Tropical Infectious Disease Consortium: Expanding and Accelerating Product Development

Lead Research Organisation: Liverpool School of Tropical Medicine

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

The Confidence in Concept scheme is a key part of MRC’s translational research strategy and provides annual awards to institutions, to be used flexibly to support the earliest stages of multiple translational research projects. The award can be used by the institution to support a number of preliminary-stage translational projects. The projects supported should aim to provide sufficient preliminary data to establish the viability of an approach –– before seeking more substantive funding.  It is intended to accelerate the transition from discovery research to translational development projects by supporting preliminary work or feasibility studies to establish the viability of an approach.

Publications

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Edwards T (2017) Analytical and clinical performance of a Chikungunya qRT-PCR for Central and South America. in Diagnostic microbiology and infectious disease

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Harrison RA (2019) The time is now: a call for action to translate recent momentum on tackling tropical snakebite into sustained benefit for victims in Transactions of The Royal Society of Tropical Medicine and Hygiene

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Ismail HM (2016) Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7. in Proceedings of the National Academy of Sciences of the United States of America

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Kaewpruk Napaporn (2016) PFMDR1 POLYMORPHISMS INFLUENCE ON IN VITRO SENSITIVITY OF THAI PLASMODIUM FALCIPARUM ISOLATES TO PRIMAQUINE, SITAMAQUINE AND TAFENOQUINE in SOUTHEAST ASIAN JOURNAL OF TROPICAL MEDICINE AND PUBLIC HEALTH

 
Description External advice to major funder with regard to antimalarial drug discovery projects 2016 to date
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description Macrofilaricide Drug Accelerator (MacDA) 2015 to date
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description Member of the MMV External Scientific Advisory Board 2017 to date
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description Building on accepted tools for malaria elimination
Amount $100,000 (USD)
Funding ID OPP1161876 
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 11/2016 
End 07/2018
 
Description DPFS
Amount £0 (GBP)
Funding ID MR/R025401/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description GHIT "E209 a tetraoxane based rapidly acting antimalarial"
Amount ¥20,775,374 (JPY)
Funding ID G2015-120R1 
Organisation Global Health Innovative Technology Fund 
Sector Public
Country Japan
Start 10/2015 
End 03/2016
 
Description Innovate UK
Amount £635,000 (GBP)
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start  
 
Description Innovate UK: - Pre-clinical Vaccines SBRI Phase 2
Amount £1,990,000 (GBP)
Funding ID 971615 
Organisation SBRI Healthcare 
Sector Private
Country United Kingdom
Start 09/2018 
End 08/2020
 
Description Internal Research England GCRF support fund
Amount £45,300 (GBP)
Organisation University of Oxford 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 07/2018
 
Description MRC Standard Grant
Amount £485,000 (GBP)
Funding ID MR/S00016X/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2018 
End 09/2021
 
Description PATH-MVI Grant
Amount $441,526 (USD)
Organisation PATH 
Department PATH Malaria Vaccine Initiative
Sector Charity/Non Profit
Country Global
Start 12/2017 
End 05/2019
 
Description The Future Vaccine Manufacturing Research Hub (Vax-Hub)
Amount £6,968,180 (GBP)
Funding ID EP/R013756/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 04/2018 
End 03/2021
 
Description Translation Award
Amount £5,000,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2017 
End 02/2021
 
Description USAID Malaria Vaccine Development Programme - VLP Vaccines
Amount $795,303 (USD)
Organisation United States Agency for International Development 
Sector Public
Country United States
Start 02/2019 
End 05/2020
 
Description Vaccines for Global Development - Preclinical
Amount £483,911 (GBP)
Funding ID 971510 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 05/2016 
End 05/2017
 
Title Cfp photoactive probe 
Description Photoactivated chermical probe for chlorfenapyr. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Probe recently synthesised, will be used for identifiying chlorfenapyr binding proteins in mosquitoes in next 4 four months. This is the first of a suite of new activity probes for tracking insecticide targets and metabolic enzymes associated with detoxification (resistance). 
 
Title RH5 structure 
Description Structure of RH5 malaria protein for design of new vaccines and small molecule inhibitors 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2014 
Provided To Others? Yes  
Impact Published 
URL http://www.ncbi.nlm.nih.gov/pubmed/25132548
 
Title Recombinase Polymerase Assay for Giardiasis 
Description Background The Recombinase Polymerase Assay (RPA) is an isothermal DNA amplification assay that employs enzymes, known as recombinases, which are capable of pairing oligonucleotide primers with homologous sequence in duplex DNA. Through this method, DNA synthesis is directed to defined points in a sample DNA. If the target sequence is indeed present, DNA amplification reaction is initiated; no other sample manipulation such as thermal or chemical melting is required. The reaction progresses rapidly and results in specific DNA amplification from just a few target copies to detectable levels typically within 3 - 10 minutes. The entire reaction system is stable as a dried formulation and can be transported safely without refrigeration. It is set to become a feasible point-of-care molecular diagnostic assay to be used in resource limited areas. The RPA for Giardia spp. proposed in this project is amplifying sequences from the ß-giardin gene. A specific FAM-labelled probe and biotin-labelled primer are used to generate an amplicon at 37°C, resulting in a specific, dual-labelled product; this can be monitored visually via its binding to a biotin ligand on a lateral flow strip with concurrent gold-labelled anti-FAM detection. Research Methods employed for this work The RPA protocol previously published (Cranell et al 2016) was found to yield an excess of false positives with negative controls. This problem was partly overcome with a change of the DNA extraction kit, the addition of betaine to the mastermix to prevent spurious products and the use of an alternate lateral flow cassette in place of the strips. The modified RPA was further applied to identify ß-giardin sequences from trophozoite-extracted DNA confirmed by sequencing and further refined by using Giardia duodenalis inactivated cysts (H3 isolate, Waterborne Inc, New Orleans , USA) spiking negative stool samples. For field validation, 375 children were screened for Giardia by stool sample in villages along Lake Albert Uganda. Rapid diagnostic assays for Giardia duodenalis (Giardia/Crypto Quick Check; Techlab,VA, USA) were performed in the field. DNA extraction and RPA assay were performed in a sub-set of samples (N=15). The RPA assay performed optimally in a small set of samples ran in the field. DNA extraction procedures had to be further refined at LSHTM where further stool samples (extraction n=219; RPA n=36) obtained from Uganda were run and compared to qPCR as the for Giardia assemblage detection. Results 20% of all the samples run were positive for Giardia RPA compared to 26 % by qPCR, showing promise for the new molecular diagnostic assay. Further analysis is also ongoing to explore the correlation between the RPA and the available RDT. We found the RPA feasible to run in low resource settings. Additionally, in conjunction with the NHM we are developing methods of multiplexing assays to characterize the assemblage(s) of Giardia duodenalis from infected people, and from environmental sampling, to further understand clinical associations and natural cycles of transmission of the various assemblages. Going forward, we intend to devise a multiplex test of Giardia duodenalis and Schistosoma mansoni, which are co-endemic. . 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Rapid diagnosis and treatment G. lamblia genotype-specific RPA will allow access to prompt diagnosis and treatment of children harbouring light and moderate infections not currently detected by available methods. The ability to detect genotypes associated with negative health outcomes will have its highest applicability in field surveys. It also has the potential to be used in institutional outbreaks where G. lamblia is known to occur (Baque et al., 2011). The development of a new genotype-specific RPA Giardia assay can be used and adopted by many groups across institutions nationally (LSHTM, LSTM) as well as internationally. The internal and external validation of the proposed work will be essential in technology transfer for a generalized use. Comparison for test validity against real-time PCR will produce robust sensitivity and specificity outcomes of the test that can act as reference for further use. Feasibility of use in low-resource settings RPA is a validated assay used for the detection of different pathogens (Rosser et al., 2015). The recombinase polymerase reaction can take place at an ambient temperature (Krolov et al., 2014), reagents are lyophilized making its use feasible in extreme temperatures. DNA amplification can be detected by visual reading of lateral flow (LF) strips, allowing flexibility in resource limited settings (Kersting et al, 2014). New endpoint for clinical trials There are ongoing trials to develop a single dose treatment that would mainstream treatment and allow mass drug administration for G. lamblia. Real-time PCR is the most sensitive test of cure, but limitations include high cost, skilled personnel, and reagents that need refrigeration. Infection clearance by POC-RPA has the potential to become a new endpoint for drug trials. 
URL http://www.twistdx.co.uk/
 
Title SpyTag/SpyCatcher VLP Vaccines 
Description Vaccine virus-like particles 
Type Of Material Technology assay or reagent 
Year Produced 2016 
Provided To Others? Yes  
Impact Grants, spinout company, publications 
 
Title InFlITE 
Description We have developed a unique tracking system to observe and track mosquito behaviour at human-baited bednets in the laboratory using infra-red cameras, automated video analysis, tracking and data handling software. This approach has provided new insights into vector behaviour and has allowed host-seeking behaviour to be recorded and classified into behavioural parameters. These parameters, in combination, constitute basic host-seeking behaviour at a human-occupied bednet with each parameter playing an important role in the efficacy of any vector control methods. By analysis of flight paths, we identified key elements of mosquito host-seeking behaviour. For example the frequency, duration and type of contact with the bednet, flight speed, tortuosity and classification of different types of host-seeking behaviour. We are using this information described above to identify behavioural parameters that can be incorporated into existing, freely available individual-based model (IBM) framework software. Existing data that describe basic mosquito host-seeking behaviour are already well established through video-tracking of behavioural assays conducted by our group. Further information is available in the literature as part of larger-scale, epidemiology-focused mosquito individual-based models, focusing on the landscape-scale. Currently a full suite of parameters is being collated and the model is being assembled using existing standardized frameworks namely processing programming language and the NetLogo platform. These modelling systems use high-level coding languages and as such are relatively accessible to novice users. Further they have wide user-bases and precedents exist for their use in small-scale spatial modelling, especially for NetLogo. Moreover, both systems allow for the incorporation of an easy to use graphic user interface to allow the quick roll-out and uptake of the simulation system for the testing and screening of potential new vector control methods, initially centred around LLIN designs, where our current expertise is most evident. Dr Jeff Jones has recently started this work and by collaborating with Dr Greg Murray of the LSTM, Dr Christian Kroner and Dr Vitaly Voloshin of Warwick University he aims to make use of both the currently existing tracking information as well as more recent developments in the filming and analysis system as well as previously collected data on window entry and contact irritancy behaviour as evidenced through small-scale thumb-test behavioural assays. Currently he is creating the modelled system in both two and three dimensions in order to assess the compromise between model utility and complexity, especially given the increased computer time associated with modelling in three dimensions. Further to this Dr Jones' level of technical ability and experience in biological computing is greater than one would expect for the advertised role, therefore are considering how best to stream-line the process of model validation and use with an eye on potential further developments, for example modelling other strains or species of mosquitoes. 
Type Of Material Computer model/algorithm 
Provided To Others? No  
Impact This project aims to provide an in silico testing environment that could assess new insecticide net treatments, or alternative net structures quickly and cheaply. The Individual Based Model would use data from small scale behavioural tests to estimate the efficacy of different control options (e.g. insecticide concentrations, net designs, different active chemicals, etc.) and provide outputs of expected efficacy against a specified mosquito population (e.g. contact time, probable mortality, locations of highest surface contact). LLIN designs that proved effective in the virtual lab would then be taken forward for larger scale field evaluation with a significant improvement in expectation of a demonstrable impact. Continued control of mosquito vectors will require constant innovation as the global health community works to combat the growing problem of insecticide resistance. This virtual testing environment will facilitate design and evaluation of new control methods, helping speed up the process of getting new nets from lab to the field. Once the system has been designed and tested for use with LLINs it may be expanded for application to other interventions such as eave tubes or window screens. The intervention will be trialled with data on Anopheles gambiae s.s. but has potential to further incorporate responses of various vector species. 
 
Description BASF Cfp probes 
Organisation BASF
Department BASF Plant Science
Country United States 
Sector Private 
PI Contribution Developing doagnostic probes for chlorfenapyr (BASF compound)
Collaborator Contribution Provided mosquito membrane extracts for biologocal assays
Impact Publication and grant application drafts - expected submission mid 2017.
Start Year 2016
 
Description BioGene and QuRapID qPCR system 
Organisation BioGene
Country United Kingdom 
Sector Private 
PI Contribution Design of primer and probes sets for the identification of anti-microbial resistance markers. Collection of bacterial isolates with AMR markers in Malawi.
Collaborator Contribution Use of Visual OMP for primer/probe design. Test rig of the QuRapID system delivered to LSTM PhD student Kavit Shah will start in March 2017 (student and bench fees to LSTM) Support with development of molecular system and transfer to qurapid.
Impact Publications have been added to relevant section on research fish. IP file in preparation for arboviral assay
Start Year 2015
 
Description Collaboration with NIRI for preparation of biocompatible membrane 
Organisation Nonwovens Innovation & Research Institute Ltd
PI Contribution Tested and demonstrated constituents of currently best performing membrane play important role in stability of vaccines. Studied properties of the constituents and estimated the size and degree of hydrolysis. Tested different grades of commercially available polymers that could be used as a raw materials for new biocompatible matrix. Identified suggestions possible method to make the membranes.
Collaborator Contribution NIRI further characterised physical properties of the membrane. They have identified possible method of making new membranes.
Impact Physical characterisation of existing membrane. Identification of method of new membrane production.
Start Year 2017
 
Description Collaboration with PHE 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution New Collaborations facilitated
Collaborator Contribution Live challenge work
Impact Assay devlopment & Live virus challenge
Start Year 2017
 
Description Contract established with Oslo University 
Organisation University of Oslo
Country Norway 
Sector Academic/University 
PI Contribution During the development of the CIC grant a gap was identified in one of the University of Oslo's grants that could be filled in this collaboration. This has brought the two teams working closer together on other aspects of the work.
Collaborator Contribution This is essentially a UoO project that we are now feeding into. While technically separate from the CIC award, should we be successful this work would benefit future work of the CIC project.
Impact Contract Project still in progress
Start Year 2016
 
Description Dr Edward Wright- generation of unique reagents necessary to facilitate works 
Organisation University of Foggia
Department Biomedical Sciences
Country Italy 
Sector Academic/University 
PI Contribution Co-Applicant, expert in field for generation of necessary resources to facilitate works.
Collaborator Contribution Collaboration in progress
Impact Collaboration in progress - works discussed in detail. Reagents already shared to facilitate generation of novel reagents to assess immunogenicity post vaccination with novel (to be generated) vaccines toward emerging pathogens.
Start Year 2016
 
Description Edward Wright 
Organisation University of Sussex
Country United Kingdom 
Sector Academic/University 
PI Contribution Development of a methodology; including the sharing of protocols and reagents.
Collaborator Contribution Development of a pseudotyped lentivirus assay for the detection of CCHFv neutralising antibodies ; including the sharing of protocols and reagents. This ongoing collaboration is facilitating cross-fertilisation of ideas to drive grant applications.
Impact Ongoing
Start Year 2019
 
Description Eric CDC- tecvlps 
Organisation Centers for Disease Control and Prevention (CDC)
Country United States 
Sector Public 
PI Contribution Assay testing
Collaborator Contribution Plasmids will be provided by the CDC for an assay neutralising antibodies againest CCHFv
Impact ongoing
Start Year 2019
 
Description ExpreS2ion Bio 
Organisation ExpreS2ion Biotechnologies
Country Denmark 
Sector Private 
PI Contribution Sharing of research reagents.
Collaborator Contribution Access to research reagents. Grant collaborator.
Impact MRC DPFS grant awarded. European Vaccine Initiative grant awarded. PATH Malaria Vaccine Initiative grant awarded
Start Year 2012
 
Description GIA Reference Centre, NIH 
Organisation Malaria GIA Reference Center - PATH MVI
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Sharing of research reagents.
Collaborator Contribution Significant experimental input.
Impact Publications. PMID: 20713623 PMID: 21698193 PMID: 21799809 PMID: 21862998 PMID: 22186897 PMID: 22363582 PMID: 22984589 PMID: 23089736 PMID: 23144611 PMID: 23872520 Joint PhD student.
Start Year 2010
 
Description Joint PhD Student with RedX Pharma 
Organisation Redx Pharma Plc
Country United Kingdom 
Sector Private 
PI Contribution This is a joint initiative between LSTM and RedX Pharma to recruit a PhD student to undertake a project at Liverpool and Alderley Park
Collaborator Contribution This is a joint initiative between LSTM and RedX Pharma to recruit a PhD student to undertake a project at Liverpool and Alderley Park
Impact None as yet
Start Year 2016
 
Description Linda/OET 
Organisation Oxford Expression Technologies
Country United Kingdom 
Sector Private 
PI Contribution Testing of OET protein
Collaborator Contribution OET are providing CCHF protein that we are testing in assays
Impact ongoing
Start Year 2019
 
Description Natural History Museum- assay development 
Organisation Natural History Museum
Department Library and Archives
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We have shared the protocol development of the assay with Dr. Bonnie Webster and her team at the NHM.
Collaborator Contribution My team works closely with Dr. Bonnie Webster's team at the NHM in optimising the Giardia RPA assay. Dr. Webster developed the RPA for Schistosoma haematobium in 2016 and has been instrumental in troubleshooting hurdles found along the way. Dr. Webster has also provided equipment and instruments needed for the assay development. Future projects with the NHM include a multiplex RPA for Giardia- Schistosoma mansoni.
Impact We have optimized the Giardia duodenalis RPA assay in close collaboration with the team at the NHM. Further work is ongoing with the NHM on the development of a multiplex Giardia-Schistosoma mansoni. Expected output of the development of this novel assay are expected for mid-2018.
Start Year 2016
 
Description Nick Lyons/ Anna Ludi 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise, intellectual input and training of staff across sites
Collaborator Contribution Development of a working relationship, to help with assay development; including the sharing of protocols and reagents. This ongoing collaboration is facilitating cross-fertilisation of ideas to drive grant applications.
Impact Ongoing
Start Year 2019
 
Description Novavax 
Organisation Novavax AB
Country Sweden 
Sector Private 
PI Contribution Malaria vaccine development using Novavax's Matrix-M adjuvant
Collaborator Contribution Provision of Matrix-M vaccine adjuvant
Impact Vaccine development and further grant writing
Start Year 2016
 
Description Novavax Matrix-M adjuvant 
Organisation Novavax AB
Country Sweden 
Sector Private 
PI Contribution Vaccine development
Collaborator Contribution Matrix-M adjuvant provision
Impact Collaborative clinical vaccine development. Joint grant applications.
Start Year 2017
 
Description Novavax collaboration 
Organisation Novavax AB
Country Sweden 
Sector Private 
PI Contribution Novavax provide an adjuvant, matrix-M for our malaria vaccine development programme and we generate malaria vaccines.
Collaborator Contribution Novavax provide their adjuvant and we pay them for this material
Impact Five clinical trials have been undertaken with their adjuvant by my team. We have also produced a lot of pre-clinical data
Start Year 2010
 
Description Partnership with another DPFS funded project 
Organisation University of Oxford
Department Jenner Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution - Results on vaccine stability, characterisation of membrane and polymer shared.
Collaborator Contribution Experimental designs, Access to different preparation of adenoviral vacccines.
Impact The current project has partnered with another DPFS project titled "GMP manufacture and Phase I clinical trial of a thermostable single-dose rabies vaccine for pre-exposure prophylaxis for children in endemic areas". Depending on the successful and timely outcome of the current project, the new membrane will also be tested with rabies vaccine.
Start Year 2017
 
Description Pirbright 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Basic and applied immunology and vaccine development
Collaborator Contribution Assay development
Impact TBC
Start Year 2017
 
Description Pirbright NDV 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution UOXF is developing a thermo-stable form of a Newcastle Disease vaccine, which will be tested at the Pirbright Institute by a group who work on this vaccine
Collaborator Contribution The Pirbright Institute will test the thermo-stable ND vaccine in vitro, and in chickens
Impact So far no outputs as all of the relevant work has been carried out at UOXF. In the next report outcomes resulting from the collaboration will be reported.
Start Year 2015
 
Description SpyTag-SpyCatcher with Prof Mark Howarth 
Organisation University of Oxford
Department Nuffield Department of Obstetrics & Gynaecology
Country United Kingdom 
Sector Academic/University 
PI Contribution Development of new VLP malaria vaccines
Collaborator Contribution Development of SpyTag-SpyCatcher technology
Impact Publications and grants
Start Year 2015
 
Description University of Warwick 
Organisation University of Warwick
Department School of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution The underlying data and information used to create the parameters for the simulation have been recorded by the named applicants as part of previous investigations into mosquito host-seeking behaviour. The behavioural assays that have been recorded to date were designed and executed by the researchers at the LSTM and made possible by the engineers at the University of Warwick. This collaboration is now developing further, as the work made possible by this award has allowed Dr Jeff Jones of the LSTM to collaborate with Dr Vitaly Voloshin of Warwick in order to re-code and improve the previous software used during video analysis. Further to this, the classification of host-seeking behaviour for use in the model will inform the re-design of the tracking software in terms of modes of mosquito behaviour that can be exploited when analysing video footage. As of January 2017 a microsoft sharespace site has been established to enable the sharing of data, information and discussions relating to these and similar projects, created by Dr Greg Murray and hosted by the LSTM.
Collaborator Contribution All behavioural assays recorded to date have been performed using technology designed and purpose-built by the applicants. The tracking software, recording system and subsequent analytical software were all produced in close collaboration with the team of engineers at the University of Warwick. Currently, this analytical software is being tested and improved alongside the modelling work. Data used during model parametrisation is thoroughly tested and so can inform the investigation into biases or inconsistencies in the original analysis software.
Impact University of Warwick - Engineering LSTM - Medical Entomology / animal behaviour
Start Year 2007
 
Title Recombinase Polymerase Assay for Giardiasis 
Description The development of an RPA for Giardia lamblia was published in 2016 (Cranell et al 2016) but never field-tested for the full assay or validated in an African context and as a field-applicable diagnostic tool to document treatment efficacy. This current project will address those gaps by refining the RPA field-test it and will provide analytical and clinical outputs by the end of 2017. The RPA assay was field tested in a rural setting in Uganda in June 2017. Analysis of the results are still ongoing. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2017
Development Status Under active development/distribution
Impact The expected outcomes of this project will be to improve on-site highly sensitive diagnosis of giardiasis and provide a reliable and low cost test-of-cure in an underdevelop African country. 
URL http://www.twistdx.co.uk/our_technology/
 
Title InFliTE - Insect Flight Testing Environment 
Description Recent advancements in video-tracking and behavioral analysis research (Angarita-Jaimes et. al, 2016, Parker et. al, 2015), has enabled the accurate recording and quantification of multiple parameters associated with mosquito flight, host-seeking, resting and other behaviors. This enables the development of Individual (agent) Based Models at much finer spatial and temporal scales than was previously possible. The behavioral parameters of Anopheles gambiae and other mosquitoes interacting with bed nets during host-seeking have recently been exploited at LSTM to create a novel virtual testing simulation, InFliTE (Insect Flight Testing Environment), allowing a wide range of innovative vector control ideas, both actual and theoretical, to be rapidly and easily assessed at marginal cost. The resulting model, described herein, represents a simple to use computer software package, capable of simulating vector behavior in a virtual mosquito population and its subsequent response to, and interactions with, environmental stimuli (including vector control tools). It allows the end user to compare, quantitatively and visually, alternative designs of vector control tools or systems, individually or in combination. To capture the complex interactions between mosquitoes and their environment we require a method which is fine-grained enough to represent individual model flight tracks and the subsequent interactions with their local environment. Yet most modelling approaches to vector behavior set the scale at the higher level (i.e. multiple houses, of transmission between villages), for example (Eckhoff, 2011, Gu et. al, 2003). The InFliTE model utilizes a novel fine-grained agent-based (or individual-based) modelling approach whereby very simple rules generate complex environment/host interactions. A population of mobile virtual mosquito insects are created. These individuals fly in a continuous 3D space representation inside a discretized spatial arena, representing an insectary or hut containing a bed net and human host. The population is introduced at the release site and begins to explore the arena. To respond to host stimulus cues, a method of generating and propagating an attractant plume via diffusion and convection is required. We adopt a discrete approach to this propagation, dividing the arena into a 3D lattice of 10CM3 regions (for computational tractability). The host bait profile is configurable to represent hosts of different sizes and the cells making up the bait profile are color-coded to indicate regions where greater concentrations of attractant (for example, CO2, skin odors) are emanated. At each scheduler step attractant is projected at bait profile locations and diffusion is implemented for all cells in the lattice volume by dispersing the attractant between the current cell and the 26 nearest neighbor cells. Convection is implemented for all cells by dispersing a fraction of each cell to the cell immediately above the current cell in the arena. Both the diffusion weight and convection weights can be specified before an experiment starts to give different attractant stimulus profile. Virtual mosquito flight behavior is designed to minimize the number of model parameters, provide a simple to understand method of flight orientation, yet also to minimize the number of assumptions on insect flight. Each virtual mosquito samples the local attractant plume gradient and orients itself towards the highest local concentration. Sensory parameters (Sensor Angle, Rotation Angle, Sensor Offset distance, Velocity) can be altered to generate foraging and host-seeking flight paths of differing tortuosity. The actual desired tortuosity value may be established from the published data based on insect flight tracking (Parker et. Al, 2015, Dekker and Cardé, 2011). Insect behavioral transitions are currently focused on host-seeking behavior and the interactions with the environment (including LLINs) and is represented by a relatively simple state transition function. This approach is expandable and allows the potential for future increases in the number and range of environmental interactions (for example, the inclusion of features such windows, doors, traps, surface coatings etc.). The InFliTE model replicates experimental findings relating to the presence or absence of a human host. We found differences in exploration of an arena when human bait is present or absent. In the presence of bait, a narrow field of the arena is explored, whereas the virtual population explores a much larger area of the arena when no host is present. The model also reproduces the findings in (Lynd and McCall, 2013) which demonstrated the most preferred landing site at a human baited bed net. The virtual mosquito population also exhibits a preference for the top surface of the bed net closest to the head of a human host. In an unbaited net, however, there are markedly fewer bed net contact events, with a random distribution of activity at the net. When no host is present there are very few contacts with the bed net as the virtual population is not attracted to the net. When a host is present, however, the number of contact events increases (following a spatial distribution at the top surface of the net). The reduction in bed net contact events when an insecticide treated net covering a human host is present, is a result of the gradual reduction in population health after cumulative bed net contact events with the treated net. These results match the findings reported in (Parker et. Al, 2015) of the rapid efficacy of LLINs and also approximate the spatio-temporal dynamics recorded by the same group using real-time image tracking equipment. With no bait and an untreated net there is approximately uniform flight path distributions. When a host is present under an untreated net there is an intense spatial distribution about the top surface of the net near the head of the host. When a treated net is used above a host there is the same spatial distribution pattern, but a rapid fall-off in mosquito activity in both experimental and model conditions. We find good correspondence between the simulation results and the experimental results using the tracking system. We continue to gather and collate data and plan to submit a paper for publication. We also propose to submit a funding application to extend the model to add additional features which we believe will be useful in the acceleration of vector control tools. 
Type Of Technology Software 
Year Produced 2017 
Impact We believe that our results provide scope to extend the model to cope with different real-life scenarios. 
URL http://www.lstm.co.uk
 
Company Name SpyBiotech 
Description Vaccine Company 
Year Established 2017 
Impact Secured £4m seed funding from Oxford Science Innovation (OSI) and GV (Google Venture)
Website http://www.spybiotech.com/web/
 
Description Attendance DHIS2 experts meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was an opportunity for LSTM to present its work, the DDMS, to the experts in the DHIS2 community whom we intend to collaborate and merge with. How this can potentially be achieved, the benefits and the challenges were presented and discussed.
Year(s) Of Engagement Activity 2016
 
Description Bluedot Festival; Can malaria be eliminated from the bluedot before we reach mars? 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Bluedot is an annual music/ science festival held at Jodrell Bank that attracts 12 - 15,000 people. The talk on recent advances in malaria control held in a 200 seater auditorium was near capacity and attracted a diverse audience and age range (toddlers to retired). The presentation generated a great deal of interest and questions, particularly from teenage/ early 20's people citing interests in career opportunities in tropical medicine.
Year(s) Of Engagement Activity 2018
URL https://www.discoverthebluedot.com/profile/can-malaria-be-eliminated-from-the-blue-dot-before-we-rea...
 
Description Bluedot: Malaria; of Man and Mosquito 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Presentation at a three day music festival at Jodrell Bank (Bluedot). The music festival attracted 15, 000 people, and the talks were attended by a wide range of public including families, young children, schools right up retirees. The talk was notable for the high level of audience participation and questions, partcularly from school leavers to consider a university career with a focus on Tropical Medicine.
Year(s) Of Engagement Activity 2017
URL http://2017.discoverthebluedot.com/profile/malaria;-of-man-and-mosquito
 
Description Conference Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of data generated from the CiC funded works at Oxford Symposia 'Emerging Viruses 2017'. Sparked a number of interesting questions, conversations and potential future collaborations.
Year(s) Of Engagement Activity 2017
URL http://lpmhealthcare.com/emerging-viruses-2017/
 
Description Confernce attendance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of work at international conference: Keynote Meeting; Immunological Memory: Innate, Adaptive and Beyond (X1)
Year(s) Of Engagement Activity 2018
URL http://www.keystonesymposia.org/18X1
 
Description Development of entomological module. Milestone 2. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact This workshop between Oslo University and LSTM was to enable the initial development of the entomology module for the DHIS2. The module has since been completed and populated with Zambia's resistance data and a dash board generated for viewing. This is the completion of stage 2 of the project allowing the final stage, in country evaluation to commence.
Year(s) Of Engagement Activity 2016
 
Description GAP analysis 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact The purpose of this engagement was to look at the two system, DDMS and DHIS2 and produce the GAP analysis (Mile stone 1 of the CIC project). This has now been completed.
Year(s) Of Engagement Activity 2016
 
Description Institutional visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Speaker at the Helmholtz Centre for Infection Research in Braunschweig, Germany
Year(s) Of Engagement Activity 2017
 
Description Lecture on CiC progress-London School of Hygiene & Tropical Medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact 50-75 people attended the update on the RPA assay development. The results were well received and there was some interesting feedback on the project.
Year(s) Of Engagement Activity 2017
 
Description Oxford University London Lecture 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This is a premier Oxford lecture each year presented at Westminster in London. I spoke on Ebola vaccines
Year(s) Of Engagement Activity 2016
 
Description Presentation at LSHTM CIC meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was a meeting in LSHTM to showcase some of the CIC awards and discuss the way forward.
Year(s) Of Engagement Activity 2017
 
Description Presentation at LSTM for lunchtime seminar series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact As the LSTM seminar series is live on the internet it allows an international reach of the work.
Year(s) Of Engagement Activity 2017
 
Description Royal Society Summer Science Exhibition 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Summer Science Exhibition 2018 at the Royal Society - 1000+ people per day from the general public for 7 days. Exhibit on "designer malaria vaccines"
Year(s) Of Engagement Activity 2018
URL https://royalsociety.org/science-events-and-lectures/2018/summer-science-exhibition/exhibits/designe...
 
Description Series of Rational Drug Discovery lectures (Undergraduate) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact To provide a better understanding how the students can translate their science / research activities to have more impact in terms of generating and developing products such as drugs, insecticides etc.
Year(s) Of Engagement Activity 2018
 
Description Series of rational drug discovery lectures (Post Graduate) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact To provide a better understanding how the students can translate their science / research activities to have mor eimpact in terms of generating and developing products such as drugs, insecticides etc.
Year(s) Of Engagement Activity 2018
 
Description Stand promoting the new tools at the Multilateral initiative on Malaria 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A stand was organised at the Multi Lateral initiative for Malaria conference that is held every four years where the African Malaria community meets. This covers operational programmes, funders and researchers.
Year(s) Of Engagement Activity 2018
 
Description VIT Visiting Adjunct Professor Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Lectures given under Adjunct Visiting Professorship Scheme. Lecture covered new advances in disease control including MRC CiC related research on Adhirons, activity based probes and DNA based resistance diagnostics.
Year(s) Of Engagement Activity 2016