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Sample records for agent coxiella burnetii

  1. Coxiella burnetii pneumonia.

    PubMed

    Marrie, T J

    2003-04-01

    This report reviews the pulmonary and extrapulmonary manifestation of infections due to Coxiella burnetii. Q fever, a zoonosis, is due to infection with C. burnetii. This spore-forming microorganism is a small gram-negative coccobacillus that is an obligate intracellular parasite. The most common animal reservoirs are goats, cattle, sheep, cats, and occasionally dogs. The organism reaches high concentrations in the placenta of infected animals. Aerosolisation occurs at the time of parturition and infection follows inhalation of this aerosol. There are three distinct clinical syndromes of the acute form of the illness: nonspecific febrile illness, pneumonia, and hepatitis. The chronic form of Q fever is almost always endocarditis, but occasionally it is manifest as hepatitis, osteomyelitis or endovascular infection. The pneumonic form of the illness can range from very mild-to-severe pneumonia requiring assisted ventilation. Multiple round opacities are a common finding on chest radiography. Treatment with doxycycline or a fluoroquinolone is preferred. Susceptibility to macrolides is variable. In conclusion, Coxiella burnetii pneumonia should be considered when there is a suitable exposure history and when outbreaks of a pneumonic illness are being investigated. PMID:12762362

  2. The survival of Coxiella burnetii in soils

    NASA Astrophysics Data System (ADS)

    Evstigneeva, A. S.; Ul'Yanova, T. Yu.; Tarasevich, I. V.

    2007-05-01

    Coxiella burnetii is a pathogen of Q-fever—a widespread zoonosis. The effective adaptation of C. burnetii to intracellular existence is in contrast with its ability to survive in the environment outside the host cells and its resistance to chemical and physical agents. Its mechanism of survival remains unknown. However, its survival appears to be related to the developmental cycle of the microorganism itself, i.e., to the formation of its dormant forms. The survival of Coxiella burnetii was studied for the first time. The pathogenic microorganism was inoculated into different types of soil and cultivated under different temperatures. The survival of the pathogen was verified using a model with laboratory animals (mice). Viable C. burnetii were found in the soil even 20 days after their inoculation. The relationship between the organic carbon content in the soils and the survival of C. burnetii was revealed. Thus, the results obtained were the first to demonstrate that the soil may serve as a reservoir for the preservation and further spreading of the Q-fever pathogen in the environment, on the one hand, and reduce the risk of epidemics, on the other.

  3. Rapid Typing of Coxiella burnetii

    PubMed Central

    Georgia, Shalamar M.; Kachur, Sergey; Birdsell, Dawn N.; Hilsabeck, Remy; Gates, Lauren T.; Samuel, James E.; Heinzen, Robert A.; Kersh, Gilbert J.; Keim, Paul; Massung, Robert F.; Pearson, Talima

    2011-01-01

    Coxiella burnetii has the potential to cause serious disease and is highly prevalent in the environment. Despite this, epidemiological data are sparse and isolate collections are typically small, rare, and difficult to share among laboratories as this pathogen is governed by select agent rules and fastidious to culture. With the advent of whole genome sequencing, some of this knowledge gap has been overcome by the development of genotyping schemes, however many of these methods are cumbersome and not readily transferable between institutions. As comparisons of the few existing collections can dramatically increase our knowledge of the evolution and phylogeography of the species, we aimed to facilitate such comparisons by extracting SNP signatures from past genotyping efforts and then incorporated these signatures into assays that quickly and easily define genotypes and phylogenetic groups. We found 91 polymorphisms (SNPs and indels) among multispacer sequence typing (MST) loci and designed 14 SNP-based assays that could be used to type samples based on previously established phylogenetic groups. These assays are rapid, inexpensive, real-time PCR assays whose results are unambiguous. Data from these assays allowed us to assign 43 previously untyped isolates to established genotypes and genomic groups. Furthermore, genotyping results based on assays from the signatures provided here are easily transferred between institutions, readily interpreted phylogenetically and simple to adapt to new genotyping technologies. PMID:22073151

  4. Genetic Diversity of the Q Fever Agent, Coxiella burnetii, Assessed by Microarray-Based Whole-Genome Comparisons†

    PubMed Central

    Beare, Paul A.; Samuel, James E.; Howe, Dale; Virtaneva, Kimmo; Porcella, Stephen F.; Heinzen, Robert A.

    2006-01-01

    Coxiella burnetii, a gram-negative obligate intracellular bacterium, causes human Q fever and is considered a potential agent of bioterrorism. Distinct genomic groups of C. burnetii are revealed by restriction fragment-length polymorphisms (RFLP). Here we comprehensively define the genetic diversity of C. burnetii by hybridizing the genomes of 20 RFLP-grouped and four ungrouped isolates from disparate sources to a high-density custom Affymetrix GeneChip containing all open reading frames (ORFs) of the Nine Mile phase I (NMI) reference isolate. We confirmed the relatedness of RFLP-grouped isolates and showed that two ungrouped isolates represent distinct genomic groups. Isolates contained up to 20 genomic polymorphisms consisting of 1 to 18 ORFs each. These were mostly complete ORF deletions, although partial deletions, point mutations, and insertions were also identified. A total of 139 chromosomal and plasmid ORFs were polymorphic among all C. burnetii isolates, representing ca. 7% of the NMI coding capacity. Approximately 67% of all deleted ORFs were hypothetical, while 9% were annotated in NMI as nonfunctional (e.g., frameshifted). The remaining deleted ORFs were associated with diverse cellular functions. The only deletions associated with isogenic NMI variants of attenuated virulence were previously described large deletions containing genes involved in lipopolysaccharide (LPS) biosynthesis, suggesting that these polymorphisms alone are responsible for the lower virulence of these variants. Interestingly, a variant of the Australia QD isolate producing truncated LPS had no detectable deletions, indicating LPS truncation can occur via small genetic changes. Our results provide new insight into the genetic diversity and virulence potential of Coxiella species. PMID:16547017

  5. European Rabbits as Reservoir for Coxiella burnetii

    PubMed Central

    González-Barrio, David; Maio, Elisa; Vieira-Pinto, Madalena

    2015-01-01

    We studied the role of European rabbits (Oryctolagus cuniculus) as a reservoir for Coxiella burnetii in the Iberian region. High individual and population seroprevalences observed in wild and farmed rabbits, evidence of systemic infections, and vaginal shedding support the reservoir role of the European rabbit for C. burnetii. PMID:25988670

  6. Coxiella burnetii in wild-caught filth flies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coxiella burnetii, the agent of Q fever, is a pathogen of vertebrates. In domestic animals, Q fever can cause abortion and reduced fertility. Infections in humans can be debilitating but are rarely fatal. House flies are vectors of Q fever in the laboratory, but infections in field caught flies have...

  7. Mouse Model of Coxiella burnetii Aerosolization.

    PubMed

    Melenotte, Cléa; Lepidi, Hubert; Nappez, Claude; Bechah, Yassina; Audoly, Gilles; Terras, Jérôme; Raoult, Didier; Brégeon, Fabienne

    2016-07-01

    Coxiella burnetii is mainly transmitted by aerosols and is responsible for multiple-organ lesions. Animal models have shown C. burnetii pathogenicity, but long-term outcomes still need to be clarified. We used a whole-body aerosol inhalation exposure system to mimic the natural route of infection in immunocompetent (BALB/c) and severe combined immunodeficient (SCID) mice. After an initial lung inoculum of 10(4) C. burnetii cells/lung, the outcome, serological response, hematological disorders, and deep organ lesions were described up to 3 months postinfection. C. burnetii-specific PCR, anti-C. burnetii immunohistochemistry, and fluorescent in situ hybridization (FISH) targeting C. burnetii-specific 16S rRNA completed the detection of the bacterium in the tissues. In BALB/c mice, a thrombocytopenia and lymphopenia were first observed, prior to evidence of C. burnetii replication. In all SCID mouse organs, DNA copies increased to higher levels over time than in BALB/c ones. Clinical signs of discomfort appeared in SCID mice, so follow-up had to be shortened to 2 months in this group. At this stage, all animals presented bone, cervical, and heart lesions. The presence of C. burnetii could be attested in situ for all organs sampled using immunohistochemistry and FISH. This mouse model described C. burnetii Nine Mile strain spread using aerosolization in a way that corroborates the pathogenicity of Q fever described in humans and completes previously published data in mouse models. C. burnetii infection occurring after aerosolization in mice thus seems to be a useful tool to compare the pathogenicity of different strains of C. burnetii. PMID:27160294

  8. Genetics of Coxiella burnetii: on the path of specialization

    PubMed Central

    Minnick, Michael F; Raghavan, Rahul

    2014-01-01

    Coxiella burnetii is an extremely infectious, zoonotic agent that causes Q fever in humans. With the exception of New Zealand, the bacterium is distributed worldwide. Coxiella is classified as a select agent based on its past and potential use as a bioweapon and its threat to public health. Despite decades of research, we know relatively little regarding Coxiella’s molecular pathogenesis, and a vaccine is not widely available. This article briefly reviews the unusual genetics of C. burnetii; a pathogen that retains telltale genetic mementos collected over the course of its evolutionary path from a free-living bacterium to an obligate intracellular parasite of eukaryotic host cell phagosomes. Understanding why these genetic elements are maintained may help us better understand the biology of this fascinating pathogen. PMID:22082290

  9. Low seroprevalence of Coxiella burnetii in Boer goats in Missouri

    PubMed Central

    2014-01-01

    Background Goats are known reservoirs of Coxiella burnetii, the etiologic agent of Q fever. However, there has been very little research on the prevalence of C. burnetii exposure and risk in meat goats farmed in the US. Banked serum samples were secondarily tested for C. burnetii specific antibodies. Findings The animal and herd-level seroprevalence estimates for C. burnetii were 1.2% (3/249) and 4.2% (1/24) respectively. Within-herd seroprevalence ranged from 0% to 1.2%. Conclusions This study indicates that seroprevalence of C. burnetii in Boer goats raised in Missouri was low, but it does not preclude the existence of a higher level of infection in Missouri’s meat goat herds. This result is inconclusive because this study was disadvantaged by the small number of individual animal and herds tested, which compromised the statistical power of this study to detect a possible higher seroprevalence of C. burnetii in this population, if present. More research is warranted to corroborate the preliminary findings reported here in order to determine the public health significance C. burnetii infection risks associated with contemporary goat production systems in the US. PMID:24994554

  10. Proteomic comparison of phase I and II coxiella burnetii cells reveals potential virulence biomarkers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coxiella burnetii, a category B biological warfare agent, causes several worldwide outbreaks of zoonotic disease each year. In order to identify C. burnetii virulence factors, the virulent phase I and avirulent phase II variants of the Nine Mile RSA strains, were propagated in embryonated hen eggs ...

  11. Coxiella burnetii Shedding by Farmed Red Deer (Cervus elaphus).

    PubMed

    González-Barrio, D; Almería, S; Caro, M R; Salinas, J; Ortiz, J A; Gortázar, C; Ruiz-Fons, F

    2015-10-01

    Wildlife and notably deer species--due to the increasing relevance of deer farming worldwide--may contribute to the maintenance of Coxiella burnetii, the causal agent of Q fever. Currently, there are no precedents linking exposure to deer species with human Q fever cases. However, a human case of Q fever was recently diagnosed in a red deer (Cervus elaphus) farm, which led us to investigate whether deer could be a source for environmental contamination with C. burnetii and ascertain the implication of C. burnetii in reproductive failure in the farm. Blood serum and vaginal swabs were collected from hinds either experiencing or not reproductive failure and tested to detect the presence of antibodies and DNA, respectively, of C. burnetii, Chlamydia abortus, Neospora caninum and Toxoplasma gondii. Serology and PCR results suggest C. burnetii was the primary cause of the reproductive failure. We identified vaginal shedding of C. burnetii in hinds, confirming red deer as a source of Q fever zoonotic infection. PMID:24127840

  12. Seroprevalence of Coxiella burnetii in Australian dogs.

    PubMed

    Shapiro, A J; Norris, J M; Heller, J; Brown, G; Malik, R; Bosward, K L

    2016-09-01

    The role of dogs in the transmission of Coxiella burnetii to humans is uncertain, and extensive seroprevalence studies of dogs have not been previously conducted in Australia. This study determined C. burnetii exposure in four diverse canine subpopulations by adapting, verifying and comparing an indirect immunofluoresence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) used to detect anti-C. burnetii antibodies in humans. Canine serum samples (n = 1223) were tested with IFA from four subpopulations [breeding establishments; household pets; free-roaming dogs in Aboriginal communities; shelter dogs]. The proportions of seropositive dogs were as follows: breeding (7/309, 2.3%), household pets (10/328, 3%), Aboriginal communities (21/321, 6.5%) and shelters (5/265, 1.9%). Dogs from Aboriginal communities were 2.8 times (CI 1.5-5.1; P < 0.001) more likely to be seropositive than dogs from other populations. The ELISA was used on 86 of 1223 sera tested with IFA, and a Cohen's Kappa coefficient of 0.60 (CI 0.43-0.78) indicated good agreement between the two assays. This study has established that Australian dogs within all four subpopulations have been exposed to C. burnetii and that a higher seroprevalence was observed amongst free-roaming dogs associated with Aboriginal communities. As C. burnetii recrudesces during pregnancy and birth products contain the highest concentration of organism, individuals assisting at the time of parturition, those handling pups shortly after birth as well as those residing in the vicinity of whelping dogs are potentially at risk of developing Q fever. However, the identification of active antigen shed in excreta from seropositive dogs is required in order to accurately define and quantify the public health risk. PMID:26729351

  13. Genome sequence of Coxiella burnetii strain Namibia

    PubMed Central

    2014-01-01

    We present the whole genome sequence and annotation of the Coxiella burnetii strain Namibia. This strain was isolated from an aborting goat in 1991 in Windhoek, Namibia. The plasmid type QpRS was confirmed in our work. Further genomic typing placed the strain into a unique genomic group. The genome sequence is 2,101,438 bp long and contains 1,979 protein-coding and 51 RNA genes, including one rRNA operon. To overcome the poor yield from cell culture systems, an additional DNA enrichment with whole genome amplification (WGA) methods was applied. We describe a bioinformatics pipeline for improved genome assembly including several filters with a special focus on WGA characteristics. PMID:25593636

  14. Structural genomics for drug design against the pathogen Coxiella burnetii.

    PubMed

    Franklin, Matthew C; Cheung, Jonah; Rudolph, Michael J; Burshteyn, Fiana; Cassidy, Michael; Gary, Ebony; Hillerich, Brandan; Yao, Zhong-Ke; Carlier, Paul R; Totrov, Maxim; Love, James D

    2015-12-01

    Coxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively as other biological agents, and very few of its proteins have been structurally characterized. To address this situation, we undertook a study of critical metabolic enzymes in C. burnetii that have great potential as drug targets. We used high-throughput techniques to produce novel crystal structures of 48 of these proteins. We selected one protein, C. burnetii dihydrofolate reductase (CbDHFR), for additional work to demonstrate the value of these structures for structure-based drug design. This enzyme's structure reveals a feature in the substrate binding groove that is different between CbDHFR and human dihydrofolate reductase (hDHFR). We then identified a compound by in silico screening that exploits this binding groove difference, and demonstrated that this compound inhibits CbDHFR with at least 25-fold greater potency than hDHFR. Since this binding groove feature is shared by many other prokaryotes, the compound identified could form the basis of a novel antibacterial agent effective against a broad spectrum of pathogenic bacteria. PMID:26033498

  15. The Intervening Sequence of Coxiella burnetii: Characterization and Evolution

    PubMed Central

    Warrier, Indu; Walter, Mathias C.; Frangoulidis, Dimitrios; Raghavan, Rahul; Hicks, Linda D.; Minnick, Michael F.

    2016-01-01

    The intervening sequence (IVS) of Coxiella burnetii, the agent of Q fever, is a 428-nt selfish genetic element located in helix 45 of the precursor 23S rRNA. The IVS element, in turn, contains an ORF that encodes a hypothetical ribosomal S23 protein (S23p). Although S23p can be synthesized in vitro in the presence of an engineered E. coli promoter and ribosome binding site, results suggest that the protein is not synthesized in vivo. In spite of a high degree of IVS conservation among different strains of C. burnetii, the region immediately upstream of the S23p start codon is prone to change, and the S23p-encoding ORF is evidently undergoing reductive evolution. We determined that IVS excision from 23S rRNA was mediated by RNase III, and IVS RNA was rapidly degraded, thereafter. Levels of the resulting 23S rRNA fragments that flank the IVS, F1 (~1.2 kb) and F2 (~1.7 kb), were quantified over C. burnetii's logarithmic growth phase (1–5 d). Results showed that 23S F1 quantities were consistently higher than those of F2 and 16S rRNA. The disparity between levels of the two 23S rRNA fragments following excision of IVS is an interesting phenomenon of unknown significance. Based upon phylogenetic analyses, IVS was acquired through horizontal transfer after C. burnetii's divergence from an ancestral bacterium and has been subsequently maintained by vertical transfer. The widespread occurrence, maintenance and conservation of the IVS in C. burnetii imply that it plays an adaptive role or has a neutral effect on fitness. PMID:27595093

  16. The Intervening Sequence of Coxiella burnetii: Characterization and Evolution.

    PubMed

    Warrier, Indu; Walter, Mathias C; Frangoulidis, Dimitrios; Raghavan, Rahul; Hicks, Linda D; Minnick, Michael F

    2016-01-01

    The intervening sequence (IVS) of Coxiella burnetii, the agent of Q fever, is a 428-nt selfish genetic element located in helix 45 of the precursor 23S rRNA. The IVS element, in turn, contains an ORF that encodes a hypothetical ribosomal S23 protein (S23p). Although S23p can be synthesized in vitro in the presence of an engineered E. coli promoter and ribosome binding site, results suggest that the protein is not synthesized in vivo. In spite of a high degree of IVS conservation among different strains of C. burnetii, the region immediately upstream of the S23p start codon is prone to change, and the S23p-encoding ORF is evidently undergoing reductive evolution. We determined that IVS excision from 23S rRNA was mediated by RNase III, and IVS RNA was rapidly degraded, thereafter. Levels of the resulting 23S rRNA fragments that flank the IVS, F1 (~1.2 kb) and F2 (~1.7 kb), were quantified over C. burnetii's logarithmic growth phase (1-5 d). Results showed that 23S F1 quantities were consistently higher than those of F2 and 16S rRNA. The disparity between levels of the two 23S rRNA fragments following excision of IVS is an interesting phenomenon of unknown significance. Based upon phylogenetic analyses, IVS was acquired through horizontal transfer after C. burnetii's divergence from an ancestral bacterium and has been subsequently maintained by vertical transfer. The widespread occurrence, maintenance and conservation of the IVS in C. burnetii imply that it plays an adaptive role or has a neutral effect on fitness. PMID:27595093

  17. Coxiella burnetii Infection in Hemodialysis and Other Vascular Grafts

    PubMed Central

    González-Del Vecchio, Marcela; Vena, Antonio; Valerio, Maricela; Marin, Mercedes; Verde, Eduardo; Muñóz, Patricia; Bouza, Emilio

    2014-01-01

    Abstract Prosthetic arteriovenous (AV) graft infection is the principal cause of morbidity related to chronic hemodialysis AV graft fistula. Coxiella burnetii is a known pathogen that causes fever, pneumonia, and intravascular infections with the limitation of negative cultures. Herein, we report the first case of a patient who presented to the emergency department of our hospital with a prosthetic hemodialysis AV graft infection due to Coxiella burnetii. We also performed a literature search with PubMed to identify studies reporting cases of Coxiella burnetii vascular graft infection. Overall, we reviewed 15 cases of vascular graft infection, including ours. We found a high prevalence of male patients (87%); mean age ± standard deviation (SD) of the entire population was 60.4 ± 9.6 years. The dacron infrarenal aortic and the aortobifemoral bypass were the most common involved grafts. The early diagnosis of infection due to Coxiella burnetii was done by serology or with polymerase chain reaction (PCR), in 12 and 3 cases, respectively. All patients underwent partial or complete resection of the infected grafts; the most common antibiotic treatment for this entity was doxycycline and hydroxycloroquine. Although this is a relatively rare disease, Coxiella burnetii should be included in the differential diagnosis of all patients who present with infection of an endovascular graft of any nature with an inconclusive etiologic diagnosis. PMID:25500706

  18. Animal Models of Q Fever (Coxiella burnetii)

    PubMed Central

    Bewley, Kevin R

    2013-01-01

    Q fever, caused by the pathogen Coxiella burnetii, is an acute disease that can progress to become a serious chronic illness. The organism leads an obligate, intracellular lifecycle, during which it multiplies in the phagolytic compartments of the phagocytic cells of the immune system of its hosts. This characteristic makes study of the organism particularly difficult and is perhaps one of the reasons why, more than 70 y after its discovery, much remains unknown about the organism and its pathogenesis. A variety of animal species have been used to study both the acute and chronic forms of the disease. Although none of the models perfectly mimics the disease process in humans, each opens a window onto an important aspect of the pathology of the disease. We have learned that immunosuppression, overexpression of IL10, or physical damage to the heart muscle in mice and guinea pigs can induce disease that is similar to the chronic disease seen in humans, suggesting that this aspect of disease may eventually be fully understood. Models using species from mice to nonhuman primates have been used to evaluate and characterize vaccines to protect against the disease and may ultimately yield safer, less expensive vaccines. PMID:24326221

  19. Right on Q: genetics begin to unravel Coxiella burnetii host cell interactions.

    PubMed

    Larson, Charles L; Martinez, Eric; Beare, Paul A; Jeffrey, Brendan; Heinzen, Robert A; Bonazzi, Matteo

    2016-07-01

    Invasion of macrophages and replication within an acidic and degradative phagolysosome-like vacuole are essential for disease pathogenesis by Coxiella burnetii, the bacterial agent of human Q fever. Previous experimental constraints imposed by the obligate intracellular nature of Coxiella limited knowledge of pathogen strategies that promote infection. Fortunately, new genetic tools facilitated by axenic culture now allow allelic exchange and transposon mutagenesis approaches for virulence gene discovery. Phenotypic screens have illuminated the critical importance of Coxiella's type 4B secretion system in host cell subversion and discovered genes encoding translocated effector proteins that manipulate critical infection events. Here, we highlight the cellular microbiology and genetics of Coxiella and how recent technical advances now make Coxiella a model organism to study macrophage parasitism. PMID:27418426

  20. Detection and differentiation of coxiella burnetii in biological fluids

    SciTech Connect

    Frazier, Marvin E.; Mallavia, Louis P.; Baca, Oswald G.; Samuel, James E.

    1989-01-01

    Methods for detecting the presence of Coxiella burnetii in biological samples, as well as a method for differentiating strains of C. burnetii that are capable of causing acute disease from those strains capable of causing chronic disease are disclosed. The methods generally comprise treating cells contained within the biological sample to expose cellular DNA, and hybridizing the cellular DNA (specifically rickettsial DNA) with a C. burnetii-specific labeled DNA probe. Radioisotope and biotin labels are preferred, allowing detection through autoradiography and colorimetric assays, respectively.

  1. Detection and differentiation of coxiella burnetii in biological fluids

    SciTech Connect

    Frazier, Marvin E.; Mallavia, Louis P.; Samuel, James E.; Baca, Oswald G.

    1993-01-01

    Methods for detecting the presence of Coxiella burnetii in biological samples, as well as a method for differentiating strains of C. burnetii that are capable of causing acute disease from those strains capable of causing chronic disease are disclosed. The methods generally comprise treating cells contained within the biological sample to expose cellular DNA, and hybridizing the cellular DNA with a DNA probe containing DNA sequences that specifically hybridize with C. burnetii DNA of strains associated with the capacity to cause acute or chronic disease.

  2. Coxiella burnetii in Central Italy: Novel Genotypes Are Circulating in Cattle and Goats

    PubMed Central

    Di Domenico, Marco; Curini, Valentina; De Massis, Fabrizio; Di Provvido, Andrea; Scacchia, Massimo

    2014-01-01

    Abstract Genotyping of bacteria is critical for diagnosis, treatment, and epidemiological surveillance. Coxiella burnetii, the etiological agent of Q fever, has been recognized to have a potential for bioterrorism purposes. Because few serosurveys have been conducted in Italy, there is still limited information about the distribution of this pathogen in natural conditions. In this paper, we describe the genotyping of C. burnetii strains by multispacer sequence typing (MST) detected in cattle and goat farms in the Abruzzi region of Italy. Biological samples (milk, aborted fetus) positive for C. burnetii DNA were sequenced in the spacer regions and compared with those already publicly available (http://ifr48.timone.univ-mrs.fr/MST_Coxiella/mst/group_detail). The MST profile of C. burnetii detected in milk samples demonstrated the presence of a new allele, whereas the C. burnetii spacer sequences from fetus and milk goat samples displayed a new allelic combination. The results suggest the circulation of novel genotypes of C. burnetii in Italy. PMID:25325314

  3. Activation of Protein Tyrosine Kinases by Coxiella burnetii: Role in Actin Cytoskeleton Reorganization and Bacterial Phagocytosis

    PubMed Central

    Meconi, Sonia; Capo, Christian; Remacle-Bonnet, Maryse; Pommier, Gilbert; Raoult, Didier; Mege, Jean-Louis

    2001-01-01

    Coxiella burnetii, the agent of Q fever, is an obligate intracellular microorganism that grows in monocytes/macrophages. The internalization of virulent organisms by monocytes is lower than that of avirulent variants and is associated with actin cytoskeleton reorganization. We studied the activation of protein tyrosine kinases (PTKs) by C. burnetii in THP-1 monocytes. Virulent organisms induced early PTK activation and the tyrosine phosphorylation of several endogenous substrates, including Hck and Lyn, two Src-related kinases. PTK activation reflects C. burnetii virulence since avirulent variants were unable to stimulate PTK. We also investigated the role of PTK activation in C. burnetii-stimulated F-actin reorganization. Tyrosine-phosphorylated proteins were colocalized with F-actin inside cell protrusions induced by C. burnetii, and PTK activity was increased in Triton X-100-insoluble fractions. In addition, lavendustin A, a PTK inhibitor, and PP1, a Src kinase inhibitor, prevented C. burnetii-induced cell protrusions and F-actin reorganization. We finally assessed the role of PTK activation in bacterial phagocytosis. Pretreatment of THP-1 cells with lavendustin A and PP1 upregulated the uptake of virulent C. burnetii but had no effect on the phagocytosis of avirulent organisms. Thus, it is likely that PTK activation by C. burnetii negatively regulates bacterial uptake by interfering with cytoskeleton organization. PMID:11254615

  4. Coxiella burnetii infections in sheep or goats: an opinionated review.

    PubMed

    Van den Brom, R; van Engelen, E; Roest, H I J; van der Hoek, W; Vellema, P

    2015-12-14

    Q fever is an almost ubiquitous zoonosis caused by Coxiella burnetii, which is able to infect several animal species, as well as humans. Cattle, sheep and goats are the primary animal reservoirs. In small ruminants, infections are mostly without clinical symptoms, however, abortions and stillbirths can occur, mainly during late pregnancy. Shedding of C. burnetii occurs in feces, milk and, mostly, in placental membranes and birth fluids. During parturition of infected small ruminants, bacteria from birth products become aerosolized. Transmission to humans mainly happens through inhalation of contaminated aerosols. In the last decade, there have been several, sometimes large, human Q fever outbreaks related to sheep and goats. In this review, we describe C. burnetii infections in sheep and goats, including both advantages and disadvantages of available laboratory techniques, as pathology, different serological tests, PCR and culture to detect C. burnetii. Moreover, worldwide prevalences of C. burnetii in small ruminants are described, as well as possibilities for treatment and prevention. Prevention of shedding and subsequent environmental contamination by vaccination of sheep and goats with a phase I vaccine are possible. In addition, compulsory surveillance of C. burnetii in small ruminant farms raises awareness and hygiene measures in farms help to decrease exposure of people to the organism. Finally, this review challenges how to contain an infection of C. burnetii in small ruminants, bearing in mind possible consequences for the human population and probable interference of veterinary strategies, human risk perception and political considerations. PMID:26315774

  5. Coxiella burnetii Infection With Severe Hyperferritinemia in an Asplenic Patient

    PubMed Central

    Paine, Allison; Miya, Tadashi; Webb, Brandon J.

    2015-01-01

    Q fever is an uncommon but likely underreported zoonotic infection. Severe hyperferritinemia has been associated with hemophagocytic lymphohistiocytosis and other infectious diseases. In this study, we report a case of Coxiella burnetii infection in an asplenic patient complicated by severe hyperferritinemia and bone marrow infiltration. In this case, the marked ferritin elevation may have been an indicator of profound systemic macrophage activation due to preferential intracellular infection of this cell type by C burnetii, perhaps exacerbated by altered mononuclear phagocyte system function in the setting of asplenia. PMID:26430699

  6. Detection and differentiation of coxiella burnetii in biological fluids

    SciTech Connect

    Frazier, Marvin E.; Mallavia, Louis P.; Samuel, James E.; Baca, Oswald G.

    1990-01-01

    Methods for detecting the presence of Coxiella burenetii in biological samples, as well as a method for differentiating strains of C. burnetii that are capable of causing acute disease from those strains capable of causing chronic disease are disclosed. The methods generally comprise treating cells contained within the biological sample to expose cellular DNA, and hybridizing the cellular DNA (specifically rickettsial DNA) with a C. burnetii-specific labeled DNA probe. Radioisotope and biotin labels are preferred, allowing detection through autoradiography and colorimetric assays, respectively.

  7. [Definitive ability of Stamp-staining, antigen-ELISA, PCR and cell culture for the detection of Coxiella burnetii].

    PubMed

    Henning, Klaus; Sting, Reinhard

    2002-01-01

    Many assays are used for the detection of the aetiological agent of Q fever, Coxiella burnetii, i.e. staining according to the method of Stamp, capture ELISA, PCR or isolation by cell culture. In this study the results of these four assays are compared for their sensitivity and specificity. Staining smears according to the method of Stamp gave many false positive or false negative results. The capture ELISA seems to be a very sensitive assay for the detection of Coxiella burnetii but it has a lack in specificity. It is a useful test system for the screening of large scales of samples. Positive ELISA results should be confirmed by PCR, a very sensitive and specific method for the detection of Coxiella burnetii but more time consumptive than the ELISA. Isolation of the agent using cell cultures was not completely satisfactory because of its lack in sensitivity. Therefore it should only be used in special cases. PMID:12357676

  8. Detection and Genotyping of Coxiella burnetii and Coxiella-Like Bacteria in Horses in South Korea.

    PubMed

    Seo, Min-Goo; Lee, Seung-Hun; VanBik, Dorene; Ouh, In-Ohk; Yun, Sun-Hee; Choi, Eunsang; Park, Yong-Soo; Lee, Sang-Eun; Kim, Jong Wan; Cho, Gil-Jae; Kwon, Oh-Deog; Kwak, Dongmi

    2016-01-01

    Coxiella burnetii and Coxiella-like bacteria (CLB) are genetically and ecologically distinct despite some genetic similarities. Furthermore, CLB are exceptionally diverse and widespread in ticks, but rarely detected in domestic animals. Since Coxiella bacteria can be transmitted from infected horses by inhalation or by coming in contact with ticks during activities such as horseback riding, it is necessary to study their prevalence. To the best of our knowledge, this is the first large-scale nationwide investigation of the prevalence of C. burnetii and CLB among horses reared in South Korea. Of 816 blood samples collected between 2007 and 2013, 11 (1.3%) were identified as C. burnetii by ELISA, and six (0.7%) as CLB by 16S rRNA sequencing. While a sequence from Jeju Island was similar (97.9-100%) to those within clade B, five sequences obtained from the northern region were categorized into a new clade, indicating the sequence diversity of the genus Coxiella. Studies until date had detected CLB only in ticks; here, we describe their detection in mammals. Given their zoonotic potential, strategic monitoring and appropriate control programs for Coxiella species need to be established. PMID:27244230

  9. Detection and Genotyping of Coxiella burnetii and Coxiella-Like Bacteria in Horses in South Korea

    PubMed Central

    Seo, Min-Goo; Lee, Seung-Hun; VanBik, Dorene; Ouh, In-Ohk; Yun, Sun-Hee; Choi, Eunsang; Park, Yong-Soo; Lee, Sang-Eun; Kim, Jong Wan; Cho, Gil-Jae; Kwon, Oh-Deog

    2016-01-01

    Coxiella burnetii and Coxiella-like bacteria (CLB) are genetically and ecologically distinct despite some genetic similarities. Furthermore, CLB are exceptionally diverse and widespread in ticks, but rarely detected in domestic animals. Since Coxiella bacteria can be transmitted from infected horses by inhalation or by coming in contact with ticks during activities such as horseback riding, it is necessary to study their prevalence. To the best of our knowledge, this is the first large-scale nationwide investigation of the prevalence of C. burnetii and CLB among horses reared in South Korea. Of 816 blood samples collected between 2007 and 2013, 11 (1.3%) were identified as C. burnetii by ELISA, and six (0.7%) as CLB by 16S rRNA sequencing. While a sequence from Jeju Island was similar (97.9–100%) to those within clade B, five sequences obtained from the northern region were categorized into a new clade, indicating the sequence diversity of the genus Coxiella. Studies until date had detected CLB only in ticks; here, we describe their detection in mammals. Given their zoonotic potential, strategic monitoring and appropriate control programs for Coxiella species need to be established. PMID:27244230

  10. Coxiella burnetii exposure in northern sea otters Enhydra lutris kenyoni.

    PubMed

    Duncan, Colleen; Gill, Verena A; Worman, Kristin; Burek-Huntington, Kathy; Pabilonia, Kristy L; Johnson, Sam; Fitzpatrick, Kelly A; Weller, Christina; Kersh, Gilbert J

    2015-05-11

    Valvular endocarditis has been well described in northern sea otters Enhydra lutris kenyoni of Alaska and in many cases no cause has been identified. It is also one of the most common conditions observed in people with chronic Coxiella burnetii infection. Given the high levels of C. burnetii exposure in marine mammals distributed throughout the same geographic range as the northern sea otter, and the presence of valvular lesions seen in otters, the objective of this study was to determine the level of C. burnetii exposure in otters and investigate any association between exposure, infection and valvular disease in this species. Archived serum from 75 live captured, apparently healthy otters (25 from each of 3 stocks) and 30 dead otters were tested for C. burnetii antibodies by indirect florescent antibody assay (IFA). Archived bone marrow and heart valves were tested for C. burnetii DNA by real-time PCR (qPCR). Overall, the seroprevalence in live otters was 17%, with significantly more exposed animals in the south central (40%) stock relative to the southwest (8%) and southeast (4%). The seroprevalence of animals sampled post mortem was 27%, although none of the bone marrow or heart valve samples were positive by qPCR. Results of this study failed to demonstrate a significant association between C. burnetii infection and valvular endocarditis in sea otters; however, the differing seroprevalence suggests that exposure opportunities vary geographically. PMID:25958809

  11. Coxiella burnetii in Humans and Ticks in Rural Senegal

    PubMed Central

    Mediannikov, Oleg; Fenollar, Florence; Socolovschi, Cristina; Diatta, Georges; Bassene, Hubert; Molez, Jean-François; Sokhna, Cheikh; Trape, Jean-François; Raoult, Didier

    2010-01-01

    Background Q fever is a worldwide zoonotic disease caused by Coxiella burnetii. Epidemiologically, animals are considered reservoirs and humans incidental hosts. Methodology/Principal Findings We investigated Q fever in rural Senegal. Human samples (e.g., sera, saliva, breast milk, feces) were screened in the generally healthy population of two villages of the Sine-Saloum region. Ticks were collected in four regions. Seroprevalence was studied by immunofluorescence, and all other samples were tested by two qPCR systems for detection of C. burnetii. Positive samples were genotyped (multispacer typing) by amplification and sequencing of three spacers. Strains were isolated by cell culture. We found that the seroprevalence may be as high as 24.5% (59 of 238 studied) in Dielmo village. We identified spontaneous excretion of C. burnetii by humans through faeces and milk. Hard and soft ticks (8 species) were infected in 0–37.6%. We identified three genotypes of C. burnetii. The previously identified genotype 6 was the most common in ticks in all studied regions and the only one found in human samples. Three strains of genotype 6 of C. burnetii were also recovered from soft tick Ornithodoros sonrai. Two other genotypes found in ticks, 35 and 36, were identified for the first time. Conclusions/Significance Q fever should be considered a significant public health threat in Senegal. Humans, similar to other mammals, may continuously excrete C. burnetii. PMID:20386603

  12. Presence of Coxiella burnetii in fleas in Cyprus.

    PubMed

    Psaroulaki, Anna; Chochlakis, Dimosthenis; Ioannou, Ioannis; Angelakis, Emmanouil; Tselentis, Yannis

    2014-09-01

    Over 40 tick species are naturally infected by Coxiella burnetii. However, little is known about the presence of C. burnetii in other ectoparasites such as fleas. During a 6-year (2000-2006) study, 1147 fleas were collected from 652 animals (252 rats, 118 foxes, and 282 hares) captured from different areas of Cyprus. Three flea species-Xenopsylla cheopis, Ctenocephalides felis, and C. canis-were identified. Fleas were pooled (153 pools) and tested by PCR for the presence of C. burnetii. The pathogen was identified in 25 (16.3%) pools. None of the fleas parasitizing hares was positive for C. burnetii, as opposed to fleas collected from rats (12% pool positivity) and foxes (47.6% pool positivity). The highest prevalence of positive pools was recorded in C. canis (38%) compared to C. felis (16.6%) and X. cheopis (10.8%). All pools of C. canis positive for C. burnetii were removed from foxes (44.4%), whereas all positive X. cheopis (10.8%) were removed from rats. The role of fleas in the maintenance and transmission of C. burnetii among wild vertebrates remains to be determined. PMID:25198524

  13. SOME BIOCHEMICAL CHANGES IN THE GUINEA PIG DURING INFECTION WITH COXIELLA BURNETII

    PubMed Central

    Paretsky, D.; Downs, C. M.; Salmon, C. W.

    1964-01-01

    Paretsky, D. (University of Kansas, Lawrence), C. M. Downs, and C. W. Salmon. Some biochemical changes in the guinea pig during infection with Coxiella burnetii. J. Bacteriol. 88:137–142. 1964.—Guinea pigs infected with Coxiella burnetii, the rickettsial agent of Q fever, were studied for 11 days postinfection. Maximal changes in liver lipids, liver phosphorylase, and uridine diphosphate glucose (UDPG)-glycogen glucosyl-transferase activities occurred 3 to 4 days post-infection. In this period, total liver lipids increased from 1.26 to 5.46 mg/mg of N, with the largest increment in the glyceride fraction. Liver glycogen virtually disappeared by the second day, with no chemically detectable restoration until the eleventh day. A pattern of altered phosphorylase and UDPG-glycogen transglucosylase activities was observed, with maximal phosphorylase and minimal glucosyltransferase activities at the third and fourth days. Histochemical observations confirmed chemical analyses for lipids and glycogen. PMID:14197878

  14. SOME BIOCHEMICAL CHANGES IN THE GUINEA PIG DURING INFECTION WITH COXIELLA BURNETII.

    PubMed

    PARETSKY, D; DOWNS, C M; SALMON, C W

    1964-07-01

    Paretsky, D. (University of Kansas, Lawrence), C. M. Downs, and C. W. Salmon. Some biochemical changes in the guinea pig during infection with Coxiella burnetii. J. Bacteriol. 88:137-142. 1964.-Guinea pigs infected with Coxiella burnetii, the rickettsial agent of Q fever, were studied for 11 days postinfection. Maximal changes in liver lipids, liver phosphorylase, and uridine diphosphate glucose (UDPG)-glycogen glucosyl-transferase activities occurred 3 to 4 days post-infection. In this period, total liver lipids increased from 1.26 to 5.46 mg/mg of N, with the largest increment in the glyceride fraction. Liver glycogen virtually disappeared by the second day, with no chemically detectable restoration until the eleventh day. A pattern of altered phosphorylase and UDPG-glycogen transglucosylase activities was observed, with maximal phosphorylase and minimal glucosyltransferase activities at the third and fourth days. Histochemical observations confirmed chemical analyses for lipids and glycogen. PMID:14197878

  15. Molecular methods routinely used to detect Coxiella burnetii in ticks cross-react with Coxiella-like bacteria

    PubMed Central

    Elsa, Jourdain; Duron, Olivier; Séverine, Barry; González-Acuña, Daniel; Sidi-Boumedine, Karim

    2015-01-01

    Background Q fever is a widespread zoonotic disease caused by Coxiella burnetii. Ticks may act as vectors, and many epidemiological studies aim to assess C. burnetii prevalence in ticks. Because ticks may also be infected with Coxiella-like bacteria, screening tools that differentiate between C. burnetii and Coxiella-like bacteria are essential. Methods In this study, we screened tick specimens from 10 species (Ornithodoros rostratus, O. peruvianus, O. capensis, Ixodes ricinus, Rhipicephalus annulatus, R. decoloratus, R. geigy, O. sonrai, O. occidentalis, and Amblyomma cajennense) known to harbor specific Coxiella-like bacteria, by using quantitative PCR primers usually considered to be specific for C. burnetii and targeting, respectively, the IS1111, icd, scvA, p1, and GroEL/htpB genes. Results We found that some Coxiella-like bacteria, belonging to clades A and C, yield positive PCR results when screened with primers initially believed to be C. burnetii-specific. Conclusions These results suggest that PCR-based surveys that aim to detect C. burnetii in ticks by using currently available methods must be interpreted with caution if the amplified products cannot be sequenced. Future molecular methods that aim at detecting C. burnetii need to take into account the possibility that cross-reactions may exist with Coxiella-like bacteria. PMID:26609691

  16. No indication of Coxiella burnetii infection in Norwegian farmed ruminants

    PubMed Central

    2012-01-01

    Background Infection with Coxiella burnetii, the cause of Q-fever, has never been detected in Norwegian animals. Recognising the increasing prevalence of the infection in neighbouring countries, the aim of the study was to perform a survey of Norwegian farmed ruminants for the prevalence of C. burnetii infection. Results Milk and blood samples from more than 3450 Norwegian dairy cattle herds, 55 beef cattle herds, 348 dairy goat herds and 118 sheep flocks were serologically examined for antibodies against C. burnetii. All samples were negative for antibodies against C. burnetii. The estimated prevalences of infected herds were 0 (95% confidence interval: 0% - 0.12%), 0 (0% - 12%), 0 (0% - 1.2%) and 0 (0% - 10%) for dairy cattle herds, beef cattle herds, goat herds and sheep flocks, respectively. Conclusions The study indicates that the prevalence of C. burnetii infection in farmed Norwegian ruminants is low, and it cannot be excluded that Norway is free of the infection. It would be beneficial if Norway was able to maintain the current situation. Therefore, preventive measures should be continued. PMID:22607497

  17. Prevalence of Coxiella burnetii in clinically healthy German sheep flocks

    PubMed Central

    2012-01-01

    Background Current epidemiological data on the situation of Coxiella (C.) burnetii infections in sheep are missing, making risk assessment and the implementation of counteractive measures difficult. Using the German state of Thuringia as a model example, the estimated sero-, and antigen prevalence of C. burnetii (10% and 25%, respectively) was assessed at flock level in 39/252 randomly selected clinically healthy sheep flocks with more than 100 ewes and unknown abortion rate. Results The CHECKIT™ Q-fever Test Kit identified 11 (28%) antibody positive herds, whereas real-time PCR revealed the presence of C. burnetii DNA in 2 (5%) of the flocks. Multiple-locus variable number of tandem repeats analysis of 9 isolates obtained from one flock revealed identical profiles. All isolates contained the plasmid QpH1. Conclusions The results demonstrate that C. burnetii is present in clinically inconspicuous sheep flocks and sporadic flare-ups do occur as the notifications to the German animal disease reporting system show. Although C. burnetii infections are not a primary veterinary concern due to the lack of significant clinical impact on animal health (with the exception of goats), the eminent zoonotic risk for humans should not be underestimated. Therefore, strategies combining the interests of public and veterinary public health should include monitoring of flocks, the identification and culling of shedders as well as the administration of protective vaccines. PMID:22429653

  18. Prevalence of Coxiella burnetii Infection in Humans Occupationally Exposed to Animals in Poland

    PubMed Central

    Galińska, Elżbieta Monika; Niemczuk, Krzysztof; Knap, Józef Piotr

    2015-01-01

    Abstract Coxiella burnetii is the etiological agent of Q fever, and outbreaks of Q fever have been reported in different parts of Europe both in animals and humans. Human infections are mostly associated with infections in ruminants, e.g., sheep, goats, and cows. Various professional groups are occupationally exposed to infection with C. burnetii. The aim of this study was investigate the prevalence of C. burnetii in farm workers. Serum samples were collected from 151 persons from six different regions of Poland. The serum samples were tested using three serological methods—complement fixation test (CFT), enzyme-linked immunosorbent assay (ELISA), and indirect fluorescent antibody (IFA). A total of 71 samples of blood were also tested by real-time PCR. The results showed that antibodies against C. burnetii were present in the tested sera. Average percentages of seropositive samples in IFA, ELISA, and CFT were 31.12%, 39.07%, and 15.23%, respectively. Positive results were noted in each testing center. Of the three test types, IFA results were considered the most sensitive. Real-time PCR confirmed the presence of DNA specific for C. burnetii in 10 patients. The farming workforce constitutes an occupational risk group with an increased risk for C. burnetii infection, presumably because of their contact with infected livestock. PMID:25897813

  19. Nitric Oxide Inhibits Coxiella burnetii Replication and Parasitophorous Vacuole Maturation

    PubMed Central

    Howe, Dale; Barrows, Lorraine F.; Lindstrom, Nicole M.; Heinzen, Robert A.

    2002-01-01

    Nitric oxide is a recognized cytotoxic effector against facultative and obligate intracellular bacteria. This study examined the effect of nitric oxide produced by inducible nitric oxide synthase (iNOS) up-regulated in response to cytokine stimulation, or by a synthetic nitric oxide donor, on replication of obligately intracellular Coxiella burnetii in murine L-929 cells. Immunoblotting and nitrite assays revealed that C. burnetii infection of L-929 cells augments expression of iNOS up-regulated in response to gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Infection in the absence of cytokine stimulation did not result in demonstrable up-regulation of iNOS expression or in increased nitrite production. Nitrite production by cytokine-treated cells was significantly inhibited by the iNOS inhibitor S-methylisothiourea (SMT). Treatment of infected cells with IFN-γ and TNF-α or the synthetic nitric oxide donor 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (DETA/NONOate) had a bacteriostatic effect on C. burnetii replication. Inhibition of replication was reversed upon addition of SMT to the culture medium of cytokine-treated cells. Microscopic analysis of infected cells revealed that nitric oxide (either cytokine induced or donor derived) inhibited formation of the mature (large) parasitophorous vacuole that is characteristic of C. burnetii infection of host cells. Instead, exposure of infected cells to nitric oxide resulted in the formation of multiple small, acidic vacuoles usually containing one C. burnetii cell. Removal of nitrosative stress resulted in the coalescence of small vacuoles to form a large vacuole harboring multiple C. burnetii cells. These experiments demonstrate that nitric oxide reversibly inhibits replication of C. burnetii and formation of the parasitophorous vacuole. PMID:12183564

  20. Coxiella burnetii Seroprevalence in Small Ruminants in The Gambia

    PubMed Central

    Klaasen, Marieke; Roest, Hendrik-Jan; van der Hoek, Wim; Goossens, Bart; Secka, Arss; Stegeman, Arjan

    2014-01-01

    Background Q fever is a zoonosis caused by Coxiella burnetii, a Gram negative bacterium present worldwide. Small ruminants are considered the main reservoirs for infection of humans. This study aimed to estimate the extent of C. burnetii infection among sheep and goats in part of The Gambia. Methodology/Principal Findings This survey was carried out from March to May 2012 at two areas in The Gambia. The first area comprised a cluster of seven rural villages situated 5–15 km west of Farafenni as well as the local abattoir. A second sampling was done at the central abattoir in Abuko (30 km from the capital, Banjul) in the Western Region. Serum samples were obtained from 490 goats and 398 sheep. In addition, 67 milk samples were obtained from lactating dams. Sera were tested with a Q fever ELISA kit. C. burnetii DNA was extracted from milk samples and then detected using a specific quantitative multiplex PCR assay, targeting the IS1111a element. A multivariable mixed logistic regression model was used to examine the relationship between seropositivity and explanatory variables. An overall seroprevalence of 21.6% was found. Goats had a significantly higher seroprevalence than sheep, respectively 24.2% and 18.5%. Seropositive animals were significantly older than seronegative animals. Animals from the villages had a significantly lower seroprevalence than animals from the central abattoir (15.1% versus 29.1%). C. burnetii DNA was detected in 2 out of 67 milk samples, whereas 8 samples gave a doubtful result. Conclusion/Significance A substantial C. burnetii seroprevalence in sheep and goats in The Gambia was demonstrated. People living in close proximity to small ruminants are exposed to C. burnetii. Q fever should be considered as a possible cause of acute febrile illness in humans in The Gambia. Future studies should include a simultaneous assessment of veterinary and human serology, and include aetiology of febrile illness in local clinics. PMID:24454863

  1. Serological characterization of surface-exposed proteins of Coxiella burnetii.

    PubMed

    Jiao, Jun; Xiong, Xiaolu; Qi, Yong; Gong, Wenping; Duan, Changsong; Yang, Xiaomei; Wen, Bohai

    2014-12-01

    The obligate intracellular Gram-negative bacterium Coxiella burnetii causes Q fever, a worldwide zoonosis. Here we labelled Cox. burnetii with biotin and used biotin-streptavidin affinity chromatography to isolate surface-exposed proteins (SEPs). Using two-dimensional electrophoresis combined with mass spectrometry, we identified 37 proteins through bioinformatics analysis. Thirty SEPs expressed in Escherichia coli (recombinant SEPs, rSEPs) were used to generate microarrays, which were probed with sera from mice experimentally infected with Cox. burnetii or sera from Q fever patients. Thirteen rSEPs were recognized as seroreactive, and the majority reacted with at least 50 % of the sera from mice infected with Cox. burnetii but not with sera from mice infected with Rickettsia rickettsii, R. heilongjiangensis, or R. typhi. Further, 13 proteins that reacted with sera from patients with Q fever did not react with sera from patients with brucellosis or mycoplasma pneumonia. Our results suggest that these seroreactive SEPs have potential as serodiagnostic antigens or as subunit vaccine antigens against Q fever. PMID:25298245

  2. Detection of Coxiella burnetii DNA in Inhalable Airborne Dust Samples from Goat Farms after Mandatory Culling

    PubMed Central

    Hogerwerf, Lenny; Still, Kelly; Heederik, Dick; van Rotterdam, Bart; de Bruin, Arnout; Nielen, Mirjam; Wouters, Inge M.

    2012-01-01

    Coxiella burnetii is thought to infect humans primarily via airborne transmission. However, air measurements of C. burnetii are sparse. We detected C. burnetii DNA in inhalable and PM10 (particulate matter with an aerodynamic size of 10 μm or less) dust samples collected at three affected goat farms, demonstrating that low levels of C. burnetii DNA are present in inhalable size fractions. PMID:22582072

  3. Host cell-free growth of the Q fever bacterium Coxiella burnetii

    PubMed Central

    Omsland, Anders; Cockrell, Diane C.; Howe, Dale; Fischer, Elizabeth R.; Virtaneva, Kimmo; Sturdevant, Daniel E.; Porcella, Stephen F.; Heinzen, Robert A.

    2009-01-01

    The inability to propagate obligate intracellular pathogens under axenic (host cell-free) culture conditions imposes severe experimental constraints that have negatively impacted progress in understanding pathogen virulence and disease mechanisms. Coxiella burnetii, the causative agent of human Q (Query) fever, is an obligate intracellular bacterial pathogen that replicates exclusively in an acidified, lysosome-like vacuole. To define conditions that support C. burnetii growth, we systematically evaluated the organism's metabolic requirements using expression microarrays, genomic reconstruction, and metabolite typing. This led to development of a complex nutrient medium that supported substantial growth (approximately 3 log10) of C. burnetii in a 2.5% oxygen environment. Importantly, axenically grown C. burnetii were highly infectious for Vero cells and exhibited developmental forms characteristic of in vivo grown organisms. Axenic cultivation of C. burnetii will facilitate studies of the organism's pathogenesis and genetics and aid development of Q fever preventatives such as an effective subunit vaccine. Furthermore, the systematic approach used here may be broadly applicable to development of axenic media that support growth of other medically important obligate intracellular pathogens. PMID:19246385

  4. Detection of Coxiella burnetii in Ambient Air after a Large Q Fever Outbreak

    PubMed Central

    de Rooij, Myrna M. T.; Borlée, Floor; Smit, Lidwien A. M.; de Bruin, Arnout; Janse, Ingmar; Heederik, Dick J. J.; Wouters, Inge M.

    2016-01-01

    One of the largest Q fever outbreaks ever occurred in the Netherlands from 2007–2010, with 25 fatalities among 4,026 notified cases. Airborne dispersion of Coxiella burnetii was suspected but not studied extensively at the time. We investigated temporal and spatial variation of Coxiella burnetii in ambient air at residential locations in the most affected area in the Netherlands (the South-East), in the year immediately following the outbreak. One-week average ambient particulate matter < 10 μm samples were collected at eight locations from March till September 2011. Presence of Coxiella burnetii DNA was determined by quantitative polymerase chain reaction. Associations with various spatial and temporal characteristics were analyzed by mixed logistic regression. Coxiella burnetii DNA was detected in 56 out of 202 samples (28%). Airborne Coxiella burnetii presence showed a clear seasonal pattern coinciding with goat kidding. The spatial variation was significantly associated with number of goats on the nearest goat farm weighted by the distance to the farm (OR per IQR: 1.89, CI: 1.31–2.76). We conclude that in the year after a large Q fever outbreak, temporal variation of airborne Coxiella burnetii is suggestive to be associated with goat kidding, and spatial variation with distance to and size of goat farms. Aerosol measurements show to have potential for source identification and attribution of an airborne pathogen, which may also be applicable in early stages of an outbreak. PMID:26991094

  5. Detection of Coxiella burnetii in Ambient Air after a Large Q Fever Outbreak.

    PubMed

    de Rooij, Myrna M T; Borlée, Floor; Smit, Lidwien A M; de Bruin, Arnout; Janse, Ingmar; Heederik, Dick J J; Wouters, Inge M

    2016-01-01

    One of the largest Q fever outbreaks ever occurred in the Netherlands from 2007-2010, with 25 fatalities among 4,026 notified cases. Airborne dispersion of Coxiella burnetii was suspected but not studied extensively at the time. We investigated temporal and spatial variation of Coxiella burnetii in ambient air at residential locations in the most affected area in the Netherlands (the South-East), in the year immediately following the outbreak. One-week average ambient particulate matter < 10 μm samples were collected at eight locations from March till September 2011. Presence of Coxiella burnetii DNA was determined by quantitative polymerase chain reaction. Associations with various spatial and temporal characteristics were analyzed by mixed logistic regression. Coxiella burnetii DNA was detected in 56 out of 202 samples (28%). Airborne Coxiella burnetii presence showed a clear seasonal pattern coinciding with goat kidding. The spatial variation was significantly associated with number of goats on the nearest goat farm weighted by the distance to the farm (OR per IQR: 1.89, CI: 1.31-2.76). We conclude that in the year after a large Q fever outbreak, temporal variation of airborne Coxiella burnetii is suggestive to be associated with goat kidding, and spatial variation with distance to and size of goat farms. Aerosol measurements show to have potential for source identification and attribution of an airborne pathogen, which may also be applicable in early stages of an outbreak. PMID:26991094

  6. Genotyping of Coxiella burnetii from domestic ruminants in northern Spain

    PubMed Central

    2012-01-01

    Background Information on the genotypic diversity of Coxiella burnetii isolates from infected domestic ruminants in Spain is limited. The aim of this study was to identify the C. burnetii genotypes infecting livestock in Northern Spain and compare them to other European genotypes. A commercial real-time PCR targeting the IS1111a insertion element was used to detect the presence of C. burnetii DNA in domestic ruminants from Spain. Genotypes were determined by a 6-loci Multiple Locus Variable number tandem repeat analysis (MLVA) panel and Multispacer Sequence Typing (MST). Results A total of 45 samples from 4 goat herds (placentas, N = 4), 12 dairy cattle herds (vaginal mucus, individual milk, bulk tank milk, aerosols, N = 20) and 5 sheep flocks (placenta, vaginal swabs, faeces, air samples, dust, N = 21) were included in the study. Samples from goats and sheep were obtained from herds which had suffered abortions suspected to be caused by C. burnetii, whereas cattle samples were obtained from animals with reproductive problems compatible with C. burnetii infection, or consisted of bulk tank milk (BTM) samples from a Q fever surveillance programme. C. burnetii genotypes identified in ruminants from Spain were compared to those detected in other countries. Three MLVA genotypes were found in 4 goat farms, 7 MLVA genotypes were identified in 12 cattle herds and 4 MLVA genotypes were identified in 5 sheep flocks. Clustering of the MLVA genotypes using the minimum spanning tree method showed a high degree of genetic similarity between most MLVA genotypes. Overall 11 different MLVA genotypes were obtained corresponding to 4 different MST genotypes: MST genotype 13, identified in goat, sheep and cattle from Spain; MST genotype 18, only identified in goats; and, MST genotypes 8 and 20, identified in small ruminants and cattle, respectively. All these genotypes had been previously identified in animal and human clinical samples from several European countries, but

  7. Coxiella burnetii infection of a bovine jugular vein conduit in a child.

    PubMed

    Tasher, Diana; Stein, Michal; Raucher-Sternfeld, Alona; Somekh, Eli

    2012-06-01

    We report a case of an 11-year-old girl with Coxiella burnetii infection of a bovine jugular vein conduit which is an extremely rare manifestation of Q fever. The role of surgery in the management of C. burnetii endovascular infection and the use of serology are discussed. PMID:22349674

  8. Draft Genome Sequences of Six Ruminant Coxiella burnetii Isolates of European Origin

    PubMed Central

    Ellis, Richard J.; Adam, Gilbert; Prigent, Myriam; Angen, Øystein; Aspán, Anna; Thiéry, Richard; Rousset, Elodie

    2014-01-01

    Coxiella burnetii is responsible for Q fever, a worldwide zoonosis attributed to the inhalation of aerosols contaminated by livestock birth products. Six draft genome sequences of European C. burnetii isolates from ruminants are presented here. The availability of these genomes will help in understanding the potential host specificity and pathogenicity and in identifying pertinent markers for surveillance and tracing. PMID:24831135

  9. Coxiella burnetii DNA detected in domestic ruminants and wildlife from Portugal.

    PubMed

    Cumbassá, Aminata; Barahona, Maria J; Cunha, Mónica V; Azórin, Beatriz; Fonseca, Carlos; Rosalino, Luís Miguel; Tilburg, Jeroen; Hagen, Ferry; Santos, Ana S; Botelho, Ana

    2015-10-22

    Coxiella burnetii is the etiological agent of Q fever or Coxiellosis, a zoonosis mainly affecting domestic ruminants. Information on the population structure and epidemiology of C. burnetii in animals is scarce in Portugal. Evidence of C. burnetti infection was sought in domestic, wild and captive animals based on the detection of bacterial DNA. Tissue samples from 152 domestic animals (cattle=24, goats=51, sheep=76 and swine=1), 55 wild carnivores (Egyptian mongoose=45, red fox=4, common genet=3, weasel=2 and European badger=1) and 22 zoo animals (antelopes=15, impala=1; rhinoceros=1, deer=2, zebras=2 and giraffe=1) were screened by nested-touchdown PCR. Cloacae swabs from 19 griffon vultures were also analysed. Among the domestic ruminants, goats presented the highest prevalence of infection (23.53%), followed by cattle, (20.83%) and sheep (10.53%). C. burnetii DNA was also detected in five Egyptian mongooses and two antelopes and one giraffe. Using a 6-locus multiple-locus variable-number tandem repeat analysis (MLVA-6) six complete genotypes, T, I and CM and the first reported CN, CO and CP, were identified, respectively, in small ruminants and Egyptian mongooses. Clustering analysis of genotypes exposed four distinct groups, according to detection source, enlightening an apparent association between C. burnetii genotype and host. PMID:26345258

  10. Proteomic and Systems Biology Analysis of the Monocyte Response to Coxiella burnetii Infection

    PubMed Central

    Shipman, Matt; Lubick, Kirk; Fouchard, David; Gurram, Rajani; Grieco, Paul; Jutila, Mark; Dratz, Edward A.

    2013-01-01

    Coxiella burnetii is an obligate intracellular bacterial pathogen and the causative agent of Q fever. Chronic Q fever can produce debilitating fatigue and C. burnetii is considered a significant bioterror threat. C. burnetii occupies the monocyte phagolysosome and although prior work has explained features of the host-pathogen interaction, many aspects are still poorly understood. We have conducted a proteomic investigation of human Monomac I cells infected with the Nine Mile Phase II strain of C. burnetii and used the results as a framework for a systems biology model of the host response. Our principal methodology was multiplex differential 2D gel electrophoresis using ZDyes, a new generation of covalently linked fluorescent protein detection dyes under development at Montana State University. The 2D gel analysis facilitated the detection of changes in posttranslational modifications on intact proteins in response to infection. The systems model created from our data a framework for the design of experiments to seek a deeper understanding of the host-pathogen interactions. PMID:23990884

  11. Complete genome sequence of the Q-fever pathogen Coxiella burnetii

    PubMed Central

    Seshadri, Rekha; Paulsen, Ian T.; Eisen, Jonathan A.; Read, Timothy D.; Nelson, Karen E.; Nelson, William C.; Ward, Naomi L.; Tettelin, Hervé; Davidsen, Tanja M.; Beanan, Maureen J.; Deboy, Robert T.; Daugherty, Sean C.; Brinkac, Lauren M.; Madupu, Ramana; Dodson, Robert J.; Khouri, Hoda M.; Lee, Kathy H.; Carty, Heather A.; Scanlan, David; Heinzen, Robert A.; Thompson, Herbert A.; Samuel, James E.; Fraser, Claire M.; Heidelberg, John F.

    2003-01-01

    The 1,995,275-bp genome of Coxiella burnetii, Nine Mile phase I RSA493, a highly virulent zoonotic pathogen and category B bioterrorism agent, was sequenced by the random shotgun method. This bacterium is an obligate intracellular acidophile that is highly adapted for life within the eukaryotic phagolysosome. Genome analysis revealed many genes with potential roles in adhesion, invasion, intracellular trafficking, host-cell modulation, and detoxification. A previously uncharacterized 13-member family of ankyrin repeat-containing proteins is implicated in the pathogenesis of this organism. Although the lifestyle and parasitic strategies of C. burnetii resemble that of Rickettsiae and Chlamydiae, their genome architectures differ considerably in terms of presence of mobile elements, extent of genome reduction, metabolic capabilities, and transporter profiles. The presence of 83 pseudogenes displays an ongoing process of gene degradation. Unlike other obligate intracellular bacteria, 32 insertion sequences are found dispersed in the chromosome, indicating some plasticity in the C. burnetii genome. These analyses suggest that the obligate intracellular lifestyle of C. burnetii may be a relatively recent innovation. PMID:12704232

  12. Genotyping and Axenic Growth of Coxiella burnetii Isolates Found in the United States Environment.

    PubMed

    Kersh, Gilbert J; Priestley, Rachael A; Hornstra, Heidie M; Self, Joshua S; Fitzpatrick, Kelly A; Biggerstaff, Brad J; Keim, Paul; Pearson, Talima; Massung, Robert F

    2016-09-01

    Coxiella burnetii is a gram-negative bacterium that is the etiologic agent of the zoonotic disease Q fever. Common reservoirs of C. burnetii include sheep, goats, and cattle. These animals shed C. burnetii into the environment, and humans are infected by inhalation of aerosols. A survey of 1622 environmental samples taken across the United States in 2006-2008 found that 23.8% of the samples contained C. burnetii DNA. To identify the strains circulating in the U.S. environment, DNA from these environmental samples was genotyped using an SNP-based approach to derive sequence types (ST) that are also compatible with multispacer sequence typing methods. Three different sequence types were observed in 31 samples taken from 19 locations. ST8 was associated with goats and ST20 with dairy cattle. ST16/26 was detected in locations with exposure to various animals and also in locations with no direct animal contact. Viable isolates were obtained for all three sequence types, but only the ST20 and ST16/26 isolates grew in acidified citrate cysteine medium (ACCM)-2 axenic media. Examination of a variety of isolates with different sequence types showed that ST8 and closely related isolates did not grow in ACCM-2. These results suggest that a limited number of C. burnetii sequence types are circulating in the U.S. environment and these strains have close associations with specific reservoir species. Growth in ACCM-2 may not be suitable for isolation of many C. burnetii strains. PMID:27304166

  13. [Detection of Coxiella burnetii in the air of a sheep barn during shearing].

    PubMed

    Schulz, J; Runge, M; Schröder, C; Ganter, M; Hartung, J

    2005-12-01

    Local epidemics of Q fever occur sporadically in Germany, mainly in rural residential communities. There is increasing evidence that these outbreaks, which are caused by Coxiella burnetii, are related particularly to the lambing season and shearing periods of nearby sheep holdings. It is assumed that this zoonotic agent is massively emitted from the placenta of infected ewes at birth and during shearing of wool contaminated with infected faeces of ticks. However, little is known about the airborne transmission and travel distance of this infectious agent, and only few attempts have been made to isolate it directly from the air. This paper describes for the first time the isolation and detection of C. burnetii in the air of an enclosed sheep barn during shearing of a herd which had tested positive for C. burnetii serologically and by PCR. Samples of inhalable dust samples were taken using I.O.M. samplers with glass fibre and polycarbonate filters at a flow rate of 2.5 l/min. The sampling time was nearly 4.5 h. Two sampling positions were set up on both sides of the shearing place at a distance of 3 m and 1.5 m above the ground. A third position with the same sampling equipment was not activated and served as a sampling and transport control. In the laboratory, the glass fibre filters were used to determine the dust concentration. The polycarbonate filters were treated in a specific breakdown procedure which inactivates PCR inhibitors, followed by amplification and sequencing of a specific DNA section of C. burnetii, which was found in the dust from both active sampling positions. The investigation clearly shows that the sampling and detection methods used in this small field study are suitable for the detection of C. burnetii in the air of sheep barns. The results confirm experimentally the high risk of airborne transmission of C. burnetii from sero-positive sheep herds during shearing. However, little is known about the effective travel distance of infective

  14. Evidence of Coxiella burnetii in Punjab province, Pakistan.

    PubMed

    Shabbir, Muhammad Zubair; Akram, Sidra; Hassan, Zia Ul; Hanif, Kashif; Rabbani, Masood; Muhammad, Javed; Chaudhary, Muhammad Hamid; Abbas, Tariq; Ghori, Muhammad Taslim; Rashid, Haroon; Jamil, Tariq; Islam, Zia-Ul-; Rasool, Haisem; Bano, Asghari; Ahmad, Arfan; Ali, Muhammad Asad; Yaqub, Tahir; McVey, Walt; Jayarao, Bhushan M

    2016-11-01

    Coxiella burnetii causes query (Q) fever, an important zoonotic disease with worldwide significance. The role of environment in the ecology of C. burnetti, and its influence on seroconversion in animals has not been elucidated in Pakistan. We carried out a cross-sectional study in Punjab province to (1) determine the prevalence and distribution of C. burnetii in soil using an ISIIII gene-based real time-polymerase chain reaction (RT-PCR) assay, (2) analyze association between the occurrence of C. burnetii in soil and its predictors i.e. soil characteristics (macro- and micro-nutrients) and several likely risk factors including the seroconversion in small ruminants at places where its genome had or had not been detected, and (3) predict homology and genetic diversity of the identified strains using sequences originated from different hosts worldwide. A total of 2425 soil samples from nine districts of Punjab province were processed. C. burnetii DNA was detected in 47 samples (1.94%, 95% CI: ±0.55) originating from 35 villages of studied districts (7.22%, 95% CI: ±2.30). The highest prevalence was found in Attock (7.11%, 95% CI: ±3.36), followed by Lahore (4.83%, 95% CI: ±3.49), Sahiwal (4.70%, 95% CI: ±2.6), Dera Ghazi Khan (2.33%, 95% CI: ±2.02), Faisalabad (1.35%, 95% CI: ±1.18) and Sheikhupura (0.68%, 95% CI: ±0.94). The odds of detecting bacterial DNA in soil was increased with a unit increase in organic matter [2.511 (95% CI: 1.453-4.340), p=0.001] and sodium [1.013 (95% CI: 1.005-1.022), p=0.001], whereas, calcium [0.984 (95% CI: 0.975-0.994), p=0.002] and potassium [0.994 (95% CI: 0.990-0.999), p=0.011] had protective effect where a unit increase in each analyte decreased odds for its occurrence by 1.0% approximately. Likewise, for categorical variables (risk factors), the odds of detecting C. burnetii were higher at locations >500m away from a main road [1.95 (95% CI: 1.06-3.78), p=0.04]. The enzyme-linked immunosorbent assay (ELISA

  15. Chronic Q-Fever (Coxiella burnetii) Causing Abdominal Aortic Aneurysm and Lumbar Osteomyelitis: A Case Report

    PubMed Central

    Leahey, P. Alexander; Tahan, Steven R.; Kasper, Ekkehard M.; Albrecht, Mary

    2016-01-01

    Coxiella burnetii is a rare cause of chronic infection that most frequently presents as endocarditis. We report a case of C burnetii causing an infected abdominal aortic aneurysm with contiguous lumbar osteomyelitis resulting in spinal cord compromise. The diagnosis was established by serologic studies consistent with chronic Q-fever (ratio of C burnetii immunoglobulin [Ig]G phase II titer to IgG phase I titer <1) and was confirmed by positive C burnetii polymerase chain reaction of vertebral tissue in addition to pathology of vertebral bone showing intracellular Gram-negative coccobacillary bacteria. The patient clinically improved after surgical decompression and prolonged treatment with doxycycline and hydroxychloroquine. PMID:26730393

  16. Chronic Q-Fever (Coxiella burnetii) Causing Abdominal Aortic Aneurysm and Lumbar Osteomyelitis: A Case Report.

    PubMed

    Leahey, P Alexander; Tahan, Steven R; Kasper, Ekkehard M; Albrecht, Mary

    2016-01-01

    Coxiella burnetii is a rare cause of chronic infection that most frequently presents as endocarditis. We report a case of C burnetii causing an infected abdominal aortic aneurysm with contiguous lumbar osteomyelitis resulting in spinal cord compromise. The diagnosis was established by serologic studies consistent with chronic Q-fever (ratio of C burnetii immunoglobulin [Ig]G phase II titer to IgG phase I titer <1) and was confirmed by positive C burnetii polymerase chain reaction of vertebral tissue in addition to pathology of vertebral bone showing intracellular Gram-negative coccobacillary bacteria. The patient clinically improved after surgical decompression and prolonged treatment with doxycycline and hydroxychloroquine. PMID:26730393

  17. Identification of Coxiella burnetii Type IV Secretion Substrates Required for Intracellular Replication and Coxiella-Containing Vacuole Formation

    PubMed Central

    Weber, Mary M.; Chen, Chen; Rowin, Kristina; Mertens, Katja; Galvan, Gloria; Zhi, Hui; Dealing, Christopher M.; Roman, Victor A.; Banga, Simran; Tan, Yunhao; Luo, Zhao-Qing

    2013-01-01

    Coxiella burnetii, the etiological agent of acute and chronic Q fever in humans, is a naturally intracellular pathogen that directs the formation of an acidic Coxiella-containing vacuole (CCV) derived from the host lysosomal network. Central to its pathogenesis is a specialized type IVB secretion system (T4SS) that delivers effectors essential for intracellular replication and CCV formation. Using a bioinformatics-guided approach, 234 T4SS candidate substrates were identified. Expression of each candidate as a TEM-1 β-lactamase fusion protein led to the identification of 53 substrates that were translocated in a Dot/Icm-dependent manner. Ectopic expression in HeLa cells revealed that these substrates trafficked to distinct subcellular sites, including the endoplasmic reticulum, mitochondrion, and nucleus. Expression in Saccharomyces cerevisiae identified several substrates that were capable of interfering with yeast growth, suggesting that these substrates target crucial host processes. To determine if any of these T4SS substrates are necessary for intracellular replication, we isolated 20 clonal T4SS substrate mutants using the Himar1 transposon and transposase. Among these, 10 mutants exhibited defects in intracellular growth and CCV formation in HeLa and J774A.1 cells but displayed normal growth in bacteriological medium. Collectively, these results indicate that C. burnetii encodes a large repertoire of T4SS substrates that play integral roles in host cell subversion and CCV formation and suggest less redundancy in effector function than has been found in the comparative Legionella Dot/Icm model. PMID:23813730

  18. The Development of Lyophilized Loop-mediated Isothermal Amplification Reagents for the Detection of Coxiella burnetii.

    PubMed

    Chen, Hua-Wei; Ching, Wei-Mei

    2016-01-01

    Coxiella burnetii, the agent causing Q fever, is an obligate intracellular bacterium. PCR based diagnostic assays have been developed for detecting C. burnetii DNA in cell cultures and clinical samples. PCR requires specialized equipment and extensive end user training, and therefore, it is not suitable for routine work especially in a resource-constrained area. We have developed a loop-mediated isothermal amplification (LAMP) assay to detect the presence of C. burnetii in patient samples. This method is performed at a single temperature around 60 °C in a water bath or heating block. The sensitivity of this LAMP assay is very similar to PCR with a detection limit of about 25 copies per reaction. This report describes the preparation of the reaction using lyophilized reagents and visualization of results using hydroxynaphthol blue (HNB) or a UV lamp with fluorescent intercalating dye in the reaction. The LAMP reagents were lyophilized and stored at room temperature (RT) for one month without loss of detection sensitivity. This LAMP assay is particularly robust because the reaction mixture preparation does not involve complex steps. This method is ideal for use in resource-limited settings where Q fever is endemic. PMID:27167168

  19. Role of B Cells in Host Defense against Primary Coxiella burnetii Infection

    PubMed Central

    Schoenlaub, Laura; Elliott, Alexandra; Freches, Danielle; Mitchell, William J.

    2015-01-01

    Despite Coxiella burnetii being an obligate intracellular bacterial pathogen, our recent study demonstrated that B cells play a critical role in vaccine-induced immunity to C. burnetii infection by producing protective antibodies. However, the role of B cells in host defense against primary C. burnetii infection remains unclear. In this study, we investigated whether B cells play an important role in host defense against primary C. burnetii infection. The results showed that peritoneal B cells were able to phagocytose virulent C. burnetii bacteria and form Coxiella-containing vacuoles (CCVs) and that C. burnetii can infect and replicate in peritoneal B1a subset B cells in vitro, demonstrating a potential role for peritoneal B cells in host defense against C. burnetii infection in vivo. In addition, the results showing that B1a cells secreted a high level of interleukin-10 (IL-10) in response to C. burnetii infection in vitro suggest that B1a cells may play an important role in inhibiting the C. burnetii infection-induced inflammatory response. The observation that adoptive transfer of peritoneal B cells did not significantly affect the severity of C. burnetii infection-induced diseases in both severe combined immunity-deficient (SCID) and μMT mice indicates that peritoneal B cells alone may not be able to control C. burnetii infection. In contrast, our finding that C. burnetii infection induced more-severe splenomegaly and a higher bacterial burden in the spleens of B1a cell-deficient Bruton's tyrosine kinase x-linked immunity-deficient (BTKxid) mice than in their wild-type counterparts further suggests that B1a cells play an important role in host defense against primary C. burnetii infection. PMID:26438792

  20. Role of B cells in host defense against primary Coxiella burnetii infection.

    PubMed

    Schoenlaub, Laura; Elliott, Alexandra; Freches, Danielle; Mitchell, William J; Zhang, Guoquan

    2015-12-01

    Despite Coxiella burnetii being an obligate intracellular bacterial pathogen, our recent study demonstrated that B cells play a critical role in vaccine-induced immunity to C. burnetii infection by producing protective antibodies. However, the role of B cells in host defense against primary C. burnetii infection remains unclear. In this study, we investigated whether B cells play an important role in host defense against primary C. burnetii infection. The results showed that peritoneal B cells were able to phagocytose virulent C. burnetii bacteria and form Coxiella-containing vacuoles (CCVs) and that C. burnetii can infect and replicate in peritoneal B1a subset B cells in vitro, demonstrating a potential role for peritoneal B cells in host defense against C. burnetii infection in vivo. In addition, the results showing that B1a cells secreted a high level of interleukin-10 (IL-10) in response to C. burnetii infection in vitro suggest that B1a cells may play an important role in inhibiting the C. burnetii infection-induced inflammatory response. The observation that adoptive transfer of peritoneal B cells did not significantly affect the severity of C. burnetii infection-induced diseases in both severe combined immunity-deficient (SCID) and μMT mice indicates that peritoneal B cells alone may not be able to control C. burnetii infection. In contrast, our finding that C. burnetii infection induced more-severe splenomegaly and a higher bacterial burden in the spleens of B1a cell-deficient Bruton's tyrosine kinase x-linked immunity-deficient (BTK(xid)) mice than in their wild-type counterparts further suggests that B1a cells play an important role in host defense against primary C. burnetii infection. PMID:26438792

  1. The Recent Evolution of a Maternally-Inherited Endosymbiont of Ticks Led to the Emergence of the Q Fever Pathogen, Coxiella burnetii

    PubMed Central

    Duron, Olivier; Noël, Valérie; McCoy, Karen D.; Bonazzi, Matteo; Sidi-Boumedine, Karim; Morel, Olivier; Vavre, Fabrice; Zenner, Lionel; Jourdain, Elsa; Durand, Patrick; Arnathau, Céline; Renaud, François; Trape, Jean-François; Biguezoton, Abel S.; Cremaschi, Julie; Dietrich, Muriel; Léger, Elsa; Appelgren, Anaïs; Dupraz, Marlène; Gómez-Díaz, Elena; Diatta, Georges; Dayo, Guiguigbaza-Kossigan; Adakal, Hassane; Zoungrana, Sébastien; Vial, Laurence; Chevillon, Christine

    2015-01-01

    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. PMID:25978383

  2. Coxiella burnetii (Q fever) Infection in Farmed Ruminants in Three Northeastern Provinces and Inner Mongolia Autonomous Region, China.

    PubMed

    Cong, Wei; Meng, Qing-Feng; Shan, Xiao-Feng; Sun, Wu-Wen; Kang, Yuan-Huan; Chen, Long; Wang, Wei-Li; Qian, Ai-Dong

    2015-08-01

    Coxiella burnetii is the pathogenic agent of Q fever, a zoonosis that occurs worldwide. In China, the organism infects people and a wide range of wild and farmed animals. However, little is known about C. burnetii infection in farmed ruminants in northeastern China, and there appears to have been no previous study on sika deer. The present study was conducted to determine the seroprevalence of C. burnetii in farmed ruminants in this region of China. A total of 3147 domestic ruminants (784 sheep, 1016 cattle, and 1347 sika deer) were randomly collected for this study. An indirect enzyme-linked immunosorbent assay kit was used to detect the antibodies to C. burnetii. The results showed an overall seroprevalence of 16.7% in domestic ruminants (24.9%, 13.5%, and 12.3% in cattle, sheep, and sika deer, respectively). This is the first report of C. burnetii seroprevalence in sika deer in China. Protective and hygiene measures should be applied in farm management to reduce the risk of exposure of C. burnetii to humans. PMID:26273813

  3. In silico biosynthesis of virenose, a methylated deoxy-sugar unique to Coxiella burnetii lipopolysaccharide

    PubMed Central

    2012-01-01

    Background Coxiella burnetii is Gram-negative bacterium responsible for the zoonosis Q-fever. While it has an obligate intracellular growth habit, it is able to persist for extended periods outside of a host cell and can resist environmental conditions that would be lethal to most prokaryotes. It is these extracellular bacteria that are the infectious stage encountered by eukaryotic hosts. The intracellular form has evolved to grow and replicate within acidified parasitophorous vacuoles. The outer coat of C. burnetii comprises a complex lipopolysaccharide (LPS) component that includes the unique methylated-6-deoxyhexose, virenose. Although potentially important as a biomarker for C. burnetii, the pathway for its biosynthesis remains obscure. Results The 6-deoxyhexoses constitute a large family integral to the LPS of many eubacteria. It is believed that precursors of the methylated-deoxyhexoses traverse common early biosynthetic steps as nucleotide-monosaccharides. As a prelude to a full biosynthetic characterization, we present herein the results from bioinformatics-based, proteomics-supported predictions of the pathway for virenose synthesis. Alternative possibilities are considered which include both GDP-mannose and TDP-glucose as precursors. Conclusion We propose that biosynthesis of the unique C. burnetii biomarker, virenose, involves an early pathway similar to that of other C-3’-methylated deoxysugars which then diverges depending upon the nucleotide-carrier involved. The alternatives yield either the D- or L-enantiomers of virenose. Both pathways require five enzymatic steps, beginning with either glucose-6-phosphate or mannose-6-phosphate. Our in silico results comprise a model for virenose biosynthesis that can be directly tested. Definition of this pathway should facilitate the development of therapeutic agents useful for treatment of Q fever, as well as allowing improvements in the methods for diagnosing this highly infectious disease. PMID:23150954

  4. Candidatus Coxiella massiliensis Infection.

    PubMed

    Angelakis, Emmanouil; Mediannikov, Oleg; Jos, Sarah-Lyne; Berenger, Jean-Michel; Parola, Philippe; Raoult, Didier

    2016-02-01

    Bacteria genetically related to Coxiella burnetii have been found in ticks. Using molecular techniques, we detected Coxiella-like bacteria, here named Candidatus Coxiella massiliensis, in skin biopsy samples and ticks removed from patients with an eschar. This organism may be a common agent of scalp eschar and neck lymphadenopathy after tick bite. PMID:26811945

  5. Candidatus Coxiella massiliensis Infection

    PubMed Central

    Mediannikov, Oleg; Jos, Sarah-Lyne; Berenger, Jean-Michel; Parola, Philippe; Raoult, Didier

    2016-01-01

    Bacteria genetically related to Coxiella burnetii have been found in ticks. Using molecular techniques, we detected Coxiella-like bacteria, here named Candidatus Coxiella massiliensis, in skin biopsy samples and ticks removed from patients with an eschar. This organism may be a common agent of scalp eschar and neck lymphadenopathy after tick bite. PMID:26811945

  6. Coxiella burnetii glycomics and proteomics--tools for linking structure to function.

    PubMed

    Toman, Rudolf; Skultety, Ludovit; Ihnatko, Robert

    2009-05-01

    Coxiella burnetii, the causative agent of Q fever, is an obligate intracellular bacterium and a highly infectious pathogen. The disease is a widespread zoonosis and is endemic throughout the world. An easy aerosol dissemination, environmental persistence, and high infectivity make the bacterium a serious threat for humans and animals. Lipopolysaccharide is considered one of the major factors of virulence expression and infection of the bacterium. Detailed glycomic studies enabled to better understand structural and functional peculiarities of this biopolymer and its role in pathogenesis and immunity of Q fever. Recent proteomic studies of C. burnetii have brought new approaches in accurate detection of the infectious agent and offered new insights into the inter- or intra-species relatedness. Thus, structure/function relationship studies are currently of utmost importance in the field. This paper will focus on glycomic and proteomic approaches providing information on unique glycan and protein species of the microorganism as the candidate molecules for the use in detection/diagnosis, therapy, and prophylaxis. PMID:19538265

  7. Serological evidence of Rickettsia and Coxiella burnetii in humans of Buenos Aires, Argentina.

    PubMed

    Cicuttin, Gabriel Leonardo; Degiuseppe, Juan Ignacio; Mamianetti, Andrea; Corin, Marcela Viviana; Linares, María Cielo; De Salvo, María Nazarena; Dohmen, Federico Eugenio Gury

    2015-12-01

    In Buenos Aires city (Argentina), the circulation of these agents has been detected mainly in vectors and animals, few human cases having been described. The aim of our study was to determine the seroprevalence of Rickettsia (spotted fever--SFG--and typhus--TG--groups) and Coxiella burnetii (Q fever agent) in residents of Buenos Aires city. The study involved 99 participants. Rickettsia IgG antibodies against SFG and TG were detected by IFA in 28.3% and 16.2% of serum samples, respectively. SFG titers were mostly 1/64 (53.6%) with a maximum of 1/512 (3.5%) whereas TG titers ranged between 1/64 (62.5%) and 1/256 (6.3%). Only one sample showed a titer of 1/32 for C. burnetii (phases I and II). The circulation of these pathogens in urban areas such as the city of Buenos Aires should be considered by health services, especially at the primary care level. PMID:26616661

  8. Coxiella burnetii infection of marine mammals in the Pacific Northwest, 1997-2010.

    PubMed

    Kersh, Gilbert J; Lambourn, Dyanna M; Raverty, Stephen A; Fitzpatrick, Kelly A; Self, Joshua S; Akmajian, Adrianne M; Jeffries, Steven J; Huggins, Jessica; Drew, Clifton P; Zaki, Sherif R; Massung, Robert F

    2012-01-01

    Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Humans are commonly exposed via inhalation of aerosolized bacteria derived from the waste products of domesticated sheep and goats, and particularly from products generated during parturition. However, many other species can be infected with C. burnetii, and the host range and full zoonotic potential of C. burnetii is unknown. Two cases of C. burnetii infection in marine mammal placenta have been reported, but it is not known if this infection is common in marine mammals. To address this issue, placenta samples were collected from Pacific harbor seals (Phoca vitulina richardsi), harbor porpoises (Phocoena phocoena), and Steller sea lions (Eumetopias jubatus). Coxiella burnetii was detected by polymerase chain reaction (PCR) in the placentas of Pacific harbor seals (17/27), harbor porpoises (2/6), and Steller sea lions (1/2) collected in the Pacific Northwest. A serosurvey of 215 Pacific harbor seals sampled in inland and outer coastal areas of the Pacific Northwest showed that 34.0% (73/215) had antibodies against either Phase 1 or Phase 2 C. burnetii. These results suggest that C. burnetii infection is common among marine mammals in this region. PMID:22247392

  9. Coxiella burnetii Endocarditis in a Child Caused by a New Genotype.

    PubMed

    Briggs, Benjamin J; Raoult, Didier; Hijazi, Ziyad M; Edouard, Sophie; Angelakis, Emmanouil; Logan, Latania K

    2016-02-01

    Coxiella burnetii endocarditis is a rare diagnosis in children. We present a case of Q fever endocarditis due to a new genotype, MST 54, and review recent literature on Q fever infections in children. Practitioners should consider Q fever in culture-negative endocarditis, particularly in children with congenital heart disease and history of travel or residence in endemic regions. PMID:26535879

  10. Coxiella burnetii Infection of a Steller Sea Lion (Eumetopias jubatus) Found in Washington State ▿

    PubMed Central

    Kersh, Gilbert J.; Lambourn, Dyanna M.; Self, Joshua S.; Akmajian, Adrianne M.; Stanton, James B.; Baszler, Timothy V.; Raverty, Stephen A.; Massung, Robert F.

    2010-01-01

    A pregnant sea lion stranded in the State of Washington was found to have placentitis caused by a unique strain of Coxiella burnetii. This is the first description of coxiellosis in a sea lion and suggests that exposure to sea lions may be a risk factor for contracting Q fever. PMID:20592144

  11. Coxiella burnetii infection of a Steller sea lion (Eumetopias jubatus) found in Washington State.

    PubMed

    Kersh, Gilbert J; Lambourn, Dyanna M; Self, Joshua S; Akmajian, Adrianne M; Stanton, James B; Baszler, Timothy V; Raverty, Stephen A; Massung, Robert F

    2010-09-01

    A pregnant sea lion stranded in the State of Washington was found to have placentitis caused by a unique strain of Coxiella burnetii. This is the first description of coxiellosis in a sea lion and suggests that exposure to sea lions may be a risk factor for contracting Q fever. PMID:20592144

  12. Secondary Aortoesophageal Fistula Associated With Aneurysmal Graft Infection by Coxiella burnetii.

    PubMed

    Okwara, Chinemerem John; Petrasek, Jan; Gibson, Maeghan; Burstein, Ezra

    2016-04-01

    Aortoesophageal fistula is a rare and serious condition that carries a high mortality rate. We present a case of overt gastrointestinal bleeding from an aortoesophageal fistula in a patient with chronic infection of an endovascular prosthesis with Coxiella burnetii. PMID:27144194

  13. Secondary Aortoesophageal Fistula Associated With Aneurysmal Graft Infection by Coxiella burnetii

    PubMed Central

    Petrasek, Jan; Gibson, Maeghan; Burstein, Ezra

    2016-01-01

    Aortoesophageal fistula is a rare and serious condition that carries a high mortality rate. We present a case of overt gastrointestinal bleeding from an aortoesophageal fistula in a patient with chronic infection of an endovascular prosthesis with Coxiella burnetii. PMID:27144194

  14. In silico biosynthesis of virenose, a methylated deoxy-sugar unique to Coxiella burnetii lipopolysaccharide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Coxiella burnetii is Gram-negative bacterium responsible for the zoonosis Q-fever. While it has an obligate intracellulargrowth habit, it is able to persist for extended periods outside of a host cell and can resist environmental conditions that would be lethal to most prokaryotes. It is...

  15. Serological cross-reactions between Bartonella quintana, Bartonella henselae, and Coxiella burnetii.

    PubMed Central

    La Scola, B; Raoult, D

    1996-01-01

    The clinical manifestations of Q fever and bartonelloses can be confused, especially in cases of infectious endocarditis. Differential diagnosis of the diseases is important because the treatments required for Q fever and bartonelloses are different. Laboratory confirmation of a suspected case of either Q fever or bartonelloses is most commonly made by antibody estimation with an indirect immunofluorescence assay. With an indirect immunofluorescence assay, 258 serum samples from patients with Q fever were tested against Bartonella henselae and Bartonella quintana antigens, and 77 serum samples from patients with infection by Bartonella sp. were tested against Coxiella burnetii antigen. Cross-reactivity was observed: more than 50% of the chronic Q fever patients tested had antibodies which reacted against B. henselae antigen to a significant level. This cross-reaction was confirmed by a cross-adsorption study and protein immunoblotting. However, because the levels of specific antibody titers in cases of Bartonella endocarditis are typically extremely high, low-level cross-reaction between C. burnetii antibodies and B. henselae antigen in cases of Q fever endocarditis should not lead to misdiagnosis, provided serology testing for both agents is performed. PMID:8862597

  16. Multiple strains of Coxiella burnetii are present in the environment of St. Paul Island, Alaska.

    PubMed

    Duncan, C; Savage, K; Williams, M; Dickerson, B; Kondas, A V; Fitzpatrick, K A; Guerrero, J L; Spraker, T; Kersh, G J

    2013-08-01

    In 2010, Coxiella burnetii was identified at a high prevalence in the placentas of Northern fur seals (Callorhinus ursinus) collected at a single rookery on St. Paul Island Alaska; an area of the United States where the agent was not known to be present. As contamination was hypothesized as a potential cause of false positives, but nothing was known about environmental C. burnetii in the region, an environmental survey was conducted to look for the prevalence and distribution of the organism on the island. While environmental prevalence was low, two strains of the organism were identified using PCR targeting the COM1 and IS1111 genes. The two strains are consistent with the organism that has been increasingly identified in marine mammals as well as a strain type more commonly found in terrestrial environments and associated with disease in humans and terrestrial animals. Further work is needed to elucidate information regarding the ecology of this organism in this region, particularly in association with the coastal environment. PMID:22747976

  17. Multiple strains of Coxiella burnetii are present in the environment of St. Paul Island, Alaska

    PubMed Central

    Duncan, Colleen; Savage, Kate; Williams, Michael; Dickerson, Bobette; Kondas, Ashley V.; Fitzpatrick, Kelly A.; Guerrero, Juan Leon; Spraker, Terry; Kersh, Gilbert J.

    2015-01-01

    Summary In 2010, Coxiella burnetii was identified at a high prevalence in the placentas of Northern fur seals (Callorhinus ursinus) collected at a single rookery on St. Paul Island Alaska; an area of the United States where the agent was not known to be present. As contamination was hypothesized as a potential cause of false positives, but nothing was known about environmental C. burnetii in the region, an environmental survey was conducted to look for the prevalence and distribution of the organism on the island. While environmental prevalence was low, two strains of the organism were identified using PCR targeting the COM1 and IS1111 genes. The two strains are consistent with the organism that has been increasingly identified in marine mammals as well as a strain type more commonly found in terrestrial environments and associated with disease in humans and terrestrial animals. Further work is needed to elucidate information regarding the ecology of this organism in this region, particularly in association with the coastal environment. PMID:22747976

  18. The contribution of proteomics towards deciphering the enigma of Coxiella burnetii.

    PubMed

    Vranakis, Iosif; Papadioti, Anastasia; Tselentis, Yannis; Psaroulaki, Anna; Tsiotis, Georgios

    2013-01-01

    Coxiella burnetii, the causative agent of Q fever, is an intracellular bacterium and a potential weapon for bioterrorism. The widespread throughout the world, zoonosis is manifested clinically as a self-limited febrile illness, as pneumonia (acute Q fever) or as a chronic illness with endocarditis being its major complication. The recent Netherlands Q fever outbreak has driven the bacterium from a relatively cryptic, underappreciated, "niche" microorganism on the sideline of bacteriology, to one of possibly great impact on public health. Advances in the study of this microorganism proceeded slowly, primarily due to the, until recently, obligatory intracellular nature of the pathogen that in its virulent phase I must be manipulated under biosafety level-3 conditions. Proteomic studies, in particular, have generated a vast amount of information concerning several aspects of the bacterium such as virulence factors, detection/diagnostic and immunogenic biomarkers, inter-/intraspecies variation, resistance to antibiotics, and secreted effector proteins with significant clinical impact. The phenomenon observed following the genomics era, that of generation and accumulation of huge amount of data that ultimately end up unexploited on several databases, begins to emerge in the proteomics field as well. This review will focus on the advances in the field of C. burnetii proteomics through MS, attempting in parallel to utilize some of the proteomics findings by suggesting future directions for the improvement of Q fever diagnosis and therapy. PMID:23255407

  19. Coxiella burnetii Effector Proteins That Localize to the Parasitophorous Vacuole Membrane Promote Intracellular Replication

    PubMed Central

    Larson, Charles L.; Beare, Paul A.; Voth, Daniel E.; Howe, Dale; Cockrell, Diane C.; Bastidas, Robert J.; Valdivia, Raphael H.

    2014-01-01

    The intracellular bacterial pathogen Coxiella burnetii directs biogenesis of a parasitophorous vacuole (PV) that acquires host endolysosomal components. Formation of a PV that supports C. burnetii replication requires a Dot/Icm type 4B secretion system (T4BSS) that delivers bacterial effector proteins into the host cell cytosol. Thus, a subset of T4BSS effectors are presumed to direct PV biogenesis. Recently, the PV-localized effector protein CvpA was found to promote C. burnetii intracellular growth and PV expansion. We predict additional C. burnetii effectors localize to the PV membrane and regulate eukaryotic vesicle trafficking events that promote pathogen growth. To identify these vacuolar effector proteins, a list of predicted C. burnetii T4BSS substrates was compiled using bioinformatic criteria, such as the presence of eukaryote-like coiled-coil domains. Adenylate cyclase translocation assays revealed 13 proteins were secreted in a Dot/Icm-dependent fashion by C. burnetii during infection of human THP-1 macrophages. Four of the Dot/Icm substrates, termed Coxiella vacuolar protein B (CvpB), CvpC, CvpD, and CvpE, labeled the PV membrane and LAMP1-positive vesicles when ectopically expressed as fluorescently tagged fusion proteins. C. burnetii ΔcvpB, ΔcvpC, ΔcvpD, and ΔcvpE mutants exhibited significant defects in intracellular replication and PV formation. Genetic complementation of the ΔcvpD and ΔcvpE mutants rescued intracellular growth and PV generation, whereas the growth of C. burnetii ΔcvpB and ΔcvpC was rescued upon cohabitation with wild-type bacteria in a common PV. Collectively, these data indicate C. burnetii encodes multiple effector proteins that target the PV membrane and benefit pathogen replication in human macrophages. PMID:25422265

  20. Physicochemical characterization of the endotoxins from Coxiella burnetii strain Priscilla in relation to their bioactivities

    PubMed Central

    Toman, Rudolf; Garidel, Patrick; Andrä, Jörg; Slaba, Katarina; Hussein, Ahmed; Koch, Michel HJ; Brandenburg, Klaus

    2004-01-01

    Background Coxiella burnetii is the etiological agent of Q fever found worldwide. The microorganism has like other Gram-negative bacteria a lipopolysaccharide (LPS, endotoxin) in its outer membrane, which is important for the pathogenicity of the bacteria. In order to understand the biological activity of LPS, a detailed physico-chemical analysis of LPS is of utmost importace. Results The lipid A moiety of LPS is tetraacylated and has longer (C-16) acyl chains than most other lipid A from enterobacterial strains. The two ester-linked 3-OH fatty acids found in the latter are lacking. The acyl chains of the C. burnetii endotoxins exhibit a broad melting range between 5 and 25°C for LPS and 10 and 40°C for lipid A. The lipid A moiety has a cubic inverted aggregate structure, and the inclination angle of the D-glucosamine disaccharide backbone plane of the lipid A part with respect to the membrane normal is around 40°. Furthermore, the endotoxins readily intercalate into phospholipid liposomes mediated by the lipopolysaccharide-binding protein (LBP). The endotoxin-induced tumor necrosis factor α (TNFα) production in human mononuclear cells is one order of magnitude lower than that found for endotoxins from enterobacterial strains, whereas the same activity as in the latter compounds is found in the clotting reaction of the Limulus amebocyte lysate assay. Conclusions Despite a considerably different chemical primary structure of the C. burnetii lipid A in comparison with enterobacterial lipid A, the data can be well understood by applying the previously presented conformational concept of endotoxicity, a conical shape of the lipid A moiety of LPS and a sufficiently high inclination of the sugar backbone plane with respect to the membrane plane. Importantly, the role of the acyl chain fluidity in modulating endotoxicity now becomes more evident. PMID:14715092

  1. Occurrence and Genotyping of Coxiella burnetii in Ixodid Ticks in Oromia, Ethiopia.

    PubMed

    Kumsa, Bersissa; Socolovschi, Cristina; Almeras, Lionel; Raoult, Didier; Parola, Philippe

    2015-11-01

    This study was conducted from September 2011 to March 2014 to address the occurrence and genotypes of Coxiella burnetii using molecular methods in ticks collected from domestic animals in Ethiopia. Ticks were tested for C. burnetii by quantitative real-time polymerase chain reaction (qPCR) targeting two different genes followed by multispacer sequence typing (MST). An overall prevalence of 6.4% (54/842) of C. burnetii was recorded. C. burnetii was detected in 28.6% (14/49) of Amblyomma gemma, 25% (31/124) of Rhipicephalus pulchellus, 7.1% (1/14) of Hyalomma marginatum rufipes, 3.2% (2/62) of Am. variegatum, 3.1% (4/128) of Am. cohaerens, 1.6% (1/63) of Rh. praetextatus, and 0.6% (1/153) of Rhipicephalus (Boophilus) decoloratus. Significantly higher overall frequencies of C. burnetii DNA were observed in Am. gemma and Rh. pulchellus than in other tick species (Mantel-Haenszel [MH], P < 0.0001). The overall frequency of C. burnetii was significantly higher (MH, P < 0.0001) in ticks from southeastern districts (Arero, Moyale, and Yabelo) than that from other districts. This study demonstrated the presence of C. burnetii genotype MST 18 in ticks in southeastern districts and genotype MST 20 in ticks in central districts. This study highlights the importance of ticks in the epidemiology of C. burnetii in Ethiopia. PMID:26392155

  2. Eight New Genomes and Synthetic Controls Increase the Accessibility of Rapid Melt-MAMA SNP Typing of Coxiella burnetii

    PubMed Central

    Byström, Mona; Forsman, Mats; Frangoulidis, Dimitrios; Janse, Ingmar; Larsson, Pär; Lindgren, Petter; Öhrman, Caroline; van Rotterdam, Bart; Sjödin, Andreas; Myrtennäs, Kerstin

    2014-01-01

    The case rate of Q fever in Europe has increased dramatically in recent years, mainly because of an epidemic in the Netherlands in 2009. Consequently, there is a need for more extensive genetic characterization of the disease agent Coxiella burnetii in order to better understand the epidemiology and spread of this disease. Genome reference data are essential for this purpose, but only thirteen genome sequences are currently available. Current methods for typing C. burnetii are criticized for having problems in comparing results across laboratories, require the use of genomic control DNA, and/or rely on markers in highly variable regions. We developed in this work a method for single nucleotide polymorphism (SNP) typing of C. burnetii isolates and tissue samples based on new assays targeting ten phylogenetically stable synonymous canonical SNPs (canSNPs). These canSNPs represent previously known phylogenetic branches and were here identified from sequence comparisons of twenty-one C. burnetii genomes, eight of which were sequenced in this work. Importantly, synthetic control templates were developed, to make the method useful to laboratories lacking genomic control DNA. An analysis of twenty-one C. burnetii genomes confirmed that the species exhibits high sequence identity. Most of its SNPs (7,493/7,559 shared by >1 genome) follow a clonal inheritance pattern and are therefore stable phylogenetic typing markers. The assays were validated using twenty-six genetically diverse C. burnetii isolates and three tissue samples from small ruminants infected during the epidemic in the Netherlands. Each sample was assigned to a clade. Synthetic controls (vector and PCR amplified) gave identical results compared to the corresponding genomic controls and are viable alternatives to genomic DNA. The results from the described method indicate that it could be useful for cheap and rapid disease source tracking at non-specialized laboratories, which requires accurate genotyping

  3. Cell-Free Propagation of Coxiella burnetii Does Not Affect Its Relative Virulence

    PubMed Central

    Kuley, Runa; Smith, Hilde E.; Frangoulidis, Dimitrios; Smits, Mari A.; Jan Roest, Hendrik I.; Bossers, Alex

    2015-01-01

    Q fever is caused by the obligate intracellular bacterium Coxiella burnetii. In vitro growth of the bacterium is usually limited to viable eukaryotic host cells imposing experimental constraints for molecular studies, such as the identification and characterisation of major virulence factors. Studies of pathogenicity may benefit from the recent development of an extracellular growth medium for C. burnetii. However, it is crucial to investigate the consistency of the virulence phenotype of strains propagated by the two fundamentally different culturing systems. In the present study, we assessed the viability of C. burnetii and the lipopolysaccaride (LPS) encoding region of the bacteria in both culture systems as indirect but key parameters to the infection potential of C. burnetii. Propidium monoazide (PMA) treatment-based real-time PCR was used for enumeration of viable C. burnetii which were validated by fluorescent infectious focus forming unit counting assays. Furthermore, RNA isolated from C. burnetiipropagated in both the culture systems was examined for LPS-related gene expression. All thus far known LPS-related genes were found to be expressed in early passages in both culturing systems indicating the presence of predominantly the phase I form of C. burnetii. Finally, we used immune-competent mice to provide direct evidence, that the relative virulence of different C. burnetii strains is essentially the same for both axenic and cell-based methods of propagation. PMID:25793981

  4. [Coxiella burnetii infections and infections with bacteria of the genus Chlamydia in dairy cattle].

    PubMed

    Sting, R; Simmert, J; Mandl, J; Seemann, G; Bay, F; Müller, K F; Schmitt, K; Mentrup, T

    2000-01-01

    Comparative studies on the prevalence of infections caused by Coxiella burnetii (C. burnetii) and Chlamydia were carried out with 592 cattle older than 2 years and 234 cattle younger than 2 years. Of these 477 originated from 24 dairy herds with considerable fertility problems (positive herds) and 349 from 14 dairy herds without major fertility problems (control herds). For the direct detection of these pathogens in the genitals capture ELISAs were employed, for the demonstration of antibodies the complement fixation test (CFT). Direct detection of C. burnetii and Chlamydia single as well as mixed infection revealed significant higher values for cattle from positive herds compared with those from the control herds. Animals revealing insemination ratios of > or = 2 showed significantly more frequent excretion of Chlamydia via the genitals and antibodies against C. burnetii than cattle with an insemination ratio of < 2. Investigations of cows which had had an abortion showed no indications of significantly more frequent C. burnetii or chlamydial infections. Inseminated but non-pregnant cows excreted significantly more C. burnetii and Chlamydia than pregnant cows. Clinical signs of endometritis were associated with an enhanced excretion of Chlamydia. Animals younger than 2 years excreted significantly more frequently C. burnetii but not Chlamydia via the genitals than animals older than 2 years. Indirect test showed results vice versa. PMID:11153221

  5. Coxiella burnetii shedding during the peripartum period and subsequent fertility in dairy cattle.

    PubMed

    Garcia-Ispierto, I; López-Helguera, I; Tutusaus, J; Serrano, B; Monleón, E; Badiola, J J; López-Gatius, F

    2013-06-01

    The objective of this study was to assess the effects of Coxiella burnetii shedding or seropositivity on post-partum recovery and subsequent fertility in high-producing dairy cows. Given the difficulty in diagnosing C. burnetii infection at the farm level, an exhaustive series of tests in 43 pregnant animals that delivered at least one live calf were conducted, including blood serology and PCR of milk or colostrum, cotyledons (only at parturition), faeces, vaginal fluid against C. burnetii on gestation Day 171-177, at parturition and on Days 1-7, 8-14, 15-21, 22-28, 29-35 and 90-97 post-partum. During scheduled herd visits, ultrasonography (US) of the genital tract and examination of vaginal fluid were performed on Days 15-21 (V1), 22-28 (V2), 29-35 (V3) and 51-57 (V4) post-partum by the same veterinarian. Logistic regression analysis revealed that the likelihood of suffering endometritis (the presence of echogenic intrauterine fluid (IUF), cervical diameter of ≥4 cm or endometrial thickness ≥0.75 cm) was lower in C. burnetii-seropositive animals (OR = 0.10), compared with C. burnetii-seronegative animals. According to Kaplan-Meier survival analysis, C. burnetii-seronegative and non-shedding cows showed a delayed return to luteal activity and conception was delayed in non-shedding animals, compared with the remaining animals. Overall, the results of our study provide useful insight into the effects of C. burnetii infection on post-partum recovery and subsequent fertility. In particular, animals not infected with Coxiella seem to be susceptible to infection and not protected against the bacterium in dairy herds. The elevated costs of determining an infection at the farm level, make monitoring of cows virtually impossible from a clinical point of view. PMID:23106514

  6. Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue.

    PubMed

    Hedges, Jodi F; Robison, Amanda; Kimmel, Emily; Christensen, Kelly; Lucas, Erin; Ramstead, Andrew; Jutila, Mark A

    2016-06-01

    Coxiella burnetii is an intracellular pathogen and the cause of Q fever. Gamma interferon (IFN-γ) is critical for host protection from infection, but a role for type I IFN in C. burnetii infection has not been determined. Type I IFN supports host protection from a related pathogen, Legionella pneumophila, and we hypothesized that it would be similarly protective in C. burnetii infection. In contrast to our prediction, IFN-α receptor-deficient (IFNAR(-/-)) mice were protected from C. burnetii-induced infection. Therefore, the role of type I IFN in C. burnetii infection was distinct from that in L. pneumophila Mice treated with a double-stranded-RNA mimetic were protected from C. burnetii-induced weight loss through an IFNAR-independent pathway. We next treated mice with recombinant IFN-α (rIFN-α). When rIFN-α was injected by the intraperitoneal route during infection, disease-induced weight loss was exacerbated. Mice that received rIFN-α by this route had dampened interleukin 1β (IL-1β) expression in bronchoalveolar lavage fluids. However, when rIFN-α was delivered to the lung, bacterial replication was decreased in all tissues. Thus, the presence of type I IFN in the lung protected from infection, but when delivered to the periphery, type I IFN enhanced disease, potentially by dampening inflammatory cytokines. To better characterize the capacity for type I IFN induction by C. burnetii, we assessed expression of IFN-β transcripts by human macrophages following stimulation with lipopolysaccharide (LPS) from C. burnetii Understanding innate responses in C. burnetii infection will support the discovery of novel therapies that may be alternative or complementary to the current antibiotic treatment. PMID:27068091

  7. Development of an Ex Vivo Tissue Platform To Study the Human Lung Response to Coxiella burnetii.

    PubMed

    Graham, Joseph G; Winchell, Caylin G; Kurten, Richard C; Voth, Daniel E

    2016-05-01

    Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute debilitating flu-like illness that can also present as chronic endocarditis. Disease typically occurs following inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In human cells, C. burnetii generates a replication niche termed the parasitophorous vacuole (PV) by directing fusion with autophagosomes and lysosomes. C. burnetii requires this lysosomal environment for replication and uses a Dot/Icm type IV secretion system to generate the large PV. However, we do not understand how C. burnetii evades the intracellular immune surveillance that triggers an inflammatory response. We recently characterized human alveolar macrophage (hAM) infection in vitro and found that avirulent C. burnetii triggers sustained interleukin-1β (IL-1β) production. Here, we evaluated infection of ex vivo human lung tissue, defining a valuable approach for characterizing C. burnetii interactions with a human host. Within whole lung tissue, C. burnetii preferentially replicated in hAMs. Additionally, IL-1β production correlated with formation of an apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)-dependent inflammasome in response to infection. We also assessed potential activation of a human-specific noncanonical inflammasome and found that caspase-4 and caspase-5 are processed during infection. Interestingly, although inflammasome activation is closely linked to pyroptosis, lytic cell death did not occur following C. burnetii-triggered inflammasome activation, indicating an atypical response after intracellular detection. Together, these studies provide a novel platform for studying the human innate immune response to C. burnetii. PMID:26902725

  8. The First Serological Study of Coxiella burnetii among Pregnant Women in Iran

    PubMed Central

    KHAYYAT KHAMENEIE, Maryam; ASADI, Javad; KHALILI, Mohammad; ABIRI, Zeinab

    2016-01-01

    Background: Q fever is a zoonotic disease caused by Coxiella burnetii. There is no information about this disease in pregnant women in Iran. The aim of this study was to investigate the seroprevalence of C. burnetii infection among pregnant women in southwestern (Ahvaz) and northern (Parsabad) Iran and further to comparison its prevalence in normal and abnormal pregnancies. Methods: A total of 400 samples were collected randomly from pregnant women who referred to diagnostic laboratories of Ahvaz and Parsabad in 2014. An indirect ELISA kit, designed in Veterinary Faculty, was used to detect the specific antibodies against phase II humanC. burnetii in serum samples. Results: The overall prevalence of C. burnetii in sera from pregnant women was 29.3% (95% confidence interval (CI): 25–34%). The prevalence of C. burnetii infection was significantly different in Ahvaz and Parsabad with, respectively, 22 (95% CI: 16–28%) and 36.5% (95% CI: 30–43%). Total prevalence of C. burnetii infection in serum was significantly higher in women with abnormal pregnancy history (39.8%) compared with normal pregnancies (23.8%). Furthermore, maternal age had significant association with seropositivity and the prevalence increased with maternal age. This could be due to higher probability of encountering C. burnetii in older women. Conclusion: The present study demonstrated ahigh seroprevalence of C. burnetii infection among pregnant women in Iran for the first time. Seropositivity was associated with adverse pregnancy outcomes and maternal age. The pregnant women who experienced abnormal pregnancy had higher seroprevalence of C. burnetii compared to women with normal pregnancy. PMID:27252922

  9. Coxiella burnetii associated reproductive disorders in domestic animals--a critical review.

    PubMed

    Agerholm, Jørgen S

    2013-01-01

    The bacterium Coxiella burnetii has been detected in the fetal membranes, birth fluids and vaginal mucus, as well as in the milk and other excretions of several domestic mammals. The finding of C. burnetii in association with abortion, parturition and in the postpartum period has led to the hypothesis that C. burnetii causes a range of reproductive diseases. This review critically evaluates the scientific basis for this hypothesis in domestic mammals.The review demonstrates a solid evidence for the association between C. burnetii infection and sporadic cases of abortion, premature delivery, stillbirth and weak offspring in cattle, sheep and goats. C. burnetii induced in-herd epidemics of this complete expression of reproductive failure have been reported for sheep and goats, but not for cattle. The single entities occur only as part of the complex and not as single events such as generally increased stillbirth rate. Studies show that C. burnetii initially infects the placenta and that subsequent spread to the fetus may occur either haematogenous or by the amniotic-oral route. The consequences for the equine, porcine, canine and feline conceptus remains to the elucidated but that infection of the conceptus may occur is documented for most species. There is no solid evidence to support a hypothesis of C. burnetii causing disorders such as subfertility, endometritis/metritis, or retained fetal membranes in any kind of domestic animal species.There is a strong need to validate non-pathology based methods such as polymerase chain reaction for their use in diagnostic and research in relation to establishing C. burnetii as the cause of abortion and to adapt an appropriate study design and include adequate control animals when linking epidemiological findings to C. burnetii or when evaluating effects of vaccination in production herds. PMID:23419216

  10. Coxiella burnetii associated reproductive disorders in domestic animals-a critical review

    PubMed Central

    2013-01-01

    The bacterium Coxiella burnetii has been detected in the fetal membranes, birth fluids and vaginal mucus, as well as in the milk and other excretions of several domestic mammals. The finding of C. burnetii in association with abortion, parturition and in the postpartum period has led to the hypothesis that C. burnetii causes a range of reproductive diseases. This review critically evaluates the scientific basis for this hypothesis in domestic mammals. The review demonstrates a solid evidence for the association between C. burnetii infection and sporadic cases of abortion, premature delivery, stillbirth and weak offspring in cattle, sheep and goats. C. burnetii induced in-herd epidemics of this complete expression of reproductive failure have been reported for sheep and goats, but not for cattle. The single entities occur only as part of the complex and not as single events such as generally increased stillbirth rate. Studies show that C. burnetii initially infects the placenta and that subsequent spread to the fetus may occur either haematogenous or by the amniotic-oral route. The consequences for the equine, porcine, canine and feline conceptus remains to the elucidated but that infection of the conceptus may occur is documented for most species. There is no solid evidence to support a hypothesis of C. burnetii causing disorders such as subfertility, endometritis/metritis, or retained fetal membranes in any kind of domestic animal species. There is a strong need to validate non-pathology based methods such as polymerase chain reaction for their use in diagnostic and research in relation to establishing C. burnetii as the cause of abortion and to adapt an appropriate study design and include adequate control animals when linking epidemiological findings to C. burnetii or when evaluating effects of vaccination in production herds. PMID:23419216

  11. [The occurrence of Coxiella burnetii in sheep and ticks of the genus Dermacentor in Baden-Wuerttemberg].

    PubMed

    Sting, R; Breitling, N; Oehme, R; Kimmig, P

    2004-10-01

    This study examined the occurrence of Coxiella burnetii (C. burnetii), the infectious agent of Q-fever, in sheep and sheep-ticks in Baden-Wuerttemberg, Germany, as a possible source of infection in Q-fever outbreaks. Using PCR, we examined a total of 1066 Dermacentor ticks from 23 herds and 49 samples of tick excrement from 18 herds for C. burnetii. We found the infectious agent in one non-engorged tick and in one sample of tick excrement from the same herd, in Efringen-Kirchen (district Loerrach). Sequencing the PCR-products confirmed the amplifications as specific for C. burnetii. Further serological tests of random samples of the four districts of Baden-Wuerttemberg showed a seroprevalence from 0 to 1.4% using complement fixation test (CFT), as well as a 0.9 to 10.2% seroprevalence, using ELISA test. Serum samples from a Q-fever-suspicious herd resulted, however, in 6% (CFT) and 53% (ELISA) positive reactions. A comparison between CFT and ELISA showed both a correlation of the two test methods that increased with higher CFT titration levels and positive reactions using ELISA for 9.4% of the serums that had tested negative using CFT. The results of the present study reveal that ticks and their excrements are important vectors of transmission of Q-fever in Baden-Wuerttemberg. Investigations on C. burnetii using PCR as well as serological surveys of sheep are important instruments for diagnosis and disease control of Q-fever. PMID:15568636

  12. Coxiella burnetii infection is associated with placentitis in cases of bovine abortion.

    PubMed

    Bildfell, R J; Thomson, G W; Haines, D M; McEwen, B J; Smart, N

    2000-09-01

    A positive score on a modified acid-fast (MAF)-stained smear test of fresh placenta was used to identify a group of bovine abortion submissions believed to be infected with Coxiella burnetii. Immunohistochemical (IHC) testing for Coxiella and Chlamydia antigens was performed on 14 MAF smear-positive cases as well as 29 MAF smear-negative cases received during the study period. Nine MAF smear-positive cases as well as 1 MAF smear-negative case were Coxiella-positive via the IHC test. No placentas were positive for Chlamydia antigen. Various histopathologic features were categorized for all placentas and the presence or absence of selected risk categories was also graded for each case. The results between Coxiella IHC-positive cases and Coxiella IHC-negative/MAF-negative cases were compared using Fisher's exact test (P value at 95% confidence). Significant associations were found between Coxiella IHC-positive cases and the presence of placental inflammation (P = 0.0027), placental necrosis (P = 0.012), fetal pneumonia (P = 0.0152), and the visibility of Coxiella-like organisms within trophoblasts on hematoxylin and eosin-stained sections (P < 0.0001). Histopathologic features of Coxiella IHC-positive placentas included infiltration of the chorionic stroma by mononuclear cells, necrosis of chorionic trophoblasts, and focal exudation of fibrin and neutrophils. The results indicate that MAF smears are a good screening tool for the presence of Coxiella in placentas from bovine abortion cases and that the detection of this pathogen in aborted placentas via traditional staining or IHC methods is usually associated with placentitis. PMID:11021428

  13. Inhibition of inflammasome activation by Coxiella burnetii type IV secretion system effector IcaA

    PubMed Central

    Cunha, Larissa D.; Ribeiro, Juliana M.; Fernandes, Talita D.; Massis, Liliana M.; Khoo, Chen Ai; Moffatt, Jennifer H.; Newton, Hayley J.; Roy, Craig R.; Zamboni, Dario S.

    2015-01-01

    Coxiella burnetii is a highly infectious bacterium that promotes its own replication in macrophages by inhibiting several host cell responses. Here, we show that C. burnetii inhibits caspase-1 activation in primary mouse macrophages. By using co-infection experiments, we determine that the infection of macrophages with C. burnetii inhibits the caspase-11-mediated non-canonical activation of the NLRP3 inflammasome induced by subsequent infection with Escherichia coli or Legionella pneumophila. Genetic screening using flagellin mutants of L. pneumophila as a surrogate host, reveals a novel C. burnetii gene (IcaA) involved in the inhibition of caspase activation. Expression of IcaA in L. pneumophila inhibited the caspase-11 activation in macrophages. Moreover, icaA- mutants of C. burnetii failed to suppress the caspase-11-mediated inflammasome activation induced by L. pneumophila. Our data reveal IcaA as a novel C. burnetii effector protein that is secreted by the Dot/Icm type IV secretion system and interferes with the caspase-11-induced, non-canonical activation of the inflammasome. PMID:26687278

  14. Serological evidence of Coxiella burnetii exposure in native marsupials and introduced animals in Queensland, Australia.

    PubMed

    Cooper, A; Goullet, M; Mitchell, J; Ketheesan, N; Govan, B

    2012-07-01

    The state of Queensland has the highest incidence of Q fever in Australia. In recent years, there has been an increase in human cases where no contacts with the typical reservoir animals or occupations were reported. The aim of this study was to determine the seroprevalence of Coxiella burnetii in Australian native animals and introduced animals in northern and southeastern Queensland. Australian native marsupials sampled included the brushtail possum (Trichosurus vulpecula) and common northern bandicoot (Isoodon macrourus). Introduced species sampled included dingoes (Canis lupus dingo), cats (Felis catus), foxes (Vulpes vulpes) and pigs (Sus scrofa). Serum samples were tested by ELISA for both phase II and phase I antigens of the organism using an Australian isolate. The serological evidence of C. burnetii infection demonstrated in these species has public health implications due to their increasing movement into residential areas in regional Queensland. This study is the first known investigation of C. burnetii seroprevalence in these species in northern Queensland. PMID:21892986

  15. Ultrastructural investigations on surface structures involved in Coxiella burnetii phase variation.

    PubMed Central

    Krauss, H; Schiefer, H G; Schmatz, H D

    1977-01-01

    By using the cytochemical staining procedure with concanavalin A, horseradish peroxidase, and diaminobenzidine, no surface carbohydrates with terminal alpha-glucosyl or sterically closely related residues could be detected on the cell walls of Coxiella burnetii phases I and II. Using a polycationized ferritin derivative as a cytochemical probe, anionic binding sites were visualized in the electron microscope on cell membranes of C. burnetii phase II, but not on phase I organisms. The sites appeared to be masked in phase I particles. Anionic sites could be demonstrated on phase I organisms after treatment with NaIO4 or dimethyl sulfoxide. A number of different biological properties of C. burnetii phases I and II may depend on the presence or absence of a net negative charge on the surface of the cell walls of these organisms. Images PMID:404251

  16. Coxiella burnetii infection in a patient from a rural area of Monteria, Colombia.

    PubMed

    Mattar, Salim; Contreras, Verónica; González, Marco; Camargo, Francisco; Álvarez, Jaime; Oteo, José A

    2014-01-01

    Q fever is a zoonosis caused by Coxiella burnetii. In Colombia, there have been very few human cases reported to date. This report describes the case of a 56-year-old patient with a background in agriculture and livestock handling. An indirect immunofluorescence assay (IFA) showed high titers of IgG for C. burnetii anti-phase I (1: 256) and anti-phase II (1:1024). For the next six months the patient's IgG antibody titers remained high, and after treatment with doxycycline, the IgG antibody titers decreased to 50% (anti-phase I 1:128 and anti-phase II 1:512); this profile suggests an infection of C. burnetii. PMID:26120864

  17. Molecular characterization of cloned variants of Coxiella burnetii isolated in China.

    PubMed

    Ning, Z; Yu, S R; Quan, Y G; Xue, Z

    1992-03-01

    To study the molecular properties of Coxiella burnetii phase variants we cloned the phase variants of C. burnetii Qiyi (CBQY) strain by the red plaque technique. Three cloned strains, CBQYIC3 (phase I), CBQYIIC7 (phase II) and CBQYIIC5 (semirough-phase) were analysed by SDS-PAGE, immunoblot assay, plasmid isolation and agarose gel electrophoresis of DNA restriction fragments. The results suggest that the unique phase-dependent substance is a lipopolysaccharide and that most protein components of phase I and phase II cells are shared. No significant differences of DNA restriction fragments were found between clonal isolates of phase I and phase II C. burnetii CBQY strains. A plasmid of approximately 56 Kb was isolated from both phase I and phase II variants indicating that phase variation probably could not be attributed to its presence or absence. PMID:1359769

  18. Ultrastructural investigations on surface structures involved in Coxiella burnetii phase variation.

    PubMed

    Krauss, H; Schiefer, H G; Schmatz, H D

    1977-03-01

    By using the cytochemical staining procedure with concanavalin A, horseradish peroxidase, and diaminobenzidine, no surface carbohydrates with terminal alpha-glucosyl or sterically closely related residues could be detected on the cell walls of Coxiella burnetii phases I and II. Using a polycationized ferritin derivative as a cytochemical probe, anionic binding sites were visualized in the electron microscope on cell membranes of C. burnetii phase II, but not on phase I organisms. The sites appeared to be masked in phase I particles. Anionic sites could be demonstrated on phase I organisms after treatment with NaIO4 or dimethyl sulfoxide. A number of different biological properties of C. burnetii phases I and II may depend on the presence or absence of a net negative charge on the surface of the cell walls of these organisms. PMID:404251

  19. Chronic Q Fever in Alberta: A Case of Coxiella burnetii Mycotic Aneurysm and Concomitant Vertebral Osteomyelitis

    PubMed Central

    Janvier, Jack; Vaughan, Stephen

    2016-01-01

    Chronic Q fever is a potentially life-threatening infection from the intracellular, Gram-negative Coxiella burnetii. It presents most commonly as endocarditis or vascular infection in people with underlying cardiac or vascular disease. We discuss a case of a 67-year-old male with Coxiella burnetii vascular infection of a perirenal abdominal aortic graft. The patient had a history of an abdominal aortic aneurysm (AAA) repair 5 years earlier. He presented with a 12 × 6 × 8 cm perirenal pseudoaneurysm and concomitant L1, L2, and L3 vertebral body discitis. He underwent an open repair which revealed a grossly infected graft perioperatively. Q fever serology revealed phase I serological IgG titer of 1 : 2048 and phase II 1 : 1024 consistent with chronic Q fever. Polymerase chain reaction (PCR) on infected vascular tissue was positive for C. burnetii. The patient was started on doxycycline and hydroxychloroquine with good clinical response and decreasing serological titers. Recognizing chronic Q fever is a difficult task as symptoms are nonspecific, exposure risk is difficult to ascertain, and diagnosis is hidden from conventional microbiological investigations. Its recognition, however, is critical as C. burnetii is inherently resistant to standard empiric therapies used in cardiovascular infections. PMID:27366178

  20. Chronic Q Fever in Alberta: A Case of Coxiella burnetii Mycotic Aneurysm and Concomitant Vertebral Osteomyelitis.

    PubMed

    Stokes, William; Janvier, Jack; Vaughan, Stephen

    2016-01-01

    Chronic Q fever is a potentially life-threatening infection from the intracellular, Gram-negative Coxiella burnetii. It presents most commonly as endocarditis or vascular infection in people with underlying cardiac or vascular disease. We discuss a case of a 67-year-old male with Coxiella burnetii vascular infection of a perirenal abdominal aortic graft. The patient had a history of an abdominal aortic aneurysm (AAA) repair 5 years earlier. He presented with a 12 × 6 × 8 cm perirenal pseudoaneurysm and concomitant L1, L2, and L3 vertebral body discitis. He underwent an open repair which revealed a grossly infected graft perioperatively. Q fever serology revealed phase I serological IgG titer of 1 : 2048 and phase II 1 : 1024 consistent with chronic Q fever. Polymerase chain reaction (PCR) on infected vascular tissue was positive for C. burnetii. The patient was started on doxycycline and hydroxychloroquine with good clinical response and decreasing serological titers. Recognizing chronic Q fever is a difficult task as symptoms are nonspecific, exposure risk is difficult to ascertain, and diagnosis is hidden from conventional microbiological investigations. Its recognition, however, is critical as C. burnetii is inherently resistant to standard empiric therapies used in cardiovascular infections. PMID:27366178

  1. Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development.

    PubMed

    Martinez, Eric; Allombert, Julie; Cantet, Franck; Lakhani, Anissa; Yandrapalli, Naresh; Neyret, Aymeric; Norville, Isobel H; Favard, Cyril; Muriaux, Delphine; Bonazzi, Matteo

    2016-06-01

    The Q fever bacterium Coxiella burnetii replicates inside host cells within a large Coxiella-containing vacuole (CCV) whose biogenesis relies on the Dot/Icm-dependent secretion of bacterial effectors. Several membrane trafficking pathways contribute membranes, proteins, and lipids for CCV biogenesis. These include the endocytic and autophagy pathways, which are characterized by phosphatidylinositol 3-phosphate [PI(3)P]-positive membranes. Here we show that the C. burnetii secreted effector Coxiella vacuolar protein B (CvpB) binds PI(3)P and phosphatidylserine (PS) on CCVs and early endosomal compartments and perturbs the activity of the phosphatidylinositol 5-kinase PIKfyve to manipulate PI(3)P metabolism. CvpB association to early endosome triggers vacuolation and clustering, leading to the channeling of large PI(3)P-positive membranes to CCVs for vacuole expansion. At CCVs, CvpB binding to early endosome- and autophagy-derived PI(3)P and the concomitant inhibition of PIKfyve favor the association of the autophagosomal machinery to CCVs for optimal homotypic fusion of the Coxiella-containing compartments. The importance of manipulating PI(3)P metabolism is highlighted by mutations in cvpB resulting in a multivacuolar phenotype, rescuable by gene complementation, indicative of a defect in CCV biogenesis. Using the insect model Galleria mellonella, we demonstrate the in vivo relevance of defective CCV biogenesis by highlighting an attenuated virulence phenotype associated with cvpB mutations. PMID:27226300

  2. Coxiella burnetii effector protein subverts clathrin-mediated vesicular trafficking for pathogen vacuole biogenesis

    PubMed Central

    Larson, Charles L.; Beare, Paul A.; Howe, Dale; Heinzen, Robert A.

    2013-01-01

    Successful macrophage colonization by Coxiella burnetii, the cause of human Q fever, requires pathogen-directed biogenesis of a large, growth-permissive parasitophorous vacuole (PV) with phagolysosomal characteristics. The vesicular trafficking pathways co-opted by C. burnetii for PV development are poorly defined; however, it is predicted that effector proteins delivered to the cytosol by a defective in organelle trafficking/intracellular multiplication (Dot/Icm) type 4B secretion system are required for membrane recruitment. Here, we describe involvement of clathrin-mediated vesicular trafficking in PV generation and the engagement of this pathway by the C. burnetii type 4B secretion system substrate Coxiella vacuolar protein A (CvpA). CvpA contains multiple dileucine [DERQ]XXXL[LI] and tyrosine (YXXΦ)-based endocytic sorting motifs like those recognized by the clathrin adaptor protein (AP) complexes AP1, AP2, and AP3. A C. burnetii ΔcvpA mutant exhibited significant defects in replication and PV development, confirming the importance of CvpA in infection. Ectopically expressed mCherry-CvpA localized to tubular and vesicular domains of pericentrosomal recycling endosomes positive for Rab11 and transferrin receptor, and CvpA membrane interactions were lost upon mutation of endocytic sorting motifs. Consistent with CvpA engagement of the endocytic recycling system, ectopic expression reduced uptake of transferrin. In pull-down assays, peptides containing CvpA-sorting motifs and full-length CvpA interacted with AP2 subunits and clathrin heavy chain. Furthermore, depletion of AP2 or clathrin by siRNA treatment significantly inhibited C. burnetii replication. Thus, our results reveal the importance of clathrin-coated vesicle trafficking in C. burnetii infection and define a role for CvpA in subverting these transport mechanisms. PMID:24248335

  3. Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit disparate host responses

    PubMed Central

    Millar, Jess A.; Valdés, Raquel; Kacharia, Fenil R.; Landfear, Scott M.; Cambronne, Eric D.; Raghavan, Rahul

    2015-01-01

    Coxiella burnetii is a bacterium that thrives in an acidic parasitophorous vacuole (PV) derived from lysosomes. Leishmania mexicana, a eukaryote, has also independently evolved to live in a morphologically similar PV. As Coxiella and Leishmania are highly divergent organisms that cause different diseases, we reasoned that their respective infections would likely elicit distinct host responses despite producing phenotypically similar parasite-containing vacuoles. The objective of this study was to investigate, at the molecular level, the macrophage response to each pathogen. Infection of THP-1 (human monocyte/macrophage) cells with Coxiella and Leishmania elicited disparate host responses. At 5 days post-infection, when compared to uninfected cells, 1057 genes were differentially expressed (746 genes up-regulated and 311 genes down-regulated) in C. burnetii infected cells, whereas 698 genes (534 genes up-regulated and 164 genes down-regulated) were differentially expressed in L. mexicana infected cells. Interestingly, of the 1755 differentially expressed genes identified in this study, only 126 genes (~7%) are common to both infections. We also discovered that 1090 genes produced mRNA isoforms at significantly different levels under the two infection conditions, suggesting that alternate proteins encoded by the same gene might have important roles in host response to each infection. Additionally, we detected 257 micro RNAs (miRNAs) that were expressed in THP-1 cells, and identified miRNAs that were specifically expressed during Coxiella or Leishmania infections. Collectively, this study identified host mRNAs and miRNAs that were influenced by Coxiella and/or Leishmania infections, and our data indicate that although their PVs are morphologically similar, Coxiella and Leishmania have evolved different strategies that perturb distinct host processes to create and thrive within their respective intracellular niches. PMID:26300862

  4. Murine Alveolar Macrophages Are Highly Susceptible to Replication of Coxiella burnetii Phase II In Vitro.

    PubMed

    Fernandes, Talita D; Cunha, Larissa D; Ribeiro, Juliana M; Massis, Liliana M; Lima-Junior, Djalma S; Newton, Hayley J; Zamboni, Dario S

    2016-09-01

    Coxiella burnetii is a Gram-negative bacterium that causes Q fever in humans. Q fever is an atypical pneumonia transmitted through inhalation of contaminated aerosols. In mammalian lungs, C. burnetii infects and replicates in several cell types, including alveolar macrophages (AMs). The innate immunity and signaling pathways operating during infection are still poorly understood, in part because of the lack of relevant host cell models for infection in vitro In the study described here, we investigated and characterized the infection of primary murine AMs by C. burnetii phase II in vitro Our data reveal that AMs show a pronounced M2 polarization and are highly permissive to C. burnetii multiplication in vitro Murine AMs present an increased susceptibility to infection in comparison to primary bone marrow-derived macrophages. AMs support more than 2 logs of bacterial replication during 12 days of infection in culture, similar to highly susceptible host cells, such as Vero and THP-1 cells. As a proof of principle that AMs are useful for investigation of C. burnetii replication, we performed experiments with AMs from Nos2(-/-) or Ifng(-/-) mice. In the absence of gamma interferon and nitric oxide synthase 2 (NOS2), AMs were significantly more permissive than wild-type cells. In contrast, AMs from Il4(-/-) mice were more restrictive to C. burnetii replication, supporting the importance of M2 polarization for the permissiveness of AMs to C. burnetii replication. Collectively, our data account for understanding the high susceptibility of alveolar macrophages to bacterial replication and support the use of AMs as a relevant model of C. burnetii growth in primary macrophages. PMID:27297388

  5. Q Fever in Pregnant Goats: Pathogenesis and Excretion of Coxiella burnetii

    PubMed Central

    Roest, Hendrik-Jan; van Gelderen, Betty; Dinkla, Annemieke; Frangoulidis, Dimitrios; van Zijderveld, Fred; Rebel, Johanna; van Keulen, Lucien

    2012-01-01

    Coxiella burnetii is an intracellular bacterial pathogen that causes Q fever. Infected pregnant goats are a major source of human infection. However, the tissue dissemination and excretion pathway of the pathogen in goats are still poorly understood. To better understand Q fever pathogenesis, we inoculated groups of pregnant goats via the intranasal route with a recent Dutch outbreak C. burnetii isolate. Tissue dissemination and excretion of the pathogen were followed for up to 95 days after parturition. Goats were successfully infected via the intranasal route. PCR and immunohistochemistry showed strong tropism of C. burnetii towards the placenta at two to four weeks after inoculation. Bacterial replication seemed to occur predominantly in the trophoblasts of the placenta and not in other organs of goats and kids. The amount of C. burnetii DNA in the organs of goats and kids increased towards parturition. After parturition it decreased to undetectable levels: after 81 days post-parturition in goats and after 28 days post-parturition in kids. Infected goats gave birth to live or dead kids. High numbers of C. burnetii were excreted during abortion, but also during parturition of liveborn kids. C. burnetii was not detected in faeces or vaginal mucus before parturition. Our results are the first to demonstrate that pregnant goats can be infected via the intranasal route. C. burnetii has a strong tropism for the trophoblasts of the placenta and is not excreted before parturition; pathogen excretion occurs during birth of dead as well as healthy animals. Besides abortions, normal deliveries in C. burnetii-infected goats should be considered as a major zoonotic risk for Q fever in humans. PMID:23152826

  6. Mechanisms that may account for differential antibiotic susceptibilities among Coxiella burnetii isolates.

    PubMed Central

    Yeaman, M R; Baca, O G

    1991-01-01

    The Nine Mile, S Q217, and Priscilla isolates, representative of the three major genetic groups of Coxiella burnetii, are known to differ in their susceptibilities to antibiotics. Mechanisms potentially responsible for these differences were investigated. Accumulation of antibiotics by infected L929 cells and purified isolates was measured. In addition, C. burnetii plasmid-transformed Escherichia coli HB101 cells were used to study the possibility that different C. burnetii plasmids are responsible for disparate antibiotic susceptibilities of the isolates. L929 cells recently or persistently infected with the Priscilla isolate exhibited a significantly reduced accumulation of [3H]tetracycline as compared with that in L929 cells infected with either the Nine Mile or S Q217 isolates; accumulation of this drug was greater in cells recently infected each isolate. In contrast, L929 cells recently or persistently infected with the different isolates accumulated [3H]norfloxacin to an equivalent extent. [3H]tetracycline accumulation was approximately the same among the purified isolates. However, as measured by both scintillation and spectrofluorometry, norfloxacin accumulation was significantly diminished in the purified Priscilla isolate. pH had no apparent effect upon isolate permeabilities. The presence of C. burnetii QpH1 or QpRS plasmids did not alter the antibiotic susceptibility of E. coli. Collectively, these results indicate that differential susceptibilities to tetracyclines or fluoroquinolones in C. burnetii isolates may be the result of distinct mechanisms involving altered host-cell (tetracyclines) or isolate-specific (fluoroquinolones) permeabilities. PMID:1854176

  7. Comparative sensitivity of four different cell lines for the isolation of Coxiella burnetii.

    PubMed

    Lockhart, Michelle G; Islam, Aminul; Fenwick, Stan G; Graves, Stephen R; Stenos, John

    2012-09-01

    Coxiella burnetii is an obligate intracellular bacterium that causes the disease Q-fever. This is usually diagnosed by serology (immunofluorescence assay) and/or PCR detection of C. burnetii DNA. However, neither of these methods can determine the viability of the bacterium. Four different cell lines were compared for their ability to amplify very low numbers of viable C. burnetii. Two different isolates of C. burnetii were used. For the Henzerling isolate, DH82 (dog macrophage) cells were the most sensitive with an ID (50) (dose required to infect 50% of cell cultures) of 14.6 bacterial copies. For the Arandale isolate, Vero (monkey epithelial) cells were the most sensitive with an ID (50) of less than one bacterium in a 100-μL inoculum. The Vero cell line appeared highly useful as vacuoles could be seen microscopically in unstained infected cells. The findings of this study favour the use of Vero and DH82 tissue culture cell lines for isolation and growth of C. burnetii in vitro. The other cell lines, XTC-2 and L929, were less suitable. PMID:22681323

  8. Analysis of the cells involved in the lymphoproliferative response to Coxiella burnetii antigens.

    PubMed Central

    Izzo, A A; Marmion, B P; Hackstadt, T

    1991-01-01

    Vaccination with an inactivated, whole cell, Q fever vaccine (Q-vax) induces lasting antibody conversion and a positive delayed-type hypersensitivity (DTH) skin reaction in about 60% of recipients but a long-lasting positive lymphoproliferative or mitogenic response to C. burnetii antigens with peripheral blood mononuclear cells (PBMC) in 85-95% of subjects. Analysis of the lymphoproliferative response to C. burnetii antigens has now been made by fractionation-reconstitution experiments with PBMC from vaccines, from past infections, and from healthy controls. The major contributor to the response in immune subjects proved to be the T lymphocyte. T cells were stimulated by both the phase I and phase II antigens of two prototype strains of C. burnetii and responses were greatly amplified by addition of IL-2. Similar T lymphocyte stimulation profiles were obtained with the 'Priscilla' strain of C. burnetii which represents a different biotype of Coxiella isolated from Q fever endocarditis; Q-vax is therefore likely to protect against endocarditis strains. Fractionation-reconstitution experiments with T and B cells from vaccines and subjects infected in the past, using various antigenic or haptenic fractions from C. burnetii indicate that protein, non-lipopolysaccharide components of the organism are responsible for the mitogenic response of immune T cells. However, the role of the lipopolysaccharide in the protective immunogen has still to be defined. PMID:2070564

  9. Emergence of Coxiella burnetii in Ruminants on Reunion Island? Prevalence and Risk Factors

    PubMed Central

    Cardinale, Eric; Esnault, Olivier; Beral, Marina; Naze, Florence; Michault, Alain

    2014-01-01

    Q fever is a widespread zoonosis that is caused by Coxiella burnetii (C. burnetii), and ruminants are identified as the main sources of human infections. Some human cases have been described, but very limited information was available about Q fever in ruminants on Reunion Island, a tropical island in the Indian Ocean. A cross-sectional study was undertaken from March 2011 to August 2012 to assess the Q fever prevalence and to identify the major risk factors of C. burnetii infection in ruminants. A total of 516 ruminants (245 cattle, 137 sheep and 134 goats) belonging to 71 farms and localized in different ecosystems of the island were randomly selected. Samples of blood, vaginal mucus and milk were concomitantly collected from females, and a questionnaire was submitted to the farmers. Ticks from positively detected farms were also collected. The overall seropositivity was 11.8% in cattle, 1.4% in sheep and 13.4% in goats. C. burnetii DNA was detected by PCR in 0.81%, 4.4% and 20.1% in cow, sheep and goat vaginal swabs, respectively. C. burnetii shedding in milk was observed in 1% of cows, 0% in sheep and 4.7% in goats. None of the ticks were detected to be positive for C. burnetii. C. burnetii infection increased when the farm was exposed to prevailing winds and when there were no specific precautions for a visitor before entering the farm, and they decreased when a proper quarantine was set up for any introduction of a new ruminant and when the animals returned to the farm at night. MLVA genotyping confirmed the role of these risk factors in infection. PMID:25101780

  10. Emergence of Coxiella burnetii in ruminants on Reunion Island? Prevalence and risk factors.

    PubMed

    Cardinale, Eric; Esnault, Olivier; Beral, Marina; Naze, Florence; Michault, Alain

    2014-08-01

    Q fever is a widespread zoonosis that is caused by Coxiella burnetii (C. burnetii), and ruminants are identified as the main sources of human infections. Some human cases have been described, but very limited information was available about Q fever in ruminants on Reunion Island, a tropical island in the Indian Ocean. A cross-sectional study was undertaken from March 2011 to August 2012 to assess the Q fever prevalence and to identify the major risk factors of C. burnetii infection in ruminants. A total of 516 ruminants (245 cattle, 137 sheep and 134 goats) belonging to 71 farms and localized in different ecosystems of the island were randomly selected. Samples of blood, vaginal mucus and milk were concomitantly collected from females, and a questionnaire was submitted to the farmers. Ticks from positively detected farms were also collected. The overall seropositivity was 11.8% in cattle, 1.4% in sheep and 13.4% in goats. C. burnetii DNA was detected by PCR in 0.81%, 4.4% and 20.1% in cow, sheep and goat vaginal swabs, respectively. C. burnetii shedding in milk was observed in 1% of cows, 0% in sheep and 4.7% in goats. None of the ticks were detected to be positive for C. burnetii. C. burnetii infection increased when the farm was exposed to prevailing winds and when there were no specific precautions for a visitor before entering the farm, and they decreased when a proper quarantine was set up for any introduction of a new ruminant and when the animals returned to the farm at night. MLVA genotyping confirmed the role of these risk factors in infection. PMID:25101780

  11. Coxiella burnetii Infects Primary Bovine Macrophages and Limits Their Host Cell Response.

    PubMed

    Sobotta, Katharina; Hillarius, Kirstin; Mager, Marvin; Kerner, Katharina; Heydel, Carsten; Menge, Christian

    2016-06-01

    Although domestic ruminants have long been recognized as the main source of human Q fever, little is known about the lifestyle that the obligate intracellular Gram-negative bacterium Coxiella burnetii adopts in its animal host. Because macrophages are considered natural target cells of the pathogen, we established primary bovine monocyte-derived macrophages (MDM) as an in vitro infection model to study reservoir host-pathogen interactions at the cellular level. In addition, bovine alveolar macrophages were included to take cell type peculiarities at a host entry site into account. Cell cultures were inoculated with the virulent strain Nine Mile I (NMI; phase I) or the avirulent strain Nine Mile II (NMII; phase II). Macrophages from both sources internalized NMI and NMII. MDM were particularly permissive for NMI internalization, but NMI and NMII replicated with similar kinetics in these cells. MDM responded to inoculation with a general upregulation of Th1-related cytokines such as interleukin-1β (IL-1β), IL-12, and tumor necrosis factor alpha (TNF-α) early on (3 h postinfection). However, inflammatory responses rapidly declined when C. burnetii replication started. C. burnetii infection inhibited translation and release of IL-1β and vastly failed to stimulate increased expression of activation markers, such as CD40, CD80, CD86, and major histocompatibility complex (MHC) molecules. Such capability of limiting proinflammatory responses may help Coxiella to protect itself from clearance by the host immune system. The findings provide the first detailed insight into C. burnetii-macrophage interactions in ruminants and may serve as a basis for assessing the virulence and the host adaptation of C. burnetii strains. PMID:27021246

  12. Coxiella burnetii Nine Mile II proteins modulate gene expression of monocytic host cells during infection

    PubMed Central

    2010-01-01

    Background Coxiella burnetii is an intracellular bacterial pathogen that causes acute and chronic disease in humans. Bacterial replication occurs within enlarged parasitophorous vacuoles (PV) of eukaryotic cells, the biogenesis and maintenance of which is dependent on C. burnetii protein synthesis. These observations suggest that C. burnetii actively subverts host cell processes, however little is known about the cellular biology mechanisms manipulated by the pathogen during infection. Here, we examined host cell gene expression changes specifically induced by C. burnetii proteins during infection. Results We have identified 36 host cell genes that are specifically regulated when de novo C. burnetii protein synthesis occurs during infection using comparative microarray analysis. Two parallel sets of infected and uninfected THP-1 cells were grown for 48 h followed by the addition of chloramphenicol (CAM) to 10 μg/ml in one set. Total RNA was harvested at 72 hpi from all conditions, and microarrays performed using Phalanx Human OneArray™ slides. A total of 784 (mock treated) and 901 (CAM treated) THP-1 genes were up or down regulated ≥2 fold in the C. burnetii infected vs. uninfected cell sets, respectively. Comparisons between the complementary data sets (using >0 fold), eliminated the common gene expression changes. A stringent comparison (≥2 fold) between the separate microarrays revealed 36 host cell genes modulated by C. burnetii protein synthesis. Ontological analysis of these genes identified the innate immune response, cell death and proliferation, vesicle trafficking and development, lipid homeostasis, and cytoskeletal organization as predominant cellular functions modulated by C. burnetii protein synthesis. Conclusions Collectively, these data indicate that C. burnetii proteins actively regulate the expression of specific host cell genes and pathways. This is in addition to host cell genes that respond to the presence of the pathogen whether or not

  13. Seroepidemiologic survey in Thailand of Coxiella burnetii infection in cattle and chickens and presence in ticks attached to dairy cattle.

    PubMed

    Muramatsu, Yasukazu; Usaki, Noriyo; Thongchai, Chalermchaikit; Kramomtong, Indhira; Kriengsak, Poonsuk; Tamura, Yutaka

    2014-09-01

    A seroepidemiologic survey of Coxiella burnetii in cattle and chickens in Thailand was carried out using indirect fluorescent antibody test. Nine of the 130 serum samples from cattle were positive for antibodies against C. burnetii, with antibody titers ranging from 32 to 64. Only one of 113 serum samples from chickens was seropositive, with antibody titer of 16. No C. burnetii-specific DNA was detected using restriction fragment length polymorphism-nested PCR in spleens of cattle and chickens. However, coxiella DNA was detected in two of 102 engorged Rhipicephalus microplus ticks attached to dairy cattle. These results indicated that infestation of C. burnetii among cattle and chickens is considerably low in Thailand. PMID:25417520

  14. Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis.

    PubMed Central

    Heinzen, R A; Scidmore, M A; Rockey, D D; Hackstadt, T

    1996-01-01

    Coxiella burnetii and Chlamydia trachomatis are bacterial obligate intracellular parasites that occupy distinct vacuolar niches within eucaryotic host cells. We have employed immunofluorescence, cytochemistry, fluorescent vital stains, and fluid-phase markers in conjunction with electron, confocal, and conventional microscopy to characterize the vacuolar environments of these pathogens. The acidic nature of the C. burnetii-containing vacuole was confirmed by its acquisition of the acidotropic base acridine orange (AO). The presence of the vacuolar-type (H+) ATPase (V-ATPase) within the Coxiella vacuolar membrane was demonstrated by indirect immunofluorescence, and growth of C. burnetii was inhibited by bafilomycin A1 (Baf A), a specific inhibitor of the V-ATPase. In contrast, AO did not accumulate in C. trachomatis inclusions nor was the V-ATPase found in the inclusion membrane. Moreover, chlamydial growth was not inhibited by Baf A or the lysosomotropic amines methylamine, ammonium chloride, and chloroquine. Vacuoles harboring C. burnetii incorporated the fluorescent fluid- phase markers, fluorescein isothiocyanate-dextran (FITC-dex) and Lucifer yellow (LY), indicating trafficking between that vacuole and the endocytic pathway. Neither FITC-dex nor LY was sequestered by chlamydial inclusions. The late endosomal-prelysosomal marker cation-independent mannose 6-phosphate receptor was not detectable in the vacuolar membranes encompassing either parasite. However, the lysosomal enzymes acid phosphatase and cathepsin D and the lysosomal glycoproteins LAMP-1 and LAMP-2 localized to the C. burnetii vacuole but not the chlamydial vacuole. Interaction of C. trachomatis inclusions with the Golgi-derived vesicles was demonstrated by the transport of sphingomyelin, endogenously synthesized from C6-NBD-ceramide, to the chlamydial inclusion and incorporation into the bacterial cell wall. Similar trafficking of C-NBD-ceramide was not evident in C. burnetii-infected cells

  15. Long-Term Dynamics of Coxiella burnetii in Farmed Red Deer (Cervus elaphus)

    PubMed Central

    González-Barrio, David; Fernández-de-Mera, Isabel G.; Ortiz, José Antonio; Queirós, João; Ruiz-Fons, Francisco

    2015-01-01

    Several aspects of the dynamics of Coxiella burnetii that are relevant for the implementation of control strategies in ruminant herds with endemic Q fever are unknown. We designed a longitudinal study to monitor the dynamics of exposure to C. burnetii in a red deer herd with endemic infection in order to allow the design of Q fever-specific control approaches. Other relevant aspects of the dynamics of C. burnetii – the effect of herd immune status, age, season, and early infection on exposure, the average half-life of antibodies, the presence and duration of maternal humoral immunity, and the age of first exposure – were analyzed. The dynamics of C. burnetii in deer herds seems to be modulated by host herd and host individual factors and by particular host life-history traits. Red deer females become exposed to C. burnetii at the beginning of their second year since maternal antibodies protect them after birth and during the main pathogen shedding season – at the end of spring-early summer. Infection pressure varies between years, probably associated with herd immunity effects, determining inter-annual variation in the risk of exposure. These results suggest that any strategy applied to control C. burnetii in deer herds should be designed to induce immunity in their first year of life immediately after losing maternal antibodies. The short average life of C. burnetii antibodies suggests that any protection based on humoral immunity would require re-vaccination every 6 months. PMID:26697437

  16. Single Nucleotide Polymorphism Genotyping and Distribution of Coxiella burnetii Strains from Field Samples in Belgium

    PubMed Central

    Dal Pozzo, Fabiana; Renaville, Bénédicte; Martinelle, Ludovic; Renaville, Robert; Thys, Christine; Smeets, François; Kirschvink, Nathalie; Grégoire, Fabien; Delooz, Laurent; Czaplicki, Guy

    2015-01-01

    The genotypic characterization of Coxiella burnetii provides useful information about the strains circulating at the farm, region, or country level and may be used to identify the source of infection for animals and humans. The aim of the present study was to investigate the strains of C. burnetii circulating in caprine and bovine Belgian farms using a single nucleotide polymorphism (SNP) technique. Direct genotyping was applied to different samples (bulk tank milk, individual milk, vaginal swab, fetal product, and air sample). Besides the well-known SNP genotypes, unreported ones were found in bovine and caprine samples, increasing the variability of the strains found in the two species in Belgium. Moreover, multiple genotypes were detected contemporarily in caprine farms at different years of sampling and by using different samples. Interestingly, certain SNP genotypes were detected in both bovine and caprine samples, raising the question of interspecies transmission of the pathogen. PMID:26475104

  17. Treatment of an Abdominal Aortic Aneurysm Infected by Coxiella Burnetii Using a Cryopreserved Allograft.

    PubMed

    Jayet, Jérémie; Raux, Maxime; Allaire, Eric; Desgranges, Pascal; Cochennec, Frédéric

    2016-05-01

    Q fever is a worldwide zoonosis caused by an intracellular bacillus named Coxiella burnetii (CB) and is a rare cause of vascular infections. We report a case of abdominal aortic aneurysm infected by CB with bilateral paravertebral abscesses and contiguous spondylodiscitis treated by open repair using a cryopreserved allograft and long-term antibiotic therapy by oral doxycycline and oral hydroxychloroquine for a duration of 18 months. Twenty months after the operation, the patient had no infections signs and vascular complication. PMID:26968369

  18. Early cytokine and antibody responses against Coxiella burnetii in aerosol infection of BALB/c mice.

    PubMed

    Schoffelen, Teske; Self, Joshua S; Fitzpatrick, Kelly A; Netea, Mihai G; van Deuren, Marcel; Joosten, Leo A B; Kersh, Gilbert J

    2015-04-01

    Coxiella burnetii, a Gram-negative intracellular bacterium, can give rise to Q fever in humans and is transmitted mainly by inhalation of infected aerosols from animal reservoirs. Serology is commonly used to diagnose Q fever, but the early cellular immune response-i.e., C. burnetii-specific interferon γ (IFN-γ) production in response to antigen challenge-might be an additional diagnostic. Detection of IFN-γ responses has been used to identify past and chronic Q fever infections, but the IFN-γ response in acute Q fever has not been described. By challenging immunocompetent BALB/c mice with aerosols containing phase I C. burnetii, the timing and extent of IFN-γ recall responses were evaluated in an acute C. burnetii infection. Other cytokines were also measured in an effort to identify other potential diagnostic markers. The data show that after initial expansion of bacteria first in lungs and then in other tissues, the infection was cleared from day 10 onwards as reflected by the decreasing number of bacteria. The antigen-induced IFN-γ production by splenocytes coincided with emergence of IgM phase II antibodies at day 10 postinfection and preceded appearance of IgG antibodies. This was accompanied by the production of proinflammatory cytokines including interleukin (IL) 6, keratinocyte-derived cytokine, and IFN-γ-induced protein 10, followed by monocyte chemotactic protein 1, but not by IL-1β and tumor necrosis factor α, and only very low production of the anti-inflammatory cytokine IL-10. These data suggest that analysis of antigen-specific IFN-γ responses could be a useful tool for diagnosis of acute Q fever. Moreover, the current model of C. burnetii infection could be used to give new insights into immunological factors that predispose to development of persistent infection. PMID:25618420

  19. The Coxiella burnetii Cryptic Plasmid Is Enriched in Genes Encoding Type IV Secretion System Substrates▿ †

    PubMed Central

    Voth, Daniel E.; Beare, Paul A.; Howe, Dale; Sharma, Uma M.; Samoilis, Georgios; Cockrell, Diane C.; Omsland, Anders; Heinzen, Robert A.

    2011-01-01

    The intracellular bacterial pathogen Coxiella burnetii directs biogenesis of a phagolysosome-like parasitophorous vacuole (PV), in which it replicates. The organism encodes a Dot/Icm type IV secretion system (T4SS) predicted to deliver to the host cytosol effector proteins that mediate PV formation and other cellular events. All C. burnetii isolates carry a large, autonomously replicating plasmid or have chromosomally integrated plasmid-like sequences (IPS), suggesting that plasmid and IPS genes are critical for infection. Bioinformatic analyses revealed two candidate Dot/Icm substrates with eukaryotic-like motifs uniquely encoded by the QpH1 plasmid from the Nine Mile reference isolate. CpeC, containing an F-box domain, and CpeD, possessing kinesin-related and coiled-coil regions, were secreted by the closely related Legionella pneumophila Dot/Icm T4SS. An additional QpH1-specific gene, cpeE, situated in a predicted operon with cpeD, also encoded a secreted effector. Further screening revealed that three hypothetical proteins (CpeA, CpeB, and CpeF) encoded by all C. burnetii plasmids and IPS are Dot/Icm substrates. By use of new genetic tools, secretion of plasmid effectors by C. burnetii during host cell infection was confirmed using β-lactamase and adenylate cyclase translocation assays, and a C-terminal secretion signal was identified. When ectopically expressed in HeLa cells, plasmid effectors trafficked to different subcellular sites, including autophagosomes (CpeB), ubiquitin-rich compartments (CpeC), and the endoplasmic reticulum (CpeD). Collectively, these results suggest that C. burnetii plasmid-encoded T4SS substrates play important roles in subversion of host cell functions, providing a plausible explanation for the absolute maintenance of plasmid genes by this pathogen. PMID:21216993

  20. Host and Environmental Factors Modulate the Exposure of Free-Ranging and Farmed Red Deer (Cervus elaphus) to Coxiella burnetii

    PubMed Central

    Velasco Ávila, Ana Luisa; Boadella, Mariana; Beltrán-Beck, Beatriz; Barasona, José Ángel; Santos, João P. V.; Queirós, João; García-Pérez, Ana L.; Barral, Marta; Ruiz-Fons, Francisco

    2015-01-01

    The control of multihost pathogens, such as Coxiella burnetii, should rely on accurate information about the roles played by the main hosts. We aimed to determine the involvement of the red deer (Cervus elaphus) in the ecology of C. burnetii. We predicted that red deer populations from broad geographic areas within a European context would be exposed to C. burnetii, and therefore, we hypothesized that a series of factors would modulate the exposure of red deer to C. burnetii. To test this hypothesis, we designed a retrospective survey of 47 Iberian red deer populations from which 1,751 serum samples and 489 spleen samples were collected. Sera were analyzed by enzyme-linked immunosorbent assays (ELISA) in order to estimate exposure to C. burnetii, and spleen samples were analyzed by PCR in order to estimate the prevalence of systemic infections. Thereafter, we gathered 23 variables—within environmental, host, and management factors—potentially modulating the risk of exposure of deer to C. burnetii, and we performed multivariate statistical analyses to identify the main risk factors. Twenty-three populations were seropositive (48.9%), and C. burnetii DNA in the spleen was detected in 50% of the populations analyzed. The statistical analyses reflect the complexity of C. burnetii ecology and suggest that although red deer may maintain the circulation of C. burnetii without third species, the most frequent scenario probably includes other wild and domestic host species. These findings, taken together with previous evidence of C. burnetii shedding by naturally infected red deer, point at this wild ungulate as a true reservoir for C. burnetii and an important node in the life cycle of C. burnetii, at least in the Iberian Peninsula. PMID:26150466

  1. ELECTRON MICROSCOPIC OBSERVATIONS OF THE DEVELOPMENT OF COXIELLA BURNETII IN THE CHICK YOLK SAC1

    PubMed Central

    Anacker, R. L.; Fukushi, K.; Pickens, E. G.; Lackman, D. B.

    1964-01-01

    Anacker, R. L. (Rocky Mountain Laboratory, Hamilton, Mont.), K. Fukushi, E. G. Pickens, and D. B. Lackman. Electron microscopic observations of the development of Coxiella burnetii in the chick yolk sac. J. Bacteriol. 88:1130–1138. 1964.—Yolk sac material, obtained daily over a period of 1 week from embryos inoculated with seed of phase I Coxiella burnetii strain Ohio 314 containing 250 units of penicillin, was examined by electron microscopy and other techniques for the presence of rickettsiae. The concentration of rickettsiae in the yolk sac, as determined by electron microscopy, light microscopy, the complement-fixation test, recovery of organisms, and mouse infectivity, was low for the first 3 days, increased rapidly 3 to 5 days after infection, and then remained relatively constant. Rickettsiae in 3- to 7-day cultures, when observed by electron microscopy, had dense fibrillar centers surrounded by less-dense cytoplasmic material containing granules approximately 15 mμ in diameter. The whole was enclosed by multiple external layers. Many appeared to be in various stages of binary fission, and one form which contained a cross-wall was observed. These forms readily combined with ferritin-labeled specific antibody. In rare instances, several kinds of ”atypical” forms which did not combine with ferritin-labeled antibody were found in the cytoplasm of yolk-sac cells 4 to 5 days after inoculation; it is not certain whether these forms are artifacts or normal stages in the maturation of C. burnetii. These atypical forms were not observed in subsequent experiments in which embryonated eggs were inoculated with doses of penicillin varying from 0 to 4,000 units per egg. Images PMID:14219028

  2. Risk factors for Coxiella burnetii antibodies in bulk tank milk from Danish dairy herds.

    PubMed

    Agger, Jens Frederik; Paul, Suman; Christoffersen, Anna-Bodil; Agerholm, Jørgen Steen

    2013-01-01

    The aim was to identify risk factors associated with Coxiella burnetii antibody positivity in bulk tank milk (BTM) samples from 100 randomly selected Danish dairy cattle herds. Antibody levels were measured by an enzyme-linked immuno-sorbent assay. Before testing the herds, the farm managers were interviewed about hired labour, biosecurity, housing and herd health during the 12 months prior to the study. Variables considered important for C. burnetii antibody positivity in multivariable logistic regression analysis included the sharing of machines between farms (OR = 3.6), human contacts (OR = 4.2), artificial insemination by other people than artificial insemination technicians (OR = 7.7), routine herd health contract with the veterinarian (OR = 4.3) and hygiene precautions taken by veterinarians (OR = 5). In addition, herd size, hired labour, trading of cattle between farms, quarantine and use of calving and disease pens also showed significant association in univariable analysis. This study demonstrates that strict biosecurity is important for the prevention of infections with C. burnetii. PMID:24228845

  3. Impact of IS1111 insertion on the MLVA genotyping of Coxiella burnetii.

    PubMed

    Sidi-Boumedine, Karim; Duquesne, Véronique; Prigent, Myriam; Yang, Elise; Joulié, Aurélien; Thiéry, Richard; Rousset, Elodie

    2015-01-01

    Q fever epidemiological investigations of the likely sources of contamination may involve Coxiella burnetii MLVA for direct and rapid typing from clinical samples. However, little information is available with regards to PCR amplification failures in C. burnetii MLVA typing. This paper focuses on difficulties encountered with MLVA loci that may impact the interpretation of MLVA data and shows that some loci may constitute hotspots for mutational events. MLVA genotyping, using 17 different loci, was used on vaginal swabs (VS) from clinically infected animals as described elsewhere (Chmielewski et al., 2009). Amplicons of interest were sequenced and identified using the BLAST software by comparison with sequences available in GenBank. All VS samples produced MLVA patterns. However, amplification failures or unexpected sizes amplicons (>to 1.5 kbp), making the interpretation of MLVA complicated, were also observed. Sequencing of these amplicons revealed the presence of IS1111 element insertion. In this C. burnetii MLVA study some difficulties encountered with genotyping are highlighted and the role of IS1111 element in genome plasticity is confirmed. Finally, the need for the selection of a set of VNTRs for an efficient MLVA scheme and the question of standardization and harmonization for comparable MLVA typing data are raised again. PMID:26342253

  4. Coxiella burnetii DNA, but not viable bacteria, in dairy products in France.

    PubMed

    Eldin, Carole; Angelakis, Emmanouil; Renvoisé, Aurélie; Raoult, Didier

    2013-04-01

    Transmission by the oral route of Coxiella burnetii is controversial. Our objective was to evaluate dairy products in the transmission of Q fever. Pasteurized, unpasteurized, and thermized dairy products were tested for C. burnetii by using a quantitative polymerase chain reaction specific for IS1111 and IS30A spacers, culturing in human embryonic lung fibroblasts cells, and inoculation into BALB/c mice. We tested 201 products and C. burnetii was identified in 64%. Cow milk origin products were more frequently positive than goat or ewe products (P = 0.006 and P = 0.0001, respectively), and industrial food was more frequently positive than artisanal food (P < 0.0001). Food made from unpasteurized milk contained higher bacteria concentrations than food made from pasteurized milk (P = 0.02). All cultures were negative and mice did not show signs of illness. Farm animals are highly infected in France but consumption of cheese and yogurt does not seem to pose a public health risk for transmission of Q fever. PMID:23382158

  5. Apoptosis in normal and Coxiella burnetii-infected placentas from Alaskan northern fur seals (Callorhinus ursinus).

    PubMed

    Myers, E; Ehrhart, E J; Charles, B; Spraker, T; Gelatt, T; Duncan, C

    2013-07-01

    In 2010, Coxiella burnetii was identified in 75% of northern fur seal placentas from a single rookery in Alaska, but nothing was known about the significance of this organism in the population. Although many infectious organisms cause increased cell death, C. burnetii has been shown to suppress apoptosis of the host macrophages as an intracellular survival mechanism. To determine if infection induces a similar functional change in the placenta, immunohistochemistry for antibodies to cleaved caspase-3 (activated caspase-3) and the (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) technique were used to compare the amount of placental apoptosis in infected and noninfected placentas. There was a statistically significant difference in the frequency of apoptotic cells between infected and uninfected placentas, with more apoptosis identified in the uninfected placentas. This finding suggests that the survival mechanism of C. burnetii in host macrophages to reduce apoptosis may also be utilized in trophoblasts. The significance of decreased trophoblastic apoptosis for the northern fur seal fetus requires further investigation. PMID:23125144

  6. Prevalence and risk factors for Coxiella burnetii (Q fever) in Dutch dairy cattle herds based on bulk tank milk testing.

    PubMed

    van Engelen, E; Schotten, N; Schimmer, B; Hautvast, J L A; van Schaik, G; van Duijnhoven, Y T H P

    2014-11-01

    Despite cattle herds can harbor Coxiella burnetii, risk factors for C. burnetii presence in dairy cattle herds are largely unknown. Therefore, C. burnetii herd prevalence and risk factors for bulk tank milk (BTM) positivity were investigated. In this cross-sectional study, a questionnaire was filled out by the farmer and BTM from 301 farms was tested by ELISA for presence of C. burnetii antibodies and PCR for presence of C. burnetii DNA. Risk factors were identified by univariable and multivariable logistic regression analyses. Antibodies to C. burnetii were detected in 81.6% (CI: 77.2-85.9) and C. burnetii DNA in 18.8% (CI: 14.4-23.1) of the BTM samples. Herd size (OR=1.1 per 10 cows), cleaning the bedding of the cubicles at most every other day (OR=2.8) and purchase of cattle from at least two addresses (OR=3.1) showed a significant and positive association with ELISA positivity and use of an automatic milking system a negative association (OR=0.3). Risk factors for PCR positivity were purchase of cattle from at least two delivery addresses (OR=3.2), presence of cows with ticks (OR=2.0), use of an automatic milking system (OR=0.2) and presence of goats or sheep on the farm (OR=0.4). Biosecurity and general hygiene seem associated with introduction and spread of C. burnetii in dairy herds. PMID:25239684

  7. Maternofetal consequences of Coxiella burnetii infection in pregnancy: a case series of two outbreaks

    PubMed Central

    2012-01-01

    Background A high complication rate of Q fever in pregnancy is described on the basis of a limited number of cases. All pregnant women with proven Q fever regardless of clinical symptoms should therefore receive long-term cotrimoxazole therapy. But cotrimoxazole as a folic acid antagonist may cause harm to the fetus. We therefore investigated the Q fever outbreaks, Soest in 2003 and Jena in 2005, to determine the maternofetal consequences of Coxiella burnetii infection contracted during pregnancy. Methods Different outbreak investigation strategies were employed at the two sides. Antibody screening was performed with an indirect immunofluorescence test. Medical history and clinical data were obtained and serological follow up performed at delivery. Available placental tissue, amniotic fluid and colostrum/milk were further investigated by polymerase chain reaction and by culture. Results 11 pregnant women from Soest (screening rate: 49%) and 82 pregnant women from Jena (screening rate: 27%) participated in the outbreak investigation. 11 pregnant women with an acute C. burnetii infection were diagnosed. Three women had symptomatic disease. Three women, who were infected in the first trimester, were put on long-term therapy. The remaining women received cotrimoxazole to a lesser extent (n=3), were treated with macrolides for three weeks (n=1) or after delivery (n=1), were given no treatment at all (n=2) or received antibiotics ineffective for Q fever (n=1). One woman and her foetus died of an underlying disease not related to Q fever. One woman delivered prematurely (35th week) and one child was born with syndactyly. We found no obvious association between C. burnetii infection and negative pregnancy outcome. Conclusions Our data do not support the general recommendation of long-term cotrimoxazole treatment for Q fever infection in pregnancy. Pregnant women with symptomatic C. burnetii infections and with chronic Q fever should be treated. The risk-benefit ratio of

  8. Coxiella burnetii Induces Inflammatory Interferon-Like Signature in Plasmacytoid Dendritic Cells: A New Feature of Immune Response in Q Fever

    PubMed Central

    Ka, Mignane B.; Mezouar, Soraya; Ben Amara, Amira; Raoult, Didier; Ghigo, Eric; Olive, Daniel; Mege, Jean-Louis

    2016-01-01

    Plasmacytoid dendritic cells (pDCs) play a major role in antiviral immunity via the production of type I interferons (IFNs). There is some evidence that pDCs interact with bacteria but it is not yet clear whether they are protective or contribute to bacterial pathogenicity. We wished to investigate whether Coxiella burnetii, the agent of Q fever, interacts with pDCs. The stimulation of pDCs with C. burnetii increased the expression of activation and migratory markers (CD86 and CCR7) as determined by flow cytometry and modulated gene expression program as revealed by a microarray approach. Indeed, genes encoding for pro-inflammatory cytokines, chemokines, and type I INF were up-regulated. The up-regulation of type I IFN was correlated with an increase in IFN-α release by C. burnetii-stimulated pDCs. We also investigated pDCs in patients with Q fever endocarditis. Using flow cytometry and a specific gating strategy, we found that the number of circulating pDCs was significantly lower in patients with Q fever endocarditis as compared to healthy donors. In addition, the remaining circulating pDCs expressed activation and migratory markers. As a whole, our study identified non-previously reported activation of pDCs by C. burnetii and their modulation during Q fever. PMID:27446817

  9. Coxiella burnetii Induces Inflammatory Interferon-Like Signature in Plasmacytoid Dendritic Cells: A New Feature of Immune Response in Q Fever.

    PubMed

    Ka, Mignane B; Mezouar, Soraya; Ben Amara, Amira; Raoult, Didier; Ghigo, Eric; Olive, Daniel; Mege, Jean-Louis

    2016-01-01

    Plasmacytoid dendritic cells (pDCs) play a major role in antiviral immunity via the production of type I interferons (IFNs). There is some evidence that pDCs interact with bacteria but it is not yet clear whether they are protective or contribute to bacterial pathogenicity. We wished to investigate whether Coxiella burnetii, the agent of Q fever, interacts with pDCs. The stimulation of pDCs with C. burnetii increased the expression of activation and migratory markers (CD86 and CCR7) as determined by flow cytometry and modulated gene expression program as revealed by a microarray approach. Indeed, genes encoding for pro-inflammatory cytokines, chemokines, and type I INF were up-regulated. The up-regulation of type I IFN was correlated with an increase in IFN-α release by C. burnetii-stimulated pDCs. We also investigated pDCs in patients with Q fever endocarditis. Using flow cytometry and a specific gating strategy, we found that the number of circulating pDCs was significantly lower in patients with Q fever endocarditis as compared to healthy donors. In addition, the remaining circulating pDCs expressed activation and migratory markers. As a whole, our study identified non-previously reported activation of pDCs by C. burnetii and their modulation during Q fever. PMID:27446817

  10. Myeloid decidual dendritic cells and immunoregulation of pregnancy: defective responsiveness to Coxiella burnetii and Brucella abortus

    PubMed Central

    Gorvel, Laurent; Ben Amara, Amira; Ka, Mignane B.; Textoris, Julien; Gorvel, Jean-Pierre; Mege, Jean-Louis

    2014-01-01

    Dendritic cells (DCs) are a component of the placental immune system, but their role in pregnancy is still poorly understood. Decidual DCs (dDCs) were selected from at-term pregnancy on the basis of CD14 and CD11c expression. A phenotypic analysis revealed that dDCs are characterized by the expression of monocyte-derived DC (moDCs) markers and specific markers such as HLA-G and its ligand ILT4. As demonstrated by whole-genome microarray, dDCs expressed a specific gene program markedly distinct from that of moDCs; it included estrogen- and progesterone-regulated genes and genes encoding immunoregulatory cytokines, which is consistent with the context of foeto-maternal tolerance. A functional analysis of dDCs showed that they were unable to mature in response to bacterial ligands such as lipopolysaccharide or peptidoglycan, as assessed by the expression of HLA-DR, CD80, CD83, and CD86. When dDCs were incubated with bacteria known for their placenta tropism, Coxiella burnetii and Brucella abortus, they were also unable to mature and to produce inflammatory cytokines. It is likely that the defective maturation of dDCs and their inability to produce inflammatory cytokines is related to the spontaneous release of IL-10 by these cells. Taken together, these results suggest that dDCs exhibit an immunoregulatory program, which may favor the pathogenicity of C. burnetii or B. abortus. PMID:25566514

  11. B-cell non-Hodgkin lymphoma linked to Coxiella burnetii.

    PubMed

    Melenotte, Cléa; Million, Matthieu; Audoly, Gilles; Gorse, Audrey; Dutronc, Hervé; Roland, Gauthier; Dekel, Michal; Moreno, Asuncion; Cammilleri, Serge; Carrieri, Maria Patrizia; Protopopescu, Camelia; Ruminy, Philippe; Lepidi, Hubert; Nadel, Bertrand; Mege, Jean-Louis; Xerri, Luc; Raoult, Didier

    2016-01-01

    Bacteria can induce human lymphomas, whereas 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 2 diseases. We screened 1468 consecutive patients of the 2004 to 2014 French National Referral Center for Q fever database. The standardized incidence ratios (SIRs) 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 ribosomal RNA 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 with 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 (IL10) 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. PMID:26463422

  12. Molecular and serologic detection of Coxiella burnetii in native Korean goats (Capra hircus coreanae).

    PubMed

    Jung, Byeong Yeal; Seo, Min-Goo; Lee, Seung-Hun; Byun, Jae-Won; Oem, Jae-Ku; Kwak, Dongmi

    2014-09-17

    The occurrence of Q fever in native Korean goats (Capra hircus coreanae) was investigated for the first time in the country using ELISA and PCR. A total of 597 blood samples were collected from goats belonging to five different provinces of Korea. To detect Coxiella burnetii, sera were separated from the whole blood and analysed by ELISA; DNA was extracted directly from the whole blood and analysed by PCR. Overall, 114 (19.1%, 95% C.I.=16.1-22.4) and 57 goats (9.5%, 95% C.I.=7.5-12.2) tested positive for C. burnetii in the ELISA- and PCR-based screening, respectively, while 18 goats (3.0%, 95% C.I.=1.9-4.7) tested positive in both the assays. There was a significant difference between the number of ELISA- and PCR-positive goats (P<0.05). The seroprevalence of Q fever was significantly higher among the adult goats (≥1y, 22.0%) than among the young goats (<1y, 13.8%) (P<0.05). While the results of the serologic analysis showed no seasonal variation, data from the PCR-based assay indicated that there were a higher number of positive cases during the cold seasons. Because Q fever infection has high rates of prevalence in native Korean goats, further studies on humans at a high risk of contracting this disease should be conducted. The PCR-based assay used in this study is a useful method for the direct detection of C. burnetii in blood samples from small ruminants. PMID:25061007

  13. Chloroform-Methanol Residue of Coxiella burnetii Markedly Potentiated the Specific Immunoprotection Elicited by a Recombinant Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B of Rickettsia rickettsii in C3H/HeN Mice

    PubMed Central

    Gong, Wenping; Wang, Pengcheng; Xiong, Xiaolu; Jiao, Jun; Yang, Xiaomei; Wen, Bohai

    2015-01-01

    The obligate intracellular bacteria, Rickettsia rickettsii and Coxiella burnetii, are the potential agents of bio-warfare/bio-terrorism. Here C3H/HeN mice were immunized with a recombinant protein fragment rOmp-4 derived from outer membrane protein B, a major protective antigen of R. rickettsii, combined with chloroform-methanol residue (CMR) extracted from phase I C. burnetii organisms, a safer Q fever vaccine. These immunized mice had significantly higher levels of IgG1 and IgG2a to rOmpB-4 and interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), two crucial cytokines in resisting intracellular bacterial infection, as well as significantly lower rickettsial loads and slighter pathological lesions in organs after challenge with R. rickettsii, compared with mice immunized with rOmpB-4 or CMR alone. Additionally, after challenge with C. burnetii, the coxiella loads in the organs of these mice were significantly lower than those of mice immunized with rOmpB-4 alone. Our results prove that CMR could markedly potentiate enhance the rOmpB-4-specific immunoprotection by promoting specific and non-specific immunoresponses and the immunization with the protective antigen of R. rickettsii combined with CMR of C. burnetii could confer effective protection against infection of R. rickettsii or C. burnetii. PMID:25909586

  14. Absence of antibodies to Rickettsia spp., Bartonella spp., Ehrlichia spp. and Coxiella burnetii in Tahiti, French Polynesia

    PubMed Central

    2014-01-01

    Abtract Background In the Pacific islands countries and territories, very little is known about the incidence of infectious diseases due to zoonotic pathogens. To our knowledge, human infections due to Rickettsia spp., Coxiella burnetii, Ehrlichia spp. and Bartonella spp. have never been reported in French Polynesia; and infections due to C. burnetti have been reported worldwide except in New Zealand. To evaluate the prevalence of this disease, we conducted a serosurvey among French Polynesian blood donors. Methods The presence of immunoglobulin G antibodies against R. felis, R. typhi, R. conorii, C. burnetii, B. henselae, B. quintana, and E. chaffeensis was evaluated by indirect immunofluorescence assay in sera from 472 French Polynesian blood donors collected from 2011 to 2013. In addition, 178 ticks and 36 cat fleas collected in French Polynesia were also collected and tested by polymerase chain reaction to detect Rickettsia spp., B. henselae and Ehrlichia spp. Results None of the blood donors had antibodies at a significant level against Rickettsia spp., Coxiella burnetii, Ehrlichia spp. and Bartonella spp. All tested ticks and cat fleas were PCR-negative for Rickettsia spp., B. henselae, and Ehrlichia spp. Conclusion We cannot conclude that these pathogens are absent in French Polynesia but, if present, their prevalence is probably very low. C. burnetii has been reported worldwide except in New Zealand. It may also be absent from French Polynesia. PMID:24885466

  15. A cross sectional study evaluating the prevalence of Coxiella burnetii, potential risk factors for infection, and agreement between diagnostic methods in goats in Indiana.

    PubMed

    Bauer, Amy E; Hubbard, Kirk R A; Johnson, April J; Messick, Joanne B; Weng, Hsin-Yi; Pogranichniy, Roman M

    2016-04-01

    Coxiella burnetii is the etiologic agent of the zoonotic disease Q fever and is considered to be endemic in domestic ruminants. Small ruminants in particular are important reservoirs for human infection. Serologic and molecular methods are both available for diagnosis of infection with C. burnetii, but there has been little research evaluating the prevalence of this organism in small ruminants outside of the context of clinical disease outbreaks. The objectives of this study were to estimate seroprevalence of C. burnetii and the prevalence of shedding of C. burnetii DNA in milk by goats in Indiana, USA, to evaluate potential risk factors for association with C. burnetii exposure and shedding, and to assess the level of agreement between the enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) tests used to estimate prevalence. A total of 649 does over 1 year of age and not pregnant at the time of sampling were included in the study. Serum samples were collected from 608 does representing 89 farms. Milk samples were collected from 387 does representing 85 farms. Both milk and serum samples were collected from 356 does representing 80 farms. The estimated individual seroprevalence and shedding prevalence in milk adjusted for clustering were 3.1% (n=23/608, 95% CI: 1.2-7.0%) and 2.5% (n=9/387, 9.5% CI: 1.0-5.6%) respectively. Estimated adjusted herd level C. burnetii seroprevalence and herd level shedding prevalence were 11.5% (n=10/89, 95% CI: 6.4-20.1%) and 7.0% (n=6/85, 95% CI: 3.3-14.6%) respectively. Based on a generalized estimating equation model (GEE), meat breeds of goat had 7.0 times increased odds of shedding C. burnetii DNA in milk samples as compared to dairy breeds. Agreement between tests as determined by Cohen's kappa was poor at both the individual (kappa=0.04, 95% CI: -0.1 to 0.2) and herd (kappa=0.2, 95% CI: -0.1 to 0.5) levels. This indicates that serologic screening alone is unlikely to prevent the introduction

  16. Coxiella burnetii seropositivity and associated risk factors in sheep in Ontario, Canada.

    PubMed

    Meadows, S; Jones-Bitton, A; McEwen, S; Jansen, J; Menzies, P

    2015-11-01

    Coxiella burnetii is a zoonotic bacterium that can cause abortion in sheep in late gestation, as well as the delivery of stillborn, and non-viable lambs (Rodolakis, 2006). A cross-sectional study was conducted in Ontario, Canada, to investigate C. burnetii exposure in sheep. Between August 2010 and January 2012, sera from 2363 reproductively active ewes from 72 farms were tested for C. burnetii specific antibodies using the CHEKIT Q fever ELISA Test kit (IDEXX Laboratories). Overall, exposure was common; sheep-level seroprevalence was 14.7% (347/2363, 95% CI: 13.3-16.2), and was higher in dairy sheep (24.3%, 181/744) than meat sheep (10.2%, 166/1619) (p<0.0001). At the farm-level, 48.6% (35/72, 95% CI: 37.2-60.1) of farms had at least one seropositive sheep. A mixed multivariable logistic model that controlled for farm-level clustering, identified risk factors associated (p<0.05) with sheep seropositivity. Increasing female flock size (logarithmic scale) was associated with increased odds of seropositivity. By way of illustration, increasing the female flock size from 100 to 200 increased the odds of seropositivity by 2.26 times (95% CI: 1.5-3.5). Sheep that lambed in an airspace separate from the flock had 11.3 times (95% CI: 2.9-43.6) the odds of seropositivity relative to other sheep. The practice of loaning sheep that returned to the farm increased odds of seropositivity by 8.1 times (95% CI: 1.8-33.6). Lambing pen hygiene practices also influenced odds of seropositivity. Relative to sheep from farms where all lambing pen hygiene measures were practiced after lambing (i.e., adding bedding, removing birth materials and disinfection), sheep from farms that only added bedding, or those that just added bedding and removed birthing materials had 5.9 times (95% CI: 1.1-32.1) and 9.0 times (95% CI: 2.2-36.9) the odds of seropositivity, respectively. These results can be used to inform prevention and control strategies with the aim of reducing C. burnetii exposure in

  17. Coxiella burnetii seropositivity and associated risk factors in goats in Ontario, Canada.

    PubMed

    Meadows, S; Jones-Bitton, A; McEwen, S; Jansen, J; Menzies, P

    2015-10-01

    Coxiella burnetii is a zoonotic bacterium, and infection in goats with this bacterium can result in abortion, stillbirth or birth of non-viable kids. A cross-sectional study was conducted to identify the seroprevalence and risk factors for C. burnetii exposure in Ontario goats. Sera were collected between August 2010 and February 2012, and tested for C. burnetii specific antibodies using an enzyme-linked immunosorbent assay (IDEXX). Overall, 63.2% (48/76, 95% CI=51.9-73.4) of farms had one or more seropositive goats. A higher farm-level seroprevalence of 78.6% (33/42) was found on dairy goat farms, compared to 44.1% (15/34) on meat goat farms (p<0.01). At the overall individual-animal level, 32.5% (714/2195, 95% CI=30.6-34.5) of goats were seropositive. Similarly, a higher individual-level seroprevalence was identified for dairy goats (43.7%, 633/1447) compared to meat goats (10.8%, 81/748) (p<0.001). A mixed multivariable logistic model that controlled for farm-level clustering identified risk factors associated with seropositivity (p<0.05). Increases in the female herd size (logarithmic scale) were associated with increased odds of seropositivity, while increases in male herd size had a negative association with seropositivity. If other sheep or goat farms were located in a 5-km radius, goats had 5.6 times (95% CI=1.01-30.8) times the odds of seropositivity compared to those that were not. Relative to goats from farms where all kidding pen hygiene was practiced (adding bedding, removing birth materials and disinfection after kidding), goats from farms which only added bedding and removed birth materials had a higher odds of seropositivity (OR=19.3, 95% CI=1.1-330.4), as did goats from farms which practiced none of these measures (OR=161.0, 95% CI=2.4-10822.2). An interaction term revealed kidding outdoors when there were no swine on farm had a protective effect on seropositivity compared to kidding indoors, or kidding outdoors with swine on the farm. These

  18. Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

    PubMed Central

    Distel, Jesús S.; Aguilera, Milton O.; Colombo, María I.; Berón, Walter

    2015-01-01

    The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that process. PMID:26674774

  19. The uptake of apoptotic cells drives Coxiella burnetii replication and macrophage polarization: a model for Q fever endocarditis.

    PubMed

    Benoit, Marie; Ghigo, Eric; Capo, Christian; Raoult, Didier; Mege, Jean-Louis

    2008-05-01

    Patients with valvulopathy have the highest risk to develop infective endocarditis (IE), although the relationship between valvulopathy and IE is not clearly understood. Q fever endocarditis, an IE due to Coxiella burnetii, is accompanied by immune impairment. Patients with valvulopathy exhibited increased levels of circulating apoptotic leukocytes, as determined by the measurement of active caspases and nucleosome determination. The binding of apoptotic cells to monocytes and macrophages, the hosts of C. burnetii, may be responsible for the immune impairment observed in Q fever endocarditis. Apoptotic lymphocytes (AL) increased C. burnetii replication in monocytes and monocyte-derived macrophages in a cell-contact dependent manner, as determined by quantitative PCR and immunofluorescence. AL binding induced a M2 program in monocytes and macrophages stimulated with C. burnetii as determined by a cDNA chip containing 440 arrayed sequences and functional tests, but this program was in part different in monocytes and macrophages. While monocytes that had bound AL released high levels of IL-10 and IL-6, low levels of TNF and increased CD14 expression, macrophages that had bound AL released high levels of TGF-beta1 and expressed mannose receptor. The neutralization of IL-10 and TGF-beta1 prevented the replication of C. burnetii due to the binding of AL, suggesting that they were critically involved in bacterial replication. In contrast, the binding of necrotic cells to monocytes and macrophages led to C. burnetii killing and typical M1 polarization. Finally, interferon-gamma corrected the immune deactivation induced by apoptotic cells: it prevented the replication of C. burnetii and re-directed monocytes and macrophages toward a M1 program, which was deleterious for C. burnetii. We suggest that leukocyte apoptosis associated with valvulopathy may be critical for the pathogenesis of Q fever endocarditis by deactivating immune cells and creating a favorable environment

  20. Applying Fluorescence Resonance Energy Transfer (FRET) to Examine Effector Translocation Efficiency by Coxiella burnetii during siRNA Silencing.

    PubMed

    Newton, Patrice; Latomanski, Eleanor A; Newton, Hayley J

    2016-01-01

    Coxiella burnetii, the causative agent of Q fever, is an intracellular pathogen that relies on a Type IV Dot/Icm Secretion System to establish a replicative niche. A cohort of effectors are translocated through this system into the host cell to manipulate host processes and allow the establishment of a unique lysosome-derived vacuole for replication. The method presented here involves the combination of two well-established techniques: specific gene silencing using siRNA and measurement of effector translocation using a FRET-based substrate that relies on β-lactamase activity. Applying these two approaches, we can begin to understand the role of host factors in bacterial secretion system function and effector translocation. In this study we examined the role of Rab5A and Rab7A, both important regulators of the endocytic trafficking pathway. We demonstrate that silencing the expression of either protein results in a decrease in effector translocation efficiency. These methods can be easily modified to examine other intracellular and extracellular pathogens that also utilize secretion systems. In this way, a global picture of host factors involved in bacterial effector translocation may be revealed. PMID:27501079

  1. Antigenic differences between Coxiella burnetii cells revealed by postembedding immunoelectron microscopy and immunoblotting.

    PubMed Central

    McCaul, T F; Banerjee-Bhatnagar, N; Williams, J C

    1991-01-01

    The aim of this study was to investigate the antigenic structures of the morphologically distinct cells of the Coxiella burnetii developmental cycle. Postembedding immunoelectron microscopy with polyclonal antibodies produced in rabbits to (i) phase I cells, (ii) a chloroform-methanol residue fraction of cells, (iii) the cell walls (CW) of large and small cells and small dense cells (SDC), and (iv) the peptidoglycan-protein complexes of small cells and SDC labelled the continuum of morphologically distinct cells. But these antibodies did not distinguish between the antigenic structures of the various cells. Monoclonal antibodies to the phase I lipopolysaccharide labelled the CW of a majority of the smaller cells, but there was diminished reactivity to the larger cells. Although monoclonal antibodies to a 29.5-kDa outer membrane protein labelled the CW of the large mother cells, the large cells, and the small cells, a minority of the SDC with compact CW were not labelled. The endogenous spore within the mother cell was not labelled by the polyclonal or monoclonal antibodies to cellular components. A selected population of SDC was prepared by osmotic lysis of large cells, differential centrifugation, Renografin step-gradient fractionation, and breakage of the small cells in a French press at 20,000 lb/in2. The pressure-resistant SDC collected as fraction CL did not contain the 29.5-kDa protein, as evidenced by the lack of (i) Coomassie brilliant blue staining of protein in the 29.5-kDa region of sodium dodecyl sulfate-polyacrylamide gels and (ii) reactivity of the 29.5-kDa protein antigenic epitopes in immunoblotting with monoclonal antibodies to the protein. In contrast, CW of the pressure-sensitive small cells contained the 29.5-kDa protein. Therefore, the observed ultrastructural differences between large and small cells and SDC reflect differences in sensitivity to breakage by pressure treatment and in cell-associated antigens. Although the process of

  2. Characterization of a Lipopolysaccharide-Targeted Monoclonal Antibody and Its Variable Fragments as Candidates for Prophylaxis against the Obligate Intracellular Bacterial Pathogen Coxiella burnetii

    PubMed Central

    Peng, Ying; Schoenlaub, Laura; Elliott, Alexandra; Mitchell, William J.

    2014-01-01

    Our previous study demonstrated that treatment of Coxiella burnetii with the phase I lipopolysaccharide (PI-LPS)-targeted monoclonal antibody (MAb) 1E4 significantly inhibited C. burnetii infection in mice, suggesting that 1E4 is a protective MAb. To determine whether passive transfer of antibodies (Abs) can provide protection against C. burnetii natural infection, we examined if passive transfer of 1E4 would protect SCID mice against C. burnetii aerosol infection. The results indicated that 1E4 conferred significant protection against aerosolized C. burnetii, suggesting that 1E4 may be useful for preventing C. burnetii natural infection. To further understand the mechanisms of 1E4-mediated protection and to test the possibility of using humanized 1E4 to prevent C. burnetii infection, we examined whether the Fab fragment of 1E4 (Fab1E4), a recombinant murine single-chain variable fragment (muscFv1E4), and a humanized single-chain variable fragment (huscFv1E4) retained the ability of 1E4 to inhibit C. burnetii infection. The results indicated that Fab1E4, muscFv1E4, and huscFv1E4 were able to inhibit C. burnetii infection in mice but that their ability to inhibit C. burnetii infection was lower than that of 1E4. In addition, treatment of C. burnetii with Fab1E4, muscFv1E4, or huscFv1E4 can block C. burnetii infection of macrophages. Interestingly, treatment of C. burnetii with huscFv1E4 can significantly reduce C. burnetii infectivity in human macrophages. This report provides the first evidence to demonstrate that the humanized variable fragments of an LPS-specific MAb can neutralize C. burnetii infection and appears to be a promising step toward the potential use of a humanized MAb as emergency prophylaxis against C. burnetii exposure. PMID:25114119

  3. Spread of Coxiella burnetii between dairy cattle herds in an enzootic region: modelling contributions of airborne transmission and trade.

    PubMed

    Pandit, Pranav; Hoch, Thierry; Ezanno, Pauline; Beaudeau, François; Vergu, Elisabeta

    2016-01-01

    Q fever, a worldwide zoonotic disease caused by Coxiella burnetii, is a looming concern for livestock and public health. Epidemiological features of inter-herd transmission of C. burnetii in cattle herds by wind and trade of cows are poorly understood. We present a novel dynamic spatial model describing the inter-herd regional spread of C. burnetii in dairy cattle herds, quantifying the ability of airborne transmission and animal trade in C. burnetii propagation in an enzootic region. Among all the new herd infections, 92% were attributed to airborne transmission and the rest to cattle trade. Infections acquired following airborne transmission were shown to cause relatively small and ephemeral intra-herd outbreaks. On the contrary, disease-free herds purchasing an infectious cow experienced significantly higher intra-herd prevalence. The results also indicated that, for short duration, both transmission routes were independent from each other without any synergistic effect. The model outputs applied to the Finistère department in western France showed satisfactory sensitivity (0.71) and specificity (0.80) in predicting herd infection statuses at the end of one year in a neighbourhood of 3 km around expected incident herds, when compared with data. The model developed here thus provides important insights into the spread of C. burnetii between dairy cattle herds and paves the way for implementation and assessment of control strategies. PMID:27048416

  4. Characterization of the GDP-D-mannose biosynthesis pathway in Coxiella burnetii: the initial steps for GDP-β-D-virenose biosynthesis.

    PubMed

    Narasaki, Craig T; Mertens, Katja; Samuel, James E

    2011-01-01

    Coxiella burnetii, the etiologic agent of human Q fever, is a gram-negative and naturally obligate intracellular bacterium. The O-specific polysaccharide chain (O-PS) of the lipopolysaccharide (LPS) of C. burnetii is considered a heteropolymer of the two unusual sugars β-D-virenose and dihydrohydroxystreptose and mannose. We hypothesize that GDP-D-mannose is a metabolic intermediate to GDP-β-D-virenose. GDP-D-mannose is synthesized from fructose-6-phosphate in 3 successive reactions; Isomerization to mannose-6-phosphate catalyzed by a phosphomannose isomerase (PMI), followed by conversion to mannose-1-phosphate mediated by a phosphomannomutase (PMM) and addition of GDP by a GDP-mannose pyrophosphorylase (GMP). GDP-D-mannose is then likely converted to GDP-6-deoxy-D-lyxo-hex-4-ulopyranose (GDP-Sug), a virenose intermediate, by a GDP-mannose-4,6-dehydratase (GMD). To test the validity of this pathway in C. burnetii, three open reading frames (CBU0671, CBU0294 and CBU0689) annotated as bifunctional type II PMI, as PMM or GMD were functionally characterized by complementation of corresponding E. coli mutant strains and in enzymatic assays. CBU0671, failed to complement an Escherichia coli manA (PMM) mutant strain. However, complementation of an E. coli manC (GMP) mutant strain restored capsular polysaccharide biosynthesis. CBU0294 complemented a Pseudomonas aeruginosa algC (GMP) mutant strain and showed phosphoglucomutase activity (PGM) in a pgm E. coli mutant strain. Despite the inability to complement a manA mutant, recombinant C. burnetii PMI protein showed PMM enzymatic activity in biochemical assays. CBU0689 showed dehydratase activity and determined kinetic parameters were consistent with previously reported data from other organisms. These results show the biological function of three C. burnetii LPS biosynthesis enzymes required for the formation of GDP-D-mannose and GDP-Sug. A fundamental understanding of C. burnetii genes that encode PMI, PMM and GMP is

  5. Molecular typing of Coxiella burnetii from animal and environmental matrices during Q fever epidemics in the Netherlands

    PubMed Central

    2012-01-01

    Background The bacterium Coxiella burnetii has caused unprecedented outbreaks of Q fever in the Netherlands between 2007 and 2010. Since 2007, over 4000 human cases have been reported, with 2354 cases in 2009 alone. Dairy goat farms were identified as most probable sources for emerging clusters of human Q fever cases in their vicinity. However, identifying individual farms as primary source for specific clusters of human cases remains a challenge, partly due to limited knowledge of the different C. burnetii strains circulating in livestock, the environment and humans. Results We used a multiplex multi-locus variable number of tandem repeats analysis (MLVA) assay to investigate the genotypic diversity of C. burnetii in different types of samples that were collected nationwide during the Dutch Q fever outbreaks between 2007 and 2010. Typing was performed on C. burnetii positive samples obtained from several independent studies investigating C. burnetii presence in animals and the environment. Six different genotypes were identified on 45 farm locations, based on sequence-confirmed estimates of repeat numbers of six MLVA markers. MLVA genotype A was observed on 38 of the 45 selected farm locations in animals and in environmental samples. Conclusions Sequence confirmation of the numbers of tandem repeats within each locus and consensus about repeat identification is essential for accurate MLVA typing of C. burnetii. MLVA genotype A is the most common genotype in animal samples obtained from goat, sheep, and rats, as well as in environmental samples such as (aerosolized) dust, which is considered to be the major transmission route from animals via the environment to humans. The finding of a single dominant MLVA genotype in patients, the environment, and livestock complicates accurate source-finding. Pinpointing individual sources in the Netherlands requires discrimination of genotypes at a higher resolution than attained by using MLVA, as it is likely that the dominant

  6. Simultaneous differential detection of Chlamydophila abortus, Chlamydophila pecorum and Coxiella burnetii from aborted ruminant's clinical samples using multiplex PCR

    PubMed Central

    2009-01-01

    Background Chlamydiosis and Q fever, two zoonosis, are important causes of ruminants' abortion around the world. They are caused respectively by strictly intracellular and Gram negative bacterium Chlamydophila abortus (Cp. abortus) and Coxiella burnetii (C. burnetii). Chlamydophila pecorum (Cp. pecorum) is commonly isolated from the digestive tract of clinically inconspicuous ruminants but the abortive and zoonotic impact of this bacterium is still unknown because Cp. pecorum is rarely suspected in abortion cases of small ruminants. We have developed a multiplex PCR (m-PCR) for rapid simultaneous differential detection of Cp. abortus, Cp. pecorum and C. burnetii in clinical samples taken from infected animals. Results Specific PCR primers were designed and a sensitive and specific m-PCR was developed to detect simultaneously, in one tube reaction, three specific fragments of 821, 526 and 687-bp long for Cp. abortus, Cp. pecorum and C. burnetii respectively. This m-PCR assay was performed on 253 clinical samples taken from infected ruminant's flocks that have showed problems of abortion diseases. Thus, 67 samples were infected by either one of the three pathogens: 16 (13 vaginal swabs and 3 placentas) were positive for Cp. abortus, 2 were positive for Cp. pecorum (1 vaginal swab and 1 placenta) and 49 samples (33 vaginal swabs, 11 raw milks, 4 faeces and 1 placenta) were positive for C. burnetii. Two vaginal swabs were m-PCR positive of both Cp. abortus and C. burnetii and none of the tested samples was shown to be infected simultaneously with the three pathogens. Conclusion We have successfully developed a rapid multiplex PCR that can detect and differentiate Cp. abortus, Cp. pecorum and C. burnetii; with a good sensitivity and specificity. The diagnosis of chlamydiosis and Q fever may be greatly simplified and performed at low cost. In addition, the improvement in diagnostic techniques will enhance our knowledge regarding the prevalence and the pathogenetic

  7. Relative contributions of neighbourhood and animal movements to Coxiella burnetii infection in dairy cattle herds.

    PubMed

    Nusinovici, Simon; Hoch, Thierry; Widgren, Stefan; Joly, Alain; Lindberg, Ann; Beaudeau, François

    2014-05-01

    Q fever in dairy cattle herds occurs mainly after inhalation of contaminated aerosols generated from excreta by shedder animals. Propagation of Coxiella burnetii, the cause of the disease between ruminant herds could result from transmission between neighbouring herds and/or the introduction of infected shedder animals in healthy herds. The objective of this study were (i) to describe the spatial distribution C. burnetii-infected dairy cattle herds in two different regions: the Finistère District in France (2,829 herds) and the island of Gotland in Sweden (119 herds) and (ii) to quantify and compare the relative contributions of C. burnetii transmission related to neighbourhood and to animal movements on the risk for a herd to be infected. An enzyme--linked immunosorbent assay was used for testing bulk tank milk in May 2012 and June 2011, respectively. Only one geographical cluster of positive herds was identified in north-western Finistère. Logistic regression was used to assess the association of risk for a herd to test positively with local cattle density (the total number of cattle located in a 5 km radius circle) and the in-degree (ID) parameter, a measure of the number of herds from which each herd had received animals directly within the last 2 years. The risk for a herd to test positively was higher for herds with a higher local cattle density [odds ratio (OR) = 2.3, 95% confidence interval (CI) = 1.6-3.2, for herds with a local density between 100 and 120 compared to herds with a local density 60]. The risk was also higher for herds with higher IDs (OR = 2.3, 95% CI = 1.6-3.2, for herds with ID 3 compared to herds that did not introduce animals). The proportion of cases attributable to infections in the neighbourhood in high-density areas was twice the proportion attributable to animal movements, suggesting that wind plays a main role in the transmission. PMID:24893024

  8. Modulation of the host transcriptome by Coxiella burnetii nuclear effector Cbu1314.

    PubMed

    Weber, Mary M; Faris, Robert; McLachlan, Juanita; Tellez, Andres; Wright, William U; Galvan, Gloria; Luo, Zhao-Qing; Samuel, James E

    2016-05-01

    Coxiella burnetii is a Gram-negative, obligate intracellular pathogen that directs the formation of a parasitophorous vacuole derived from the host lysosomal network. Biogenesis and maintenance of this replicative compartment is dependent on bacterial protein synthesis and results in differential expression of specific host genes. However, the mechanisms by which the pathogen induces changes in the host transcriptome is poorly understood. In the current study we identified a Dot/Icm secreted effector, Cbu1314, which encodes two nuclear localization signals that are required for nuclear localization and association with host chromatin. Chromatin immunoprecipitation (ChIP) and deep sequencing revealed that Cbu1314 associated with host genes involved in transcription, cell signaling, and the immune response. RNA sequencing of cells overexpressing Cbu1314 demonstrated that Cbu1314 modulates the host transcriptome and these transcriptional changes required a functional nuclear localization signal. Of the differentially expressed genes, sixteen were also identified as Cbu1314 targets using ChIP sequencing. Collectively these results suggest that Cbu1314 associates with host chromatin and plays a role in modulating the host transcriptome. PMID:26827929

  9. Survey of laboratory animal technicians in the United States for Coxiella burnetii antibodies and exploration of risk factors for exposure.

    PubMed

    Whitney, Ellen A Spotts; Massung, Robert F; Kersh, Gilbert J; Fitzpatrick, Kelly A; Mook, Deborah M; Taylor, Douglas K; Huerkamp, Michael J; Vakili, Jessica C; Sullivan, Patrick J; Berkelman, Ruth L

    2013-11-01

    Little is known about the prevalence of zoonotic infections among laboratory animal care technicians (LAT). Q fever, a disease caused by Coxiella burnetii, is a known occupational hazard for persons caring for livestock. We sought to determine the seroprevalence of C. burnetii antibodies among LAT and to identify risk factors associated with C. burnetii seropositivity. A survey was administered and serum samples collected from a convenience sample of 97 LAT. Samples were screened by using a Q fever IgG ELISA. Immunofluorescent antibody assays for phase I and phase II IgG were used to confirm the status of samples that were positive or equivocal by ELISA; positive samples were titered to endpoint. Antibodies against C. burnetii were detected in 6 (6%) of the 97 respondents. In our sample of LAT, seropositivity to C. burnetii was therefore twice as high in LAT as compared with the general population. Age, sex, and working with sheep regularly were not associated with seropositivity. Risk factors associated with seropositivity included breeding cattle within respondent's research facility, any current job contact with waste from beef cattle or goats, and exposure to animal waste during previous jobs or outside of current job duties. Only 15% of responding LAT reported being aware that sheep, goats, and cattle can transmit Q fever. Research facilities that use cattle or goats should evaluate their waste-management practices and educational programs in light of these findings. Additional efforts are needed to increase awareness among LAT regarding Q fever and heightened risk of exposure to infectious materials. Physicians should consider the risk of infection with C. burnetii when treating LAT with potential occupational exposures. PMID:24351760

  10. Survey of Laboratory Animal Technicians in the United States for Coxiella burnetii Antibodies and Exploration of Risk Factors for Exposure

    PubMed Central

    Whitney, Ellen A Spotts; Massung, Robert F; Kersh, Gilbert J; Fitzpatrick, Kelly A; Mook, Deborah M; Taylor, Douglas K; Huerkamp, Michael J; Vakili, Jessica C; Sullivan, Patrick J; Berkelman, Ruth L

    2013-01-01

    Little is known about the prevalence of zoonotic infections among laboratory animal care technicians (LAT). Q fever, a disease caused by Coxiella burnetii, is a known occupational hazard for persons caring for livestock. We sought to determine the seroprevalence of C. burnetii antibodies among LAT and to identify risk factors associated with C. burnetii seropositivity. A survey was administered and serum samples collected from a convenience sample of 97 LAT. Samples were screened by using a Q fever IgG ELISA. Immunofluorescent antibody assays for phase I and phase II IgG were used to confirm the status of samples that were positive or equivocal by ELISA; positive samples were titered to endpoint. Antibodies against C. burnetii were detected in 6 (6%) of the 97 respondents. In our sample of LAT, seropositivity to C. burnetii was therefore twice as high in LAT as compared with the general population. Age, sex, and working with sheep regularly were not associated with seropositivity. Risk factors associated with seropositivity included breeding cattle within respondent's research facility, any current job contact with waste from beef cattle or goats, and exposure to animal waste during previous jobs or outside of current job duties. Only 15% of responding LAT reported being aware that sheep, goats, and cattle can transmit Q fever. Research facilities that use cattle or goats should evaluate their waste-management practices and educational programs in light of these findings. Additional efforts are needed to increase awareness among LAT regarding Q fever and heightened risk of exposure to infectious materials. Physicians should consider the risk of infection with C. burnetii when treating LAT with potential occupational exposures. PMID:24351760

  11. Molecular characterization by MLVA of Coxiella burnetii strains infecting dairy cows and goats of north-eastern Italy.

    PubMed

    Ceglie, Letizia; Guerrini, Eulalia; Rampazzo, Erika; Barberio, Antonio; Tilburg, Jeroen J H C; Hagen, Ferry; Lucchese, Laura; Zuliani, Federica; Marangon, Stefano; Natale, Alda

    2015-01-01

    Q fever is a worldwide zoonotic disease caused by Coxiella burnetii (C. burnetii), an obligate intracellular bacterium. In ruminants, shedding into the environment mainly occurs during parturition or abortion, but the bacterium is shed also in milk, vaginal mucus, stools and urine. In Italy few surveys have been conducted and reported seroprevalence values ranged between 10% and 60%, even if few human cases have been described. Genotyping of bacteria is crucial for enhancing diagnostic methods and for epidemiological surveillance. The objective of this study was to investigate genotypic differences of C. burnetii genotypes directly in 34 samples, collected during a 3-years survey among 11 dairy cattle and 11 goat farms in the north-eastern part of Italy using a 6-locus multiple loci variable number of tandem repeat analysis (MLVA) method. The samples analysed included 13 bulk tank milk (BTM), 6 individual milk, 11 vaginal swabs and 4 foetal spleens. MLVA-type 2 was determined as the most prevalent in cattle in this study. C. burnetii strains circulating in the studied cattle population are very similar to genotypes previously described, while genotypes from goats showed an important variability. Further investigation are needed to understand the reason of this pattern. PMID:26526416

  12. Estimation of the cytoplasmic pH of Coxiella burnetii and effect of substrate oxidation on proton motive force.

    PubMed Central

    Hackstadt, T

    1983-01-01

    The magnitude of the proton motive force generated during in vitro substrate oxidation by Coxiella burnetii was examined. The intracellular pH of C. burnetii varied from about 5.1 to 6.95 in resting cells over an extracellular pH range of 2 to 7. Similarly, delta psi varied from about 15 mV to -58 mV over approximately the same range of extracellular pH. Both components of the proton motive force increased during substrate oxidation, resulting in an increase in proton motive force from about -92 mV in resting cells to -153 mV in cells metabolizing glutamate at pH 4.2. The respiration-dependent increase in proton motive force was blocked by respiratory inhibitors, but the delta pH was not abolished even by the addition of proton ionophores such as carbonyl cyanide-m-chlorophenyl hydrazone or 2,4-dinitrophenol. Because of this apparently passive component of delta pH maintenance, the largest proton motive force was obtained at an extracellular pH too low to permit respiration. C. burnetii appears, therefore, to behave in many respects like other acidophilic bacteria. Such responses are proposed to contribute to the extreme resistance of C. burnetii to environmental conditions and subsequent activation upon entry into the phagolysosome of eucaryotic cells in which this organism multiplies. PMID:6302078

  13. Coxiella burnetii Infection in a Community Operating a Large-Scale Cow and Goat Dairy, Missouri, 2013.

    PubMed

    Biggs, Holly M; Turabelidze, George; Pratt, Drew; Todd, Suzanne R; Jacobs-Slifka, Kara; Drexler, Naomi A; McCurdy, Gail; Lloyd, Jennifer; Evavold, Charles L; Fitzpatrick, Kelly A; Priestley, Rachael A; Singleton, Joseph; Sun, David; Tang, Minh; Kato, Cecilia; Kersh, Gilbert J; Anderson, Alicia

    2016-03-01

    Coxiella burnetii is a zoonotic pathogen that causes Q fever in humans and is transmitted primarily from infected goats, sheep, or cows. Q fever typically presents as an acute febrile illness; however, individuals with certain predisposing conditions, including cardiac valvulopathy, are at risk for chronic Q fever, a serious manifestation that may present as endocarditis. In response to a cluster of Q fever cases detected by public health surveillance, we evaluated C. burnetii infection in a community that operates a large-scale cow and goat dairy. A case was defined as an individual linked to the community with a C. burnetii phase II IgG titer ≥ 128. Of 135 participants, 47 (35%) cases were identified. Contact with or close proximity to cows, goats, and their excreta was associated with being a case (relative risk 2.7, 95% confidence interval 1.3-5.3). Cases were also identified among individuals without cow or goat contact and could be related to windborne spread or tracking of C. burnetii on fomites within the community. A history of injection drug use was reported by 26/130 (20%) participants; follow-up for the presence of valvulopathy and monitoring for development of chronic Q fever may be especially important among this population. PMID:26811433

  14. Comparative virulence of intra- and interstrain lipopolysaccharide variants of Coxiella burnetii in the guinea pig model.

    PubMed Central

    Moos, A; Hackstadt, T

    1987-01-01

    We compared the relative infectivity and virulence of lipopolysaccharide (LPS) variants of the Nine Mile strain of Coxiella burnetii with those of the Priscilla strain, a representative of endocarditis-type strains. In agreement with results of previous studies, Nine Mile phase I (9mi/I) organisms were highly infectious, eliciting seroconversion and fever with inocula containing as few as four organisms. Viable 9mi/I was recovered from the spleens of infected animals 30 days postinfection. Nine Mile phase II (9mi/II) organisms did not elicit fever or seroconversion except with very large inocula, and viable organisms could not be recovered at 30 days postinfection. The Nine Mile/Crazy variant, bearing the intermediate-type LPS, was also highly infectious, as determined by fever response and seroconversion, although, as with 9mi/II, viable organisms could not be recovered 30 days postinfection. The Priscilla strain in phase I (Pris/I) was as infectious as 9mi/I, as determined by seroconversion and its presence in the spleen 30 days postinfection; but in contrast to 9mi/I, more than 10(5) Pris/I isolates were required to induce fever. The temporal appearances of anti-phase I and II antibodies were similar for the two strains. A variety of serological techniques measuring antibody response against whole-cell and purified LPS antigens in agglutination, immunofluorescence, enzyme-linked immunosorbent, and immunoblot assays did not demonstrate sufficient specificity to distinguish between 9mi/I and Pris/I infections. Results of vaccine cross-challenge experiments showed a significant degree of protection between homologous and heterologous challenge strains. protection between homologous Images PMID:3570458

  15. Progression of Coxiella burnetii infection after implementing a two-year vaccination program in a naturally infected dairy cattle herd

    PubMed Central

    2014-01-01

    Background The high prevalence of Coxiella burnetii infection in dairy cattle herds recently reported and the long survival time of the bacterium in the environment pose a risk to human and animal health that calls for the implementation of control measures at herd level. This study presents the results of a 2-year vaccination program with an inactivated phase I vaccine in a Spanish dairy herd naturally infected with C. burnetii. Calves older than 3 months and non-pregnant heifers and cows were vaccinated in April 2011 and the farm was subsequently visited at a monthly basis for vaccination of recently calved cows and calves that reached the age of 3 months. Annual booster doses were given to previous vaccinated animals as well. The effectiveness of the vaccine was assessed in terms of level of C. burnetii shedding through milk and uterine fluids and environmental contamination as determined by polymerase chain reaction (PCR). Results The percentage of shedder animals through uterine fluids and milk progressively decreased, and C. burnetii DNA load in bulk-tank milk samples was low at the end of the study. The average seroconversion rate in not yet vaccinated animals, which acted as control group, was 8.6% during the first year and 0% in the second year. DNA of C. burnetii was found in aerosols and dust samples taken in the calving area only at the beginning of the study, whereas slurry samples remained C. burnetii PCR positive for at least 18 months. Multiple Locus Variable number tandem-repeat Analysis identified the same genotype in all C. burnetii DNA positive samples. Conclusions In the absence of any changes in biosecurity, the overall reduction of C. burnetii infection in animals to 1.2% milk shedders and the reduced environment contamination found at the end of the study was ascribed to the effects of vaccination together with the culling of milk shedders. Vaccination has to be planned as a medium-long term strategy to suppress risks of re

  16. Circulation of Coxiella burnetii in a Naturally Infected Flock of Dairy Sheep: Shedding Dynamics, Environmental Contamination, and Genotype Diversity

    PubMed Central

    Joulié, A.; Laroucau, K.; Bailly, X.; Prigent, M.; Gasqui, P.; Lepetitcolin, E.; Blanchard, B.; Rousset, E.; Sidi-Boumedine, K.

    2015-01-01

    Q fever is a worldwide zoonosis caused by Coxiella burnetii. Domestic ruminants are considered to be the main reservoir. Sheep, in particular, may frequently cause outbreaks in humans. Because within-flock circulation data are essential to implementing optimal management strategies, we performed a follow-up study of a naturally infected flock of dairy sheep. We aimed to (i) describe C. burnetii shedding dynamics by sampling vaginal mucus, feces, and milk, (ii) assess circulating strain diversity, and (iii) quantify barn environmental contamination. For 8 months, we sampled vaginal mucus and feces every 3 weeks from aborting and nonaborting ewes (n = 11 and n = 26, respectively); for lactating females, milk was obtained as well. We also sampled vaginal mucus from nine ewe lambs. Dust and air samples were collected every 3 and 6 weeks, respectively. All samples were screened using real-time PCR, and strongly positive samples were further analyzed using quantitative PCR. Vaginal and fecal samples with sufficient bacterial burdens were then genotyped by multiple-locus variable-number tandem-repeat analysis (MLVA) using 17 markers. C. burnetii burdens were higher in vaginal mucus and feces than in milk, and they peaked in the first 3 weeks postabortion or postpartum. Primiparous females and aborting females tended to shed C. burnetii longer and have higher bacterial burdens than nonaborting and multiparous females. Six genotype clusters were identified; they were independent of abortion status, and within-individual genotype diversity was observed. C. burnetii was also detected in air and dust samples. Further studies should determine whether the within-flock circulation dynamics observed here are generalizable. PMID:26253679

  17. Circulation of Coxiella burnetii in a Naturally Infected Flock of Dairy Sheep: Shedding Dynamics, Environmental Contamination, and Genotype Diversity.

    PubMed

    Joulié, A; Laroucau, K; Bailly, X; Prigent, M; Gasqui, P; Lepetitcolin, E; Blanchard, B; Rousset, E; Sidi-Boumedine, K; Jourdain, E

    2015-10-01

    Q fever is a worldwide zoonosis caused by Coxiella burnetii. Domestic ruminants are considered to be the main reservoir. Sheep, in particular, may frequently cause outbreaks in humans. Because within-flock circulation data are essential to implementing optimal management strategies, we performed a follow-up study of a naturally infected flock of dairy sheep. We aimed to (i) describe C. burnetii shedding dynamics by sampling vaginal mucus, feces, and milk, (ii) assess circulating strain diversity, and (iii) quantify barn environmental contamination. For 8 months, we sampled vaginal mucus and feces every 3 weeks from aborting and nonaborting ewes (n=11 and n=26, respectively); for lactating females, milk was obtained as well. We also sampled vaginal mucus from nine ewe lambs. Dust and air samples were collected every 3 and 6 weeks, respectively. All samples were screened using real-time PCR, and strongly positive samples were further analyzed using quantitative PCR. Vaginal and fecal samples with sufficient bacterial burdens were then genotyped by multiple-locus variable-number tandem-repeat analysis (MLVA) using 17 markers. C. burnetii burdens were higher in vaginal mucus and feces than in milk, and they peaked in the first 3 weeks postabortion or postpartum. Primiparous females and aborting females tended to shed C. burnetii longer and have higher bacterial burdens than nonaborting and multiparous females. Six genotype clusters were identified; they were independent of abortion status, and within-individual genotype diversity was observed. C. burnetii was also detected in air and dust samples. Further studies should determine whether the within-flock circulation dynamics observed here are generalizable. PMID:26253679

  18. Creating standards for absolute quantification of Coxiella burnetii in real-time PCR--a comparative study based on transmission electron microscopy.

    PubMed

    Sting, Reinhard; Molz, Kerstin; Hoferer, Marc

    2015-01-01

    Quantitative standards are a prerequisite for quality control and quantification of pathogens. In this study the creation of quantitative standards for use in qPCR is described using the pathogen Coxiella burnetii. Quantification of Coxiella burnetii particles by transmission electron microscopy (TEM) was used as primary standard and compared with data obtained by light microscopy as well as genome equivalents (GE) and plasmid units (recombinant plasmid). Based on pathogen quantification using TEM and light microscopy, pathogen detection limits of 6 and 2 C. burnetii particles could be determined per com1 qPCR reaction, respectively. In comparison, the detection limits were 17 and 13 pathogen units using GE and plasmid units, respectively. The standard generated by TEM can be used as gold standard for universal application due to high accuracy, quantitative control of the producing process and supplying intact pathogen particles. PMID:25465354

  19. The Type IV Secretion System Effector Protein CirA Stimulates the GTPase Activity of RhoA and Is Required for Virulence in a Mouse Model of Coxiella burnetii Infection.

    PubMed

    Weber, Mary M; Faris, Robert; van Schaik, Erin J; McLachlan, Juanita Thrasher; Wright, William U; Tellez, Andres; Roman, Victor A; Rowin, Kristina; Case, Elizabeth Di Russo; Luo, Zhao-Qing; Samuel, James E

    2016-09-01

    Coxiella burnetii, the etiological agent of Q fever in humans, is an intracellular pathogen that replicates in an acidified parasitophorous vacuole derived from host lysosomes. Generation of this replicative compartment requires effectors delivered into the host cell by the Dot/Icm type IVb secretion system. Several effectors crucial for C. burnetii intracellular replication have been identified, but the host pathways coopted by these essential effectors are poorly defined, and very little is known about how spacious vacuoles are formed and maintained. Here we demonstrate that the essential type IVb effector, CirA, stimulates GTPase activity of RhoA. Overexpression of CirA in mammalian cells results in cell rounding and stress fiber disruption, a phenotype that is rescued by overexpression of wild-type or constitutively active RhoA. Unlike other effector proteins that subvert Rho GTPases to modulate uptake, CirA is the first effector identified that is dispensable for uptake and instead recruits Rho GTPase to promote biogenesis of the bacterial vacuole. Collectively our results highlight the importance of CirA in coopting host Rho GTPases for establishment of Coxiella burnetii infection and virulence in mammalian cell culture and mouse models of infection. PMID:27324482

  20. Absence of serological evidence of Rickettsia spp., Bartonella spp., Ehrlichia spp. and Coxiella burnetii infections in American Samoa.

    PubMed

    Lau, Colleen; Musso, Didier; Fournier, Pierre-Edouard; Parola, Philippe; Raoult, Didier; Weinstein, Philip

    2016-07-01

    Little is known about the epidemiology of zoonotic diseases in American Samoa (Pacific). A review of literature did not identify any published information on human Rickettsia spp., Bartonella spp., Ehrlichia spp. or Coxiella burnetii infections in this country. To determine the presence of these diseases, we conducted a serosurvey of American Samoans. The presence of immunoglobulin G antibodies against Rickettsia felis, Rickettsia typhi, Rickettsia conorii, C. burnetii, Bartonella henselae, Bartonella quintana, and Ehrlichia chaffeensis was evaluated by indirect immunofluorescence assay in sera from 197 American Samoan adults. None of the samples had antibodies at a significant level against Rickettsia spp., Bartonella spp., Ehrlichia spp. or C. burnetii (seroprevalence 0%; one-tailed 95% CI 0-1.86%). We cannot conclude that these pathogens are absent in American Samoa but, if present, their prevalence is probably very low. Q fever has been reported worldwide except in New Zealand and French Polynesia; these new data suggest that the prevalence of Q fever is likely to be very low in the Pacific Islands. PMID:26965788

  1. Sex-Related Differences in Gene Expression Following Coxiella burnetii Infection in Mice: Potential Role of Circadian Rhythm

    PubMed Central

    Textoris, Julien; Ban, Leang Heng; Capo, Christian; Raoult, Didier; Leone, Marc; Mege, Jean-Louis

    2010-01-01

    Background Q fever, a zoonosis due to Coxiella burnetii infection, exhibits sexual dimorphism; men are affected more frequently and severely than women for a given exposure. Here we explore whether the severity of C. burnetii infection in mice is related to differences in male and female gene expression profiles. Methodology/Principal Findings Mice were infected with C. burnetii for 24 hours, and gene expression was measured in liver cells using microarrays. Multiclass analysis identified 2,777 probes for which expression was specifically modulated by C. burnetti infection. Only 14% of the modulated genes were sex-independent, and the remaining 86% were differentially expressed in males and females. Castration of males and females showed that sex hormones were responsible for more than 60% of the observed gene modulation, and this reduction was most pronounced in males. Using functional annotation of modulated genes, we identified four clusters enriched in males that were related to cell-cell adhesion, signal transduction, defensins and cytokine/Jak-Stat pathways. Up-regulation of the IL-10 and Stat-3 genes may account for the high susceptibility of men with Q fever to C. burnetii infection and autoantibody production. Two clusters were identified in females, including the circadian rhythm pathway, which consists of positive (Clock, Arntl) and negative (Per) limbs of a feedback loop. We found that Clock and Arntl were down-modulated whereas Per was up-regulated; these changes may be associated with efficient bacterial elimination in females but not in males, in which an exacerbated host response would be prominent. Conclusion This large-scale study revealed for the first time that circadian rhythm plays a major role in the anti-infectious response of mice, and it provides a new basis for elucidating the role of sexual dimorphism in human infections. PMID:20730052

  2. Seroepidemiologic Survey for Coxiella burnetii Among US Military Personnel Deployed to Southwest and Central Asia in 2005

    PubMed Central

    Royal, Joseph; Riddle, Mark S.; Mohareb, Emad; Monteville, Marshall R.; Porter, Chad K.; Faix, Dennis J.

    2013-01-01

    We used a seroepidemiologic study to estimate Q fever (Coxiella burnetii) seroprevalence, seroincidence, and risk factors for seroconversion in two deployed military populations in 2005. The first study group resided in an area with a known Q fever outbreak history (Al Asad, Iraq). Of this population, 7.2% seroconverted for an incidence rate of 10.6 seroconversions per 1,000 person-months. The second population included personnel transiting through Qatar on mid-deployment leave from southwest/central Asia. In this group, we found 2.1% prevalence with 0.92 seroconversions per 1,000 person-months. However, no significant risk factors for Q fever seroconversion were found in either population. PMID:24043692

  3. Transcriptional Profiling of Coxiella burnetii Reveals Extensive Cell Wall Remodeling in the Small Cell Variant Developmental Form.

    PubMed

    Sandoz, Kelsi M; Popham, David L; Beare, Paul A; Sturdevant, Daniel E; Hansen, Bryan; Nair, Vinod; Heinzen, Robert A

    2016-01-01

    A hallmark of Coxiella burnetii, the bacterial cause of human Q fever, is a biphasic developmental cycle that generates biologically, ultrastructurally, and compositionally distinct large cell variant (LCV) and small cell variant (SCV) forms. LCVs are replicating, exponential phase forms while SCVs are non-replicating, stationary phase forms. The SCV has several properties, such as a condensed nucleoid and an unusual cell envelope, suspected of conferring enhanced environmental stability. To identify genetic determinants of the LCV to SCV transition, we profiled the C. burnetii transcriptome at 3 (early LCV), 5 (late LCV), 7 (intermediate forms), 14 (early SCV), and 21 days (late SCV) post-infection of Vero epithelial cells. Relative to early LCV, genes downregulated in the SCV were primarily involved in intermediary metabolism. Upregulated SCV genes included those involved in oxidative stress responses, arginine acquisition, and cell wall remodeling. A striking transcriptional signature of the SCV was induction (>7-fold) of five genes encoding predicted L,D transpeptidases that catalyze nonclassical 3-3 peptide cross-links in peptidoglycan (PG), a modification that can influence several biological traits in bacteria. Accordingly, of cross-links identified, muropeptide analysis showed PG of SCV with 46% 3-3 cross-links as opposed to 16% 3-3 cross-links for LCV. Moreover, electron microscopy revealed SCV with an unusually dense cell wall/outer membrane complex as compared to LCV with its clearly distinguishable periplasm and inner and outer membranes. Collectively, these results indicate the SCV produces a unique transcriptome with a major component directed towards remodeling a PG layer that likely contributes to Coxiella's environmental resistance. PMID:26909555

  4. Effect of a phase I Coxiella burnetii inactivated vaccine on body temperature and milk yield in dairy cows.

    PubMed

    Schulze, L S-Ch; Borchardt, S; Ouellet, V; Heuwieser, W

    2016-01-01

    Q fever is a zoonotic disease caused by Coxiella burnetii. The pathogen is prevalent in ruminants (goats, sheep, cows), which are the main sources of human infection. In the cattle industry around the world, animal (15 to 20%) and herd (38 to 72%) level prevalences of C. burnetii are high. Vaccination of ruminants against Q fever is considered important to prevent spreading of the disease and risk of infection in humans. However, published information on side effects of the Q fever vaccination under field conditions is limited for cows. The objective of this study was to investigate the effect of the phase I C. burnetii inactivated vaccine Coxevac on body temperature and milk yield in dairy cows. In 2 experiments, a total of 508 cows were randomly divided into 2 groups to determine the effect of first vaccination on body temperature and milk yield. The C. burnetii serostatus of all cows was tested before vaccination with an indirect ELISA. The first experiment took place in the teaching and research barn of the Clinic of Animal Reproduction at the Freie Universität Berlin. Temperature was measured vaginally in 10 cows in a crossover design. The second experiment was conducted on a commercial dairy farm. Milk yield of 498 cows was measured 1 wk before and 1 wk after vaccination. In a subset of 41 cows, temperature was measured rectally. In both experiments, body temperature increased significantly after vaccination (1.0 ± 0.9°C and 0.7 ± 0.8°C). A significant difference was also found in body temperature between vaccinated and control cows. Thirty percent of the vaccinated animals in experiment 1 showed reversible swelling at the injection site as a reaction to the vaccination. The results indicate that vaccination against Q fever causes a transient increase of body temperature that peaks in the first 12 to 24h and declines after that. In experiment 2, vaccinated cows (26.8 ± 0.39 kg/d) produced significantly less milk than did control cows (28.2 ± 0.44 kg

  5. A Probably Minor Role for Land-Applied Goat Manure in the Transmission of Coxiella burnetii to Humans in the 2007–2010 Dutch Q Fever Outbreak

    PubMed Central

    van den Brom, René; Roest, Hendrik-Jan; de Bruin, Arnout; Dercksen, Daan; Santman-Berends, Inge; van der Hoek, Wim; Dinkla, Annemiek; Vellema, Jelmer; Vellema, Piet

    2015-01-01

    In 2007, Q fever started to become a major public health problem in the Netherlands, with small ruminants as most probable source. In order to reduce environmental contamination, control measures for manure were implemented because of the assumption that manure was highly contaminated with Coxiella burnetii. The aims of this study were 1) to clarify the role of C. burnetii contaminated manure from dairy goat farms in the transmission of C. burnetii to humans, 2) to assess the impact of manure storage on temperature profiles in dunghills, and 3) to calculate the decimal reduction time of the Nine Mile RSA 493 reference strain of C. burnetii under experimental conditions in different matrices. For these purposes, records on distribution of manure from case and control herds were mapped and a potential relation to incidences of human Q fever was investigated. Additionally, temperatures in two dunghills were measured and related to heat resistance of C. burnetii. Results of negative binomial regression showed no significant association between the incidence of human Q fever cases and the source of manure. Temperature measurements in the core and shell of dunghills on two farms were above 40°C for at least ten consecutive days which would result in a strong reduction of C. burnetii over time. Our findings indicate that there is no relationship between incidence of human Q fever and land applied manure from dairy goat farms with an abortion wave caused by C. burnetii. Temperature measurements in dunghills on two farms with C. burnetii shedding dairy goat herds further support the very limited role of goat manure as a transmission route during the Dutch human Q fever outbreak. It is very likely that the composting process within a dunghill will result in a clear reduction in the number of viable C. burnetii. PMID:25816149

  6. Generation and Multi-phenotypic High-content Screening of Coxiella burnetii Transposon Mutants

    PubMed Central

    Martinez, Eric; Cantet, Franck; Bonazzi, Matteo

    2015-01-01

    Invasion and colonization of host cells by bacterial pathogens depend on the activity of a large number of prokaryotic proteins, defined as virulence factors, which can subvert and manipulate key host functions. The study of host/pathogen interactions is therefore extremely important to understand bacterial infections and develop alternative strategies to counter infectious diseases. This approach however, requires the development of new high-throughput assays for the unbiased, automated identification and characterization of bacterial virulence determinants. Here, we describe a method for the generation of a GFP-tagged mutant library by transposon mutagenesis and the development of high-content screening approaches for the simultaneous identification of multiple transposon-associated phenotypes. Our working model is the intracellular bacterial pathogen Coxiellaburnetii, the etiological agent of the zoonosis Q fever, which is associated with severe outbreaks with a consequent health and economic burden. The obligate intracellular nature of this pathogen has, until recently, severely hampered the identification of bacterial factors involved in host pathogen interactions, making of Coxiella the ideal model for the implementation of high-throughput/high-content approaches. PMID:25992686

  7. Coxiella burnetii Seroprevalence and Risk Factors in Cattle Farmers and Farm Residents in Three Northeastern Provinces and Inner Mongolia Autonomous Region, China.

    PubMed

    Sun, Wu-Wen; Cong, Wei; Li, Mao-Hui; Wang, Chun-Feng; Shan, Xiao-Feng; Qian, Ai-Dong

    2016-01-01

    Little is known about Coxiella burnetii infection among cattle farmers and farm residents in China. Thus, the present study was conducted to detect the seroprevalence of C. burnetii infection and estimate associated risk factors among cattle farmers and farm residents in China. A cross-sectional study was designed, and sera of 362 people living or working on 106 cattle farms were tested for C. burnetii IgG and IgM antibodies by immunofluorescence assay. Overall C. burnetii seroprevalence was 35.6% (129/362, 95% CI: 30.70-40.57), and 112 participants had experienced a past infection and seventeen (4.7%) had experienced a relatively recent infection. In the final combined multilevel model, the following activities were significantly associated with presence of antibodies against C. burnetii: milking cattle, providing general healthcare to cattle, providing birth assistance, contact dead-born animals, urbanization, and presence of mice and/or rats in the stable. Moreover, presence of disinfection equipment was a significant protective factor. This is the first study addressing the seroprevalence and risk factors of C. burnetii infection in cattle farmers and farm residents in three northeastern provinces and Inner Mongolia Autonomous Region, China. PMID:26966688

  8. Coxiella burnetii Seroprevalence and Risk Factors in Cattle Farmers and Farm Residents in Three Northeastern Provinces and Inner Mongolia Autonomous Region, China

    PubMed Central

    Sun, Wu-Wen; Cong, Wei; Li, Mao-Hui; Wang, Chun-Feng; Shan, Xiao-Feng; Qian, Ai-Dong

    2016-01-01

    Little is known about Coxiella burnetii infection among cattle farmers and farm residents in China. Thus, the present study was conducted to detect the seroprevalence of C. burnetii infection and estimate associated risk factors among cattle farmers and farm residents in China. A cross-sectional study was designed, and sera of 362 people living or working on 106 cattle farms were tested for C. burnetii IgG and IgM antibodies by immunofluorescence assay. Overall C. burnetii seroprevalence was 35.6% (129/362, 95% CI: 30.70–40.57), and 112 participants had experienced a past infection and seventeen (4.7%) had experienced a relatively recent infection. In the final combined multilevel model, the following activities were significantly associated with presence of antibodies against C. burnetii: milking cattle, providing general healthcare to cattle, providing birth assistance, contact dead-born animals, urbanization, and presence of mice and/or rats in the stable. Moreover, presence of disinfection equipment was a significant protective factor. This is the first study addressing the seroprevalence and risk factors of C. burnetii infection in cattle farmers and farm residents in three northeastern provinces and Inner Mongolia Autonomous Region, China. PMID:26966688

  9. Studying Coxiella burnetii Type IV Substrates in the Yeast Saccharomyces cerevisiae: Focus on Subcellular Localization and Protein Aggregation

    PubMed Central

    Rodríguez-Escudero, María; Cid, Víctor J.; Molina, María; Schulze-Luehrmann, Jan; Lührmann, Anja; Rodríguez-Escudero, Isabel

    2016-01-01

    Coxiella burnetii is a Gram-negative obligate parasitic bacterium that causes the disease Q-fever in humans. To establish its intracellular niche, it utilizes the Icm/Dot type IVB secretion system (T4BSS) to inject protein effectors into the host cell cytoplasm. The host targets of most cognate and candidate T4BSS-translocated effectors remain obscure. We used the yeast Saccharomyces cerevisiae as a model to express and study six C. burnetii effectors, namely AnkA, AnkB, AnkF, CBU0077, CaeA and CaeB, in search for clues about their role in C. burnetii virulence. When ectopically expressed in HeLa cells, these effectors displayed distinct subcellular localizations. Accordingly, GFP fusions of these proteins produced in yeast also decorated distinct compartments, and most of them altered cell growth. CaeA was ubiquitinated both in yeast and mammalian cells and, in S. cerevisiae, accumulated at juxtanuclear quality-control compartments (JUNQs) and insoluble protein deposits (IPODs), characteristic of aggregative or misfolded proteins. AnkA, which was not ubiquitinated, accumulated exclusively at the IPOD. CaeA, but not AnkA or the other effectors, caused oxidative damage in yeast. We discuss that CaeA and AnkA behavior in yeast may rather reflect misfolding than recognition of conserved targets in the heterologous system. In contrast, CBU0077 accumulated at vacuolar membranes and abnormal ER extensions, suggesting that it interferes with vesicular traffic, whereas AnkB associated with the yeast nucleolus. Both effectors shared common localization features in HeLa and yeast cells. Our results support the idea that C. burnetii T4BSS effectors manipulate multiple host cell targets, which can be conserved in higher and lower eukaryotic cells. However, the behavior of CaeA and AnkA prompt us to conclude that heterologous protein aggregation and proteostatic stress can be a limitation to be considered when using the yeast model to assess the function of bacterial effectors

  10. Transcriptional Profiling of Coxiella burnetii Reveals Extensive Cell Wall Remodeling in the Small Cell Variant Developmental Form

    PubMed Central

    Sandoz, Kelsi M.; Popham, David L.; Beare, Paul A.; Sturdevant, Daniel E.; Hansen, Bryan; Nair, Vinod; Heinzen, Robert A.

    2016-01-01

    A hallmark of Coxiella burnetii, the bacterial cause of human Q fever, is a biphasic developmental cycle that generates biologically, ultrastructurally, and compositionally distinct large cell variant (LCV) and small cell variant (SCV) forms. LCVs are replicating, exponential phase forms while SCVs are non-replicating, stationary phase forms. The SCV has several properties, such as a condensed nucleoid and an unusual cell envelope, suspected of conferring enhanced environmental stability. To identify genetic determinants of the LCV to SCV transition, we profiled the C. burnetii transcriptome at 3 (early LCV), 5 (late LCV), 7 (intermediate forms), 14 (early SCV), and 21 days (late SCV) post-infection of Vero epithelial cells. Relative to early LCV, genes downregulated in the SCV were primarily involved in intermediary metabolism. Upregulated SCV genes included those involved in oxidative stress responses, arginine acquisition, and cell wall remodeling. A striking transcriptional signature of the SCV was induction (>7-fold) of five genes encoding predicted L,D transpeptidases that catalyze nonclassical 3–3 peptide cross-links in peptidoglycan (PG), a modification that can influence several biological traits in bacteria. Accordingly, of cross-links identified, muropeptide analysis showed PG of SCV with 46% 3–3 cross-links as opposed to 16% 3–3 cross-links for LCV. Moreover, electron microscopy revealed SCV with an unusually dense cell wall/outer membrane complex as compared to LCV with its clearly distinguishable periplasm and inner and outer membranes. Collectively, these results indicate the SCV produces a unique transcriptome with a major component directed towards remodeling a PG layer that likely contributes to Coxiella’s environmental resistance. PMID:26909555

  11. Treatment and Prophylactic Strategy for Coxiella burnetii Infection of Aneurysms and Vascular Grafts: A Retrospective Cohort Study.

    PubMed

    Eldin, Carole; Mailhe, Morgane; Lions, Caroline; Carrieri, Patrizia; Safi, Hazem; Brouqui, Philippe; Raoult, Didier

    2016-03-01

    Coxiella burnetii vascular infections continue to be very severe diseases and no guidelines exist about their prevention. In terms of treatment, the benefit of the surgical removal of infected tissues has been suggested by 1 retrospective study.We present a case of a C burnetii abdominal aortic graft infection for which we observed a dramatic clinical and biological recovery after surgery. We thus performed a retrospective cohort study to evaluate the impact of surgery on survival and serological outcome for patients with Q fever vascular infections diagnosed in our center.Between 1986 and February 2015, 100 patients were diagnosed with Q fever vascular infections. The incidence of these infections has significantly increased over the past 5 years, in comparison with the mean annual incidence over the preceding 22 years (8.83 cases per year versus 3.14 cases per year, P = 0.001). A two-and-a-half-year follow-up was available for 66 patients, of whom 18.2% died. We observed 6.5% of deaths in the group of patients who were operated upon at 2 and a half years, in comparison with 28.6% in the group which were not operated upon (P = 0.02). Surgery was the only factor that had a positive impact on survival at 2 and a half years using univariate analysis [hazard ratio: 0.17 [95% CI]: [0.039-0.79]; P = 0.024]. Surgery was also associated with a good serological outcome (74.1% vs 57.1% of patients, P = 0.03). In the group of patients with vascular graft infections (n = 47), surgery had a positive impact on serological outcome at 2 and a half years (85.7% vs 42.9%, P < 0.001) [hazard ratio: 0.40 [95% CI]: [0.17-098]; P = 0.046] and tended to be associated with lower although not statistically significant mortality (11.1% vs 27.6% of deaths, P = 0.19).Surgical treatment confers a benefit in terms of survival following C burnetii vascular infections. However, given the high mortality of these infections and their rising incidence, we propose a

  12. Screening-level risk assessment of Coxiella burnetii (Q fever) transmission via aeration of drinking water.

    PubMed

    Sales-Ortells, Helena; Medema, Gertjan

    2012-04-01

    A screening-level risk assessment of Q fever transmission through drinking water produced from groundwater in the vicinity of infected goat barnyards that employed aeration of the water was performed. Quantitative data from scientific literature were collected and a Quantitative Microbial Risk Assessment approach was followed. An exposure model was developed to calculate the dose to which consumers of aerated groundwater are exposed through aerosols inhalation during showering. The exposure assessment and hazard characterization were integrated in a screening-level risk characterization using a dose-response model for inhalation to determine the risk of Q fever through tap water. A nominal range sensitivity analysis was performed. The estimated risk of disease was lower than 10(-4) per person per year (pppy), hence the risk of transmission of C. burnetii through inhalation of drinking water aerosols is very low. The sensitivity analysis shows that the most uncertain parameters are the aeration process, the transport of C. burnetii in bioaerosols via the air, the aerosolization of C. burnetii in the shower, and the air filtration efficiency. The risk was compared to direct airborne exposure of persons in the vicinity of infected goat farms; the relative risk of exposure through inhalation of drinking water aerosols was 0.002%. PMID:22309101

  13. Electron microscopic study on the interaction between normal guinea pig peritoneal macrophages and Coxiella burnetii.

    PubMed Central

    Kishimoto, R A; Veltri, B J; Canonico, P G; Shirey, F G; Walker, J S

    1976-01-01

    An electron microscopic study was conducted to explore the interaction between normal guinea pig peritoneal macrophages and phase I and II Coxeilla burnetii previously treated with either normal or immune serum. A comparison was made on the efficiency of phagocytosis and subsequent killing of rickettsiae by macrophages. Both phases of rickettsiae previously treated with normal serum multiplied within phagosomes after phagocytosis with resultant destruction of macrophages. In contrast, suspending rickettsiae in immune serum rendered them more susceptible to phagocytosis and potentiated their destruction within macrophages. Images PMID:825466

  14. Massive Infection of Seabird Ticks with Bacterial Species Related to Coxiella burnetii

    PubMed Central

    Dietrich, Muriel; Lebarbenchon, Camille; Jaeger, Audrey; Le Rouzic, Céline; Bastien, Matthieu; Lagadec, Erwan; McCoy, Karen D.; Pascalis, Hervé; Le Corre, Matthieu; Dellagi, Koussay; Tortosa, Pablo

    2014-01-01

    Seabird ticks are known reservoirs of bacterial pathogens of medical importance; however, ticks parasitizing tropical seabirds have received less attention than their counterparts from temperate and subpolar regions. Recently, Rickettsia africae was described to infect seabird ticks of the western Indian Ocean and New Caledonia, constituting the only available data on bacterial pathogens associated with tropical seabird tick species. Here, we combined a pyrosequencing-based approach with a classical molecular analysis targeting bacteria of potential medical importance in order to describe the bacterial community in two tropical seabird ticks, Amblyomma loculosum and Carios (Ornithodoros) capensis. We also investigated the patterns of prevalence and host specificity within the biogeographical context of the western Indian Ocean islands. The bacterial community of the two tick species was characterized by a strong dominance of Coxiella and Rickettsia. Our data support a strict Coxiella-host tick specificity, a pattern resembling the one found for Rickettsia spp. in the same two seabird tick species. Both the high prevalence and stringent host tick specificity suggest that these bacteria may be tick symbionts with probable vertical transmission. Detailed studies of the pathogenicity of these bacteria will now be required to determine whether horizontal transmission can occur and to clarify their status as potential human pathogens. More generally, our results show that the combination of next generation sequencing with targeted detection/genotyping approaches proves to be efficient in poorly investigated fields where research can be considered to be starting from scratch. PMID:24657860

  15. Exposure and Risk Factors to Coxiella burnetii, Spotted Fever Group and Typhus Group Rickettsiae, and Bartonella henselae among Volunteer Blood Donors in Namibia

    PubMed Central

    Noden, Bruce H.; Tshavuka, Filippus I.; van der Colf, Berta E.; Chipare, Israel; Wilkinson, Rob

    2014-01-01

    Background The role of pathogen-mediated febrile illness in sub-Saharan Africa is receiving more attention, especially in Southern Africa where four countries (including Namibia) are actively working to eliminate malaria. With a high concentration of livestock and high rates of companion animal ownership, the influence of zoonotic bacterial diseases as causes of febrile illness in Namibia remains unknown. Methodology/Principal Findings The aim of the study was to evaluate exposure to Coxiella burnetii, spotted fever and typhus group rickettsiae, and Bartonella henselae using IFA and ELISA (IgG) in serum collected from 319 volunteer blood donors identified by the Blood Transfusion Service of Namibia (NAMBTS). Serum samples were linked to a basic questionnaire to identify possible risk factors. The majority of the participants (64.8%) had extensive exposure to rural areas or farms. Results indicated a C. burnetii prevalence of 26.1% (screening titre 1∶16), and prevalence rates of 11.9% and 14.9% (screening titre 1∶100) for spotted fever group and typhus group rickettsiae, respectively. There was a significant spatial association between C. burnetii exposure and place of residence in southern Namibia (P<0.021). Donors with occupations involving animals (P>0.012), especially cattle (P>0.006), were also significantly associated with C. burnetii exposure. Males were significantly more likely than females to have been exposed to spotted fever (P<0.013) and typhus (P<0.011) group rickettsiae. Three (2.9%) samples were positive for B. henselae possibly indicating low levels of exposure to a pathogen never reported in Namibia. Conclusions/Significance These results indicate that Namibians are exposed to pathogenic fever-causing bacteria, most of which have flea or tick vectors/reservoirs. The epidemiology of febrile illnesses in Namibia needs further evaluation in order to develop comprehensive local diagnostic and treatment algorithms. PMID:25259959

  16. 18F-FDG PET/CT as a central tool in the shift from chronic Q fever to Coxiella burnetii persistent focalized infection: A consecutive case series.

    PubMed

    Eldin, Carole; Melenotte, Cléa; Million, Matthieu; Cammilleri, Serge; Sotto, Albert; Elsendoorn, Antoine; Thuny, Franck; Lepidi, Hubert; Roblot, France; Weitten, Thierry; Assaad, Souad; Bouaziz, Anissa; Chapuzet, Claire; Gras, Guillaume; Labussiere, Anne-Sophie; Landais, Cécile; Longuet, Pascale; Masseau, Agathe; Mundler, Olivier; Raoult, Didier

    2016-08-01

    Because Q fever is mostly diagnosed serologically, localizing a persistent focus of Coxiella burnetii infection can be challenging. F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) could be an interesting tool in this context.We performed a retrospective study on patients diagnosed with C burnetii infection, who had undergone F-FDG PET/CT between 2009 and 2015. When positive F-FDG PET/CT results were obtained, we tried to determine if it changed the previous diagnosis by discovering or confirming a suspected focus of C burnetii infection.One hundred sixty-seven patients benefited from F-FDG PET/CT. The most frequent clinical subgroup before F-FDG PET/CT was patients with no identified focus of infection, despite high IgG1 serological titers (34%). For 59% (n = 99) of patients, a hypermetabolic focus was identified. For 62 patients (62.6%), the positive F-FDG PET/CT allowed the diagnosis to be changed. For 24 of them, (38.7%), a previously unsuspected focus of infection was discovered. Forty-two (42%) positive patients had more than 1 hypermetabolic focus. We observed 21 valvular foci, 34 vascular foci, and a high proportion of osteoarticular localizations (n = 21). We also observed lymphadenitis (n = 27), bone marrow hypermetabolism (n = 11), and 9 pulmonary localizations.We confirmed thatF-FDG PET/CT is a central tool in the diagnosis of C burnetii focalized persistent infection. We proposed new diagnostic scores for 2 main clinical entities identified using F-FDG PET/CT: osteoarticular persistent infections and lymphadenitis. PMID:27559944

  17. The Coxiella burnetii Ankyrin Repeat Domain-Containing Protein Family Is Heterogeneous, with C-Terminal Truncations That Influence Dot/Icm-Mediated Secretion ▿

    PubMed Central

    Voth, Daniel E.; Howe, Dale; Beare, Paul A.; Vogel, Joseph P.; Unsworth, Nathan; Samuel, James E.; Heinzen, Robert A.

    2009-01-01

    Coxiella burnetii is an obligate intracellular bacterium that directs biogenesis of a parasitophorous vacuole (PV) for replication. Effectors of PV maturation are likely translocated into the host cytosol by a type IV secretion system (T4SS) with homology to the Dot/Icm apparatus of Legionella pneumophila. Since secreted bacterial virulence factors often functionally mimic the activities of host proteins, prokaryotic proteins with eukaryotic features are considered candidate T4SS substrates. Genes encoding proteins with eukaryotic-type ankyrin repeat domains (Anks) were identified upon genome sequencing of the C. burnetii Nine Mile reference isolate, which is associated with a case of human acute Q fever. Interestingly, recent genome sequencing of the G and K isolates, derived from human chronic endocarditis patients, and of the Dugway rodent isolate revealed remarkable heterogeneity in the Ank gene family, with the Dugway isolate harboring the largest number of full-length Ank genes. Using L. pneumophila as a surrogate host, we identified 10 Dugway Anks and 1 Ank specific to the G and K endocarditis isolates translocated into the host cytosol in a Dot/Icm-dependent fashion. A 10-amino-acid C-terminal region appeared to be necessary for translocation, with some Anks also requiring the chaperone IcmS for secretion. Ectopically expressed Anks localized to a variety of subcellular regions in mammalian cells, including microtubules, mitochondria, and the PV membrane. Collectively, these data suggest that C. burnetii isolates translocate distinct subsets of the Ank protein family into the host cytosol, where they modulate diverse functions, some of which may be unique to C. burnetii pathotypes. PMID:19411324

  18. Complement fixation test to C. burnetii

    MedlinePlus

    ... ency/article/003520.htm Complement fixation test to C burnetii To use the sharing features on this ... JavaScript. The complement fixation test to Coxiella burnetii ( C burnetti ) is a blood test that checks for ...

  19. Isolation of Coxiella burnetii by a centrifugation shell-vial assay from ticks collected in Cyprus: detection by nested polymerase chain reaction (PCR) and by PCR-restriction fragment length polymorphism analyses.

    PubMed

    Spyridaki, Ioanna; Psaroulaki, Anna; Loukaides, Fidias; Antoniou, Maria; Hadjichristodolou, Christos; Tselentis, Yannis

    2002-01-01

    Ticks are the principal vectors and reservoirs of Coxiella burnetii. The identification of isolates is necessary for understanding the clinical diversity of Q fever in different geographic areas. This is the first report of isolation of C. burnetii from ticks by the shell-vial assay and by nested polymerase chain reaction (PCR) assay for the detection of this pathogen in ticks. Of 141 ticks collected in Cyprus (Rhipicephalus sanguineus and Hyalloma spp.), 10% were found to be infected with C. burnetii. Three ticks were positive by hemolymph test, and 11 triturated ticks were positive by nested PCR. Three isolates were obtained by the centrifugation shell-vial technique. Analysis by PCR, then restriction fragment length polymorphism showed that the 3 Cyprus isolates had identical restriction profiles to reference strains Nine Mile and Q212. The methods described are useful in studying the epidemiology and ecology of C. burnetii. PMID:12135275

  20. Bulk tank milk surveillance as a measure to detect Coxiella burnetii shedding dairy goat herds in the Netherlands between 2009 and 2014.

    PubMed

    Van den Brom, R; Santman-Berends, I; Luttikholt, S; Moll, L; Van Engelen, E; Vellema, P

    2015-06-01

    In the period from 2005 to 2009, Coxiella burnetii was a cause of abortion waves at 28 dairy goat farms and 2 dairy sheep farms in the Netherlands. Two years after the first abortion waves, a large human Q fever outbreak started mainly in the same region, and aborting small ruminants were regarded as most probable source. To distinguish between infected and noninfected herds, a surveillance program started in October 2009, based on PCR testing of bulk tank milk (BTM) samples, which had never been described before. The aim of this study was to analyze the effectiveness of this surveillance program and to evaluate both the effect of culling of pregnant dairy goats on positive farms and of vaccination on BTM results. Bulk tank milk samples were tested for C. burnetii DNA using a real-time PCR, and results were analyzed in relation to vaccination, culling, and notifiable (officially reported to government) C. burnetii abortion records. In spring and autumn, BTM samples were also tested for antibodies using an ELISA, and results were evaluated in relation to the compulsory vaccination campaign. Between October 2009 and April 2014, 1,660 (5.6%) out of 29,875 BTM samples from 401 dairy goat farms tested positive for C. burnetii DNA. The percentage of positive samples dropped from 20.5% in 2009 to 0.3% in 2014. In a multivariable model, significantly higher odds of being PCR positive in the BTM surveillance program were found in farms of which all pregnant dairy goats were culled. Additionally, the risk for C. burnetii BTM PCR positivity significantly decreased after multiple vaccinations. Bulk tank milk ELISA results were significantly higher after vaccination than before. The ELISA results were higher after multiple vaccinations compared with a single vaccination, and ELISA results on officially declared infected farms were significantly higher compared with noninfected farms. In conclusion, BTM surveillance is an effective and useful tool to detect C. burnetii shedding

  1. Brucellosis and Coxiella burnetii Infection in Householders and Their Animals in Secure Villages in Herat Province, Afghanistan: A Cross-Sectional Study

    PubMed Central

    Akbarian, Zarif; Ziay, Ghulam; Schauwers, Willy; Noormal, Bashir; Saeed, Islam; Qanee, Abul Hussain; Shahab, Zabiullah; Dennison, Tania; Dohoo, Ian; Jackson, Ronald

    2015-01-01

    Background Brucellosis and coxiellosis are known to be endemic in ruminant populations throughout Afghanistan, but information about their prevalence and factors that affect prevalence in householders and livestock under diverse husbandry systems and pastoral settings is sparse. Methods/Principal Findings We conducted a cross-sectional survey to investigate the seroprevalence of brucellosis and Coxiella burnetii in humans and livestock in six secure districts in Herat from 26th December 2012–17th January 2013. A total of 204 households with livestock were surveyed in six Kuchi and five sedentary type villages. Blood samples from 1,017 humans, 1,143 sheep, 876 goats and 344 cattle were tested for brucellosis and Q fever. About one in six households (15.7%) had at least one Brucella seropositive person, about one in eight households (12.3%) had at least one Brucella seropositive animal and about one in four (24.5%) had either seropositive animals or humans. Ninety-seven percent of households had at least one C. burnetii seropositive person and 98.5% of households had one or more C. burnetii seropositive animals. Forty- seven householders had serological evidence of exposure to both C. burnetii and Brucella and eight animals were serologically positive for both diseases. Drinking unpasteurised milk (OR 1.6), treating animals for ticks (OR 1.4), milking sheep (OR 1.4), male gender (OR 1.4) and seropositivity to Brucella (OR 4.3) were identified as risk factors for seropositivity to C. burnetii in householders. Household factors associated with households having either Brucella seropositive animals or humans were Kuchi households (OR 2.5), having ≤4 rooms in the house (OR 2.9) and not owning land (OR 2.9). Conclusions The results from this study provide baseline information for the planning and monitoring of future interventions against these diseases. The implementation of this study greatly improved collaboration, coordination and capability of veterinary and

  2. Modifications in the glycerophospholipid composition between the Coxiella burnetii phase I and phase II cells suggest an association with phase variation of the bacterium.

    PubMed

    Frimmelová, M; Toman, R; Pompach, P; Škultéty, L

    2016-03-01

    Glycerophospholipids (GP) extracted from the Coxiella burnetii strain Nine Mile in virulent phase I (NM I) and low virulent phase II (NM II) were analyzed by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) that gave a superior mass resolution and mass accuracy allowing unambiguous peak recognition and precise assignment of ions. We showed that GP present in the pathogen's outer membrane underwent considerable modifications during the phase variation that might be related to impact of various environmental factors. It was found that GP from phase I cells were much more complex than those from phase II cells. While glycerophosphoethanolamines (PE), glycerophosphocholines (PC) and glycerophosphoglycerols (PG) were present in both phases of C. burnetii, major differences were observed in the presence of glycerophosphates (PA) and glycerophosphoserines (PS). Thus, PA but no PS were detected in NM I variant in contrast with NM II cells where PS but no PA were identified. It is suggested that enzymes for PA head group modifications to form PS, PE, and PG become active during the phase variation of the bacterium. PMID:26982464

  3. The inhibition of the apoptosis pathway by the Coxiella burnetii effector protein CaeA requires the EK repetition motif, but is independent of survivin.

    PubMed

    Bisle, Stephanie; Klingenbeck, Leonie; Borges, Vítor; Sobotta, Katharina; Schulze-Luehrmann, Jan; Menge, Christian; Heydel, Carsten; Gomes, João Paulo; Lührmann, Anja

    2016-05-18

    ABSRTACT Coxiella burnetii is an obligate intracellular bacterium that causes Query (Q) fever, a zoonotic disease. It requires a functional type IV secretion system (T4SS) which translocate bacterial effector proteins into the host cell cytoplasm and thereby facilitates bacterial replication. To date, more than 130 effector proteins have been identified, but their functions remain largely unknown. Recently, we demonstrated that one of these proteins, CaeA (CBU1524) localized to the host cell nucleus and inhibited intrinsic apoptosis of HEK293 or CHO cells. In the present study we addressed the question whether CaeA also affects the extrinsic apoptosis pathway. Ectopic expression of CaeA reduced extrinsic apoptosis and prevented the cleavage of the executioner caspase 7, but did not impair the activation of initiator caspase 9. CaeA expression resulted in an up-regulation of survivin (an inhibitor of activated caspases), which, however, was not causal for the anti-apoptotic effect of CaeA. Comparing the sequence of CaeA from 25 different C. burnetii isolates we identified an EK (glutamic acid/ lysine) repetition motif as a site of high genetic variability. The EK motif of CaeA was essential for the anti-apoptotic activity of CaeA. From these data, we conclude that the C. burnetii effector protein CaeA interferes with the intrinsic and extrinsic apoptosis pathway. The process requires the EK repetition motif of CaeA, but is independent of the upregulated expression of survivin. PMID:26760129

  4. First Complete Genome Sequence of the Dutch Veterinary Coxiella burnetii Strain NL3262, Originating from the Largest Global Q Fever Outbreak, and Draft Genome Sequence of Its Epidemiologically Linked Chronic Human Isolate NLhu3345937

    PubMed Central

    Kuley, Runa; Smith, Hilde E.; Janse, Ingmar; Harders, Frank L.; Baas, Frank; Schijlen, Elio; Nabuurs-Franssen, Marrigje H.; Smits, Mari A.; Roest, Hendrik I. J.

    2016-01-01

    The largest global Q fever outbreak occurred in The Netherlands during 2007 to 2010. Goats and sheep were identified as the major sources of disease. Here, we report the first complete genome sequence of Coxiella burnetii goat outbreak strain NL3262 and that of an epidemiologically linked chronic human strain, both having the outbreak-related CbNL01 multilocus variable-number tandem-repeat analysis (MLVA) genotype. PMID:27103714

  5. Characterization of a phase I Coxiella burnetii chloroform-methanol residue vaccine that induces active immunity against Q fever in C57BL/10 ScN mice.

    PubMed Central

    Williams, J C; Damrow, T A; Waag, D M; Amano, K

    1986-01-01

    The effect of phase I Coxiella burnetii chloroform-methanol residue vaccine (CMRV) on the response of murine splenic lymphocytes to mitogenic and antigenic stimuli was evaluated in C57BL/10 ScN endotoxinnonresponder mice with an in vitro lymphocyte proliferation assay. Intraperitoneal injection of phase I CMRV resulted in antibody production against phases I and II antigens. Lymphocytes were responsive in vitro to concanavalin A, phytohemagglutinin, pokeweed mitogen, and specific recall antigens. Antibodies against phases I and II antigens were not detected after intraperitoneal injection of chloroform-methanol extract (CME). Lymphocytes also were only slightly hyporesponsive to mitogens. Reconstitution of the CMRV with the CME of phase I whole cells restored the immunopathological reactions that were associated with the phase I whole cell vaccine (WCV). The CMRV was more mitogenic than the WCV for lymphocytes from mice injected with saline. Lymphocytes from phase I WCV-injected mice were negatively modulated with nontoxic concentrations of homologous WCV or CMRV. Lymphocytes from phase I CMRV-injected mice were only slightly hyporesponsive to mitogens and were significantly stimulated by antigens of either WCV or CMRV as recall antigens. Vaccination of mice with 100 micrograms of CMRV, CME, or WCV provided 80, 0, or 50% protection, respectively, against a lethal intraperitoneal challenge with viable phase I C. burnetii. The epitopes which induce immunological hyporesponsiveness, negative modulation, and the death of lymphocytes were fractionated into the CMRV and CME. The CMRV provides at least one of the determinants which induce immunosuppression, whereas CME contains specific or nonspecific components or both. Collectively, these results show that the CMRV may be a potential candidate to replace the WCV currently used for human vaccination. PMID:3949384

  6. Prevalence and risk factors for Campylobacter spp., Salmonella spp., Coxiella burnetii, and Newcastle disease virus in feral pigeons (Columba livia) in public areas of Montreal, Canada

    PubMed Central

    Gabriele-Rivet, Vanessa; Fairbrother, Julie-Hélène; Tremblay, Donald; Harel, Josée; Côté, Nathalie; Arsenault, Julie

    2016-01-01

    Feral pigeons (Columbia livia) can harbor a range of zoonotic pathogens. A transversal study was undertaken to estimate the prevalence of feral pigeons infected by various pathogens in public areas in Montreal, Quebec. Cloacal swabs from captured birds were cultured for Salmonella spp. and Campylobacter spp. and tested by real-time polymerase chain reaction (RT-PCR) for the detection of Coxiella burnetii. An oropharyngeal swab was also submitted to real-time reverse-transcription polymerase chain reaction (RRT-PCR) for the detection of Newcastle disease virus. Among the 187 pigeons tested from 10 public areas, 9.1% (95% CI: 3.0 to 15.2) were positive for Campylobacter spp. with all strains identified as Campylobacter jejuni. The Campylobacter status of birds was not associated with individual characteristics of birds, with the exception of body score. None of the pigeons tested positive for the other pathogens. Direct or indirect contacts with feral pigeons may constitute a potential risk for Campylobacter infection in humans. PMID:26733736

  7. Chromosomal DNA Deletions Explain Phenotypic Characteristics of Two Antigenic Variants, Phase II and RSA 514 (Crazy), of the Coxiella burnetii Nine Mile Strain†

    PubMed Central

    Hoover, T. A.; Culp, D. W.; Vodkin, M. H.; Williams, J. C.; Thompson, H. A.

    2002-01-01

    After repeated passages through embyronated eggs, the Nine Mile strain of Coxiella burnetii exhibits antigenic variation, a loss of virulence characteristics, and transition to a truncated lipopolysaccharide (LPS) structure. In two independently derived strains, Nine Mile phase II and RSA 514, these phenotypic changes were accompanied by a large chromosomal deletion (M. H. Vodkin and J. C. Williams, J. Gen. Microbiol. 132:2587-2594, 1986). In the work reported here, additional screening of a cosmid bank prepared from the wild-type strain was used to map the deletion termini of both mutant strains and to accumulate all the segments of DNA that comprise the two deletions. The corresponding DNAs were then sequenced and annotated. The Nine Mile phase II deletion was completely nested within the deletion of the RSA 514 strain. Basic alignment and homology studies indicated that a large group of LPS biosynthetic genes, arranged in an apparent O-antigen cluster, was deleted in both variants. Database homologies identified, in particular, mannose pathway genes and genes encoding sugar methylases and nucleotide sugar epimerase-dehydratase proteins. Candidate genes for addition of sugar units to the core oligosaccharide for synthesis of the rare sugar 6-deoxy-3-C-methylgulose (virenose) were identified in the deleted region. Repeats, redundancies, paralogous genes, and two regions with reduced G+C contents were found within the deletions. PMID:12438347

  8. Bacterial tick-borne diseases caused by Bartonella spp., Borrelia burgdorferi sensu lato, Coxiella burnetii, and Rickettsia spp. among patients with cataract surgery

    PubMed Central

    Chmielewski, Tomasz; Brydak-Godowska, Joanna; Fiecek, Beata; Rorot, Urszula; Sędrowicz, Elżbieta; Werenowska, Małgorzata; Kopacz, Dorota; Hevelke, Agata; Michniewicz, Magdalena; Kęcik, Dariusz; Tylewska-Wierzbanowska, Stanisława

    2014-01-01

    Background Clinical data have shown that tick-borne diseases caused by Borrelia burgdorferi sensu lato, Bartonella spp., Coxiella burnetii, and Rickettsia spp. can affect the central nervous system, including the eye. The aim of this study was to establish a relationship between the incidence of cataract and evidence of bacterial infections transmitted by ticks. Material/Methods Fluid with lenticular masses from inside of the eye and blood from 109 patients were tested by PCR and sequencing. Sera from patients and the control group were subjected to serological tests to search specific antibodies to the bacteria. Results Microbiological analysis revealed the presence of Bartonella sp. DNA in intraoperative specimens from the eye in 1.8% of patients. Serological studies have shown that infections caused by B. burgdorferi sensu lato and Bartonella sp. were detected in 34.8% and 4.6% of patients with cataract surgery, respectively. Conclusions Presence of DNA of yet uncultured and undescribed species of Bartonella in eye liquid indicates past infection with this pathogen. Specific antibodies to B. burgdorferi sensu lato and Bartonella sp. are detected more frequently in patients with cataract compared to the control group. This could indicate a possible role of these organisms in the pathological processes within the eyeball, leading to changes in the lens. Further studies are needed to identify Bartonella species, as well as to recognize the infectious mechanisms involved in cataract development. PMID:24902636

  9. Prevalence and risk factors for Campylobacter spp., Salmonella spp., Coxiella burnetii, and Newcastle disease virus in feral pigeons (Columba livia) in public areas of Montreal, Canada.

    PubMed

    Gabriele-Rivet, Vanessa; Fairbrother, Julie-Hélène; Tremblay, Donald; Harel, Josée; Côté, Nathalie; Arsenault, Julie

    2016-01-01

    Feral pigeons (Columbia livia) can harbor a range of zoonotic pathogens. A transversal study was undertaken to estimate the prevalence of feral pigeons infected by various pathogens in public areas in Montreal, Quebec. Cloacal swabs from captured birds were cultured for Salmonella spp. and Campylobacter spp. and tested by real-time polymerase chain reaction (RT-PCR) for the detection of Coxiella burnetii. An oropharyngeal swab was also submitted to real-time reverse-transcription polymerase chain reaction (RRT-PCR) for the detection of Newcastle disease virus. Among the 187 pigeons tested from 10 public areas, 9.1% (95% CI: 3.0 to 15.2) were positive for Campylobacter spp. with all strains identified as Campylobacter jejuni. The Campylobacter status of birds was not associated with individual characteristics of birds, with the exception of body score. None of the pigeons tested positive for the other pathogens. Direct or indirect contacts with feral pigeons may constitute a potential risk for Campylobacter infection in humans. PMID:26733736

  10. Bayesian Validation of the Indirect Immunofluorescence Assay and Its Superiority to the Enzyme-Linked Immunosorbent Assay and the Complement Fixation Test for Detecting Antibodies against Coxiella burnetii in Goat Serum.

    PubMed

    Muleme, Michael; Stenos, John; Vincent, Gemma; Campbell, Angus; Graves, Stephen; Warner, Simone; Devlin, Joanne M; Nguyen, Chelsea; Stevenson, Mark A; Wilks, Colin R; Firestone, Simon M

    2016-06-01

    Although many studies have reported the indirect immunofluorescence assay (IFA) to be more sensitive in detection of antibodies to Coxiella burnetii than the complement fixation test (CFT), the diagnostic sensitivity (DSe) and diagnostic specificity (DSp) of the assay have not been previously established for use in ruminants. This study aimed to validate the IFA by describing the optimization, selection of cutoff titers, repeatability, and reliability as well as the DSe and DSp of the assay. Bayesian latent class analysis was used to estimate diagnostic specifications in comparison with the CFT and the enzyme-linked immunosorbent assay (ELISA). The optimal cutoff dilution for screening for IgG and IgM antibodies in goat serum using the IFA was estimated to be 1:160. The IFA had good repeatability (>96.9% for IgG, >78.0% for IgM), and there was almost perfect agreement (Cohen's kappa > 0.80 for IgG) between the readings reported by two technicians for samples tested for IgG antibodies. The IFA had a higher DSe (94.8%; 95% confidence interval [CI], 80.3, 99.6) for the detection of IgG antibodies against C. burnetii than the ELISA (70.1%; 95% CI, 52.7, 91.0) and the CFT (29.8%; 95% CI, 17.0, 44.8). All three tests were highly specific for goat IgG antibodies. The IFA also had a higher DSe (88.8%; 95% CI, 58.2, 99.5) for detection of IgM antibodies than the ELISA (71.7%; 95% CI, 46.3, 92.8). These results underscore the better suitability of the IFA than of the CFT and ELISA for detection of IgG and IgM antibodies in goat serum and possibly in serum from other ruminants. PMID:27122484

  11. A Coxiella-Like Endosymbiont Is a Potential Vitamin Source for the Lone Star Tick

    PubMed Central

    Smith, Todd A; Driscoll, Timothy; Gillespie, Joseph J; Raghavan, Rahul

    2015-01-01

    Amblyomma americanum (Lone star tick) is an important disease vector in the United States. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness. Blood-feeding insects (Class Insecta) depend on bacterial endosymbionts to provide vitamins and cofactors that are scarce in blood. It is unclear how this deficiency is compensated in ticks (Class Arachnida) that feed exclusively on mammalian blood. A bacterium related to Coxiella burnetii, the agent of human Q fever, has been observed previously within cells of A. americanum. Eliminating this bacterium (CLEAA, Coxiella-like endosymbiont of A. americanum) with antibiotics reduced tick fecundity, indicating that it is an essential endosymbiont. In an effort to determine its role within this symbiosis, we sequenced the CLEAA genome. While highly reduced (656,901 bp) compared with C. burnetii (1,995,281 bp), the CLEAA genome encodes most major vitamin and cofactor biosynthesis pathways, implicating CLEAA as a vitamin provisioning endosymbiont. In contrast, CLEAA lacks any recognizable virulence genes, indicating that it is not a pathogen despite its presence in tick salivary glands. As both C. burnetii and numerous “Coxiella-like bacteria” have been reported from several species of ticks, we determined the evolutionary relationship between the two bacteria. Phylogeny estimation revealed that CLEAA is a close relative of C. burnetii, but was not derived from it. Our results are important for strategies geared toward controlling A. americanum and the pathogens it vectors, and also contribute novel information regarding the metabolic interdependencies of ticks and their nutrient-provisioning endosymbionts. PMID:25618142

  12. Serological survey of Bartonella spp., Borrelia burgdorferi, Brucella spp., Coxiella burnetii, Francisella tularensis, Leptospira spp., Echinococcus, Hanta-, TBE- and XMR-virus infection in employees of two forestry enterprises in North Rhine-Westphalia, Germany, 2011-2013.

    PubMed

    Jurke, Annette; Bannert, N; Brehm, K; Fingerle, V; Kempf, V A J; Kömpf, D; Lunemann, M; Mayer-Scholl, A; Niedrig, M; Nöckler, K; Scholz, H; Splettstoesser, W; Tappe, D; Fischer, Silke F

    2015-10-01

    We initiated a survey to collect basic data on the frequency and regional distribution of various zoonoses in 722 employees of forestry enterprises in the German state of North Rhine-Westphalia (NRW) from 2011 to 2013. Exposures associated with seropositivity were identified to give insight into the possible risk factors for infection with each pathogen. 41.2% of participants were found to be seropositive for anti-Bartonella IgG, 30.6% for anti-Borrelia burgdorferi IgG, 14.2% for anti-Leptospira IgG, 6.5% for anti-Coxiella burnetii IgG, 6.0% for anti-Hantavirus IgG, 4.0% for anti-Francisella tularensis IgG, 3.4% for anti-TBE-virus IgG, 1.7% for anti-Echinococcus IgG, 0.0% for anti-Brucella IgG and anti-XMRV IgG. Participants seropositive for B. burgdorferi were 3.96 times more likely to be professional forestry workers (univariable analysis: OR 3.96; 95% CI 2.60-6.04; p<0.001); and participants seropositive for Hantavirus 3.72 times more likely (univariable analysis: OR 3.72; 95% CI 1.44-9.57; p=0.007). This study found a surprisingly high percentage of participants seropositive for anti-B. henselae IgG and for anti-F. tularensis IgG. The relatively high seroprevalence for anti-Leptospira IgG seen in this study could be related to living conditions rather than to exposure at work. No specific risk for exposure to C. burnetii and Echinococcus was identified, indicating that neither forestry workers nor office workers represent a risk population and that NRW is not a typical endemic area. Forestry workers appear to have higher risk for contact with B. burgdorferi-infected ticks and a regionally diverse risk for acquiring Hantavirus-infection. The regional epidemiology of zoonoses is without question of great importance for public health. Knowledge of the regional risk factors facilitates the development of efficient prevention strategies and the implementation of such prevention measures in a sustainable manner. PMID:26422407

  13. Coxiella-like endosymbiont in argasid ticks (Ornithodoros muesebecki) from a Socotra Cormorant colony in Umm Al Quwain, United Arab Emirates.

    PubMed

    Al-Deeb, Mohammad A; Frangoulidis, Dimitrios; Walter, Mathias C; Kömpf, Daniela; Fischer, Silke F; Petney, Trevor; Muzaffar, Sabir Bin

    2016-02-01

    Coxiella burnetii is a pathogen causing Q fever in domestic animals and humans. Seabirds have been implicated as possible reservoirs of this bacterium in the Arabian Gulf and in the Western Indian Ocean. Recently, Coxiella species closely related to C. burnetii was detected from ticks collected from oil rigs used as roosting areas by Socotra Cormorants (Phalacrocorax nigrogularis) in the western Arabian Gulf. We collected ticks from the largest breeding colony of Socotra Cormorants in the United Arab Emirates on the eastern extreme of the species' breeding range to determine the prevalence of C. burnetii and evaluate its role as a wild reservoir. All ticks were identified as Ornithodoros muesebecki and genomic DNA was extracted from larval and nymph/adult tick pools. Multiplex PCR tests were performed targeting three C. burnetii specific genes. C. burnetii was not detected although a Coxiella-like endosymbiont was identified that was closely related to Coxiella symbionts from Ornithodoros capensis ticks. Because domestic and wild ungulates are the primary source of C. burnetii, we suggest that the presence of free-ranging, native and non-native ungulates in some off-shore islands in the Arabian Gulf could disseminate C. burnetii to seabirds. More comprehensive studies on seabird colonies are needed to better understand the diversity and prevalence of Coxiella symbionts and to establish if C. burnetii is endemic on some of these islands. PMID:26515059

  14. [Q fever, a potential biowarfare agent].

    PubMed

    Bossi, Philippe; Guihot, Amélie; Bricaire, François

    2003-10-18

    SEVERAL POSSIBLE METHODS OF TRANSFUSION: Q fever is a zoonosis due to Coxiella burnetii. Its interest as a potential biowarfare agent is in its possible transmission by inhalation of sprayed particles. This form of transmission would probably be used: the inhalation of 1 to 10 bacteria could provoke the development of an infection in humans. Another possible method of transmission in the context of a terrorist act would be the intentional introduction of the bacteria into foodstuff. A DISABLING WEAPON: However, C. burnetii has never been used as a biological weapon. The probability that this germ could be used is very low: indeed, the incubation of Q fever is very long, and the majority of the infections is asymptomatic and mortality is low. In fact C. burnetii would more likely be used as a disabling weapon. PMID:14576588

  15. First Complete Genome Sequence of the Dutch Veterinary Coxiella burnetii Strain NL3262, Originating from the Largest Global Q Fever Outbreak, and Draft Genome Sequence of Its Epidemiologically Linked Chronic Human Isolate NLhu3345937.

    PubMed

    Kuley, Runa; Smith, Hilde E; Janse, Ingmar; Harders, Frank L; Baas, Frank; Schijlen, Elio; Nabuurs-Franssen, Marrigje H; Smits, Mari A; Roest, Hendrik I J; Bossers, Alex

    2016-01-01

    The largest global Q fever outbreak occurred in The Netherlands during 2007 to 2010. Goats and sheep were identified as the major sources of disease. Here, we report the first complete genome sequence of ITALIC! Coxiella burnetiigoat outbreak strain NL3262 and that of an epidemiologically linked chronic human strain, both having the outbreak-related ITALIC! CbNL01multilocus variable-number tandem-repeat analysis (MLVA) genotype. PMID:27103714

  16. Inactivation of Coxiella burnetti by gamma irradiation

    SciTech Connect

    Scott, G.H.; McCaul, T.F.; Williams, J.C.

    1989-01-01

    The gamma radiation inactivation kinetics for Coxiella burnetii at - 79 C were exponential. The radiation dose needed to reduce the number of infective C. burnetii by 90% varied from 0-64 to 1.2 kGy depending on the phase of hte micro-organism, purity of the culture and composition of suspending menstruum. The viability of preparations containing C. burnetti was completely abolished by 10 kGy without diminishing antigenicity or ability to elicit a protective immune response in vaccinated mice. Immunocytochemical examinations using monoclonal antibodies and electron microscopy demonstrated that radiation doses of 20 kGy did not alter cell-wall morphology or cell-surface antigenic epitopes.

  17. Detection of Lyme Disease and Q Fever Agents in Wild Rodents in Central Italy

    PubMed Central

    Di Domenico, Marco; Dall'Acqua, Francesca; Sozio, Giulia; Cammà, Cesare

    2015-01-01

    Abstract The maintenance of tick-borne disease agents in the environment strictly depends on the relationship between tick vectors and their hosts, which act as reservoirs for these pathogens. A pilot study aimed to investigate wild rodents as reservoirs for zoonotic tick-borne pathogens (Borrelia burgdorferi sensu lato (s.l.), Coxiella burnetii, Francisella tularensis, and Anaplasma phagocytophilum) was carried out in an area of Gran Sasso e Monti della Laga National Park (Abruzzi Region, central Italy), a wide protected area where, despite sporadic reports of infection in humans and animals, eco-epidemiological data on these diseases are still not available. Rodents were trapped and released at the capture site after the collection of feeding ticks and blood samples. In all, 172 ticks were collected; the most frequent species was Ixodes acuminatus (53%). Out of 88 tick pools, 11 resulted positive for C. burnetii and 13 for B. burgdorferi s.l.; the Borrelia afzelii genospecies was identified in one Ixodes ricinus tick collected from one Apodemus sp. rodent. Out of 143 blood samples, seven Apodemus spp. and five Myodes glareolus were positive for B. burgdorferi s.l. and two Apodemus spp. were positive for C. burnetii. All samples (ticks and blood) were negative for F. tularensis and A. phagocytophilum. This is the first report of B. burgdorferi s.l. in the environment for Abruzzi Region. Data on the presence of B. burgdorferi s.l. are similar to that observed in other Mediterranean countries. The present work is also the first report of C. burnetii in wild rodents in Italy. C. burnetii infection has been largely investigated in Italy in ruminant farms by serology and molecular methods, but information on ecology and on the wild cycle are still lacking. Further studies including genotyping should be performed and species-specific differences between wild rodent reservoirs of Q fever and Lyme disease agents should be investigated. PMID:26134933

  18. Detection of Lyme Disease and Q Fever Agents in Wild Rodents in Central Italy.

    PubMed

    Pascucci, Ilaria; Di Domenico, Marco; Dall'Acqua, Francesca; Sozio, Giulia; Cammà, Cesare

    2015-07-01

    The maintenance of tick-borne disease agents in the environment strictly depends on the relationship between tick vectors and their hosts, which act as reservoirs for these pathogens. A pilot study aimed to investigate wild rodents as reservoirs for zoonotic tick-borne pathogens (Borrelia burgdorferi sensu lato (s.l.), Coxiella burnetii, Francisella tularensis, and Anaplasma phagocytophilum) was carried out in an area of Gran Sasso e Monti della Laga National Park (Abruzzi Region, central Italy), a wide protected area where, despite sporadic reports of infection in humans and animals, eco-epidemiological data on these diseases are still not available. Rodents were trapped and released at the capture site after the collection of feeding ticks and blood samples. In all, 172 ticks were collected; the most frequent species was Ixodes acuminatus (53%). Out of 88 tick pools, 11 resulted positive for C. burnetii and 13 for B. burgdorferi s.l.; the Borrelia afzelii genospecies was identified in one Ixodes ricinus tick collected from one Apodemus sp. rodent. Out of 143 blood samples, seven Apodemus spp. and five Myodes glareolus were positive for B. burgdorferi s.l. and two Apodemus spp. were positive for C. burnetii. All samples (ticks and blood) were negative for F. tularensis and A. phagocytophilum. This is the first report of B. burgdorferi s.l. in the environment for Abruzzi Region. Data on the presence of B. burgdorferi s.l. are similar to that observed in other Mediterranean countries. The present work is also the first report of C. burnetii in wild rodents in Italy. C. burnetii infection has been largely investigated in Italy in ruminant farms by serology and molecular methods, but information on ecology and on the wild cycle are still lacking. Further studies including genotyping should be performed and species-specific differences between wild rodent reservoirs of Q fever and Lyme disease agents should be investigated. PMID:26134933

  19. Molecular detection of Rickettsia, Anaplasma, Coxiella and Francisella bacteria in ticks collected from Artiodactyla in Thailand.

    PubMed

    Sumrandee, Chalao; Baimai, Visut; Trinachartvanit, Wachareeporn; Ahantarig, Arunee

    2016-07-01

    A total of 79 ticks collected from Sambar deer (Cervus unicolor), Barking deer (Muntiacus muntjak) and Wild boar (Sus scrofa) were examined by PCR for the presence of Rickettsia, Anaplasma, Coxiella, and Francisella bacteria. Of the 79 ticks, 13% tested positive for Rickettsia, 15% tested positive for Anaplasma, 4% tested positive for Coxiella, and 3% tested positive for Francisella. Interestingly, triple infection with Anaplasma, Rickettsia and Francisella was determined in a Dermacentor auratus tick. Moreover, another triple infection with Rickettsia, Anaplasma, and Coxiella was found in a Haemaphysalis lagrangei tick. Double infection of Rickettsia with Coxiella was also detected in another H. lagrangei tick. From the phylogenetic analyses, we found a Rickettsia sp. with a close evolutionary relationship to Rickettsia bellii in the H. lagrangei tick. We also found the first evidence of a Rickettsia sp. that is closely related to Rickettsia tamurae in Rhipicephalus (Boophilus) microplus ticks from Thailand. H. lagrangei and Haemaphysalis obesa ticks collected from Sambar deer tested positive for Anaplasma species form the same clade with Anaplasma bovis. In contrast, other H. lagrangei ticks collected from Sambar deer and D. auratus ticks collected from Wild boar were also reported for the first time to be infected with an Anaplasma species that is closely related to Anaplasma platys. The phylogenetic analysis of the 16S rRNA gene of Coxiella bacteria revealed that Coxiella symbionts from H. lagrangei formed a distinctly different lineage from Coxiella burnetii (a human pathogen). Additionally, Francisella bacteria identified in D. auratus ticks were found to be distantly related to a group of pathogenic Francisella species. The identification of these bacteria in several feeding ticks suggests the risk of various emerging tick-borne diseases and endosymbionts in humans, wildlife, and domestic animals in Thailand. PMID:26934997

  20. Q fever: the neglected biothreat agent.

    PubMed

    Oyston, P C F; Davies, C

    2011-01-01

    Coxiella burnetii is the causative agent of Q fever, a disease with a spectrum of presentations from the mild to fatal, including chronic sequelae. Since its discovery in 1935, it has been shown to infect a wide range of hosts, including humans. A recent outbreak in Europe reminds us that this is still a significant pathogen of concern, very transmissible and with a very low infectious dose. For these reasons it has also featured regularly on various threat lists, as it may be considered by the unscrupulous for use as a bioweapon. As an intracellular pathogen, it has remained an enigmatic organism due to the inability to culture it on laboratory media. As a result, interactions with the host have been difficult to elucidate and we still have a very limited understanding of the molecular mechanisms of virulence. However, two recent developments will open up our understanding of C. burnetii: the first axenic growth medium capable of supporting cell-free growth, and the production of the first isogenic mutant. We are approaching an exciting time for expanding our knowledge of this organism in the next few years. PMID:21030501

  1. In vitro studies of interaction of rickettsia and macrophages: effect of ultraviolet light on Coxiella burnetti inactivation and macrophage enzymes

    SciTech Connect

    Little, J.S.; Kishimoto, R.A.; Canonico, P.G.

    1980-03-01

    The inactivation of Coxiella burnetii in suspension or in cultures of guinea pig peritoneal macrophages by ultraviolet (uv) light was studied. The effect of uv treatment on the activity of macrophage organelle marker enzymes and their subsequent equilibration in linear sucrose gradients was also determined. It was shown that uv treatment for 15 s at a distance of 10 cm inactivated C. burnetti, either in suspension or within guinea pig peritoneal macrophages. Similar uv treatment had little effect on the activity or equilibration of macrophage organelle marker enzymes in linear sucrose gradients.

  2. Molecular detection of Rickettsia, Coxiella and Rickettsiella DNA in three native Australian tick species.

    PubMed

    Vilcins, Inger-Marie E; Old, Julie M; Deane, Elizabeth

    2009-11-01

    Three Australian native animal species yielded 60 samples composed of three indigenous ticks. Hosts included twelve koalas, two echidnas and one wombat from Victoria, and ticks were of the species Ixodes tasmani (n = 42), Bothriocroton concolor (n = 8) and B. auruginans (n = 10), respectively. PCR screening and sequencing detected a species of Coxiella, sharing closest sequence identity to C. burnetii (>98%), in all B. auruginans, as well as a species of Rickettsia, matching closest to R. massiliae, in 70% of the same samples. A genotype sharing closest similarity to Rickettsia bellii (>99%) was identified in three female B. concolor collected from one of the echidnas. Three samples of I. tasmani, taken from three koalas, yielded different genotypes of Rickettsiella. These results represent the first detection of the three genera in each tick species and identify a high level of previously undetected bacterial diversity in Australian ticks. PMID:19296229

  3. Microbiological and parasitological survey of zoonotic agents in apparently healthy feral pigeons.

    PubMed

    Marenzoni, M L; Morganti, G; Moretta, I; Crotti, S; Agnetti, F; Moretti, A; Pitzurra, L; Casagrande Proietti, P; Sechi, P; Cenci-Goga, B; Franciosini, M P

    2016-01-01

    Microbiological and parasitological investigation was carried out on a colony of feral pigeons, located in a green area near the main hospital of a Central Italy city. One hundred pigeons were submitted to clinical examination. Cloacal swabs, grouped in pool of 4 samples, were analyzed to detect the presence of Coxiella burnetii, Chlamydia psittaci, Chlamydophila spp. using a biomolecular procedure, while individual cloacal samples were examined for Salmonella spp., Campylobacter spp., and yeasts by means of a specific culture media. An ELISA test was used to determine the presence of Giardia spp., and Cryptosporidium spp. coproantigens. Individual serological samples were also tested with the modified agglutination test (MAT) in order to detect antibodies against Toxoplasma gondii. The pigeons did not show any clinical signs. The cloacal pools proved to be negative for C. burnetii DNA while three pools were positive for C. psittaci or Chlamydophila spp. DNAs. Salmonella spp. was not detected. C. jejuni and C. coli were found in 13% and 4% of the samples, respectively. No Giardia spp. and Cryptosporidium spp. were detected. Thirty-three out of 100 samples (33%) were positive for yeast colonies. The seroprevalence for T. gondii was 8%. Although with moderate incidence, potentially zoonotic agents were present thus highlighting the need for sanitary surveillance on feral pigeon colonies. PMID:27487504

  4. Further characterization of a lipopolysaccharide from Coxiella burneti.

    PubMed Central

    Chan, M L; McChesney, J; Paretsky, D

    1976-01-01

    The lipopolysaccharide previously isolated from the rickettsial agent of Q fever, Coxiella burneti, phase I, has been further characterized. The sugar residues ribose, mannose, gluclose, D-glycero-D-mannoheptose, and L-glycerto-D-mannoheptose are present. Two sugars remain unidentified, one of which is a minor and the other a major constituent. Isomyristic, palmitic, and beta-hydroxymyristic acids are the major fatty acid residues of the 15 identified. The nature and content of other lipopolysaccharide constituents are presented. Images PMID:971947

  5. Rickettsial agents in Egyptian ticks collected from domestic animals.

    PubMed

    Loftis, Amanda D; Reeves, Will K; Szumlas, Daniel E; Abbassy, Magda M; Helmy, Ibrahim M; Moriarity, John R; Dasch, Gregory A

    2006-01-01

    To assess the presence of rickettsial pathogens in ticks from Egypt, we collected ticks from domestic and peridomestic animals between June 2002 and July 2003. DNA extracts from 1019 ticks were tested, using PCR and sequencing, for Anaplasma spp., Bartonella spp., Coxiella burnetii, Ehrlichia spp., and Rickettsia spp. Ticks included: 29 Argas persicus, 10 Hyalomma anatolicum anatolicum, 55 Hyalomma anatolicum excavatum, 174 Hyalomma dromedarii, 2 Hyalomma impeltatum, 3 Hyalomma marginatum rufipes, 55 unidentified nymphal Hyalomma, 625 Rhipicephalus (Boophilus) annulatus, 49 Rhipicephalus sanguineus, and 17 Rhipicephalus turanicus. Ticks were collected predominantly (>80%) from buffalo, cattle, and camels, with smaller numbers from chicken and rabbit sheds, sheep, foxes, a domestic dog, a hedgehog, and a black rat. We detected Anaplasma marginale, Coxiella burnetii, Rickettsia aeschlimannii, and four novel genotypes similar to: "Anaplasma platys," Ehrlichia canis, Ehrlichia spp. reported from Asian ticks, and a Rickettsiales endosymbiont of Ixodes ricinus. PMID:17004028

  6. Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the Coxiella-Containing Vacuole

    PubMed Central

    Kohler, Lara J.; Reed, Shawna R.; Sarraf, Shireen A.; Arteaga, David D.

    2016-01-01

    ABSTRACT Coxiella burnetii replicates in an acidified lysosome-derived vacuole. Biogenesis of the Coxiella-containing vacuole (CCV) requires bacterial effector proteins delivered into host cells by the Dot/Icm secretion system. Genetic and cell biological analysis revealed that an effector protein called Cig2 promotes constitutive fusion of autophagosomes with the CCV to maintain this compartment in an autolysosomal stage of maturation. This distinguishes the CCV from other pathogen-containing vacuoles that are targeted by the host autophagy pathway, which typically confers host resistance to infection by delivering the pathogen to a toxic lysosomal environment. By maintaining the CCV in an autolysosomal stage of maturation, Cig2 enabled CCV homotypic fusion and enhanced bacterial virulence in the Galleria mellonella (wax moth) model of infection by a mechanism that decreases host tolerance. Thus, C. burnetii residence in an autolysosomal organelle alters host tolerance of infection, which indicates that Cig2-dependent manipulation of a lysosome-derived vacuole influences the host response to infection. PMID:27435465

  7. Risk factor analysis for antibodies to Brucella, Leptospira and C. burnetii among cattle in the Adamawa Region of Cameroon: a cross-sectional study.

    PubMed

    Mazeri, Stella; Scolamacchia, Francesca; Handel, Ian G; Morgan, Kenton L; Tanya, Vincent N; Bronsvoort, Barend M deC

    2013-02-01

    Brucellosis, leptospirosis and Q fever are important livestock diseases, commonly responsible for significant production losses, yet their epidemiology in sub-Saharan Africa is largely unknown. Animal reservoirs pose the main risk of transmission to humans, where serious disease can occur. In the developing world setting, the flu-like symptoms of the acute stages of these diseases can be misdiagnosed as malaria, which can result in the administration of the wrong treatment, prolonged disease and increase in antibiotic resistance. Multivariable mixed-effects logistic regression models in this study revealed potential risk factors associated with the aforementioned pathogens in cattle in the Adamawa Region of Cameroon, with wildlife, namely, buffaloes, playing a major role in both Brucella and Coxiella burnetii seropositivity. Cattle mixing with other herds at night and cattle grazing in an area on a route taken by herds on transhumance appear to be positively associated with Leptospira seropositivity, while female cows and whether buffaloes are seen during grazing or transhumance are positively associated with C. burnetii seropositivity. On the other hand, animals that have been on transhumance in the past year and animals belonging to herdsmen of the Fulbe ethnic group appear to be protected against Leptospira and C. burnetii, respectively. Cattle of more than 2 years old appear to have increased odds of being seropositive to either pathogen. Further research is needed to confirm these findings and improve the knowledge of the epidemiology of these three pathogens in Africa, taking particular consideration of the wildlife involvement in the disease transmission. PMID:23117621

  8. Epizootiologic investigations of selected abortive agents in free-ranging Alpine ibex (Capra ibex ibex) in Switzerland.

    PubMed

    Marreros, Nelson; Hüssy, Daniela; Albini, Sarah; Frey, Caroline F; Abril, Carlos; Vogt, Hans-Rudolf; Holzwarth, Nathalie; Wirz-Dittus, Sophie; Friess, Martina; Engels, Monika; Borel, Nicole; Willisch, Christian S; Signer, Claudio; Hoelzle, Ludwig E; Ryser-Degiorgis, Marie-Pierre

    2011-07-01

    In the early 2000s, several colonies of Alpine ibex (Capra ibex ibex) in Switzerland ceased growing or began to decrease. Reproductive problems due to infections with abortive agents might have negatively affected recruitment. We assessed the presence of selected agents of abortion in Alpine ibex by serologic, molecular, and culture techniques and evaluated whether infection with these agents might have affected population densities. Blood and fecal samples were collected from 651 ibex in 14 colonies throughout the Swiss Alps between 2006 and 2008. All samples were negative for Salmonella spp., Neospora caninum, and Bovine Herpesvirus-1. Antibodies to Coxiella burnetii, Leptospira spp., Chlamydophila abortus, Toxoplasma gondii, and Bovine Viral Diarrhea virus were detected in at least one ibex. Positive serologic results for Brucella spp. likely were false. Overall, 73 samples (11.2%) were antibody-positive for at least one abortive agent. Prevalence was highest for Leptospira spp. (7.9%, 95% CI=5.0-11.7). The low prevalences and the absence of significant differences between colonies with opposite population trends suggest these pathogens do not play a significant role in the population dynamics of Swiss ibex. Alpine ibex do not seem to be a reservoir for these abortive agents or an important source of infection for domestic livestock in Switzerland. Finally, although interactions on summer pastures occur frequently, spillover from infected livestock to free-ranging ibex apparently is uncommon. PMID:21719818

  9. Zoonotic agents in small ruminants kept on city farms in southern Germany.

    PubMed

    Schilling, Anna-Katarina; Hotzel, Helmut; Methner, Ulrich; Sprague, Lisa D; Schmoock, Gernot; El-Adawy, Hosny; Ehricht, Ralf; Wöhr, Anna-Caroline; Erhard, Michael; Geue, Lutz

    2012-06-01

    Sheep and goats are popular examples of livestock kept on city farms. In these settings, close contacts between humans and animals frequently occur. Although it is widely accepted that small ruminants can carry numerous zoonotic agents, it is unknown which of these agents actually occur in sheep and goats on city farms in Germany. We sampled feces and nasal liquid of 48 animals (28 goats, 20 sheep) distributed in 7 city farms and on one activity playground in southern Germany. We found that 100% of the sampled sheep and 89.3% of the goats carried Shiga toxin-producing Escherichia coli (STEC). The presence of Staphylococcus spp. in 75% of both sheep and goats could be demonstrated. Campylobacter spp. were detected in 25% and 14.3% of the sheep and goats, respectively. Neither Salmonella spp. nor Coxiella burnetii was found. On the basis of these data, we propose a reasonable hygiene scheme to prevent transmission of zoonotic agents during city farm visits. PMID:22447607

  10. Zoonotic Agents in Small Ruminants Kept on City Farms in Southern Germany

    PubMed Central

    Schilling, Anna-Katarina; Hotzel, Helmut; Methner, Ulrich; Sprague, Lisa D.; Schmoock, Gernot; El-Adawy, Hosny; Ehricht, Ralf; Wöhr, Anna-Caroline; Erhard, Michael

    2012-01-01

    Sheep and goats are popular examples of livestock kept on city farms. In these settings, close contacts between humans and animals frequently occur. Although it is widely accepted that small ruminants can carry numerous zoonotic agents, it is unknown which of these agents actually occur in sheep and goats on city farms in Germany. We sampled feces and nasal liquid of 48 animals (28 goats, 20 sheep) distributed in 7 city farms and on one activity playground in southern Germany. We found that 100% of the sampled sheep and 89.3% of the goats carried Shiga toxin-producing Escherichia coli (STEC). The presence of Staphylococcus spp. in 75% of both sheep and goats could be demonstrated. Campylobacter spp. were detected in 25% and 14.3% of the sheep and goats, respectively. Neither Salmonella spp. nor Coxiella burnetii was found. On the basis of these data, we propose a reasonable hygiene scheme to prevent transmission of zoonotic agents during city farm visits. PMID:22447607

  11. The absence of zoonotic agents in invasive bullfrogs (Lithobates catesbeianus) in Belgium and The Netherlands.

    PubMed

    Martel, An; Adriaensen, Connie; Sharifian-Fard, Mojdeh; Spitzen-van der Sluijs, Annemarieke; Louette, Gerald; Baert, Kristof; Crombaghs, Ben; Dewulf, Jeroen; Pasmans, Frank

    2013-12-01

    Exotic invasive bullfrogs (Lithobates catesbeianus) are considered to exert a considerable negative impact on native amphibian communities. This can be due to competition and predation, but they are also a notorious source of the infectious diseases chytridiomycosis and ranavirosis, affecting amphibian populations globally. Little is known regarding their carriage of other microbial agents that might be transferred to humans or other animals. In this study we determined the occurrence of the amphibian pathogens Ranavirus and Batrachochytrium dendrobatidis and of the zoonotic agents Coxiella burnetii, Neospora caninum, Leptospira sp., Toxoplasma gondii, Mycoplasma sp., Campylobacter sp., Salmonella sp. and extended-spectrum beta-lactamase producing Escherichia coli in 164 bullfrogs from three populations in Belgium and The Netherlands. Although B. dendrobatidis was present at a high prevalence of 63%, mean infection loads were low with an average of 10.9 genomic equivalents (SD 35.5), confirming the role of bullfrogs as B. dendrobatidis carriers, but questioning their role as primary reservoirs for B. dendrobatidis transmission to native amphibian communities. All tested samples were negative for the other infectious agents examined. These results suggest a limited role of bullfrogs as carrier of these pathogens. PMID:24162797

  12. Survey of nine abortifacient infectious agents in aborted bovine fetuses from dairy farms in Beijing, China, by PCR.

    PubMed

    Yang, Na; Cui, Xia; Qian, Weifeng; Yu, Shanshan; Liu, Qun

    2012-03-01

    Abortion in dairy cattle causes considerable economic losses to the dairy industry. Aborted fetuses and samples from the corresponding aborting dams from 12 dairy herds in Beijing were tested for 9 abortifacient infectious pathogens by PCR between 2008 and 2010. From a total of 80 abortion cases collected during this period, infectious agents were detected in 45 (56.3%) cases, 22 (48.9%) of which represented co-infections with two or three infectious agents. The detected pathogens included infectious bovine rhinotracheitis virus (36.3%) and Neospora caninum (31.3%), followed by bovine viral diarrhoea virus (7.5%), Brucella abortus (6.3%), Tritrichomonas foetus (5%) and Toxoplasma gondii (1.3%). Campylobacter fetus, Coxiella burnetii and Chlamydophila psittaci were not detected in any abortion case. Findings from this study indicated that infectious bovine rhinotracheitis virus and Neospora caninum were the main potential causes of abortions in Beijing dairy herds, whereas the bacterial pathogens were not, in contrast to reports from other countries. This is the first study to test nine abortifacient infectious agents by PCR at the same time, and it is also the first time to report the involvement of a variety of infectious agents in bovine abortion cases in China. PMID:22366134

  13. Molecular Survey of Zoonotic Agents in Rodents and Other Small Mammals in Croatia.

    PubMed

    Tadin, Ante; Tokarz, Rafal; Markotić, Alemka; Margaletić, Josip; Turk, Nenad; Habuš, Josipa; Svoboda, Petra; Vucelja, Marko; Desai, Aaloki; Jain, Komal; Lipkin, W Ian

    2016-02-01

    Croatia is a focus for many rodent-borne zoonosis. Here, we report a survey of 242 rodents and small mammals, including 43 Myodes glareolus, 131 Apodemus flavicollis, 53 Apodemus agrarius, three Apodemus sylvaticus, six Sorex araneus, four Microtus arvalis, one Microtus agrestis, and one Muscardinus avellanarius, collected at eight sites in Croatia over an 8-year period. Multiplex MassTag polymerase chain reaction (PCR) was used for detection of Borrelia, Rickettsia, Bartonella, Babesia, Ehrlichia, Anaplasma, Francisella tularensis, and Coxiella burnetii. Individual PCR assays were used for detection of Leptospira, lymphocytic choriomeningitis virus, orthopoxviruses, flaviviruses, hantaviruses, and Toxoplasma gondii. Of the rodents, 52 (21.5%) were infected with Leptospira, 9 (3.7%) with Borrelia miyamotoi, 5 (2%) with Borrelia afzelii, 29 (12.0%) with Bartonella, 8 (3.3%) with Babesia microti, 2 (0.8%) with Ehrlichia, 4 (1.7%) with Anaplasma, 2 (0.8%) with F. tularensis, 43 (17.8%) with hantaviruses, and 1 (0.4%) with an orthopoxvirus. Other agents were not detected. Multiple infections were found in 32 rodents (13.2%): dual infections in 26 rodents (10.7%), triple infections in four rodents (2.9%), and quadruple infections in two rodents (0.8%). Our findings indicate that rodents in Croatia harbor a wide range of bacteria and viruses that are pathogenic to humans. PMID:26711522

  14. Detection of Microbial Agents in Ticks Collected from Migratory Birds in Central Italy

    PubMed Central

    Toma, Luciano; Mancini, Fabiola; Di Luca, Marco; Cecere, Jacopo G.; Bianchi, Riccardo; Khoury, Cristina; Quarchioni, Elisa; Manzia, Francesca; Rezza, Giovanni

    2014-01-01

    Abstract Tick species characterization and molecular studies were performed within ornithological surveys conducted during 2010 and 2011 in the Lazio Region of central Italy. A total of 137 ticks were collected from 41 migratory birds belonging to 17 species (four partial migrants and 13 long-distance migrants). Most ticks were nymphs, with a predominance of Hyalomma marginatum marginatum and H. m. rufipes, and a small portion of Ixodes and Amblyomma species. All tick species analyzed were infected, and the molecular pathogen recognition revealed the presence of Rickettsia aeschlimannii, Rickettsia africae, Erlichia spp., Coxiella burnetii, Borrelia burgdorferi sensu lato group, and Babesia microti, whereas no genomic DNA of Bartonella spp. or Francisella tularensis was detected. The results of the survey show that H. marginatum ticks appear to be a vector of microbial agents that may affect human and animal health and that migratory birds may be an important carrier of these ticks. Additional studies are needed to better investigate the role of migratory birds in the epidemiology of these pathogens. PMID:24576218

  15. Evaluation of a new serological test for the detection of anti-Coxiella and anti-Rickettsia antibodies.

    PubMed

    Bizzini, Alain; Péter, Olivier; Baud, David; Edouard, Sophie; Meylan, Pascal; Greub, Gilbert

    2015-01-01

    Coxiella burnetii and members of the genus Rickettsia are obligate intracellular bacteria. Since cultivation of these organisms requires dedicated techniques, their diagnosis usually relies on serological or molecular biology methods. Immunofluorescence is considered the gold standard to detect antibody-reactivity towards these organisms. Here, we assessed the performance of a new automated epifluorescence immunoassay (InoDiag) to detect IgM and IgG against C. burnetii, Rickettsia typhi and Rickettsia conorii. Samples were tested with the InoDiag assay. A total of 213 sera were tested, of which 63 samples from Q fever, 20 from spotted fever rickettsiosis, 6 from murine typhus and 124 controls. InoDiag results were compared to micro-immunofluorescence. For acute Q fever, the sensitivity of phase 2 IgG was only of 30% with a cutoff of 1 arbitrary unit (AU). In patients with acute Q fever with positive IF IgM, sensitivity reached 83% with the same cutoff. Sensitivity for chronic Q fever was 100% whereas sensitivity for past Q fever was 65%. Sensitivity for spotted Mediterranean fever and murine typhus were 91% and 100%, respectively. Both assays exhibited a good specificity in control groups, ranging from 79% in sera from patients with unrelated diseases or EBV positivity to 100% in sera from healthy patients. In conclusion, the InoDiag assay exhibits an excellent performance for the diagnosis of chronic Q fever but a very low IgG sensitivity for acute Q fever likely due to low reactivity of phase 2 antigens present on the glass slide. This defect is partially compensated by the detection of IgM. Because it exhibits a good negative predictive value, the InoDiag assay is valuable to rule out a chronic Q fever. For the diagnosis of rickettsial diseases, the sensitivity of the InoDiag method is similar to conventional immunofluorescence. PMID:26432518

  16. Development of a set of multiplex standard polymerase chain reaction assays for the identification of infectious agents from aborted bovine clinical samples.

    PubMed

    Tramuta, Clara; Lacerenza, Daniela; Zoppi, Simona; Goria, Mariella; Dondo, Alessandro; Ferroglio, Ezio; Nebbia, Patrizia; Rosati, Sergio

    2011-07-01

    The current study describes the development of a set of 5 multiplex polymerase chain reaction (mPCR) assays for the simultaneous detection of abortive infection agents in bovine fetal tissues, including Brucella spp., Leptospira spp., and Campylobacter fetus (mPCR1); Hammondia heydorni, Neospora caninum, and Toxoplasma gondii (mPCR2); Coxiella burnetii and Chlamydophila psittaci (mPCR3); Mycoplasma bovis, Mycoplasma bovigenitalium, and Ureaplasma diversum (mPCR4); and Bovine viral diarrhea virus (BVDV) and Bovine herpesvirus-1 (BoHV-1; mPCR5). The protocol was tested on different tissue samples collected from 50 aborted bovine fetuses, and it showed that out of the 50 fetuses, 7 (14%, mPCR2) were PCR-positive for N. caninum, 4 (8%, mPCR5) were PCR-positive for BVDV, and 2 (4%, mPCR4) were PCR-positive for U. diversum. The results obtained by using each multiplex PCR were 100% concordant with those obtained by using the respective PCR assays targeting single genes on the same specimens. Moreover, all multiplex PCR assays on clinical samples were compared with reference methods, obtaining a perfect accordance in all samples and confirming the validity of the set of multiplex PCR assays. The proposed set of multiplex PCR assays is, therefore, suitable for the simultaneous detection of the main infectious agents responsible for bovine abortion. PMID:21908306

  17. Prevalence and Correlation of Infectious Agents in Hospitalized Children with Acute Respiratory Tract Infections in Central China

    PubMed Central

    Li, Fu; Wen, Zhou; Liu, Weiyong; Li, Tongya; Qin, Kai; Wu, Jianguo; Liu, Yingle

    2015-01-01

    Acute respiratory tract infections (ARTIs) are associated with significant morbidity and mortality worldwide, especially in children under the age of 5 years. Almost 2 million children die from ARTIs each year, and most of them are from developing countries. The prevalence and correlation of pathogens in ARTIs are poorly understood, but are critical for improving case prevention, treatment, and management. In this study, we investigated the prevalence and correlation of infectious agents in children with ARTIs. A total of 39,756 children with one or more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis, herpangina, pneumonia, and bronchiolitis, were enrolled in the study. All patients were hospitalized in Wuhan Children’s Hospital between October 1, 2010 and September 30, 2012, and were evaluated for infectious agents. Pathogens, including Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened simultaneously in patient blood samples using anti-pathogen IgM tests. Regression analysis was used to reveal correlations among the pathogens. Our results showed that one or more pathogens were identified in 10,206 patients, and that Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading infectious agents. Mixed-infections of pathogens were detected in 2,391 cases, with Mycoplasma pneumoniae as the most frequent pathogen. The most common agents in the co-infections were Mycoplasma pneumoniae and influenza B virus. Regression analysis revealed a linear correlation between the proportion of mixed infections and the incidence of multi-pathogen infections. The prevalence of infectious agents in children with ARTIs was determined. Equations were established to estimate multiple infections by single-pathogen detection. This revealed a linear correlation for pathogens in children

  18. Prevalence and correlation of infectious agents in hospitalized children with acute respiratory tract infections in Central China.

    PubMed

    Liu, Jia; Ai, Hongwu; Xiong, Ying; Li, Fu; Wen, Zhou; Liu, Weiyong; Li, Tongya; Qin, Kai; Wu, Jianguo; Liu, Yingle

    2015-01-01

    Acute respiratory tract infections (ARTIs) are associated with significant morbidity and mortality worldwide, especially in children under the age of 5 years. Almost 2 million children die from ARTIs each year, and most of them are from developing countries. The prevalence and correlation of pathogens in ARTIs are poorly understood, but are critical for improving case prevention, treatment, and management. In this study, we investigated the prevalence and correlation of infectious agents in children with ARTIs. A total of 39,756 children with one or more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis, herpangina, pneumonia, and bronchiolitis, were enrolled in the study. All patients were hospitalized in Wuhan Children's Hospital between October 1, 2010 and September 30, 2012, and were evaluated for infectious agents. Pathogens, including Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened simultaneously in patient blood samples using anti-pathogen IgM tests. Regression analysis was used to reveal correlations among the pathogens. Our results showed that one or more pathogens were identified in 10,206 patients, and that Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading infectious agents. Mixed-infections of pathogens were detected in 2,391 cases, with Mycoplasma pneumoniae as the most frequent pathogen. The most common agents in the co-infections were Mycoplasma pneumoniae and influenza B virus. Regression analysis revealed a linear correlation between the proportion of mixed infections and the incidence of multi-pathogen infections. The prevalence of infectious agents in children with ARTIs was determined. Equations were established to estimate multiple infections by single-pathogen detection. This revealed a linear correlation for pathogens in children with

  19. Q fever.

    PubMed

    Tissot-Dupont, Hervé; Raoult, Didier

    2008-09-01

    Q fever is a worldwide zoonosis caused by the pathogen Coxiella burnetii causing acute and chronic clinical manifestations. The name "Q fever" derives from "Query fever" and was given in 1935 following an outbreak of febrile illness in an abattoir in Queensland, Australia. C burnetii is considered a potential agent of bioterrorism (class B by the Centers for Disease Control). PMID:18755387

  20. A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents

    PubMed Central

    Madrid, Peter B.; Chopra, Sidharth; Manger, Ian D.; Gilfillan, Lynne; Keepers, Tiffany R.; Shurtleff, Amy C.; Green, Carol E.; Iyer, Lalitha V.; Dilks, Holli Hutcheson; Davey, Robert A.; Kolokoltsov, Andrey A.; Carrion, Ricardo; Patterson, Jean L.; Bavari, Sina; Panchal, Rekha G.; Warren, Travis K.; Wells, Jay B.; Moos, Walter H.; Burke, RaeLyn L.; Tanga, Mary J.

    2013-01-01

    Background The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. Methodology/Principal Findings A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. Conclusions/Significance The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses. PMID:23577127

  1. Serologic screening for 13 infectious agents in roe deer (Capreolus capreolus) in Flanders

    PubMed Central

    Tavernier, Paul; Sys, Stanislas U.; De Clercq, Kris; De Leeuw, Ilse; Caij, Anne Brigitte; De Baere, Miet; De Regge, Nick; Fretin, David; Roupie, Virginie; Govaerts, Marc; Heyman, Paul; Vanrompay, Daisy; Yin, Lizi; Kalmar, Isabelle; Suin, Vanessa; Brochier, Bernard; Dobly, Alexandre; De Craeye, Stéphane; Roelandt, Sophie; Goossens, Els; Roels, Stefan

    2015-01-01

    Introduction In order to investigate the role of roe deer in the maintenance and transmission of infectious animal and human diseases in Flanders, we conducted a serologic screening in 12 hunting areas. Materials and methods Roe deer sera collected between 2008 and 2013 (n=190) were examined for antibodies against 13 infectious agents, using indirect enzyme-linked immunosorbent assay, virus neutralisation, immunofluorescence, or microagglutination test, depending on the agent. Results and discussion High numbers of seropositives were found for Anaplasma phagocytophilum (45.8%), Toxoplasma gondii (43.2%) and Schmallenberg virus (27.9%), the latter with a distinct temporal distribution pattern following the outbreak in domestic ruminants. Lower antibody prevalence was found for Chlamydia abortus (6.7%), tick-borne encephalitis virus (5.1%), Neospora caninum (4.8%), and Mycobacterium avium subsp paratuberculosis (4.1%). The lowest prevalences were found for Leptospira (1.7%), bovine viral diarrhoea virus 1 (1.3%), and Coxiella burnetii (1.2%). No antibodies were found against Brucella sp., bovine herpesvirus 1, and bluetongue virus. A significant difference in seroprevalence between ages (higher in adults >1 year) was found for N. caninum. Four doubtful reacting sera accounted for a significant difference in seroprevalence between sexes for C. abortus (higher in females). Conclusions Despite the more intensive landscape use in Flanders, the results are consistent with other European studies. Apart from maintaining C. abortus and MAP, roe deer do not seem to play an important role in the epidemiology of the examined zoonotic and domestic animal pathogens. Nevertheless, their meaning as sentinels should not be neglected in the absence of other wild cervid species. PMID:26609692

  2. Chronic Q Fever in the United States

    PubMed Central

    Karakousis, Petros C.; Trucksis, Michele; Dumler, J. Stephen

    2006-01-01

    Infections due to Coxiella burnetii, the causative agent of Q fever, are uncommon in the United States. Cases of chronic Q fever are extremely rare and most often manifest as culture-negative endocarditis in patients with underlying valvular heart disease. We describe a 31-year-old farmer from West Virginia with a history of congenital heart disease and recurrent fevers for 14 months who was diagnosed with Q fever endocarditis based on an extremely high antibody titer against Coxiella burnetii phase I antigen. Despite treatment with doxycycline, he continued to have markedly elevated Coxiella burnetii phase I antibody titers for 10 years after the initial diagnosis. To our knowledge, this case represents the longest follow-up period for a patient with chronic Q fever in the United States. We review all cases of chronic Q fever reported in the United States and discuss important issues pertaining to epidemiology, diagnosis, and management of this disease. PMID:16757641

  3. [Unanticipated outbreak of Q fever during a study using sheep, and its significance for further projects].

    PubMed

    Henning, Klaus; Hotzel, Helmut; Peters, Martin; Welge, Peter; Popps, Walter; Theegarten, Dirk

    2009-01-01

    Effective measures for protection of laboratory staff against infections due to experiments with pathogens are a challenge for safeguarding against hazards. Investigations on limited epidemic infections and their causes are of high relevance. During an experiment with pregnant sheep 5 of 7 persons who took part in the operation procedures developed Q fever 10 to 24 days after exposure. One sheep aborted spontaneously 3 days after the third experiment. Examinations of the aborted material revealed Coxiella burnetii, Chlamydophila psittaci, and Staphylococcus chromogenes. Coxiella burnetii and Chlamydophila psittaci were also detected in some of the other placentae. This outbreak of Q fever during an experiment with infected sheep affected more than 70% of the people involved with this experiment and shows the high risk of working with the zoonotic agent Coxiella burnetii. Hence, technical, organizational, and personnel measures have to be taken, and laboratory animals are to be monitored to prevent further infections. PMID:19226931

  4. 76 FR 44309 - Notice of Intent To Grant a Partially Exclusive Patent License; TransMembrane Bioscience, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-25

    ... No. 7,329,503: Recombinant antigens for the detection of Coxiella burnetii; U.S. Patent No. 7,824,875: Recombinant antigens for the detection of Coxiella burnetii; and U.S. Patent No. 7,824,909: Recombinant... using recombinant, immunodominant C. burnetii polypeptides and the development of veterinary vaccines...

  5. [Differential diagnostic and therapeutic aspects of Q-fever in a male prisoner. Case report].

    PubMed

    Vanya, Melinda; Szili, Károly; Zámolyi, Szilvia; Magyar, Hajnalka; Kőrösi, Gábor; Benkő, Árpád; Hornyák, Anna; Hegedűs, Zsolt; György, Lajos

    2015-05-01

    The authors describe the case of a 46-year-old man, who developed atypical pneumonia caused by Coxiella burnetii. Chest X-ray revealed interstitial pneumonia. Western blot and ELISA test were positive for Coxiella burnetii antibody. After treatment with doxycyclin and amoxicillin supplemented with vitamin B6 for 10 days, the patient displayed a clinical improvement. The authors conclude that in cases with atypical pneumonia, Coxiella burnetii antibody as well as other bacterial or viral antibodies should be determined. PMID:26042781

  6. Distinctive Genome Reduction Rates Revealed by Genomic Analyses of Two Coxiella-Like Endosymbionts in Ticks

    PubMed Central

    Gottlieb, Yuval; Lalzar, Itai; Klasson, Lisa

    2015-01-01

    Genome reduction is a hallmark of symbiotic genomes, and the rate and patterns of gene loss associated with this process have been investigated in several different symbiotic systems. However, in long-term host-associated coevolving symbiont clades, the genome size differences between strains are normally quite small and hence patterns of large-scale genome reduction can only be inferred from distant relatives. Here we present the complete genome of a Coxiella-like symbiont from Rhipicephalus turanicus ticks (CRt), and compare it with other genomes from the genus Coxiella in order to investigate the process of genome reduction in a genus consisting of intracellular host-associated bacteria with variable genome sizes. The 1.7-Mb CRt genome is larger than the genomes of most obligate mutualists but has a very low protein-coding content (48.5%) and an extremely high number of identifiable pseudogenes, indicating that it is currently undergoing genome reduction. Analysis of encoded functions suggests that CRt is an obligate tick mutualist, as indicated by the possible provisioning of the tick with biotin (B7), riboflavin (B2) and other cofactors, and by the loss of most genes involved in host cell interactions, such as secretion systems. Comparative analyses between CRt and the 2.5 times smaller genome of Coxiella from the lone star tick Amblyomma americanum (CLEAA) show that many of the same gene functions are lost and suggest that the large size difference might be due to a higher rate of genome evolution in CLEAA generated by the loss of the mismatch repair genes mutSL. Finally, sequence polymorphisms in the CRt population sampled from field collected ticks reveal up to one distinct strain variant per tick, and analyses of mutational patterns within the population suggest that selection might be acting on synonymous sites. The CRt genome is an extreme example of a symbiont genome caught in the act of genome reduction, and the comparison between CLEAA and CRt

  7. Novel Detection of Coxiella spp., Theileria luwenshuni, and T. ovis Endosymbionts in Deer Keds (Lipoptena fortisetosa).

    PubMed

    Lee, Seung-Hun; Kim, Kyoo-Tae; Kwon, Oh-Deog; Ock, Younsung; Kim, Taeil; Choi, Donghag; Kwak, Dongmi

    2016-01-01

    We describe for the first time the detection of Coxiella-like bacteria (CLB), Theileria luwenshuni, and T. ovis endosymbionts in blood-sucking deer keds. Eight deer keds attached to a Korean water deer were identified as Lipoptena fortisetosa (Diptera: Hippoboscidae) by morphological and genetic analyses. Among the endosymbionts assessed, CLB, Theileria luwenshuni, and T. ovis were identified in L. fortisetosa by PCR and nucleotide sequencing. Based on phylogeny, CLB 16S rRNA sequences were classified into clade B, sharing 99.4% identity with CLB from Haemaphysalis longicornis in South Korea. Although the virulence of CLB to vertebrates is still controversial, several studies have reported clinical symptoms in birds due to CLB infections. The 18S rRNA sequences of T. luwenshuni and T. ovis in this study were 98.8-100% identical to those in GenBank, and all of the obtained sequences of T. ovis and T. luwenshuni in this study were 100% identical to each other, respectively. Although further studies are required to positively confirm L. fortisetosa as a biological vector of these pathogens, strong genetic relationships among sequences from this and previous studies suggest potential transmission among mammalian hosts by ticks and keds. PMID:27244561

  8. Novel Detection of Coxiella spp., Theileria luwenshuni, and T. ovis Endosymbionts in Deer Keds (Lipoptena fortisetosa)

    PubMed Central

    Lee, Seung-Hun; Kim, Kyoo-Tae; Kwon, Oh-Deog; Ock, Younsung; Kim, Taeil; Choi, Donghag

    2016-01-01

    We describe for the first time the detection of Coxiella-like bacteria (CLB), Theileria luwenshuni, and T. ovis endosymbionts in blood-sucking deer keds. Eight deer keds attached to a Korean water deer were identified as Lipoptena fortisetosa (Diptera: Hippoboscidae) by morphological and genetic analyses. Among the endosymbionts assessed, CLB, Theileria luwenshuni, and T. ovis were identified in L. fortisetosa by PCR and nucleotide sequencing. Based on phylogeny, CLB 16S rRNA sequences were classified into clade B, sharing 99.4% identity with CLB from Haemaphysalis longicornis in South Korea. Although the virulence of CLB to vertebrates is still controversial, several studies have reported clinical symptoms in birds due to CLB infections. The 18S rRNA sequences of T. luwenshuni and T. ovis in this study were 98.8–100% identical to those in GenBank, and all of the obtained sequences of T. ovis and T. luwenshuni in this study were 100% identical to each other, respectively. Although further studies are required to positively confirm L. fortisetosa as a biological vector of these pathogens, strong genetic relationships among sequences from this and previous studies suggest potential transmission among mammalian hosts by ticks and keds. PMID:27244561

  9. Vaccination against Q fever for biodefense and public health indications

    PubMed Central

    Ruiz, Sara; Wolfe, Daniel N.

    2014-01-01

    Coxiella burnetii is the etiological agent of Q fever, a disease that is often spread to humans via inhalational exposure to the bacteria from contaminated agricultural sources. Outbreaks have been observed all over the world with larger foci generating interest in vaccination programs, most notably in Australia and the Netherlands. Importantly, exposure rates among military personnel deployed to the Middle East can be relatively high as measured by seroconversion to C. burnetii-specific antibodies. Q fever has been of interest to the biodefense community over the years due to its low infectious dose and environmental stability. Recent advances in cell-free growth and genetics of C. burnetii also make this organism easier to culture and manipulate. While there is a vaccine that is licensed for use in Australia, the combination of biodefense- and public health-related issues associated with Q fever warrant the development of a safer and more effective vaccine against this disease. PMID:25566235

  10. Molecular Evidence for a Novel Coxiella from Argas monolakensis (Acari: Argasidae) from Mono Lake, California, USA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Argasid ticks are vectors of viral and bacterial agents of humans and animals. Recent reports indicate that some ornithophilic argasids harbored rickettsial agents. A Nearctic tick, Argas monolakensis Schwan, Corwin, Brown is ornithophilic and has not previously been examined for rickettsial agents....

  11. Seroprevalence of seven zoonotic pathogens in pregnant women from the Caribbean.

    PubMed

    Wood, Heidi; Drebot, Michael A; Dewailly, Eric; Dillon, Liz; Dimitrova, Kristina; Forde, Martin; Grolla, Allen; Lee, Elise; Loftis, Amanda; Makowski, Kai; Morrison, Karen; Robertson, Lyndon; Krecek, Rosina C

    2014-09-01

    Studies examining the prevalence of zoonotic agents in the Caribbean are very limited. The objective of this study was to examine the seroprevalence of seven zoonotic agents among individuals residing on 10 English-speaking Caribbean countries. Sera from healthy, pregnant women were collected from Antigua-Barbuda, Belize, Bermuda, Dominica, Grenada, Jamaica, Montserrat, St. Kitts-Nevis, St. Lucia, and St. Vincent-Grenadines and tested for the presence of IgG antibodies to dengue virus, hepatitis E virus, hantaviruses, leptospiral agents, spotted fever group rickettsiae (SFGR), typhus group rickettsiae (TGR), and Coxiella burnetii (Q fever). The highest seroprevalence values were observed for dengue virus, SFGR, and leptospirosis, although the lowest seroprevalence values were observed for hepatitis E virus, C. burnetii, and TGR. Antibodies to hantaviruses were not detected in any individuals. PMID:24914001

  12. Seroprevalence of Seven Zoonotic Pathogens in Pregnant Women from the Caribbean

    PubMed Central

    Wood, Heidi; Drebot, Michael A.; Dewailly, Eric; Dillon, Liz; Dimitrova, Kristina; Forde, Martin; Grolla, Allen; Lee, Elise; Loftis, Amanda; Makowski, Kai; Morrison, Karen; Robertson, Lyndon; Krecek, Rosina C.

    2014-01-01

    Studies examining the prevalence of zoonotic agents in the Caribbean are very limited. The objective of this study was to examine the seroprevalence of seven zoonotic agents among individuals residing on 10 English-speaking Caribbean countries. Sera from healthy, pregnant women were collected from Antigua-Barbuda, Belize, Bermuda, Dominica, Grenada, Jamaica, Montserrat, St. Kitts-Nevis, St. Lucia, and St. Vincent-Grenadines and tested for the presence of IgG antibodies to dengue virus, hepatitis E virus, hantaviruses, leptospiral agents, spotted fever group rickettsiae (SFGR), typhus group rickettsiae (TGR), and Coxiella burnetii (Q fever). The highest seroprevalence values were observed for dengue virus, SFGR, and leptospirosis, although the lowest seroprevalence values were observed for hepatitis E virus, C. burnetii, and TGR. Antibodies to hantaviruses were not detected in any individuals. PMID:24914001

  13. Rickettsial pathogens in the tropical rat mite Ornithonyssus bacoti (Acari: Macronyssidae) from Egyptian rats (Rattus spp.).

    PubMed

    Reeves, Will K; Loftis, Amanda D; Szumlas, Daniel E; Abbassy, Magda M; Helmy, Ibrahim M; Hanafi, Hanafi A; Dasch, Gregory A

    2007-01-01

    We collected and tested 616 tropical rat mites (Ornithonyssus bacoti (Hirst)) from rats (Rattus norvegicus (Berkenhout) and R. rattus (Linnaeus)) throughout 14 governorates in Egypt and tested DNA extracts from pools of these mites for Bartonella spp., Coxiella burnetii, and Rickettsia spp. by PCR amplification and sequencing. Three different mite-associated bacterial agents, including one Bartonella and two Rickettsia spp., were detected in eight pools of mites. Further research could demonstrate the vector potential of mites and pathogenicity of these agents to humans or animals. PMID:17225079

  14. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... millions of gallons of Agent Orange and other herbicides on trees and vegetation during the Vietnam War. ...

  15. Q fever

    MedlinePlus

    ... People at highest risk for this infection are: Farmers Laboratory workers who work with Coxiella burnetii Sheep ... People at risk (for example, farmers and veterinarians) should ... Disinfect any contaminated areas Thoroughly wash their hands ...

  16. Q Fever: Statistics and Epidemiology

    MedlinePlus

    ... infection with the obligate, intracellular bacterium, Coxiella burnetii . Cattle, sheep, and goats are commonly infected and may ... and plains states where ranching and rearing of cattle are common. In other states, areas where sheep, ...

  17. Seroconversions for Coxiella and Rickettsial Pathogens among US Marines Deployed to Afghanistan, 2001-2010.

    PubMed

    Farris, Christina M; Pho, Nhien; Myers, Todd E; Richards, Allen L

    2016-08-01

    We assessed serum samples from 1,000 US Marines deployed to Afghanistan during 2001-2010 to find evidence of 4 rickettsial pathogens. Analysis of predeployment and postdeployment samples showed that 3.4% and 0.5% of the Marines seroconverted for the causative agents of Q fever and spotted fever group rickettsiosis, respectively. PMID:27434653

  18. Seroconversions for Coxiella and Rickettsial Pathogens among US Marines Deployed to Afghanistan, 2001–2010

    PubMed Central

    Pho, Nhien; Myers, Todd E.; Richards, Allen L.

    2016-01-01

    We assessed serum samples from 1,000 US Marines deployed to Afghanistan during 2001–2010 to find evidence of 4 rickettsial pathogens. Analysis of predeployment and postdeployment samples showed that 3.4% and 0.5% of the Marines seroconverted for the causative agents of Q fever and spotted fever group rickettsiosis, respectively. PMID:27434653

  19. Q Fever in French Guiana

    PubMed Central

    Eldin, Carole; Mahamat, Aba; Demar, Magalie; Abboud, Philippe; Djossou, Félix; Raoult, Didier

    2014-01-01

    Coxiella burnetii, the causative agent of Q fever, is present worldwide. Recent studies have shown that this bacterium is an emerging pathogen in French Guiana and has a high prevalence (24% of community-acquired pneumonia). In this review, we focus on the peculiar epidemiology of Q fever in French Guiana. We place it in the context of the epidemiology of the disease in the surrounding countries of South America. We also review the clinical features of Q fever in this region, which has severe initial presentation but low mortality rates. These characteristics seem to be linked to a unique genotype (genotype 17). Finally, we discuss the issue of the animal reservoir of C. burnetii in French Guiana, which is still unknown. Further studies are necessary to identify this reservoir. Identification of this reservoir will improve the understanding of the Q fever epidemic in French Guiana and will provide new tools to control this public health problem. PMID:25092817

  20. Surgical and Antimicrobial Management of a Thoracic Aortic Aneurysm Due to Q Fever: A Case Report and Brief Review.

    PubMed

    Robinson, William P; Schuksz, Manuela

    2016-05-01

    Coxiella burnetii, the etiologic agent of Q fever, has been associated with vascular infection and aneurysm formation. We report the case of a 36-year-old woman from Iraq who presented with long-standing malaise as well as vague chest and shoulder discomfort and was found to have a saccular aneurysm of the descending thoracic aorta. Serology assays were positive for chronic C burnetii infection. She was treated with successful aneurysm resection and aortic replacement with a rifampin-impregnated Maquet Hemashield (TM) Dacron interposition graft interposition graft in addition to 18 months of doxycycline and hydroxychloroquine. The patient is without evidence of recurrent infection on follow-up at 3 years. To our knowledge, this is the first case of aortic aneurysm secondary to Q fever reported in the United States. We review the diagnosis, surgical management, antibiotic therapy, and surveillance of a thoracic aortic aneurysm secondary to Q fever. PMID:27075992

  1. Current developments in therapeutic and diagnostic strategies for Q fever: glimpses of patent analysis.

    PubMed

    Chauhan, Rashi; Wadhwa, Gulshan; Sharma, Sanjeev K; Jain, Chakresh K

    2014-01-01

    Coxiella burnetii is an infectious and etiological agent responsible for causing Q fever. There are mainly two forms of the Q fever that are chronic and acute. Though the acute type is usually linked with symptoms like pneumonia and hepatitis, the chronic form is shown to have mortality rate of 5%. Percentage of mortality rate might increases from 5% to 25% if left untreated. The present treatments of disease include the recommended dose of drugs and vaccine. Presently, extensive attempt is in progress to find novel therapies to combat the disease. This review is projected to provide a brief introduction of C. burnetii and Q fever while emphasizing therapeutics, prophylactic measures and diagnostic applications based on recent patents prospects. PMID:25409874

  2. Biological Agents

    MedlinePlus

    ... to Z Index Contact Us FAQs What's New Biological Agents This page requires that javascript be enabled ... and Health Topics A-Z Index What's New Biological agents include bacteria, viruses, fungi, other microorganisms and ...

  3. Q fever diagnosis and control in domestic ruminants.

    PubMed

    Roest, H I J; Bossers, A; Rebel, J M J

    2013-01-01

    Q fever is a zoonosis caused by the bacterium Coxiella burnetii, a highly infectious agent that can survive in the environment. Therefore, Q fever has a major public health impact when outbreaks occur. Small ruminants are identified as the source in the majority of outbreaks in humans. Accurate diagnosis and effective control strategies are necessary to limit the zoonotic and veterinary impact of Q fever. For this, knowledge of the pathogenesis of Q fever and excretion routes of C. burnetii from infected animals is crucial. Abortions as well as normal parturitions in infected small ruminants are the most important excretion routes of C. burnetii. Excretion of C. burnetii via faeces and vaginal mucus has also been suggested. However, contamination of these samples by bacteria present in the environment may influence the results. This hampers the accurate identification of infected animals by these samples; however, the detection of C. burnetii in milk samples seems not to be influenced by environmental contamination. Q fever in animals can be detected by direct (immunohistochemistry and PCR) and indirect (complement fixation test (CFT), enzyme- linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA) methods. A combination of both direct and indirect methods is recommended in current protocols to detect Q fever on herd level. For the control of Q fever in domestic animals, vaccination with a phase 1 C. burnetii whole cell inactivated vaccine is reported to be effective in preventing abortion and reducing bacterial shedding, especially after several years of administration. Vaccination might not be effective in already infected animals nor in pregnant animals. Furthermore, the complicated vaccine production process, requiring biosafety level 3 facilities, could hamper vaccine availability. Future challenges include the development of improved, easier to produce Q fever vaccines. PMID:23689896

  4. Survey of infectious etiologies of bovine abortion during mid- to late gestation in dairy herds.

    PubMed

    Barkallah, Mohamed; Gharbi, Yaakoub; Hassena, Amal Ben; Slima, Ahlem Ben; Mallek, Zouhir; Gautier, Michel; Greub, Gilbert; Gdoura, Radhouane; Fendri, Imen

    2014-01-01

    Bovine abortion of unknown infectious etiology still remains a major economic problem. Thus, we investigated whether Brucella spp., Listeria monocytogenes, Salmonella spp., Campylobacter spp. and Coxiella burnetii are associated with abortion and/or stillbirth in Tunisian dairy cattle. Using a pan-Chlamydiales PCR, we also investigated the role of Chlamydiaceae, Waddlia chondrophila, Parachlamydia acanthamoebae and other members of the Chlamydiales order in this setting. Veterinary samples taken from mid to late-term abortions from twenty dairy herds were tested. From a total of 150 abortion cases collected, infectious agents were detected by PCR in 73 (48.66%) cases, 13 (8.66%) of which represented co-infections with two infectious agents. Detected pathogens include Brucella spp (31.3%), Chlamydiaceae (4.66%), Waddlia chondrophila (8%), Parachlamydia acanthamoebae (5.33%), Listeria monocytogenes (4.66%) and Salmonella spp. (3.33%). In contrast, Campylobacter spp. and Coxiella burnetii DNA were not detected among the investigated veterinary samples. This demonstrates that different bacterial agents may cause bovine abortion in Tunisia. This is the first report suggesting the role of Parachlamydia acanthamoebae in bovine abortion in Africa. Further studies with a larger number of samples are necessary to confirm whether this emerging pathogen is directly linked to abortion in cattle. PMID:24662769

  5. First serologic survey of Q fever in free-range yaks in China.

    PubMed

    Yin, M Y; Tan, Q D; Qin, S Y; Hu, L Y; Liu, G H; Zhou, D H; Zhu, X Q

    2015-01-01

    The objective of the present investigation was to determine the seroprevalence of Coxiella burnetii infection in free-range yaks in China. A total of 552 serum samples were collected from yaks in Gansu province, northwest China between April 2013 and January 2014, and antibodies against C. burnetii were evaluated using enzyme-linked immunosorbent assay (ELISA). Overall, 13.59% (75/552, 95% CI: 10.73-16.45) of the examined animals were positive for C. burnetii antibodies. There was no significant difference in C. burnetii seroprevalence between female yaks (13.78%, 95% CI: 10.36-17.19) and male yaks (13.13%, 95% CI: 7.89-18.36) (P>0.05). Coxiella burnetii seroprevalence in yaks in different age groups ranged from 10.88% to 15.26%, but the difference was not statistically significant (P>0.05). Coxiella burnetii seroprevalence in yaks sampled in different seasons ranged from 12.06% (autumn) to 18.33% (summer), but the difference was not statistically significant (P>0.05). This is the first report of C. burnetii seroprevalence in free-range yaks in China, indicating the need for measures to be taken to control C. burnetii infection in free-range yaks in China. PMID:27175178

  6. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  7. Application of a Broad-Range Resequencing Array for Detection of Pathogens in Desert Dust Samples from Kuwait and Iraq ▿

    PubMed Central

    Leski, Tomasz A.; Malanoski, Anthony P.; Gregory, Michael J.; Lin, Baochuan; Stenger, David A.

    2011-01-01

    A significant percentage of the human population is exposed to high levels of naturally occurring airborne dusts. Although the link between airborne particulate inhalation and a variety of respiratory diseases has long been established, little is known about the pathogenic role of the microbial component of the dust. In this study, we applied highly multiplexed PCR and a high-density resequencing microarray (RPM-TEI version 1.0) to screen samples of fine topsoil particles and airborne dust collected in 19 locations in Iraq and Kuwait for the presence of a broad range of human pathogens. The results indicated the presence of potential human pathogens, including Mycobacterium, Brucella, Coxiella burnetii, Clostridium perfringens, and Bacillus. The presence of Coxiella burnetii, a highly infectious potential biowarfare agent, was confirmed and detected in additional samples by use of a more sensitive technique (real-time PCR), indicating a high prevalence of this organism in the analyzed samples. The detection of potentially viable pathogens in breathable dusts from arid regions of Iraq and Kuwait underscores the importance of further study of these environments. PMID:21571877

  8. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  9. Antiparasitic agents.

    PubMed

    Rosenblatt, J E

    1999-11-01

    Several important developments have occurred in recent years in the chemotherapy for and prophylaxis of parasitic infections. Although mefloquine is clearly the most effective agent for prevention of chloroquine-resistant falciparum malaria, its use has been compromised by side effects, both real and imagined. Well-designed studies have shown that side effects occur no more frequently with low-dose mefloquine than with chloroquine. Use of mefloquine in pregnant women has not been associated with birth defects, but the incidence of stillbirths may be increased. Malarone is a new agent that combines atovaquone and proguanil, and it may be as effective as mefloquine; however, it is not yet available in the United States. Several newer agents have appeared in response to the development of multidrug resistant Plasmodium falciparum, especially in Southeast Asia. Halofantrine is available for the treatment of mild to moderate malaria due to P. falciparum and for P. vivax infections. Because of severe toxic effects, use of halofantrine should be restricted to only those unusual and rare situations in which other agents cannot be used. Artemisinin (an extract of the Chinese herbal remedy qinghaosu) and two derivatives, artesunate and artemether, are active against multidrug resistant P. falciparum and are widely used in Asia in oral, parenteral, and rectal forms. The antibacterial azithromycin in combination with atovaquone or quinine has now been reported to treat babesiosis effectively in experimental animals and in a few patients. Azithromycin in combination with paromomycin has also shown promise in the treatment of cryptosporidiosis (and toxoplasmosis when combined with pyrimethamine) in patients with the acquired immunodeficiency syndrome (AIDS). Albendazole is currently the only systemic agent available for treatment of microsporidiosis, an infection primarily of patients with AIDS. In addition, albendazole and ivermectin have emerged as effective broad

  10. Unusual Bacterial Infections and the Pleura

    PubMed Central

    Kummerfeldt, Carlos E; Huggins, John T; Sahn, Steven A

    2012-01-01

    Rickettsiosis, Q fever, tularemia, and anthrax are all bacterial diseases that can affect the pleura. Rocky Mountain Spotted Fever (RMSF) and Mediterranean Spotted Fever (MSF) are caused by Rickettsia rickettsii and Rickettsia conorii, respectively. Pleural fluid from a patient with MSF had a neutrophil-predominant exudate. Coxiella burnetii is the causative agent of Q fever. Of the two cases described in the literature, one was an exudate with a marked eosinophilia while the other case was a transudate due to a constrictive pericarditis. Francisella tularensis is the causative agent of tularemia. Pleural fluid from three tularemia patients showed a lymphocyte predominant exudate. Bacillus anthracis is the causative agent of anthrax. Cases of inhalational anthrax from a recent bioterrorist attack evidenced the presence of a serosanguineous exudative pleural effusion. These four bacterial microorganisms should be suspected in patients presenting with a clinical history, exposure to known risk factors and an unexplained pleural effusion. PMID:22977649

  11. A transversal study on antibodies against selected pathogens in dromedary camels in the Canary Islands, Spain.

    PubMed

    Mentaberre, Gregorio; Gutiérrez, Carlos; Rodríguez, Noé F; Joseph, Sunitha; González-Barrio, David; Cabezón, Oscar; de la Fuente, José; Gortazar, Christian; Boadella, Mariana

    2013-12-27

    The Canary Islands contain the most important dromedary camel (Camelus dromedarius) population in the European Union and are the main export point of dromedaries to continental Europe and Latin America. We investigated the presence of antibodies against relevant disease agents in 100 Canarian camel sera. Selected blood samples of the same animals were also tested by PCR. Sera were tested for antibodies against Bluetongue virus (BTV; 0%), Bovine Viral Diarrhoea virus (BVDV; 0%), Camelpox virus (CPV; 8% by serum neutralization, 16% by ELISA), Peste des Petits Ruminants virus (PPRV, 0%), Rift Valley Fever virus (RVFV; 0%) and West Nile Fever virus (WNV; 3%), the bacterial pathogens Anaplasma sp. (3%), Brucella sp. (1%), Coxiella burnetii (19%), Mycobacterium avium paratuberculosis (MAP; 22%), Mycobacterium tuberculosis complex (MTC; 10%) and Rickettsia sp. (83%), and the parasites Toxoplasma gondii (36%) and Neospora caninum (86%). The most remarkable findings were the detection of antibodies against CPV and the high antibody prevalence against C. burnetii, Rickettsia sp., T. gondii and N. caninum. By PCR, we found no C. burnetii, N. caninum and Anaplasma sp. DNA in the tested samples. However, Rickettsia sp. DNA was detected in six antibody positive tested samples. These results should be taken into consideration in order to implement adequate control measures and avoid a potential dissemination of infections to other territories. PMID:23992795

  12. Antifungal agents.

    PubMed

    Ryder, N S

    1999-12-01

    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  13. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  14. Acute and probable chronic Q fever during anti-TNFα and anti B-cell immunotherapy: a case report

    PubMed Central

    2014-01-01

    Background Q fever is caused by the intracellular bacterium Coxiella burnetii. Initial infection can present as acute Q fever, while a minority of infected individuals develops chronic Q fever endocarditis or vascular infection months to years after initial infection. Serology is an important diagnostic tool for both acute and chronic Q fever. However, since immunosuppressive drugs may hamper the humoral immune response, diagnosis of Q fever might be blurred when these drugs are used. Case presentation A 71-year-old Caucasian male was diagnosed with symptomatic acute Q fever (based on positive C. burnetii PCR followed by seroconversion) while using anti-tumor necrosis factor-α (anti-TNFα) drugs for rheumatoid arthritis (RA). He was treated for two weeks with moxifloxacin. After 24 months of follow-up, the diagnosis of probable chronic Q fever was established based on increasing anti-C. burnetii phase I IgG antibody titres in a immunocompromised patient combined with clinical suspicion of endocarditis. At the time of chronic Q fever diagnosis, he had been treated with anti B-cell therapy for 16 months. Antibiotic therapy consisting of 1.5 years doxycycline and hydroxychloroquine was started and successfully completed and no signs of relapse were seen after more than one year of follow-up. Conclusion The use of anti-TNFα agents for RA in the acute phase of Q fever did not hamper the C. burnetii-specific serological response as measured by immunofluorescence assay. However, in the presented case, an intact humoral response did not prevent progression to probable chronic C. burnetii infection, most likely because essential cellular immune responses were suppressed during the acute phase of the infection. Despite the start of anti-B-cell therapy with rituximab after the acute Q fever episode, an increase in anti-C. burnetii phase I IgG antibodies was observed, supporting the notion that C. burnetii specific CD20-negative memory B-cells are responsible for this

  15. Health care agents

    MedlinePlus

    Durable power of attorney for health care; Health care proxy; End-of-life - health care agent; Life support treatment - ... Respirator - health care agent; Ventilator - health care agent; Power of attorney - health care agent; POA - health care ...

  16. Agent Building Software

    NASA Technical Reports Server (NTRS)

    2000-01-01

    AgentBuilder is a software component developed under an SBIR contract between Reticular Systems, Inc., and Goddard Space Flight Center. AgentBuilder allows software developers without experience in intelligent agent technologies to easily build software applications using intelligent agents. Agents are components of software that will perform tasks automatically, with no intervention or command from a user. AgentBuilder reduces the time and cost of developing agent systems and provides a simple mechanism for implementing high-performance agent systems.

  17. STUDIES ON THE PHYSIOLOGY OF RICKETTSIAE V.

    PubMed Central

    Mallavia, L.; Paretsky, D.

    1963-01-01

    Mallavia, L. (University of Kansas, Lawrence) and D. Paretsky. Studies on the physiology of rickettsiae. V. Metabolism of carbamyl phosphate by Coxiella burnetii. J. Bacteriol. 86:232–238. 1963.—Preparations of disrupted Coxiella burnetii catalyze synthesis of citrulline from ornithine and carbamyl phosphate at an optimal pH of 7.0 to 7.5. Rickettsial synthesis of the pyrimidine precursor, ureidosuccinate, is demonstrated and confirmed by isolating C14-labeled ureidosuccinate from reaction mixtures of carbamyl phosphate and labeled aspartate. The data suggest a further rickettsial synthesis of orotate and imply rickettsial competence for host-independent pyrimidine synthesis. PMID:14058946

  18. Pathogen Prevalence in Ticks Collected from the Vegetation and Livestock in Nigeria

    PubMed Central

    Reye, Anna L.; Arinola, Olatunbosun G.; Hübschen, Judith M.

    2012-01-01

    Ticks are important disease vectors that can cause considerable economic losses by affecting animal health and productivity, especially in tropical and subtropical regions. In this study, we investigated the prevalence and diversity of bacterial and protozoan tick-borne pathogens in ticks collected from the vegetation and cattle in Nigeria by PCR. The infection rates of questing ticks were 3.1% for Rickettsia species, 0.1% for Coxiella burnetii and 0.4% for Borrelia species. Other pathogens, such as Babesia, Theileria, Anaplasma, and Ehrlichia species, were not detected in ticks from the vegetation. Feeding ticks collected from cattle displayed infection rates of 12.5% for Rickettsia species, 14% for Coxiella burnetii, 5.9% for Anaplasma species, 5.1% for Ehrlichia species, and 2.9% for Theileria mutans. Babesia and Borrelia species were not detected in ticks collected from cattle. Mixed infections were found only in feeding ticks and mainly Rickettsia species and Coxiella burnetii were involved. The diversity of tick-borne pathogens in Nigeria was higher in feeding than in questing ticks, suggesting that cattle serve as reservoirs for at least some of the pathogens studied, in particular C. burnetii. The total estimated herd infection rates of 20.6% for a Rickettsia africae-like species, 27% for Coxiella burnetii, and 8.5% for Anaplasma marginale/centrale suggest that these pathogens may have considerable implications for human and animal health. PMID:22327584

  19. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  20. Remote Agent Demonstration

    NASA Technical Reports Server (NTRS)

    Dorais, Gregory A.; Kurien, James; Rajan, Kanna

    1999-01-01

    We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

  1. Development of Liposomal Ciprofloxacin to Treat Lung Infections

    PubMed Central

    Cipolla, David; Blanchard, Jim; Gonda, Igor

    2016-01-01

    Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively). Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin®) that are in development by Aradigm Corporation are described here. PMID:26938551

  2. Development of Liposomal Ciprofloxacin to Treat Lung Infections.

    PubMed

    Cipolla, David; Blanchard, Jim; Gonda, Igor

    2016-01-01

    Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively). Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin(®) and Pulmaquin(®)) that are in development by Aradigm Corporation are described here. PMID:26938551

  3. Delayed diagnosis of Q fever endocarditis in a rheumatoid arthritis patient

    PubMed Central

    Shah, Shailee Y.; Kovacs, Christopher; Tan, Carmela D.; Pettersson, Gosta; Shrestha, Nabin K.; Lutwick, Larry; Gordon, Steven M.

    2015-01-01

    Chronic Q fever caused by Coxiella burnetii is uncommon in the United States and is most often associated with infective endocarditis. We present a 52-year-old woman with a history of aortic valve replacement and rheumatoid arthritis treated with Etanercept with chronic Q fever manifesting as prosthetic valve infective endocarditis. Explanted valve tissue showed organisms confirmed to be C. burnetii by PCR (polymerase chain reaction) sequencing. She subsequently reported consumption of unpasteurized cow milk which was the likely source of C. burnetii. She continues to do well 6 months after valve replacement on oral doxycycline and hydroxychloroquine. PMID:26793469

  4. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  5. Epidemiology of rickettsial diseases.

    PubMed

    Walker, D H; Fishbein, D B

    1991-05-01

    Rickettsial diseases have a diversity of epidemiologic characteristics reflective of the variety of ecologic situations in which the obligate intracellular bacteria are transmitted to humans. For the spotted fever group (SFG) rickettsiae, Rickettsia typhi, R. tsutsugamushi, Coxiella burnetii, and the human ehrlichial agent, humans are a dead-end host who plays no role in the maintenance of the organism in nature. All rickettsioses exist as zoonoses. Moreover, all rickettsiae are found in infected arthopods, which generally serve as the natural hosts and can transmit the infection to the next generation of ticks, mites, chiggers, or fleas. From our anthropocentric viewpoint, Q fever aerosol infection from parturient animals and Brill-Zinsser disease ignited epidemics of louse-borne epidemic typhus are exceptions. However, silent cycles of C. burnetii in ticks and R. prowazekii in the flying squirrel flea may have maintained these agents in transovarial or enzootic cycles for eons before humans and their domestic animals arrived on the scene. Thus, the epidemiology of rickettsial diseases must be recognized as an unfortunate aberration of the rickettsial economy. Several excellent reviews of rickettsial ecology contain a wealth of useful information. PMID:1884775

  6. Chronic Fatigue Syndrome (CFS): Causes

    MedlinePlus

    ... Ross River Fever, a mosquito-borne tropical disease Coxiella burnetti , the agent that causes Q fever Human ... with Epstein-Barr virus, Ross River virus, and Coxiella burnetti will lead to a post-infective condition ...

  7. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  8. Mobile Agents Applications.

    ERIC Educational Resources Information Center

    Martins, Rosane Maria; Chaves, Magali Ribeiro; Pirmez, Luci; Rust da Costa Carmo, Luiz Fernando

    2001-01-01

    Discussion of the need to filter and retrieval relevant information from the Internet focuses on the use of mobile agents, specific software components which are based on distributed artificial intelligence and integrated systems. Surveys agent technology and discusses the agent building package used to develop two applications using IBM's Aglet…

  9. Q fever as a possible cause of bilateral optic neuritis.

    PubMed Central

    Schuil, J; Richardus, J H; Baarsma, G S; Schaap, G J

    1985-01-01

    A 59-year-old farmer developed a bilateral optic neuritis in the course of an infection with Coxiella burnetii (Q fever), resulting in a lasting unilateral blindness. A complete medical (including neurological) evaluation gave no evidence of other possible causes. A possible source of infection was cattle. Images PMID:4016056

  10. Q Fever

    MedlinePlus

    ... chronic stages caused by the bacteria Coxiella burnetii . Cattle, sheep, and goats are the primary reservoirs although ... animals. Other modes of transmission to humans, including tick bites, ingestion of unpasteurized milk or dairy products, and human to human transmission, are rare. Humans ... Symptoms, Diagnosis, and Treatment Signs of illness, ...

  11. Multiple Infections of Rodents with Zoonotic Pathogens in Austria

    PubMed Central

    Schmidt, Sabrina; Essbauer, Sandra S.; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H.; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald

    2014-01-01

    Abstract Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host–pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans. PMID

  12. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, Steven Y.

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  13. Host-Directed Antimicrobial Drugs with Broad-Spectrum Efficacy against Intracellular Bacterial Pathogens

    PubMed Central

    Czyż, Daniel M.; Potluri, Lakshmi-Prasad; Jain-Gupta, Neeta; Riley, Sean P.; Martinez, Juan J.; Steck, Theodore L.; Crosson, Sean; Gabay, Joëlle E.

    2014-01-01

    ABSTRACT We sought a new approach to treating infections by intracellular bacteria, namely, by altering host cell functions that support their growth. We screened a library of 640 Food and Drug Administration (FDA)-approved compounds for agents that render THP-1 cells resistant to infection by four intracellular pathogens. We identified numerous drugs that are not antibiotics but were highly effective in inhibiting intracellular bacterial growth with limited toxicity to host cells. These compounds are likely to target three kinds of host functions: (i) G protein-coupled receptors, (ii) intracellular calcium signals, and (iii) membrane cholesterol distribution. The compounds that targeted G protein receptor signaling and calcium fluxes broadly inhibited Coxiella burnetii, Legionella pneumophila, Brucella abortus, and Rickettsia conorii, while those directed against cholesterol traffic strongly attenuated the intracellular growth of C. burnetii and L. pneumophila. These pathways probably support intracellular pathogen growth so that drugs that perturb them may be therapeutic candidates. Combining host- and pathogen-directed treatments is a strategy to decrease the emergence of drug-resistant intracellular bacterial pathogens. PMID:25073644

  14. Molecular evidence of vector-borne pathogens in dogs and cats and their ectoparasites in Algiers, Algeria.

    PubMed

    Bessas, Amina; Leulmi, Hamza; Bitam, Idir; Zaidi, Sara; Ait-Oudhia, Khatima; Raoult, Didier; Parola, Philippe

    2016-04-01

    In Algeria, only limited information is currently available on the prevalence of emergent canine and feline vector-borne diseases. The aim of the present work was to detect by qPCR vector-associated bacteria in stray dogs and cats and their ectoparasites from Algiers. 18/117 (15.38%) dogs and 2/107 (1.87%) cats were positive for at least one vector-borne agent. Coxiella burnetii and Bartonella henselae were identified in 1/117 (0.85%) dog individually. Ehrlichia canis DNA was detected in 17/117 (14.52%) dogs. 1/107 (0.93%) cat was positive to C. burnetii and another 1/107 (0.93%) to B. henselae. DNA of Rickettsia massiliae, Rickettsia conorii and E. canis was detected in Rhipicephalus sanguineus. Cat fleas were infected with Rickettsia felis, B. henselae and Bartonella clarridgeiae. B. vinsonii subsp. berkhoffii was identified in Xenopsylla cheopis collected from dogs. The findings of this study indicate that dogs and cats from Algeria are exposed to multiple tick and flea-borne pathogens. PMID:27012917

  15. Agent Architectures for Compliance

    NASA Astrophysics Data System (ADS)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  16. Chemical crowd control agents.

    PubMed

    Menezes, Ritesh G; Hussain, Syed Ather; Rameez, Mansoor Ali Merchant; Kharoshah, Magdy A; Madadin, Mohammed; Anwar, Naureen; Senthilkumaran, Subramanian

    2016-03-01

    Chemical crowd control agents are also referred to as riot control agents and are mainly used by civil authorities and government agencies to curtail civil disobedience gatherings or processions by large crowds. Common riot control agents used to disperse large numbers of individuals into smaller, less destructive, and more easily controllable numbers include chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminearsine, and oleoresin capsicum. In this paper, we discuss the emergency medical care needed by sufferers of acute chemical agent contamination and raise important issues concerning toxicology, safety and health. PMID:26658556

  17. Q fever in pregnant goats: humoral and cellular immune responses

    PubMed Central

    2013-01-01

    Q fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii. Both humoral and cellular immunity are important in the host defence against intracellular bacteria. Little is known about the immune response to C. burnetii infections in domestic ruminants even though these species are the major source of Q fever in humans. To investigate the goat’s immune response we inoculated groups of pregnant goats via inhalation with a Dutch outbreak isolate of C. burnetii. All animals were successfully infected. Phase 1 and Phase 2 IgM- and IgG-specific antibodies were measured. Cellular immune responses were investigated by interferon-gamma, enzyme-linked immunosorbent spot test (IFN-γ Elispot), lymphocyte proliferation test (LPT) and systemic cytokines. After two weeks post inoculation (wpi), a strong anti-C. burnetii Phase 2 IgM and IgG antibody response was observed while the increase in IgM anti-Phase 1 antibodies was less pronounced. IgG anti-Phase 1 antibodies started to rise at 6 wpi. Cellular immune responses were observed after parturition. Our results demonstrated humoral and cellular immune responses to C. burnetii infection in pregnant goats. Cell-mediated immune responses did not differ enough to distinguish between Coxiella-infected and non-infected pregnant animals, whereas a strong-phase specific antibody response is detected after 2 wpi. This humoral immune response may be useful in the early detection of C. burnetii-infected pregnant goats. PMID:23915213

  18. Change Agent Survival Guide

    ERIC Educational Resources Information Center

    Dunbar, Folwell L.

    2011-01-01

    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  19. Travel Agent Course Outline.

    ERIC Educational Resources Information Center

    British Columbia Dept. of Education, Victoria.

    Written for college entry-level travel agent training courses, this course outline can also be used for inservice training programs offered by travel agencies. The outline provides information on the work of a travel agent and gives clear statements on what learners must be able to do by the end of their training. Material is divided into eight…

  20. Pediatric Antifungal Agents

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Smith, P Brian

    2009-01-01

    Purpose of review In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of this report is to review the most recent literature addressing the use of antifungal agents in children. Recent findings Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins. Summary Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary. PMID:19741525

  1. How do agents represent?

    NASA Astrophysics Data System (ADS)

    Ryan, Alex

    Representation is inherent to the concept of an agent, but its importance in complex systems has not yet been widely recognised. In this paper I introduce Peirce's theory of signs, which facilitates a definition of representation in general. In summary, representation means that for some agent, a model is used to stand in for another entity in a way that shapes the behaviour of the agent with respect to that entity. Representation in general is then related to the theories of representation that have developed within different disciplines. I compare theories of representation from metaphysics, military theory and systems theory. Additional complications arise in explaining the special case of mental representations, which is the focus of cognitive science. I consider the dominant theory of cognition — that the brain is a representational device — as well as the sceptical anti-representational response. Finally, I argue that representation distinguishes agents from non-representational objects: agents are objects capable of representation.

  2. Standard Agent Framework 1

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4)more » Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.« less

  3. Biological warfare agents

    PubMed Central

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

  4. Dioxin, agent orange

    SciTech Connect

    Gough, M.

    1986-01-01

    This book presents information on the following topics: dioxin, a prevalent problem; nobody wanted dioxin; agent organe and Vietnam; what we know about and may learn about agent orange and Veterans' health; agent organe and birth defects; dioxin in Missouri; 2, 4, 5-T: the U.S.' disappearing herbicide; Seveso: high-level environmental exposure; the nitro explosion; industrial exposures to dioxin; company behavior in the face of dioxin exposures; dioxin and specific cancers; animal tests of dioxin toxicity; dioxin decions; the present and the future.

  5. Agent oriented programming

    NASA Technical Reports Server (NTRS)

    Shoham, Yoav

    1994-01-01

    The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

  6. Radioactive diagnostic agent

    SciTech Connect

    Shigematsu, A.; Aihara, M.; Matsuda, M.; Suzuki, A.; Tsuya, A.

    1984-02-07

    A radioactive diagnostic agent for renal cortex, adrenal cortex, myocardium, brain stem, spinal nerve, etc., which comprises as an essential component monoiodoacetic acid wherein the iodine atom is radioactive.

  7. Riot Control Agents

    MedlinePlus

    ... your clothing, rapidly wash your entire body with soap and water, and get medical care as quickly ... agent from your skin with large amounts of soap and water. Washing with soap and water will ...

  8. Agent amplified communication

    SciTech Connect

    Kautz, H.; Selman, B.; Milewski, A.

    1996-12-31

    We propose an agent-based framework for assisting and simplifying person-to-person communication for information gathering tasks. As an example, we focus on locating experts for any specified topic. In our approach, the informal person-to-person networks that exist within an organization are used to {open_quotes}referral chain{close_quotes} requests for expertise. User-agents help automate this process. The agents generate referrals by analyzing records of e-mail communication patterns. Simulation results show that the higher responsiveness of an agent-based system can be effectively traded for the higher accuracy of a completely manual approach. Furthermore, preliminary experience with a group of users on a prototype system has shown that useful automatic referrals can be found in practice. Our experience with actual users has also shown that privacy concerns are central to the successful deployment of personal agents: an advanced agent-based system will therefore need to reason about issues involving trust and authority.

  9. Agent independent task planning

    NASA Technical Reports Server (NTRS)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  10. MpcAgent

    SciTech Connect

    Nutaro, James

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of the building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.

  11. MpcAgent

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of themore » building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.« less

  12. Gadofullerene MRI contrast agents.

    PubMed

    Bolskar, Robert D

    2008-04-01

    A promising new class of MRI contrast-enhancing agents with high relaxivities is based on gadolinium-containing metallofullerenes, which are also termed gadofullerenes. Detailed study of the water-proton relaxivity properties and intermolecular nanoclustering behavior of gadofullerene derivatives has revealed valuable information about their relaxivity mechanisms and given a deeper understanding of this new class of paramagnetic contrast agent. Here, the latest findings on water-solubilized gadofullerene materials and how these findings relate to their future applications in MRI are reviewed and discussed. PMID:18373426

  13. Agent Persuasion Mechanism of Acquaintance

    NASA Astrophysics Data System (ADS)

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

    Agent persuasion can improve negotiation efficiency in dynamic environment based on its initiative and autonomy, and etc., which is being affected much more by acquaintance. Classification of acquaintance on agent persuasion is illustrated, and the agent persuasion model of acquaintance is also illustrated. Then the concept of agent persuasion degree of acquaintance is given. Finally, relative interactive mechanism is elaborated.

  14. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 107.1620 Section 107.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance...

  15. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 108.1620 Section 108.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA...

  16. Can Subscription Agents Survive?

    ERIC Educational Resources Information Center

    Tuttle, Marcia

    1985-01-01

    With the saturation of traditional markets for their services, subscription agents have evolved from orders and invoices to serving customers by communicating with librarians and publishers and making automated and paper products available. Magazine fulfillment centers, publisher discounts, and electronic publishing will influence the subscription…

  17. Remote Agent Experiment

    NASA Technical Reports Server (NTRS)

    Benard, Doug; Dorais, Gregory A.; Gamble, Ed; Kanefsky, Bob; Kurien, James; Millar, William; Muscettola, Nicola; Nayak, Pandu; Rouquette, Nicolas; Rajan, Kanna; Norvig, Peter (Technical Monitor)

    2000-01-01

    Remote Agent (RA) is a model-based, reusable artificial intelligence (At) software system that enables goal-based spacecraft commanding and robust fault recovery. RA was flight validated during an experiment on board of DS1 between May 17th and May 21th, 1999.

  18. E-Learning Agents

    ERIC Educational Resources Information Center

    Gregg, Dawn G.

    2007-01-01

    Purpose: The purpose of this paper is to illustrate the advantages of using intelligent agents to facilitate the location and customization of appropriate e-learning resources and to foster collaboration in e-learning environments. Design/methodology/approach: This paper proposes an e-learning environment that can be used to provide customized…

  19. Battlefield agent collaboration

    NASA Astrophysics Data System (ADS)

    Budulas, Peter P.; Young, Stuart H.; Emmerman, Philip J.

    2001-09-01

    Small air and ground physical agents (robots) will be ubiquitous on the battlefield of the 21st century, principally to lower the exposure to harm of our ground forces in urban and open terrain scenarios. Teams of small collaborating physical agents conducting tasks such as Reconnaissance, Surveillance, and Target Acquisition (RSTA), intelligence, chemical and biological agent detection, logistics, decoy, sentry; and communications relay will have advanced sensors, communications, and mobility characteristics. It is anticipated that there will be many levels of individual and team collaboration between the soldier and robot, robot to robot, and robot to mother ship. This paper presents applications and infrastructure components that illustrate each of these levels. As an example, consider the application where a team of twenty small robots must rapidly explore and define a building complex. Local interactions and decisions require peer to peer collaboration. Global direction and information fusion warrant a central team control provided by a mother ship. The mother ship must effectively deliver/retrieve, service, and control these robots as well as fuse the information gathered by these highly mobile robot teams. Any level of collaboration requires robust communications, specifically a mobile ad hoc network. The application of fixed ground sensors and mobile robots is also included in this paper. This paper discusses on going research at the U.S. Army Research Laboratory that supports the development of multi-robot collaboration. This research includes battlefield visualization, intelligent software agents, adaptive communications, sensor and information fusion, and multi-modal human computer interaction.

  20. Mobility control agent

    SciTech Connect

    Argabright, P.A.; Phillips, B.L.; Rhudy, J.S.

    1983-05-17

    Polymer mobility control agents useful in supplemental oil recovery processes, which give improved reciprocal relative mobilities, are prepared by initiating the polymerization of a monomer containing a vinyl group with a catalyst comprising a persulfate and ferrous ammonium sulfate. The vinyl monomer is an acrylyl, a vinyl cyanide, a styryl and water soluble salts thereof.

  1. Distributed Agents for Autonomy

    NASA Astrophysics Data System (ADS)

    Blake, Rick; Amigoni, Francesco; Brambilla, Andrea; de la Rosa Steinz, Sonia; Lavagna, Michele; le Duc, Ian; Page, Jonathan; Page, Oliver; Steel, Robin; Wijnands, Quirien

    2010-08-01

    The Distributed Agents for Autonomy (DAFA) Study has been performed for ESA by SciSys UK Ltd, Vega GmbH and Politecnico di Milano. An analysis of past, present and future space missions has been conducted, structured around a set of three pre-defined mission scenarios: Formation Flying, Earth Observation and Planetary Exploration. This analysis led to the definition of a framework of use cases where the application of distributed autonomy seems necessary or appropriate, and a set of metrics that may be used to assess such deployments. Agent technology and architectures were extensively surveyed and the results used to elaborate each of the mission scenarios to the point where a software prototype could be constructed. Such a prototype was developed for a scenario based on the ExoMars mission and this has been used to highlight the advantages of a DAFA approach to the mission architecture.

  2. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  3. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  4. Surface polymerization agents

    SciTech Connect

    Taylor, C.; Wilkerson, C.

    1996-12-01

    This is the final report of a 1-year, Laboratory-Directed R&D project at LANL. A joint technical demonstration was proposed between US Army Missile Command (Redstone Arsenal) and LANL. Objective was to demonstrate that an unmanned vehicle or missile could be used as a platform to deliver a surface polymerization agent in such a manner as to obstruct the filters of an air-breathing mechanism, resulting in operational failure.

  5. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  6. Perioperative allergy: uncommon agents.

    PubMed

    Caimmi, S; Caimmi, D; Cardinale, F; Indinnimeo, L; Crisafulli, G; Peroni, D G; Marseglia, G L

    2011-01-01

    Anesthesia may often be considered as a high-risk procedure and anaphylaxis remains a major cause of concern for anesthetists who routinely administer many potentially allergenic agents. Neuromuscular blocking agents, latex and antibiotics are the substances involved in most of the reported reactions. Besides these three agents, a wide variety of substances may cause an anaphylactic reaction during anesthesia. Basically all the administered drugs or substances may be potential causes of anaphylaxis. Among them, those reported the most in literature include hypnotics, opioids, local anesthetics, colloids, dye, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Iodinated Contrast Media (ICM), antiseptics, aprotinin, ethylene oxyde and formaldehyde, and protamine and heparins. No premedication can effectively prevent an allergic reaction and a systematic preoperative screening is not justified for all patients; nevertheless, an allergy specialist should evaluate those patients with a history of anesthesia-related allergy. Patients must be fully informed of investigation results, and advised to provide a detailed report prior to future anesthesia. PMID:22014927

  7. Anaplasma marginale and Theileria annulata in questing ticks from Portugal.

    PubMed

    Antunes, S; Ferrolho, J; Domingues, N; Santos, A S; Santos-Silva, M M; Domingos, A

    2016-09-01

    Ticks are ubiquitous arthropods and vectors of several pathogenic agents in animals and humans. Monitoring questing ticks is of great importance to ascertain the occurrence of pathogens and the potential vector species, offering an insight into the risk of disease transmission in a given area. In this study 428 host-seeking ticks, belonging to nine species of Ixodidae and collected from 17 of the 23 Portuguese mainland subregions, were screened for several tick-borne agents with veterinary relevance: Anaplasma marginale, Anaplasma ovis, Anaplasma centrale, Babesia spp., Coxiella burnetii and Theileria spp. Prevalence was assessed by PCR and amplified amplicons sequenced for validation of results. Twenty ticks, in a total of 428, were found positive: one Ixodes ventalloi for Theileria annulata and four Dermacentor marginatus, one Haemaphysalis punctata, five Ixodes ricinus, five I. ventalloi, and four Rhipicephalus sanguineus sensu lato for A. marginale. According to the reviewed literature, this is the first report of A. marginale and T. annulata detection in I. ventalloi. Furthermore, the amplification of A. marginale DNA in several tick species suggests a broad range for this agent in Portugal that might include other uncommon species as R. sanguineus s.l. This work provides new data towards a better understanding of tick-pathogen associations and also contributes to the surveillance of tick-borne agents in geographic areas with limited information. PMID:27394441

  8. Large vessel vasculitis in a patient with acute Q-fever: A case report

    PubMed Central

    Baziaka, Fotini; Karaiskos, Ilias; Galani, Lamprini; Barmpouti, Eleftheria; Konstantinidis, Stilianos; Kitas, George; Giamarellou, Helen

    2014-01-01

    Q fever is a zoonosis caused by the rickettsial organism Coxiella burnetii. Infection has an acute course, usually with a self-limited febrile illness and the possibility of the evaluation to a chronic course with endocardial involvement. The presence of autoantibodies and various autoimmune disorders have also been associated with C. burnetii infection. We report a case of acute Q fever in which the patient developed large vessel vasculitis. The FDG-PET/CT scan detected inflammation of the thoracic aortic wall, suggesting an unusual immunologic host response to acute Q fever infection. PMID:26952153

  9. Liposome encapsulation of chelating agents

    DOEpatents

    Rahman, Yueh Erh

    1976-01-13

    A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

  10. Hydroxypyridonate and hydroxypyrimidinone chelating agents

    SciTech Connect

    Raymond, Kenneth N.; Doble, Daniel M.; Sunderland, Christopher J.; Thompson, Marlon

    2005-01-25

    The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

  11. Collaborating with Autonomous Agents

    NASA Technical Reports Server (NTRS)

    Trujillo, Anna C.; Cross, Charles D.; Fan, Henry; Hempley, Lucas E.; Motter, Mark A.; Neilan, James H.; Qualls, Garry D.; Rothhaar, Paul M.; Tran, Loc D.; Allen, B. Danette

    2015-01-01

    With the anticipated increase of small unmanned aircraft systems (sUAS) entering into the National Airspace System, it is highly likely that vehicle operators will be teaming with fleets of small autonomous vehicles. The small vehicles may consist of sUAS, which are 55 pounds or less that typically will y at altitudes 400 feet and below, and small ground vehicles typically operating in buildings or defined small campuses. Typically, the vehicle operators are not concerned with manual control of the vehicle; instead they are concerned with the overall mission. In order for this vision of high-level mission operators working with fleets of vehicles to come to fruition, many human factors related challenges must be investigated and solved. First, the interface between the human operator and the autonomous agent must be at a level that the operator needs and the agents can understand. This paper details the natural language human factors e orts that NASA Langley's Autonomy Incubator is focusing on. In particular these e orts focus on allowing the operator to interact with the system using speech and gestures rather than a mouse and keyboard. With this ability of the system to understand both speech and gestures, operators not familiar with the vehicle dynamics will be able to easily plan, initiate, and change missions using a language familiar to them rather than having to learn and converse in the vehicle's language. This will foster better teaming between the operator and the autonomous agent which will help lower workload, increase situation awareness, and improve performance of the system as a whole.

  12. Chemical warfare agents.

    PubMed

    Ganesan, K; Raza, S K; Vijayaraghavan, R

    2010-07-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided. PMID:21829312

  13. Pharmacologic agents targeting autophagy

    PubMed Central

    Vakifahmetoglu-Norberg, Helin; Xia, Hong-guang; Yuan, Junying

    2015-01-01

    Autophagy is an important intracellular catabolic mechanism critically involved in regulating tissue homeostasis. The implication of autophagy in human diseases and the need to understand its regulatory mechanisms in mammalian cells have stimulated research efforts that led to the development of high-throughput screening protocols and small-molecule modulators that can activate or inhibit autophagy. Herein we review the current landscape in the development of screening technology as well as the molecules and pharmacologic agents targeting the regulatory mechanisms of autophagy. We also evaluate the potential therapeutic application of these compounds in different human pathologies. PMID:25654545

  14. Chemical warfare agents

    PubMed Central

    Ganesan, K.; Raza, S. K.; Vijayaraghavan, R.

    2010-01-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided. PMID:21829312

  15. Cleaning agents and asthma.

    PubMed

    Quirce, S; Barranco, P

    2010-01-01

    Although cleaners represent a significant part of the working population worldwide, they remain a relatively understudied occupational group. Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. Cleaning workers are exposed to a large variety of cleaning products containing both irritants and sensitizers, as well as to common indoor allergens and pollutants. Thus, the onset or aggravation of asthma in this group could be related to an irritant-induced mechanism or to specific sensitization. The main sensitizers contained in cleaning products are disinfectants, quaternary ammonium compounds (such as benzalkonium chloride), amine compounds, and fragrances.The strongest airway irritants in cleaning products are bleach (sodium hypochlorite), hydrochloric acid, and alkaline agents (ammonia and sodium hydroxide), which are commonly mixed together. Exposure to the ingredients of cleaning products may give rise to both new-onset asthma, with or without a latency period, and work-exacerbated asthma. High-level exposure to irritants may induce reactive airways dysfunction syndrome. Cleaning workers may also have a greater relative risk of developing asthma due to prolonged low-to-moderate exposure to respiratory irritants. In addition, asthma-like symptoms without confirmed asthma are also common after exposure to cleaning agents. In many cleaners, airway symptoms induced by chemicals and odors cannot be explained by allergic or asthmatic reactions. These patients may have increased sensitivity to inhaled capsaicin, which is known to reflect sensory reactivity, and this condition is termed airway sensory hyperreactivity. PMID:21313993

  16. [New agents for hypercholesterolemia].

    PubMed

    Pintó, Xavier; García Gómez, María Carmen

    2016-02-19

    An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. PMID:25817449

  17. Holograms as Teaching Agents

    NASA Astrophysics Data System (ADS)

    Walker, Robin A.

    2013-02-01

    Hungarian physicist Dennis Gabor won the Pulitzer Prize for his 1947 introduction of basic holographic principles, but it was not until the invention of the laser in 1960 that research scientists, physicians, technologists and the general public began to seriously consider the interdisciplinary potentiality of holography. Questions around whether and when Three-Dimensional (3-D) images and systems would impact American entertainment and the arts would be answered before educators, instructional designers and students would discover how much Three-Dimensional Hologram Technology (3DHT) would affect teaching practices and learning environments. In the following International Symposium on Display Holograms (ISDH) poster presentation, the author features a traditional board game as well as a reflection hologram to illustrate conventional and evolving Three-Dimensional representations and technology for education. Using elements from the American children's toy Operation® (Hasbro, 2005) as well as a reflection hologram of a human brain (Ko, 1998), this poster design highlights the pedagogical effects of 3-D images, games and systems on learning science. As teaching agents, holograms can be considered substitutes for real objects, (human beings, organs, and animated characters) as well as agents (pedagogical, avatars, reflective) in various learning environments using many systems (direct, emergent, augmented reality) and electronic tools (cellphones, computers, tablets, television). In order to understand the particular importance of utilizing holography in school, clinical and public settings, the author identifies advantages and benefits of using 3-D images and technology as instructional tools.

  18. Learning models of intelligent agents

    SciTech Connect

    Carmel, D.; Markovitch, S.

    1996-12-31

    Agents that operate in a multi-agent system need an efficient strategy to handle their encounters with other agents involved. Searching for an optimal interactive strategy is a hard problem because it depends mostly on the behavior of the others. In this work, interaction among agents is represented as a repeated two-player game, where the agents` objective is to look for a strategy that maximizes their expected sum of rewards in the game. We assume that agents` strategies can be modeled as finite automata. A model-based approach is presented as a possible method for learning an effective interactive strategy. First, we describe how an agent should find an optimal strategy against a given model. Second, we present an unsupervised algorithm that infers a model of the opponent`s automaton from its input/output behavior. A set of experiments that show the potential merit of the algorithm is reported as well.

  19. Flexible, secure agent development framework

    DOEpatents

    Goldsmith; Steven Y.

    2009-04-07

    While an agent generator is generating an intelligent agent, it can also evaluate the data processing platform on which it is executing, in order to assess a risk factor associated with operation of the agent generator on the data processing platform. The agent generator can retrieve from a location external to the data processing platform an open site that is configurable by the user, and load the open site into an agent substrate, thereby creating a development agent with code development capabilities. While an intelligent agent is executing a functional program on a data processing platform, it can also evaluate the data processing platform to assess a risk factor associated with performing the data processing function on the data processing platform.

  20. New antifungal agents.

    PubMed

    Gupta, Aditya K; Tomas, Elizabeth

    2003-07-01

    Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments. Liposomal formulations of AmB have a broad spectrum of activity against invasive fungi, such as Candida spp., C. neoformans, and Aspergillus spp., but not dermatophyte fungi. The liposomal AmB is associated with significantly less toxicity and good rates of efficacy, which compare or exceed that of standard AmB. These factors may provide enough of an advantage to patients to overcome the increased costs of these formulations. Three new azole drugs have been developed, and may be of use in both systemic and superficial fungal infections. Voriconazole, ravuconazole, and posaconazole are triazoles, with broad-spectrum activity. Voriconazole has a high bioavailability, and has been used with success in immunocompromised patients with invasive fungal infections. Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients. Preliminary in vivo studies with posaconazole indicated potential use in a variety of invasive fungal infections including oropharyngeal candidiasis. Echinocandins and pneumocandins are a new class of antifungals, which act as fungal cell wall beta-(1,3)-D-glucan synthase enzyme complex inhibitors. Caspofungin (MK-0991) is the first of the echinocandins to receive Food and Drug Administration approval for patients with invasive aspergillosis not responding or intolerant to other antifungal therapies, and has been effective in patients with oropharyngeal and esophageal candidiasis. Standardization of MIC value determination has improved the

  1. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  2. Hepatocytes as Immunological Agents.

    PubMed

    Crispe, Ian N

    2016-01-01

    Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance. PMID:26685314

  3. Seroprevalence of infectious diseases in saiga antelope (Saiga tatarica tatarica) in Kazakhstan 2012-2014.

    PubMed

    Orynbayev, Mukhit B; Beauvais, Wendy; Sansyzbay, Abylay R; Rystaeva, Rashida A; Sultankulova, Kulyaisan T; Kerimbaev, Aslan A; Kospanova, Madina N; Kock, Richard A

    2016-05-01

    286 serum samples were collected from three sub-populations of saiga in Kazakhstan (Betpakdala, Ustyurt and Volga-Ural) between 2012 and 2014, and were tested for the presence of antibodies to Brucella spp., bluetongue virus, peste des petits ruminants (PPR) virus, Akabane virus, Schmallenberg virus, Chlamydophila, Toxoplasma, Mycobacterium avium subspecies paratuberculosis and Coxiella burnetii (Q Fever). Seropositives to Coxiella burnetii of saiga were detected and the adjusted seroprevalence of Q Fever antibodies was 0.07 (95% confidence interval (CI): 0.03-0.10). Seropositives to Akabane virus were detected in all three populations and the adjusted seroprevalence values for this virus were very high (all were>0.13). Lower adjusted seroprevalence values were estimated for PPR Virus and Mycobacterium avium subsp. paratuberculosis (0.005 and 0.006). No seropositives for bluetongue, Toxoplasma, Brucella or Schmallenberg were detected. PMID:27094147

  4. Agent Assignment for Process Management: Pattern Based Agent Performance Evaluation

    NASA Astrophysics Data System (ADS)

    Jablonski, Stefan; Talib, Ramzan

    In almost all workflow management system the role concept is determined once at the introduction of workflow application and is not reevaluated to observe how successfully certain processes are performed by the authorized agents. This paper describes an approach which evaluates how agents are working successfully and feed this information back for future agent assignment to achieve maximum business benefit for the enterprise. The approach is called Pattern based Agent Performance Evaluation (PAPE) and is based on machine learning technique combined with post processing technique. We report on the result of our experiments and discuss issues and improvement of our approach.

  5. Agent-based enterprise integration

    SciTech Connect

    N. M. Berry; C. M. Pancerella

    1998-12-01

    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. The enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of the effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses the planned future work.

  6. Collaborating Fuzzy Reinforcement Learning Agents

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1997-01-01

    Earlier, we introduced GARIC-Q, a new method for doing incremental Dynamic Programming using a society of intelligent agents which are controlled at the top level by Fuzzy Relearning and at the local level, each agent learns and operates based on ANTARCTIC, a technique for fuzzy reinforcement learning. In this paper, we show that it is possible for these agents to compete in order to affect the selected control policy but at the same time, they can collaborate while investigating the state space. In this model, the evaluator or the critic learns by observing all the agents behaviors but the control policy changes only based on the behavior of the winning agent also known as the super agent.

  7. New agents for prostate cancer.

    PubMed

    Agarwal, N; Di Lorenzo, G; Sonpavde, G; Bellmunt, J

    2014-09-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid

  8. Q Fever, Scrub Typhus, and Rickettsial Diseases in Children, Kenya, 2011–2012

    PubMed Central

    Farris, Christina M.; Odhiambo, Antony; Jiang, Ju; Laktabai, Jeremiah; Armstrong, Janice; Holland, Thomas; Richards, Allen L.; O’Meara, Wendy P.

    2016-01-01

    To increase knowledge of undifferentiated fevers in Kenya, we tested paired serum samples from febrile children in western Kenya for antibodies against pathogens increasingly recognized to cause febrile illness in Africa. Of patients assessed, 8.9%, 22.4%, 1.1%, and 3.6% had enhanced seroreactivity to Coxiella burnetii, spotted fever group rickettsiae, typhus group rickettsiae, and scrub typhus group orientiae, respectively. PMID:27088502

  9. Q Fever, Scrub Typhus, and Rickettsial Diseases in Children, Kenya, 2011-2012.

    PubMed

    Maina, Alice N; Farris, Christina M; Odhiambo, Antony; Jiang, Ju; Laktabai, Jeremiah; Armstrong, Janice; Holland, Thomas; Richards, Allen L; O'Meara, Wendy P

    2016-05-01

    To increase knowledge of undifferentiated fevers in Kenya, we tested paired serum samples from febrile children in western Kenya for antibodies against pathogens increasingly recognized to cause febrile illness in Africa. Of patients assessed, 8.9%, 22.4%, 1.1%, and 3.6% had enhanced seroreactivity to Coxiella burnetii, spotted fever group rickettsiae, typhus group rickettsiae, and scrub typhus group orientiae, respectively. PMID:27088502

  10. Broad-spectrum antiviral agents

    PubMed Central

    Zhu, Jun-Da; Meng, Wen; Wang, Xiao-Jia; Wang, Hwa-Chain R.

    2015-01-01

    Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents. PMID:26052325

  11. The Agent of Change: The Agent of Conflict.

    ERIC Educational Resources Information Center

    Hatfield, C. R., Jr.

    This speech examines the role of change agents in third world societies and indicates that the change agent must, to some extent, manipulate the social situation, even if his view of society is a more optimistic one than he finds in reality. If he considers strains and stresses to be the lubricants of change, then his focus on conflict as a…

  12. Incorporating BDI Agents into Human-Agent Decision Making Research

    NASA Astrophysics Data System (ADS)

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  13. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  14. TACtic- A Multi Behavioral Agent for Trading Agent Competition

    NASA Astrophysics Data System (ADS)

    Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

    Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

  15. Gelled Anti-icing Agents

    NASA Technical Reports Server (NTRS)

    Markles, O. F.; Sperber, H. H.

    1983-01-01

    Pectin added to antifreeze/water mixture. Formulations include water with dimethyl sulfoxide (DMSO) as deicer and pectin as gel former. Without gelling agent, deicer runs off vertical surfaces. Without pectin solution will completely evaporate in far less time. Agents developed have wide potential for ice prevention on runways, highways, bridges and sidewalks.

  16. Agent-Based Literacy Theory

    ERIC Educational Resources Information Center

    McEneaney, John E.

    2006-01-01

    The purpose of this theoretical essay is to explore the limits of traditional conceptualizations of reader and text and to propose a more general theory based on the concept of a literacy agent. The proposed theoretical perspective subsumes concepts from traditional theory and aims to account for literacy online. The agent-based literacy theory…

  17. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs. PMID:18991707

  18. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  19. Markov Tracking for Agent Coordination

    NASA Technical Reports Server (NTRS)

    Washington, Richard; Lau, Sonie (Technical Monitor)

    1998-01-01

    Partially observable Markov decision processes (POMDPs) axe an attractive representation for representing agent behavior, since they capture uncertainty in both the agent's state and its actions. However, finding an optimal policy for POMDPs in general is computationally difficult. In this paper we present Markov Tracking, a restricted problem of coordinating actions with an agent or process represented as a POMDP Because the actions coordinate with the agent rather than influence its behavior, the optimal solution to this problem can be computed locally and quickly. We also demonstrate the use of the technique on sequential POMDPs, which can be used to model a behavior that follows a linear, acyclic trajectory through a series of states. By imposing a "windowing" restriction that restricts the number of possible alternatives considered at any moment to a fixed size, a coordinating action can be calculated in constant time, making this amenable to coordination with complex agents.

  20. Ectoparasites and associated pathogens of free-roaming and captive animals in zoos of South Carolina.

    PubMed

    Nelder, Mark P; Reeves, Will K; Adler, Peter H; Wozniak, Arthur; Wills, William

    2009-10-01

    A survey of ectoparasites and their associated pathogens was conducted in two South Carolina zoos, from 2004 to 2007. Dead, wild birds and mammals, as well as captive animals examined during routine veterinary checks constituted the study populations. Ectoparasites were tested for species of Anaplasma, Bartonella, Coxiella burnetii, Ehrlichia, Rickettsia, and Trypanosoma. Forty-six species of ectoparasites were collected from 133 free-roaming and captive hosts and their associated nesting and bedding materials. Six vector-borne pathogens were detected molecularly in the ectoparasites, including Anaplasma phagocytophilum in the tick Ixodes dentatus Marx from an eastern cottontail rabbit, Bartonella clarridgeiae in the cat flea Ctenocephalides felis (Bouché) from a Virginia opossum, Bartonella sp. Oh6 in the squirrel flea Orchopeas howardi (Baker) from an eastern grey squirrel, Bartonella sp. T7498 in the sucking louse Neohaematopinus sciuri Jancke from a squirrel, Rickettsia sp. Rf2125 in C. felis from a zookeeper and a grizzly bear, and Rickettsiales sp. Ib 2006 in Ixodes brunneus Koch from an American crow. While the pathology of some of these pathogens is poorly known, Anaplasma phagocytophilum (causative agent of human granulocytic anaplasmosis) and Bartonella clarridgeiae (causative agent of a disease similar to cat-scratch disease) can infect humans. Ectoparasites and their pathogens, especially those originating from free-roaming animals, present a potential threat to captive animals and humans. PMID:18973443

  1. Endocarditis Due to Rare and Fastidious Bacteria

    PubMed Central

    Brouqui, P.; Raoult, D.

    2001-01-01

    The etiologic diagnosis of infective endocarditis is easily made in the presence of continuous bacteremia with gram-positive cocci. However, the blood culture may contain a bacterium rarely associated with endocarditis, such as Lactobacillus spp., Klebsiella spp., or nontoxigenic Corynebacterium, Salmonella, Gemella, Campylobacter, Aeromonas, Yersinia, Nocardia, Pasteurella, Listeria, or Erysipelothrix spp., that requires further investigation to establish the relationship with endocarditis, or the blood culture may be uninformative despite a supportive clinical evaluation. In the latter case, the etiologic agents are either fastidious extracellular or intracellular bacteria. Fastidious extracellular bacteria such as Abiotrophia, HACEK group bacteria, Clostridium, Brucella, Legionella, Mycobacterium, and Bartonella spp. need supplemented media, prolonged incubation time, and special culture conditions. Intracellular bacteria such as Coxiella burnetii cannot be isolated routinely. The two most prevalent etiologic agents of culture-negative endocarditis are C. burnetti and Bartonella spp. Their diagnosis is usually carried out serologically. A systemic pathologic examination of excised heart valves including periodic acid-Schiff (PAS) staining and molecular methods has allowed the identification of Whipple's bacillus endocarditis. Pathologic examination of the valve using special staining, such as Warthin-Starry, Gimenez, and PAS, and broad-spectrum PCR should be performed systematically when no etiologic diagnosis is evident through routine laboratory evaluation. PMID:11148009

  2. Knowledge focus via software agents

    NASA Astrophysics Data System (ADS)

    Henager, Donald E.

    2001-09-01

    The essence of military Command and Control (C2) is making knowledge intensive decisions in a limited amount of time using uncertain, incorrect, or outdated information. It is essential to provide tools to decision-makers that provide: * Management of friendly forces by treating the "friendly resources as a system". * Rapid assessment of effects of military actions againt the "enemy as a system". * Assessment of how an enemy should, can, and could react to friendly military activities. Software agents in the form of mission agents, target agents, maintenance agents, and logistics agents can meet this information challenge. The role of each agent is to know all the details about its assigned mission, target, maintenance, or logistics entity. The Mission Agent would fight for mission resources based on the mission priority and analyze the effect that a proposed mission's results would have on the enemy. The Target Agent (TA) communicates with other targets to determine its role in the system of targets. A system of TAs would be able to inform a planner or analyst of the status of a system of targets, the effect of that status, adn the effect of attacks on that system. The system of TAs would also be able to analyze possible enemy reactions to attack by determining ways to minimize the effect of attack, such as rerouting traffic or using deception. The Maintenance Agent would scheudle maintenance events and notify the maintenance unit. The Logistics Agent would manage shipment and delivery of supplies to maintain appropriate levels of weapons, fuel and spare parts. The central idea underlying this case of software agents is knowledge focus. Software agents are createad automatically to focus their attention on individual real-world entities (e.g., missions, targets) and view the world from that entities perspective. The agent autonomously monitors the entity, identifies problems/opportunities, formulates solutions, and informs the decision-maker. The agent must be

  3. Agent Communications using Distributed Metaobjects

    SciTech Connect

    Goldsmith, Steven Y.; Spires, Shannon V.

    1999-06-10

    There are currently two proposed standards for agent communication languages, namely, KQML (Finin, Lobrou, and Mayfield 1994) and the FIPA ACL. Neither standard has yet achieved primacy, and neither has been evaluated extensively in an open environment such as the Internet. It seems prudent therefore to design a general-purpose agent communications facility for new agent architectures that is flexible yet provides an architecture that accepts many different specializations. In this paper we exhibit the salient features of an agent communications architecture based on distributed metaobjects. This architecture captures design commitments at a metaobject level, leaving the base-level design and implementation up to the agent developer. The scope of the metamodel is broad enough to accommodate many different communication protocols, interaction protocols, and knowledge sharing regimes through extensions to the metaobject framework. We conclude that with a powerful distributed object substrate that supports metaobject communications, a general framework can be developed that will effectively enable different approaches to agent communications in the same agent system. We have implemented a KQML-based communications protocol and have several special-purpose interaction protocols under development.

  4. Q fever: baseline monitoring of a sheep and a goat flock associated with human infections

    PubMed Central

    EIBACH, R.; BOTHE, F.; RUNGE, M.; FISCHER, S. F.; PHILIPP, W.; GANTER, M.

    2012-01-01

    SUMMARY Animal losses due to abortion and weak offspring during a lambing period amounted up to 25% in a goat flock and up to 18% in a sheep flock kept at an experimental station on the Swabian Alb, Germany. Fifteen out of 23 employees and residents on the farm tested positive for Coxiella burnetii antibodies by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay. Ninety-four per cent of the goats and 47% of the sheep were seropositive for C. burnetii by ELISA. Blood samples of 8% of goats and 3% of sheep were PCR positive. C. burnetii was shed by all tested animals through vaginal mucus, by 97% of the goats and 78% of the sheep through milk, and by all investigated sheep through faeces (PCR testing). In this outbreak human and animal infection were temporally related suggesting that one was caused by the other. PMID:22217267

  5. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, Paul H.; Brainard, James R.; Jarvinen, Gordon D.; Ryan, Robert R.

    1997-01-01

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC.sub.16 H.sub.14 N.sub.6. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques.

  6. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, P.H.; Brainard, J.R.; Jarvinen, G.D.; Ryan, R.R.

    1997-12-30

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC{sub 16}H{sub 14}N{sub 6}. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques. 10 figs.

  7. Introducing Infectious Agents and Cancer

    PubMed Central

    Buonaguro, Franco M; Lewis, George K; Pelicci, PierGiuseppe

    2006-01-01

    Infectious Agents and Cancer is a new open access, peer-reviewed, online journal, which encompasses all aspects of basic, clinical and translational research that provide an insight into the association between chronic infections and cancer. PMID:23509916

  8. Diamine curing agents for polyurethanes

    NASA Technical Reports Server (NTRS)

    Bell, V. L.; St. Clair, T. L.

    1975-01-01

    Three aromatic diamines have properties that make them promising candidates as curing agents for converting isocyanates to polyurethanes with higher adhesive strengths, higher softening temperatures, better toughness, and improved abrasion resistance.

  9. Triggered pore-forming agents

    DOEpatents

    Bayley, Hagan; Walker, Barbara J.; Chang, Chung-yu; Niblack, Brett; Panchal, Rekha

    1998-01-01

    An inactive pore-forming agent which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell.

  10. Tissue Penetration of Antifungal Agents

    PubMed Central

    Felton, Timothy; Troke, Peter F.

    2014-01-01

    SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

  11. AL Amyloidosis and Agent Orange

    MedlinePlus

    ... for survivors' benefits . Research on AL amyloidosis and herbicides The Health and Medicine Division (formally known as ... to the compounds of interest found in the herbicide Agent Orange and AL amyloidosis." VA made a ...

  12. Agent-based forward analysis

    SciTech Connect

    Kerekes, Ryan A.; Jiao, Yu; Shankar, Mallikarjun; Potok, Thomas E.; Lusk, Rick M.

    2008-01-01

    We propose software agent-based "forward analysis" for efficient information retrieval in a network of sensing devices. In our approach, processing is pushed to the data at the edge of the network via intelligent software agents rather than pulling data to a central facility for processing. The agents are deployed with a specific query and perform varying levels of analysis of the data, communicating with each other and sending only relevant information back across the network. We demonstrate our concept in the context of face recognition using a wireless test bed comprised of PDA cell phones and laptops. We show that agent-based forward analysis can provide a significant increase in retrieval speed while decreasing bandwidth usage and information overload at the central facility. n

  13. Launch Commit Criteria Monitoring Agent

    NASA Technical Reports Server (NTRS)

    Semmel, Glenn S.; Davis, Steven R.; Leucht, Kurt W.; Rowe, Dan A.; Kelly, Andrew O.; Boeloeni, Ladislau

    2005-01-01

    The Spaceport Processing Systems Branch at NASA Kennedy Space Center has developed and deployed a software agent to monitor the Space Shuttle's ground processing telemetry stream. The application, the Launch Commit Criteria Monitoring Agent, increases situational awareness for system and hardware engineers during Shuttle launch countdown. The agent provides autonomous monitoring of the telemetry stream, automatically alerts system engineers when predefined criteria have been met, identifies limit warnings and violations of launch commit criteria, aids Shuttle engineers through troubleshooting procedures, and provides additional insight to verify appropriate troubleshooting of problems by contractors. The agent has successfully detected launch commit criteria warnings and violations on a simulated playback data stream. Efficiency and safety are improved through increased automation.

  14. What makes virtual agents believable?

    NASA Astrophysics Data System (ADS)

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon

    2016-01-01

    In this paper we investigate the concept of believability and make an attempt to isolate individual characteristics (features) that contribute to making virtual characters believable. As the result of this investigation we have produced a formalisation of believability and based on this formalisation built a computational framework focused on simulation of believable virtual agents that possess the identified features. In order to test whether the identified features are, in fact, responsible for agents being perceived as more believable, we have conducted a user study. In this study we tested user reactions towards the virtual characters that were created for a simulation of aboriginal inhabitants of a particular area of Sydney, Australia in 1770 A.D. The participants of our user study were exposed to short simulated scenes, in which virtual agents performed some behaviour in two different ways (while possessing a certain aspect of believability vs. not possessing it). The results of the study indicate that virtual agents that appear resource bounded, are aware of their environment, own interaction capabilities and their state in the world, agents that can adapt to changes in the environment and exist in correct social context are those that are being perceived as more believable. Further in the paper we discuss these and other believability features and provide a quantitative analysis of the level of contribution for each such feature to the overall perceived believability of a virtual agent.

  15. 46 CFR Sec. 2 - General Agents' authority.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE EMERGENCY REPAIRS IN FOREIGN PORTS Sec. 2 General Agents' authority. The General Agents are hereby delegated authority to undertake for the account of the...

  16. A amphoteric copolymer profile modification agent

    SciTech Connect

    Wang HongGuan; Yu LianCheng; Tian HongKun

    1995-11-01

    This report provides a new gel profile modification agent prepared by an amphoteric copolymer (FT-213) and a novel crosslinking agent (BY), and introduces the preparations of the amphoteric polymer, the crosslinking agent and the profile modification agent, the action mechanism, the test conditions and the evaluations of the performance of the agent. The 45 well treatments in oilfields demonstrate that the agent can be prepared conveniently, the agent has better compatibility and application performances, and the treatment life is longer with the use of the agent. 80,000 tons incremental oil and 60,000 m{sup 3} decreasing water production have been achieved.

  17. A multi-agent architecture for geosimulation of moving agents

    NASA Astrophysics Data System (ADS)

    Vahidnia, Mohammad H.; Alesheikh, Ali A.; Alavipanah, Seyed Kazem

    2015-10-01

    In this paper, a novel architecture is proposed in which an axiomatic derivation system in the form of first-order logic facilitates declarative explanation and spatial reasoning. Simulation of environmental perception and interaction between autonomous agents is designed with a geographic belief-desire-intention and a request-inform-query model. The architecture has a complementary quantitative component that supports collaborative planning based on the concept of equilibrium and game theory. This new architecture presents a departure from current best practices geographic agent-based modelling. Implementation tasks are discussed in some detail, as well as scenarios for fleet management and disaster management.

  18. Next Generation Remote Agent Planner

    NASA Technical Reports Server (NTRS)

    Jonsson, Ari K.; Muscettola, Nicola; Morris, Paul H.; Rajan, Kanna

    1999-01-01

    In May 1999, as part of a unique technology validation experiment onboard the Deep Space One spacecraft, the Remote Agent became the first complete autonomous spacecraft control architecture to run as flight software onboard an active spacecraft. As one of the three components of the architecture, the Remote Agent Planner had the task of laying out the course of action to be taken, which included activities such as turning, thrusting, data gathering, and communicating. Building on the successful approach developed for the Remote Agent Planner, the Next Generation Remote Agent Planner is a completely redesigned and reimplemented version of the planner. The new system provides all the key capabilities of the original planner, while adding functionality, improving performance and providing a modular and extendible implementation. The goal of this ongoing project is to develop a system that provides both a basis for future applications and a framework for further research in the area of autonomous planning for spacecraft. In this article, we present an introductory overview of the Next Generation Remote Agent Planner. We present a new and simplified definition of the planning problem, describe the basics of the planning process, lay out the new system design and examine the functionality of the core reasoning module.

  19. Optical recognition of biological agents

    NASA Astrophysics Data System (ADS)

    Baumgart, Chris W.; Linder, Kim Dalton; Trujillo, Josh J.

    2008-04-01

    Differentiation between particulate biological agents and non-biological agents is typically performed via a time-consuming "wet chemistry" process or through the use of fluorescent and spectroscopic analysis. However, while these methods can provide definitive recognition of biological agents, many of them have to be performed in a laboratory environment, or are difficult to implement in the field. Optical recognition techniques offer an additional recognition approach that can provide rapid analysis of a material in-situ to identify those materials that may be biological in nature. One possible application is to use these techniques to "screen" suspicious materials and to identify those that are potentially biological in nature. Suspicious materials identified by this screening process can then be analyzed in greater detail using the other, more definitive (but time consuming) analysis techniques. This presentation will describe the results of a feasibility study to determine whether optical pattern recognition techniques can be used to differentiate biological related materials from non-biological materials. As part of this study, feature extraction algorithms were developed utilizing multiple contrast and texture based features to characterize the macroscopic properties of different materials. In addition, several pattern recognition approaches using these features were tested including cluster analysis and neural networks. Test materials included biological agent simulants, biological agent related materials, and non-biological materials (suspicious white powders). Results of a series of feasibility tests will be presented along with a discussion of the potential field applications for these techniques.

  20. Inhalational exposure to nerve agents.

    PubMed

    Niven, Alexander S; Roop, Stuart A

    2004-03-01

    The respiratory system plays a major role in the pathogenesis of nerve agent toxicity. It is the major route of entry and absorption of nerve agent vapor, and respiratory failure is the most common cause of death follow-ing exposure. Respiratory symptoms are mediated by chemical irritation,muscarinic and nicotinic receptor overstimulation, and central nervous system effects. Recent attacks have demonstrated that most patients with an isolated vapor exposure developed respiratory symptoms almost immediately. Most patients had only mild and transient respiratory effects, and those that did develop significant respiratory compromise did so rapidly. These observations have significant ramifications on triage of patients in a mass-casualty situation, because patients with mild-to-moderate exposure to nerve agent vapor alone do not require decontamination and are less likely to develop progressive symptoms following initial antidote therapy. Limited data do not demonstrate significant long-term respiratory effects following nerve agent exposure and treatment. Provisions for effective respiratory protection against nerve agents is a vital consideration in any emergency preparedness or health care response plan against a chemical attack. PMID:15062227

  1. Investigational antimicrobial agents of 2013.

    PubMed

    Pucci, Michael J; Bush, Karen

    2013-10-01

    New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  2. Investigational Antimicrobial Agents of 2013

    PubMed Central

    Pucci, Michael J.

    2013-01-01

    SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  3. Environmentally responsive MRI contrast agents

    PubMed Central

    Davies, Gemma-Louise; Kramberger, Iris; Davis, Jason J.

    2015-01-01

    Biomedical imaging techniques can provide a vast amount of anatomical information, enabling diagnosis and the monitoring of disease and treatment profile. MRI uniquely offers convenient, non-invasive, high resolution tomographic imaging. A considerable amount of effort has been invested, across several decades, in the design of non toxic paramagnetic contrast agents capable of enhancing positive MRI signal contrast. Recently, focus has shifted towards the development of agents capable of specifically reporting on their local biochemical environment, where a switch in image contrast is triggered by a specific stimulus/biochemical variable. Such an ability would not only strengthen diagnosis but also provide unique disease-specific biochemical insight. This feature article focuses on recent progress in the development of MRI contrast switching with molecular, macromolecular and nanoparticle-based agents. PMID:24040650

  4. Polycatechol Nanoparticle MRI Contrast Agents.

    PubMed

    Li, Yiwen; Huang, Yuran; Wang, Zhao; Carniato, Fabio; Xie, Yijun; Patterson, Joseph P; Thompson, Matthew P; Andolina, Christopher M; Ditri, Treffly B; Millstone, Jill E; Figueroa, Joshua S; Rinehart, Jeffrey D; Scadeng, Miriam; Botta, Mauro; Gianneschi, Nathan C

    2016-02-01

    Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement. PMID:26681255

  5. Chemical warfare. Nerve agent poisoning.

    PubMed

    Holstege, C P; Kirk, M; Sidell, F R

    1997-10-01

    The threat of civilian and military casualties from nerve agent exposure has become a greater concern over the past decade. After rapidly assessing that a nerve agent attack has occurred, emphasis must be placed on decontamination and protection of both rescuers and medical personnel from exposure. The medical system can become rapidly overwhelmed and strong emotional reactions can confuse the clinical picture. Initially, care should first be focused on supportive care, with emphasis toward aggressive airway maintenance and decontamination. Atropine should be titrated, with the goal of therapy being drying of secretions and the resolution of bronchoconstriction and bradycardia. Early administration of pralidoxime chloride maximizes antidotal efficacy. Benzodiazepines, in addition to atropine, should be administered if seizures develop. Early, aggressive medical therapy is the key to prevention of the morbidity and mortality associated with nerve agent poisoning. PMID:9330846

  6. Agent review phase one report.

    SciTech Connect

    Zubelewicz, Alex Tadeusz; Davis, Christopher Edward; Bauer, Travis LaDell

    2009-12-01

    This report summarizes the findings for phase one of the agent review and discusses the review methods and results. The phase one review identified a short list of agent systems that would prove most useful in the service architecture of an information management, analysis, and retrieval system. Reviewers evaluated open-source and commercial multi-agent systems and scored them based upon viability, uniqueness, ease of development, ease of deployment, and ease of integration with other products. Based on these criteria, reviewers identified the ten most appropriate systems. The report also mentions several systems that reviewers deemed noteworthy for the ideas they implement, even if those systems are not the best choices for information management purposes.

  7. Haloprogin: a Topical Antifungal Agent

    PubMed Central

    Harrison, E. F.; Zwadyk, P.; Bequette, R. J.; Hamlow, E. E.; Tavormina, P. A.; Zygmunt, W. A.

    1970-01-01

    Haloprogin was shown to be a highly effective agent for the treatment of experimentally induced topical mycotic infections in guinea pigs. Its in vitro spectrum of activity also includes yeasts, yeastlike fungi (Candida species), and certain gram-positive bacteria. The in vitro and in vivo antifungal activity of haloprogin against dermatophytes was equal to that observed with tolnaftate. The striking differences between the two agents were the marked antimonilial and selective antibacterial activities shown by haloprogin, contrasted with the negligible activities found with tolnaftate. Addition of serum decreased the in vitro antifungal activity of haloprogin to a greater extent than that of tolnaftate; however, diminished antifungal activity was not observed when haloprogin was applied topically to experimental dermatophytic infections. Based on its broad spectrum of antimicrobial activity, haloprogin may prove to be a superior topical agent in the treatment of dermatophytic and monilial infections in man. PMID:5422306

  8. Thyroid dysfunction from antineoplastic agents.

    PubMed

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen

    2011-11-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  9. Erythropoietic agents and the elderly.

    PubMed

    Agarwal, Neeraj; Prchal, Josef T

    2008-10-01

    Erythropoietin (Epo) is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development that either act as ligands for the cell surface receptors of Epo or promote Epo production, which stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents under active investigation include continuous erythropoietin receptor activator (CERA) or proline hydroxylase inhibitors that increase hypoxia-inducible factor-1 (HIF-1), thereby stimulating Epo production and iron availability and supply. Erythropoietic agents have been shown to promote neuronal regeneration and to decrease post-stroke infarct size in mouse models. They have also been reported to shorten survival when used to treat anemia in many cancer patients and to increase thromboembolism. In contrast, rapid decrease of Epo levels as observed in astronauts and high-altitude dwellers upon rapid descent to sea level leads to the decrease of erythroid mass, a phenomenon known as "neocytolysis." The relative decrease in the serum Epo level is known to occur in some subjects with otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor physical function in the elderly and is a significant economic burden on society. One out of every five persons in the United States will be elderly by 2050. Erythropoietic agents, by preventing and treating otherwise unexplained anemias of the elderly and anemia associated with other disease conditions of the elderly, have the potential to improve the functional capacity and to decrease the morbidity and mortality in the elderly, thereby alleviating the overall burden of medical care in society. PMID:18809098

  10. Erythropoietic Agents and the Elderly

    PubMed Central

    Agarwal, Neeraj; Prchal, Josef T.

    2008-01-01

    Erythropoietin is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development, which either act as ligands for the cell surface receptors of erythropoietin or promote erythropoietin production that stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents stimulating erythropoiesis (such as continuous erythropoietin receptor activator (CERA) or proline hydroxylase inhibitors that increase HIF-1 thereby stimulating erythropoietin production and iron availability and supply) are under active investigation. Erythropoietic agents have been shown to promote neuronal regeneration and to decrease post-stroke infarct size in mouse models. They have also been reported to shorten survival when used to treat anemia in many cancer patients and to increase thromboembolism. In contrast, rapid decrease of erythropoietin levels as observed in astronauts and high-altitude dwellers upon rapid descent to sea level leads to the decrease of erythroid mass, a phenomenon known as neocytolysis. The relative decrease in the serum erythropoietin level is known to occur in some subjects with otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor physical function in the elderly and is a significant economic burden on society. One out of every five persons in the United States will be elderly by 2050. Erythropoietic agents, by preventing and treating otherwise unexplained anemias of the elderly and anemia associated with other disease conditions of the elderly, have the potential to improve the functional capacity and to decrease the morbidity and mortality in the elderly, thereby alleviating the overall burden of medical care in society. PMID:18809098

  11. Q Fever Outbreak Among Travelers to Germany Who Received Live Cell Therapy--United States and Canada, 2014.

    PubMed

    Robyn, Misha P; Newman, Alexandra P; Amato, Michael; Walawander, Mary; Kothe, Cynthia; Nerone, James D; Pomerantz, Cynthia; Behravesh, Casey Barton; Biggs, Holly M; Dahlgren, F Scott; Pieracci, Emily G; Whitfield, Yvonne; Sider, Doug; Ozaldin, Omar; Berger, Lisa; Buck, Peter A; Downing, Mark; Blog, Debra

    2015-10-01

    During September–November 2014, the New York State Department of Health (NYSDOH) was notified of five New York state residents who had tested seropositive for Coxiella burnetii, the causative agent of Q fever. All five patients had symptoms compatible with Q fever (e.g., fever, fatigue, chills, and headache) and a history of travel to Germany to receive a medical treatment called "live cell therapy" (sometimes called "fresh cell therapy") in May 2014. Live cell therapy is the practice of injecting processed cells from organs or fetuses of nonhuman animals (e.g., sheep) into human recipients. It is advertised to treat a variety of health conditions. This practice is unavailable in the United States; however, persons can travel to foreign locations to receive injections. Local health departments interviewed the patients, and NYSDOH notified CDC and posted a report on CDC’s Epidemic Information Exchange to solicit additional cases. Clinical and exposure information for each patient was reported to the Robert Koch Institute in Germany, which forwarded the information to local health authorities. A Canada resident who also received live cell therapy in May 2014 was diagnosed with Q fever in July 2014. Clinicians should be aware of health risks, such as Q fever and other zoonotic diseases, among patients with a history of receiving treatment with live cell therapy products. PMID:26421460

  12. Autonomous sensor manager agents (ASMA)

    NASA Astrophysics Data System (ADS)

    Osadciw, Lisa A.

    2004-04-01

    Autonomous sensor manager agents are presented as an algorithm to perform sensor management within a multisensor fusion network. The design of the hybrid ant system/particle swarm agents is described in detail with some insight into their performance. Although the algorithm is designed for the general sensor management problem, a simulation example involving 2 radar systems is presented. Algorithmic parameters are determined by the size of the region covered by the sensor network, the number of sensors, and the number of parameters to be selected. With straight forward modifications, this algorithm can be adapted for most sensor management problems.

  13. An overview of inotropic agents.

    PubMed

    Vroom, Margreeth B

    2006-09-01

    The use of inotropic agents has been surrounded by many controversies. Recent guidelines for the treatment of patients with chronic and acute heart failure have elucidated some of the issues, but many remain. As a result, a substantial variability in the use of agents between institutions and caregivers remains, which mainly results from the lack of uniform data in the literature. Prospective randomized trials with a long-term follow-up and sufficient power are clearly needed, and a number of trials are currently in progress. PMID:16959760

  14. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2013-01-01 2013-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  15. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2012-01-01 2012-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  16. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2014-01-01 2014-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  17. Why Do Extension Agents Resign?

    ERIC Educational Resources Information Center

    Manton, Linda Nunes; van Es, J. C.

    1985-01-01

    Past and current Illinois extension agents were surveyed via mail questionnaires as to reasons for staying or leaving extension programs. Reasons for leaving included family changes, family moves, opportunity to advance, better salary/benefits, dissatisfaction with administration, and too much time away from family. (CT)

  18. Foodborne illness and microbial agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foodborne illnesses result from the consumption of food containing microbial agents such as bacteria, viruses, parasites or food contaminated by poisonous chemicals or bio-toxins. Pathogen proliferation is due to nutrient composition of foods, which are capable of supporting the growth of microorgan...

  19. Superintendents: The Key Influence Agents.

    ERIC Educational Resources Information Center

    Powell, Randy

    1990-01-01

    By the nature of their positions in schools, administrators are either influence agents or targets. Based on personal interviews with 140 Oregon administrators and a survey of 319 administrators around the state, this article highlights administrators' comments about their administrative influence and about constraints on their influence.…

  20. Triggered pore-forming agents

    DOEpatents

    Bayley, H.; Walker, B.J.; Chang, C.Y.; Niblack, B.; Panchal, R.

    1998-07-07

    An inactive pore-forming agent is revealed which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell. 30 figs.

  1. Nucleotide cleaving agents and method

    DOEpatents

    Que, Jr., Lawrence; Hanson, Richard S.; Schnaith, Leah M. T.

    2000-01-01

    The present invention provides a unique series of nucleotide cleaving agents and a method for cleaving a nucleotide sequence, whether single-stranded or double-stranded DNA or RNA, using and a cationic metal complex having at least one polydentate ligand to cleave the nucleotide sequence phosphate backbone to yield a hydroxyl end and a phosphate end.

  2. SEM: A Cultural Change Agent

    ERIC Educational Resources Information Center

    Barnes, Bradley; Bourke, Brian

    2015-01-01

    The authors advance the concept that institutional culture is a purposeful framework by which to view SEM's utility, particularly as a cultural change agent. Through the connection of seemingly independent functions of performance and behavior, implications emerge that deepen the understanding of the influence of culture on performance outcomes…

  3. Direct Vasodilators and Sympatholytic Agents.

    PubMed

    McComb, Meghan N; Chao, James Y; Ng, Tien M H

    2016-01-01

    Direct vasodilators and sympatholytic agents were some of the first antihypertensive medications discovered and utilized in the past century. However, side effect profiles and the advent of newer antihypertensive drug classes have reduced the use of these agents in recent decades. Outcome data and large randomized trials supporting the efficacy of these medications are limited; however, in general the blood pressure-lowering effect of these agents has repeatedly been shown to be comparable to other more contemporary drug classes. Nevertheless, a landmark hypertension trial found a negative outcome with a doxazosin-based regimen compared to a chlorthalidone-based regimen, leading to the removal of α-1 adrenergic receptor blockers as first-line monotherapy from the hypertension guidelines. In contemporary practice, direct vasodilators and sympatholytic agents, particularly hydralazine and clonidine, are often utilized in refractory hypertension. Hydralazine and minoxidil may also be useful alternatives for patients with renal dysfunction, and both hydralazine and methyldopa are considered first line for the treatment of hypertension in pregnancy. Hydralazine has also found widespread use for the treatment of systolic heart failure in combination with isosorbide dinitrate (ISDN). The data to support use of this combination in African Americans with heart failure are particularly robust. Hydralazine with ISDN may also serve as an alternative for patients with an intolerance to angiotensin antagonists. Given these niche indications, vasodilators and sympatholytics are still useful in clinical practice; therefore, it is prudent to understand the existing data regarding efficacy and the safe use of these medications. PMID:26033778

  4. Improving agents using reliable communication

    NASA Astrophysics Data System (ADS)

    Zheng, Jinbin

    2013-10-01

    Recent advances in introspective modalities and linear time symmetries do not necessarily obviate the need for web browsers [1]. In our research, we disprove the exploration of agents, which embodies the appropriate principles of electrical engineering. Here we demonstrate that even though semaphores and XML [1] are mostly incompatible, randomized algorithms and write-back caches are mostly incompatible.

  5. Echographic studies of osmotic agents.

    PubMed

    Vucicevic, Z M; Tark, E; Ahmad, S

    1979-09-01

    The effectiveness of osmotic agents, acetazolamide (Diamox), urea, glycerol, and mannitol, and massages (5 and 10 minutes) for inducing hypotony in rabbit eyes was evaluated by ultrasonography. Mannitol was found to have the greatest hypotonic effect followed closely by urea and glycerol, then acetazolamide. The difference between the 5 and 10 minute massages was negligible. PMID:122221

  6. An Autonomous Spacecraft Agent Prototype

    NASA Technical Reports Server (NTRS)

    Pell, Barney; Bernard, Douglas E.; Chien, Steve A.; Gat, Erann; Muscettola, Nicola; Nayak, P. Pandurang; Wagner, Michael D.; Williams, Brian C.

    1997-01-01

    This paper describes the New Millennium Remote Agent (NMRA) architecture for autonomous spacecraft control systems. This architecture integrates traditional real-time monitoring and control with constraint-based planning and scheduling, robust multi-threaded execution, and model-based diagnosis and reconfiguration.

  7. Limonene and tetrahydrofurfurly alcohol cleaning agent

    SciTech Connect

    Bohnert, George W.; Carter, Richard D.; Hand, Thomas E.; Powers, Michael T.

    1997-10-21

    The present invention is a tetrahydrofurfuryl alcohol and limonene cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  8. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, George W.; Carter, Richard D.; Hand, Thomas E.; Powers, Michael T.

    1996-05-07

    The present invention is a tetrahydrofurfuryl alcohol and limonene or terpineol cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  9. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, G.W.; Carter, R.D.; Hand, T.E.; Powers, M.T.

    1997-10-21

    The present invention is a tetrahydrofurfuryl alcohol and limonene cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  10. Halide test agent replacement study

    SciTech Connect

    Banks, E.M.; Freeman, W.P.; Kovach, B.J.

    1995-02-01

    The intended phaseout of the chlorofluorocarbons (CFCs) from commercial use required the evaluation of substitute materials for the testing for leak paths through both individual adsorbers and installed adsorbent banks. The American Society of Mechanical Engineers (ASME) Committee on Nuclear Air and Gas Treatment (CONAGT) is in charge of maintaining the standards and codes specifying adsorbent leak test methods for the nuclear safety related air cleaning systems. The currently published standards and codes cite the use of R-11, R-12 and R-112 for leak path test agents. All of these compounds are CFCs. There are other agencies and organizations (USDOE, USDOD and USNRC) also specifying testing for leak paths or in some cases for special life tests using the above compounds. The CONAGT has recently developed criteria for the suitability evaluation of substitute test agents. On the basis of these criteria, several compounds were evaluated for their acceptability as adsorbent bed leak and life test agents. The ASME CONAGT Test Agent Qualification Criteria. The test agent qualification is based on the following parameters: (1) Similar retention times on activated carbons at the same concentration levels as one of the following: R-11, R-12, R-112 or R-112a. (2) Similar lower detection limit sensitivity and precision in the concentration range of use as R-11, R-12, R-112 and R-112a. (3) Gives the same in-place leak test results as R-11, R-12, R-112, or R-112a. (4) Chemical and radiological stability under the use conditions. (5) Causes no degradation of the carbon and its impregnant or of the other NATS components under the use conditions. (6) Is listed in the USEPA Toxic Substances Control Act (TSCA) inventory for commercial use.

  11. Biologic agents in juvenile spondyloarthropathies.

    PubMed

    Katsicas, María Martha; Russo, Ricardo

    2016-01-01

    The juvenile spondyloarthropathies (JSpA) are a group of related rheumatic diseases characterized by involvement of peripheral large joints, axial joints, and entheses (enthesitis) that begin in the early years of life (prior to 16(th) birthday).The nomenclature and concept of spondyloarthropathies has changed during the last few decades. Although there is not any specific classification of JSpA, diseases under the spondyloarthropathy nomenclature umbrella in the younger patients include: the seronegative enthesitis and arthropathy (SEA) syndrome, juvenile ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease-associated arthritis. Moreover, the ILAR criteria for Juvenile Idiopathic Arthritis includes two categories closely related to spondyloarthritis: Enthesitis-related arthritis and psoriatic arthritis.We review the pathophysiology and the use of biological agents in JSpA. JSpA are idiopathic inflammatory diseases driven by an altered balance in the proinflammatory cytokines. There is ample evidence on the role of tumor necrosis factor (TNF) and interleukin-17 in the physiopathology of these entities. Several non-biologic and biologic agents have been used with conflicting results in the treatment of these complex diseases. The efficacy and safety of anti-TNF agents, such as etanercept, infliximab and adalimumab, have been analysed in controlled and uncontrolled trials, usually showing satisfactory outcomes. Other biologic agents, such as abatacept, tocilizumab and rituximab, have been insufficiently studied and their role in the therapy of SpA is uncertain. Interleukin-17-blocking agents are promising alternatives for the treatment of JSpA patients in the near future. Recommendations for the treatment of patients with JSpA have recently been proposed and are discussed in the present review. PMID:26968522

  12. Laser interrogation of surface agents (LISA) for chemical agent reconnaissance

    NASA Astrophysics Data System (ADS)

    Higdon, N. S.; Chyba, Thomas H.; Richter, Dale A.; Ponsardin, Patrick L.; Armstrong, Wayne T.; Lobb, C. T.; Kelly, Brian T.; Babnick, Robert D.; Sedlacek, Arthur J., III

    2002-06-01

    Laser Interrogation of Surface Agents (LISA) is a new technique which exploits Raman scattering to provide standoff detection and identification of surface-deposited chemical agents. ITT Industries, Advanced Engineering and Sciences Division is developing the LISA technology under a cost-sharing arrangement with the US Army Soldier and Biological Chemical Command for incorporation on the Army's future reconnaissance vehicles. A field-engineered prototype LISA-Recon system is being designed to demonstrate on-the- move measurements of chemical contaminants. In this article, we will describe the LISA technique, data form proof-of- concept measurements, the LISA-Recon design, and some of the future realizations envisioned for military sensing applications.

  13. The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development

    ERIC Educational Resources Information Center

    Baker, Lauri M.; Hadley, Gregg

    2014-01-01

    The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…

  14. Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

    NASA Technical Reports Server (NTRS)

    Andrews, R. J.

    1999-01-01

    The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved

  15. Comparative Genomics Reveal Extensive Transposon-Mediated Genomic Plasticity and Diversity among Potential Effector Proteins within the Genus Coxiella▿ †

    PubMed Central

    Beare, Paul A.; Unsworth, Nathan; Andoh, Masako; Voth, Daniel E.; Omsland, Anders; Gilk, Stacey D.; Williams, Kelly P.; Sobral, Bruno W.; Kupko, John J.; Porcella, Stephen F.; Samuel, James E.; Heinzen, Robert A.

    2009-01-01

    Genetically distinct isolates of Coxiella burnetii, the cause of human Q fever, display different phenotypes with respect to in vitro infectivity/cytopathology and pathogenicity for laboratory animals. Moreover, correlations between C. burnetii genomic groups and human disease presentation (acute versus chronic) have been described, suggesting that isolates have distinct virulence characteristics. To provide a more-complete understanding of C. burnetii's genetic diversity, evolution, and pathogenic potential, we deciphered the whole-genome sequences of the K (Q154) and G (Q212) human chronic endocarditis isolates and the naturally attenuated Dugway (5J108-111) rodent isolate. Cross-genome comparisons that included the previously sequenced Nine Mile (NM) reference isolate (RSA493) revealed both novel gene content and disparate collections of pseudogenes that may contribute to isolate virulence and other phenotypes. While C. burnetii genomes are highly syntenous, recombination between abundant insertion sequence (IS) elements has resulted in genome plasticity manifested as chromosomal rearrangement of syntenic blocks and DNA insertions/deletions. The numerous IS elements, genomic rearrangements, and pseudogenes of C. burnetii isolates are consistent with genome structures of other bacterial pathogens that have recently emerged from nonpathogens with expanded niches. The observation that the attenuated Dugway isolate has the largest genome with the fewest pseudogenes and IS elements suggests that this isolate's lineage is at an earlier stage of pathoadaptation than the NM, K, and G lineages. PMID:19047403

  16. CATS-based Agents That Err

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.

    2002-01-01

    This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

  17. Software agents in molecular computational biology.

    PubMed

    Keele, John W; Wray, James E

    2005-12-01

    Progress made in applying agent systems to molecular computational biology is reviewed and strategies by which to exploit agent technology to greater advantage are investigated. Communities of software agents could play an important role in helping genome scientists design reagents for future research. The advent of genome sequencing in cattle and swine increases the complexity of data analysis required to conduct research in livestock genomics. Databases are always expanding and semantic differences among data are common. Agent platforms have been developed to deal with generic issues such as agent communication, life cycle management and advertisement of services (white and yellow pages). This frees computational biologists from the drudgery of having to re-invent the wheel on these common chores, giving them more time to focus on biology and bioinformatics. Agent platforms that comply with the Foundation for Intelligent Physical Agents (FIPA) standards are able to interoperate. In other words, agents developed on different platforms can communicate and cooperate with one another if domain-specific higher-level communication protocol details are agreed upon between different agent developers. Many software agent platforms are peer-to-peer, which means that even if some of the agents and data repositories are temporarily unavailable, a subset of the goals of the system can still be met. Past use of software agents in bioinformatics indicates that an agent approach should prove fruitful. Examination of current problems in bioinformatics indicates that existing agent platforms should be adaptable to novel situations. PMID:16420735

  18. [Alternative agents used in ADHD].

    PubMed

    Hässler, Frank; Dück, Alexander; Reis, Olaf; Buchmann, Johannes

    2009-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is, with a prevalence of 2% to 6%, one of the most common neurobehavioral disorder affecting children and adolescents, persisting into adulthood. Comorbidity and psychosocial circumstances enter into the choice of intervention strategies. Several agents have been demonstrated effective in treating individuals with ADHD. Direct or indirect attenuation of dopamine and norepinephrine neurotransmission appears closely related to both the stimulant and nonstimulant medications efficacious in ADHD. However, important differences concerning efficacy and side effects exist both between and with the specific classes of agents like neuroleptics, antidepressants, antiepileptics, alpha-agonists, beta-blockers, buspiron, l-dopa, melatonin, pycnogenol, zinc, magnesium, polyunsaturated fatty acids, and homeopathy. Elucidating the various mechanisms of action of ADHD medications may lead to better choices in matching potential responses to the characteristics of individuals. We review the purported mechanism of action and available evidence for selected complementary and alternative medicine therapies for ADHD in childhood and adolescence. PMID:19105161

  19. [Infectious agents and autoimmune diseases].

    PubMed

    Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R

    1992-01-01

    In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352

  20. Oral agents in multiple sclerosis.

    PubMed

    Lorefice, L; Fenu, G; Frau, J; Coghe, G C; Marrosu, M G; Cocco, E

    2015-01-01

    Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS. PMID:25924620

  1. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  2. Injectable agents affecting subcutaneous fats.

    PubMed

    Chen, David Lk; Cohen, Joel L; Green, Jeremy B

    2015-09-01

    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. PMID:26566569

  3. Agent planning in AgScala

    NASA Astrophysics Data System (ADS)

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

    2013-10-01

    Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

  4. New therapeutic agents for acromegaly.

    PubMed

    Melmed, Shlomo

    2016-02-01

    The currently available somatostatin receptor ligands (SRLs) and growth hormone (GH) antagonists are used to control levels of GH and insulin-like growth factor 1 (IGF-1) in patients with acromegaly. However, these therapies are limited by wide variations in efficacy, associated adverse effects and the need for frequent injections. A phase III trial of oral octreotide capsules demonstrated that this treatment can safely sustain suppressed levels of GH and IGF-1 and reduce the severity of symptoms in patients with acromegaly previously controlled by injectable SRL therapy, with the added benefit of no injection-site reactions. Phase I and phase II trials of the pan-selective SRL DG3173, the liquid crystal octreotide depot CAM2029 and an antisense oligonucleotide directed against the GH receptor have shown that these agents can be used to achieve biochemical suppression in acromegaly and have favourable safety profiles. This Review outlines the need for new therapeutic agents for patients with acromegaly, reviews clinical trial data of investigational agents and considers how these therapies might best be integrated into clinical practice. PMID:26610414

  5. Chemotherapy and Dietary Phytochemical Agents

    PubMed Central

    Sak, Katrin

    2012-01-01

    Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way. PMID:23320169

  6. Pharmacologic Agents for Chronic Diarrhea

    PubMed Central

    2015-01-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  7. Multi-agent autonomous system

    NASA Technical Reports Server (NTRS)

    Fink, Wolfgang (Inventor); Dohm, James (Inventor); Tarbell, Mark A. (Inventor)

    2010-01-01

    A multi-agent autonomous system for exploration of hazardous or inaccessible locations. The multi-agent autonomous system includes simple surface-based agents or craft controlled by an airborne tracking and command system. The airborne tracking and command system includes an instrument suite used to image an operational area and any craft deployed within the operational area. The image data is used to identify the craft, targets for exploration, and obstacles in the operational area. The tracking and command system determines paths for the surface-based craft using the identified targets and obstacles and commands the craft using simple movement commands to move through the operational area to the targets while avoiding the obstacles. Each craft includes its own instrument suite to collect information about the operational area that is transmitted back to the tracking and command system. The tracking and command system may be further coupled to a satellite system to provide additional image information about the operational area and provide operational and location commands to the tracking and command system.

  8. Pharmacologic Agents for Chronic Diarrhea.

    PubMed

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  9. Chelating agents and cadmium intoxication

    SciTech Connect

    Shinobu, L.A.

    1985-01-01

    A wide range of conventional chelating agents have been screened for (a) antidotal activity in acute cadmium poisoning and (b) ability to reduce aged liver and kidney deposits of cadmium. Chelating agents belonging to the dithiocarbamate class have been synthesized and tested in both the acute and chronic modes of cadmium intoxication. Several dithiocarbamates, not only provide antidotal rescue, but also substantially decrease the intracellular deposits of cadmium associated with chronic cadmium intoxication. Fractionating the cytosol from the livers and kidneys of control and treated animals by Sephadex G-25 gel filtration clearly demonstrates that the dithiocarbamates are reducing the level of metallothionein-bound cadmium. However, the results of cell culture (Ehrlich ascites) studies designed to investigate the removal of cadmium from metallothionein and subsequent transport of the resultant cadmium complex across the cell membrane were inconclusive. In other in vitro investigations, the interaction between isolated native Cd, Zn-metallothionein and several chelating agents was explored. Ultracentrifugation, equilibrium dialysis, and Sephadex G-25 gel filtration studies have been carried out in an attempt to determine the rate of removal of cadmium from metallothionein by these small molecules. Chemical shifts for the relevant cadmium-dithiocarbamate complexes have been determined using natural abundance Cd-NMR.

  10. Chemopreventive Agent Development | Division of Cancer Prevention

    Cancer.gov

    This group promotes and supports research on early chemopreventive agent development, from preclinical studies to phas | Research on early chemopreventive agent development, from preclinical studies to phase I clinical trials.

  11. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  12. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  13. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  14. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  15. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  16. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  17. Intelligent Agent Architectures: Reactive Planning Testbed

    NASA Technical Reports Server (NTRS)

    Rosenschein, Stanley J.; Kahn, Philip

    1993-01-01

    An Integrated Agent Architecture (IAA) is a framework or paradigm for constructing intelligent agents. Intelligent agents are collections of sensors, computers, and effectors that interact with their environments in real time in goal-directed ways. Because of the complexity involved in designing intelligent agents, it has been found useful to approach the construction of agents with some organizing principle, theory, or paradigm that gives shape to the agent's components and structures their relationships. Given the wide variety of approaches being taken in the field, the question naturally arises: Is there a way to compare and evaluate these approaches? The purpose of the present work is to develop common benchmark tasks and evaluation metrics to which intelligent agents, including complex robotic agents, constructed using various architectural approaches can be subjected.

  18. Security Measures to Protect Mobile Agents

    NASA Astrophysics Data System (ADS)

    Dadhich, Piyanka; Govil, M. C.; Dutta, Kamlesh

    2010-11-01

    The security issues of mobile agent systems have embarrassed its widespread implementation. Mobile agents that move around the network are not safe because the remote hosts that accommodate the agents initiates all kinds of attacks. These hosts try to analyze the agent's decision logic and their accumulated data. So, mobile agent security is the most challenging unsolved problems. The paper analyzes various security measures deeply. Security especially the attacks performed by hosts to the visiting mobile agent (the malicious hosts problem) is a major obstacle that prevents mobile agent technology from being widely adopted. Being the running environment for mobile agent, the host has full control over them and could easily perform many kinds of attacks against them.

  19. Intelligent Agents as Cognitive Tools for Education.

    ERIC Educational Resources Information Center

    Baylor, Amy

    1999-01-01

    Examines the educational potential for intelligent agents as cognitive tools. Discusses the role of intelligent agents: managing large amounts of information (information overload), serving as a pedagogical expert, and creating programming environments for the learner. (AEF)

  20. Learning other agents` preferences in multiagent negotiation

    SciTech Connect

    Bui, H.H.; Kieronska, D.; Venkatesh, S.

    1996-12-31

    In multiagent systems, an agent does not usually have complete information about the preferences and decision making processes of other agents. This might prevent the agents from making coordinated choices, purely due to their ignorance of what others want. This paper describes the integration of a learning module into a communication-intensive negotiating agent architecture. The learning module gives the agents the ability to learn about other agents` preferences via past interactions. Over time, the agents can incrementally update their models of other agents` preferences and use them to make better coordinated decisions. Combining both communication and learning, as two complement knowledge acquisition methods, helps to reduce the amount of communication needed on average, and is justified in situations where communication is computationally costly or simply not desirable (e.g. to preserve the individual privacy).

  1. Extinguishing agent for combustible metal fires

    DOEpatents

    Riley, John F.; Stauffer, Edgar Eugene

    1976-10-12

    A low chloride extinguishing agent for combustible metal fires comprising from substantially 75 to substantially 94 weight percent of sodium carbonate as the basic fire extinguishing material, from substantially 1 to substantially 5 weight percent of a water-repellent agent such as a metal stearate, from substantially 2 to substantially 10 weight percent of a flow promoting agent such as attapulgus clay, and from substantially 3 to substantially 15 weight percent of a polyamide resin as a crusting agent.

  2. 14 CFR 221.11 - Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Agent. 221.11 Section 221.11 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Who is Authorized To Issue and File Tariffs § 221.11 Agent. An agent may issue and...

  3. STUDIES OF WATERBORNE AGENTS OF VIRAL GASTROENTERITIS

    EPA Science Inventory

    The etiologic agent of a large outbreak of waterborne viral gastroenteritis was detected employing immune electron microscopy (IEM) and a newly developed solid phase radioimmunoassay (RIA). This agent, referred to as the Snow Mountain Agent (SMA), is 27-32 nm. in diameter, has cu...

  4. Agent-based modeling of complex infrastructures

    SciTech Connect

    North, M. J.

    2001-06-01

    Complex Adaptive Systems (CAS) can be applied to investigate complex infrastructures and infrastructure interdependencies. The CAS model agents within the Spot Market Agent Research Tool (SMART) and Flexible Agent Simulation Toolkit (FAST) allow investigation of the electric power infrastructure, the natural gas infrastructure and their interdependencies.

  5. 24 CFR 232.1011 - Management agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Management agents. 232.1011 Section... Management agents. (a) An operator or borrower may, with the prior written approval of HUD, execute a management agent agreement setting forth the duties and procedures for matters related to the management...

  6. 24 CFR 232.1011 - Management agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Management agents. 232.1011 Section... Management agents. (a) An operator or borrower may, with the prior written approval of HUD, execute a management agent agreement setting forth the duties and procedures for matters related to the management...

  7. 46 CFR 153.1106 - Cleaning agents.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cleaning agents. 153.1106 Section 153.1106 Shipping... Handling of Categories A, B, C, and D Cargo and Nls Residue § 153.1106 Cleaning agents. No tank cleaning agent other than water or steam may be used to clean an NLS residue from a cargo tank except...

  8. Online Deception Detection Using BDI Agents

    ERIC Educational Resources Information Center

    Merritts, Richard A.

    2013-01-01

    This research has two facets within separate research areas. The research area of Belief, Desire and Intention (BDI) agent capability development was extended. Deception detection research has been advanced with the development of automation using BDI agents. BDI agents performed tasks automatically and autonomously. This study used these…

  9. The Ontogenesis of Agent: Linguistic Expression.

    ERIC Educational Resources Information Center

    Olswang, Lesley Barrett; Carpenter, Robert L.

    1982-01-01

    Some of the findings of a longitudinal study of three infants between their 11th and 22nd months to document development of linguistic expression of the agent concept indicated that first vocalizations were inconsistently associated with nonverbal agentive behaviors and later mature utterances coded agent-action-recipient events. (MC)

  10. Infants Attribute to Agents Goals and Dispositions

    ERIC Educational Resources Information Center

    Luo, Yuyan; Choi, You-jung

    2012-01-01

    This commentary article is to be published alongside: Hernik, M., & Southgate, V. (2012). What do infants know about agents' goals? The authors see this issue consisting of two closely related questions. First, what is an agent to infants? Second, how do infants attribute goals to agents? Hernik and Southgage (H&S) focused on the second question.…

  11. Construction and Evaluation of Animated Teachable Agents

    ERIC Educational Resources Information Center

    Bodenheimer, Bobby; Williams, Betsy; Kramer, Mattie Ruth; Viswanath, Karun; Balachandran, Ramya; Belynne, Kadira; Biswas, Gautam

    2009-01-01

    This article describes the design decisions, technical approach, and evaluation of the animation and interface components for an agent-based system that allows learners to learn by teaching. Students learn by teaching an animated agent using a visual representation. The agent can answer questions about what she has been taught and take quizzes.…

  12. Hydroxypyridonate chelating agents and synthesis thereof

    DOEpatents

    Raymond, K.N.; Scarrow, R.C.; White, D.L.

    1985-11-12

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

  13. Honey - A Novel Antidiabetic Agent

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd S. Ab

    2012-01-01

    Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects. PMID:22811614

  14. Copper complexes as anticancer agents.

    PubMed

    Marzano, Cristina; Pellei, Maura; Tisato, Francesco; Santini, Carlo

    2009-02-01

    Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field. PMID:19199864

  15. Pathogenic agents in freshwater resources

    NASA Astrophysics Data System (ADS)

    Geldreich, Edwin E.

    1996-02-01

    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  16. Anticancer agents from marine sponges.

    PubMed

    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics. PMID:25402340

  17. Fluorescent whitening agents in detergents.

    PubMed

    Eckhardt, C; von Rütte, R

    1975-01-01

    Washing is a form of textile care which is characterized by its repetitive nature. Washing methods vary enormously in different parts of the world. The main types of detergents and fluorescent whitening agents (FWAs) are described. Washing slows down the deterioration in use of white goods, and yellowing is counteracted by FWAs. FWAs also enhance the freshness and brightness of most pale shades. Cost calculations show clearly the economic advantages of using FWAs in washing: the useful life of textiles can be prolonged considerably for a very small additional cost. PMID:1064549

  18. Method For Detecting Biological Agents

    DOEpatents

    Chen, Liaohai; McBranch, Duncan W.; Wang, Hsing-Lin; Whitten, David G.

    2005-12-27

    A sensor is provided including a polymer capable of having an alterable measurable property from the group of luminescence and electrical conductivity, the polymer having an intermediate combination of a recognition element, a tethering element and a property-altering element bound thereto and capable of altering the measurable property, the intermediate combination adapted for subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the intermediate combination from the polymer results in a detectable change in the alterable measurable property, and, detecting said detectable change in the alterable measurable property.

  19. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century.

    PubMed

    Rolain, Jean-Marc; Colson, Philippe; Raoult, Didier

    2007-10-01

    Chloroquine (CQ) and its hydroxyl analogue hydroxychloroquine (HCQ) are weak bases with a half-century long use as antimalarial agents. Apart from this antimalarial activity, CQ and HCQ have gained interest in the field of other infectious diseases. One of the most interesting mechanisms of action is that CQ leads to alkalinisation of acid vesicles that inhibit the growth of several intracellular bacteria and fungi. The proof of concept of this effect was first used to restore intracellular pH allowing antibiotic efficacy for Coxiella burnetii, the agent of Q fever, and doxycycline plus HCQ is now the reference treatment for chronic Q fever. There is also strong evidence of a similar effect in vitro against Tropheryma whipplei, the agent of Whipple's disease, and a clinical trial is in progress. Other bacteria and fungi multiply in an acidic environment and encouraging in vitro data suggest that this concept may be generalised for all intracellular organisms that multiply in an acidic environment. For viruses, CQ led to inhibition of uncoating and/or alteration of post-translational modifications of newly synthesised proteins, especially inhibition of glycosylation. These effects have been well described in vitro for many viruses, with human immunodeficiency virus (HIV) being the most studied. Preliminary in vivo clinical trials suggest that CQ alone or in combination with antiretroviral drugs might represent an interesting way to treat HIV infection. In conclusion, our review re-emphasises the paradigm that activities mediated by lysosomotropic agents may offer an interesting weapon to face present and future infectious diseases worldwide. PMID:17629679

  20. Mobile agent location in distributed environments

    NASA Astrophysics Data System (ADS)

    Fountoukis, S. G.; Argyropoulos, I. P.

    2012-12-01

    An agent is a small program acting on behalf of a user or an application which plays the role of a user. Artificial intelligence can be encapsulated in agents so that they can be capable of both behaving autonomously and showing an elementary decision ability regarding movement and some specific actions. Therefore they are often called autonomous mobile agents. In a distributed system, they can move themselves from one processing node to another through the interconnecting network infrastructure. Their purpose is to collect useful information and to carry it back to their user. Also, agents are used to start, monitor and stop processes running on the individual interconnected processing nodes of computer cluster systems. An agent has a unique id to discriminate itself from other agents and a current position. The position can be expressed as the address of the processing node which currently hosts the agent. Very often, it is necessary for a user, a processing node or another agent to know the current position of an agent in a distributed system. Several procedures and algorithms have been proposed for the purpose of position location of mobile agents. The most basic of all employs a fixed computing node, which acts as agent position repository, receiving messages from all the moving agents and keeping records of their current positions. The fixed node, responds to position queries and informs users, other nodes and other agents about the position of an agent. Herein, a model is proposed that considers pairs and triples of agents instead of single ones. A location method, which is investigated in this paper, attempts to exploit this model.

  1. Triazole: A Promising Antitubercular Agent.

    PubMed

    Keri, Rangappa S; Patil, Siddappa A; Budagumpi, Srinivasa; Nagaraja, Bhari Mallanna

    2015-10-01

    Tuberculosis is a contagious disease with comparatively high mortality worldwide. The statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. Therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. The literature reveals that, heterocyclic moieties have drawn attention of the chemists, pharmacologists, microbiologists, and other researchers owing to its indomitable biological potential as anti-infective agents. Among heterocyclic compounds, triazole (1,2,3-triazole/1,2,4-triazole) nucleus is one of the most important and well-known heterocycles, which is a common and integral feature of a variety of natural products and medicinal agents. Triazole core is considered as a privileged structure in medicinal chemistry and is widely used as 'parental' compounds to synthesize molecules with medical benefits, especially with infection-related activities. In the present review, we have collated published reports on this versatile core to provide an insight so that its complete therapeutic potential can be utilized for the treatment of tuberculosis. This review also explores triazole as a potential targeted core moiety against tuberculosis and various research ongoing worldwide. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic triazole-based antituberculosis drugs. PMID:25643871

  2. Chemopreventive agents targeting tumor microenvironment.

    PubMed

    Sharma, Sharada H; Thulasingam, Senthilkumar; Nagarajan, Sangeetha

    2016-01-15

    Recent studies have shown that tumor development and progression depend not only on the perturbed genes that govern cell proliferation, but is also highly determined by the non-tumor cells of the stromal compartment surrounding the tumor called tumor microenvironment (TME). These findings highlight the importance of targeting the microenvironment in combination with therapies aimed at tumor cells as a valuable approach. The innate and adaptive immune cells in the TME interact among themselves and also with the endothelial cells, pericytes and mast cells of the stromal compartment through various autocrine and paracrine manner to regulate abnormal cell proliferation. Direct cytotoxic killing of cancer cells and/or reversion of the immunosuppressive TME are to be considered as better strategies for chemoprevention and chemotherapy. With a growing emphasis on a "hallmark targeting" strategy for cancer therapy, the TME now appears as a promising target for cancer prevention using natural products. Clarification on the nontumor stromal cells, the mediators involved, interactions with immune response cells, and immune-evasive mechanisms are needed in order to manipulate the characteristics of the TME by natural pharmacological agents to design effective therapies. This review will provide a glimpse on the roles played by various non-tumor cells in tumor progression and their intervention by pharmacological agents. PMID:26679106

  3. A Review of Luting Agents

    PubMed Central

    Pameijer, Cornelis H.

    2012-01-01

    Due to the availability of a large number of luting agents (dental cements) proper selection can be a daunting task and is usually based on a practitioner's reliance on experience and preference and less on in depth knowledge of materials that are used for the restoration and luting agent properties. This review aims at presenting an overview of current cements and discusses physical properties, biocompatibility and other properties that make a particular cement the preferred choice depending on the clinical indication. Tables are provided that outline the different properties of the generic classification of cements. It should be noted that no recommendations are made to use a particular commercial cement for a hypothetical clinical situation. The choice is solely the responsibility of the practitioner. The appendix is intended as a guide for the practitioner towards a recommended choice under commonly encountered clinical scenarios. Again, no commercial brands are recommended although the author recognizes that some have better properties than others. Please note that this flowchart strictly presents the author's opinion and is based on research, clinical experience and the literature. PMID:22505909

  4. Nanoparticle-based theranostic agents

    PubMed Central

    Xie, Jin; Lee, Seulki; Chen, Xiaoyuan

    2010-01-01

    Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology. PMID:20691229

  5. Innovative Agents in Multiple Myeloma

    PubMed Central

    Faiman, Beth; Richards, Tiffany

    2014-01-01

    Multiple myeloma (MM) remains an incurable cancer of the bone marrow plasma cells. However, the overall survival of patients with MM has increased dramatically within the past decade. This is due, in part, to newer agents such as immunomodulatory drugs (lenalidomide, thalidomide, and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, MLN9708). These and several other new classes of drugs have arisen from an improved understanding of the complex environment in which genetic changes occur. Improved understanding of genetic events will enable clinicians to better stratify risk before and during therapy, tailor treatment, and test the value of personalized interventions. The ultimate goal in this incurable disease setting is to reduce the impact of cancer- or chemotherapy-related side effects. Nurses and advanced practitioners are integral to the treatment team. Thus, each should be aware of changes to the current drug landscape. Targeted drugs with sophisticated mechanisms of action are currently under investigation. Patients gain access to newer drugs within the context of clinical trials. Awareness of such trials will help accrual and determine if therapeutic benefit exists. In this article, we will describe new agents with unique and targeted mechanisms of action that have activity in patients with relapsed and/or refractory multiple myeloma. PMID:25089218

  6. Surfactants as blackbird stressing agents

    USGS Publications Warehouse

    Lefebvre, P.W.; Seubert, J.L.

    1970-01-01

    Applications of wetting-agent solutions produce mortality in birds. The exact cause of death is undetermined but it is believed that destruction of the insulating qualities of the plumage permits ambient cold temperatures and evaporation to lower the body temperature to a lethal level. The original concept of using these materials as bird-control tools was developed in 1958 at the Patuxent Wildlife Research Center, Bureau of Sport Fisheries and Wildlife Laurel, Maryland. Early field trials by personnel of the Division of Wildlife Services and the Denver Wildlife Research Center indicated that ground-application techniques had promise but limitations of the equipment precluded successful large-scale roost treatments. In 1966, Patuxent Center personnel began using tanker-type aircraft to evaluate high-volume aerial applications of wetting agents. The success of these tests led to the use of small aircraft to make low-volume, high-concentration aerial applications just prior to expected rainfall. Recent trials of the low-volume method show that, with some limitations, it is effective, inexpensive, and safe to the environment. Current research emphasizes the screening of new candidate materials for efficacy, biodegradability, and toxicity to plants and non-target animals, as well as basic investigations of the avian physiological mechanisms involved. Field trials to develop more effective application techniques will continue.

  7. Electric power market agent design

    NASA Astrophysics Data System (ADS)

    Oh, Hyungseon

    The electric power industry in many countries has been restructured in the hope of a more economically efficient system. In the restructured system, traditional operating and planning tools based on true marginal cost do not perform well since information required is strictly confidential. For developing a new tool, it is necessary to understand offer behavior. The main objective of this study is to create a new tool for power system planning. For the purpose, this dissertation develops models for a market and market participants. A new model is developed in this work for explaining a supply-side offer curve, and several variables are introduced to characterize the curve. Demand is estimated using a neural network, and a numerical optimization process is used to determine the values of the variables that maximize the profit of the agent. The amount of data required for the optimization is chosen with the aid of nonlinear dynamics. To suggest an optimal demand-side bidding function, two optimization problems are constructed and solved for maximizing consumer satisfaction based on the properties of two different types of demands: price-based demand and must-be-served demand. Several different simulations are performed to test how an agent reacts in various situations. The offer behavior depends on locational benefit as well as the offer strategies of competitors.

  8. Camouflaging Agents for Vitiligo Patients.

    PubMed

    Hossain, Claudia; Porto, Dennis A; Hamzavi, Iltefat; Lim, Henry W

    2016-04-01

    Vitiligo is an acquired condition resulting in patches of depigmented skin that is cosmetically disfiguring and can subsequently be psychologically disturbing. For patients seeking to mask their vitiligo, camouflage options have historically been limited and been designated as a cosmetic, rather than a medical, concern. As research has indicated that proper concealment of vitiligo lesions can vastly improve quality of life, we believe it is essential that dermatologists become aware of all the options available to their patients and that discussions of camouflage options be broached from the first visit. Methods for concealment include cosmetic tattoos, dihydroxyacetone, general cosmetics, and various topical camouflage agents, including the newest product, Microskin™. We conducted a literature review of all of the available options for vitiligo concealment and evaluated their advantages and disadvantages. Ultimately, temporary methods of concealment are recommended; but the particular agent used can come from discussion with the patient based on the location of the lesions, degree of concealment desired, cost, and availability. PMID:27050692

  9. Anchor Toolkit - a secure mobile agent system

    SciTech Connect

    Mudumbai, Srilekha S.; Johnston, William; Essiari, Abdelilah

    1999-05-19

    Mobile agent technology facilitates intelligent operation insoftware systems with less human interaction. Major challenge todeployment of mobile agents include secure transmission of agents andpreventing unauthorized access to resources between interacting systems,as either hosts, or agents, or both can act maliciously. The Anchortoolkit, designed by LBNL, handles the transmission and secure managementof mobile agents in a heterogeneous distributed computing environment. Itprovides users with the option of incorporating their security managers.This paper concentrates on the architecture, features, access control anddeployment of Anchor toolkit. Application of this toolkit in a securedistributed CVS environment is discussed as a case study.

  10. SAF1. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, S.Y

    1997-06-01

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  11. Nerve agents: implications for anesthesia providers.

    PubMed

    Hrobak, Paula Kay

    2008-04-01

    Anesthesia providers may be called to treat injuries from chemical weapons or spills, for which prompt treatment is vital. It is therefore important to understand the mechanism of action of nerve agents and the resultant pathophysiology and to be able to quickly recognize the signs and symptoms of nerve agent exposure. This review article addresses the different types of nerve agents that are currently being manufactured as well as the symptomatic and definitive treatment of the patient who presents with acute nerve agent toxicity. This article also reviews the physiology of the neuromuscular junction and the autonomic nervous system receptors that nerve agent toxicity affects. PMID:18478812

  12. Reversal agents in anaesthesia and critical care

    PubMed Central

    Pani, Nibedita; Dongare, Pradeep A; Mishra, Rajeeb Kumar

    2015-01-01

    Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice. PMID:26644615

  13. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the Department authorized to serve as passport...

  14. 30 CFR 250.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false How do I designate an agent or a local agent? 250.145 Section 250.145 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND... SHELF General Special Types of Approvals § 250.145 How do I designate an agent or a local agent? (a)...

  15. Mother ship and physical agents collaboration

    NASA Astrophysics Data System (ADS)

    Young, Stuart H.; Budulas, Peter P.; Emmerman, Philip J.

    1999-07-01

    This paper discusses ongoing research at the U.S. Army Research Laboratory that investigates the feasibility of developing a collaboration architecture between small physical agents and a mother ship. This incudes the distribution of planning, perception, mobility, processing and communications requirements between the mother ship and the agents. Small physical agents of the future will be virtually everywhere on the battlefield of the 21st century. A mother ship that is coupled to a team of small collaborating physical agents (conducting tasks such as Reconnaissance, Surveillance, and Target Acquisition (RSTA); logistics; sentry; and communications relay) will be used to build a completely effective and mission capable intelligent system. The mother ship must have long-range mobility to deploy the small, highly maneuverable agents that will operate in urban environments and more localized areas, and act as a logistics base for the smaller agents. The mother ship also establishes a robust communications network between the agents and is the primary information disseminating and receiving point to the external world. Because of its global knowledge and processing power, the mother ship does the high-level control and planning for the collaborative physical agents. This high level control and interaction between the mother ship and its agents (including inter agent collaboration) will be software agent architecture based. The mother ship incorporates multi-resolution battlefield visualization and analysis technology, which aids in mission planning and sensor fusion.

  16. Intelligent agent support for automated radiology exam

    NASA Astrophysics Data System (ADS)

    Shang, Yi; Popescu, Mihail

    2000-10-01

    A difficult problem in automatic medical image understanding is that for every image type such as x-ray and every body organ such as heart, there exist specific solutions that do not allow for generalization. Just collecting all the specific solutions will not achieve the vision of a computerized physician. To address this problem, we propose an intelligent agent approach that is based on agent-oriented programming is that it combines the benefits of object-oriented programming and expert system. For radiology image understanding, we present a multi- agent system that is composed of two major types of intelligent agents: radiologist agents and patient agents. A patient agent asks for multiple opinions from radiologists agents in interpreting a given set of images and then integrates the opinions. A radiologist agent decomposes the image recognition task into smaller problems that are solved collectively by multiple intelligent sub-agents. Finally, we present a preliminary implementation and running examples of the multi-agent system.

  17. Knowledge Management in Role Based Agents

    NASA Astrophysics Data System (ADS)

    Kır, Hüseyin; Ekinci, Erdem Eser; Dikenelli, Oguz

    In multi-agent system literature, the role concept is getting increasingly researched to provide an abstraction to scope beliefs, norms, goals of agents and to shape relationships of the agents in the organization. In this research, we propose a knowledgebase architecture to increase applicability of roles in MAS domain by drawing inspiration from the self concept in the role theory of sociology. The proposed knowledgebase architecture has granulated structure that is dynamically organized according to the agent's identification in a social environment. Thanks to this dynamic structure, agents are enabled to work on consistent knowledge in spite of inevitable conflicts between roles and the agent. The knowledgebase architecture is also implemented and incorporated into the SEAGENT multi-agent system development framework.

  18. Other potentially useful new injectable anesthetic agents.

    PubMed

    Ilkiw, J E

    1992-03-01

    Ultrashort barbiturates are not ideal injectable anesthetic agents, and new agents continue to be released as investigators pursue the goal of finding a more ideal agent. Of the new injectable agents discussed, propofol seems to be the most promising drug. Propofol should find a place in veterinary practice as an outpatient anesthetic agent because it has a rapid, smooth, and complete recovery even after repeated or continuous administration. Midazolam does not induce anesthesia in healthy, small animals and, as such, can only be used in combination with other injectable agents, such as ketamine or the thiobarbiturates. In our practice, Telazol has found a place in the anesthetic management of feral cats and aggressive dogs, where it is used for heavy sedation or to induce anesthesia. The role of flumazenil, as a reversal agent, in veterinary practice remains to be determined; however, the role in small domestic animals is unlikely to be significant. PMID:1585555

  19. Drug therapy reviews: antirheumatic agents.

    PubMed

    Evens, R P

    1979-05-01

    The pathophysiology, symptoms and drug treatment of rheumatic disease are reviewed. Antirheumatic drugs reviewed are salicylates (including aspirin, sodium salicylate, choline salicylate, choline magnesium salicylate, salsalate), phenylpropionic acid derivatives (fenoprofen, ibuprofen, naproxen), indole derivatives (sulindac, tolmetin and indomethacin), pyrazolone derivatives (phenylbutazone, oxyphenbutazone), gold compounds, penicillamine, antimalarials mefenamic acid, corticosteroids and immunosuppressives. Simple analgesic therapy (acetaminophen, aspirin, propoxyphene) is used in the early stage of the disease. As the disease progresses, aspirin remains the drug of choice for antiinflammatory activity but the phenylpropionic acid or indole derivatives may be preferred in patients unable to tolerate salicylates. If such nonsteroidal antiinflammatory agents are not effective, parenteral therapy with gold compounds or oral penicillamine usually is indicated. Indomethacin or phenylbutazone, then antimalarials, are resorted to next. Corticosteroids or immunosuppressives are reserved for patients who are unsuccessfully controlled or who have major side effects with the other drugs. Mefenamic acid occupies a very secondary place in rheumatoid arthritis treatment. PMID:377958

  20. [Anticonvulsant agents in neuralgic pain.].

    PubMed

    Jurna, I; Zenz, M

    1992-06-01

    The anticonvulsants, carbamazepine, clonazepam, phenytoin, and valproic acid are capable of depressing attacks of shooting pain in neuralgia. Shooting pain is perceived in trigeminal, intercostal, and other neuralgias, as a consequence of infectious diseases such as herpes zoster, and in the course of polyneuropathies of various causes. It is due to injury of nociceptive afferents, which generate bursts of activity in response to appropriate environmental changes. The anticonvulsant agents have no analgesic property per se, so that background pain remains unchanged. The depression of shooting pain results from the anticonvulsant action of the compounds. Both carbamazepine and phenytoin block synaptic transmission of neuronal hyperactivity by a direct depressant action that includes reduction of sodium conductance and by activation of inhibitory control. Clonazepam and valproic acid act by enhancing GABA-mediated inhibition of synaptic transmission. Carbamazepine is by far the most widely used compound; phenytoin, clonazepam, and valproic acid are not so popular because of their side effects. PMID:18415623

  1. Biotherapeutic agents and vaginal health.

    PubMed

    Al-Ghazzewi, F H; Tester, R F

    2016-07-01

    Treatment of vaginal infection requires different drugs although the recurrence rate post treatment remains high due to adverse effects on the beneficial microbiota. Thus, there are clear clinical advantages for the use of biotherapeutic agents (prebiotics and/or probiotics) for treating these infections. Pre- and probiotic beneficial effects can be delivered topically or systemically. In general, both approaches have the potential to optimize, maintain and restore the ecology of the vaginal ecosystem. Specific carbohydrates provide a therapeutic approach for controlling infections by stimulating the growth of the indigenous lactobacilli but inhibiting the growth and adhesion of pathogens to the vaginal epithelial cells. Overall, little evidence exists to promote the prevention or treatment of vaginal disease with prebiotic carbohydrates in formulations such as pessaries, creams or douches. However, recent reports have promoted prebiotic applications in ecosystems other than the gut and include the mouth, skin and vagina. This review focuses on the utilization of pre- and probiotics for vaginal health. PMID:26757173

  2. Agent Reward Shaping for Alleviating Traffic Congestion

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan; Agogino, Adrian

    2006-01-01

    Traffic congestion problems provide a unique environment to study how multi-agent systems promote desired system level behavior. What is particularly interesting in this class of problems is that no individual action is intrinsically "bad" for the system but that combinations of actions among agents lead to undesirable outcomes, As a consequence, agents need to learn how to coordinate their actions with those of other agents, rather than learn a particular set of "good" actions. This problem is ubiquitous in various traffic problems, including selecting departure times for commuters, routes for airlines, and paths for data routers. In this paper we present a multi-agent approach to two traffic problems, where far each driver, an agent selects the most suitable action using reinforcement learning. The agent rewards are based on concepts from collectives and aim to provide the agents with rewards that are both easy to learn and that if learned, lead to good system level behavior. In the first problem, we study how agents learn the best departure times of drivers in a daily commuting environment and how following those departure times alleviates congestion. In the second problem, we study how agents learn to select desirable routes to improve traffic flow and minimize delays for. all drivers.. In both sets of experiments,. agents using collective-based rewards produced near optimal performance (93-96% of optimal) whereas agents using system rewards (63-68%) barely outperformed random action selection (62-64%) and agents using local rewards (48-72%) performed worse than random in some instances.

  3. Antagonistic formation motion of cooperative agents

    NASA Astrophysics Data System (ADS)

    Lu, Wan-Ting; Dai, Ming-Xiang; Xue, Fang-Zheng

    2015-02-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonistic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all of the agents make an antagonistic formation motion in a distributed manner. It is shown that all of the agents can be spontaneously divided into several groups and that agents in the same group collaborate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results. Project supported by the National Natural Science Foundation of China (Grant Nos. 61203080 and 61473051) and the Natural Science Foundation of Chongqing City (Grant No. CSTC 2011BB0081).

  4. Persuasive Conversational Agent with Persuasion Tactics

    NASA Astrophysics Data System (ADS)

    Narita, Tatsuya; Kitamura, Yasuhiko

    Persuasive conversational agents persuade people to change their attitudes or behaviors through conversation, and are expected to be applied as virtual sales clerks in e-shopping sites. As an approach to create such an agent, we have developed a learning agent with the Wizard of Oz method in which a person called Wizard talks to the user pretending to be the agent. The agent observes the conversations between the Wizard and the user, and learns how to persuade people. In this method, the Wizard has to reply to most of the user's inputs at the beginning, but the burden gradually falls because the agent learns how to reply as the conversation model grows.

  5. Pinning synchronization of a mobile agent network

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Sun, You-xian

    2009-11-01

    We investigate the problem of controlling a group of mobile agents in a plane in order to move them towards a desired orbit via pinning control, in which each agent is associated with a chaotic oscillator coupled with those of neighboring agents, and the pinning strategy is to have the common linear feedback acting on a small fraction of agents by random selection. We explore the effects of the pinning probability, feedback gains and agent density in the pinning synchronization of a mobile agent network under a fast-switching constraint, and perform numerical simulations for validation. In particular, we show that there exists a critical pinning density for network synchronization with an unbounded region: above the threshold, the dynamical network can be controlled by pinning; below it, anarchy prevails. And for the network with a single bounded synchronization region, pinning control has little effect as regards enhancing network synchronizability.

  6. Evolutionary algorithms and multi-agent systems

    NASA Astrophysics Data System (ADS)

    Oh, Jae C.

    2006-05-01

    This paper discusses how evolutionary algorithms are related to multi-agent systems and the possibility of military applications using the two disciplines. In particular, we present a game theoretic model for multi-agent resource distribution and allocation where agents in the environment must help each other to survive. Each agent maintains a set of variables representing actual friendship and perceived friendship. The model directly addresses problems in reputation management schemes in multi-agent systems and Peer-to-Peer distributed systems. We present algorithms based on evolutionary game process for maintaining the friendship values as well as a utility equation used in each agent's decision making. For an application problem, we adapted our formal model to the military coalition support problem in peace-keeping missions. Simulation results show that efficient resource allocation and sharing with minimum communication cost is achieved without centralized control.

  7. A New Understanding of Chemical Agent Release

    SciTech Connect

    Nakafuji, G; Greenman, R; Theofanous, T

    2002-07-24

    The evolution of thickened chemical agent released at supersonic velocities, due to a missile defense intercept or a properly functioning warhead, has been misunderstood. Current and historical experimental and modeling efforts have attributed agent breakup to a variety of droplet breakup mechanisms. According to this model, drops of agent fragment into subsequent generations of smaller drops until a stable drop size is reached. Recent experimental data conducted in a supersonic wind tunnel show that agent breakup is not driven by any droplet breakup mechanism. The breakup of agent is instead governed by viscoelastic behavior and aerodynamic history effects. This viscoelastic breakup mechanism results in the formation of threads and sheets of liquid, instead of drops. The evolution and final state of agent released has broad implications not only for aerobreakup models, but also for all atmospheric dispersion models.

  8. Multi-Agent Information Classification Using Dynamic Acquaintance Lists.

    ERIC Educational Resources Information Center

    Mukhopadhyay, Snehasis; Peng, Shengquan; Raje, Rajeev; Palakal, Mathew; Mostafa, Javed

    2003-01-01

    Discussion of automated information services focuses on information classification and collaborative agents, i.e. intelligent computer programs. Highlights include multi-agent systems; distributed artificial intelligence; thesauri; document representation and classification; agent modeling; acquaintances, or remote agents discovered through…

  9. Anaphylactoid and adverse reactions to radiocontrast agents.

    PubMed

    Hagan, John B

    2004-08-01

    Over the past 75 years, radiocontrast agents have provided numerous diagnostic and therapeutic advances. The benefits of these agents must be weighed against the potential risks for each individual undergoing radiologic tests. This summary is intended to be a guide for the allergy and immunology specialist to direct him or her to the current literature regarding adverse reactions to traditional and less commonly used radiologic contrast agents. PMID:15242724

  10. Massive Multi-Agent Systems Control

    NASA Technical Reports Server (NTRS)

    Campagne, Jean-Charles; Gardon, Alain; Collomb, Etienne; Nishida, Toyoaki

    2004-01-01

    In order to build massive multi-agent systems, considered as complex and dynamic systems, one needs a method to analyze and control the system. We suggest an approach using morphology to represent and control the state of large organizations composed of a great number of light software agents. Morphology is understood as representing the state of the multi-agent system as shapes in an abstract geometrical space, this notion is close to the notion of phase space in physics.

  11. The EO-1 Autonomous Science Agent Architecture

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Sherwood, Rob; Tran, Daniel; Cichy, Benjamin; Rabideau, Gregg; Castano, Rebecca; Davies, Ashley; Lee, Rachel; Mandl, Dan; Frye, Stuart; Trout, Bruce; Hengemihle, Jerry; D'Agostino, Jeff; Shulman, Seth; Ungar, Stephen; Brakke, Thomas; Boyer, Darrell; Van Gaasbeck, Jim; Greeley, Ronald; Doggett, Thomas; Baker, Victor; Dohm, James; Ip, Felipe

    2004-01-01

    An Autonomous Science Agent is currently flying onboard the Earth Observing One Spacecraft. This software enables the spacecraft to autonomously detect and respond to science events occurring on the Earth. The package includes software systems that perform science data analysis, deliberative planning, and run-time robust execution. Because of the deployment to a remote spacecraft, this Autonomous Science Agent has stringent constraints of autonomy, reliability, and limited computing resources. We describe these constraints and how they are reflected in our agent architecture.

  12. Departments as Agents of Change

    NASA Astrophysics Data System (ADS)

    Lagowski, J. J.

    1996-07-01

    Higher education is changing because it has no choice. And, for the most part, outside influences are dictating the processes of change. The more fortunate institutions have had a flat budget during this period, but most have been forced to deal with a declining revenue stream as well. Legislators seem bent on micromanaging state-supported institutions, even as they cut their support. Regulators demand greater institutional accountability. Students and their parents expect more service at lower prices and increased flexibility. Technological advances have dramatically affected the availability and accessibility of extant knowledge. It is no longer a question of whether institutions will change, but rather, who will control the change. Most institutions possess long-standing academic traditions, but these are placed at risk in an increasingly competitive market that holds little sympathy for such traditions and may even see them as obstacles or barriers. As a result, the change agents will undoubtedly have a profound effect on the very nature of academic institutions. From the academic point of view, it would seem prudent to attempt to manage the changes that will inevitably occur. A number of concerned observers, notably the Pew Higher Education Roundtable and the American Association for Higher Education, argue persuasively that the academic department is the logical focus for responding to the current winds of change. Using a marketing metaphor, the academic department has been likened to a "producers' cooperative" of services that consumers seek. Thus, the department should be held accountable for the quality of teaching delivered by its members, for the coherence of its major, for its contributions to the general education curriculum, and for supervising and rewarding its individual faculty members. If departments are to be held accountable, it is surely in their best interest to act in such a way that they are accountable. Expecting academic departments to be

  13. Radioiodine: the classic theranostic agent.

    PubMed

    Silberstein, Edward B

    2012-05-01

    Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and

  14. Emergency department management of nerve agent exposure.

    PubMed

    Pfaff, B L

    1998-01-01

    Nerve agents are toxic chemicals developed for use by the military, but used by terrorists against civilian populations. As threats of terrorism increase, it is possible that health care providers will be confronted with multiple victims of nerve agent exposure. Nerve agents are highly toxic forms of organophosphate poisons that potentially could cause harm to anyone who comes in contact. Emergency personnel need to be familiar with the agents, know how to prepare for encountering and treating victims, and know how to protect all people involved from further poisoning. PMID:9855972

  15. Characterization of chemical agent transport in paints.

    PubMed

    Willis, Matthew P; Gordon, Wesley; Lalain, Teri; Mantooth, Brent

    2013-09-15

    A combination of vacuum-based vapor emission measurements with a mass transport model was employed to determine the interaction of chemical warfare agents with various materials, including transport parameters of agents in paints. Accurate determination of mass transport parameters enables the simulation of the chemical agent distribution in a material for decontaminant performance modeling. The evaluation was performed with the chemical warfare agents bis(2-chloroethyl) sulfide (distilled mustard, known as the chemical warfare blister agent HD) and O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), an organophosphate nerve agent, deposited on to two different types of polyurethane paint coatings. The results demonstrated alignment between the experimentally measured vapor emission flux and the predicted vapor flux. Mass transport modeling demonstrated rapid transport of VX into the coatings; VX penetrated through the aliphatic polyurethane-based coating (100 μm) within approximately 107 min. By comparison, while HD was more soluble in the coatings, the penetration depth in the coatings was approximately 2× lower than VX. Applications of mass transport parameters include the ability to predict agent uptake, and subsequent long-term vapor emission or contact transfer where the agent could present exposure risks. Additionally, these parameters and model enable the ability to perform decontamination modeling to predict how decontaminants remove agent from these materials. PMID:23872337

  16. Oak Ridge Mobile Agent Community (ORMAC)

    2003-06-30

    The Oak Ridge Mobile Agent Community (ORMAC) framework software facilitates the execution of a collection of mobile software agents across a heterogeneous collection of computer systems. ORMAC provides the software agents with the ability to communicate with each other in a synchronous and asynchronous manner. Also, ORMAC allows the software agents to move to any computer system in the community and continue execution there. ORMAC is intended to aid programmers in solving a very generalmore » set of distributed software problems.« less

  17. Dentine and enamel bonding agents.

    PubMed

    Bowen, R L; Tung, M S; Blosser, R L; Asmussen, E

    1987-09-01

    Previous studies have shown that sequential use of aqueous FO (ferric oxalate containing a small concentration of HNO3), acetone solutions of NPG (N-phenylglycine), and PMDM (the reaction product of pyromellitic dianhydride and 2-hydroxyethylmethacrylate) yields strong adhesive bonding of composite resins to both dentine and enamel. The purpose of this study was to determine if aluminum ions could be substituted for ferric ions and if the procedure could be simplified. Aqueous solutions containing aluminum oxalate and aluminum nitrate, followed in sequence by acetone solutions of NPG and PMDM, gave strong tensile adhesive bond strengths between a composite and extracted human teeth. Comparable values have been obtained with FO, NPG and PMDM. Aluminum oxalate solutions containing no nitrate gave lower bond strengths, as was the case with FO. Aqueous solutions of acidified aluminum oxalate can dissolve NPG, thereby allowing a simplification of the procedure. Tested for comparison, commercially available dentine bonding agents gave lower average bond strengths on dentine than did some of the experimental materials. PMID:3316044

  18. Cold as a therapeutic agent.

    PubMed

    Wang, H; Olivero, W; Wang, D; Lanzino, G

    2006-05-01

    The use of cold as a therapeutic agent has a long and colorful history. The Edwin Smith Papyrus, the most ancient medical text known, dated 3500 B.C., made numerous references to the use of cold as therapy. Baron de Larrey, a French army surgeon during Napoleon's Russian campaign, packed the limbs in ice prior to amputations to render the procedures painless. In the early twentieth century, a neurosurgeon, Temple Fay, pioneered "human refrigeration" as a treatment for malignancies and head injuries. In 1961, Irving Cooper developed the first closed cryoprobe system and ushered in the modern era of cryogenic surgery with his imperturbable convictions. Fay's early work fell victim to the disruptive sequel of the World War II. The Nazis confiscated his data (presented before the Third International Cancer Congress in 1939) forwarded to Belgium for publication and brutally applied his refrigeration techniques experimentally without any benefit of anesthesia in the concentration camps, especially Dachau. Hypothermia became associated in the public mind with the atrocities exposed at the war trials in Nürnberg. After lying dormant for decades, the interest was rekindled in the late 80s when mild hypothermia was shown to confer dramatic neuroprotection in a number of experimental models of brain injury. With several large multi-center clinical studies currently under way, hypothermia is receiving unprecedented attention from the medical and scientific communities. PMID:16489500

  19. Direct anti-HCV agents.

    PubMed

    Zhang, Xingquan

    2016-01-01

    Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the "cure HCV" goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others. PMID:26904396

  20. Departments as Agents of Change

    NASA Astrophysics Data System (ADS)

    Lagowski, J. J.

    1996-07-01

    Higher education is changing because it has no choice. And, for the most part, outside influences are dictating the processes of change. The more fortunate institutions have had a flat budget during this period, but most have been forced to deal with a declining revenue stream as well. Legislators seem bent on micromanaging state-supported institutions, even as they cut their support. Regulators demand greater institutional accountability. Students and their parents expect more service at lower prices and increased flexibility. Technological advances have dramatically affected the availability and accessibility of extant knowledge. It is no longer a question of whether institutions will change, but rather, who will control the change. Most institutions possess long-standing academic traditions, but these are placed at risk in an increasingly competitive market that holds little sympathy for such traditions and may even see them as obstacles or barriers. As a result, the change agents will undoubtedly have a profound effect on the very nature of academic institutions. From the academic point of view, it would seem prudent to attempt to manage the changes that will inevitably occur. A number of concerned observers, notably the Pew Higher Education Roundtable and the American Association for Higher Education, argue persuasively that the academic department is the logical focus for responding to the current winds of change. Using a marketing metaphor, the academic department has been likened to a "producers' cooperative" of services that consumers seek. Thus, the department should be held accountable for the quality of teaching delivered by its members, for the coherence of its major, for its contributions to the general education curriculum, and for supervising and rewarding its individual faculty members. If departments are to be held accountable, it is surely in their best interest to act in such a way that they are accountable. Expecting academic departments to be

  1. Novel antibodies as anticancer agents.

    PubMed

    Zafir-Lavie, I; Michaeli, Y; Reiter, Y

    2007-05-28

    In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents. PMID:17530025

  2. New therapeutic agents for hypertension

    PubMed Central

    REID, JOHN L.

    1996-01-01

    1Over the last 40 years a range of therapeutic strategies has been introduced for the long term treatment of hypertension. 2Although safe effective agents are available a significant number of patients are unable or unwilling to take these drugs as long term treatment. 3Both insufficient efficacy and adverse effects justify the search for new antihypertensive strategies. 4Recent developments include orally active angiotensin (AT1) receptor antagonists (ARA) which appear to offer the benefits of prevention of angiotensin II effects without the adverse effects of bradykinin potentiation, such as cough, which limit the usefulness of angiotensin converting enzyme (ACE) inhibitors. 5Imidazoline receptor agonists offer the potential of centrally active antihypertensives without the adverse effects of sedation and dry mouth. Further clinical experience is necessary to confirm whether the clinical efficacy and good tolerability are confirmed with long term use. 6Both ARA and imidazoline preferring substances offer the bonus of a desirable haemodynamic profile in patients with heart failure and may open new therapeutic avenues in the management of cardiac failure. PMID:8807142

  3. Direct anti-HCV agents

    PubMed Central

    Zhang, Xingquan

    2015-01-01

    Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others. PMID:26904396

  4. Radiation recall with anticancer agents.

    PubMed

    Burris, Howard A; Hurtig, Jane

    2010-01-01

    Radiation recall is an acute inflammatory reaction confined to previously irradiated areas that can be triggered when chemotherapy agents are administered after radiotherapy. It remains a poorly understood phenomenon, but increased awareness may aid early diagnosis and appropriate management. A diverse range of drugs used in the treatment of cancer has been associated with radiation recall. As most data come from case reports, it is not possible to determine the true incidence, but to date the antineoplastic drugs for which radiation recall reactions have been most commonly reported include the anthracycline doxorubicin, the taxanes docetaxel and paclitaxel, and the antimetabolites gemcitabine and capecitabine. Radiation recall is drug-specific for any individual patient; it is not possible to predict which patients will react to which drugs, and rechallenge does not uniformly induce a reaction. There are no identifiable characteristics of drugs that cause radiation recall, and thus, it is a possibility that must be kept in mind with use of any drug after radiotherapy, including those from new drug classes. Although it is not yet possible to design treatment regimens to eliminate the risk of radiation recall, it seems likely that risks can be minimized by prolonging the interval between completion of radiotherapy and initiation of chemotherapy. PMID:21045191

  5. Safe motion planning for mobile agents: A model of reactive planning for multiple mobile agents

    SciTech Connect

    Fujimura, Kikuo.

    1990-01-01

    The problem of motion planning for multiple mobile agents is studied. Each planning agent independently plans its own action based on its map which contains a limited information about the environment. In an environment where more than one mobile agent interacts, the motions of the robots are uncertain and dynamic. A model for reactive agents is described and simulation results are presented to show their behavior patterns. 18 refs., 2 figs.

  6. The Design of Motivational Agents and Avatars

    ERIC Educational Resources Information Center

    Baylor, Amy L.

    2011-01-01

    While the addition of an anthropomorphic interface agent to a learning system generally has little direct impact on learning, it potentially has a huge impact on learner motivation. As such agents become increasingly ubiquitous on the Internet, in virtual worlds, and as interfaces for learning and gaming systems, it is important to design them to…

  7. VIRAL GASTROENTERITIS AGENTS AND WATERBORNE DISEASE

    EPA Science Inventory

    The application of electron microscopic techniques in the study of human gastroenteritis led in the 1970's to the identification of new viral agents that had previously escaped detection by routine cell culture procedures. These agents have been the focus of study by researchers ...

  8. Improving Disability Awareness among Extension Agents

    ERIC Educational Resources Information Center

    Mahadevan, Lakshmi; Peterson, Rick L.; Grenwelge, Cheryl

    2014-01-01

    Increasing prevalence rates and legislative mandates imply that educators, parents, and Extension agents will need better tools and resources to meet the needs of special populations. The Texas A&M AgriLife Extension Service addresses this issue by using e-learning tools. Extension agents can take advantage of these courses to gain critical…

  9. 21 CFR 178.3125 - Anticorrosive agents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... section may be used as anticorrosive agents in food-contact materials subject to the provisions of this... component of resinous and polymeric food-contact coatings intended for repeated use in contact with dry... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Anticorrosive agents. 178.3125 Section...

  10. 21 CFR 178.3125 - Anticorrosive agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... section may be used as anticorrosive agents in food-contact materials subject to the provisions of this... component of resinous and polymeric food-contact coatings intended for repeated use in contact with dry... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Anticorrosive agents. 178.3125 Section...

  11. 21 CFR 178.3125 - Anticorrosive agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... agents in food-contact materials subject to the provisions of this section: Substances Limitations Zinc... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Anticorrosive agents. 178.3125 Section 178.3125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  12. 46 CFR Sec. 3 - General Agents' responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false General Agents' responsibilities. Sec. 3 Section 3 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY AUTHORITY AND RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE EMERGENCY REPAIRS IN FOREIGN PORTS Sec. 3 General...

  13. 46 CFR Sec. 2 - General Agents' authority.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false General Agents' authority. Sec. 2 Section 2 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY AUTHORITY AND RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE IN CONTINENTAL UNITED STATES PORTS VOYAGE REPAIRS AND...

  14. 7 CFR 58.722 - Emulsifying agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.722 Emulsifying agents. Emulsifying agents shall be those permitted by the Food and Drug Administration for the specific pasteurized process cheese product, and shall be free from extraneous...

  15. 7 CFR 58.722 - Emulsifying agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.722 Emulsifying agents. Emulsifying agents shall be those permitted by the Food and Drug Administration for the specific pasteurized process cheese product, and shall be free from extraneous...

  16. Security of Mobile Agents on the Internet.

    ERIC Educational Resources Information Center

    Corradi, Antonio; Montanari, Rebecca; Stefanelli, Cesare

    2001-01-01

    Discussion of the Internet focuses on new programming paradigms based on mobile agents. Considers the security issues associated with mobile agents and proposes a security architecture composed of a wide set of services and components capable of adapting to a variety of applications, particularly electronic commerce. (Author/LRW)

  17. Marine Natural Products as Prototype Agrochemical Agents

    PubMed Central

    Peng, Jiangnan; Shen, Xiaoyu; El Sayed, Khalid A.; Dunbar, D. C Harles; Perry, Tony L.; Wilkins, Scott P.; Hamann, Mark T.; Bobzin, Steve; Huesing, Joseph; Camp, Robin; Prinsen, Mike; Krupa, Dan; Wideman, Margaret A.

    2016-01-01

    In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents. PMID:12670165

  18. 13 CFR 120.952 - Fiscal agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Fiscal agent. 120.952 Section 120.952 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company... Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production...

  19. Assurance in Agent-Based Systems

    SciTech Connect

    Gilliom, Laura R.; Goldsmith, Steven Y.

    1999-05-10

    Our vision of the future of information systems is one that includes engineered collectives of software agents which are situated in an environment over years and which increasingly improve the performance of the overall system of which they are a part. At a minimum, the movement of agent and multi-agent technology into National Security applications, including their use in information assurance, is apparent today. The use of deliberative, autonomous agents in high-consequence/high-security applications will require a commensurate level of protection and confidence in the predictability of system-level behavior. At Sandia National Laboratories, we have defined and are addressing a research agenda that integrates the surety (safety, security, and reliability) into agent-based systems at a deep level. Surety is addressed at multiple levels: The integrity of individual agents must be protected by addressing potential failure modes and vulnerabilities to malevolent threats. Providing for the surety of the collective requires attention to communications surety issues and mechanisms for identifying and working with trusted collaborators. At the highest level, using agent-based collectives within a large-scale distributed system requires the development of principled design methods to deliver the desired emergent performance or surety characteristics. This position paper will outline the research directions underway at Sandia, will discuss relevant work being performed elsewhere, and will report progress to date toward assurance in agent-based systems.

  20. Practice among Novice Change Agents in Schools

    ERIC Educational Resources Information Center

    Blossing, Ulf

    2016-01-01

    The aim of the article is to understand practice as negotiation of meaning among novice and internal change agents in school organisations. The research question is as follows: What themes of participation and reification/management occur among the change agents? The study was qualitative in design using the social learning theory of community of…