Coxiella burnetii: Emerging threats, molecular insights, and advances in diagnosis and control measures.

Coxiella burnetii, a Gram-negative, obligate intracellular bacterium and causative agent of Q fever, is a re-emerging zoonotic pathogen with a complex transmission cycle involving livestock (cattle, sheep, and goats), diverse terrestrial and aquatic wildlife, arthropod vectors (ticks and fleas), and resilient environmental reservoirs, such as free-living amoebae. Humans are mainly infected by inhaling contaminated aerosols, especially during parturition. This review offers an integrative synthesis of current research across six key domains: ecological reservoirs, diagnostic strategies, molecular epidemiology, therapeutic challenges, vaccine development, and the One Health approach. We first examined emerging insights into host and vector diversity, including underexplored aquatic and semi-aquatic species, and environmental factors sustaining endemicity. We then assessed recent diagnostic innovations, such as multiplex and digital PCR, LAMP, metagenomic sequencing, and immunohistochemistry, alongside conventional serological tools, such as ELISA and IFA. Given the taxonomic complexity introduced by genetically related Coxiella-like endosymbionts, we highlight the necessity of high-resolution molecular typing platforms, such as MLVA, MST, and SNP analysis, for accurate strain discrimination. In clinical and environmental contexts, sample matrices now include blood, milk, feces, urine, respiratory secretions, and ectoparasites, enabling more sensitive surveillance. Despite this progress, Q fever control remains challenging because of nonspecific symptoms, diagnostic delays, chronic complications, and reliance on prolonged antibiotic therapy. Advances in antimicrobial testing and evolving vaccine strategies offer hope; however, durable cross-strain protection remains elusive. Adopting a One Health approach, this review highlights the key knowledge gaps and strategic priorities for reducing the global burden of C. burnetii across human, animal, and environmental health sectors.