Plasmodium vivax is considered the most difficult species of human malaria parasite to eliminate because of the inability of conventional diagnostics to detect individuals who carry dormant liver forms and sustain malaria transmission. The consortium has developed the first diagnostic test that addresses this problem. PvSeroRDT aims to develop a point-of-care (POC) rapid diagnostic test (RDT) to transfer the consortium’s validated lab-based test to the field to support implementation of the P. vivax Serological Test and Treatment (PvSeroTAT) malaria control strategy. The PvSeroRDT specific objectives are: 1) Develop a POC RDT using lateral flow technology to measure antibodies to four P. vivax proteins that are biomarkers for the dormant liver-stage of P. vivax. 2) Establish Africa-based manufacturing capacity at DIATROPIX (Senegal) following RDT development at Abingdon Health, a UK-based SME specialising in lateral flow assays. 3) Validate RDT performance with bio-banked samples, followed by field-based clinical validation on freshly collected samples in Ethiopia and Madagascar. 4) Develop a clear regulatory strategy to streamline market authorization and access to this first-in-class P. vivax serological testing. PvSeroRDT addresses all expected outcomes and impacts of this call topic and work program, respectively. Specifically, it will contribute a robust POC diagnostic to the pipeline in sub-Saharan Africa (SSA) and enable the implementation of the AU-EU Innovation Agenda for public health. The project is designed to address the WHO’s preferred profile for P. vivax diagnosis, to translate an SME prototype to Africa-based industrial design, and to test clinical performance in several SSA sites, thus enhancing international cooperation in SSA and improving training opportunities in SSA. Ultimately, PvSeroRDT will facilitate implementation of PvSeroTAT – a new intervention for malaria elimination.

Cryptosporidium is an intestinal parasite causing cryptosporidiosis, a prevalent diarrheal disease among young children in low- and middle-income countries. This infection causes approximately 48,000 deaths and the loss of 7.9 million disability-adjusted life-years annually. Despite the existence of a low-cost drug, access to treatment is hindered by the limited availability of affordable, straightforward, point-of-care (POC) diagnostic tests. LED microscopy of auramine-phenol (AP) stained fecal smears has demonstrated promising diagnostic accuracy in detecting cryptosporidiosis. In this project, we will implement a test-and-treat strategy in a stepped-wedge cluster randomized trial. The aim is to assess the clinical effectiveness of LED-AP testing, in conjunction with access to targeted drug treatment, in reducing the duration of cryptosporidiosis-induced diarrhea. We will evaluate diagnostic accuracy, operational issues, cost-effectiveness, and test turnaround times in realistic setting in two Sub-Saharan African (SSA) countries. Additionally, we will investigate whether rectal swab samples can expedite test turnaround times compared to bulk stool samples. This project aligns with the UN Sustainable Development Goal 3 and WHO initiatives to reduce the burden of diarrheal diseases. Effective POC diagnostics and treatment are expected to alleviate diarrhea and reduce long-term complications. The findings will be instrumental in updating current diarrheal treatment guidelines, which primarily advocate for syndromic treatment. The outcomes will be of significant interest to health facility staff, ministries of health in SSA, WHO, and the scientific community. This study will provide crucial data on optimizing LED-AP testing to guide clinical decision-making and targeted treatment, thereby preventing the overuse of antibiotics. The introduction of cryptosporidiosis testing can enhance surveillance of this critical pathogen.

BACKGROUND - Leprosy is a significant public health problem. Early detection, treatment, and prevention are crucial to reduce transmission and disabilities. The World Health Organization (WHO) recommends single-dose rifampicin post-exposure prophylaxis (SDR-PEP) for screened contacts of leprosy patients. The PEP4LEP 2.0 study builds upon the EDCTP2-PEP4LEP project to identify the most effective intervention to screen individuals for leprosy, other skin neglected infectious diseases (skinNIDs) and common skin diseases, and to provide SDR-PEP. The study takes place in leprosy high-endemic areas in Ethiopia, Tanzania and Mozambique. It determines which intervention has most effect on leprosy case finding and detection delay. However, the COVID-19 pandemic hampered the initial PEP4LEP study through delayed interventions and medication shortages, affecting the main outcome indicator: case detection delay. METHODS - PEP4LEP 2.0 is a two-arm, cluster-randomized implementation trial to compare two interventions: 1) a community-based skin camp intervention, screening 100 leprosy patient's community contacts for leprosy and other skin diseases, and administering SDR-PEP; and 2) a health centre-based screening intervention, inviting leprosy patients’ household contacts to health centres for screening and SDR-PEP. To ensure a scientific sound analysis, PEP4LEP 2.0 collects additional data, increasing the sample size by 25%, to understand the pandemic's effects and enable analysis with and without COVID-19 influences. Skin camp organization, skinNID distribution, health staff capacity and acceptability will also be studied. Results will be modelled to assess the long-term impact related to costs. IMPACT - PEP4LEP 2.0 results will reflect scientific, societal and economic impact towards reduced leprosy transmission. They will be disseminated to all stakeholders: scientists, policymakers, WHO, health staff, affected communities, NGOs and the general public in the EU and Africa.

Pneumonia is a leading cause of morbidity and mortality especially among children in sub-Saharan Africa. Nigeria and Ethiopia are among the 5 countries that account for half of the under-five pneumonia deaths. Majority of the deaths from pneumonia are however preventable with early diagnosis and appropriate management. In children with pneumonia, hypoxemia is quite common and constitutes a major risk factor for death. The WHO and other leading child health agencies urge widespread access to oxygen therapy. Bubble continuous positive airway pressure (bCPAP) is a method of delivering oxygen and positive pressure into the airways thus keeping the alveoli open for improved gas exchange. While use of bCPAP devices appears safe and effective worldwide, scaling of quality bCPAP devices in low- and middle-income countries (LMICs) has been limited. This has prevented most children in LMICs from receiving life-saving non-invasive respiratory support which could have saved many lives. Achieving Sustainable Development Goal (SDG) 3.2 of the reduction of under-5 mortality to at least as low as 25 per 1,000 live births by 2030 will likely not be possible without access to innovative and low cost interventions devices such as bCPAP in LMICs. The aim of the OPT-bCPAP is to perform context-appropriate scale-up of bCPAP in settings of very high disease burden (Nigeria, Ethiopia and Malawi) using the the positive results and the lessons learned from clinical trials conducted in Ethiopia, Bangladesh and Ghana. In addition to scaling up bCPAP, we will deeply explore additional factors associated with treatment failure and mortality from severe pneumonia, we aim to generate data on adherence to treatment guidelines, healthcare-seeking behaviour, magnitude of respiratory syncytial virus infection, antimicrobial resistance, PK/PD of commonly used antibiotics and generate novel recommendations for antibiotic treatments tailored to the populations in these diverse settings.

Cutaneous leishmaniasis (CL) is a neglected tropical disease affecting more than one million people globally each year. In Ethiopia alone more than 40,000 people are thought to be affected annually. Infection results in stigmatising, visible, chronic, scarring skin lesions which cause permanent morbidity and significantly affect mental health, household financial stability and life chances. There is a major need for new therapeutics for CL. The current first line therapy is intramuscular sodium stibogluconate. Treatment is often ineffective, painful, and associated with adverse effects. The complexities of administration mean treatment is restricted to a small number of centralised facilities. As a result the majority of patients receive no treatment. There are a number of promising alternative and novel therapeutics for cutaneous leishmaniasis which may be more effective, more tolerable and more suitable for widespread scale up. However the evidence for these therapies is lacking and this vacuum means that policy cannot be easily changed. Our consortium of leading European and African research institutions proposes a step-change in the evidence base for CL. We will use a multi-arm, multi-stage randomised trial – MAMS4CL - to simultaneously evaluate multiple novel therapeutic interventions. This approach will reduce the time required to identify optimal treatment strategies for CL and transform the therapeutic landscape. We will identify and test five candidate interventions and assess their safety, efficacy, cost-effectiveness, and acceptability. The interventions have been selected as they offer: more tolerable administration, shorter treatment duration or home-based therapy. We will embed within MAMS4CL detailed pharmacokinetic, health economic and social science studies to provide a comprehensive analysis to inform regulators, policy makers and programmes.