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Concept: Coxiella burnetii


BACKGROUND: The tick Rhipicephalus sanguineus is the species with the largest worldwide distribution and is proven to be involved in the transmission of pathogens such as Babesia canis, Ehrlichia canis, Coxiella burnetii, Rickettsia ricketsii, Rickettsia conorii, among others. Studies have demonstrated acquisition of resistance to some of the active principles used in commercial formulations of acaricides. Tagetes patula (Asteraceae) is a plant with highlighted economic and commercial importance due to the production of secondary metabolites with insecticide and acaricide potential, mainly flavonoids, thiophenes and terpenes. METHODS: The in vitro acaricide action of the ethanolic 70% extract from aerial parts of T. patula, obtained by percolation, was evaluated against larvae and engorged adult females of Rhipicephalus sanguineus by immersion test for 5 minutes. The chemical characterization of this extract was done by liquid chromatography coupled with mass spectrometry (LC-MS), using direct injection of sample. RESULTS: Despite T. patula not proving lethal to adults in any of the concentrations tested, at 50.0 mg/mL oviposition rate decreased by 21.5% and eliminated 99.78% of the larvae. Also it was determined that the best results were obtained with 5 minutes of immersion. From the chromatographic analysis twelve O-glycosylated flavonoids were identified. CONCLUSIONS: This is the first report on the acaricidal activity of T. patula extract against Rh. sanguineus. If we consider the application of the product in the environment, we could completely eliminate the larval stage of development of the ixodid Rh. sanguineus.

Concepts: Larva, Coxiella burnetii, Q fever, Chromatography, Analytical chemistry, Rhipicephalus sanguineus, Asteraceae, Tagetes patula


Ticks carry and transmit a remarkable array of pathogens including bacteria, protozoa and viruses, which may be of veterinary and/or of medical significance. With little to no information regarding the presence of tick-borne zoonotic pathogens or their known vectors in southern Africa, the aim of our study was to screen for Anaplasma phagocytophilum, Borrelia burgdorferi, Coxiella burnetii, Rickettsia species and Ehrlichia ruminantium in ticks collected and identified from ruminants in the Eastern Cape, Free State, KwaZulu-Natal and Mpumalanga Provinces of South Africa. The most abundant tick species identified in this study were Rhipicephalus evertsi evertsi (40%), Rhipicephalus species (35%), Amblyomma hebraeum (10%) and Rhipicephalus decoloratus (14%). A total of 1,634 ticks were collected. DNA was extracted, and samples were subjected to PCR amplification and sequencing. The overall infection rates of ticks with the target pathogens in the four Provinces were as follows: A. phagocytophilum, 7%; C. burnetii, 7%; E. ruminantium, 28%; and Rickettsia spp., 27%. The presence of B. burgdorferi could not be confirmed. The findings of this study show that zoonotic pathogens are present in ticks in the studied South African provinces. This information will aid in the epidemiology of tick-borne zoonotic diseases in the country as well as in raising awareness about such diseases in the veterinary, medical and tourism sectors, as they may be the most affected.

Concepts: Bacteria, Africa, Coxiella burnetii, Q fever, Lyme disease, South Africa, Borrelia burgdorferi, Eastern Cape


Background. In early 2009, a dairy-goat annex care farm in South Limburg, the Netherlands, reported 220 Coxiella burnetii-related abortions in 450 pregnant goats. These preceded human cases and occurred in a region that was Q-fever free before 2009, providing a unique quasi-experimental setting for investigating regional transmission patterns associated with a Q-fever point source. Methods. Index-farm residents/employees, visitors, and their household contacts were traced and screened for C. burnetii. Distribution of community cases was analysed using a geographic information system. True incidence, including undetected infections, was estimated regionwide by seroprevalence in a pre- versus postoutbreak sample, and near-farm by immunoglobulin M seroprevalence in a municipal population sample. Environmental bacterial load was repeatedly measured in surface and aerosol samples. Results. Serological attack rate was 92% (24/26) in index-farm residents/employees, 56% (28/50) in visitors, and 50% (7/14) in household contacts, and the clinical attack rate (ie, the proportion of persons seropositive for acute infection who also had clinical illness) was ≥80%. Notified symptomatic community cases (n = 253) were scattered downwind from the index farm, following a significant exposure-response gradient. Observed incidence ranged from 6.3% (0-1 km) to 0.1% (4-5 km), and remained high beyond. True incidence of infections was estimated at 2.9% regionwide, extrapolating to 8941 infections; estimated near-farm incidence was 12%. Coxiella burnetii load was high on-farm (2009), and lower off-farm (2009-2010). Conclusions. Linking a single dairy-goat farm to a human Q-fever cluster, we show widespread transmission, massive numbers of undetected infections, and high attack rates on- and off-farm, even beyond a 5-km high-risk zone. Our investigation may serve as an essential case study for risk assessment in public health and related fields such as bioterrorism response and preparedness.

Concepts: Immune system, Epidemiology, Coxiella burnetii, Q fever, Geographic information system, Proteobacteria, Coxiella, Legionellales


The obligate intracellular pathogen Coxiella burnetii replicates in a large phagolysosomal-like vacuole. Currently, both host and bacterial factors required for creating this replicative parasitophorous C. burnetii-containing vacuole (PV) are poorly defined. Here, we assessed the contributions of the most abundant proteins of the lysosomal membrane, LAMP-1 and LAMP-2, to the establishment and maintenance of the PV. Whereas these proteins were not critical for uptake of C. burnetii, they influenced the intracellular replication of C. burnetii. In LAMP-½ double-deficient fibroblasts as well as in LAMP-½ knock-down cells C. burnetii establishes a significantly smaller, yet faster maturing vacuole, which harbored more bacteria. The accelerated maturation of PVs in LAMP double-deficient fibroblasts, which was partially or fully reversed by ectopic expression of LAMP-1 or LAMP-2, respectively, was characterized by an increased fusion rate with endosomes, lysosomes and bead-containing phagosomes, but not by different fusion kinetics with autophagy vesicles. These findings establish that LAMP proteins are critical for the maturation delay of PVs. Unexpectedly, neither the creation of the spacious vacuole nor the delay in maturation was found to be prerequisites for the intracellular replication of C. burnetii.

Concepts: Cell, Bacteria, Cell membrane, Organelle, Coxiella burnetii, Q fever, Proteobacteria, Lysosome


Q fever is a highly infectious disease with a worldwide distribution. Its causative agent, the intracellular bacterium Coxiella burnetii, infects a variety of vertebrate species, including humans. Its evolutionary origin remains almost entirely unknown and uncertainty persists regarding the identity and lifestyle of its ancestors. A few tick species were recently found to harbor maternally-inherited Coxiella-like organisms engaged in symbiotic interactions, but their relationships to the Q fever pathogen remain unclear. Here, we extensively sampled ticks, identifying new and atypical Coxiella strains from 40 of 58 examined species, and used this data to infer the evolutionary processes leading to the emergence of C. burnetii. Phylogenetic analyses of multi-locus typing and whole-genome sequencing data revealed that Coxiella-like organisms represent an ancient and monophyletic group allied to ticks. Remarkably, all known C. burnetii strains originate within this group and are the descendants of a Coxiella-like progenitor hosted by ticks. Using both colony-reared and field-collected gravid females, we further establish the presence of highly efficient maternal transmission of these Coxiella-like organisms in four examined tick species, a pattern coherent with an endosymbiotic lifestyle. Our laboratory culture assays also showed that these Coxiella-like organisms were not amenable to culture in the vertebrate cell environment, suggesting different metabolic requirements compared to C. burnetii. Altogether, this corpus of data demonstrates that C. burnetii recently evolved from an inherited symbiont of ticks which succeeded in infecting vertebrate cells, likely by the acquisition of novel virulence factors.

Concepts: Infectious disease, Bacteria, Evolution, Infection, Coxiella burnetii, Q fever, Symbiosis, Phylogenetics


Evidence suggests that the intracellular bacterial pathogen Coxiella burnetii (which causes Q fever) is widespread, with a near global distribution. While there has been increasing attention to Q fever epidemiology in high-income settings, a recent systematic review highlighted significant gaps in our understanding of the prevalence, spatial distribution and risk factors for Q fever infection across Africa. This research aimed to provide a One Health assessment of Q fever epidemiology in parts of Western and Nyanza Provinces, Western Kenya, in cattle and humans. A cross-sectional survey was conducted: serum samples from 2049 humans and 955 cattle in 416 homesteads were analysed for C. burnetii antibodies. Questionnaires covering demographic, socio-economic and husbandry information were also administered. These data were linked to environmental datasets based on geographical locations (e.g., land cover). Correlation and spatial-cross correlation analyses were applied to assess the potential link between cattle and human seroprevalence. Multilevel regression analysis was used to assess the relationships between a range of socio-economic, demographic and environmental factors and sero-positivity in both humans and animals. The overall sero-prevalence of C. burnetii was 2.5% in humans and 10.5% in cattle, but we found no evidence of correlation between cattle and human seroprevalence either within households, or when incorporating spatial proximity to other households in the survey. Multilevel modelling indicated the importance of several factors for exposure to the organism. Cattle obtained from market (as opposed to those bred in their homestead) and those residing in areas with lower precipitation levels had the highest sero-prevalence. For humans, the youngest age group had the highest odds of seropositivity, variations were observed between ethnic groups, and frequent livestock contact (specifically grazing and dealing with abortion material) was also a risk factor. These results illustrate endemicity of C. burnetii in western Kenya, although prevalence is relatively low. The analysis indicates that while environmental factors may play a role in cattle exposure patterns, human exposure patterns are likely to be driven more strongly by livestock contacts. The implication of livestock markets in cattle exposure risks suggests these may be a suitable target for interventions.

Concepts: Epidemiology, Coxiella burnetii, Q fever, Cross-sectional study, Risk, Livestock, Coxiella, Legionellales


In a previous study of a Q fever outbreak in Birmingham, our group identified a non-infective complex of Coxiella burnetii (C.b.) antigens able to survive in the host and provoked aberrant humoral and cell-mediated immunity responses. The study led to recognition of a possible pathogenic link between C.b. infection and subsequent long-term post Q fever fatigue syndrome (QFS). This report presents an unusually severe case of C.b. antigen and DNA detection in post-mortem specimens from a patient with QFS.

Concepts: Immune system, Antibody, Bacteria, Virus, Coxiella burnetii, Q fever, Humoral immunity, Cell-mediated immunity


Bacteria can induce human lymphomas, while lymphoproliferative disorders have been described in patients with Q fever. We observed a lymphoma in a patient with Q fever that prompted us to investigate the association between the two diseases. We screened 1,468 consecutive patients of the 2004-2014 French National Referral Center for Q fever database. The standardized incidence ratios (SIR) of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were calculated comparatively to the 2012 Francim registry. The presence of Coxiella burnetii was tested using immunofluorescence and fluorescence in situ hybridization using a specific 16S rRNA probe and genomic DNA probe. Seven patients (0.48%) presented mature B-cell lymphoma consisting of 6 DLBCL and 1 FL. An excess risk of DLBCL and FL was found in Q fever patients compared to the general population (SIR [95% confidence interval], 25.4 [11.4-56.4] and 6.7 [0.9-47.9], respectively). C. burnetii was detected in CD68(+) macrophages within both lymphoma and lymphadenitis tissues but localization in CD123(+) plasmacytoid dendritic cells (pDCs) was found only in lymphoma tissues. Q fever patients with persistent focalized infection were found more at risk of lymphoma (hazard ratio 9.35 [1.10-79.4]). Interleukin-10 overproduction (P = .0003) was found in patients developing lymphoma. These results suggest that C. burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma, possibly by the infection of pDCs and IL10 overproduction. Screening for early lymphoma diagnosis should be considered in the management of patients with Q fever, especially those with persistent focalized infections.

Concepts: HIV, Coxiella burnetii, Q fever, Types of cancer, Lymphoma, Diffuse large B cell lymphoma, Non-Hodgkin lymphoma, Follicular lymphoma


We evaluated culture-negative, community-acquired endocarditis by using indirect immunofluorescent assays and molecular analyses for Bartonella spp. and Coxiella burnetii and found a prevalence of 19.6% and 7.8%, respectively. Our findings reinforce the need to study these organisms in patients with culture-negative, community-acquired endocarditis, especially B. henselae in cat owners.

Concepts: Coxiella burnetii, Q fever, Bartonella, Bartonella henselae, Coxiella


Coxiella burnetii causes Q fever in humans and Coxiellosis in animals; symptoms range from general malaise to fever, pneumonia, endocarditis and death. Livestock are a significant source of human infection as they shed C. burnetii cells in birth tissues, milk, urine and feces. Although prevalence of C. burnetii is high, few Q fever cases are reported in the U.S. and we have a limited understanding of their connectedness due to difficulties in genotyping. Here, we develop canonical SNP genotyping assays to evaluate spatial and temporal relationships among C. burnetii environmental samples and compare them across studies. Given the genotypic diversity of historical collections, we hypothesized that the current enzootic of Coxiellosis is caused by multiple circulating genotypes. We collected A) 23 milk samples from a single bovine herd, B) 134 commercial bovine and caprine milk samples from across the U.S., and C) 400 bovine and caprine samples from six milk processing plants over three years.

Concepts: DNA, Genetics, Coxiella burnetii, Q fever, Cattle, Malaise, Coxiella, SNP genotyping