Search

Tularemia is caused by subspecies of Francisella tularensis and can manifest in a variety of disease states, with the pneumonic presentation resulting in the greatest mortality. Despite decades of research, there are no approved vaccines against F. tularensis in the United States. Traditional vaccination strategies, such as live-attenuated or subunit vaccines, are not favorable due to inadequate protection or safety concerns. Because of this, novel vaccination strategies are needed to combat tularemia. Here we discuss the current state of and challenges to the tularemia vaccine field and suggest novel vaccine approaches going forward that might be better suited for protecting against F. tularensis infection. [ABSTRACT FROM AUTHOR]

Background Francisella tularensis , the causative agent of tularemia, is endemic throughout the Northern Hemisphere and requires as few as 10 organisms to cause disease, making this potential bioterrorism agent one of the most infectious bacterial pathogens known. Aminoglycosides, tetracyclines, and, more recently, fluoroquinolones are used for treatment of tularemia; however, data on the relative effectiveness of these and other antimicrobial classes are limited. Methods Nine databases, including Medline, Global Health, and Embase, were systematically searched for articles containing terms related to tularemia. Articles with case-level data on tularemia diagnosis, antimicrobial treatment, and patient outcome were included. Patient demographics, clinical findings, antimicrobial administration, and outcome (eg, intubation, fatality) were abstracted using a standardized form. Results Of the 8878 publications identified and screened, 410 articles describing 870 cases from 1993 to 2023 met inclusion criteria. Cases were reported from 35 countries; more than half were from the United States, Turkey, or Spain. The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease. Among patients treated with aminoglycosides (n = 452 [52%]), fluoroquinolones (n = 339 [39%]), or tetracyclines (n = 419 [48%]), the fatality rate was 0.7%, 0.9%, and 1.2%, respectively. Patients with pneumonic disease who received ciprofloxacin had no fatalities and the lowest rates of thoracentesis/pleural effusion drainage and intubation compared to those who received aminoglycosides and tetracyclines. Conclusions Aminoglycosides, fluoroquinolones, and tetracyclines are effective antimicrobials for treatment of tularemia, regardless of clinical manifestation. For pneumonic disease specifically, ciprofloxacin may have slight advantages compared to other antimicrobials. [ABSTRACT FROM AUTHOR]

Background Tularemia, a potentially fatal zoonosis caused by Francisella tularensis , has been reported from nearly all US states. Information on relative effectiveness of various antimicrobials for treatment of tularemia is limited, particularly for newer classes such as fluoroquinolones. Methods Data on clinical manifestations, antimicrobial treatment, and illness outcome of patients with tularemia are provided voluntarily through case report forms to the US Centers for Disease Control and Prevention by state and local health departments. We summarized available demographic and clinical information submitted during 2006–2021 and evaluated survival according to antimicrobial treatment. We grouped administered antimicrobials into those considered effective for treatment of tularemia (aminoglycosides, fluoroquinolones, and tetracyclines) and those with limited efficacy. Logistic regression models with a bias-reduced estimation method were used to evaluate associations between antimicrobial treatment and survival. Results Case report forms were available for 1163 US patients with tularemia. Francisella tularensis was cultured from a clinical specimen (eg, blood, pleural fluid) in approximately half of patients (592; 50.9%). Nearly three-quarters (853; 73.3%) of patients were treated with a high-efficacy antimicrobial. A total of 27 patients (2.3%) died. After controlling for positive culture as a proxy for illness severity, use of aminoglycosides, fluoroquinolones, and tetracyclines was independently associated with increased odds of survival. Conclusions Most US patients with tularemia received high-efficacy antimicrobials; their use was associated with improved odds of survival regardless of antimicrobial class. Our findings provide supportive evidence that fluoroquinolones are an effective option for treatment of tularemia. [ABSTRACT FROM AUTHOR]

Tularemia is a disease caused by Francisella tularensis , a highly infectious bacteria that can be transmitted to humans by direct contact with infected animals. Because of the potential for zoonotic transmission of F. tularensis , veterinary occupational risk is a concern. Here, we report on a human case of tularemia in a veterinarian after an accidental needlestick injury during abscess drainage in a sick dog. The veterinarian developed ulceroglandular tularemia requiring hospitalization but fully recovered after abscess drainage and a course of effective antibiotics. To systematically assess veterinary occupational transmission risk of F. tularensis , we conducted a survey of veterinary clinical staff after occupational exposure to animals with confirmed tularemia. We defined a high-risk exposure as direct contact to the infected animal's body fluids or potential aerosol inhalation without use of standard personal protective equipment (PPE). Survey data included information on 20 veterinary occupational exposures to animals with F. tularensis in 4 states. Veterinarians were the clinical staff most often exposed (40%), followed by veterinarian technicians and assistants (30% and 20%, respectively). Exposures to infected cats were most common (80%). Standard PPE was not used during 80% of exposures; a total of 7 exposures were categorized as high risk. Transmission of F. tularensis in the veterinary clinical setting is possible but overall risk is likely low. Veterinary clinical staff should use standard PPE and employ environmental precautions when handling sick animals to minimize risk of tularemia and other zoonotic infections; postexposure prophylaxis should be considered after high-risk exposures to animals with suspected or confirmed F. tularensis infection to prevent tularemia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Tularemia disease attracts attention as an important contagious zoonosis that has increased its impact in recent years. The aim of the study is to analyze the publications on tularemia between 1980 and 2020. Methods: We performed literature retrieval in the Web of Science (WoS) on 22 September 2021. Search terms were "Francisella tularensis" and "Tularemia" in the article title for the period between January 1980 and December 2020. We determined the number of articles, keywords, countries, authors, and institutions for each publication. We visualized the data with the VOS viewer tool. Results: After all inclusion and exclusion criteria were applied finally, 1688 articles were analyzed. The number of articles has increased in recent years. The three most productive countries in tularemia were the USA (777 articles 46.03%), Sweden (113 articles 6.69%), and Turkey (95 articles, 5.63%). Most of the articles were from the journal of Infection and Immunity (II), Plos one, Journal of Clinical Microbiology (JCM), Emerging Infectious Diseases (EID), and Vaccine. Sjostedt A. and Umea University—Sweden were the most influential author and institution. Conclusions: Productivity trend has been shown to increase in tularemia. High-income countries had a great influence on the literature in the field. Publications from the USA were in a high percentage among all articles. Related work may lead to the future direction of this dossier in the next years. [ABSTRACT FROM AUTHOR]

Tularemia is caused by the highly infectious bacterium Francisella tularensis, which is recognized as a Tier 1 bioterrorism agent. Tularemia has a range of recognized clinical manifestations, but fewer than 20 bone or joint infections from 6 countries have been reported in the literature to date. This series includes 13 cases of F. tularensis septic arthritis or osteomyelitis in the United States during 2004-2023 and describes exposures, clinical presentation, diagnosis, and outcomes for this rare but severe form of tularemia. Clinicians should consider F. tularensis in patients with compatible exposures or a history of joint replacement or immunosuppression., 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. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Dogs have been implicated in the zoonotic transmission of numerous pathogens. Whereas cats are known to transmit Francisella tularensis to humans via bite and other routes, the role of dogs in facilitating infection is much less understood. We reviewed tularaemia case investigation records collected through national surveillance during 2006–2016 to summarize those with dog involvement, characterize the nature of dog‐related exposure and describe associated clinical characteristics. Among 1,814 human tularaemia cases, 735 (41%) supplemental case investigation records were available for review; and of those, 24 (3.3%) were classified as dog‐related. Median age of patients was 51 years (range: 1–82); 54% were female. Two thirds (67%) of cases presented with ulceroglandular/glandular tularaemia; pneumonic (13%) and oropharyngeal (13%) illness occurred less frequently. Dog‐related exposures were classified as follows: direct contact via bite, scratch or face snuggling/licking (n = 12; 50%); direct contact with dead animals retrieved by domestic dogs (n = 8; 33%); and contact with infected ticks acquired from domestic dogs (n = 4; 17%). Prevention of dog‐related tularaemia necessitates enhanced tularaemia awareness and tick avoidance among pet owners, veterinarians, health care providers and the general public. [ABSTRACT FROM AUTHOR]

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation. [ABSTRACT FROM AUTHOR]

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation. [ABSTRACT FROM AUTHOR]

We examined 5 tularemia cases in Arizona, USA, during 2015-2017. All were caused by Francisella tularensis group A.II. Genetically similar isolates were found across large spatial and temporal distances, suggesting that group A.II strains are dispersed across long distances by wind and exhibit low replication rates in the environment. [ABSTRACT FROM AUTHOR]

Over 600,000 vector-borne disease cases were reported in the United States (U.S.) in the past 13 years, of which more than three-quarters were tick-borne diseases. Although Lyme disease accounts for the majority of tick-borne disease cases in the U.S., tularemia cases have been increasing over the past decade, with >220 cases reported yearly. However, when comparing Borrelia burgdorferi (causative agent of Lyme disease) and Francisella tularensis (causative agent of tularemia), the low infectious dose (<10 bacteria), high morbidity and mortality rates, and potential transmission of tularemia by multiple tick vectors have raised national concerns about future tularemia outbreaks. Despite these concerns, little is known about how F. tularensis is acquired by, persists in, or is transmitted by ticks. Moreover, the role of one or more tick vectors in transmitting F. tularensis to humans remains a major question. Finally, virtually no studies have examined how F. tularensis adapts to life in the tick (vs. the mammalian host), how tick endosymbionts affect F. tularensis infections, or whether other factors (e.g., tick immunity) impact the ability of F. tularensis to infect ticks. This review will assess our current understanding of each of these issues and will offer a framework for future studies, which could help us better understand tularemia and other tick-borne diseases. [ABSTRACT FROM AUTHOR]

Francisella tularensis can cause the zoonotic disease tularemia and is partitioned into subspecies due to differences in chromosomal organization and virulence. The subspecies holarctica (type B) is generally considered more clonal than the other subpopulations with moderate virulence compared to the hypervirulent A.I clade. We performed whole genome sequencing (WGS) on six type B strains isolated from the blood of patients with tularemia within a one-year period from the same United States region, to better understand the associated pathogenicity. The WGS data were compared to the prototype strain for this subspecies, specifically FSC200, which was isolated from a patient with tularemia in Europe. These findings revealed 520–528 single nucleotide polymorphisms (SNPs) between the six United States type B strains compared to FSC200, with slightly higher A+T content in the latter strain. In contrast, comparisons between the six type B isolates showed that five of the six type B isolates had only 4–22 SNPs, while one of the strains had 47–53 SNPs. Analysis of SNPs in the core genome for the six United States type B isolates and the FSC200 strain gave similar results, suggesting that some of these mutations may have been nonsynonymous, resulting in altered protein function and pathogenicity. [ABSTRACT FROM AUTHOR]

In the United States, tick-borne diseases are increasing in incidence and cases are reported over an expanding geographical area. Avoiding tick bites is a key strategy in tick-borne disease prevention, and this requires current and accurate information on where humans are at risk for exposure to ticks. Based on a review of published literature and records in the U.S. National Tick Collection and National Ecological Observatory Network databases, we compiled an updated county-level map showing the reported distribution of the American dog tick, Dermacentor variabilis (Say). We show that this vector of the bacterial agents causing Rocky Mountain spotted fever and tularemia is widely distributed, with records derived from 45 states across the contiguous United States. However, within these states, county-level records of established tick populations are limited. Relative to the range of suitable habitat for this tick, our data imply that D. variabilis is currently underreported in the peer-reviewed literature, highlighting a need for improved surveillance and documentation of existing tick records., (Published by Oxford University Press on behalf of Entomological Society of America 2019.)

Francisella tularensis , the causative agent of the zoonotic disease tularemia, is characterized by high morbidity and mortality rates in over 190 different mammalian species, including humans. Based on its low infectious dose, multiple routes of infection, and ability to induce rapid and lethal disease, F. tularensis has been recognized as a severe public health threat-being designated as a NIH Category A Priority Pathogen and a CDC Tier 1 Select Agent. Despite concerns over its use as a bioweapon, most U.S. tularemia cases are tick-mediated and ticks are believed to be the major environmental reservoir for F. tularensis in the U.S. The American dog tick ( Dermacentor variabilis ) has been reported to be the primary tick vector for F. tularensis , but the lone star tick ( Amblyomma americanum ) and other tick species also have been shown to harbor F. tularensis . This review highlights what is known, not known, and is debated, about the roles of different tick species as environmental reservoirs and transmission vectors for a variety of F. tularensis genotypes/strains.

After George McCoy accidentally discovered a new infection in 1911 while investigating bubonic plague in squirrels, he transmitted the disease to experimental animals and isolated the causative organism. He called it Bacterium tularense, after Tulare County, California. In 1919, Edward Francis determined that an infection called "deer-fly fever" was the same disease, naming it "tularemia." He demonstrated that it occurred in wild rabbits and inadvertently showed that it was highly infectious, for he and all his laboratory assistants contracted the illness. This characteristic led to studies of its potential as a biological weapon, including involuntary human experimentation by Japan among civilian, political and military prisoners, and its probable use in warfare during World War II. Later, in the United States, voluntary human experimentation occurred in the 1950s-1960s with penitentiary inmates and non-combatant soldiers. Soviet Union scientists allegedly developed a vaccine-resistant strain, which they tested as a biological weapon in 1982-1983., (Published by Elsevier Inc.)

Francisella tularensis subsp. tularensis strain SchuS4 (Ftt) is a highly virulent intracellular bacterium. Inhalation of 10 or fewer organisms results in an acute and potentially lethal disease called pneumonic tularemia. Ftt infections occur naturally in the U.S. and Ftt was developed as a bioweapon. Thus, there is a need for vaccines that protect against this deadly pathogen. Although a live vaccine strain of Francisella tularensis (LVS) exists, LVS fails to generate long-lived protective immunity against modest challenge doses of Ftt. We recently identified an important role for high avidity CD4 + T cells in short-term protection and hypothesized that expanding this pool of cells would improve overall vaccine efficacy with regard to longevity and challenge dose. In support of our hypothesis, application of a prime/boost vaccination strategy increased the pool of high avidity CD4 + T cells which correlated with improved survival following challenge with either increased doses of virulent Ftt or at late time points after vaccination. In summary, we demonstrate that both epitope selection and vaccination strategies that expand antigen-specific T cells correlate with superior immunity to Ftt as measured by survival., (Copyright © 2017. Published by Elsevier Ltd.)