New Salivary Biomarkers of Human Exposure to Malaria Vector Bites

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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

Numerical homogenization methods for parabolic monotone problems

In this paper we review various numerical homogenization methods for monotone parabolic problems with multiple scales. The spatial discretisation is based on finite element methods and the multiscale strategy relies on the heterogeneous multiscale method. The time discretization is performed by several classes of Runge-Kutta methods (strongly A-stable or explicit stabilized methods). We discuss the construction and the analysis of such methods for a range of problems, from linear parabolic problems to nonlinear monotone parabolic problems in the very general Lp(W1,p) setting. We also show that under appropriate assumptions, a computationally attractive linearized method can be constructed for nonlinear problems

Evaluation of the Human IgG Antibody Response to Aedes albopictus Saliva as a New Specific Biomarker of Exposure to Vector Bites

Aedes-borne viruses like dengue and chikungunya are a major problem in Reunion Island. Assessing exposure to Aedes bites is crucial to estimating the risk of pathogen transmission. Currently, the exposure of populations to Aedes albopictus bites is mainly evaluated by entomological methods which are indirect and difficult to apply on a large scale. Recent findings suggest that evaluation of human antibody responses against arthropod salivary proteins could be useful in assessing exposure to mosquito bites. The results indicate that 88% of the studied population produce IgG to Ae. albopictus saliva antigens in Reunion Island and show that this biomarker can detect different levels of individual exposure. In addition, little cross-reactivity is observed with Aedes aegypti saliva, suggesting that this could be a specific marker for exposure to Aedes albopictus bites. Taken together, these results suggest that antibody responses to saliva could constitute a powerful immuno-epidemiological tool for evaluating exposure to Aedes albopictus and therefore the risk of arbovirus infection

Correction: A Seroepidemiological Study of Serogroup A Meningococcal Infection in the African Meningitis Belt.

[This corrects the article DOI: 10.1371/journal.pone.0147928.]

Human-vector interaction, studies of Aedes immunogenic salivary proteins, toward a specific biomarker of exposure to Aedes albopictus

Les arbovirus transmis par les moustiques Aedes représentent un problème majeur de santé publique dans les pays du Sud et certains comme la dengue et le chikungunya risquent d'émerger dans les pays du Nord. La lutte contre ces maladies repose essentiellement sur le contrôle des populations de vecteurs. Pour un meilleur contrôle de ces arbovirus, beaucoup d'efforts sont déployés pour développer de nouveaux outils. La mesure de la réponse anticorps (Ac) de l'homme contre les protéines salivaires des arthropodes a été utilisée pour évaluer son exposition aux piqûres des vecteurs et estimer le risque de transmission des pathogènes. L'objectif de notre travail a été de valider par une approche immuno-épidémiologique le concept « réponse Ac anti salive comme bio-marqueur d'exposition aux Aedes ». Nous avons également évalué la spécificité de cette réponse par rapport aux populations exposées uniquement à Ae. aegypti ou Ae. albopictus. Dans un second volet, nous avons identifié les protéines salivaires d'Ae. albopictus impliquées dans cette réponse. Et enfin, nous avons évalué la potentialité d'utiliser ce bio-marqueur comme critère d'efficacité de la lutte anti vectorielle contre Ae. albopictus. Nos résultats montrent une corrélation entre la réponse Ac anti salive et l'intensité d'exposition aux vecteurs indiquant ainsi la pertinence de son utilisation comme bio-marqueur d'exposition aux piqûres des Aedes. Nous notons une faible réaction croisée de cette réponse Ac entre la salive d'Ae. aegypti et d'Ae. albopictus. Les protéines salivaires antigéniques d'Ae. albopictus identifiées sont essentiellement impliquées dans la prise du repas sanguin. L'utilisation de ce bio-marqueur a permis de détecter la baisse de la densité vectorielle après les mesures de lutte contre Ae. albopictus, suggérant son utilité pour mesurer l'efficacité des stratégies de contrôle. L'ensemble de ces travaux contribuent à une meilleure connaissance de l'interaction de l'homme avec les Aedes. L'identification de protéines/peptides spécifiques d'espèce permettrait d'améliorer l'utilisation de ce bio-marqueur.Aedes borne virus are considered to be public health problems in Southern countries while several such diseases like dengue and chikungunya threaten to emerge in the developed world. The control of these diseases is currently based on vector population control. Much effort is being devoted to develop new tools to control such arbovirus. Recent findings suggest that the evaluation of human antibody (Ab) response to arthropod salivary proteins is relevant to measure the level of human exposure to mosquito bites and to evaluate the risk of pathogen transmission. Using an immuno-epidemiological approach, the present study aimed to validate the concept “anti saliva Ab response, biomarker of Aedes exposure”. We evaluated the specificity of this Ab response according to populations only exposed to Ae. aegypti and Ae. albopictus, respectively. Ae. albopictus salivary proteins involved in this Ab response were also identified. We evaluated the usefulness of this biomarker for measuring the efficacy of Ae. albopictus control strategies. Our results showed a significant correlation between anti saliva Ab response and exposure level to vectors bites, thus indicating its usefulness as biomarker of Aedes exposure. We observed low Ab cross reactivity between Ae. aegypti and Ae. albopictus salivary gland extracts. The Ae. albopictus antigenic salivary proteins which were identified are mostly involved in blood feeding. The decrease of Ae. albopictus density after control measures has been detected by this biomarker, suggesting its usefulness for evaluating control strategies.This work contributes significantly to the study of human antibody response to Aedes salivary proteins which remains so far poorly documented. The identification of species specific salivary proteins/peptides should improve the use of this biomarker

Salivary Biomarkers in the Control of Mosquito-Borne Diseases

Vector control remains the most effective measure to prevent the transmission of mosquito-borne diseases. However, the classical entomo-parasitological methods used to evaluate the human exposure to mosquito bites and the effectiveness of control strategies are indirect, labor intensive, and lack sensitivity in low exposure/transmission areas. Therefore, they are limited in their accuracy and widespread use. Studying the human antibody response against the mosquito salivary proteins has provided new biomarkers for a direct and accurate evaluation of the human exposure to mosquito bites, at community and individual levels. In this review, we discuss the development, applications and limits of these biomarkers applied to Aedes- and Anopheles-borne diseases

Interactions homme-vecteur, études des protéines salivaires immunogéniques d'Aedes, vers un bio-marqueur d'exposition spécifique à Aedes albopictus.

Les arbovirus transmis par les moustiques Aedes représentent un problème majeur de santé publique dans les pays du Sud et certains comme la dengue et le chikungunya risquent d'émerger dans les pays du Nord. La lutte contre ces maladies repose essentiellement sur le contrôle des populations de vecteurs. Pour un meilleur contrôle de ces arbovirus, beaucoup d'efforts sont déployés pour développer de nouveaux outils. La mesure de la réponse anticorps (Ac) de l'homme contre les protéines salivaires des arthropodes a été utilisée pour évaluer son exposition aux piqûres des vecteurs et estimer le risque de transmission des pathogènes. L'objectif de notre travail a été de valider par une approche immuno-épidémiologique le concept réponse Ac anti salive comme bio-marqueur d'exposition aux Aedes . Nous avons également évalué la spécificité de cette réponse par rapport aux populations exposées uniquement à Ae. aegypti ou Ae. albopictus. Dans un second volet, nous avons identifié les protéines salivaires d'Ae. albopictus impliquées dans cette réponse. Et enfin, nous avons évalué la potentialité d'utiliser ce bio-marqueur comme critère d'efficacité de la lutte anti vectorielle contre Ae. albopictus. Nos résultats montrent une corrélation entre la réponse Ac anti salive et l'intensité d'exposition aux vecteurs indiquant ainsi la pertinence de son utilisation comme bio-marqueur d'exposition aux piqûres des Aedes. Nous notons une faible réaction croisée de cette réponse Ac entre la salive d'Ae. aegypti et d'Ae. albopictus. Les protéines salivaires antigéniques d'Ae. albopictus identifiées sont essentiellement impliquées dans la prise du repas sanguin. L'utilisation de ce bio-marqueur a permis de détecter la baisse de la densité vectorielle après les mesures de lutte contre Ae. albopictus, suggérant son utilité pour mesurer l'efficacité des stratégies de contrôle. L'ensemble de ces travaux contribuent à une meilleure connaissance de l'interaction de l'homme avec les Aedes. L'identification de protéines/peptides spécifiques d'espèce permettrait d'améliorer l'utilisation de ce bio-marqueur.Aedes borne virus are considered to be public health problems in Southern countries while several such diseases like dengue and chikungunya threaten to emerge in the developed world. The control of these diseases is currently based on vector population control. Much effort is being devoted to develop new tools to control such arbovirus. Recent findings suggest that the evaluation of human antibody (Ab) response to arthropod salivary proteins is relevant to measure the level of human exposure to mosquito bites and to evaluate the risk of pathogen transmission. Using an immuno-epidemiological approach, the present study aimed to validate the concept anti saliva Ab response, biomarker of Aedes exposure . We evaluated the specificity of this Ab response according to populations only exposed to Ae. aegypti and Ae. albopictus, respectively. Ae. albopictus salivary proteins involved in this Ab response were also identified. We evaluated the usefulness of this biomarker for measuring the efficacy of Ae. albopictus control strategies. Our results showed a significant correlation between anti saliva Ab response and exposure level to vectors bites, thus indicating its usefulness as biomarker of Aedes exposure. We observed low Ab cross reactivity between Ae. aegypti and Ae. albopictus salivary gland extracts. The Ae. albopictus antigenic salivary proteins which were identified are mostly involved in blood feeding. The decrease of Ae. albopictus density after control measures has been detected by this biomarker, suggesting its usefulness for evaluating control strategies.This work contributes significantly to the study of human antibody response to Aedes salivary proteins which remains so far poorly documented. The identification of species specific salivary proteins/peptides should improve the use of this biomarker.MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Salivary Biomarkers in the Control of Mosquito-Borne Diseases

Vector control remains the most effective measure to prevent the transmission of mosquito-borne diseases. However, the classical entomo-parasitological methods used to evaluate the human exposure to mosquito bites and the effectiveness of control strategies are indirect, labor intensive, and lack sensitivity in low exposure/transmission areas. Therefore, they are limited in their accuracy and widespread use. Studying the human antibody response against the mosquito salivary proteins has provided new biomarkers for a direct and accurate evaluation of the human exposure to mosquito bites, at community and individual levels. In this review, we discuss the development, applications and limits of these biomarkers applied to Aedes- and Anopheles-borne diseases