Onchocerciasis overview: pathogenesis, clinical spectrum, and therapeutic challenges of a neglected tropical disease

Onchocerciasis is still a major health burden in sub-Saharan Africa and Yemen, where many cases occur as control efforts face persistent obstacles, while smaller, well-defined transmission foci remain in Brazil and Venezuela. Caused by the filarial nematode Onchocerca volvulus and transmitted by blackflies, the disease causes progressive disability, economic loss, and hampers community development. Despite decades of mass drug administration with ivermectin, the inability of the drug to kill adult worms, increasing concerns over resistance, and the lack of effective vaccines continue to hinder elimination strategies. This review provides an overview of the disease, discussing its transmission dynamics, pathogenesis, clinical manifestations, diagnosis, and treatment. It also examines the immune-mediated responses that drive tissue damage and chronic morbidity, with an emphasis on skin and ocular complications. We highlight the need for rapid, non-invasive, and cost-effective diagnostic tools to enhance disease surveillance and assessment of treatment. Finally, we discuss the limitations of current therapies and recent progress in vaccine development, particularly subunit and multi-epitope vaccine candidates identified through reverse vaccinology approaches. Together, these insights reinforce the need for integrated strategies, combining improved diagnostics, novel treatments, and vaccines, to drive progress toward onchocerciasis elimination.