UNASSIGNED: Coxiella burnetii (C. burnetii)-infected livestock and wildlife have been epidemiologically linked to human Q fever outbreaks. Despite this growing zoonotic threat, knowledge of coxiellosis in wild animals remains limited, and studies to understand their epidemiologic role are needed. In C. burnetii-endemic areas, ticks have been reported to harbor and spread C. burnetii and may serve as indicators of risk of infection in wild animal habitats. Therefore, the aim of this study was to compare molecular techniques for detecting C. burnetii DNA in ticks.
UNASSIGNED: In total, 169 ticks from wild animals and cattle in wildlife conservancies in northern Kenya were screened for C. burnetii DNA using a conventional PCR (cPCR) and two field-friendly techniques: Biomeme\'s C. burnetii qPCR Go-strips (Biomeme) and a new C. burnetii PCR high-resolution melt (PCR-HRM) analysis assay. Results were evaluated, in the absence of a gold standard test, using Bayesian latent class analysis (BLCA) to characterize the proportion of C. burnetii positive ticks and estimate sensitivity (Se) and specificity (Sp) of the three tests.
UNASSIGNED: The final BLCA model included main effects and estimated that PCR-HRM had the highest Se (86%; 95% credible interval: 56-99%), followed by the Biomeme (Se = 57%; 95% credible interval: 34-90%), with the estimated Se of the cPCR being the lowest (24%, 95% credible interval: 10-47%). Specificity estimates for all three assays ranged from 94 to 98%. Based on the model, an estimated 16% of ticks had C. burnetii DNA present.
UNASSIGNED: These results reflect the endemicity of C. burnetii in northern Kenya and show the promise of the PCR-HRM assay for C. burnetii surveillance in ticks. Further studies using ticks and wild animal samples will enhance understanding of the epidemiological role of ticks in Q fever.

BACKGROUND: Q fever, caused by the zoonotic pathogen Coxiella burnetii, exhibits a worldwide prevalence. In China, Q fever is not recognized as a notifiable disease, and the disease is overlooked and underestimated in clinical practice, leading to diagnostic challenges.
METHODS: We present a case series of three patients diagnosed with persistent Q fever between 2022 and 2023. The average age of our three cases was 63.33 years old, consisting of two males and one female. The medical history of the individuals included previous valve replacement, aneurysm followed by aortic stent-graft placement and prosthetic hip joint replacement. At the onset of the disease, only one case exhibited acute fever, while the remaining two cases were devoid of any acute symptoms. The etiology was initially overlooked until metagenomic next-generation sequencing test identified Coxiella burnetii from the blood or biopsy samples. Delayed diagnosis was noted, with a duration ranging from three months to one year between the onset of the disease and its confirmation. The epidemiological history uncovered that none of the three cases had direct exposure to domestic animals or consumption of unpasteurized dairy products. Case 1 and 2 resided in urban areas, while Case 3 was a rural resident engaged in farming. All patients received combination therapy of doxycycline and hydroxychloroquine, and no recurrence of the disease was observed during the follow-up period.
CONCLUSIONS: Q fever is rarely diagnosed and reported in clinical practice in our country. We should be aware of persistent Q fever in high-risk population, even with unremarkable exposure history. Metagenomic next-generation sequencing holds great potential as a diagnostic tool for identifying rare and fastidious pathogens such as Coxiella burnetii.

Intracellular bacterial pathogens divert multiple cellular pathways to establish their niche and persist inside their host. Coxiella burnetii, the causative agent of Q fever, secretes bacterial effector proteins via its Type 4 secretion system to generate a Coxiella-containing vacuole (CCV). Manipulation of lipid and protein trafficking by these effectors is essential for bacterial replication and virulence. Here, we have characterized the lipid composition of CCVs and found that the effector Vice interacts with phosphoinositides and membranes enriched in phosphatidylserine and lysobisphosphatidic acid. Remarkably, eukaryotic cells ectopically expressing Vice present compartments that resemble early CCVs in both morphology and composition. We found that the biogenesis of these compartments relies on the double function of Vice. The effector protein initially localizes at the plasma membrane of eukaryotic cells where it triggers the internalization of large vacuoles by macropinocytosis. Then, Vice stabilizes these compartments by perturbing the ESCRT machinery. Collectively, our results reveal that Vice is an essential C. burnetii effector protein capable of hijacking two major cellular pathways to shape the bacterial replicative niche.

UNASSIGNED: Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In this study, we share our decade-long clinical experience with acute Q fever, highlighting the challenges that clinicians encounter from making an initial diagnosis and performing risk stratification to determining the appropriate prophylaxis regimen and duration.
UNASSIGNED: We retrieved records of adult Mayo Clinic patients (≥18 years) with positive Coxiella burnetii serology results between 1 January 2012 and 31 March 2022. Patients with Q fever anti-phase II immunoglobulin G ≥1:256 by indirect immunofluorescence were further analyzed.
UNASSIGNED: Thirty-one patients were included. Their median age was 58 years (IQR, 50-64), and the majority were men (84%). Acute hepatitis (29%), flu-like illness (25.8%), and pneumonia (16%) were the most common presentations. Thirteen patients (42%) received antibiotic prophylaxis to prevent disease progression, with significant variation in the indications and duration across physicians. The combination of doxycycline and hydroxychloroquine was the preferred regimen. Prophylaxis was administered for a median 333 days (IQR, 168-414). Four patients (13%) progressed to Q fever native valve infective endocarditis, with elevated anticardiolipin immunoglobulin G levels being the sole risk factor in 2 cases. The small sample size precluded drawing conclusions on the impact of prophylaxis in preventing disease progression.
UNASSIGNED: Management of acute Q fever is complicated by the lack of comprehensive clinical guidelines leading to varied clinical practices. There is a critical need for randomized trials to establish robust evidence-based protocols for management.

Q fever is a zoonotic infection caused by Coxiella burnetii. In rare cases, it can lead to vascular complications, including infected aneurysms. Successful treatment involves surgery and antibiotics, but there is no established consensus or clear recommendation for the choice of material graft. We report a case of abdominal aortic aneurysm infected by C. burnetii treated by open surgery with complete resection of the aneurysm and homemade bovine pericardial bifurcated graft reconstruction and long-term antibiotherapy using doxycycline. One year postoperatively, the patient had no sign of persistent infection or vascular complication. Moreover, C. burnetii immunoglobulins titers decreased 6 months postoperatively.

Coxiella burnetii is the worldwide zoonotic infectious agent for Q fever in humans and animals. Farm animals are the main reservoirs of C. burnetii infection, which is mainly transmitted via tick bites. In humans, oral, percutaneous, and respiratory routes are the primary sources of infection transmission. The clinical signs vary from flu-like symptoms to endocarditis for humans\' acute and chronic Q fever. While it is usually asymptomatic in livestock, abortion, stillbirth, infertility, mastitis, and endometritis are its clinical consequences. Infected farm animals shed C. burnetii in birth products, milk, feces, vaginal mucus, and urine. Milk is an important source of infection among foods of animal origin. This study aimed to determine the prevalence and molecular characterization of C. burnetii in milk samples of dairy animals from two districts in Punjab, Pakistan, as it has not been reported there so far. Using a convenience sampling approach, the current study included 304 individual milk samples from different herds of cattle, buffalo, goats, and sheep present on 39 farms in 11 villages in the districts of Kasur and Lahore. PCR targeting the IS1111 gene sequence was used for its detection. Coxiella burnetii DNA was present in 19 of the 304 (6.3%) samples. The distribution was 7.2% and 5.2% in districts Kasur and Lahore, respectively. The results showed the distribution in ruminants as 3.4% in buffalo, 5.6% in cattle, 6.7% in goats, and 10.6% in sheep. From the univariable analysis, the clinical signs of infection i.e. mastitis and abortion were analyzed for the prevalence of Coxiella burnetii. The obtained sequences were identical to the previously reported sequence of a local strain in district Lahore, Sahiwal and Attock. These findings demonstrated that the prevalence of C. burnetii in raw milk samples deserves more attention from the health care system and veterinary organizations in Kasur and Lahore of Punjab, Pakistan. Future studies should include different districts and human populations, especially professionals working with animals, to estimate the prevalence of C. burnetii.

UNASSIGNED: Coxiella burnetii is a gram-negative obligate intracellular bacterium and a zoonotic pathogen that causes human Q fever. The lack of effective antibiotics and a licensed vaccine for Coxiella in the U.S. warrants further research into Coxiella pathogenesis. Within the host cells, Coxiella replicates in an acidic phagolysosome-like vacuole termed Coxiella-containing vacuole (CCV). Previously, we have shown that the CCV pH is critical for Coxiella survival and that the Coxiella Type 4B secretion system regulates CCV pH by inhibiting the host endosomal maturation pathway. However, the trafficking pattern of the \'immature\' endosomes in Coxiella- infected cells remained unclear.
UNASSIGNED: We transfected HeLa cells with GFP-tagged Rab proteins and subsequently infected them with mCherry-Coxiella to visualize Rab protein localization. Infected cells were immunostained with anti-Rab antibodies to confirm the Rab localization to the CCV, to quantitate Rab11a and Rab35- positive CCVs, and to quantitate total recycling endosome content of infected cells. A dual-hit siRNA mediated knockdown combined with either immunofluorescent assay or an agarose-based colony-forming unit assay were used to measure the effects of Rab11a and Rab35 knockdown on CCV area and Coxiella intracellular growth.
UNASSIGNED: The CCV localization screen with host Rab proteins revealed that recycling endosome-associated proteins Rab11a and Rab35 localize to the CCV during infection, suggesting that CCV interacts with host recycling endosomes during maturation. Interestingly, only a subset of CCVs were Rab11a or Rab35-positive at any given time point. Quantitation of Rab11a/Rab35-positive CCVs revealed that while Rab11a interacts with the CCV more at 3 dpi, Rab35 is significantly more prevalent at CCVs at 6 dpi, suggesting that the CCV preferentially interacts with Rab11a and Rab35 depending on the stage of infection. Furthermore, we observed a significant increase in Rab11a and Rab35 fluorescent intensity in Coxiella-infected cells compared to mock, suggesting that Coxiella increases the recycling endosome content in infected cells. Finally, siRNA-mediated knockdown of Rab11a and Rab35 resulted in significantly smaller CCVs and reduced Coxiella intracellular growth, suggesting that recycling endosomal Rab proteins are essential for CCV expansion and bacterial multiplication.
UNASSIGNED: Our data, for the first time, show that the CCV dynamically interacts with host recycling endosomes for Coxiella intracellular survival and potentially uncovers novel host cell factors essential for Coxiella pathogenesis.

Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp., Anaplasma phagocytophilum, and Ehrlichia spp. This study aims to investigate the distribution and prevalence of tick-borne pathogens in southwestern Korea from 2019 to 2022. A total of 13,280 ticks were collected during the study period, with H. longicornis accounting for 86.1% of the collected ticks. H. flava, I. nipponensis and A. testudinarium comprised 9.4%, 3.6%, and 0.8% of the ticks, respectively. Among 983 pools tested, Rickettsia spp. (216 pools, 1.6% MIR) were the most prevalent pathogens across all tick species, with R. japonica and R. monacensis frequently detected in I. nipponensis and Haemaphysalis spp., respectively. Borrelia spp. (28 pools, 0.2% MIR) were predominantly detected in I. nipponensis (27 pools, 13.8% MIR, P < 0.001). Co-infections, mainly involving Rickettsia monacensis and Borrelia afzelii, were detected in I. nipponensis. Notably, this study identified R. monacensis for the first time in A. testudinarium in South Korea. These findings offer valuable insights into the tick population and associated pathogens in the region, underscoring the importance of tick-borne disease surveillance and prevention measures.

UNASSIGNED: Query fever (Q fever) is an endemic zoonotic disease and ruminants are considered to be the primary source of infection in humans. It is caused by Coxiella burnetii which is an obligate intracellular bacterial pathogen with a worldwide distribution. This study estimated the prevalence of Q fever in livestock with a history of abortion in Makkah Province, Saudi Arabia.
UNASSIGNED: Sera from 341 camels, 326 sheep, and 121 goats of either sex from various locations (Makkah, Jeddah, AL-Taif, AL-Qunfudah, AL-Laith, and AL-Kamil) were examined using a Q fever indirect enzyme-linked immunosorbent assay.
UNASSIGNED: Among the 788 serum samples, 356 animals had anti-Coxiella burnetii immunoglobulin G antibodies with an overall seroprevalence of 45.4%. Significant differences were observed in seroprevalence between species and locations. Camels had the highest percentage of Q fever-positive sera, with a prevalence of 50.4%, followed by goats (44.6%) and sheep (36.8%), with a high significant difference between animals (p = 0.000). The prevalence was significantly higher in Makkah (65.4%) than in Jeddah (28.8%).
UNASSIGNED: C. burnetii infection is prevalent in agricultural animals, especially camels maintained at livestock farms in Makkah province. Therefore, these animals considered as the main source of Q fever infections in Saudi Arabia, which is also a reason for the abortion in these animals. Therefore, there is an urgent need for further studies on Q fever infection with interventional approaches for prevention and control.

Q fever is a disease caused by Coxiella burnetii that affects many animal species and humans. In ruminants, the disease is responsible for several reproductive disorders (such as abortions, stillbirths, premature births, weak offspring, retained foetal membranes and infertility). An inactivated vaccine based on a phase I antigen of C. burnetii is available for cattle, goats and sheep. This review aims to summarise the scientific literature regarding the efficacy and safety of this vaccine to control the infection in these three domestic ruminant species. Forty-five publications and one experimental veterinary thesis reporting on experimental studies, case reports, mathematical modelling and intervention studies were selected according to the PRISMA guidelines. Although some studies lack control groups or statistical analyses, for all three species, published data show that vaccination often results in a reduction in abortions and an improvement in reproductive performance in comparison with absence of vaccination. There is also evidence, including in infected herds and animals, that vaccination is associated with a reduction in bacterial shedding, both in intensity and duration in comparison with absence of vaccination. For these reasons, in case of human outbreaks, vaccination is one of the pillars of control measures. Vaccination is generally well tolerated, despite the rare occurrence of mild, transient side-effects, such as hyperthermia and reduction in milk yield.