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1.
PLoS Negl Trop Dis ; 18(9): e0012225, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292716

RESUMEN

BACKGROUND: Orally transmitted acute Chagas disease (ACD) primarily affects low-visibility and low-income individuals in tropical and subtropical zones. Managing ACD remains challenging even after more than 100 years of its discovery. Its spread to non-endemic areas has made it a global health issue. The aim of this work is to demonstrate the difficulties encountered in handling a real-life situation. METHODOLOGY AND FINDINGS: This report examines an outbreak of 39 cases of ACD due to oral transmission by bacaba juice ingestion that occurred in Pedro do Rosário, Maranhão, Brazil. A clinical and epidemiological investigation, including an entomological search, was conducted. Diagnosis criteria included positive peripheral blood smear (PBS), seroconversion of IgG, and a two-fold increase in IgG titer (laboratory criteria); and clinical findings, epidemiological exposure, and at least one positive IgG test (clinical-epidemiological criteria). In-house conventional polymerase chain reaction (PCR) was performed on 33 samples. All patients were treated with benznidazole. After 4.5 years, IgG levels were reassessed in 26 individuals. The mean age was 33.6 years, with no gender difference. The mean incubation period was 13.8 days, and the mean between symptom onset and treatment was 16.6 days. The most common symptoms were fever and lymphadenopathy (90%). Diagnostic success rates were 66.6% (laboratory criteria), 23% (clinical-epidemiological criteria), and 10.2% (high clinical suspicion despite negative tests). Test positivity rates were 69.7% (PBS), 91.4% (serology), and 100% (PCR). There were no deaths. Serological cure was achieved in 34.6% of cases, and IgG titers decreased in 15.3%. CONCLUSIONS AND SIGNIFICANCE: We encountered several barriers in managing ACD, including population vulnerability, reliance on outdated diagnostic techniques, lack of standardized molecular biology methods, and limited therapeutic options. This report underscores the importance of rapid surveillance and early treatment to prevent fatalities. We recommend the standardization of conventional PCR in diagnostic routines.

2.
Pathogens ; 12(7)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37513737

RESUMEN

Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit several treatments. She worsened after a pregnancy, developing disseminated lesions. Miltefosine with amphotericin B and pentamidine resulted in remission. Lesions reappeared after one year, accompanied by intra-nasal infiltration of the disease. The nasal spraying of a single ampoule of pentavalent antimoniate resulted in the sustained disappearance of the nasal symptoms and all the cutaneous lesions. After over eight years, she remains disease-free, albeit under renal replacement therapy. The high nasal mucosal antimonial concentration may explain the long-lasting cure via new MHC class I epitope-specific CD8+ cell clones against L. amazonensis present in the nasal mucosa.

3.
Sci Rep ; 10(1): 10543, 2020 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-32601369

RESUMEN

Tegumentary leishmaniasis (TL) is a parasitic disease that can result in wide spectrum clinical manifestations. It is necessary to understand host and parasite determinants of clinical outcomes to identify novel therapeutic targets. Previous studies have indicated that the polyamine biosynthetic pathway is critical for Leishmania growth and survival. Despite its importance, expression of the such pathway has not been previously investigated in TL patients. We performed an exploratory analysis employing Systems Biology tools to compare circulating polyamines and amino acid concentration as well as polyamine pathway gene expression in cutaneous lesions patients presenting with distinct TL disease presentations. Diffuse cutaneous leishmaniasis (DCL) was associated with higher concentrations of amino acids, polyamines and its substrate transporters than mucosal cutaneous leishmaniasis or localized cutaneous leishmaniasis. In addition, the RNA expression of polyamine-related genes of patients lesions from two separate cohorts demonstrated that differential activation of this pathway is associated with parasite loads and able to discriminate the clinical spectrum of TL. Taken together, our findings highlight a new aspect of DCL immunopathogenesis indicating that the polyamine pathway may be explored as a novel therapeutic target to control disease burden.


Asunto(s)
Aminoácidos/metabolismo , Vías Biosintéticas/fisiología , Leishmaniasis Cutánea Difusa/metabolismo , Poliaminas/metabolismo , Piel/metabolismo , Adulto , Aminoácidos/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Membrana Mucosa/metabolismo , Poliaminas/sangre
5.
Parasitology ; 145(14): 1801-1818, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29806575

RESUMEN

Coinfection with human visceral leishmaniasis (HVL) and human immunodeficiency virus (HIV) has become an emerging public health problem in several parts of the world, with high morbidity and mortality rates. A systematic review was carried out in the literature available in PubMed, Scielo and Lilacs related to HVL associated with HIV coinfection, seeking to analyze epidemiological, clinical and laboratory aspects. Of the 265 articles found, 15 articles were included in the qualitative analysis, which referred to the results of HVL treatment in patients coinfected with HIV. In the published articles between 2007 and 2015, 1171 cases of HVL/HIV coinfection were identified, 86% males, average age 34 years, liposomal amphotericin B was the most commonly used drug, cure rates 68 and 20% relapses and 19% deaths, five different countries, bone marrow was used in 10/15 manuscripts. HVL/HIV coinfection is a major challenge for public health, mainly due to the difficulty in establishing an accurate diagnosis, low response to treatment with high relapse rates and evolution to death. In addition, these two pathogens act concomitantly for the depletion of the immune system, contributing to worsening the clinical picture of these diseases, which requires effective surveillance and epidemiological control measures.


Asunto(s)
Coinfección/epidemiología , Infecciones por VIH/epidemiología , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/epidemiología , Anfotericina B/uso terapéutico , Coinfección/tratamiento farmacológico , Coinfección/mortalidad , VIH/patogenicidad , Infecciones por VIH/inmunología , Humanos , Leishmania donovani/patogenicidad , Leishmaniasis Visceral/tratamiento farmacológico , Masculino , Salud Pública
6.
Diagn Microbiol Infect Dis ; 91(4): 312-318, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29653798

RESUMEN

Hsp70 is a cytoplasmic heat-shock protein, encoded by a multicopy tandemly repeated gene that has recently been gaining popularity as a valuable marker for typing Leishmania species. In this study, we used a previously described hsp70 PCR-RFLP method for identifying Brazilian Leishmania isolates. We identified two distinct L. (L.) amazonensis hsp70 alleles that resulted in two different RFLP patterns. Also, we found RFLP polymorphisms amongst L. (Viannia) naiffi strains. The profiles of both L. (V.) shawi and L. (V.) lindenbergi were very similar to those of other L. (Viannia) species. The observations described herein reflect the polymorphism found within species of Leishmania and indicate that results from this hsp70 PCR-RFLP method should be used with caution when typing isolates from clinical cases of leishmaniasis and Leishmania species from Brazil.


Asunto(s)
Proteínas HSP70 de Choque Térmico/genética , Leishmania/genética , Leishmaniasis Cutánea/parasitología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción/genética , Proteínas Protozoarias/genética , Alelos , Animales , Brasil , ADN Protozoario/genética , Genoma de Protozoos/genética , Humanos , Leishmania/clasificación , Leishmania braziliensis/genética , Leishmaniasis Cutánea/diagnóstico , Filogenia , Análisis de Secuencia de ADN
7.
Sci Rep ; 7: 46363, 2017 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-28393908

RESUMEN

Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators. Whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. We addressed this question in the current study by assessing circulating levels of D-series resolvins in tegumentary leishmaniasis patients presenting with localized or diffuse disease. We found heightened expression of resolvin D1 in diffuse cutaneous leishmaniasis which was correlated with expression profile of biomarkers associated with disease pathogenesis. Additional in vitro experiments using primary human macrophages indicated that resolvin D1 may promote intracellular Leishmania amazonensis replication through a mechanism associated with induction of heme oxygenase-1. These results suggest that targeting resolvin D1 could serve as potential strategy for host directed therapy in diffuse cutaneous leishmaniasis.


Asunto(s)
Ácidos Docosahexaenoicos/sangre , Leishmaniasis/sangre , Macrófagos/parasitología , Adolescente , Adulto , Biomarcadores/metabolismo , Niño , Femenino , Humanos , Leishmania , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Adulto Joven
8.
Mem Inst Oswaldo Cruz ; 111(4): 241-51, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27074253

RESUMEN

Localised cutaneous leishmaniasis (LCL) is the most common form of cutaneous leishmaniasis characterised by single or multiple painless chronic ulcers, which commonly presents with secondary bacterial infection. Previous culture-based studies have found staphylococci, streptococci, and opportunistic pathogenic bacteria in LCL lesions, but there have been no comparisons to normal skin. In addition, this approach has strong bias for determining bacterial composition. The present study tested the hypothesis that bacterial communities in LCL lesions differ from those found on healthy skin (HS). Using a high throughput amplicon sequencing approach, which allows for better populational evaluation due to greater depth coverage and the Quantitative Insights Into Microbial Ecology pipeline, we compared the microbiological signature of LCL lesions with that of contralateral HS from the same individuals.Streptococcus, Staphylococcus,Fusobacterium and other strict or facultative anaerobic bacteria composed the LCL microbiome. Aerobic and facultative anaerobic bacteria found in HS, including environmental bacteria, were significantly decreased in LCL lesions (p < 0.01). This paper presents the first comprehensive microbiome identification from LCL lesions with next generation sequence methodology and shows a marked reduction of bacterial diversity in the lesions.


Asunto(s)
Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Leishmaniasis Cutánea/microbiología , Piel/microbiología , Adulto , Femenino , Bacterias Gramnegativas/clasificación , Bacterias Grampositivas/clasificación , Humanos , Masculino , Persona de Mediana Edad , Piel/parasitología , Adulto Joven
9.
Mem. Inst. Oswaldo Cruz ; 111(4): 241-251, Apr. 2016. tab, graf
Artículo en Inglés | LILACS | ID: lil-779002

RESUMEN

Localised cutaneous leishmaniasis (LCL) is the most common form of cutaneous leishmaniasis characterised by single or multiple painless chronic ulcers, which commonly presents with secondary bacterial infection. Previous culture-based studies have found staphylococci, streptococci, and opportunistic pathogenic bacteria in LCL lesions, but there have been no comparisons to normal skin. In addition, this approach has strong bias for determining bacterial composition. The present study tested the hypothesis that bacterial communities in LCL lesions differ from those found on healthy skin (HS). Using a high throughput amplicon sequencing approach, which allows for better populational evaluation due to greater depth coverage and the Quantitative Insights Into Microbial Ecology pipeline, we compared the microbiological signature of LCL lesions with that of contralateral HS from the same individuals.Streptococcus, Staphylococcus,Fusobacterium and other strict or facultative anaerobic bacteria composed the LCL microbiome. Aerobic and facultative anaerobic bacteria found in HS, including environmental bacteria, were significantly decreased in LCL lesions (p < 0.01). This paper presents the first comprehensive microbiome identification from LCL lesions with next generation sequence methodology and shows a marked reduction of bacterial diversity in the lesions.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Leishmaniasis Cutánea/microbiología , Piel/microbiología , Bacterias Gramnegativas/clasificación , Bacterias Grampositivas/clasificación , Piel/parasitología
10.
Int J Parasitol ; 46(5-6): 343-50, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26953255

RESUMEN

Repeated treatments with praziquantel reduce schistosomiasis prevalence and morbidity, but transmission persists and populations often recover within a few years. To identify factors associated with persistence, we surveyed and treated all identified Schistosoma mansoni infections in two rural Brazilian communities (Jenipapo and Volta do Rio) in 2009, 2012 and 2013. Eggs were collected from all infected individuals and genotyped with 11 microsatellite markers to evaluate parasite differentiation and diversity. After successive rounds of community-wide treatment, prevalence decreased from 45% to 24% then 16%. Intensity of infection decreased by 57% over this period, and the number of eggs transmitted to the environment decreased by 92%. During all time periods the majority of eggs were excreted by those >15years of age. The incidence was 23% in 2012 and 15% in 2013, consistent with a decrease in transmission. There was little immigration or gene flow over a distance of 6km. On reinfection, infrapopulations were moderately differentiated indicating that pretreatment multilocus genotypes were not fully reacquired. The effective population size responded to census population decline more rapidly than differentiation. Reinfection was concentrated in the downstream portion of Jenipapo, consistent with the observed increased human fecal contamination. At this scale and in this area S. mansoni infections exist on a fragmented landscape with a highly focal pattern of transmission that may facilitate future elimination.


Asunto(s)
Antihelmínticos/administración & dosificación , Praziquantel/administración & dosificación , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Brasil/epidemiología , Niño , Preescolar , Heces/parasitología , Femenino , Frecuencia de los Genes , Técnicas de Genotipaje , Humanos , Incidencia , Lactante , Estudios Longitudinales , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Recuento de Huevos de Parásitos , Praziquantel/farmacología , Praziquantel/uso terapéutico , Prevalencia , Factores de Riesgo , Población Rural , Schistosoma mansoni/clasificación , Schistosoma mansoni/genética , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/transmisión , Adulto Joven
11.
J Infect Dis ; 213(7): 1143-7, 2016 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-26582954

RESUMEN

Unfettered inflammation is thought to play critical role in the development of different clinical forms of tegumentary leishmaniasis. Eicosanoids are potent mediators of inflammation and tightly associated with modulation of immune responses. In this cross-sectional exploratory study, we addressed whether targets from the eicosanoid biosynthetic pathway, assessed by multiplexed expression assays in lesion biopsy and plasma specimens, could highlight a distinct biosignature in patients with mucocutaneous leishmaniasis (MCL) or localized cutaneous leishmaniasis (LCL). Differences in immunopathogenesis between MCL and LCL may result from an imbalance between prostaglandins and leukotrienes, which may serve as targets for future host-directed therapies.


Asunto(s)
Antiprotozoarios/uso terapéutico , Eicosanoides/metabolismo , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/metabolismo , Adulto , Anciano , Estudios Transversales , Eicosanoides/sangre , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/metabolismo , Leishmaniasis Mucocutánea/tratamiento farmacológico , Leishmaniasis Mucocutánea/metabolismo , Masculino , Persona de Mediana Edad
12.
PLoS Negl Trop Dis ; 9(3): e0003521, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25775457

RESUMEN

Urbanization is increasing across the globe, and diseases once considered rural can now be found in urban areas due to the migration of populations from rural endemic areas, local transmission within the city, or a combination of factors. We investigated the epidemiologic characteristics of urban immigrants and natives living in a neighborhood of Salvador, Brazil where there is a focus of transmission of Schistosoma mansoni. In a cross-sectional study, all inhabitants from 3 sections of the community were interviewed and examined. In order to determine the degree of parasite differentiation between immigrants and the native born, S. mansoni eggs from stools were genotyped for 15 microsatellite markers. The area received migrants from all over the state, but most infected children had never been outside of the city, and infected snails were present at water contact sites. Other epidemiologic features suggested immigration contributed little to the presence of infection. The intensity and prevalence of infection were the same for immigrants and natives when adjusted for age, and length of immigrant residence in the community was positively associated with prevalence of infection. The population structure of the parasites also supported that the contribution from immigration was small, since the host-to-host differentiation was no greater in the urban parasite population than a rural population with little distant immigration, and there had been little differentiation in the urban population over the past 7 years. Public health efforts should focus on eliminating local transmission, and once eliminated, reintroduction from distant migration is unlikely.


Asunto(s)
Emigración e Inmigración , Esquistosomiasis/epidemiología , Adulto , Animales , Brasil/epidemiología , Estudios Transversales , Heces/parasitología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Schistosoma mansoni/genética , Esquistosomiasis/etiología , Población Urbana
13.
J Invest Dermatol ; 135(2): 400-410, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25207817

RESUMEN

In this study, we used proteomics and biological network analysis to evaluate the potential biological processes and components present in the identified proteins of biopsies from cutaneous leishmaniasis (CL) patients infected by Leishmania braziliensis in comparison with normal skin. We identified 59 proteins differently expressed in samples from infected and normal skin. Biological network analysis employing identified proteins showed the presence of networks that may be involved in the cell death mediated by cytotoxic T lymphocytes. After immunohistochemical analyses, the expression of caspase-9, caspase-3, and granzyme B was validated in the tissue and positively correlated with the lesion size in CL patients. In conclusion, this work identified differentially expressed proteins in the inflammatory site of CL, revealed enhanced expression of caspase-9, and highlighted mechanisms associated with the progression of tissue damage observed in lesions.


Asunto(s)
Leishmaniasis Cutánea/metabolismo , Proteoma , Caspasa 3/análisis , Caspasa 9/análisis , Granzimas/análisis , Humanos , Inmunohistoquímica , Leishmaniasis Cutánea/patología , Piel/patología
14.
J Infect Dis ; 211(3): 426-35, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25124926

RESUMEN

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of tegumentary leishmaniasis. The molecular mechanisms underlying DCL pathogenesis remain unclear, and there is no efficient treatment available. This study investigated the systemic and in situ expression of the inflammatory response that might contribute to suppression in DCL. The plasma levels of arginase I, ornithine decarboxylase (ODC), transforming growth factor ß (TGF-ß), and prostaglandin E2 (PGE2) were higher in patients with DCL, compared with patients with localized cutaneous leishmaniasis (LCL) or with controls from an area of endemicity. In situ transcriptomic analyses reinforced the association between arginase I expression and enzymes involved in prostaglandin and polyamine synthesis. Immunohistochemistry confirmed that arginase I, ODC, and cyclooxygenase2 expression was higher in lesion biopsy specimens from patients with DCL than in those from patients with LCL. Inhibition of arginase I or ODC abrogates L. amazonensis replication in infected human macrophages. Our data implicate arginase I, ODC, PGE2, and TGF-ß in the failure to mount an efficient immune response and suggest perspectives in the development of new strategies for therapeutic intervention for patients with DCL.


Asunto(s)
Arginasa/genética , Dinoprostona/genética , Inflamación/genética , Leishmaniasis Cutánea Difusa/genética , Poliaminas/metabolismo , Adolescente , Adulto , Anciano , Arginasa/sangre , Niño , Preescolar , Dinoprostona/sangre , Femenino , Humanos , Inflamación/sangre , Leishmaniasis Cutánea Difusa/sangre , Masculino , Persona de Mediana Edad , Ornitina Descarboxilasa/sangre , Ornitina Descarboxilasa/genética , Poliaminas/sangre , Transducción de Señal/genética , Transcriptoma/genética , Factor de Crecimiento Transformador beta/sangre , Factor de Crecimiento Transformador beta/genética , Adulto Joven
15.
J Infect Dis ; 210(2): 306-10, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-24511100

RESUMEN

We show that increased plasma superoxide dismutase 1 (SOD1) levels are statistically significant predictors of the failure of pentavalent antimony treatment for cutaneous leishmaniasis caused by Leishmania braziliensis. In Leishmania amazonensis-infected patients, host SOD1 levels can be used to discriminate between localized and drug-resistant diffuse cutaneous leishmaniasis. Using in situ transcriptomics (nCounter), we demonstrate a significant positive correlation between host SOD1 and interferon α/ß messenger RNA (mRNA) levels, as well as interkingdom correlation between host SOD1 and parasite SOD2/4 mRNA levels. In human macrophages, in vitro treatment with SOD1 increases the parasite burden and induces a diffuse cutaneous leishmaniasis-like morphology. Thus, SOD1 is a clinically relevant biomarker and a therapeutic target in both localized and diffuse cutaneous leishmaniasis.


Asunto(s)
Antimonio/uso terapéutico , Antiprotozoarios/uso terapéutico , Biomarcadores/sangre , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/patología , Superóxido Dismutasa/sangre , Adulto , Células Cultivadas , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Superóxido Dismutasa-1 , Insuficiencia del Tratamiento
16.
PLoS Negl Trop Dis ; 7(12): e2572, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24340115

RESUMEN

BACKGROUND: Brazil remains the country in the Americas with the highest prevalence of schistosomiasis. A combination of control efforts and development, however, has sharply reduced its intensity and distribution. The acquisition of specific schistosome populations may be dependent on host characteristics such as sex, age, geography, work, habits and culture. How these and other host characteristics align with parasite subpopulations may guide approaches to improve control. METHODOLOGY: A cohort of more than 90% of the residents in two rural communities in Brazil participated in an epidemiologic survey of demographic, socio-economic and behavioral characteristics. The variables sex, age, intensity of infection, socio-economic index, % lifetime spent on site, previous infection, and trips outside the district were used to group parasites infecting individuals. Schistosoma mansoni infection status was determined by examination of stools submitted on 3 different days. The aggregate of eggs collected from the whole stool was used to determine degree of population differentiation from allele frequencies for 15 microsatellites. CONCLUSIONS/SIGNIFICANCE: Infection prevalence was 41% for these communities, and the epidemiologic characteristics were similar to many of the endemic areas of Brazil and the world. Parasite population structuring was observed between the two communities (Jost's D 0.046, CI95% 0.042-0.051), although separated by only 8 km and connected by a highway. No structuring was observed when infected individuals were stratified by host's biologic, demographic or epidemiologic characteristics. Those most heavily infected best reflected the communities' overall parasite diversity. The lack of differentiation within villages suggests that individuals are likely to get infected at the same sites or that the same parasite multilocus genotypes can be found at most sites. The geographic structuring between villages and the lack of structuring by age of the host further supports the impression of a population little affected by migration or drift.


Asunto(s)
Variación Genética , Schistosoma mansoni/clasificación , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/parasitología , Adolescente , Adulto , Animales , Brasil , Niño , Preescolar , Heces/parasitología , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Lactante , Estilo de Vida , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Prevalencia , Población Rural , Schistosoma mansoni/genética , Adulto Joven
17.
PLoS One ; 8(6): e66110, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23776617

RESUMEN

BACKGROUND: Exposure to Leishmania induces a humoral immune response that can be used as a marker of parasite exposure. METHODOLOGY/PRINCIPAL FINDINGS: Herein, ELISA was used to screen sera from patients with Tegumentary Leishmaniasis (TL) against different L. infantum-chagasi-derived recombinant proteins (rHSP70, rH2A, rH2B, rH3, rH4 and rKMP11). Among the recombinant proteins, rHSP70 and rH2A showed the best reactivity against human sera obtained from endemic areas of TL. Receiver-Operator Characteristics (ROC) curve analysis was used to identify the effectiveness of these proteins for serodiagnosis of TL. ROC curves confirmed the superior performance of rHSP70 and rH2A, in comparison to the other tested recombinant proteins. Additionally, we evaluated the specificity of the response to rHSP70 and rH2A by testing sera obtained from patients with Chagas' disease, Tuberculosis, Leprosy or Systemic Lupus Erythematosus. In this case, rHSP70 displayed an increased ability to discriminate diseases, in comparison to SLA. CONCLUSION: Our results raise possibility of using rHSP70 for the serodiagnosis of TL.


Asunto(s)
Leishmania/inmunología , Leishmaniasis/sangre , Leishmaniasis/diagnóstico , Proteínas Protozoarias , Proteínas Recombinantes , Pruebas Serológicas/métodos , Ensayo de Inmunoadsorción Enzimática , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Leishmania/genética , Oligonucleótidos/genética , Curva ROC , Estadísticas no Paramétricas
18.
J Invest Dermatol ; 133(6): 1533-40, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23321919

RESUMEN

A protective or deleterious role of CD8(+)T cells in human cutaneous leishmaniasis (CL) has been debated. The present report explores the participation of CD8(+)T cells in disease pathogenesis as well as in parasite killing. CD8(+)T cells accumulated in CL lesions as suggested by a higher frequency of CD8(+)CD45RO(+)T cells and CD8(+)CLA(+)T cells compared with peripheral blood mononuclear cells. Upon Leishmania braziliensis restimulation, most of the CD8(+)T cells from the lesion expressed cytolytic markers, CD107a and granzyme B. Granzyme B expression in CL lesions positively correlated with lesion size and percentage of TUNEL-positive cells. We also observed a significantly higher percentage of TUNEL-positive cells and granzyme B expression in the biopsies of patients showing a more intense necrotic process. Furthermore, coculture of infected macrophages and CD8(+)T lymphocytes resulted in the release of granzyme B, and the use of granzyme B inhibitor, as well as z-VAD, Fas:Fc, or anti-IFN-γ, had no effect upon parasite killing. However, coculture of infected macrophages with CD4(+)T cells strongly increased parasite killing, which was completely reversed by anti-IFN-γ. Our results reveal a dichotomy in human CL: CD8(+) granzyme B(+)T cells mediate tissue injury, whereas CD4(+)IFN-γ(+)T cells mediate parasite killing.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Granzimas/inmunología , Interferón gamma/inmunología , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/inmunología , Adolescente , Adulto , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/parasitología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/parasitología , Movimiento Celular/inmunología , Células Cultivadas , Técnicas de Cocultivo , Femenino , Humanos , Etiquetado Corte-Fin in Situ , Leishmaniasis Cutánea/patología , Masculino , Persona de Mediana Edad , Piel/inmunología , Piel/parasitología , Piel/patología , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/parasitología , Adulto Joven
19.
PLoS One ; 7(5): e36595, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22574191

RESUMEN

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of leishmaniasis, characterized by an inefficient parasite-specific cellular response and heavily parasitized macrophages. In Brazil, Leishmania (Leishmania) amazonensis is the main species involved in DCL cases. In the experimental model, recognition of phosphatidylserine (PS) molecules exposed on the surface of amastigotes forms of L. amazonensis inhibits the inflammatory response of infected macrophages as a strategy to evade the host immune surveillance. In this study, we examined whether PS exposure on L. amazonensis isolates from DCL patients operated as a parasite pathogenic factor and as a putative suppression mechanism of immune response during the infection. Peritoneal macrophages from F1 mice (BALB/c×C57BL/6) were infected with different L. amazonensis isolates from patients with localized cutaneous leishmaniasis (LCL) or DCL. DCL isolates showed higher PS exposure than their counterparts from LCL patients. In addition, PS exposure was positively correlated with clinical parameters of the human infection (number of lesions and time of disease) and with characteristics of the experimental infection (macrophage infection and anti-inflammatory cytokine induction). Furthermore, parasites isolated from DCL patients displayed an increased area in parasitophorous vacuoles (PV) when compared to those isolated from LCL patients. Thus, this study shows for the first time that a parasite factor (exposed PS) might be associated with parasite survival/persistence in macrophages and lesion exacerbation during the course of DCL, providing new insights regarding pathogenic mechanism in this rare chronic disease.


Asunto(s)
Leishmania/efectos de los fármacos , Leishmania/patogenicidad , Leishmaniasis Cutánea Difusa/parasitología , Fosfatidilserinas/farmacología , Animales , Enfermedad Crónica , Citocinas/biosíntesis , Relación Dosis-Respuesta a Droga , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea Difusa/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/parasitología , Ratones
20.
Res. rep. trop. med ; 3: 69-77, Apr. 2012.
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-1066224

Asunto(s)
Leishmaniasis
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