Search

Francisella tularensis is the causative agent of tularemia. We tested the susceptibility of 278 F. tularensis isolates from the United States received during 2009-2018 to 8 antimicrobial drugs (ciprofloxacin, levofloxacin, doxycycline, tetracycline, gentamicin, streptomycin, chloramphenicol, and erythromycin). All isolates were susceptible to all tested drugs., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Tick-transmitted Borrelia fall into 2 heterogeneous bacterial complexes comprised of multiple species, the relapsing fever (RF) group and the Borrelia burgdorferi sensu lato group, which are the causative agents of Lyme borreliosis (LB), the most common tickborne disease in the Northern Hemisphere. Geographic expansion of LB in the United States and discovery of emerging Borrelia pathogens underscores the importance of surveillance for disease-causing Borrelia., Methods: De-identified clinical specimens, submitted by providers throughout the United States, for patients suspected of LB, anaplasmosis, ehrlichiosis, or babesiosis were screened using a Borrelia genus-level TaqMan polymerase chain reaction (PCR). Borrelia species and sequence types (STs) were characterized by multilocus sequence typing (MLST) utilizing next-generation sequencing., Results: Among 7292 specimens tested, 5 Borrelia species were identified: 2 causing LB, B. burgdorferi (n = 25) and B. mayonii (n = 9), and 3 RF borreliae, B. hermsii (n = 1), B. miyamotoi (n = 8), and Candidatus B. johnsonii (n = 1), a species previously detected only in the bat tick, Carios kelleyi. ST diversity was greatest for B. burgdorferi-positive specimens, with new STs identified primarily among synovial fluids., Conclusions: These results demonstrate that broad PCR screening followed by MLST is a powerful surveillance tool for uncovering the spectrum of disease-causing Borrelia species, understanding their geographic distribution, and investigating the correlation between B. burgdorferi STs and joint involvement. Detection of Candidatus B. johnsonii in a patient with suspected tickborne disease suggests this species may be a previously undetected cause of illness in humans exposed to bat ticks.

A total of 6,255 ticks belonging to three genera and six species (Haemaphysalis flava Neumann, Haemaphysalis longicornis Neumann, Haemaphysalis phasiana Saito, Ixodes nipponensis Kitaoka & Saito, Ixodes persulcatus Schulze, and Amblyomma testudinarium Koch) collected from May-August, 2013, at four southwestern provinces in the Republic of Korea (ROK) were submitted to the Armed Forces Research Institute of Medical Sciences and assayed for selected tick-borne pathogens. One pool each of H. flava and H. phasiana was positive by PCR and sequencing for a Francisella-like endosymbiont, while all pools were negative for Francisella tularensis, the causative agent of tularemia., (Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.)

Borrelia mayonii is a newly described member of the Borrelia burgdorferi sensu lato complex that is vectored by the black-legged tick (Ixodes scapularis Say) and a cause of Lyme disease in Minnesota and Wisconsin. Vertebrate reservoir hosts involved in the enzootic maintenance of B. mayonii have not yet been identified. Here, we describe the first isolation of B. mayonii from naturally infected white-footed mice (Peromyscus leucopus Rafinesque) and an American red squirrel (Tamiasciurus hudsonicus Erxleben) from Minnesota, thus implicating these species as potential reservoir hosts for this newly described spirochete., (Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.)

Background: Francisella novicida is a rare cause of human illness despite its close genetic relationship to Francisella tularensis, the agent of tularemia. During April-July 2011, 3 inmates at a Louisiana correctional facility developed F. novicida bacteremia; 1 inmate died acutely., Methods: We interviewed surviving inmates; reviewed laboratory, medical, and housing records; and conducted an environmental investigation. Clinical and environmental samples were tested by culture, real-time polymerase chain reaction (PCR), and multigene sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE)., Results: Clinical isolates were identified as F. novicida based on sequence analyses of the 16S ribosomal RNA, pgm, and pdpD genes. PmeI PFGE patterns for the clinical isolates were indistinguishable. Source patients were aged 40-56 years, male, and African American, and all were immunocompromised. Two patients presented with signs of bacterial peritonitis; the third had pyomyositis of the thigh. The 3 inmates had no contact with one another; their only shared exposures were consumption of municipal water and of ice that was mass-produced at the prison in an unenclosed building. Swabs from one set of ice machines and associated ice scoops yielded evidence of F. novicida by PCR and sequencing. All other environmental specimens tested negative., Conclusions: To our knowledge, this is the first reported common-source outbreak of F. novicida infections in humans. Epidemiological and laboratory evidence implicate contaminated ice as the likely vehicle of transmission; liver disease may be a predisposing factor. Clinicians, laboratorians, and public health officials should be aware of the potential for misidentification of F. novicida as F. tularensis., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Plague, a primarily flea-borne disease caused by Yersinia pestis, is characterized by rapidly spreading epizootics separated by periods of quiescence. Little is known about how and where Y. pestis persists between epizootics. It is commonly proposed, however, that Y pestis is maintained during interepizootic periods in enzootic cycles involving flea vectors and relatively resistant host populations. According to this model, while susceptible individuals serve as infectious sources for feeding fleas and subsequently die of infection, resistant hosts survive infection, develop antibodies to the plague bacterium, and continue to provide bloodmeals to infected fleas. For Y. pestis to persist under this scenario, fleas must remain infected after feeding on hosts carrying antibodies to Y. pestis. Studies of other vector-borne pathogens suggest that host immunity may negatively impact pathogen survival in the vector. Here, we report infection rates and bacterial loads for fleas (both Xenopsylla cheopis (Rothschild) and Oropsylla montana (Baker)) that consumed an infectious bloodmeal and subsequently fed on an immunized or age-matched naive mouse. We demonstrate that neither the proportion of infected fleas nor the bacterial loads in infected fleas were significantly lower within 3 d of feeding on immunized versus naive mice. Our findings thus provide support for one assumption underlying the enzootic host model of interepizootic maintenance of Y. pestis.

The American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae), has been implicated as a potential bridging vector to humans of Francisella tularensis, the etiological agent of tularemia. Since the initial studies evaluating vector competency of D. variabilis were conducted, F. tularensis has been subdivided into subspecies and clades that differ in their geographical distribution in the United States and in the severity of infections caused in humans. Here, we demonstrate that D. variabilis nymphs efficiently acquire, transtadially maintain, and transmit each of the strains tested (clades A1b and A2, and type B). Transmission efficiency by adult females was similarly high among infection groups and ranged from 58% for type B to 89% for A2 infections. In addition, we demonstrated that transmission can occur shortly after tick attachment. These findings support the concept that D. variabilis adults may play a significant role in epizootic transmission of F. tularensis, and as a bridging vector to humans.

Francisella tularensis is a facultative, intracellular, zoonotic pathogen and the causative agent of tularemia. Historically, F. tularensis has been subdivided into subspecies on the basis of phenotypic traits, including biochemical reactivity and virulence. More recently, a number of genotypic methods, ranging from relatively insensitive methods to full genome sequencing, have been used to investigate genetic diversity within F. tularensis. These analyses indicate that F. tularensis is a pathogen of low sequence diversity with pair-wise average nucleotide identities > 99.2% across subspecies. Nonetheless, genomic rearrangements and sequence deletions exist between and within F. tularensis subspecies, creating polymorphisms detectable by genotyping methods. Genetic subpopulations intermediate to the subspecies and strain level have been identified within F. tularensis subsp. tularensis and F. tularensis subsp. holarctica by several different typing methods. These genetic subpopulations have been associated with differences in disease severity, geographic distribution, and transmission patterns. For example, one F. tularensis subsp. tularensis subpopulation has been found to be significantly associated with mortality in humans. Additionally, genotypic analyses of Francisella spp. have provided information for use in the rational design of strain panels for validation of F. tularensis diagnostic tests. This review provides a guide to the various F. tularensis genotyping methods.

Background: Primary pneumonic plague is a rare but often fatal form of Yersinia pestis infection that results from direct inhalation of bacteria and is potentially transmissible from person to person. We describe a case of primary pneumonic plague in a wildlife biologist who was found deceased in his residence 1 week after conducting a necropsy on a mountain lion., Methods: To determine cause of death, a postmortem examination was conducted, and friends and colleagues were interviewed. Physical evidence was reviewed, including specimens from the mountain lion and the biologist's medical chart, camera, and computer. Human and animal tissues were submitted for testing. Persons in close contact (within 2 meters) to the biologist after he had developed symptoms were identified and offered chemoprophylaxis., Results: The biologist conducted the necropsy in his garage without the use of personal protective equipment. Three days later, he developed fever and hemoptysis and died approximately 6 days after exposure. Gross examination showed consolidation and hemorrhagic fluid in the lungs; no buboes were noted. Plague was diagnosed presumptively by polymerase chain reaction and confirmed by culture. Tissues from the mountain lion tested positive for Y. pestis, and isolates from the biologist and mountain lion were indistinguishable by pulsed-field gel electrophoresis. Among 49 contacts who received chemoprophylaxis, none developed symptoms consistent with plague., Conclusions: The biologist likely acquired pneumonic plague through inhalation of aerosols generated during postmortem examination of an infected mountain lion. Enhanced awareness of zoonotic diseases and appropriate use of personal protective equipment are needed for biologists and others who handle wildlife.

Background: In the United States, tularemia is caused by Francisella tularensis subsps. tularensis (type A) and holarctica (type B). Molecular subtyping has further divided type A into 2 subpopulations, A1 and A2. Significant mortality differences were previously identified between human infections caused by A1 (14%), A2 (0%) and type B (7%). To verify these findings and to further define differences among genotypes, we performed a large-scale molecular epidemiologic analysis of F. tularensis isolates from humans and animals., Methods: Pulsed-field gel electrophoresis with PmeI was performed on 302 type A and 61 type B isolates. Pulsed-field gel electrophoresis pattern and epidemiologic analyses were performed. Logistic regression was used to assess factors associated with human mortality., Results: Pulsed-field gel electrophoresis typing identified 4 distinct type A genotypes, A1a, A1b, A2a, and A2b, as well as type B. Genotypic and geographic divisions observed among isolates from humans were mirrored among isolates from animals, specifically among animal species that are linked to human infection and to enzootic maintenance of tularemia. Significant differences between human infections caused by different genotypes were identified with respect to patient age, site of organism recovery, and mortality. Human infections due to A1b resulted in significantly higher mortality (24%) than those caused by A1a (4%), A2 (0%), and type B (7%)., Conclusions: Three type A genotypes, A1a, A1b, and A2, were shown to be epidemiologically important. Our analysis suggests that A1b strains may be significantly more virulent in humans than A1a, A2, or type B strains. These findings have important implications for disease progression, disease prevention, and basic research programs.

Motivation: An important application of protein microarray data analysis is identifying a serodiagnostic antigen set that can reliably detect patterns and classify antigen expression profiles. This work addresses this problem using antibody responses to protein markers measured by a novel high-throughput microarray technology. The findings from this study have direct relevance to rapid, broad-based diagnostic and vaccine development., Results: Protein microarray chips are probed with sera from individuals infected with the bacteria Francisella tularensis, a category A biodefense pathogen. A two-step approach to the diagnostic process is presented (1) feature (antigen) selection and (2) classification using antigen response measurements obtained from F.tularensis microarrays (244 antigens, 46 infected and 54 healthy human sera measurements). To select antigens, a ranking scheme based on the identification of significant immune responses and differential expression analysis is described. Classification methods including k-nearest neighbors, support vector machines (SVM) and k-Means clustering are applied to training data using selected antigen sets of various sizes. SVM based models yield prediction accuracy rates in the range of approximately 90% on validation data, when antigen set sizes are between 25 and 50. These results strongly indicate that the top-ranked antigens can be considered high-priority candidates for diagnostic development., Availability: All software programs are written in R and available at http://www.igb.uci.edu/index.php?page=tools and at http://www.r-project.org., Supplementary Information: Supplementary data are available at Bioinformatics online.