ORCID Profile
0000-0002-8442-0525
Current Organisations
International Institute for Applied Systems Analysis
,
Imperial College London
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Publisher: eLife Sciences Publications, Ltd
Date: 19-06-2018
DOI: 10.7554/ELIFE.35213
Abstract: Anti-malarial pre-erythrocytic vaccines (PEV) target transmission by inhibiting human infection but are currently partially protective. It has been posited, but never demonstrated, that co-administering transmission-blocking vaccines (TBV) would enhance malaria control. We hypothesized a mechanism that TBV could reduce parasite density in the mosquito salivary glands, thereby enhancing PEV efficacy. This was tested using a multigenerational population assay, passaging Plasmodium berghei to Anopheles stephensi mosquitoes. A combined efficacy of 90.8% (86.7–94.2%) was observed in the PEV +TBV antibody group, higher than the estimated efficacy of 83.3% (95% CrI 79.1–87.0%) if the two antibodies acted independently. Higher PEV efficacy at lower mosquito parasite loads was observed, comprising the first direct evidence that co-administering anti-sporozoite and anti-transmission interventions act synergistically, enhancing PEV efficacy across a range of TBV doses and transmission intensities. Combining partially effective vaccines of differing anti-parasitic classes is a pragmatic, powerful way to accelerate malaria elimination efforts.
Publisher: Elsevier BV
Date: 10-2013
Publisher: Public Library of Science (PLoS)
Date: 26-01-2021
DOI: 10.1371/JOURNAL.PNTD.0009036
Abstract: In the absence of vaccines or drugs, insecticides are the mainstay of Aedes -borne disease control. Their utility is challenged by the slow deployment of resources, poor community compliance and inadequate household coverage. Novel application methods are required. A 10% w/w metofluthrin “emanator” that passively disseminates insecticide from an impregnated net was evaluated in a randomized trial of 200 houses in Mexico. The devices were introduced at a rate of 1 per room and replaced at 3-week intervals. During each of 7 consecutive deployment cycles, indoor resting mosquitoes were s led using aspirator collections. Assessments of mosquito landing behaviours were made in a subset of houses. Pre-treatment, there were no differences in Aedes aegypti indices between houses recruited to the control and treatment arms. Immediately after metofluthrin deployment, the entomological indices between the trial arms erged. Averaged across the trial, there were significant reductions in Abundance Rate Ratios for total Ae . aegypti , female abundance and females that contained blood meals (2.5, 2.4 and 2.3-times fewer mosquitoes respectively P .001). Average efficacy was 60.2% for total adults, 58.3% for females, and 57.2% for blood-fed females. The emanators also reduced mosquito landings by 90% from 12.5 to 1.2 per 10-minute s ling period (P .05). Homozygous forms of the pyrethroid resistant kdr alleles V410L, V1016L and F1534C were common in the target mosquito population found in 39%, 24% and 95% of mosquitoes collected during the trial. This is the first randomized control trial to evaluate the entomological impact of any volatile pyrethroid on urban Ae . aegypti . It demonstrates that volatile pyrethroids can have a sustained impact on Ae . aegypti population densities and human-vector contact indoors. These effects occur despite the presence of pyrethroid-resistant alleles in the target population. Formulations like these may have considerable utility for public health vector control responses.
Publisher: Springer Science and Business Media LLC
Date: 11-06-2015
DOI: 10.1038/SREP11193
Abstract: Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected in idual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63 and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25 and Pfs48/45 were generated. Antibody responses primed in idually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2022
DOI: 10.1038/S41597-022-01332-3
Abstract: Spatially explicit information on forest management at a global scale is critical for understanding the status of forests, for planning sustainable forest management and restoration, and conservation activities. Here, we produce the first reference data set and a prototype of a globally consistent forest management map with high spatial detail on the most prevalent forest management classes such as intact forests, managed forests with natural regeneration, planted forests, plantation forest (rotation up to 15 years), oil palm plantations, and agroforestry. We developed the reference dataset of 226 K unique locations through a series of expert and crowdsourcing c aigns using Geo-Wiki ( www.geo-wiki.org/ ). We then combined the reference s les with time series from PROBA-V satellite imagery to create a global wall-to-wall map of forest management at a 100 m resolution for the year 2015, with forest management class accuracies ranging from 58% to 80%. The reference data set and the map present the status of forest ecosystems and can be used for investigating the value of forests for species, ecosystems and their services.
Publisher: Cold Spring Harbor Laboratory
Date: 02-10-2020
DOI: 10.1101/2020.10.02.20198663
Abstract: As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination c aign launches, cases and deaths are rising across the island. We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine roll-out. C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled-out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination c aign. Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact. In many settings, limited SARS-CoV-2 testing makes it difficult to estimate the true trajectory and associated burden of the virus. Non-pharmaceutical interventions (NPIs) are key tools to mitigate SARS-CoV-2 transmission. Vaccines show promise but effectiveness depends upon prioritization strategies, roll-out and uptake. This study gives evidence of the value of syndrome-based mortality as a metric, which is less dependent upon testing capacity with which to estimate transmission trends and evaluate intervention impact. NPIs implemented in Java earlier in the pandemic have substantially slowed the course of the epidemic with movement restrictions during Ramadan preventing spread to more vulnerable rural populations. Population-level immunity remains below proposed herd-immunity thresholds for the virus, though it is likely substantially higher in Jakarta. Given current levels of control, upwards trends in deaths are likely to continue in many provinces while the vaccine is scheduled to be rolled out. A key exception is Jakarta where population-level immunity may increase to a level where the epidemic begins to decline before the vaccine c aign has reached high coverage. Further relaxation of measures would lead to more rapidly progressing epidemics, depleting the eventual incremental effectiveness of the vaccine. Maintaining adherence to control measures in Jakarta may be particularly challenging if the epidemic enters a decline phase but will remain necessary to prevent a subsequent large wave. Elsewhere, higher levels of control with NPIs are likely to yield high synergistic vaccine impact.
Publisher: Springer Science and Business Media LLC
Date: 25-01-2018
DOI: 10.1038/S41598-017-18831-8
Abstract: An anti-malarial transmission blocking vaccine (TBV) would be an important tool for disease control or elimination, though current candidates have failed to induce high efficacy in clinical studies. The ookinete surface protein P25 is a primary target for TBV development, but heterologous expression of P25 with appropriate conformation is problematic and a pre-requisite for achieving functional titers. A potential alternative to recombinant/sub-unit vaccine is immunization with a non-pathogenic, whole-parasite vaccine. This study examines the ability of a purified transgenic rodent-malaria parasite ( Pb Pfs25DR3), expressing Plasmodium falciparum P25 in native conformation on the P. berghei ookinete surface, to act as a TBV. Vaccination with purified Pb Pfs25DR3 ookinetes produces a potent anti-Pfs25 response and high transmission-blocking efficacy in the laboratory, findings that are then translated to experimentation on natural field isolates of P. falciparum from infected in iduals in Burkina Faso. Efficacy is demonstrated in the lab and the field (up to 93.3%/97.1% reductions in transmission intensity respectively), with both a homologous strategy with one and two boosts, and as part of a prime-boost regime, providing support for the future development of a whole-parasite TBV.
Publisher: Springer Science and Business Media LLC
Date: 07-05-2013
DOI: 10.1038/NCOMMS2840
Publisher: Springer Science and Business Media LLC
Date: 07-08-2020
Publisher: Public Library of Science (PLoS)
Date: 22-08-2012
Publisher: Public Library of Science (PLoS)
Date: 24-04-2012
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.IJPARA.2012.09.002
Abstract: The standard membrane feeding assay (SMFA) is currently considered to be the 'gold standard' for assessing the effectiveness of malaria transmission blocking interventions (TBIs) in vivo. The operation and analysis of SMFAs has varied between laboratories: field scientists often measure TBI efficacy as a reduction in the prevalence of infected mosquitoes whilst laboratory scientists are more likely to quote efficacy as a change in the number of oocysts within the mosquito. These metrics give outputs that differ widely, resulting in a need for greater understanding of how the SMFA informs TBI assessment. Using data from 536 different assays (conducted on Plasmodium falciparum and Plasmodium berghei, in either Anopheles gambiae or Anopheles stephensi) it is shown that the relationship between these metrics is complex, yet predictable. Results demonstrate that the distribution of oocysts between mosquitoes is highly aggregated, making efficacy estimates based on reductions in intensity highly uncertain. Analysis of 30 SMFAs carried out on the same TBI confirms that the observed reduction in prevalence depends upon the parasite exposure (as measured by oocyst intensity in the control group), with assays which have lower exposure appearing more effective. By contrast, if efficacy is estimated as a reduction in oocyst intensity, then this candidate demonstrated constant efficacy, irrespective of the exposure level. To report transmission-blockade efficacy accurately, the results of SMFAs should give both the prevalence and intensity of oocysts in both the control and intervention group. Candidates should be assessed against a range of parasite exposures to allow laboratory results to be extrapolated to different field situations. Currently, many studies assessing TBIs are underpowered and uncertainties in efficacy estimates rarely reported. Statistical techniques that account for oocyst over-dispersion can reduce the number of mosquitoes that need to be dissected and allow TBI candidates from different laboratories to be accurately compared.
Publisher: eLife Sciences Publications, Ltd
Date: 10-05-2018
Publisher: Springer Science and Business Media LLC
Date: 27-03-2018
DOI: 10.1038/S41598-018-22712-Z
Abstract: Mosquito control with bednets, residual sprays or fumigation remains the most effective tool for preventing vector-borne diseases such as malaria, dengue and Zika, though there are no widely used entomological methods for directly assessing its efficacy. Mosquito age is the most informative metric for evaluating interventions that kill adult mosquitoes but there is no simple or reliable way of measuring it in the field. Near-Infrared Spectroscopy (NIRS) has been shown to be a promising, high-throughput method that can estimate the age of mosquitoes. Currently the ability of NIRS to measure mosquito age is biased, and has relatively high in idual mosquito measurement error, though its capacity to rigorously monitor mosquito populations in the field has never been assessed. In this study, we use machine learning methods from the chemometric literature to generate more accurate, unbiased estimates of in idual mosquito age. These unbiased estimates produce precise population-level measurements, which are relatively insensitive to further increases in NIRS accuracy when feasible numbers of mosquitoes are s led. The utility of NIRS to directly measure the impact of pyrethroid resistance on mosquito control is illustrated, showing how the technology has potential as a highly valuable tool for directly assessing the efficacy of mosquito control interventions.
Publisher: Pensoft Publishers
Date: 26-01-2022
DOI: 10.3897/ARPHAPREPRINTS.E81207
Abstract: Observations are key to understand the drivers of bio ersity loss, and the impacts on ecosystem services and ultimately on people. Many EU policies and initiatives demand unbiased, integrated and regularly updated bio ersity and ecosystem service data. However, efforts to monitor bio ersity are spatially and temporally fragmented, taxonomically biased, and lack integration in Europe. EuropaBON aims to bridge this gap by designing an EU-wide framework for monitoring bio ersity and ecosystem services. EuropaBON harnesses the power of modelling essential variables to integrate different reporting streams, data sources, and monitoring schemes. These essential variables provide consistent knowledge about multiple dimensions of bio ersity change across space and time. They can then be analyzed and synthesized to support decision-making at different spatial scales, from the sub-national to the European scale, through the production of indicators and scenarios. To develop essential bio ersity and ecosystem variables workflows that are policy relevant, EuropaBON is built around stakeholder engagement and knowledge exchange (WP2). EuropaBON will work with stakeholders to identify user and policy needs for bio ersity monitoring and investigate the feasibility of setting up a center to coordinate monitoring activities across Europe (WP2). Together with stakeholders, EuropaBON will assess current monitoring efforts to identify gaps, data and workflow bottlenecks, and analyse cost-effectiveness of different schemes (WP3). This will be used to co-design improved monitoring schemes using novel technologies to become more representative temporally, spatially and taxonomically, delivering multiple benefits to users and society (WP4). Finally, EuropaBON will demonstrate in a set of showcases how workflows tailored to the Birds Directive, Habitats Directive, Water Framework Directive, Climate and Restoration Policy, and the Bioeconomy Strategy, can be implemented (WP5).
Publisher: Pensoft Publishers
Date: 30-03-2022
DOI: 10.3897/ARPHAPREPRINTS.E84517
Abstract: In this report, we present the analysis of the different available bio ersity data streams at the EU and national level, both baseline bio ersity data and monitoring data. We assess how these bio ersity data inform and trigger policy action and identify the related challenges the different European countries and relevant EU agencies face and the solutions to overcome them. To do this, we consulted with more than 350 expert stakeholders from policy, research and practice. The assessment identified a fragmented bio ersity data landscape that cannot currently easily answer all relevant policy questions. Quantity and quality of bio ersity baseline datasets differ for the different countries, ranging from non-existent bio ersity monitoring due to capacity issues, to regular monitoring of ecosystem processes and state. By engaging stakeholders and experts in both member states and non-member states and from several EU bodies, we identified key challenges and ways to address these with targeted solutions towards building a joint European Bio ersity Monitoring Network. Solutions include focussing on cooperation and coordination, enhanced data standardisation and sharing, as well as the use of models and new technologies. These solutions can however only be realised with dedicated funding and capacity building, in coordination with all stakeholders in partnership.
Publisher: Wiley
Date: 15-02-2013
DOI: 10.1111/EVO.12063
Publisher: American Society for Microbiology
Date: 02-2014
DOI: 10.1128/IAI.01222-13
Abstract: Malaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of the Plasmodium parasite, the Anopheles mosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission of Plasmodium falciparum and Plasmodium vivax across distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria.
Publisher: Public Library of Science (PLoS)
Date: 12-01-2017
Publisher: Springer Science and Business Media LLC
Date: 17-06-2015
DOI: 10.1038/NATURE14451
Publisher: American Society for Microbiology
Date: 2015
DOI: 10.1128/AAC.03942-14
Abstract: To achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how in idual antimalarial drugs can impact the number of secondary Plasmodium berghei infections over a cycle of transmission. We examine the impact of multiple clinical and preclinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine ( mg/kg of body weight) and NITD609 (8.1 mg/kg) have significant impacts across multiple transmission settings, but artemether and lumefantrine (57 and 11.8 mg/kg), OZ439 (6.5 mg/kg), and primaquine ( .25 mg/kg) demonstrated potent efficacy only at lower-transmission settings. While directly demonstrating the impact of antimalarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of in idual drugs within epidemiologically relevant settings, supporting their usage within elimination c aigns.
Location: Austria
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Thomas Churcher.