Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Más filtros

Intervalo de año de publicación
1.
N Engl J Med ; 388(17): 1582-1596, 2023 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-37099341

RESUMEN

BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).


Asunto(s)
Adyuvantes Inmunológicos , Vacuna BCG , COVID-19 , Personal de Salud , Humanos , Vacuna BCG/uso terapéutico , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/uso terapéutico , Método Doble Ciego , SARS-CoV-2 , Adyuvantes Inmunológicos/uso terapéutico
2.
Mem Inst Oswaldo Cruz ; 118: e220044, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36995847

RESUMEN

BACKGROUND: Dendritic cells (DCs) specific intercellular adhesion molecule (ICAM)-3-grabbing non integrin receptor (DC-SIGN) binds to subgenera Leishmania promastigotes mediating its interaction with DC and neutrophils, potentially influencing the infection outcome. OBJECTIVES: In this work, we investigated whether DC-SIGN receptor is expressed in cells from cutaneous leishmaniasis (CL) lesions as well as the in vitro binding pattern of Leishmania (Viannia) braziliensis (Lb) and L. (L.) amazonensis (La) promastigotes. METHODS: DC-SIGN receptor was labeled by immunohistochemistry in cryopreserved CL tissue fragments. In vitro binding assay with CFSE-labeled Lb or La promastigotes and RAJI-transfecting cells expressing DC-SIGN (DC-SIGNPOS) or mock-transfected (DC-SIGNNEG) were monitored by flow cytometry at 2 h, 24 h and 48 h in co-culture. RESULTS: In CL lesion infiltrate, DC-SIGNPOS cells were present in the dermis and near the epidermis. Both Lb and La bind to DC-SIGNPOS cells, while binding to DC-SIGNNEG was low. La showed precocious and higher affinity to DC-SIGNhi population than to DC-SIGNlow, while Lb binding was similar in these populations. CONCLUSION: Our results demonstrate that DC-SIGN receptor is present in L. braziliensis CL lesions and interact with Lb promastigotes. Moreover, the differences in the binding pattern to Lb and La suggest DC-SIGN can influence in a difference way the intake of the parasites at the first hours after Leishmania infection. These results raise the hypothesis that DC-SIGN receptor could participate in the immunopathogenesis of American tegumentary leishmaniasis accounting for the differences in the outcome of the Leishmania spp. infection.


Asunto(s)
Leishmania braziliensis , Leishmania , Leishmaniasis Cutánea , Humanos , Leishmania braziliensis/metabolismo , Leishmaniasis Cutánea/parasitología , Moléculas de Adhesión Celular/metabolismo
3.
J Infect Dis ; 224(12): 2064-2072, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34008010

RESUMEN

BACKGROUND: It is unknown whether dysglycemia is associated with Mycobacterium tuberculosis transmission. METHODS: We assessed epidemiological and clinical characteristics of patients with culture-confirmed pulmonary tuberculosis and their close contacts, enrolled in a multicenter prospective cohort in Brazil. Contacts were investigated at baseline and 6 months after enrollment. QuantiFERON positivity at baseline and conversion (from negative to positive at month 6) were compared between subgroups of contacts according to glycemic status of persons with tuberculosis (PWTB) as diabetes mellitus (DM) or prediabetes. Multivariable mixed-effects logistic regression models were performed to test independent associations with baseline QuantiFERON positive and QuantiFERON conversion. RESULTS: There were 592 PWTB (153 DM, 141 prediabetes, 211 normoglycemic) and 1784 contacts, of whom 658 were QuantiFERON-positive at baseline and 106 converters. Multivariable analyses demonstrated that tuberculosis-prediabetes cases, acid-fast bacilli-positive, pulmonary cavities, and living with someone who smoked were independently associated with QuantiFERON positive in contacts at baseline. DM, persistent cough, acid-fast bacilli-positive, and pulmonary cavities in tuberculosis source cases were associated with QuantiFERON conversion. CONCLUSIONS: Contacts of persons with pulmonary tuberculosis and dysglycemia were at increased risk of being QuantiFERON positive at baseline or month 6. Increased focus on such close contacts could improve tuberculosis control.


Asunto(s)
Trazado de Contacto/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Interferón gamma/sangre , Mycobacterium tuberculosis/patogenicidad , Estado Prediabético/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/transmisión , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Femenino , Humanos , Interferón gamma/inmunología , Ensayos de Liberación de Interferón gamma , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prueba de Tuberculina , Tuberculosis/epidemiología
4.
Neuroimmunomodulation ; 27(2): 113-122, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32756050

RESUMEN

INTRODUCTION: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive myelopathy associated with an inflammation of the central nervous system (CNS), being characterized by perivascular infiltration of inflammatory cells. HTLV-1-infected cells have the capacity to migrate through endothelial layers by enhancing adhesion receptor expression and corresponding ligands. T cells interact with the extracellular matrix via integrin receptors and these interactions affect both cell migration and proliferation. The importance of these interactions in retrovirus-induced diseases, however, remains less clear. METHODS: Herein we studied the expression of 3 integrin alpha chains (CD49d, CD49e, and CD49f) on the membrane of T-cell subsets in patients infected by HTLV-1, both HAM/TSP patients and oligo/asymptomatic subjects who were asymptomatic or presented slight manifestations related to the virus infection. RESULTS: We observed higher peripheral blood frequency of CD49dhiCD4+ and CD49dhiCD8+ T cells in HTLV-1-infected patients. CONCLUSION: Our findings suggest that the increased expression of adhesion molecules, such as CD49d on T lymphocytes from HTLV-1-infected patients may contribute to the pathogenesis of the disease, in both oligo/asymptomatic and HAM/TSP-infected subjects. Accordingly, it is conceivable that there is a potential use of CD49d as target for a therapeutic approach aiming at blocking migration of activated T cells from HTLV-1-infected patients into the CNS, thus avoiding the progression to HAM/TSP.


Asunto(s)
Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Sistema Nervioso Central , Humanos , Inflamación , Subgrupos de Linfocitos T
5.
BMC Infect Dis ; 15: 74, 2015 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-25870976

RESUMEN

BACKGROUND: Leishmaniasis is an important parasitic disease affecting millions worldwide. Human cutaneous leishmaniasis (CL) is endemic in Rio de Janeiro, Brazil, where is caused by Leishmania braziliensis. The adaptive immune response is accountable for the healing of CL and despite of key role of CD8+ T cells in this immune response little is known about the CD8+ T lymphocytes frequencies, apoptosis and antigen-responsive CD8+ T lymphocytes of CL patients during antimonial therapy. METHODS: Using flow cytometry, we examined total and effector CD8+ T cells from CL patients before (PBT), during (PDT) and after (PAT) treatment for apoptosis and frequencies upon isolation and after in vitro L. braziliensis antigens (LbAg)-stimulation culture. Besides, a correlation study between immunological findings and lesion size was done. RESULTS: PDT showed lower frequencies of total CD8+ T lymphocytes and higher levels of apoptosis of these cells, which were also observed following LbAg-stimulation culture. Regarding effector CD8+ T cells, high frequencies were observed in PDT, while lower frequencies were observed in PAT. Interestingly, PDT showed higher frequencies of apoptotic-effector CD8+ T lymphocytes. Similar results were seen after in vitro antigenic-stimulation assays. Correlation analysis showed that the greater the size of lesion, the smaller the frequency of effector CD8+ T lymphocytes in PDT and PAT, as well as a positive correlation between apoptotic-effector CD8+ T cells frequency and lesion size of PDT. CONCLUSIONS: Changes in effector CD8+ T-lymphocyte frequencies, during and after treatment, seem to represent a critical stage to generate an efficient immune response and suggest that these cells would be evolved in the triggering or in the resolution of lesion, under the influence of therapy. This hypothesis opens new perspectives to clarify controversial statements about the protective or deleterious role of CD8+ T cells in the cure or aggravation of CL and the new approach of evaluating patients during treatment proved to be of utmost importance for understanding the immune response in the healing process of human CL.


Asunto(s)
Antiprotozoarios/uso terapéutico , Apoptosis , Linfocitos T CD8-positivos/fisiología , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/inmunología , Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Adulto , Antígenos de Protozoos/inmunología , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Brasil , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Estudios de Cohortes , Femenino , Citometría de Flujo , Humanos , Leishmania braziliensis/efectos de los fármacos , Leishmania braziliensis/inmunología , Masculino , Antimoniato de Meglumina , Persona de Mediana Edad , Adulto Joven
6.
Mem Inst Oswaldo Cruz ; 110(6): 797-800, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26517660

RESUMEN

In the Brazilian Amazon, American tegumentary leishmaniasis (ATL) is endemic and presents a wide spectrum of clinical manifestations due, in part, to the circulation of at least seven Leishmania species. Few reports of Leishmania (Viannia) naiffi infection suggest that its occurrence is uncommon and the reported cases present a benign clinical course and a good response to treatment. This study aimed to strengthen the clinical and epidemiological importance of L. (V.) naiffi in the Amazon Region (Manaus, state of Amazonas) and to report therapeutic failure in patients infected with this species. Thirty Leishmania spp samples isolated from cutaneous lesions were characterised by multilocus enzyme electrophoresis. As expected, the most common species was Leishmania (V.) guyanensis (20 cases). However, a relevant number of L. (V.) naiffi patients (8 cases) was observed, thus demonstrating that this species is not uncommon in the region. No patient infected with L. (V.) naiffi evolved to spontaneous cure until the start of treatment, which indicated that this species may not have a self-limiting nature. In addition, two of the patients experienced a poor response to antimonial or pentamidine therapy. Thus, either ATL cases due to L. (V.) naiffi cannot be as uncommon as previously thought or this species is currently expanding in this region.


Asunto(s)
Leishmania/clasificación , Leishmaniasis/parasitología , Enfermedades Raras/parasitología , Adolescente , Adulto , Gluconato de Sodio Antimonio/uso terapéutico , Antiprotozoarios/uso terapéutico , Brasil , Demografía , Electroforesis/métodos , Geografía , Humanos , Leishmania/aislamiento & purificación , Leishmaniasis/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pentamidina/uso terapéutico , Densidad de Población , Bosque Lluvioso , Enfermedades Raras/tratamiento farmacológico , Remisión Espontánea , Piel/parasitología , Insuficiencia del Tratamiento , Adulto Joven
7.
Infect Immun ; 82(12): 5203-13, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25287925

RESUMEN

The golden hamster (Mesocricetus auratus) is a susceptible model to Leishmania (Viannia) spp.; however, available studies employ different infection protocols, which account for clinical and pathological presentation differences. Herein, L. (V.) braziliensis preparations were standardized to contain 10(4), 10(5), or 10(6) parasites to determine an optimal inoculum that ensured cutaneous lesions without causing a disseminated infection in hamsters. Lesion development was followed for 105 days by size measurements, and skin, draining lymph node, spleen, and sera were investigated to check parasite load, spleen visceralization, cytokine expression, histopathological changes, and anti-Leishmania IgG levels. The lesion emergence time was inversely proportional to the parasite concentration in the inocula. Animals infected by 10(4) parasites presented nodular lesions, while those infected with 10(6) parasites often exhibited ulcerated lesions. The differences in the final lesion sizes were observed between 10(4) and 10(5) inocula or 10(4) and 10(6) inocula. High IFNG expression, anti-Leishmania IgG levels, and parasite load occurred independently of the inoculum used. A mild inflammatory skin involvement was observed in animals infected with 10(4) parasites, while extensive tissue damage and parasite spleen visceralization occurred with 10(5) and 10(6) parasites. These results indicate that inocula with different concentrations of parasites generate differences in the time of lesion emergence, clinical presentation, and systemic commitment, despite high and similar IFNG expression and parasite load. This suggests that a modulation in the immune response to different parasite numbers occurs in an early phase of the infection, which could dictate the establishment and magnitude of the chronic phase of the disease.


Asunto(s)
Citocinas/análisis , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/patología , Carga de Parásitos , Piel/patología , Estructuras Animales/parasitología , Estructuras Animales/patología , Animales , Anticuerpos Antiprotozoarios/sangre , Modelos Animales de Enfermedad , Femenino , Histocitoquímica , Inmunoglobulina G/sangre , Leishmaniasis Cutánea/parasitología , Ganglios Linfáticos/parasitología , Ganglios Linfáticos/patología , Mesocricetus , Piel/parasitología , Bazo/parasitología , Bazo/patología , Factores de Tiempo
8.
Sci Rep ; 14(1): 9870, 2024 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-38684845

RESUMEN

Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum. Clinically, VL evolves with systemic impairment, immunosuppression and hyperactivation with hypergammaglobulinemia. Although renal involvement has been recognized, a dearth of understanding about the underlying mechanisms driving acute kidney injury (AKI) in VL remains. We aimed to evaluate the involvement of immunoglobulins (Igs) and immune complexes (CIC) in the occurrence of AKI in VL patients. Fourteen VL patients were evaluated between early treatment and 12 months post-treatment (mpt). Anti-Leishmania Igs, CIC, cystatin C, C3a and C5a were assessed and correlated with AKI markers. Interestingly, high levels of CIC were observed in VL patients up to 6 mpt. Concomitantly, twelve patients met the criteria for AKI, while high levels of cystatin C were observed up to 6 mpt. Plasmatic cystatin C was positively correlated with CIC and Igs. Moreover, C5a was correlated with cystatin C, CIC and Igs. We did not identify any correlation between amphotericin B use and kidney function markers in VL patients, although this association needs to be further explored in subsequent studies. Our data reinforce the presence of an important renal function impairment during VL, suggesting the involvement of Igs, CIC, and C5a in this clinical condition.


Asunto(s)
Lesión Renal Aguda , Complejo Antígeno-Anticuerpo , Leishmaniasis Visceral , Humanos , Leishmaniasis Visceral/inmunología , Leishmaniasis Visceral/sangre , Lesión Renal Aguda/sangre , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/parasitología , Masculino , Femenino , Complejo Antígeno-Anticuerpo/sangre , Adulto , Biomarcadores/sangre , Persona de Mediana Edad , Cistatina C/sangre , Adolescente , Adulto Joven , Anfotericina B/uso terapéutico , Leishmania infantum/inmunología
9.
Front Immunol ; 15: 1357360, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38994357

RESUMEN

Background: The impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored. Methods: An observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil. TB was defined as a positive Xpert-MTB/RIF Ultra and/or a positive culture of Mycobacterium tuberculosis from sputum. Stored plasma was used to perform specific serology to identify previous SARS-CoV-2 infection (TB/Prex-SCoV-2 group) and confirm the non- infection of the tuberculosis group (TB group). Plasmatic cytokine/chemokine/growth factor profiling was performed using Luminex technology. Tuberculosis severity was assessed by clinical and laboratory parameters. Participants from TB group (4.55%) and TB/Prex-SCoV-2 (0.00%) received the complete COVID-19 vaccination. Results: Among 35 participants with pulmonary TB, 22 were classified as TB/Prex-SCoV-2. The parameters associated with TB severity, together with hematologic and biochemical data were similar between the TB and TB/Prex-SCoV-2 groups. Among the signs and symptoms, fever and dyspnea were significantly more frequent in the TB group than the TB/Prex-SCoV-2 group (p < 0,05). A signature based on lower amount of plasma EGF, G-CSF, GM-CSF, IFN-α2, IL-12(p70), IL-13, IL-15, IL-17, IL-1ß, IL-5, IL-7, and TNF-ß was observed in the TB/Prex-SCoV-2 group. In contrast, MIP-1ß was significantly higher in the TB/Prex-SCoV-2 group than the TB group. Conclusion: TB patients previously infected with SARS-CoV-2 had an immunomodulation that was associated with lower plasma concentrations of soluble factors associated with systemic inflammation. This signature was associated with a lower frequency of symptoms such as fever and dyspnea but did not reflect significant differences in TB severity parameters observed at baseline.


Asunto(s)
COVID-19 , Citocinas , SARS-CoV-2 , Tuberculosis Pulmonar , Humanos , COVID-19/inmunología , COVID-19/sangre , Masculino , Femenino , Estudios Transversales , Adulto , Persona de Mediana Edad , SARS-CoV-2/inmunología , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/sangre , Citocinas/sangre , Citocinas/inmunología , Brasil/epidemiología
10.
PLoS Negl Trop Dis ; 18(6): e0012210, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38923969

RESUMEN

Gold miners working illegally in mines live in poor health conditions related to their strenuous work and precarious housing. Therefore, they are at higher risk for infectious diseases. American tegumentary leishmaniasis (ATL) appears to be of great concern to the population living in the Guiana Shield region. Our aim was to describe their demographic characteristics, the clinical features of cutaneous leishmaniasis (CL), and the frequency of Leishmania infection in people working in illegal gold mines in French Guiana. A cross-sectional study was carried out from October to December 2019 in Oiapoque city, Amapá, Brazil. Indeed, many gold miners working in French Guiana are originally from Brazil, and from Oiapoque in particular. A total of 105 participants from 31 different mining sites in French Guiana were recruited. Suspected Leishmania infection was confirmed by the following: detection of kDNA in blood or the lesion site; detection of specific antibodies; or detection of IFN-γ release after blood incubation with leishmanial antigens (IGRA-Leish). Nine active CL cases, 38 healed ATL (hATL) and 58 cases with no history of ATL (noATL), were identified. Only half of the treated hATL (50.0%; n = 14) reported having been assisted by a health care unit and the others treated themselves. PCR-kDNA for Leishmania was positive in the blood of 100% of CL cases. Curiously, blood PCR-kDNA was positive in 13% of hATL patients and in 15.5% of noATL patients. The IGRA-Leish was positive in 60.5% of hATL and in 37.9% of noATL. In addition to scars suggestive of CL, 71% of hATL had laboratory evidence of Leishmania infection. Restriction fragment polymorphism (RFLP) of the hsp70 gene identified a sympatric circulation of L. (V.) guyanensis (n = 4), L. (V.) braziliensis (n = 1), L. (L.) amazonensis (n = 2), L. (V.) shawi (n = 1) and L. (V.) naiffi/shawi (n = 1). Taking the laboratory techniques and the clinical evaluations together, 76% (n = 80) of the 105 participants had evidence of Leishmania infection. These results suggests that illegal gold miners working in French Guiana are at high risk for infection with different species of Leishmania, but their illegal condition and remoteness make it difficult for them to access health services.


Asunto(s)
Oro , Leishmaniasis Cutánea , Mineros , Minería , Humanos , Guyana Francesa/epidemiología , Brasil/epidemiología , Adulto , Masculino , Estudios Transversales , Persona de Mediana Edad , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/parasitología , Leishmania/genética , Leishmania/aislamiento & purificación , Leishmania/clasificación , Leishmania/inmunología , Femenino , Adulto Joven
11.
Cytokine ; 61(1): 168-72, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23068083

RESUMEN

American tegumentary leishmaniasis (ATL) is an infectious disease caused mostly by Leishmania(Viannia)braziliensis in Southeast Brazil. The clinical manifestations are vast, ranging from asymptomatic to severe mucosal leishmaniasis (ML). It has been suggested that variation of the pathogen does not fully explain the response spectrum and the variability of clinical manifestations. Previous data have shown that host genetics also play a role in disease outcome. Herein, we have tested the association of TNF, IL10, IL12 and MIF single nucleotide polymorphisms (SNPs) using a case-control study design including 110 cutaneous leishmaniasis (CL) patients and 682 healthy subjects. The genotype-phenotype correlation was also assessed using leishmania antigens to stimulate peripheral blood mononuclear cells obtained from cured CL patients. Results demonstrated that the MIF -173C allele is associated with leishmaniasis outcome and also with lower levels of MIF in culture supernatants. Also, the TNF -308AA genotype was statistically increased among leishmaniasis patients. The results showed here suggest that the lower levels of MIF produced by MIF -173C carriers could influence the host-Leishmania interaction, favoring infection and disease progression. On the other hand, high TNF levels can contribute to tissue damage, consequently leading to skin lesions.


Asunto(s)
Oxidorreductasas Intramoleculares/genética , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/genética , Leishmaniasis Cutánea/inmunología , Factores Inhibidores de la Migración de Macrófagos/genética , Adulto , Alelos , Estudios de Casos y Controles , Células Cultivadas , Femenino , Estudios de Asociación Genética , Genotipo , Interacciones Huésped-Patógeno/genética , Humanos , Interleucina-10/genética , Interleucina-12/genética , Leucocitos Mononucleares/inmunología , Macrófagos/inmunología , Macrófagos/microbiología , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/genética
12.
Parasitology ; 140(6): 771-9, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23369503

RESUMEN

The lack of an adequate model for Leishmania (Viannia) braziliensis infection is a limiting factor for studying American tegumentary leishmaniasis (ATL). The golden hamster (Mesocricetus auratus) is a promising model because besides being highly susceptible to dermotropic Leishmania infection, the lesions are very similar to cutaneous leishmaniasis (CL) in humans. However, different Leishmania isolates or species and/or protocols have resulted in different outcomes, whereas no study has evaluated the reproducibility of L. braziliensis infection in this model. The natural history of L. braziliensis infection in 34 hamsters was evaluated by using a single parasite isolate in 8 independent experiments under similar experimental conditions. Clinical, histological and immunological analyses were performed. The hamsters presented skin ulcers similar to those observed in ATL. The intra-experiment lesion increment tended to show an intermediary variance. Histological analysis of infected skins showed granulomatous reaction, scarce amastigotes, and Schaumann's bodies. Blood lymphocytes proliferated in response to leishmanial antigens. The severity of the infection was positively correlated to spleen weight, and the titres of anti-Leishmania IgG antibodies. Our findings indicate that the hamster is an appropriate model for immunopathogenesis studies of CL caused by L. braziliensis, supporting its use in clinical, vaccine and chemotherapy experimental protocols.


Asunto(s)
Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/inmunología , Modelos Animales de Enfermedad , Leishmania braziliensis/patogenicidad , Leishmaniasis Cutánea/patología , Mesocricetus , Animales , Cricetinae , Femenino , Humanos , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Mucocutánea/parasitología , Leishmaniasis Mucocutánea/patología , Linfocitos/inmunología , Reproducibilidad de los Resultados , Piel/parasitología , Piel/patología , Bazo/parasitología , Bazo/patología
13.
Artículo en Inglés | MEDLINE | ID: mdl-37703118

RESUMEN

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.


Asunto(s)
Leishmania , Leishmaniasis Cutánea , Masculino , Humanos , Brasil/epidemiología , Leishmaniasis Cutánea/epidemiología , Sistemas de Información Geográfica , Examen Físico
14.
Vaccines (Basel) ; 11(7)2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37514945

RESUMEN

Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. A well-modulated immune response that is established after the long-lasting clinical cure of leishmaniasis can represent a standard requirement for a vaccine. Previous studies demonstrated that Leishmania (Viannia) naiffi causes benign disease and its antigens induce well-modulated immune responses in vitro. In this work we aimed to identify the immunodominant proteins present in the soluble extract of L. naiffi (sLnAg) as candidates for composing a pan-specific anti-leishmaniasis vaccine. After immunoblotting using cured patients of cutaneous leishmaniasis sera and proteomics approaches, we identified a group of antigenic proteins from the sLnAg. In silico analyses allowed us to select mildly similar proteins to the host; in addition, we evaluated the binding potential and degree of promiscuity of the protein epitopes to HLA molecules and to B-cell receptors. We selected 24 immunodominant proteins from a sub-proteome with 328 proteins. Homology analysis allowed the identification of 13 proteins with the most orthologues among seven Leishmania species. This work demonstrated the potential of these proteins as promising vaccine targets capable of inducing humoral and cellular pan-specific immune responses in humans, which may in the future contribute to the control of leishmaniasis.

15.
Viruses ; 14(9)2022 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-36146692

RESUMEN

SARS-CoV-2 is a virus that belongs to the Betacoronavirus genus of the Coronaviridae family. Other coronaviruses, such as SARS-CoV and MERS-CoV, were associated with complications in pregnant women. Therefore, this study aimed to report the clinical history of five pregnant women infected with SARS-CoV-2 (four symptomatic and one asymptomatic who gave birth to a stillborn child) during the COVID-19 pandemic. They gave birth between August 2020 to January 2021, a period in which there was still no vaccination for COVID-19 in Brazil. In addition, their placental alterations were later investigated, focusing on macroscopic, histopathological, and ultrastructural aspects compared to a prepandemic sample. Three of five placentas presented SARS-CoV-2 RNA detected by RT-PCRq at least two to twenty weeks after primary pregnancy infection symptoms, and SARS-CoV-2 spike protein was detected in all placentas by immunoperoxidase assay. The macroscopic evaluation of the placentas presented congested vascular trunks, massive deposition of fibrin, areas of infarctions, and calcifications. Histopathological analysis showed fibrin deposition, inflammatory infiltrate, necrosis, and blood vessel thrombosis. Ultrastructural aspects of the infected placentas showed a similar pattern of alterations between the samples, with predominant characteristics of apoptosis and detection of virus-like particles. These findings contribute to a better understanding of the consequences of SARS-CoV-2 infection in placental tissue, vertical transmission.


Asunto(s)
COVID-19 , Complicaciones Infecciosas del Embarazo , Femenino , Fibrina , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Pandemias , Placenta , Embarazo , ARN Viral , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus
16.
Front Immunol ; 13: 890003, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35757685

RESUMEN

Introduction: Tuberculosis (TB) is a common opportunistic infection among people living with HIV. Diagnostic tests such as culture, Xpert-MTB-RIF, and ULTRA have low sensitivity in paucibacillary TB disease; a blood biomarker could improve TB diagnostic capabilities. We assessed soluble factors to identify biomarkers associated with TB among persons with advanced HIV. Methods: A case-control (1:1) study was conducted, with participants from Rio de Janeiro and Manaus, Brazil. People living with HIV presenting with CD4 count ≤100 cells/mm3 were eligible to participate. Cases had culture-confirmed TB (N=15) (positive for Mycobacterium tuberculosis [Mtb]); controls had HIV-infection only (N=15). Study visits included baseline, month 2 and end of TB therapy, during which samples of peripheral blood were obtained. A panel containing 29 biomarkers including cytokines, chemokines and growth factors was utilized to assess candidate biomarkers using Luminex technology in cryopreserved EDTA plasma samples. We used neural network analysis, based on machine learning, to identify biomarkers (single or in combination) that best distinguished cases from controls. Additional multi-dimensional analyses provided detailed profiling of the systemic inflammatory environment in cases and controls. Results: Median CD4 count and HIV-1 RNA load values were similar between groups at all timepoints. Persons with TB had lower body mass index (BMI) (median=19.6, Interquartile Range [IQR]=18.6-22.3) than controls (23.7; IQR: 21.8 = 25.5, p=0.004). TB coinfection was also associated with increased frequency of other comorbidities. The overall profile of plasma cytokines, chemokines and growth factors were distinct between the study groups at all timepoints. Plasma concentrations of IL-15 and IL-10 were on average lower in TB cases than in controls. When used in combination, such markers were able to discriminate between TB cases and controls with the highest degree of accuracy at each study timepoint. Conclusion: Among persons with advanced HIV, plasma concentrations of IL-15 and IL-10 can be used in combination to identify TB disease regardless of time on anti-TB treatment.


Asunto(s)
Infecciones por VIH , Tuberculosis , Biomarcadores , Brasil , Quimiocinas , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Humanos , Interleucina-10 , Interleucina-15 , Sensibilidad y Especificidad , Tuberculosis/microbiología
17.
PLoS Negl Trop Dis ; 15(11): e0009987, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34813597

RESUMEN

BACKGROUND: Several infectious diseases are associated with hypothalamic-pituitary-adrenal (HPA) axis disorders by elevating circulating glucocorticoids (GCs), which are known to have an immunosuppressive potential. We conducted this study in golden hamsters, a suitable model for human visceral leishmaniasis (VL), to investigate the relationship of Leishmania (L.) infantum infection on cortisol production and VL severity. METHODS: L. infantum-infected (n = 42) and uninfected hamsters (n = 30) were followed-up at 30, 120, and 180 days post-infection (dpi). Plasma cortisol was analyzed by radioimmunoassay and cytokines, inducible nitric oxide synthase (iNOS), and arginase by RT-qPCR. RESULTS: All hamsters showed splenomegaly at 180 dpi. Increased parasite burden was associated with higher arginase expression and lower iNOS induction. Cortisol levels were elevated in infected animals in all-time points evaluated. Except for monocytes, all other leucocytes showed a strong negative correlation with cortisol, while transaminases were positively correlated. Immunological markers as interleukin (IL)-6, IL-1ß, IL-10, and transforming growth-factor-ß (TGF-ß) were positively correlated to cortisol production, while interferon-γ (IFN-γ) presented a negative correlation. A network analysis showed cortisol as an important knot linking clinical status and immunological parameters. CONCLUSIONS: These results suggest that L. infantum increases the systemic levels of cortisol, which showed to be associated with hematological, biochemical, and immunological parameters associated to VL severity.


Asunto(s)
Hidrocortisona/sangre , Leishmaniasis Visceral/sangre , Animales , Cricetinae , Glucocorticoides/sangre , Humanos , Interleucinas/sangre , Leishmania infantum/genética , Leishmania infantum/aislamiento & purificación , Leishmania infantum/fisiología , Leishmaniasis Visceral/parasitología , Leucocitos/inmunología , Masculino , Mesocricetus , Factor de Crecimiento Transformador beta/sangre
18.
Front Immunol ; 12: 656919, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34276650

RESUMEN

The golden hamster is a suitable model for studying cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis. Immunopathological mechanisms are well established in the L. (L.) major-mouse model, in which IL-4 instructs a Th2 response towards progressive infection. In the present study, we evaluated the natural history of L. braziliensis infection from its first stages up to lesion establishment, with the aim of identifying immunological parameters associated with the disease outcome and parasitism fate. To this end, hamsters infected with 104, 105, or 106 promastigotes were monitored during the first hours (4h, 24h), early (15 days, 30 days) and late (50 days) post-infection (pi) phases. Cytokines, iNOS and arginase gene expression were quantified in the established lesions by reverse transcription-quantitative PCR. Compared to the 105 or 106 groups, 104 animals presented lower lesions sizes, less tissue damage, and lower IgG levels. Basal gene expression in normal skin was high for TGF-ß, and intermediary for TNF, IL-6, and IL-4. At 4hpi, no cytokine induction was observed in the 104 group, while an upregulation of IL-6, IL-10, and IL-4 was observed in the 106 group. At 15dpi, lesion appearance was accompanied by an increased expression of all assessed cytokines, markedly in the 105 and 106 groups. Upregulation of all investigated cytokines was observed in the late phase, although less expressive in the 104 group. IFN-γ was the depending variable influencing tissue damage, while IL-6 was associated to parasite load. The network correlating gene expression and clinical and laboratorial parameters indicated inoculum-independent associations at 15 and 30dpi. A strong positive network correlation was observed in the 104 group, but not in the 105 or 106 groups. In conclusion, IL-4, IL-6, IL-10, and TGF-ß are linked o L. braziliensis progression. However, a balanced cytokine network is the key for an immune response able to reduce the ongoing infection and reduce pathological damage.


Asunto(s)
Citocinas/metabolismo , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/metabolismo , Leishmaniasis Cutánea/parasitología , Transducción de Señal , Animales , Biomarcadores , Biología Computacional/métodos , Cricetinae , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Expresión Génica , Interacciones Huésped-Parásitos/inmunología , Inmunomodulación , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Carga de Parásitos
19.
Microbiol Spectr ; 9(3): e0116321, 2021 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-34851140

RESUMEN

The interferon gamma release assay (IGRA) has emerged as a useful tool for identifying latent tuberculosis infection (LTBI). This assay can be performed through testing platforms such as the QuantiFERON-TB Gold Plus (QFT-Plus) assay. This in vitro test has been incorporated into several guidelines worldwide and has recently been considered by the World Health Organization (WHO) for the diagnosis of LTBI. The possibility of systematically implementing IGRAs such as the QFT-Plus assay in centers that perform LTBI screening has been accelerated by the decreased availability of the tuberculin skin test (TST) in several countries. Nevertheless, the process to implement IGRA testing in routine clinical care has many gaps. The study utilized the expertise acquired by the laboratory teams of the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil consortium during study protocol implementation of LTBI screening of tuberculosis (TB) close contacts. RePORT-Brazil includes clinical research sites from Brazilian cities and is the largest multicenter cohort of TB close contacts in the country to date. Operational and logistical challenges faced during IGRA implementation in all study laboratories are described, as well as the solutions that were developed and led to the successful establishment of IGRA testing in RePORT-Brazil. The descriptions of the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with large TB burdens, such as Brazil. IMPORTANCE The IGRA has emerged as a useful tool for identifying persons with LTBI. Although the implementation of IGRAs is of utmost importance, to our knowledge there is scarce information on the identification of logistical and technical challenges for systematic screening for LTBI on a large scale. Thus, the descriptions of the problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with large TB burdens, such as Brazil.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tamizaje Masivo/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Brasil/epidemiología , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Tuberculosis Latente/tratamiento farmacológico , Estudios Prospectivos , Control de Calidad , Reproducibilidad de los Resultados , Manejo de Especímenes/métodos , Tuberculosis/tratamiento farmacológico , Tuberculosis/prevención & control
20.
Rev Soc Bras Med Trop ; 52: e20180323, 2019 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-30994803

RESUMEN

We report the case of a 32-year-old man from Rio de Janeiro, who was infected in the Amazon region of Brazil by Leishmania (Viannia) naiffi. Generally, patients with L. naiffi cutaneous leishmaniasis exhibit a good therapeutic response to either pentavalent antimonials or pentamidine. However, after pentamidine treatment, this patient's infection evolved to therapeutic failure. To understand this clinical outcome, we investigated the presence of the Leishmania RNA virus (LRV) in parasites isolated from the cutaneous lesion; herein, we discuss the possible association between a poor response to pentamidine therapy and the presence of the LRV.


Asunto(s)
Leishmania/virología , Leishmaniasis Cutánea/tratamiento farmacológico , Pentamidina/uso terapéutico , Virus ARN/genética , Tripanocidas/uso terapéutico , Adulto , Humanos , Masculino , Pentamidina/efectos adversos , Reacción en Cadena de la Polimerasa , Insuficiencia del Tratamiento , Tripanocidas/efectos adversos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA