Preclinical animal models for onchocerciasis and loiasis: A systematic review of applications in drug screening

BACKGROUND: Onchocerciasis and loiasis are co-endemic filarial neglected tropical diseases in Central and West Africa. While ivermectin-based mass drug administration has reduced onchocerciasis burden, it can trigger severe neurological adverse events in individuals with high Loa loa microfilaraemia. This limitation highlights the urgent need for safe macrofilaricidal therapies and appropriate preclinical models. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a systematic review following PRISMA guidelines to evaluate animal models used for preclinical drug screening in onchocerciasis and loiasis. Studies published between 1990 and 2025 were retrieved from PubMed and Google Scholar, and one-hundred and one eligible study were included in the qualitative synthesis. Models were assessed based on parasite stage permissiveness, survival duration, physiological relevance, host immune status, and suitability for drug evaluation. The bovine Onchocerca ochengi natural infection system emerged as the most physiologically relevant model, supporting the full parasite life cycle. Immunocompromised mouse models, including SCID and humanised NSG mice, allow controlled evaluation of parasite development and direct drug effects but incompletely reproduce human infection. Intraperitoneal adult male O. ochengi implant models in SCID mice and gerbils provide robust platforms for macrofilaricide screening. Semi-permissive rodent models offer practical systems for early-stage screening but are limited by non-physiological parasite localisation. For loiasis, non-human primate models, particularly Papio anubis, remain the most representative system. CONCLUSIONS/SIGNIFICANCE: No single model fully recapitulates human co-endemic infection. While the bovine model remains the gold standard, rodent implant models enable scalable screening. The absence of a physiologically relevant co-infection model remains a major barrier to developing safe macrofilaricides.