P. vivax is considered the most difficult human malaria to eliminate because of the inability of conventional diagnostics to detect individuals with latent liver forms. These individuals account for 80% of all infections and can readily infect mosquitoes. Currently countries can test knowing this has little impact or and the treat everyone which exposes individuals to drugs with potentially dangerous side effects. Parasite specific antibody responses have been shown to correlate with the likelihood of hypnozoite carriage and can be used to identify individuals who should be treated. Aim is to implement a Cluster-Randomised Trial in Ethiopia and Madagascar to demonstrate the effectiveness of a new anti-malaria intervention based on Plasmodium vivax serological testing and treatment (PvSTATEM) with primaquine to prevent the relapse infections responsible for maintaining P. vivax transmission. Simultaneously, we will assess social and health system acceptability of such an approach as well as refine new mobile technologies which interface with point-of-care diagnostic tests and guide treatment decisions. We aim to reduce malaria burden at both the individual and population level in two countries which experience the highest levels of P.vivax in Africa. We expect to have a significant effect in reducing morbidity and improving health. We will ensure community engagement and assess the adoption of new technologies that align with those existing in the health system. The proposal is built on equal partnership and shared capacity to address a substantial public health burden.

Current anti-tuberculosis (TB) drug regimens face serious limitations at times of increasing antimicrobial drug resistance. Fortunately, for the first time for centuries, several novel anti-TB compounds are available for clinical evaluation. As the traditional approach to testing these in multiple combination regimens is too slow and inefficient new approaches of clinical phase 2 study designs are required if we are to meet the targets of the WHO EndTB strategy to save the lives of millions into the near future. Our consortium brings together a unique group of European and international leaders in TB research and leading industry partners. Together we will provide the necessary comprehensive range of expertise to meet the demands of the UNITE4TB scientific research agenda. Specifically, we will develop a new global standard for phase 2 TB clinical trial designs, utilising simulation tools to identify optimal doses in phase 2A trials and apply a multi-arm multi-stage adaptive randomised controlled 2B/C trial design capable of rapid and simultaneous evaluation of the best candidate regimens. Our innovative phase 2 trials will be performed to the highest regulatory standards, incorporating state-of-the-art microbiology, biomarker investigation and clinical pharmacology. We will take advantage of existing global TB clinical trial networks with the capacity to enrol patients at an unprecedented pace and number across four continents. Artificial intelligence/machine learning technologies will be applied to validate state-of-the art molecular and imaging tools as treatment decision biomarkers with the aim of establishing new, real-time outcome measures. Our consortium will evaluate 3-5 new chemical entities (NCEs) at phase 2A and up to 17 novel combination regimens in phase 2B/C. Our objective is to identify those that have the greatest chance of success in subsequent definitive phase 3 clinical trials and of becoming the global gold-standard TB regimens of the future.

We are proposing to develop a molecular assay for the safe, rapid, specific and sensitive detection of Ebola Virus Infection in capillary (or venous) blood samples combining ALTONA’s Pan-filo screening IVD test with the existing Alere™ q point of care molecular diagnostics platform. The purpose of this project is to utilize existing and proven PCR assay(s) designed for laboratory use and to take advantage of the Alere™ q point of care molecular instrument and cartridge design to simplify Ebola testing so that molecular testing can be expanded to sites beyond which high end laboratory infrastructure is not available while simultaneously greatly reducing infection risk for the test operator. The project aims for the fast development of a point of care Nucleic Acid Test (POC-NAT) system for filovirus specific RNA, from human sample material, especially from blood samples. The POC-NAT system will have the following features: 1. Field proven stand alone, mobile and easy to use instrumentation 2. ready to use cartridge, safely disposable nucleic acid test format with integrated sample preparation 3. assay for specific detection of RNA of all known species from the virus genera Ebola- and Marburgvirus . 4. process duration from sampling to result less than 45 min 5. no additional equipment and no logistics and storage at -20°C needed The POC-NAT is based on two already existing technologies: The instrument platform “Alere™q complete” developed and manufactured by Alere , an instrument for POC diagnostics recently used p.e. for Alere´s HIV-1/2 Detect cartridges, and altona Diagnostics´ RealStar® Filovirus RT-PCR kit 1.0, a commercial central laboratory real-time PCR test. The project partner aim for having the integration of platform and assay as a prototypic system completed until end of March 2015. The verification and validation of the workflow starts April 2015 at altona Diagnostics, BNITM and INMI. The aim of this project phase is to finally CE IVD mark the test system