, Jesús / San Martín, Juan Víctor / Carrillo, Eugenia / Sánchez, Carmen / Moreno, Javier / Alves, Fabiana / Alvar, Jorge

PLoS neglected tropical diseases

2020 Band 14, Heft 4, Seite(n) e0008253

Abstract: Background: In the Mediterranean basin, Leishmania infantum is the causative agent of visceral leishmaniasis (VL), a zoonosis in which the dog is the primary domestic reservoir, although wildlife may have a leading role in the sylvatic cycle of the ... ...

Abstract	Background: In the Mediterranean basin, Leishmania infantum is the causative agent of visceral leishmaniasis (VL), a zoonosis in which the dog is the primary domestic reservoir, although wildlife may have a leading role in the sylvatic cycle of the disease in some areas. Infections without disease are very frequent. There is limited information regarding the role that VL patients and asymptomatic infected individuals could be playing in the transmission of L. infantum. Xenodiagnosis of leishmaniasis has been used in this descriptive study to explore the role of symptomatic and asymptomatic infected individuals as reservoirs in a recent focus of leishmaniasis in southwestern Madrid, Spain. Methodology and main findings: Asymptomatic blood donors (n = 24), immunocompetent patients who were untreated (n = 12) or treated (n = 11) for visceral leishmaniasis (VL), and immunocompromised patients with VL (n = 3) were enrolled in the study. Their infectivity to Phlebotomus perniciosus was studied by indirect xenodiagnosis on peripheral blood samples. Quantitative polymerase chain reaction of blood samples from immunocompetent patients untreated for VL and immunocompromised untreated, treated and under secondary prophylaxis for VL was performed. Antibodies against Leishmania were studied by indirect fluorescent antibody and rK39-immunochromatographic tests. A lymphoproliferative assay with a soluble Leishmania antigen was used to screen for leishmaniasis infection in the healthy population. Sixty-two xenodiagnostic tests were carried out and 5,080 sand flies were dissected. Positive xenodiagnosis was recorded in four patients, with different sand fly infection rates: 1 immunosuppressed HIV / L. infantum coinfected asymptomatic patient, 1 immunosuppressed patient with multiple myeloma and symptomatic active VL, and 2 immunocompetent patients with untreated active VL. All blood donors were negative for both xenodiagnosis and conventional PCR. Conclusions / significance: There is no consensus amongst authors on the definition of an 'asymptomatic case' nor on the tools for screening; we, therefore, have adopted one for the sake of clarity. Immunocompetent subjects, both infected asymptomatics and those treated for VL, are limited in number and appear to have no epidemiological relevance. The impact is limited for immunocompetent patients with untreated active VL, whilst immunosuppressed individuals undergoing immunosuppressive therapy and immunosuppressed individuals HIV / L. infantum coinfected were the most infectious towards sand flies. It is noteworthy that the HIV / L. infantum coinfected patient with asymptomatic leishmaniasis was easily infectious to sand flies for a long time, despite being under continuous prophylaxis for leishmaniasis. Accordingly, screening for latent Leishmania infection in HIV-infected patients is recommended in scenarios where transmission occurs. In addition, screening for VL in HIV-infected patients who have spent time in VL-endemic areas should also be implemented in non-endemic areas. More research is needed to better understand if some asymptomatic coinfected individuals contribute to transmission as 'super-spreaders'.
Mesh-Begriff(e)	Adult ; Animals ; Antibodies, Protozoan/blood ; Asymptomatic Diseases/epidemiology ; DNA, Protozoan/blood ; Disease Reservoirs ; Disease Transmission, Infectious ; Female ; Humans ; Leishmania infantum/isolation & purification ; Leishmaniasis, Visceral/epidemiology ; Leishmaniasis, Visceral/transmission ; Leukocytes, Mononuclear/immunology ; Male ; Middle Aged ; Psychodidae/parasitology ; Spain/epidemiology
Chemische Substanzen	Antibodies, Protozoan ; DNA, Protozoan
Sprache	Englisch
Erscheinungsdatum	2020-04-23
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0008253
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Evaluation in a Cytokine Storm Model In Vivo of the Safety and Efficacy of Intravenous Administration of PRS CK STORM (Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells).

Lapuente, Juan Pedro / Gómez, Gonzalo / Marco-Brualla, Joaquín / Fernández, Pablo / Desportes, Paula / Sanz, Jara / García-Gil, Mario / Bermejo, Fernando / San Martín, Juan Víctor / Algaba, Alicia / De Gregorio, Juan Carlos / Lapuente, Daniel / De Gregorio, Almudena / Lapuente, Belén / Gómez, Sergio / Andrés, María de Las Viñas / Anel, Alberto

Biomedicines

2022 Band 10, Heft 5

Abstract: Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti- ... ...

Abstract	Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti-inflammatory and anti-fibrotic effects, avoiding the overexpression of pro-inflammatory cytokines by the innate immune system at a given time. One of these products is the drug PRS CK STORM, a medium conditioned by allogenic M2-polarized macrophages, from coculture, with those macrophages M2 with MSC from fat, whose composition, in vitro safety, and efficacy we studied. In the present work, we publish the results obtained in terms of safety (pharmacodynamics and pharmacokinetics) and efficacy of the intravenous application of this biological drug in a murine model of cytokine storm associated with severe infectious processes, including those associated with COVID-19. The results demonstrate the safety and high efficacy of PRS CK STORM as an intravenous drug to prevent and treat the cytokine storm associated with infectious processes, including COVID-19.
Sprache	Englisch
Erscheinungsdatum	2022-05-08
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10051094
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Asymptomatic immune responders to Leishmania among HIV positive patients.

Botana, Laura / Ibarra-Meneses, Ana Victoria / Sánchez, Carmen / Castro, Alicia / San Martin, Juan Victor / Molina, Laura / Ruiz-Giardin, Jose Manuel / Carrillo, Eugenia / Moreno, Javier

PLoS neglected tropical diseases

2019 Band 13, Heft 6, Seite(n) e0007461

Abstract: Concomitant infection with human immunodeficiency virus (HIV) and the Leishmania parasite is a growing public health problem, the result of the former spreading to areas where the latter is endemic. Leishmania infection is usually asymptomatic in ... ...

Abstract	Concomitant infection with human immunodeficiency virus (HIV) and the Leishmania parasite is a growing public health problem, the result of the former spreading to areas where the latter is endemic. Leishmania infection is usually asymptomatic in immunocompetent individuals, but the proportion of HIV+ individuals in contact with the parasite who remain asymptomatic is not known. The aim of the present work was to examine the use of cytokine release assays in the detection of asymptomatic immune responders to Leishmania among HIV+ patients with no previous leishmaniasis or current symptomatology. Eighty two HIV+ patients (all from Fuenlabrada, Madrid, Spain, where a leishmaniasis outbreak occurred in 2009) were examined for Leishmania infantum infection using molecular and humoral response-based methods. None returned a positive molecular or serological result for the parasite. Thirteen subjects showed a positive lymphoproliferative response to soluble Leishmania antigen (SLA), although the mean CD4+ T lymphocyte counts of these patients was below the normal range. Stimulation of peripheral blood mononuclear cells (PBMC) or whole blood with SLA (the lymphoproliferative assay and whole blood assay respectively), led to the production of specific cytokines and chemokines. Thus, despite being immunocompromised, HIV+ patients can maintain a Th1-type cellular response to Leishmania. In addition, cytokine release assays would appear to be useful tools for detecting these individuals via the identification of IFN-γ in the supernatants of SLA-stimulated PBMC, and of IFN-γ, MIG and IL-2 in SLA-stimulated whole blood. These biomarkers appear to be 100% reliable for detecting asymptomatic immune responders to Leishmania among HIV+ patients.
Mesh-Begriff(e)	Adult ; Aged ; Asymptomatic Diseases/epidemiology ; Cell Proliferation ; Cytokines/metabolism ; Female ; HIV ; HIV Infections/complications ; Humans ; Leishmania infantum/immunology ; Leishmaniasis, Visceral/epidemiology ; Leukocytes, Mononuclear/immunology ; Male ; Middle Aged ; Spain/epidemiology ; Young Adult
Chemische Substanzen	Cytokines
Sprache	Englisch
Erscheinungsdatum	2019-06-03
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0007461
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Correction: Epidemiological Changes in Leishmaniasis in Spain According to Hospitalization-Based Records, 1997-2011: Raising Awareness towards Leishmaniasis in Non-HIV Patients.

Herrador, Zaida / Gherasim, Alin / Jimenez, B Carolina / Del Sol Granados, Maria / San Martín, Juan Victor / Aparicio, Pilar

PLoS neglected tropical diseases

2016 Band 10, Heft 1, Seite(n) e0004379

Sprache	Englisch
Erscheinungsdatum	2016-01
Erscheinungsland	United States
Dokumenttyp	Published Erratum
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0004379
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Epidemiological changes in leishmaniasis in Spain according to hospitalization-based records, 1997-2011: raising awareness towards leishmaniasis in non-HIV patients.

Herrador, Zaida / Gherasim, Alin / Jimenez, B Carolina / Granados, Maria del sol / Granados, Marisol / San Martín, Juan Victor / Aparicio, Pilar

PLoS neglected tropical diseases

2015 Band 9, Heft 3, Seite(n) e0003594

Abstract: In Spain, Leishmania infantum is endemic, human visceral and cutaneous leishmaniasis cases occurring both in the Peninsula, as well as in the Balearic Islands. We aimed to describe the clinical characteristics of leishmaniasis patients and the changes in ...

Abstract	In Spain, Leishmania infantum is endemic, human visceral and cutaneous leishmaniasis cases occurring both in the Peninsula, as well as in the Balearic Islands. We aimed to describe the clinical characteristics of leishmaniasis patients and the changes in the disease evolution after the introduction of antiretroviral therapy in 1997. In this descriptive study, we used Spanish Centralized Hospital Discharge Database for the hospitalized leishmaniasis cases between 1997 and 2011. We included in the analysis only the records having leishmaniasis as the first registered diagnosis and calculated the hospitalization rates. Disease trend was described taking into account the HIV status. Adjusted odds-ratio was used to estimate the association between clinical and socio-demographic factors and HIV co-infection. Of the total 8010 Leishmaniasis hospitalizations records, 3442 had leishmaniasis as first diagnosis; 2545/3442 (75.6%) were males and 2240/3442 (65.1%) aged between 14-65 years. Regarding disease forms, 2844/3442 (82.6%) of hospitalizations were due to visceral leishmaniasis (VL), while 118/3442 (3.4%) hospitalizations were cutaneous leishmaniasis (CL). Overall, 1737/2844 of VL (61.1%) were HIV negatives. An overall increasing trend was observed for the records with leishmaniasis as first diagnosis (p=0.113). Non-HIV leishmaniasis increased during this time period (p=0.021) while leishmaniasis-HIV co-infection hospitalization revealed a slight descending trend (p=0.717). Leishmaniasis-HIV co-infection was significantly associated with male sex (aOR=1.6; 95% CI: 1.25-2.04), 16-64 years age group (aOR=17.4; 95%CI: 2.1-143.3), visceral leishmaniasis aOR=6.1 (95%CI: 3.27-11.28) and solid neoplasms 4.5 (95% CI: 1.65-12.04). The absence of HIV co-infection was associated with lymph/hematopoietic neoplasms (aOR=0.3; 95%CI:0.14-0.57), other immunodeficiency (aOR=0.04; 95% CI:0.01-0.32) and transplant (aOR=0.01; 95%CI:0.00-0.07). Our findings suggest a significant increase of hospitalization in the absence of HIV co-infection, with a predomination of VL. We consider that clinicians in Spain should be aware of leishmaniasis not only in the HIV population but also in non HIV patients, especially for those having immunosuppression as an associate condition.
Mesh-Begriff(e)	Adolescent ; Adult ; Aged ; Coinfection/epidemiology ; Female ; HIV Infections/epidemiology ; Hospitalization/statistics & numerical data ; Humans ; Leishmaniasis/epidemiology ; Male ; Middle Aged ; Retrospective Studies ; Spain/epidemiology ; Time Factors
Sprache	Englisch
Erscheinungsdatum	2015-03-10
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0003594
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients.

Carrillo, Eugenia / Carrasco-Antón, Nerea / López-Medrano, Francisco / Salto, Efrén / Fernández, Laura / San Martín, Juan Víctor / Alvar, Jorge / Aguado, Jose María / Moreno, Javier

PLoS neglected tropical diseases

2015 Band 9, Heft 10, Seite(n) e0004179

Abstract: Spain has one of the world's largest pools of organ donors and is a global leader in terms of the number of transplants it performs. The current outbreak of leishmaniasis in Fuenlabrada (in the southwest of the region of Madrid, Spain) has involved 600 ... ...

Abstract	Spain has one of the world's largest pools of organ donors and is a global leader in terms of the number of transplants it performs. The current outbreak of leishmaniasis in Fuenlabrada (in the southwest of the region of Madrid, Spain) has involved 600 clinical cases since late 2009 (prevalence 0.2%). It may therefore be wise to monitor the town's transplanted population for Leishmania infantum; its members are immunosuppressed and at greater risk of infection and relapse following treatment. The present work examines the use of cytokine release assays to determine the prevalence of Leishmania infection in this population, and to confirm recovery following treatment for visceral leishmaniasis (VL). The humoral and cellular immune responses to L. infantum were characterized in 63 solid organ transplant (SOT) recipients from Fuenlabrada, 57 of whom reported no previous episode of VL (NVL subjects), and six of whom had been cured of VL (CVL subjects). Seventeen subjects (12 NVL and 5 CVL) showed a patent lymphoproliferative response to soluble Leishmania antigen (SLA). Stimulation of peripheral blood mononuclear cell cultures and of whole blood with SLA led to the production of different combinations of cytokines that might serve to confirm Leishmania infection or recovery from VL and help prevent cured patients from relapsing into this serious condition.
Mesh-Begriff(e)	Antibodies, Protozoan/blood ; Cell Proliferation ; Clinical Laboratory Techniques/methods ; Cytokines/metabolism ; Drug Monitoring/methods ; Humans ; Immunocompromised Host ; Leishmania infantum/immunology ; Leishmaniasis/diagnosis ; Leishmaniasis/epidemiology ; Leukocytes, Mononuclear/immunology ; Spain/epidemiology ; Transplant Recipients ; Transplants
Chemische Substanzen	Antibodies, Protozoan ; Cytokines
Sprache	Englisch
Erscheinungsdatum	2015-10-23
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0004179
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Leishmaniasis: A new method for confirming cure and detecting asymptomatic infection in patients receiving immunosuppressive treatment for autoimmune disease.

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Artikel ; Online: Role of asymptomatic and symptomatic humans as reservoirs of visceral leishmaniasis in a Mediterranean context.

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Artikel: Evaluation in a Cytokine Storm Model In Vivo of the Safety and Efficacy of Intravenous Administration of PRS CK STORM (Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells).

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Artikel ; Online: Asymptomatic immune responders to Leishmania among HIV positive patients.

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Artikel ; Online: Correction: Epidemiological Changes in Leishmaniasis in Spain According to Hospitalization-Based Records, 1997-2011: Raising Awareness towards Leishmaniasis in Non-HIV Patients.

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Artikel ; Online: Epidemiological changes in leishmaniasis in Spain according to hospitalization-based records, 1997-2011: raising awareness towards leishmaniasis in non-HIV patients.

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Artikel ; Online: Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients.

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