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Infected Subjects (infected + subject)

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Medical Sciences	100%

Selected Abstracts

Severe functional impairment and elevated PD-1 expression in CD1d-restricted NKT cells retained during chronic HIV-1 infection

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2009
Markus Moll
Abstract Invariant CD1d-restricted NKT cells play important roles in regulating both innate and adaptive immunity. They are targeted by HIV-1 infection and severely reduced in number or even lost in many infected subjects. Here, we have investigated the characteristics of NKT cells retained by some patients despite chronic HIV-1 infection. NKT cells preserved under these circumstances displayed an impaired ability to proliferate and produce IFN-, in response to CD1d-restricted lipid antigen as compared with cells from uninfected control subjects. HIV-1 infection was associated with an elevated expression of the inhibitory programmed death-1 (PD-1) receptor (CD279) on the CD4, subset of NKT cells. However, blocking experiments indicated that the functional defects in NKT cells were largely PD-1-independent. Furthermore, the elevated PD-1 expression and the functional defects were not restored by anti-retroviral treatment, and the NKT cell numbers in blood did not recover significantly in response to treatment. The functional phenotype of NKT cells in these patients suggests an irreversible immune exhaustion due to chronic activation in vivo. The data demonstrate a severe functional impairment in the remaining NKT-cell compartment in HIV-1-infected patients, which limits the prospects to mobilize these cells in immunotherapy approaches in patients. [source]

Distribution of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in an Australian population

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 12 2001
S. M. Hamlet
Abstract Background, aim: The present study describes (i) the natural distribution of the three putative periodontopathogens Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans in an Australian population and (ii) the relationship between these organisms, pocket depths and supragingival plaque scores. Methods: Subgingival plaque was collected from the shallowest and deepest probing site in each sextant of the dentition. In total, 6030 subgingival plaque samples were collected from 504 subjects. An ELISA utilising pathogen-specific monoclonal antibodies was used to quantitate bacterial numbers. Results::A. actinomycetemcomitans was the most frequently detected organism (22.8% of subjects) followed by P. gingivalis and P. intermedia (14.7% and 9.5% of subjects respectively). The majority of infected subjects (83%) were colonised by a single species of organism. A. actinomycetemcomitans presence was over-represented in the youngest age group but under-represented in the older age groups. Conversely, P. gingivalis and P. intermedia presence was under-represented in the youngest age group but over-represented in the older age groups. Differing trends in the distribution of these bacteria were observed between subjects depending upon the site of the infection or whether a single or mixed infection was present; however, these differences did not reach significance. Bacterial presence was strongly associated with pocket depth for both A. actinomycetemcomitans and P. gingivalis. For A. actinomycetemcomitans, the odds of a site containing this bacterium decrease with deeper pockets. In contrast, for P. gingivalis the odds of a site being positive are almost six times greater for pockets >3 mm than for pockets 3 mm. These odds increase further to 15.3 for pockets deeper than 5 mm. The odds of a site being P. intermedia positive were marginally greater (1.16) for pockets deeper than 3 mm. Conclusions: This cross-sectional study in a volunteer Australian population, demonstrated recognised periodontal pathogens occur as part of the flora of the subgingival plaque. Prospective longitudinal studies are needed to examine the positive relationship between pocket depth and pathogen presence with periodontal disease initiation and/or progression. Zusammenfassung Hintergrund: Die vorliegende Studie beschreibt: 1.) die natürliche Verteilung der 3 vermutlichen Parodontalpathogene Porphyromonas gingivalis und Prevotella intermedia und Actinobacillus actinomycetemcomitans in einer Australischen Population und 2.) das Verhältnis zwischen diesen Organismen, der Taschentiefe und den supragingivalen Plaquewerten. Methoden: In jedem Sextanten des Gebisses wurde subgingivale Plaque von der flachsten und tiefsten Stelle entnommen. Insgesamt wurden 6030 subgingivalen Plaqueproben bei 504 Personen entnommen. Um die Anzahl der Bakterien zu quantifizieren wurde ein ELISA, welcher mit pathogen-spezifische monoklonale Antikörper arbeitet, verwendet. Ergebnisse:A. actinomycetemcomitans war der Keim, der am häufigsten nachgewiesen wurde (22.8% der Personen), gefolgt von P. gingivalis und P. intermedia (14.7% bzw. 9.5% der Personen). Die Mehrheit der Personen (83%) wurde von einer einzigen Spezies eines Organismus kolonisiert. Das Vorkommen von A. actinomycetemcomitans war in der jüngsten Altersgruppe überrepräsentiert, aber in der älteren Altersgruppen unterrepräsentiert. Im Gegensatz dazu war das Vorkommen von P. gingivalis und P. intermedia in der jüngsten Altersgruppe unterepräsentiert, aber in der älteren Altersgruppen überrepräsentiert. Zwischen der Personen wurden unterschiedliche Trends in der Verteilung dieser Bakterien beobachtet. Diese waren abhängig von der Stelle der Infektion oder ob eine Monoinfektion oder Mischinfektion vorhanden war. Jedoch erreichten diese Unterschiede nicht den Bereich der Signifikanz. Sowohl für A. actinomycetemcomitans als auch P. gingivalis war das Vorkommen von Bakterien stark mit der Taschentiefe assoziiert. Für A. actinomycetemcomitans nimmt die Odds einer Stelle welche das Bakterium enthält mit der Tiefe der Tasche ab. Im Gegensatz dazu ist die Odds einer Stelle die positiv für P. gingivalis ist fast sechsmal größer für Taschen >3 mm als für Taschen 3 mm. Diese Odds erhöht sich weiter auf 15.3 für Taschen die tiefer als 5 mm sind. Die Odds einer Stelle die positive für P. intermedia ist war nur etwas größer (1.16) für Taschen, die tiefer als 3 mm sind. Schlussfolgerung: Diese Querschnittsstudie einer Australischen Population von Freiwillingen zeigte, dass die erkannten Parodontalpathogene ein Bestandteil der Flora der subgingivalen Plaque sind. Prospektive Langzeitstudien sind notwendig, um die positive Beziehung zwischen der Taschentiefe und dem Vorkommen von Pathogenen mit dem Beginn und der Progression einer Parodontalerkrankung zu untersuchen. Résumé Origine: Cette étude décrit (i) la distribution naturelle des 3 parodontopathogènes présume,Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis et Prevotella intermedia dans une population australienne et (ii) la relation entre ces organismes, les profondeurs de poche et les scores de plaque supragingivale. Méthodes: La plaque sous-gingivale a été prélevée sur le site le moins profond et sur le site le plus profond de chaque sextant de la denture. Au total, 6030 échantillons de plaque sous-gingivale ont été prélevés chez 504 sujets. Un test ELISA par anticorps monoclonaux spécifiques des pathogènes a permis de quantifier les nombres de bactéries. Résultats:Actinobacillus actinomycetemcomitans était l'organisme le plus fréquement détecté (22.8%) des sujets) suivi de Porphyromonas gingivalis et Prevotella intermedia (14.7% et 9.5% des sujets, respectivement). La majorité des sujets infectés (83%) étaient colonisés par une unique espèce d'organisme. La présence d'Actinobacillus actinomycetemcomitansétait surreprésentée dans le groupe des plus jeunes mais sous-représentée dans les groupes plus agés. Des tendances différentes de la distribution de ces bactéries étaient observées entre les sujets selon le site d'infection ou la présence d'une infection unique ou mixte. Cependant, ces différences n'étaient pas significatives. La présence bactérienne était fortement associée avec la profondeur de poche pour Actinobacillus actinomycetemcomitans et Porphyromonas gingivalis, pour Actinobacillus actinomycetemcomitans, les chances d'un site de contenir cette bactérie diminuant avec la profondeur de poche, alors que pour Porphyromonas gingivalis, les chances d'un site d'être positif étaient 6× plus grande pour des poches >3 mm que pour les poches 3 mm. Ces chances augmentaient en plus à 15.3 pour les poches >5 mm. Les chances d'un site d'être positif pour P. intermediaétaient légèrement plus importantes pour les poches de plus de 3 mm. Conclusions: Cette étude croisée dans une population volontaire australienne a démontré que des pathogènes parodontaux reconnus font partie de leur plaque sous-gingivale. Des études prospectives longitudinales sont nécessaires pour examiner les relations positives entre la profondeur de poche et la présence de pathogènes et l'initiation et/ou la progression de la maladie. [source]

Reconstructing and predicting the hepatitis C virus epidemic in Greece: increasing trends of cirrhosis and hepatocellular carcinoma despite the decline in incidence of HCV infection

JOURNAL OF VIRAL HEPATITIS, Issue 4 2004
V. Sypsa
Summary., In this study, a comprehensive methodology for modelling the hepatitis C virus (HCV) epidemic is proposed to predict the future disease burden and assess whether the recent decline in the incidence of HCV may affect the future occurrence of cirrhosis and hepatocellular carcinoma (HCC) cases. Using the prevalence of HCV, the distribution of chronic hepatitis C (CHC) patients within the various transmission groups and their infection-onset times, it was possible to reconstruct the incident infections per year in the past that progressed to CHC in Greece. The natural history of the disease was simulated in subcohorts of newly infected subjects using transition probabilities derived either empirically between fibrosis stages 0,4 or from literature review. Annual estimates of the incidence and prevalence of CHC by fibrosis stage, HCC and mortality in Greece were obtained up to 2030. HCV incidence peaked in the late 1980s at five new infections/10 000 person-years. Under the assumption of 20,100% decline in HCV incidence after 1990, the cumulative number of incident cirrhosis and HCC cases from 2002,2030 was projected to be lower by 9.6,48.2% and 5.9,29.5%, respectively, than that estimated under the assumption of no decline. However, the prevalent cirrhotic/HCC cases and HCV-related deaths are predicted to decline in the next 30 years only under the assumption of complete elimination of new HCV infections after 1990. Despite the progress in the reduction of HCV transmission, primary prevention does not seem adequate to reverse the rise in the incidence of cirrhosis and HCC. [source]

Association between parasite infection and immune responses in multiple sclerosis

ANNALS OF NEUROLOGY, Issue 2 2007
Jorge Correale MD
Objective To assess whether parasite infection is correlated with a reduced number of exacerbations and altered immune reactivity in multiple sclerosis (MS). Methods A prospective, double-cohort study was performed to assess the clinical course and radiological findings in 12 MS patients presenting associated eosinophilia. All patients presented parasitic infections with positive stool specimens. In all parasite-infected MS patients, the eosinophilia was not present during the 2 previous years. Eosinophil counts were monitored at 3- to 6-month intervals. When counts became elevated, patients were enrolled in the study. Interleukin (IL)-4, IL-10, IL-12, transforming growth factor (TGF)-,, and interferon-, production by myelin basic protein,specific peripheral blood mononuclear cells were studied using enzyme-linked immunospot (ELISPOT). FoxP3 and Smad7 expression were studied by reverse-transcriptase polymerase chain reaction. Results During a 4.6-year follow-up period, parasite-infected MS patients showed a significantly lower number of exacerbations, minimal variation in disability scores, as well as fewer magnetic resonance imaging changes when compared with uninfected MS patients. Furthermore, myelin basic protein,specific responses in peripheral blood showed a significant increase in IL-10 and TGF-, and a decrease in IL-12 and interferon-,,secreting cells in infected MS patients compared with noninfected patients. Myelin basic protein,specific T cells cloned from infected subjects were characterized by the absence of IL-2 and IL-4 production, but high IL-10 and/or TGF-, secretion, showing a cytokine profile similar to the T-cell subsets Tr1 and Th3. Moreover, cloning frequency of CD4+CD25+ FoxP3+ T cells was substantially increased in infected patients compared with uninfected MS subjects. Finally, Smad7 messenger RNA was not detected in T cells from infected MS patients secreting TGF-,. Interpretation Increased production of IL-10 and TGF-,, together with induction of CD25+CD4+ FoxP3+ T cells, suggests that regulatory T cells induced during parasite infections can alter the course of MS. Ann Neurol 2007 [source]

HIV-1 DNA proviral load in treated and untreated HIV-1 seropositive patients

CLINICAL MICROBIOLOGY AND INFECTION, Issue 6 2010
M. C. Re
Clin Microbiol Infect 2010; 16: 640,646 Abstract As proviral human immunodeficiency virus type 1 (HIV-1) DNA can replenish and revive viral infection upon activation, its detection might offer significant therapeutic information, complementing the input provided by plasma RNA determination in the follow-up of infected individuals. A selected group of acutely infected subjects was studied to verify both total and 2-long terminal repeat (2-LTR) DNA proviral load during the acute phase of infection and thereafter. Patients were divided in two sex- and age-matched groups: 19 naive individuals who did not receive antiretroviral therapy during the observation period and 20 subjects treated according to current guidelines. Total and 2-LTR HIV-1 DNA proviral load, in addition to RNA viral load and CD4 cell count, were determined in peripheral blood mononuclear cells (PBMC) at baseline, 6 and 12 months after the first sampling. Total and 2-LTR HIV-1 DNA proviral load exhibited no significant variation at any time in the naive patients (total HIV-1 DNA ranging from 896 ± 731 to 715 ± 673 copies/105 PBMC and 2-LTR HIV-1 DNA ranging from 94 ± 105 to 65 ± 44 copies/105 PBMC), whereas a significant reduction in both total HIV-1 DNA (ranging from 997 ± 676 to 262 ± 174 copies/105 PBMC) and 2-LTR HIV-1 DNA proviral load (ranging from 116 ± 55 to 26 ± 35 copies/105 PBMC) was detected in highly active antiretroviral therapy (HAART) patients, together with a CD4+ T cell count increase and RNA load decrease. HAART negatively affects both the labile HIV burden and the integrated proviral DNA, at least in the initial period of successful treatment, suggesting that quantification of HIV-1 DNA proviral load may be an important parameter in monitoring HIV infection. [source]