RESUMEN
BACKGROUND: Hepatitis E Virus (HEV) infection is globally increasing. The present study was performed to investigate the HEV seroprevalence, exposure risks as well as occupational risks for military personnel in Austria, a Central European country. METHODS AND FINDINGS: A nationwide cross-sectional seroprevalence study was performed in 997 healthy Austrian adults, professional soldiers and civilians. Routine laboratory and HEV specific antibodies were determined. In addition, epidemiological information on possible risk factors for exposure to HEV was obtained. The overall seropositivity for HEV antibodies was 14.3% and significantly increased with age. Seroprevalence was significantly higher among individuals with previous military employments abroad (21.4% vs. 9.9%) and among professional soldiers aged 30-39 years (20.2% vs. 7.3%). No association was found for private travel, occupational or private animal contact or regular outdoor activities. Individuals who tested positive for antibodies against HEV had significantly higher laboratory values regarding liver enzymes, lipid levels and blood fasting glucose. CONCLUSIONS: Exposure to HEV is common in Austria. Military employment abroad could be a potential risk factor for HEV infection. Further studies are required to investigate the significance of pathological laboratory results found among asymptomatic individuals previously exposed to HEV.
Asunto(s)
Virus de la Hepatitis E/fisiología , Hepatitis E/epidemiología , Hepatitis E/virología , Estudios Seroepidemiológicos , Adolescente , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Austria/epidemiología , Glucemia/metabolismo , Estudios Transversales , Femenino , Geografía , Anticuerpos Antihepatitis/sangre , Hepatitis E/sangre , Virus de la Hepatitis E/inmunología , Interacciones Huésped-Patógeno , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Personal Militar/estadística & datos numéricos , Salud Pública/estadística & datos numéricos , Factores de Riesgo , Adulto JovenRESUMEN
In areas where Plasmodium falciparum malaria is highly endemic, naturally acquired immunity develops slowly with increasing age. The mechanisms that lead to this protective immunity against P. falciparum are under intense investigation, as they might serve as models for the development of an efficient vaccine. In this study, we aimed to investigate the potential contribution of cell-mediated immune responses to the build-up of anti-malarial immunity by comparing the phenotypes and frequencies of both P. falciparum-specific and non-specific, cytokine-expressing T cells in a cross-sectional study of healthy children and adults, living in a malaria-endemic area in Central Africa. An increased capacity of CD3+ cells to produce interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, and of the TCRgammadelta+ subset to produce TNF-alpha was seen in adults after stimulation of peripheral blood mononuclear cells (PBMC) with a late-stage, schizont-rich, parasite preparation. Mitogenic stimulation with PMA and ionomycin induced much higher frequencies of IFN-gamma- and TNF-alpha-expressing CD4+, CD8+ as well as TCRgammadelta+ cells in adults, while differences for interleukin (IL)-2 expression were restricted to CD4+ and CD8+ T cells. For IL-10, neither specific nor non-specific stimulations of PBMC were associated with significant age-dependent alterations. Impressive increases in the capacity to produce P. falciparum-specific and non-specific IFN-gamma and TNF-alpha appear to be the main cellular correlates of naturally acquired immunity in Central Africa.
Asunto(s)
Citocinas/biosíntesis , Malaria Falciparum/inmunología , Plasmodium falciparum/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , África Central/epidemiología , Factores de Edad , Anciano , Animales , Complejo CD3/inmunología , Niño , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Malaria Falciparum/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
An understanding of T cell responses that are crucial for control of Mycobacterium tuberculosis (MTB) has major implications for the development of immune-based interventions. We studied the frequency of purified protein derivative (PPD)-specific CD3) cells expressing interleukin-2 (IL)-2, gamma interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and IL-10 in HIV-negative pulmonary tuberculosis patients (TB, n=30) as well as in healthy individuals (controls, n=21) from Central Africa. Increased frequencies of PPD-stimulated CD3+ cells expressing IL-2, IFN-gamma, and TNF-alpha in TB were seen when compared with frequencies of controls. The presence of type 1 cytokine biased responses in TB patients was supported by a shift in the distribution pattern of cytokine expression from exclusively IL-2 or TNF-alpha expression seen in controls towards an increased frequency of IFN-gamma/IL-2 or IFN-gamma/TNF-alpha co-expression in TB. Higher levels of PPD-induced IFN-gamma in the supernatants from TB patients than from controls were found, which correlated with its intracellular expression. PPD was a weak inducer of IL-10 in T cells and insufficient in promoting cytokine production in TCRgammadelta+CD3+ cells. Non-specific stimulation with PMA and ionomycin revealed increased frequencies of CD4+ cells expressing IFN-gamma in controls, while expression of IL-2, IL-4, IL-10, IL-13, and TNF-alpha was not different. Non-specific cytokine responses of TCRgammadelta+CD3+ cells were similar in all groups. Pulmonary TB in Central Africa is associated with enhanced expression and secretion of specifically induced cytokines that are frequently implicated in host defense against MTB.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Citocinas/inmunología , Subgrupos de Linfocitos T/inmunología , Tuberculosis Pulmonar/inmunología , Adolescente , Adulto , Anciano , Brefeldino A/farmacología , Complejo CD3/análisis , Células Cultivadas , Femenino , Gabón , Humanos , Interferón gamma/análisis , Interleucina-10/análisis , Interleucina-2/análisis , Ionomicina/farmacología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Tuberculina/inmunología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Circulating levels of sIL-4R, IL-18 and IFN-gamma were studied by ELISA in 36 Gabonese patients with Plasmodium falciparum malaria (29 children, 7 adults). Drug induced clearance of parasitemia, studied in 22 patients with mild disease, was accompanied by a rapid decrease of sIL-4R and IFN-gamma to normal values and an increase of circulating IL-18, suggesting the downregulation of a type 2 biased immune response and a dissociated type 1 responsiveness while resolving parasitemia. Comparing subgroups with hyperparasitemia/severe anemia and mild malaria, children with severe malaria had significant higher levels of sIL-4R and IFN-gamma, whereas IL-18 levels were not statistically different. Furthermore, among those children, higher levels of circulating IL-18 correlated with a lower degree of parasitemia.
Asunto(s)
Interleucina-18/sangre , Malaria Falciparum/sangre , Receptores de Interleucina-4/sangre , Adolescente , Adulto , Niño , Preescolar , Gabón , Humanos , Interferón gamma/sangre , Malaria Falciparum/diagnóstico , Parasitemia/sangreRESUMEN
The frequency of P. falciparum-specific interleukin (IL)-2-, interferon (IFN)-gamma-, tumor necrosis factor (TNF)-alpha- and IL-10-expressing CD3+ cells was studied in healthy Gabonese children segregated according to their clinical presentation at admission to a longitudinal study of severe and mild malaria. The percentage of IL-2- and TNF-alpha- expressing P. falciparum-specific CD3+ cells was significantly higher in the children with prior mild malaria and less frequent reinfections compared to the children with prior severe malaria and more frequent reinfections. No differences were shown for P. falciparum-specific IFN-gamma and IL-10 expression within CD3+ cells and parasite-non-specific expression of IL-2, IL-4, IL-6, IL-10, IL-13, TNF-alpha, and IFN-gamma within the CD4+, CD8+, TCRgamma\delta+ CD3+ and CD94+ CD3- cell populations, indicating that immunological determinants regulating the susceptibility to malaria in age-matched children are parasite-specific. The ability of P. falciparum-specific T cells to mount a rapid IL-2 and TNF-alpha response might be of significance in preventing severe disease and reinfection.
Asunto(s)
Interleucina-2/inmunología , Malaria Falciparum/inmunología , Plasmodium falciparum/inmunología , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Adolescente , África , Animales , Secuencia de Bases , Niño , Estudios de Cohortes , Cartilla de ADN , Femenino , Citometría de Flujo , Humanos , Estudios Longitudinales , MasculinoRESUMEN
CD3+ T cells are important sources of both pro- and anti-inflammatory cytokines during Plasmodium falciparum malaria. We studied the frequency of interleukin-2 (IL-2), gamma interferon (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-10 expressing CD3+ cells in 10 non-immune malaria patients with uncomplicated malaria and in one patient with cerebral malaria after P. falciparum-specific and non-specific mitogenic stimulation. Analysis by fluorescence-activated cell sorting was performed after drug-induced clearance of parasites to allow previously sequestered T cells to be detected in peripheral blood. CD3+ cells of patients responded to P. falciparum infected erythrocytes with significant increases in the percentage of IL-2, IFN-gamma, and TNF-alpha, but also IL-10, positive cells. CD3+ cells from malaria-naïve donors were also responsive to specific stimulation albeit to a much lesser extent. Mitogenic stimulation of PBMC revealed no significant differences between cells of patients and controls. CD3+ cells of the patient with cerebral malaria were hyporesponsive both to the infecting parasite isolate as well as to our laboratory-adapted P. falciparum isolate, whereas two patients with uncomplicated disease were more responsive to their infecting parasites than to the laboratory-adapted isolate. The results indicate that the increased responsiveness of in vivo primed compared to malaria-naïve CD3+ cells is Plasmodium-specific and biased towards production of IFN-gamma and TNF-alpha.
Asunto(s)
Citocinas/biosíntesis , Malaria Falciparum/inmunología , Plasmodium falciparum/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Animales , Antígenos de Protozoos/administración & dosificación , Complejo CD3/metabolismo , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Humanos , Técnicas In Vitro , Interferón gamma/biosíntesis , Interleucina-10/biosíntesis , Interleucina-2/biosíntesis , Activación de Linfocitos , Malaria Cerebral/inmunología , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Cytokine profiles of CD4+ and CD8+ T-cell subsets were evaluated in 8 patients with infectious mononucleosis (IM). Intracellular detection of cytokines using flow cytometry revealed an expansion of IFN-gamma-expressing CD4+ T cells, and particularly CD8+ T cells, while IL-2 expressing cells were less frequently encountered when compared to healthy controls. Single TNF-alpha-expressing CD4+ and CD8+ T cells were likewise reduced and shifted towards IFN-gamma/TNF-alpha co-production. The predominant pro-inflammatory type 1-biased immune response during IM was emphasized by low frequencies of IL-10 expression in both T cell subsets, although some patients displayed elevated serum levels. Six months later, a decreased, but still elevated IFN-gamma expression within the CD8+ T cell subset, and an increased percentage of IL-2-expressing CD4+ and CD8+ T cells, reaching values shown for controls, were noted. Type 2-associated cytokines such as IL-4 and IL-13, as well as IL-6 and TNF-alpha were not significantly different when compared to controls at study entry and at follow-up. The striking expansion of IFN-gamma-producing CD8+ T cells with rather low expression of IL-10, appears to be a key factor for clinically overt disease, but is nevertheless compatible with successful control of the viral infection.