Publications
151 results found
Parham PE, Waldock J, Christophides GK, et al., 2015, Climate, environmental and socio-economic change: weighing up the balance in vector-borne disease transmission, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436
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- Citations: 151
Parham PE, Waldock J, Christophides GK, et al., 2015, Climate change and vector-borne diseases of humans Preface, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436
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- Citations: 37
Proestos Y, Christophides GK, Erguler K, et al., 2015, Present and future projections of habitat suitability of the Asian tiger mosquito, a vector of viral pathogens, from global climate simulation, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 370, Pages: 1-16, ISSN: 0962-8436
Climate change can influence the transmission of vector-borne diseases (VBDs) through altering the habitat suitability of insect vectors. Here we present global climate model simulations and evaluate the associated uncertainties in view of the main meteorological factors that may affect the distribution of the Asian tiger mosquito (Aedes albopictus), which can transmit pathogens that cause chikungunya, dengue fever, yellow fever and various encephalitides. Using a general circulation model at 50 km horizontal resolution to simulate mosquito survival variables including temperature, precipitation and relative humidity, we present both global and regional projections of the habitat suitability up to the middle of the twenty-first century. The model resolution of 50 km allows evaluation against previous projections for Europe and provides a basis for comparative analyses with other regions. Model uncertainties and performance are addressed in light of the recent CMIP5 ensemble climate model simulations for the RCP8.5 concentration pathway and using meteorological re-analysis data (ERA-Interim/ECMWF) for the recent past. Uncertainty ranges associated with the thresholds of meteorological variables that may affect the distribution of Ae. albopictus are diagnosed using fuzzy-logic methodology, notably to assess the influence of selected meteorological criteria and combinations of criteria that influence mosquito habitat suitability. From the climate projections for 2050, and adopting a habitat suitability index larger than 70%, we estimate that approximately 2.4 billion individuals in a land area of nearly 20 million km2 will potentially be exposed to Ae. albopictus. The synthesis of fuzzy-logic based on mosquito biology and climate change analysis provides new insights into the regional and global spreading of VBDs to support disease control and policy making.
Dembo EG, Abay SM, Dahiya N, et al., 2015, Impact of repeated NeemAzal (R)-treated blood meals on the fitness of Anopheles stephensi mosquitoes, Parasites & Vectors, Vol: 8, ISSN: 1756-3305
Background: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in theabsence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designedfor prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community atlarge. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that causethe clinical manifestations of malaria and on those responsible for infection in the vector. Furthermore, neem secondarymetabolites have been shown to interfere with various physiological processes in insect vectors. This studywas undertaken to assess the impact of the standardised neem extract NeemAzal® on the fitness of the malariavector Anopheles stephensi following repeated exposure to the product through consecutive blood meals ontreated mice.Methods: Batches of An. stephensi mosquitoes were offered 5 consecutive blood meals on female BALB/cmice treated with NeemAzal® at an azadirachtin A concentration of 60, 105 or 150 mg/kg. The blood feedingcapacity was estimated by measuring the haematin content of the rectal fluid excreted by the mosquitoesduring feeding. The number of eggs laid was estimated by image analysis and their hatchability assessed bydirect observations.Results: A dose and frequency dependent impact of NeemAzal® treatment on the mosquito feeding capacity,oviposition and egg hatchability was demonstrated. In the 150 mg/kg treatment group, the mosquito feedingcapacity was reduced by 50% already at the second blood meal and by 50 to 80% in all treatment groups atthe fifth blood meal. Consequently, a 50 – 65% reduction in the number of eggs laid per female mosquitowas observed after the fifth blood meal in all treatment groups. Similarly, after the fifth treated blood mealexposure, hatchability was found to be reduced by 62% and 70% in the 105 and 150 mg/kg group re
Dembo EG, Abay SM, Dahiya N, et al., 2015, Impact of repeated NeemAzal-treated blood meals on the fitness of Anopheles stephensi mosquitoes., Parasit Vectors, Vol: 8
BACKGROUND: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in the absence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designed for prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community at large. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that cause the clinical manifestations of malaria and on those responsible for infection in the vector. Furthermore, neem secondary metabolites have been shown to interfere with various physiological processes in insect vectors. This study was undertaken to assess the impact of the standardised neem extract NeemAzal on the fitness of the malaria vector Anopheles stephensi following repeated exposure to the product through consecutive blood meals on treated mice. METHODS: Batches of An. stephensi mosquitoes were offered 5 consecutive blood meals on female BALB/c mice treated with NeemAzal at an azadirachtin A concentration of 60, 105 or 150 mg/kg. The blood feeding capacity was estimated by measuring the haematin content of the rectal fluid excreted by the mosquitoes during feeding. The number of eggs laid was estimated by image analysis and their hatchability assessed by direct observations. RESULTS: A dose and frequency dependent impact of NeemAzal treatment on the mosquito feeding capacity, oviposition and egg hatchability was demonstrated. In the 150 mg/kg treatment group, the mosquito feeding capacity was reduced by 50% already at the second blood meal and by 50 to 80% in all treatment groups at the fifth blood meal. Consequently, a 50 - 65% reduction in the number of eggs laid per female mosquito was observed after the fifth blood meal in all treatment groups. Similarly, after the fifth treated blood meal exposure, hatchability was found to be reduced by 62% and 70% in the 105 and 150 mg/kg group resp
Akinosoglou KA, Bushell ESC, Ukegbu CV, et al., 2015, Characterization of <i>Plasmodium</i> developmental transcriptomes in <i>Anopheles gambiae</i> midgut reveals novel regulators of malaria transmission, CELLULAR MICROBIOLOGY, Vol: 17, Pages: 254-268, ISSN: 1462-5814
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- Citations: 24
Gendrin M, Rodgers FH, Yerbanga RS, et al., 2015, Antibiotics in ingested human blood affect the mosquito microbiota and capacity to transmit malaria, Nature Communications, Vol: 6, Pages: 1-7, ISSN: 2041-1723
Malaria reduction is most efficiently achieved by vector control whereby human populations at high risk of contracting and transmitting the disease are protected from mosquito bites. Here, we identify the presence of antibiotics in the blood of malaria-infected people as a new risk of increasing disease transmission. We show that antibiotics in ingested blood enhance the susceptibility of Anopheles gambiae mosquitoes to malaria infection by disturbing their gut microbiota. This effect is confirmed in a semi-natural setting by feeding mosquitoes with blood of children naturally infected with Plasmodium falciparum. Antibiotic exposure additionally increases mosquito survival and fecundity, which are known to augment vectorial capacity. These findings suggest that malaria transmission may be exacerbated in areas of high antibiotic usage, and that regions targeted by mass drug administration programs against communicable diseases may necessitate increased vector control.
Upton LM, Povelones M, Christophides GK, 2015, Anopheles gambiae blood feeding Initiates an anticipatory defense response to plasmodium berghei, Journal of Innate Immunity, Vol: 7, Pages: 74-86, ISSN: 1662-8128
Mosquitoes have potent innate defense mechanisms that protect them from infection by diverse pathogens. Much remains unknown about how different pathogens are sensed and specific responses triggered. Leucine-Rich repeat IMmune proteins (LRIMs) are a mosquito-specific family of putative innate receptors. Although some LRIMs have been implicated in mosquito immune responses, the function of most family members is largely unknown. We screened Anopheles gambiae LRIMs by RNAi for effects on mosquito infection by rodent malaria and found that LRIM9 is a Plasmodium berghei antagonist with phenotypes distinct from family members LRIM1 and APL1C, which are key components of the mosquito complement-like pathway. LRIM9 transcript and protein levels are significantly increased after blood feeding but are unaffected by Plasmodium or midgut microbiota. Interestingly, LRIM9 in the hemolymph is strongly upregulated by direct injection of the ecdysteroid, 20-hydroxyecdysone. Our data suggest that LRIM9 may define a novel anti-Plasmodium immune defense mechanism triggered by blood feeding and that hormonal changes may alert the mosquito to bolster its defenses in anticipation of exposure to blood-borne pathogens.
Neafsey DE, Waterhouse RM, Abai MR, et al., 2015, Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes, Science, Vol: 347
Giraldo-Calderon GI, Emrich SJ, MacCallum RM, et al., 2014, VectorBase: an updated bioinformatics resource for invertebrate vectors and other organisms related with human diseases, Nucleic Acids Research, Vol: 43, Pages: D707-D713, ISSN: 1362-4962
VectorBase is a National Institute of Allergy and Infectious Diseases supported Bioinformatics Resource Center (BRC) for invertebrate vectors of human pathogens. Now in its 11th year, VectorBase currently hosts the genomes of 35 organisms including a number of non-vectors for comparative analysis. Hosted data range from genome assemblies with annotated gene features, transcript and protein expression data to population genetics including variation and insecticide-resistance phenotypes. Here we describe improvements to our resource and the set of tools available for interrogating and accessing BRC data including the integration of Web Apollo to facilitate community annotation and providing Galaxy to support user-based workflows. VectorBase also actively supports our community through hands-on workshops and online tutorials. All information and data are freely available from our website at https://www.vectorbase.org/.
Yassine H, Kamareddine L, Chamat S, et al., 2014, A Serine Protease Homolog Negatively Regulates TEP1 Consumption in Systemic Infections of the Malaria Vector Anopheles gambiae, JOURNAL OF INNATE IMMUNITY, Vol: 6, Pages: 806-818, ISSN: 1662-811X
Talman AM, Prieto JH, Marques S, et al., 2014, Proteomic analysis of the <i>Plasmodium</i> male gamete reveals the key role for glycolysis in flagellar motility, MALARIA JOURNAL, Vol: 13
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- Citations: 37
Yerbanga RS, Lucantoni L, Ouedraogo RK, et al., 2014, Transmission blocking activity of Azadirachta indica and Guiera senegalensis extracts on the sporogonic development of Plasmodium falciparum field isolates in Anopheles coluzzii mosquitoes, Parasites and Vectors, Vol: 7, Pages: 1-10, ISSN: 1756-3305
BackgroundTargeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control. Research efforts to identify compounds that are active against these stages have significantly increased in recent years. However, at present, only two drugs are available, namely primaquine and artesunate, which reportedly act on late stage gametocytes.MethodsIn this study, we assessed the antiplasmodial effects of 5 extracts obtained from the neem tree Azadirachta indica and Guiera senegalensis against the early vector stages of Plasmodium falciparum, using field isolates. In an ex vivo assay gametocytaemic blood was supplemented with the plant extracts and offered to Anopheles coluzzii females by membrane feeding. Transmission blocking activity was evaluated by assessing oocyst prevalence and density on the mosquito midguts.ResultsInitial screening of the 5 plant extracts at 250 ppm revealed transmission blocking activity in two neem preparations. Up to a concentration of 70 ppm the commercial extract NeemAzal® completely blocked transmission and at 60 ppm mosquitoes of 4 out of 5 replicate groups remained uninfected. Mosquitoes fed on the ethyl acetate phase of neem leaves at 250 ppm showed a reduction in oocyst prevalence of 59.0% (CI95 12.0 - 79.0; p < 10-4) and in oocyst density of 90.5% (CI95 86.0 - 93.5; p < 10-4 ), while the ethanol extract from the same plant part did not exhibit any activity. No evidence of transmission blocking activity was found using G. senegalensis ethyl acetate extract from stem galls.ConclusionsThe results of this study highlight the potential of antimalarial plants for the discovery of novel transmission blocking molecules, and open up the potential of developing standardized transmission blocking herbal formulations as malaria control tools to complement currently used antimalarial drugs and combination treatment
Stathopoulos S, Neafsey DE, Lawniczak MKN, et al., 2014, Genetic dissection of anopheles gambiae Gut epithelial responses to serratia marcescens, PLoS Pathogens, Vol: 10, Pages: 1-19, ISSN: 1553-7366
Genetic variation in the mosquito Anopheles gambiae profoundly influences its ability to transmit malaria. Mosquito gut bacteria are shown to influence the outcome of infections with Plasmodium parasites and are also thought to exert a strong drive on genetic variation through natural selection; however, a link between antibacterial effects and genetic variation is yet to emerge. Here, we combined SNP genotyping and expression profiling with phenotypic analyses of candidate genes by RNAi-mediated silencing and 454 pyrosequencing to investigate this intricate biological system. We identified 138 An. gambiae genes to be genetically associated with the outcome of Serratia marcescens infection, including the peptidoglycan recognition receptor PGRPLC that triggers activation of the antibacterial IMD/REL2 pathway and the epidermal growth factor receptor EGFR. Silencing of three genes encoding type III fibronectin domain proteins (FN3Ds) increased the Serratia load and altered the gut microbiota composition in favor of Enterobacteriaceae. These data suggest that natural genetic variation in immune-related genes can shape the bacterial population structure of the mosquito gut with high specificity. Importantly, FN3D2 encodes a homolog of the hypervariable pattern recognition receptor Dscam, suggesting that pathogen-specific recognition may involve a broader family of immune factors. Additionally, we showed that silencing the gene encoding the gustatory receptor Gr9 that is also associated with the Serratia infection phenotype drastically increased Serratia levels. The Gr9 antibacterial activity appears to be related to mosquito feeding behavior and to mostly rely on changes of neuropeptide F expression, together suggesting a behavioral immune response following Serratia infection. Our findings reveal that the mosquito response to oral Serratia infection comprises both an epithelial and a behavioral immune component.
Midega J, Blight J, Lombardo F, et al., 2014, Discovery and characterization of two Nimrod superfamily members in Anopheles gambiae, Pathogens and Global Health, Vol: 107, Pages: 463-474, ISSN: 2047-7724
Anti-bacterial proteins in mosquitoes are known to play an important modulatory role on immune responses to infections with human pathogens including malaria parasites. In this study we characterized two members of the Anopheles gambiae Nimrod superfamily, namely AgNimB2 and AgEater. We confirm that current annotation of the An. gambiae genome incorrectly identifies AgNimB2 and AgEater as a single gene, AGAP009762. Through in silico and experimental approaches, it has been shown that AgNimB2 is a secreted protein that mediates phagocytosis of Staphylococcus aureus but not of Escherichia coli bacteria. We also reveal that this function does not involve a direct interaction of AgNimB2 with S. aureus. Therefore, AgNimB2 may act downstream of complement-like pathway activation, first requiring bacterial opsonization. In addition, it has been shown that AgNimB2 has an anti-Plasmodium effect. Conversely, AgEater is a membrane-bound protein that either functions redundantly or is dispensable for phagocytosis of E. coli or S. aureus. Our study provides insights into the role of members of the complex Nimrod superfamily in An. gambiae, the most important African vector of human malaria.
Povelones M, Christophides GK, 2013, Meeting report of the Mosquito Kolymbari Meeting 2013, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 393-399, ISSN: 2047-7724
Waldock J, Parham PE, Lelieveld J, et al., 2013, Climate and Human Health: The Impact of Climate Change on Vector-Borne Diseases, Paphos, Cyprus (17-19 October 2012), PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 387-392, ISSN: 2047-7724
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- Citations: 3
Christophides GK, Crisanti A, 2013, Vector and vector-borne disease research: need for coherence, vision and strategic planning, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 385-386, ISSN: 2047-7724
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- Citations: 1
Slater HC, Churcher TS, Christophides GK, et al., 2013, PLASMODIUM-ANOPHELES INTERACTIONS: UNDERSTANDING WHAT'S BEST FOR THE PARASITE AND THE MOSQUITO, Publisher: MANEY PUBLISHING, Pages: 404-405, ISSN: 2047-7724
Midega J, Smith D, Olotu A, et al., 2013, WIND DIRECTION AND PROXIMITY TO LARVAL SITES DETERMINES MALARIA RISK IN KILIFI, KENYA, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 446-447, ISSN: 2047-7724
Habtewold T, Christophides G, 2013, LEARNING HOW TO FIGHT MALARIA FROM NON-VECTOR MOSQUITOES, Publisher: MANEY PUBLISHING, Pages: 405-405, ISSN: 2047-7724
Gendrin M, Rodgers F, Cohuet A, et al., 2013, IMPACT OF ANTIBIOTIC USE ON MOSQUITO MICROBIOTA AND ON MALARIA TRANSMISSION, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 425-425, ISSN: 2047-7724
Stathopoulos S, Christophides GK, 2013, GENETIC MAPPING OF ANOPHELES GAMBIAE GUT EPITHELIAL RESPONSES TO SERRATIA MARCESCENS, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 422-423, ISSN: 2047-7724
Lawniczak M, Cohuet A, Christophides G, 2013, GENOME WIDE ASSOCIATION STUDIES IDENTIFYING LOCI UNDERLYING ANOPHELES GAMBIAE SUSCEPTIBILITY TO PLASMODIUM FALCIPARUM, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 403-404, ISSN: 2047-7724
Povelones M, Upton L, Christophides G, 2013, EVIDENCE OF AN ANTI-PLASMODIUM ANTICIPATORY IMMUNE RESPONSE IN ANOPHELES GAMBIAE STIMULATED BY BLOOD FEEDING, Publisher: MANEY PUBLISHING, Pages: 401-401, ISSN: 2047-7724
Rinker DC, Zhou X, Pitts RJ, et al., 2013, Antennal transcriptome profiles of anopheline mosquitoes reveal human host olfactory specialization in Anopheles gambiae, BMC Genomics, Vol: 14, ISSN: 1471-2164
BACKGROUND: Two sibling members of the Anopheles gambiae species complex display notable differences in female blood meal preferences. An. gambiae s.s. has a well-documented preference for feeding upon human hosts, whereas An. quadriannulatus feeds on vertebrate/mammalian hosts, with only opportunistic feeding upon humans. Because mosquito host-seeking behaviors are largely driven by the sensory modality of olfaction, we hypothesized that hallmarks of these divergent host seeking phenotypes will be in evidence within the transcriptome profiles of the antennae, the mosquito's principal chemosensory appendage. RESULTS: To test this hypothesis, we have sequenced antennal mRNA of non-bloodfed females from each species and observed a number of distinct quantitative and qualitative differences in their chemosensory gene repertoires. In both species, these gene families show higher rates of sequence polymorphisms than the overall rates in their respective transcriptomes, with potentially important divergences between the two species. Moreover, quantitative differences in odorant receptor transcript abundances have been used to model potential distinctions in volatile odor receptivity between the two sibling species of anophelines. CONCLUSION: This analysis suggests that the anthropophagic behavior of An. gambiae s.s. reflects the differential distribution of olfactory receptors in the antenna, likely resulting from a co-option and refinement of molecular components common to both species. This study improves our understanding of the molecular evolution of chemoreceptors in closely related anophelines and suggests possible mechanisms that underlie the behavioral distinctions in host seeking that, in part, account for the differential vectorial capacity of these mosquitoes.
Akhouayri IG, Habtewold T, Christophides GK, 2013, Melanotic pathology and vertical transmission of the gut commensal Elizabethkingia meningoseptica in the Major Malaria Vector Anopheles gambiae, PLoS One, Vol: 8, Pages: 1-12, ISSN: 1932-6203
BackgroundThe resident gut flora is known to have significant impacts on the life history of the host organism. Endosymbiotic bacterial species in the Anopheles mosquito gut are potent modulators of sexual development of the malaria parasite, Plasmodium, and thus proposed as potential control agents of malaria transmission.ResultsHere we report a melanotic pathology in the major African malaria vector Anopheles gambiae, caused by the dominant mosquito endosymbiont Elizabethkingia meningoseptica. Transfer of melanised tissues into the haemolymph of healthy adult mosquitoes or direct haemolymph inoculation with isolated E. meningoseptica bacteria were the only means for transmission and de novo formation of melanotic lesions, specifically in the fat body tissues of recipient individuals. We show that E. meningoseptica can be vertically transmitted from eggs to larvae and that E. meningoseptica-mono-associated mosquitoes display significant mortality, which is further enhanced upon Plasmodium infection, suggesting a synergistic impact of E. meningoseptica and Plasmodium on mosquito survival.ConclusionThe high pathogenicity and permanent association of E. meningoseptica with An. Gambiae through vertical transmission constitute attractive characteristics towards the potential design of novel mosquito/malaria biocontrol strategies.
Povelones M, Bhagavatula L, Yassine H, et al., 2013, The CLIP-domain serine protease homolog SPCLIP1 regulates complement recruitment to microbial surfaces in the malaria mosquito Anopheles gambiae, PLOS Pathogens, Vol: 9, ISSN: 1553-7366
The complement C3-like protein TEP1 of the mosquito Anopheles gambiae is required for defense against malaria parasites and bacteria. Two forms of TEP1 are present in the mosquito hemolymph, the full-length TEP1-F and the proteolytically processed TEP1cut that is part of a complex including the leucine-rich repeat proteins LRIM1 and APL1C. Here we show that the non-catalytic serine protease SPCLIP1 is a key regulator of the complement-like pathway. SPCLIP1 is required for accumulation of TEP1 on microbial surfaces, a reaction that leads to lysis of malaria parasites or triggers activation of a cascade culminating with melanization of malaria parasites and bacteria. We also demonstrate that the two forms of TEP1 have distinct roles in the complement-like pathway and provide the first evidence for a complement convertase-like cascade in insects analogous to that in vertebrates. Our findings establish that core principles of complement activation are conserved throughout the evolution of animals.
Mitraka E, Stathopoulos S, Siden-Kiamos I, et al., 2013, <i>Asaia</i> accelerates larval development of <i>Anopheles gambiae</i>, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 305-311, ISSN: 2047-7724
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- Citations: 74
Neafsey DE, Christophides GK, Collins FH, et al., 2013, The Evolution of the <i>Anopheles</i> 16 Genomes Project, G3-GENES GENOMES GENETICS, Vol: 3, Pages: 1191-1194, ISSN: 2160-1836
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- Citations: 40
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