Loiasis, a filarial infection caused by Loa loa, affects millions of people in Central Africa. A high number of microfilariae in the blood is associated with a risk of cardiac, renal, or neurological complications, as well as reduced life expectancy. The HYLO project aims to shed light on the clinical impact of loasis on the spleen, via functional hyposplenism (FHoS). More specifically, this project aims to confirm the existence of an association between microfilarial density in Loa and the presence and severity of FHoS, and to establish a correlation between HoSF associated with loasis and the increase in cases of bacterial infection. To achieve these objectives, we will conduct a three-year cohort study in the Republic of Congo and a hospital-based matched case-control study. In 2025, we will assess individual Loa microfilariae densities and IgM+/IgD+ memory B lymphocyte (MBL) levels. In addition, we will measure membrane and soluble biomarkers such as opsonin (tuftsin) and CD14/CD169/CD63 to better understand the mechanisms associated with FHoS, including possible deficiencies in macrophage activation. For all cases of fever, we will carry out bacteriological diagnostics using a decentralized laboratory. In addition, standardized verbal autopsies will be used to investigate all causes of death. We will compare the incidence of clinical and bacteriological diagnoses according to measurements of microfilarial density in Loa, BMLs, and biomarkers. Finally, this project aims to elucidate some of the underlying mechanisms associated with loiasis-associated FHoS and to highlight the clinical repercussions of loiasis on the spleen, as well as the respective contribution of possible antibiotic resistance to the unfavorable outcome of bacterial cases (both time in hospital and outcome as death). Our results could pave the way for specific vaccine recommendations, with the potential to reduce, for example, the burden of lower respiratory infections, which are over-represented in this region of the world.