Implication of haematophagous arthropod salivary proteins in host-vector interactions

The saliva of haematophagous arthropods contains an array of anti-haemostatic, anti-inflammatory and immunomodulatory molecules that contribute to the success of the blood meal. The saliva of haematophagous arthropods is also involved in the transmission and the establishment of pathogens in the host and in allergic responses. This survey provides a comprehensive overview of the pharmacological activity and immunogenic properties of the main salivary proteins characterised in various haematophagous arthropod species. The potential biological and epidemiological applications of these immunogenic salivary molecules will be discussed with an emphasis on their use as biomarkers of exposure to haematophagous arthropod bites or vaccine candidates that are liable to improve host protection against vector-borne diseases

Plasmodium falciparum proteome changes in response to doxycycline treatment

<p>Abstract</p> <p>Background</p> <p>The emergence of <it>Plasmodium falciparum </it>resistance to most anti-malarial compounds has highlighted the urgency to develop new drugs and to clarify the mechanisms of anti-malarial drugs currently used. Among them, doxycycline is used alone for malaria chemoprophylaxis or in combination with quinine or artemisinin derivatives for malaria treatment. The molecular mechanisms of doxycycline action in <it>P. falciparum </it>have not yet been clearly defined, particularly at the protein level.</p> <p>Methods</p> <p>A proteomic approach was used to analyse protein expression changes in the schizont stage of the malarial parasite <it>P. falciparum </it>following doxycycline treatment. A comparison of protein expression between treated and untreated protein samples was performed using two complementary proteomic approaches: two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and isobaric tagging reagents for relative and absolute quantification (iTRAQ).</p> <p>Results</p> <p>After doxycycline treatment, 32 and 40 <it>P. falciparum </it>proteins were found to have significantly deregulated expression levels by 2D-DIGE and iTRAQ methods, respectively. Although some of these proteins have been already described as being deregulated by other drug treatments, numerous changes in protein levels seem to be specific to doxycycline treatment, which could perturb apicoplast metabolism. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm this hypothesis.</p> <p>Conclusions</p> <p>In this study, a specific response to doxycycline treatment was distinguished and seems to involve mitochondrion and apicoplast organelles. These data provide a starting point for the elucidation of drug targets and the discovery of mechanisms of resistance to anti-malarial compounds.</p

Specific antibody responses against membrane proteins of erythrocytes infected by Plasmodium falciparum of individuals briefly exposed to malaria

International audienceBACKGROUND: Plasmodium falciparum infections could lead to severe malaria, principally in non-immune individuals as children and travellers from countries exempted of malaria. Severe malaria is often associated with the sequestration of P. falciparum-infected erythrocytes in deep micro-vascular beds via interactions between host endothelial receptors and parasite ligands expressed on the surface of the infected erythrocyte. Although, serological responses from individuals living in endemic areas against proteins expressed at surface of the infected erythrocyte have been largely studied, seldom data are available about the specific targets of antibody response from travellers. METHODS: In order to characterize antigens recognized by traveller sera, a comparison of IgG immune response against membrane protein extracts from uninfected and P. falciparum-infected red blood cells (iRBC), using immunoblots, was performed between non exposed individuals (n = 31) and briefly exposed individuals (BEI) (n = 38) to malaria transmission. RESULTS: Immune profile analysis indicated that eight protein bands from iRBC were significantly detected more frequently in the BEI group. Some of these antigenic proteins were identified by an original immuno-proteomic approach. CONCLUSION: Collectively, these data may be useful to characterize the singular serological immune response against a primary malaria infection in individuals briefly exposed to transmission

Altered Protein Networks and Cellular Pathways in Severe West Nile Disease in Mice

Background:The recent West Nile virus (WNV) outbreaks in developed countries, including Europe and the United States, have been associated with significantly higher neuropathology incidence and mortality rate than previously documented. The changing epidemiology, the constant risk of (re-)emergence of more virulent WNV strains, and the lack of effective human antiviral therapy or vaccines makes understanding the pathogenesis of severe disease a priority. Thus, to gain insight into the pathophysiological processes in severe WNV infection, a kinetic analysis of protein expression profiles in the brain of WNV-infected mice was conducted using samples prior to and after the onset of clinical sympt

Kinetic analysis of mouse brain proteome alterations following chikungunya virus infection before and after appearance of clinical symptoms

Recent outbreaks of Chikungunya virus (CHIKV) infection have been characterized by an increasing number of severe cases with atypical manifestations including neurological complications. In parallel, the risk map of CHIKV outbreaks has expanded because of improved vector competence. These features make CHIKV infection a major public health concern that requires a better understanding of the underlying physiopathological processes for the development of antiviral strategies to protect individuals from severe disease. To decipher the mechanisms of CHIKV in

Antimalarial drug use in general populations of tropical Africa

<p>Abstract</p> <p>Background</p> <p>The burden of <it>Plasmodium falciparum </it>malaria has worsened because of the emergence of chloroquine resistance. Antimalarial drug use and drug pressure are critical factors contributing to the selection and spread of resistance. The present study explores the geographical, socio-economic and behavioural factors associated with the use of antimalarial drugs in Africa.</p> <p>Methods</p> <p>The presence of chloroquine (CQ), pyrimethamine (PYR) and other antimalarial drugs has been evaluated by immuno-capture and high-performance liquid chromatography in the urine samples of 3,052 children (2–9 y), randomly drawn in 2003 from the general populations at 30 sites in Senegal (10), Burkina-Faso (10) and Cameroon (10). Questionnaires have been administered to the parents of sampled children and to a random sample of households in each site. The presence of CQ in urine was analysed as dependent variable according to individual and site characteristics using a random – effect logistic regression model to take into account the interdependency of observations made within the same site.</p> <p>Results</p> <p>According to the sites, the prevalence rates of CQ and PYR ranged from 9% to 91% and from 0% to 21%, respectively. In multivariate analysis, the presence of CQ in urine was significantly associated with a history of fever during the three days preceding urine sampling (OR = 1.22, p = 0.043), socio-economic level of the population of the sites (OR = 2.74, p = 0.029), age (2–5 y = reference level; 6–9 y OR = 0.76, p = 0.002), prevalence of anti-circumsporozoite protein (CSP) antibodies (low prevalence: reference level; intermediate level OR = 2.47, p = 0.023), proportion of inhabitants who lived in another site one year before (OR = 2.53, p = 0.003), and duration to reach the nearest tarmacked road (duration less than one hour = reference level, duration equal to or more than one hour OR = 0.49, p = 0.019).</p> <p>Conclusion</p> <p>Antimalarial drug pressure varied considerably from one site to another. It was significantly higher in areas with intermediate malaria transmission level and in the most accessible sites. Thus, <it>P. falciparum </it>strains arriving in cross-road sites or in areas with intermediate malaria transmission are exposed to higher drug pressure, which could favour the selection and the spread of drug resistance.</p

Relationship between Exposure to Vector Bites and Antibody Responses to Mosquito Salivary Gland Extracts

Mosquito-borne diseases are major health problems worldwide. Serological responses to mosquito saliva proteins may be useful in estimating individual exposure to bites from mosquitoes transmitting these diseases. However, the relationships between the levels of these IgG responses and mosquito density as well as IgG response specificity at the genus and/or species level need to be clarified prior to develop new immunological markers to assess human/vector contact. To this end, a kinetic study of antibody levels against several mosquito salivary gland extracts from southeastern French individuals living in three areas with distinct ecological environments and, by implication, distinct Aedes caspius mosquito densities were compared using ELISA. A positive association was observed between the average levels of IgG responses against Ae. caspius salivary gland extracts and spatial Ae. caspius densities. Additionally, the average level of IgG responses increased significantly during the peak exposure to Ae. caspius at each site and returned to baseline four months later, suggesting short-lived IgG responses. The species-specificity of IgG antibody responses was determined by testing antibody responses to salivary gland extracts from Cx. pipiens, a mosquito that is present at these three sites at different density levels, and from two other Aedes species not present in the study area (Ae. aegypti and Ae. albopictus). The IgG responses observed against these mosquito salivary gland extracts contrasted with those observed against Ae. caspius salivary gland extracts, supporting the existence of species-specific serological responses. By considering different populations and densities of mosquitoes linked to environmental factors, this study shows, for the first time, that specific IgG antibody responses against Ae. caspius salivary gland extracts may be related to the seasonal and geographical variations in Ae. caspius density. Characterisation of such immunological-markers may allow the evaluation of the effectiveness of vector-control strategies or estimation of the risk of vector-borne disease transmission

Cerebrospinal fluid biomarker candidates associated with human WNV neuroinvasive disease

During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinal fluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presente

Promontofixation coelioscopique (évaluation de la continence à l'effort et des résultats anatomiques)

Objectif : Analyser les résultats fonctionnels de la promonto-fixation coelioscopique (PFC) à moyen terme et rechercher un facteur influençant l'apparition d'une incontinence urinaire d'effort post opératoire de novo ou d'une récidive anatomique. Matériel et méthodes : Etude rétrospective mono centrique (décembre 1997 à décembre 2005) menée chez 97 patientes consécutives, d'âge moyen 59,5ans au moment de l'intervention (extrêmes : 30,8-81), opérées d'un prolapsus génito-urinaire symptomatique par PFC. L'indication opératoire de la cure d'incontinence découlait d'un dépistage d'une incontinence masquée et d'une IUE rapportée. Le bilan incluait : bilan urodynamique, échographie post mictionnelle, cystoscopie avec examen uro-gynécologique, catalogue mictionnel. Les patientes ont été revues à distance avec interrogatoire et examen uro-gynécologique. Résultats : 57% avaient une IUE (masquée par le prolapsus dans 50%). La PFC était réalisée avec une double bandelette dans 96%. Il a été réalisé 45 bandelettes sous urétrales, 6 colposuspensions et 1 sphincter artificiel. 82 patientes (90%) ont été revues avec un recul moyen de 14,3 mois. 6 patientes (7%) ont présenté une IUE " de novo ". Il n'a pas été mis en évidence de facteur clinique influençant son apparition. 9 patientes (11%) ont présenté une récidive anatomique allant de la rectocèle distale tardive à la récidive complète précoce. Aucun facteur influençant son apparition n'a été mis en évidence. Conclusion : La PFC est une technique reproductible et offre de bons résultats fonctionnels. La réduction des taux d'incontinence post opératoire et de récidive anatomique est dépendante de la qualité de l'expertise préopératoire.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Radiothérapie externe exclusive pour cancer de prostate localisé (étude reprospective sur 10 ans)

La radiothérapie externe fait partie de l'arsenal thérapeutique du cancer de prostate localisé. Elle peut être concentionnelle ou plus récemment de conformation grâce aux progrès technologique qui ont permis de conformer le volume irradié au plus près du volume cible. Le but principal du traitement du cancer est d'augmenter la durée de vie du patient voire sa guérison. Cependant, la qualité de vie des patients doit influencer le choix thérapeutique Une étude rétrospective sur 10 ans (1989-1999) a été réalisée, portant sur 116 patients consécutifs, porteurs d'un cancer de prostate localisé Nx M0, traités par radiothérapie externe (conventionnelle ou de conformation) exclusive avec ou sans hormonothérapie nèoadjuvante. Les objectifs de cette étude ont été : l'évaluation des résultats de ce traitement (en fonction du stade clinique, du PSA Nadir...), L'identification des facteurs pronostiques, le point sur les complications (urinaires, digestives et sexuelles), et l'analyse de la qualité de vie qui en a résulté grâce à un questionnaire (traduction fidèle du "UCLA/RAND PROSTATE CANCER INDEX"). Après homogénisation des sous-populations, les comparaisons ont été réalisées à l'aide des tests statistiques de Chi-2 ou t de Student, et les résultats en terme de contrôle biochimique (selon la définition de l'ASTRO) ont été évalués par l'estimation non paramétrique de Kaplan-Meier.PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF