Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for coinfections of Leishmania and HIV to improve the consistency of research on the current situation of VL-HIV coinfections. Such a network would improve the collection of vital data and samples for better understanding of the clinical manifestations and immunopathogenic aspects of VL in immunosuppressed patients. Ultimately, a concerted effort would improve trials for new diagnostic methodologies and therapeutics, which could accelerate the implementation of more specific and effective diagnosis as well as public policies for treatments to reduce the impact of VL-HIV coinfections on the Latin American population.
Host arginase 1 (arg1) expression is a significant contributor to the pathogenesis of progressive visceral leishmaniasis (VL), a neglected tropical disease caused by the intracellular protozoan Leishmania donovani. Previously we found that parasite-induced arg1 expression in macrophages was dependent on STAT6 activation. Arg1 expression was amplified by, but did not require, IL-4, and required de novo synthesis of unknown protein(s). To further explore the mechanisms involved in arg1 regulation in VL, we screened a panel of kinase inhibitors and found that inhibitors of growth factor signaling reduced arg1 expression in splenic macrophages from hamsters with VL. Analysis of growth factors and their signaling pathways revealed that the Fibroblast Growth Factor Receptor 1 (FGFR-1) and Insulin-like Growth Factor 1 Receptor (IGF-1R) and a number of downstream signaling proteins were activated in splenic macrophages isolated from hamsters infected with L. donovani. Recombinant FGF-2 and IGF-1 increased the expression of arg1 in L. donovani infected hamster macrophages, and this induction was augmented by IL-4. Inhibition of FGFR-1 and IGF-1R decreased arg1 expression and restricted L. donovani replication in both in vitro and ex vivo models of infection. Inhibition of the downstream signaling molecules JAK and AKT also reduced the expression of arg1 in infected macrophages. STAT6 was activated in infected macrophages exposed to either FGF-2 or IGF-1, and STAT6 was critical to the FGFR-1- and IGF-1R-mediated expression of arg1. The converse was also true as inhibition of FGFR-1 and IGF-1R reduced the activation of STAT6 in infected macrophages. Collectively, these data indicate that the FGFR/IGF-1R and IL-4 signaling pathways converge at STAT6 to promote pathologic arg1 expression and intracellular parasite survival in VL. Targeted interruption of these pathological processes offers an approach to restrain this relentlessly progressive disease.
Immunofluorescence tests (IF) for toxoplasmosis were performed on a total of 608 schoolchildren in elementary and junior high grades. 166 being in the Bonsucesso district (an urban region of Rio de Janeiro) and 442 children from locations within the lowlands of Jacarepaguá (with rural characteristics). All the IF-IgM were nonreactive, whilst 416 schoolchildren (68.4%) were IF-IgG serum-reactive (greater than or equal to 1:16). The percentages of serum-reactives in Jacarepaguá were significantly higher than in Bonsucesso, both as regards the total number of schoolchildren (p less than 0.001), as also when subdivided according to the age-grades from six to eight years (p less than 0.001) or from twelve to fourteen (p less than 0.05). Both in Jacarepaguá and in Bonsucesso, the prevalence of reactions in the 12 to 14 year age-grade was significantly greater than in the 6 to 8 year age-grade (p less than 0.001 in both cases). Expressively larger prevalences of serum reactions were found in Jacarepaguá among schoolchildren who preferred eating raw or undercooked meat, as well as among those having cats as pets; this occurred equally in the 6 to 8 year and in the 12 to 14 year age-grades. In Bonsucesso, the only significant difference was in the 6 to 8 year age-grades that had cats as pets. Thus, it has been verified that the risk of infection is greater and more precocious in localities with rural characteristics than in urban regions.
BACKGROUND Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODSThe iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4 + T cell counts, serum iron, haematological and anthropometrics parameters were recorded.FINDINGS Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4 + T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01].MAIN CONCLUSIONS This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.
Introdução: As pessoas idosas soropositivas apresentam demandas de cuidado diferenciadas; necessita-se de maior atenção em saúde, pois alguns apresentam idade avançada e aspectos de saúde singulares, devendo os enfermeiros e a equipe multiprofissional assegurar um cuidado para além da doença. Objetivo: A partir disso, tem-se como objetivo deste estudo compreender, a partir das narrativas de vida dos idosos que envelheceram com vírus da imunodeficiência humana/aids, como se deram as relações familiares e afetivas pós- -diagnóstico. Métodos: Tratou-se de um estudo de abordagem qualitativa, com método de narrativa de vida por Daniel Bertaux. As entrevistas aconteceram em um hospital universitário em Niterói (RJ) e contamos com 13 participantes cuja coleta de dados ocorreu entre outubro de 2019 e março de 2020. Resultados: Nos resultados tivemos que estudos mostram que o vírus da imunodeficiência humana/aids é uma doença familiar, visto que a família tem um importante papel no apoio aos membros afetados com a doença. Nota-se que, se a família for capaz de lidar efetivamente com a enfermidade, ela enxergará as exigências do membro afetado como manejáveis, podendo desenvolver um sistema de significados coerentes e adaptativos relacionados às condições e aos desafios de saúde. Revela-se que o apoio familiar a pessoas que vivem com vírus da imunodeficiência humana é fundamental para a revelação do diagnóstico, o tratamento e a continuidade de vida dos pacientes. O diagnóstico de vírus da imunodeficiência humana/aids no contexto familiar desencadeou sentimento de pânico no que diz respeito à revelação da soropositividade ao cônjuge e ao desejo de não estar infectado com o vírus. Conclusão: O fato de a contaminação partir do cônjuge traz uma série de questões de culpabilização, principalmente quando o resultado da parceira não é favorável (negativo), sendo a saída para minimização da culpa o pedido de perdão e a reconciliação. Essa dinâmica familiar precisa ser considerada em todo processo, inclusive no tratamento, pois representa uma estrutura de apoio importante para a pessoa que vive com o vírus da imunodeficiência humana.
This work aims at the technological and innovative development of a noninjectable vaccine against a American Tegumentary Leishmaniasis (ATL), a neglected disease highly endemic in Brazil, leishmaniasis. Previous studies in the murine model demonstrated the efficacy of the intranasal route for the effective release of crude antigens (total lysate of Leishmania amazonensis-LaAg promastigotes) and DNA (LACK DNA) in the protection against cutaneous (L. (L.) amazonensis) and visceral (L. (L.) infantum) leishmaniasis. As most strains of mice are resistant to infection by species of the subgenus Viannia (L. braziliensis and L. guyanensis), the main responsible for cutaneous leishmaniasis in America (LTA), our group recently established the golden hamster L. braziliensis model for the study of pathogenesis and vaccine protection for ATL. We demonstrated the effectiveness of the intranasal vaccine with LaAg against infection by L. braziliensis hamster model. We have previously evidence that antigens called LVAL (not allowed disclosure-potential of patentability) could induce in vitro well modulated response in human cells. Then we hipotesize LVAL antigen could be a vaccine candidate against ATL. Objective: Thus, this work aims to evaluate the intranasal vaccine efficacy of the LVAL antigen and evaluate the immunological potential of the immunodominant fractions against infection by L. (V.) braziliensis in the hamster model. This study is part of a project with license number L7/17, approved by the CEUA/IOC-Fiocruz. Methodology: Hamsters were immunized with two doses of 20 μg LaAg or LVAL either intranasally or intramuscularly, with a 14-day interval between doses. The control group received PBS. After 14 days of the second immunization, the hamsters were infected on the dorsum of hind paw with 1 x 10 5 promastigotes of L. braziliensis. The lesion development was monitored weekly through the morphometry of the infected paw compared to the contralateral paw. Immunoblot methodology was performed to identify immunodominant antigenic fractions of the LaAg and LVAL antigens using serum samples from patients who evolved to cure spontaneous or posttreatment of LTA. Results: Hamsters vaccinated with LaAg and LVAL intramuscularly were not protected. The percentage of hamsters vaccinated with LaAg and LVAL that were considered protected (nodular lesions less than 1mm thick) was 50% and 43%, respectively, compared to 17% in the control group. Based on the immunoblot analysis, the fractions of the LVAL soluble antigens most frequently recognized by antibodies from sera from cured LTA individuals had molecular weight between 40 and 70 kDa. The molecules related to these bands will be fractionated and characterized biochemically. Conclusion: The identification and characterization of promising vaccine antigens may contribute to the definition of an active antigenic formulation in the protection against leishmaniasis that may serve for subsequent studies and evaluation of its potential clinical application.
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