Coxiella burnetii, the bacterium responsible for Q fever, is a highly infectious, environmentally resilient, and aerosol-transmissible zoonotic pathogen. While molecular and serological assays are the primary tools for routine diagnosis, isolating viable C. burnetii remains crucial for comprehensive pathogen characterization, including whole-genome sequencing, phenotypic analysis, antimicrobial susceptibility testing, vaccine development, and diagnostic assay validation. This review examines the literature on two key factors for successful C. burnetii recovery: selecting an appropriate specimen source and choosing a compatible cultivation platform. Viable organisms can be recovered from human clinical specimens, such as acute-phase blood and tissues from focal chronic infections (e.g., cardiac valves), provided that bacterial burden and viability are maintained. Animal-derived specimens, especially reproductive tissues, placental material, fetal tissues, milk, urine, feces, and genital secretions, are vital sources for veterinary investigations and zoonotic risk assessment. However, contamination with other microorganisms often complicates recovery from these samples. Tick-derived and environmental samples can broaden epidemiological insights, but their interpretation requires caution, as Coxiella-like endosymbionts and low viable bacterial burdens may hinder culture recovery. Regarding culture platforms, mammalian cell culture, particularly shell vial-based systems, is the most widely applicable method for primary isolation. Embryonated chicken eggs and animal inoculation are still valuable for biological amplification or generating phase variants. Furthermore, host cell-free axenic media have revolutionized C. burnetii propagation, metabolic analysis, and genetic studies. Successful isolation hinges on several factors: specimen type, processing, storage conditions, bacterial viability, strain characteristics, and compatibility with the chosen culture system. Future advancements should incorporate viability-based molecular preselection, high-throughput image-based culture screening, optimized cell-line selection, axenic media with broader strain permissiveness, and standardized reporting of culture attempts. These improvements will expand available isolate collections and diversify studies on C. burnetii biology, epidemiology, and control.

French Guiana (FG), an Amazonian French territory, represents a unique ecological and epidemiological setting for tick-borne diseases (TBDs). In contrast to mainland France, where TBDs are well-documented, data from FG remain scarce. We carried out a systematic review using the PRISMA criteria for our search of the PubMed, ScienceDirect, and SciELO data bases. We identified 68 articles, of which 43 met our inclusion criteria. Data from FG were compared with those originating from mainland France. Albeit highly prevalent in Europe, and notwithstanding detection of a distinct Borrelia species in bird-associated ticks, there have been no confirmed autochthonous cases of Lyme disease in French Guiana. Conversely, Q fever occurs more frequently in this overseas territory than in mainland France, even though its causative agent, Coxiella burnetii, has been detected only one time in a local tick. While Rickettsia spp. are widely present in tick populations, no human rickettsiosis has been reported. As for Anaplasma and Ehrlichia spp., they have been identified in wildlife, domestic animals, and ticks, but with only one documented human case of chronic anaplasmosis, which was caused by a novel species, Candidatus Anaplasma sparouinense. Other pathogens, including Babesia, Bartonella, and filarial nematodes, have been detected in animals or ticks, but without evidence of human infection. Of note, emerging conditions have been described, one example being alpha-gal syndrome, an allergy triggered by tick bites to mammalian meat. To summarize, available data remain limited, and in all likelihood, the burden of TBDs in FG is underestimated. Integrated research combining human, animal and environmental surveillance is needed to more precisely characterize epidemiology, assess risks, and facilitate preventive strategies.

Coxiella burnetii (Cb), the causative agent of Q fever, replicates within host macrophages by modulating innate immune responses through its type IVB secretion system (T4SS). Host cells sense pathogens via Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), to recognize pathogen-associated molecular patterns (PAMPs) and initiate signaling pathways that drive pro-inflammatory cytokine and interferon responses. Toll-like receptor 3 (TLR3) triggers the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Interferon regulatory factors (IRFs) resulting in pro-inflammatory cytokine production and type I interferon (IFN-I) induction. Here we demonstrate that Cb requires T4SS to suppress TLR3-induced NF-κB and IRF transcriptional responses. Furthermore, RNA purified from both virulent and avirulent Cb is sufficient to activate TLR3, identifying pathogen RNA as a relevant PAMP in this context. Using a pulmonary infection model with virulent Cb, we found that TLR3/ Toll-Interleukin-1 Receptor Domain-Containing Adapter Protein Inducing Interferon Beta (TRIF)-dependent innate immune pathway inhibits cachexia. In contrast, signaling through the interferon-α/β receptor (IFNAR) restricts bacterial dissemination, indicating that these pathways play distinct but complementary roles in host defense. Mechanistically, Cb suppresses TLR3/TRIF signaling in a T4SS-dependent manner by preventing host TLR3 recruitment to the Coxiella-containing vacuole (CCV) and disrupting TRIF-TNF Receptor-Associated Factor 6 (TRAF6) interactions, thereby selectively inhibiting impairing NF-κB activation. Consistent with this, we identify five T4SS effector proteins that attenuate TLR3-induced NF-κB signaling, including CBU1292, which suppresses both NF-κB and IRF-dependent responses downstream of TLR3.

The recent serological detection of Coxiella burnetii exposure in Somali livestock (12.6% seroprevalence among 372 ruminants) is an important addition to the limited epidemiological evidence on zoonotic disease ecology in the Horn of Africa. This finding, combined with prior molecular evidence of a novel C. burnetii genotype (D21) in ticks infesting Somali camels and high seroprevalence (21.4%) in febrile patients in neighboring Ethiopia, provides a rationale for investigating Q fever as a potentially under-recognized zoonosis in the region. However, critical knowledge gaps persist, including limited geographic sampling, absence of published human serosurveillance from Somalia, lack of molecular characterization of circulating strains in livestock, and inadequate understanding of transmission dynamics at the human-animal-environment interface. This correspondence synthesizes available evidence, identifies specific research priorities, and proposes a context-adapted One Health surveillance framework as a conceptual proposal requiring feasibility assessment and stakeholder adaptation. We argue that the serological evidence of C. burnetii exposure in Somali ruminants should catalyze coordinated, cross-sectoral interventions feasible within Somalia's current resource-limited setting.

Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute and chronic Q fever in humans. Neutrophils are considered the major innate cells with a primary role in controlling extracellular bacteria. Despite the obligate intracellular lifestyle of C. burnetii, our previous study demonstrated that neutrophils are crucial for host defense against C. burnetii infection in mice. Our recent study also showed that virulent C. burnetii Nine Mile phase I (NMI) and avirulent NM phase II (NMII) strains differentially modulate autophagy and apoptosis in murine neutrophils. However, the interaction between human neutrophils and Coxiella remains unexplored. In this study, we investigated how human neutrophils interact with C. burnetii. The results indicated that NMII bacteria were able to infect and reside in autophagolysosomal compartments of human neutrophils. Additionally, NMII bacteria inhibited the expression of ANNEXIN-V and the activation of caspase-3, resulting in delayed apoptosis in neutrophils. Live imaging showed that NMII bacteria actively swarm and recruit human neutrophils to form localized neutrophil clusters, which deploy neutrophil extracellular traps (NETs) to restrain bacteria. The deployment of slow-diffusing NETs in localized clusters was observed with NMII-infected human neutrophils in a dose-dependent manner. Furthermore, the observation of Coxiella colocalization with the deployed NETs demonstrates the ability of human neutrophils to immobilize and contain C. burnetii. We also found that the neutrophil's decision to undergo constitutive apoptosis or NETosis depends on the activation of the PI3K-autophagic pathway. Collectively, this study provides novel information for understanding the mechanism of human neutrophil interaction with Coxiella.

Coxiella burnetii, the etiological agent of Q fever, is a globally distributed zoonotic pathogen and a One Health priority. Despite increasing recognition of wildlife as potential reservoirs, data on C. burnetii circulation in European wild ungulates remain scarce. This study estimated exposure to C. burnetii in free-ranging wild boar (Sus scrofa) and red deer (Cervus elaphus) from two major hunting regions in east-central and northeastern Portugal and evaluated the performance of a commercial multi-species ELISA in these hosts. Between 2011 and 2021, 279 serum samples (162 wild boar; 117 red deer) from legally hunted animals in Portugal were tested using an indirect multi-species ELISA using an empirical species-specific threshold derived from a Gaussian mixture model. Overall seroprevalence was 6.8% (CI 95%; 3.4-11.8) in wild boar and 13.7% (CI 95%; 8.0-21.3) in red deer, with higher exposure in wild boar from Beira Baixa (east-central Portugal) than from Trás-os-Montes (northeastern Portugal). The manufacturer's ruminant cut-off classified almost no animals as seropositive (0.6% and 2.6%, respectively) and showed slight to fair agreement with the species-specific thresholds, underscoring the need for validated, wildlife-appropriate diagnostic criteria. These findings confirm exposure to C. burnetii in both species, suggesting their possible involvement in local maintenance of the pathogen at the wildlife-livestock-human interface. The results reinforce the value of integrating wildlife surveillance into national Q fever surveillance and control strategies to safeguard both public health and livestock production within a One Health context.

Bulk tank milk (BTM) provides a practical, non-invasive matrix for repeated herd-level surveillance in dairy farms. This study evaluated a four-season BTM framework for bovine brucellosis, influenza A virus, and Q fever in Korean dairy farms. In 2025, 602 BTM samples were collected from 167 farms in spring and summer and 134 farms in autumn and winter. Seasonal comparisons were interpreted cautiously because farm composition changed after summer. Bovine brucellosis was tested by milk ring test, influenza A virus by M-gene real-time RT-PCR, and Q fever antibodies by ELISA. An exploratory avian influenza virus (AIV) antibody ELISA was also applied to whey. Coxiella burnetii PCR testing was restricted to nine participating farms in Daegu Metropolitan City, and one BTM real-time PCR-positive farm was further investigated using sera from 105 lactating cows. All BTM samples were negative for bovine brucellosis, no influenza A virus M-gene RNA was detected, and no samples exceeded the positivity threshold in the exploratory AIV antibody ELISA. Q fever antibodies were detected in 343 of 602 BTM samples (57.0%). C. burnetii DNA was detected by real-time PCR only in spring and summer BTM samples from one of the nine Daegu farms. In this farm, all serum samples were PCR-negative, whereas 46 of 105 cows were antibody-positive (43.8%). These findings support repeated BTM testing as a complementary herd-level screening approach, particularly for Q fever monitoring.

Background: The "doxycycline deficiency syndrome" is a colloquial term used in tropical Australia to describe the overlapping, non-specific findings seen in leptospirosis, Q fever, and the rickettsial diseases scrub typhus and Queensland tick typhus (QTT). A laboratory confirmed diagnosis is frequently delayed, however, early differentiation of these potentially life-threatening infections has important implications for clinical management. Methods: We examined consecutive laboratory-confirmed cases of leptospirosis, Q fever, and rickettsial diseases managed at a referral centre in tropical Australia. The patients' symptoms, clinical signs and simple laboratory and radiology investigations at presentation were compared. Results: There were 111 cases of leptospirosis, 59 cases of Q fever, and 34 cases of rickettsial disease (17 cases of QTT and 17 of scrub typhus). Patients with leptospirosis had a shorter duration of symptoms and were more likely to have gastrointestinal symptoms, arthralgia, haemoptysis, hypotension, conjunctival suffusion and abnormal chest auscultation at presentation than patients with the other infections. They were more likely to have renal impairment and an elevated creatine kinase but less likely to have an elevated serum ferritin and serum lactate dehydrogenase. Patients with leptospirosis were more likely to have alveolar and multilobar changes on chest imaging. Patients with Q fever were more likely to have abnormal liver function tests at presentation but were more likely to have preserved renal function and normal chest imaging. Patients with rickettsial disease were more likely to have a rash, an eschar, lymphadenopathy and splenomegaly. Overall, 76/204 (37%) required ICU admission, of whom 56 (74%) had leptospirosis, but all 204 patients survived to hospital discharge. Conclusions: Leptospirosis, Q fever, and rickettsial diseases can have a similar presentation, but simple clinical, laboratory and imaging findings can help distinguish these infections and expedite their optimal management.

We describe two patients in Far North Queensland with acute Q fever. One patient had their infection complicated by a splenic abscess, the other developed a hepatic abscess. Both patients had contact with small Australian marsupials in the weeks before presentation and both required prolonged doxycycline to treat their infection.

[This corrects the article DOI: 10.3389/fcimb.2026.1835140.].