 Ieithio, wrth gweithio, dyw'r gwnaes. Gweithio, dyma'n gweithio'r projektyr i MSF yn y gweithio'r cyffredin mwyaf, ym mhwyfyddiaeth. Mae'n gweithio'r cyffredin. Mae'n gweithio'r cyffredin yn 50% o gondolatau. Gweld wight. Mae'r swydd gweithio'r cyffredin ym mwyaf ar gyfer y Lohau Lai Gweithio, a'u cyffredin yn cyfrion ar gyfer y sylfaen ac lawer o gweithio. We've obviously been very involves to work on FIVA as a subject. That's about 10 million people per year in government income countries hospitalised with acute fever symptoms. Actually, although I've put there that MSF medical seems to face approximately over 178,000 patients per year with difficulty diagnosed fever. infact, we don't really have good numbers on this because it's been impossible to measure. One of the reasons we want to work more on diagnostic solutions for this is because it's really hard, difficult to diagnose fevers and we need better numbers from our science as well. There's also a lack of microbiology labs, lack of the ability to diagnose the cause of fever. There are a realisation that we need to move from a syndromic to an etiological approach to better manage fevers. Felly, y cael ei fod ymylgell Inspanyl yw'r hyn yr hyn yn ymwysig iawn yn y cyflym rydd. Felly, Oherwydd, yr hynny mae ei ddelir yn ac yn y rhwng i hynny yn iawn i gael cyfrifiadau t Next Gelf, ac mae eich cyfrifiadau yna mae yna'r cyfrifiadau a'u cyfrifiadau ar y laatfynyau unig o gyfrifiadau. A cwrs, mae'r cyfrifiadau芽eddydd fel mwy f сид o adael cyfrifiadau yn y cyfrifiadau ar allan o'r ddiwyllol ar y dyma, Of course, we also wanted to be affordable and robust at the moment we would like for it to be able to test for biomarkers to identify bacteria versus non-bacterial infections to be able to tell whether the patient needed antibiotics or not. We also wanted to detect fever-causing pathogens. This is a bit more difficult because obviously there's geographic variation, but there are some generally well-accepted pathogens that would need to be on there. And finally, we probably also wanted the test to be able to measure antibiotic susceptibility. So there's a number of projects underway in this area. The multiplex is not the only one. For example, there's been quite a lot of work on rapid diagnostic tests and point-of-care tests. Probably the most work at the moment is being done on biomarker or biomarker signatures that can differentiate bacterial and non-bacterial pathogens. These are usually host biomarkers. There's also initiatives to measure actual pathogens, whether in single RDTs or multiplex. And then combinations of different types of RDTs. For example, a malaria RDT paired with a biomarker to differentiate bacteria and non-bacterial biomarkers paired with pathogen detection. And then host response signatures, which would, for example, measure the transcriptome so you would see how the patient is responding to a pathogen for better clinical follow-up. And finally, severity markers to be able to triage patients better to see who needed urgent referral. And some of these existing initiatives include the MSF's eCare, which is a panoramic fever diagnostic technology that is run on a tablet. Clotilda's here, she can tell you more about that. There's also the original almanac that she worked on from the Swiss Tropical Institute, which has now become the epoch. MSF and FIND also work together to bring out a target product profile for the biomarkers in terms of the type of test we would want to see. It'd be useful for MSF and feasible for us to do in the field. And finally, they also published a review of the biomarker, the performance of the biomarkers, to distinguish bacteria and non-bacterial. There's actually very few studies from resource-limited settings for that, though. FIND are also continuing with other work on rapid diagnostic tests. For example, they're working with Cambio on a five-pathogen test for fever-causing pathogens in Southeast Asia. Okaba working with the University of Toronto on severity markers. And finally, there's a range of price funds, including from the NIH, the EU horizon, and longitudinal here in the UK. There's also the MINILA, which is an MSF OCP project, which aims to have a simplified feasible lab to miniaturise blood culture and also bone culture. And that's underway already, and we hope to be able to validate it in MSF sites at the end of next year. And finally, the multiplex, which is the least well-developed so far. We are undertaking six work streams to complete this preparation phase, which will probably take up until the end of next year. These work streams will enable an informed decision about whether it will be worth continuing with the full products or not. Part of this landscaping work, which has been quite extensive, was a review of 440 companies to see which manufacturers of both the instrument and the cartridges would be aligned with MSF ambitions, and we have about 20 at the moment. The methods, the feasibility study that was done examined patient needs potential funding to bring the products to market, the technical requirements and the regulatory requirements. It being an open system, the regulatory requirements are slightly more complex than a closed system, and just a good analogy of that would be like your Nespresso for coffee where you've got your Nespresso machine and you buy your cartridges from the same store and pop them in as opposed to going to another store and buying other generic cartridges, which you could run on the same machine. And so we're trying to move away from the Nespresso monopolistic system to a more open system, more customizable, more flexible and hopefully more competitive as well. And the target product profile is already in draft form. It's already been developed with input from MSF stakeholders and find, and interviews have been held as diagnostic companies to gauge their interest in bringing this product forward as well. Ethics, this innovation project did not involve human participants or their individual data, and the MSF ethics framework for innovation was applied to help identify and mitigate potential harms. The results so far, the target product profile is available, but just to highlight some variables from that. The intended use of the test would be for the detection or identification of priority pathogens and the ability to differentiate bacterial or non-bacterial infections in support of the diagnostic management of undifferentiated ffibril illness with sign of severity. The target use setting at a minimum would be for MSF referral facilities. So this is once you've ruled out malaria with an RdT and perhaps some other infections with available RdTs and you're still stuck as to what is causing the fever, so at a referral facility. And they would need to be a functional laboratory trained personnel, water electricity, limited climate control and medical staff on site. Ideally, we would like to bring the test down to the primary level as well. The target population, all patients, adult children, HIV positive, malnourished, et cetera. And the system importantly would need to combine different technologies because based on the ability to detect the pathogen, whether by molecular or serological means, you either need to measure depending on the kinetics, the pathogen itself or the immune response to the pathogen. But also for the biomarker tests and other maybe antibiotic sensitivity testing or severity markers, it needs to be a platform able to measure different types of things by different techniques. The draft pathogen is so far was developed by a consultation with MSF experts and find because we have very little good prevalence data to go on whether within MSF or from other studies that have been done. This was mostly done based on expert opinion and so needs to be honed a little more. It's also, you can see, includes both bacteria and viruses. Some are vaccine preventable, some are on the WHO priority pathogenist already. So quite a spread geographically as well. What is planned for the funding structure going ahead would be a milestone prize, so pool funding. Prizes have been quite popular in recent years to try and incentivise manufacturers to work on a product that would meet the target product profile. We estimate that the prize would be between 90 and 105 million R&D investment over six to eight years and it would be a milestone prize of three phases. In the first milestone it would be for proof of concept. So the concept being that you would be able to individually measure the pathogens and demonstrate that the platform technology can detect each of the pathogens identified in the TPP. This would be years zero to three, five to six awards of 78 million, captured 40 million. At the second milestone it would be a prototype built through initial clinical evaluation to demonstrate that the prototype meets the minimal requirements in the TPP. It is four to six, two to three awards at five to six million dollars, captured 20 million and finally the end prize for regulatory approval and field validation. This would be to demonstrate the clinical validation in the field, so at first MSF field sites, but others as well, and to fulfil the minimal requirements in the TPP. And this would be year eight, one award for 40 million. So in conclusion, by some of the landscaping work done, it does seem to be feasible to develop this product. There's a convincing business case for the project that meets MSF needs, which is not always easy. And the partnership with outside organisations are essential. The next steps, we have an agreement with the WHO to take the target product profile forward in a consensus process. So through the WHO, which is a normative body, we will finalise the target product profile, including the need to add on antibiotic resistance testing or not, and prioritisation of the pathogen list, finalising the pathogen list. We'll also have a menu of test cartridges defined to be able to sustain the market and with the geographic variation. We'll define how the multiplex will change clinical practice and improve patient care. So importantly, this test is used as part of a clinical algorithm and a diagnostic workup. So a lot of work is going into defining how this test would actually be used as part of a clinical algorithm for fever. And finally, compiling data points for the final decision-making on moving forward with the programme or not after these workstreams have been completed. And so at the moment the project is hosted by MSF USA who are undertaking these workstreams. So I'd just like to acknowledge everyone who's been involved in this. It's been at least the last two years. And that includes many people from MSF. And we've also worked with outside organisations to get the project to this point so far. Thank you.