Monte-Carlo simulations of the background of the coded-mask camera for X- and Gamma-rays on-board the Chinese-French GRB mission SVOM

For several decades now, wide-field coded mask cameras have been used with success to localise Gamma-ray bursts (GRBs). In these instruments, the event count rate is dominated by the photon background due to their large field of view and large effective area. It is therefore essential to estimate the instrument background expected in orbit during the early phases of the instrument design in order to optimise the scientific performances of the mission. We present here a detailed study of the instrument background and sensitivity of the coded-mask camera for X- and Gamma-rays (CXG) to be used in the detection and localisation of high-redshift GRBs on-board the international GRB mission SVOM. To compute the background spectrum, a Monte-Carlo approach was used to simulate the primary and secondary interactions between particles from the main components of the space environment that SVOM will encounter along its Low Earth Orbit (LEO) (with an altitude of 600 km and an inclination of ~ 30 deg) and the body of the CXG. We consider the detailed mass model of the CXG in its latest design. According to our results, i) the design of the passive shield of the camera ensures that in the 4-50 keV imaging band the cosmic X-Gamma-ray background is dominant whilst the internal background should start to become dominant above 70-90 keV; ii) the current camera design ensures that the CXG camera will be more sensitive to high-redshift GRBs than the Swift Burst Alert Telescope thanks to a low-energy threshold of 4 keV.Comment: 16 pages, 10 figures (1 colour), accepted for publication in Nuclear Instruments and Methods in Physics Research: Section

Caractérisation de détecteurs CdTe Schottky pour la Caméra X/Gamma d'ECLAIRs

Cette thèse est consacrée à la caractérisation de détecteurs solides à semi-conducteur de Tellurure de Cadmium (CdTe) pour une application d'astrophysique spatiale des hautes énergies. De dimension 4*4*1 mm3, avec un contact Schottky à l'anode, ils formeront le plan de détection (1024 cm²) de la Caméra X/Gamma d'ECLAIRs. ECLAIRs est l'instrument central de la future mission Sino-française SVOM dédiée à l'étude des sursauts gamma, un phénomène violent de haute énergie ayant lieu à des distances cosmologiques. ECLAIRs sera sensible de 4 à 250 keV. Les instruments actuels utilisant du CdTe, tels que BAT sur Swift ou ISGRI sur INTEGRAL, présentent un seuil bas de ~15 keV qui limite la détection des sursauts les plus mous, qui sont potentiellement les plus lointains. ECLAIRs relève le défi de détecter les photons à partir de 4 keV, en associant une électronique de lecture bas bruit aux diodes CdTe polarisées en inverse. Un tel objectif ne saurait être atteint sans une connaissance approfondie des détecteurs utilisés. C'est l'objet de cette étude. Des mesures systématiques sont réalisées sur les détecteurs avant de les monter par 32 en modules élémentaires de détection. L'objectif de ces tests est de sélectionner les 6400 détecteurs du modèle de vol, parmi plus de 12000 unités. Diverses populations de détecteurs ont été mises en évidence. Une analyse des résultats, complétée par des tests dédiés, permet d'expliquer les comportements particuliers. La population principale, qui compte aujourd'hui ~79% des détecteurs testés, répond à des critères qui sont optimum pour l'application d'ECLAIRs. Cependant, les détecteurs CdTe Schottky souffrent d'instabilités réversibles qu'il est important de prendre en compte. Elles peuvent être atténuées et ralenties par une température de fonctionnement basse et une tension de polarisation élevée, typiquement -20°C et -600 V. Afin d'anticiper la réponse spectrale du plan de détection, des simulations Monte-Carlo utilisant l'outil Geant4 ont été effectuées. Un modèle du module élémentaire de la caméra a donc été développé en parallèle des mesures. A basse énergie, les événements multiples entre pixels voisins est quasi nul et la rétrodiffusion inexistante. Ces taux augmentent avec l'énergie et créent des raies caractéristiques dans les spectres. Finalement, au regard de cette étude, des essais à réaliser sur les modules élémentaires de détection sont présentés.This work reports on the study of Cadmium Telluride (CdTe) solid state semiconductor detectors, for a space application in high energy astrophysics. With a Schottky contact at the anode and dimensions of 4*4*1 mm3, they will make up the detection plane (1024 cm²) of the ECLAIRs X- and Gamma-ray Camera. ECLAIRs is the main instrument of the upcoming Chinese-French mission SVOM dedicated to the study of gamma-ray bursts, violent and highly energetic phenomena which occur at cosmological distances. ECLAIRs will be sensitive from 4 to 250 keV. Current instruments using CdTe detectors, such as BAT for Swift or ISGRI on board INTEGRAL, show a low threshold of ?15 keV, which limits the detection of the softest bursts, most likely the most distant ones. ECLAIRs takes up the challenge to detect photons from 4 keV, by associating low noise readout electronics to the CdTe diodes polarized in reverse mode. Such an objective requires an in-depth knowledge of the detectors used. This is the subject of this research. Systematic measurements are performed on the detectors before mounting on elementary detection modules. The goal of these tests is to select the 6400 flight-model detectors, out of 12000 units. Several populations of detectors have been identified. The analysis of the results, together with dedicated tests, enables us to explain peculiar behaviours. The main population, which includes ?79% of the detectors tested at the moment, fulfils criteria which are optimum for ECLAIRs. However, CdTe Schottky detectors suffer from reversible instabilities, which have to be taken into account. Their effect can be reduced and slowed down by lowering the operating temperature and using high reverse bias voltage, typically -20°C and -600 V. In order to compute the spectral response of the detection plane, Monte-Carlo simulations using the Geant4 toolkit have been developed. A model of the elementary module of the camera has been set up, and the results compared to the measurements. At low energy, the charge sharing between neighbouring pixels is close to zero and the backscattering is negligible. These rates increase with energy, imprinting peaks at well defined energies in the spectra. Finally, following this study, tests to be performed on the elementary detection modules are presented

New Salivary Biomarkers of Human Exposure to Malaria Vector Bites

International audienc

An insight into immunogenic salivary proteins of Anopheles gambiae in African children

<p>Abstract</p> <p>Background</p> <p>During blood feeding, the mosquito injects saliva into the vertebrate host. This saliva contains bioactive components which may play a role in pathogen transmission and in host-vector relationships by inducing an immune response in the vertebrate host. The evaluation of human immune responses to arthropod bites might also represent a research direction for assessing individual exposure to the bite of a malaria vector.</p> <p>Methods</p> <p>The present study examined the antibody (Ab) IgG response during the season of exposure to <it>Anopheles gambiae </it>bites in young children living in a malaria endemic area. Immunoblots were performed with <it>An. gambiae </it>saliva to detect anti-saliva Ab bands and the evolution of immunogenic bands at the peak of, and following, the transmission period.</p> <p>Results</p> <p>The results showed that anti-<it>Anopheles </it>Ab was directed against a limited number of salivary proteins (175, 115, 72 and 30 kDa bands). Specific IgG responses to mosquito salivary proteins were variable among exposed individuals; nevertheless, two major bands (175 and 72 kDa) were observed in all immune-responder children. Analysis of the intensity of immunogenic bands revealed that IgG levels against the 175 kDa band were significantly higher during the peak period compared to the end period malaria transmission.</p> <p>Conclusion</p> <p>This preliminary work supports the potential of using anti-saliva immune responses as a measure of exposure to <it>Anopheles </it>bites. The use of immunoblots coupled with evaluation of band intensity could be an adequate tool for distinguishing immunogenic salivary proteins as candidate markers of bite exposure. Furthermore, this study may open the way to design new epidemiological tools for evaluating the risk of malaria exposure.</p

Human IgG response to a salivary peptide, gSG6-P1, as a new immuno-epidemiological tool for evaluating low-level exposure to Anopheles bites

<p>Abstract</p> <p>Background</p> <p>Human populations exposed to low malaria transmission present particular severe risks of malaria morbidity and mortality. In addition, in a context of low-level exposure to <it>Anopheles </it>vector, conventional entomological methods used for sampling <it>Anopheles </it>populations are insufficiently sensitive and probably under-estimate the real risk of malaria transmission. The evaluation of antibody (Ab) responses to arthropod salivary proteins constitutes a novel tool for estimating exposure level to insect bites. In the case of malaria, a recent study has shown that human IgG responses to the gSG6-P1 peptide represented a specific biomarker of exposure to <it>Anopheles gambiae </it>bites. The objective of this study was to investigate if this biomarker can be used to estimate low-level exposure of individuals to <it>Anopheles </it>vector.</p> <p>Methods</p> <p>The IgG Ab level to gSG6-P1 was evaluated at the peak and at the end of the <it>An. gambiae </it>exposure season in children living in Senegalese villages, where the <it>Anophele</it>s density was estimated to be very low by classical entomological trapping but where malaria transmission occurred during the studied season.</p> <p>Results</p> <p>Specific IgG responses to gSG6-P1 were observed in children exposed to very low-level of <it>Anopheles </it>bites. In addition, a significant increase in the specific IgG Ab level was observed during the <it>Anopheles </it>exposure season whereas classical entomological data have reported very few or no <it>Anopheles </it>during the studied period. Furthermore, this biomarker may also be applicable to evaluate the heterogeneity of individual exposure.</p> <p>Conclusion</p> <p>The results strengthen the hypothesis that the evaluation of IgG responses to gSG6-P1 during the season of exposure could reflect the real human contact with anthropophilic <it>Anopheles </it>and suggest that this biomarker of low exposure could be used at the individual level. This promising immuno-epidemiological marker could represent a useful tool to assess the risk to very low exposure to malaria vectors as observed in seasonal, urban, altitude or travellers contexts. In addition, this biomarker could be used for the surveillance survey after applying anti-vector strategy.</p

Novel Peptide Marker Corresponding to Salivary Protein gSG6 Potentially Identifies Exposure to Anopheles Bites

BACKGROUND: In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites. METHODOLOGY/PRINCIPAL FINDINGS: Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i) their potential antigenic properties and ii) the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1. CONCLUSIONS/SIGNIFICANCE: This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could also represent a direct criterion of efficacy in evaluation of vector control strategies

Anopheles gambiae salivary protein expression modulated by wild Plasmodium falciparum infection: Highlighting of new antigenic peptides as candidates of An. gambiae bites

Background: Malaria is the major parasitic disease worldwide caused by Plasmodium infection. The objective of integrated malaria control programs is to decrease malaria transmission, which needs specific tools to be accurately assessed. In areas where the transmission is low or has been substantially reduced, new complementary tools have to be developed to improve surveillance. A recent approach, based on the human antibody response to Anopheles salivary proteins, has been shown to be efficient in evaluating human exposure to Anopheles bites. The aim of the present study was to identify new An. gambiae salivary proteins as potential candidate biomarkers of human exposure to P. falciparum-infective bites. Methods: Experimental infections of An. gambiae by wild P. falciparum were carried out in semi-field conditions. Then a proteomic approach, combining 2D-DIGE and mass spectrometry, was used to identify the overexpressed salivary proteins in infected salivary glands compared to uninfected An. gambiae controls. Subsequently, a peptide design of each potential candidate was performed in silico and their antigenicity was tested by an epitope-mapping technique using blood from individuals exposed to Anopheles bites. Results: Five salivary proteins (gSG6, gSG1b, TRIO, SG5 and long form D7) were overexpressed in the infected salivary glands. Eighteen peptides were designed from these proteins and were found antigenic in children exposed to the Anopheles bites. Moreover, the results showed that the presence of wild P. falciparum in salivary glands modulates the expression of several salivary proteins and also appeared to induce post-translational modifications. Conclusions: This study is, to our knowledge, the first that compares the sialome of An. gambiae both infected and not infected by wild P. falciparum, making it possible to mimic the natural conditions of infection. This is a first step toward a better understanding of the close interactions between the parasite and the salivary gland of mosquitoes. In addition, these results open the way to define biomarkers of infective bites of Anopheles, which could, in the future, improve the estimation of malaria transmission and the evaluation of malaria vector control tools. (Résumé d'auteur

Schistosomiasis Coinfection in Children Influences Acquired Immune Response against Plasmodium falciparum Malaria Antigens

Background: Malaria and schistosomiasis coinfection frequently occurs in tropical countries. This study evaluates the influence of Schistosoma haematobium infection on specific antibody responses and cytokine production to recombinant merozoite surface protein-1-19 (MSP1-19) and schizont extract of Plasmodium falciparum in malaria-infected children. Methodology: Specific IgG1 to MSP1- 19, as well as IgG1 and IgG3 to schizont extract were significantly increased in coinfected children compared to P. falciparum mono-infected children. Stimulation with MSP1- 19 lead to a specific production of both interleukin-10 (IL-10) and interferon-c (IFN-c), whereas the stimulation with schizont extract produced an IL-10 response only in the coinfected group. Conclusions: Our study suggests that schistosomiasis coinfection favours anti-malarial protective antibody responses, which could be associated with the regulation of IL-10 and IFN-c production and seems to be antigen-dependent. This study demonstrates the importance of infectious status of the population in the evaluation of acquired immunity against malari