Q fever in the 21st century: Uncovering diagnostic, epidemiological, and one health gaps in a re-emerging zoonosis.

Q fever, caused by the gram negative obligate intracellular bacterium Coxiella burnetii, remains a globally relevant but underappreciated zoonosis in the 21st century. Despite decades of research, the disease continues to pose diagnostic, epidemiological, and clinical challenges that hinder timely recognition and effective management. This review aims to synthesize current advances in the epidemiology, pathogenesis, and diagnosis of C. burnetii, while critically examining the One Health gaps that sustain its persistence as a re-emerging zoonosis. We evaluate the strengths and limitations of existing diagnostic platforms, summarize recent progress in molecular epidemiology, and explore the underrecognized contributions of environmental and wildlife reservoirs to transmission. We further highlight disparities in surveillance and reporting, particularly in regions such as Africa and Asia, where the disease remains neglected. Looking ahead, we outline key priorities for research and practice. These include elucidating molecular mechanisms of host-pathogen interactions, identifying novel diagnostic biomarkers, deploying genomic epidemiology to capture global strain diversity, developing safer and more accessible vaccines, and operationalizing One Health frameworks to integrate veterinary, medical, and environmental surveillance. By clarifying these research and policy gaps, this review provides a roadmap for reducing the global burden of Q fever and offers broader insights into tackling other neglected zoonotic diseases at the human-animal-environment interface.