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.

Control of soil transmitted helminths (STH) and Schistosomiasis (SCH) has been part of routine programmes for many years, yet, the efficacy and effectiveness of these programmes is challenged by low and failing drug efficacy and growing concerns of anthelmintic resistance, calling for a revision of the MDA-drug strategies. In this regard, the novel fixed-dose co-formulation (FDC) including albendazole and ivermectin has proven to be safe and to overcome most of the challenges in drug efficacy for STH. For T. solium the situation is very different from STH and SCH as currently there are no countries routinely implementing control. 3SI-CONTROL will assess the safety and cost-effectiveness of the FDC co-administration with praziquantel in reducing the prevalence of T. solium, STH and SCH, in a randomised controlled trial embedded in solid implementation research. Results from 3SI-CONTROL will thereby provide a scientific evidence base on the safety and effectiveness of integration of T. solium control with STH and SCH, considering the One Health approach. Beyond this, the substantial implementation research component will enable bridging the gap between the evidence-based practice (results on safety and effectiveness) and the actual implementation in the routine, real-world setting. These results, joined by a comprehensive dissemination and advocacy plan, will provide leverage to stimulate uptake of T. solium in the existing routine NTD control programmes, enabling the implementation of a safe and integrated control strategy with a higher effectiveness, tackling three top ranking NTDs. By harnessing advanced concepts in One Health, implementation research, and pharmacovigilance, our project aims to deliver transformative impacts in NTD control, reducing the individual, social and economic burdens of resource poor rural populations.

The main concern of clinicians when addressing sick patients is to promptly identify -i.e., “not miss”- those at higher risk of severe disease, so as to prioritize their care and better target therapeutic interventions. Unfortunately, risk-stratification practices for infections remain suboptimal and prone to misclassification, leading to adverse outcomes and misallocation of resources, particularly in children (and even more so among newborns) from Sub-Saharan Africa (SSA). We recently developed “B-Triage”, a point-of-care rapid triaging test, designed for the quantitative assessment of sTREM-1, a biomarker of sepsis, and a highly performing prognostic marker, irrespective of underlying disease. Levels of sTREM-1 stand out as a quantitative and independent predictor of severity and death in all-cause infections, being superior to other markers and clinical scores, showing promise also for risk-stratification of non-communicable diseases. We propose to specifically validate B-Triage for risk-stratification of all cause sickness in the newborn, the age group concentrating ~50% of all child mortality. ACROBAT-newborns aims to continue and accelerate the valorisation of our device, with clinical studies in Mozambique, Ethiopia, Uganda and Gabon; the industrialization of its prototype; and a go-to market strategy for SSA. The project includes strong components of health economics and impact assessment, as well as socio-behavioural sciences (usability, acceptability, and feasibility studies), with the overarching aim of generating the necessary evidence to support B-Triage’s introduction to the African market. The proactive use of our device for risk-stratification of the sick newborn at first clinical presentation, will determine, objectively and with high precision, those at risk of severe outcome and death, resulting in improved outcomes and survival, and an optimized use of healthcare resources, including antibiotics and high value therapeutics.

AFRICAI-RI is a groundbreaking initiative designed to substantially improve healthcare in Sub-Saharan Africa (SSA) by establishing the region's first federated, multi-institutional imaging research infrastructure. The project will leverage European and African expertise to adapt successful data infrastructures and imaging solutions to diverse environments across SSA. AFRICAI-RI will address the critical challenges posed by infectious diseases and the scarcity of medical imaging experts in the region. Furthermore, it will foster healthcare innovation by deploying federated learning technologies to enhanced access to large imaging data in a privacy-preserving, trusted fashion. Furthermore, the project will develop AI tools optimised for the diagnosis of tuberculosis and pneumonia in both adults and children, while ensuring their applicability across different imaging modalities such as X-ray and ultrasound. AFRICAI-RI is also committed to building local capacity by enhancing expertise in AI and clinical research through extensive training and stakeholder engagement. Additionally, the project aims to drive academic and economic opportunities by promoting new models of IP management and AI certification specific to the needs of SSA. The consortium will work closely with both local and international public health organisations to develop ethical guidelines and policy frameworks that enable the sustainable integration of AI in imaging diagnostics across SSA. Ultimately, AFRICAI-RI aspires to create a lasting infrastructure that not only addresses immediate healthcare needs but also fosters ongoing innovation and collaboration within the African continent and beyond.

The COVID-19 pandemic had a devastating impact on tuberculosis (TB) control. In 2020, the number of people newly diagnosed with TB decreased by 18% despite a rising global TB burden. Intensified efforts to improve TB case detection are critically needed, especially in populations in whom bacteriological confirmation is suboptimal, such as children and people living with HIV (PLHIV) who have also been disproportionately affected by the pandemic. The need for highly sensitive sputum-free diagnostic tools for TB has never been greater. STool4TB, an EDCTP-2 funded diagnostic trial, began its activities in 2020 shortly after the onset of the COVID-19 pandemic. The study aims to validate a novel quantitative PCR assay utilizing a stool homogenization and DNA isolation method that yields a highly sensitive and specific detection of Mycobacterium tuberculosis. STool4TB is implemented in high TB & HIV burden settings of Mozambique, Eswatini, and Uganda under the hypothesis that it will contribute to narrow the large TB case detection gap by improving TB lab-confirmation rates in children and PLHIV, while proving feasible and acceptable. New evidence suggests that this platform has a higher sensitivity when compared to sputum culture and Xpert Ultra and could have an additive lab-confirmation yield of up to 20%. STool4TB is also evaluating the qPCR platform as a treatment monitoring tool. This assay has the potential to be adapted to a POC diagnostic test which could be easily implemented in decentralized levels of care. Given the impact of the COVID-19 pandemic on TB notifications at the three participating sites and on several STool4TB core activities, we request additional funding to finalize recruitment of participants and achieve the target sample size, ensuring full execution of all project’s objectives. The observed upward trend in global TB burden makes the development of promising diagnostic tools, such as this novel stool-based qPCR, more important than ever.