Ultrasound and ultrasound shear-wave elastography evaluation of ulceroglandular type of tularemia.

INTRODUCTION: Ultrasound (US) has an important place in imaging ulceroglandular type patients with tularemia. This study is a case series addressing the imaging findings of US and US shear-wave elastography in ulceroglandular type tularemia. DESCRIPTION: Three patients, two women, and one man, were included in our case series. The patients were admitted to our hospital with neck swelling, pain, and a palpable mass. After the diagnosis of tularemia was made as a result of the examinations performed on the patients, they were evaluated again with US and US shear-wave elastography. DISCUSSION: Since there are many diagnoses including ulceroglandular tularemia in the differential diagnosis of swelling, pain, and palpable mass in the neck, the patient must undergo a thorough evaluation process. US shear-wave elastography can provide significant benefits in identification and treatment follow-up in order to understand the ulceroglandular mass formation observed in the neck in tularemia and the stiffness and morphology of the tissues in the lymph nodes where involvement is observed and to distinguish them from the surrounding tissue.

Discovery of D8-03 as an Inhibitor of Intracellular Growth of Francisella tularensis.

Francisella tularensis is a Gram-negative facultative intracellular bacterial pathogen that is classified by the Centers for Disease Control and Prevention as a Tier 1 Select Agent. F. tularensis infection causes the disease tularemia, also known as rabbit fever. Treatment of tularemia is limited to few effective antibiotics which are associated with high relapse rates, toxicity, and potential emergence of antibiotic-resistant strains. Consequently, new therapeutic options for tularemia are needed. Through screening a focused chemical library and subsequent structure-activity relationship studies, we have discovered a new and potent inhibitor of intracellular growth of Francisella tularensis, D8-03. Importantly, D8-03 effectively reduces bacterial burden in mice infected with F. tularensis. Preliminary mechanistic investigations suggest that D8-03 works through a potentially novel host-dependent mechanism and serves as a promising lead compound for further development.

Causes of morbidity and mortality in wild cottontail rabbits in the eastern United States, 2013-2022.

Interest in causes of mortality of free-ranging, native North American lagomorphs has grown with the emergence of rabbit hemorrhagic disease virus 2 (RHDV2). Over the years 2013-2022, the Southeastern Cooperative Wildlife Disease Study received 119 Sylvilagus spp. case submissions from the central and eastern United States, comprising 147 rabbits. Most (86%) of these submissions occurred after detecting RHDV2 in the United States in 2020. Laboratory data from these rabbits were retrospectively evaluated for major causes, contributors to mortality, and pathogen detections. Gross and histologic examination was performed for 112 rabbits. Common primary causes of death included trauma (n = 49), bacterial disease (n = 31), emaciation (n = 6), and parasitism (n = 6). Among the 32 rabbits with bacterial disease, 12 were diagnosed with tularemia and 7 with pasteurellosis. Rabbits with pasteurellosis had disseminated abscessation, septicemia, and/or polyserositis. Less commonly, cutaneous fibroma (n = 2), notoedric mange (n = 2), encephalitozoonosis (n = 2), neoplasia (round-cell sarcoma; n = 1), and congenital abnormalities (n = 1) were diagnosed. RHDV2 was not detected in 123 rabbits tested. Although RHDV2 has not been detected in wild lagomorphs in the eastern United States, detections in domestic rabbits from the region emphasize the need for continued surveillance. Furthermore, continued surveillance for Francisella tularensis informs public health risk. Overall, increased knowledge of Sylvilagus spp. health furthers our understanding of diseases affecting these important prey and game species.

Disease and Mortality in Free-Ranging Leporids in Canada, 1990-2019: A Retrospective Study.

Passive surveillance of wildlife disease is a valuable tool for the identification of emerging and changing disease patterns. Free-ranging leporids play an important role in their ecosystem and in the culture and diet of Canadians; however, little is known about their health status and the zoonotic pathogens they may carry. We summarized major causes of mortality and morbidity, as well as incidental infections and lesions, of free-ranging leporids submitted to the Canadian Wildlife Health Cooperative (CWHC) between 1990 and 2019. We identified Canadian leporids as competent hosts for several zoonotic pathogens, most notably Francisella tularensis (20/569; 3.5%). Trauma was the most frequent cause of mortality or morbidity among leporids, accounting for 46.0% of cases submitted to the CWHC, followed by bacterial infections (13.7%) and emaciation (5.1%). Human-mediated mortalities, such as those involving machines (23.7%), were the most common trauma case type, with apparently healthy individuals overrepresented within this mortality group. Harvesters proved to be a valuable resource for the monitoring of diseased and infected animals, as more than half (69.6%) of the animals submitted by this group had an incidental infection or lesion. The results from this study provide a scientific understanding the cause of mortality in free-ranging leporids in Canada with relevance to public health, wildlife biologists, veterinarians, and potential future surveillance programs.

The Epidemiological Investigation of Yersinia pestis, Francisella tularensis, and Arenavirus Infections in Small Mammals in Northwestern Iran.

Background: The control and prevention of rodent-borne diseases are mainly based on our knowledge of ecology and the infectious status of their reservoir hosts. This study aimed to evaluate the prevalence of Francisella tularensis, Yersinia pestis, and arenavirus infections in small mammals and to assess the potential of disease occurrence in East Azerbaijan, northwest of Iran, in 2017 and 2018. Methods: Spleen and lung samples were obtained from all trapped small mammals. The real-time quantitative PCR (qPCR) method was used to detect nucleic acid sequences of F. tularensis, Y. pestis, and arenaviruses. Serum samples were tested for antibodies indicating the host response to F. tularensis and Y. pestis infections using the standard tube agglutination test and enzyme-linked immunosorbent assay (ELISA), respectively. Results: A total of 205 rodents, four Eulipotyphla, and one carnivore were captured. The most common rodent species captured (123 of 205 rodents, 60%) belonged to the genus Meriones (mainly Persian jird, Meriones persicus). In total, 317 fleas were removed from trapped animals. Flea species belonged to Xenopsylla buxtoni, Xenopsylla nuttalli, Stenoponia tripectinata, Paraceras melis, Ctenophthalmus rettigi smiti, Rhadinopsylla bivirgis, Paradoxopsyllus grenieri, and Nosopsyllus iranus. Using the qPCR tests, five spleen samples from M. persicus were positive for F. tularensis. The qPCR tests were negative for the detection of Y. pestis and arenaviruses. Finally, all serum samples tested were negative for antibodies against Y. pestis and F. tularensis. Conclusions: F. tularensis was the only zoonotic agent detected in rodents captured in East Azerbaijan. However, the diversity of trapped rodents and fleas provides the potential for the spread of various rodent-borne viral and bacterial diseases in the studied areas.

Tick-Borne Diseases.

Ticks are responsible for the vast majority of vector-borne illnesses in the United States. The number of reported tick-borne disease (TBD) cases has more than doubled in the past 20 years. The majority of TBD cases occur in warm weather months in individuals with recent outdoor activities in wooded areas. The risk of contracting a TBD is also highly dependent on geographic location. Between 24 and 48 hours of tick attachment is required for most disease transmission to occur. Only 50% to 70% of patients with a TBD will recall being bitten by a tick, and TBDs are often initially misdiagnosed as a viral illness. Most TBDs are easily treated when diagnosed early in their course.

Pediatric Oropharyngeal Tularemia Cases: Challenges in Management.

Background: Tularemia is one of the most prevalent zoonoses across the world. Patients in Turkiye mostly contract the oropharyngeal form, acquired through drinking, or contact with microorganism-contaminated water. Methods: Patients with oropharyngeal tularemia aged under 18 years and diagnosed between January 01, 2017, and December 31, 2020, were evaluated retrospectively. Tularemia was diagnosed in patients with compatible histories, symptoms, clinical presentations, and laboratory test results. Results: The mean age of 38 children was 12.1 ± 3.4 years, and the female/male ratio was 0.58 (14/24). The mean duration of symptoms on admission was 33.8 ± 26.2 days. All children had enlarged lymph nodes. Malaise, fever, and loss of appetite were other frequent symptoms. Patients were treated with antibiotics for a mean of 26.2 ± 18.8 days. Gentamycin was the most frequently used antibiotic (either alone or in combination) (n = 29, 76.3%). Twenty-six (68.4%) patients underwent surgical procedures in addition to antibiotherapy. Five (13.2%) required secondary total excision. Patients with higher leukocyte counts at admission received a combination of antibiotherapy plus surgery, rather than antibiotics alone. No relapses, reretreatment requirement, or mortality were observed after 12 months of follow-up. Conclusions: Oropharyngeal tularemia in children can require longer courses of antibiotic treatment with more than one drug and more frequent surgery than previously suggested in the literature, especially if the patients are admitted late to the hospital, symptom duration is prolonged, and appropriate treatment is initiated late. Higher leukocyte counts on admission may be prognostic for longer antibiotic treatment course and suppurative complications that require surgery. Raising awareness among patients and physicians is essential.

Wild lagomorphs as potential sources of Francisella tularensis in an urban zoo: a case study.

A 9-y-old captive male Pallas' cat (Otocolobus manul) had a 1-mo history of worsening lameness and was euthanized. The animal was submitted to the North Dakota State University-Veterinary Diagnostic Laboratory for autopsy with differential diagnoses of suspected degenerative joint disease or neoplasia. Autopsy revealed icteric tissues and pinpoint foci in the liver, spleen, and all lung lobes. PCR testing was positive for Francisella tularensis, the causative agent of tularemia. Additional cases of tularemia were later identified in wild eastern cottontail rabbits found dead at the same urban zoo. Tularemia has been reported in captive non-human primates and rodent populations with one case linked to wild lagomorph exposure, which was likely the route of exposure in our Pallas' cat case. Tularemia is an occupational risk for zoo staff and laboratorians. Pest management and disease surveillance of wild lagomorph populations in zoos are important preventive measures.

Francisella tularensis-specific antibody levels in sera from Swedish patients with suspected tularemia during a 13-year period.

Introduction: For a majority of tularemia patients, serology is the basis for the diagnosis. The aim of this study was to perform an analysis of the samples analyzed at a Swedish reference laboratory for the presence of Francisella tularensis-specific antibody levels in sera from individuals with suspected tularemia. Annual and monthly variations of the total number of samples and proportions of positive samples were analyzed, as well as the influence of age and gender. Methods: We performed a retrospective analysis of the presence of F. tularensis-specific antibodies in serological samples from patients with suspected tularemia analyzed during the period 2010 - 2022 at the University Hospital of Umeå in Sweden, a national reference laboratory, by use of various statistical methods. In total, some 15,100 serum samples had been analyzed for the presence of IgG and IgM antibodies by ELISA during the 13-year period. Results: Overall, there were higher number of samples with IgG positive or borderline titers, 2,522 and 921, respectively, than with IgM positive or borderline titers, 1,802 and 409, respectively. Repeated samples were obtained from some 1,930 individuals and approximately a third of the cases, which were initially seronegative, had seroconverted when resampled. Peak number of monthly samples were recorded in August and September, > 3,000. Annual numbers varied greatly and peak numbers were observed in 2015 and 2019, 1,832 and 2,250, respectively, whereas some other years the numbers were 700 - 800. There was also much variation in the annual and monthly percentages of positive samples and they varied between less than 10% to greater than 20%. The highest percentages of positive samples were recorded in September and October. IgG and IgM titers declined with age and these differences were highly significant for IgG titers, with decreasing average titers for each 20-year interval. Discussion: Collectively, the data demonstrate the marked annual and seasonal variations in tularemia sampling occurring in Sweden. Also, the proportion of positive samples increased during months and years with peak number of samples. Another notable finding was that average antibody titers decreased with increased age.

Tularemia on the rise in Switzerland? A one health approach is needed!

In the last 10 years, an increase in tularemia cases has been observed in both humans and animals in Switzerland. In these, infection with Francisella tularensis, the causative agent of the zoonotic disease tularemia, can occur through arthropod vectors or contact to infected animals or exposure to contaminated environmental sources. Currently, we are only able to postulate potential aetiologies: (i) behavioral changes of humans with more exposure to endemic habitats of infected arthropod vectors; (ii) an increased rate of tularemia infected ticks; (iii) increasing number and geographical regions of tick biotopes; (iv) increasing and/or more diverse reservoir populations; (v) increasing presence of bacteria in the environment; (vi) raised awareness and increased testing among physicians; (vii) improved laboratory techniques including molecular testing. To approach these questions, a one-health strategy is necessary. A functioning collaboration between public health, human medicine, and diagnostic and veterinary units for the control of tularemia must be established. Furthermore, the public should be included within citizen-supported-science-projects.

Field-Collected Ticks From Benton County, Arkansas, and Prevalence of Associated Pathogens.

The recovery of a Haemaphysalis longicornis Neumann (Acari: Ixodidae) tick from a dog in Benton County, Arkansas, in 2018 triggered a significant environmental sampling effort in Hobbs State Park Conservation Area. The objective of the investigation was to assess the tick population density and diversity, as well as identify potential tick-borne pathogens that could pose a risk to public health. During a week-long sampling period in August of 2018, a total of 6,154 ticks were collected, with the majority identified as Amblyomma americanum (L), (Acari: Ixodidae) commonly known as the lone star tick. No H. longicornis ticks were found despite the initial detection of this species in the area. This discrepancy highlights the importance of continued monitoring efforts to understand the dynamics of tick populations and their movements. The investigation also focused on pathogen detection, with ticks being pooled by species, age, and sex before being processed with various bioassays. The results revealed the presence of several tick-borne pathogens, including agents associated with ehrlichiosis (n = 12), tularemia (n = 2), and Bourbon virus (BRBV) disease (n = 1), as well as nonpathogenic rickettsial and anaplasmosis organisms. These findings emphasize the importance of public health messaging to raise awareness of the risks associated with exposure to tick-borne pathogens. Prevention measures, such as wearing protective clothing, using insect repellent, and conducting regular tick checks, should be emphasized to reduce the risk of tick-borne diseases. Continued surveillance efforts and research are also essential to improve our understanding of tick-borne disease epidemiology and develop effective control strategies.

Characterization of tularemia foci in the Republic of Kazakhstan from 2000 to 2020.

The wide distribution of tularemia in the territory of Kazakhstan is associated with landscape and geographical characteristics. This is explained by a combination of natural factors: the presence of certain types of rodents-reservoirs and sources, ectoparasites-carriers of the causative agent of tularemia. The study of the current spatial and temporal characterization of tularemia in Kazakhstan from 2000 to 2020 will determine the epidemiological status of tularemia and improve the monitoring system in Kazakhstan. In this work we demonstrated the results of a retrospective survey of natural foci of tularemia: analysis of vector, small mammal and human data. The spatial and temporal characteristics of tularemia from 2000 to 2020 in the territory of Kazakhstan were studied in comparison with historical data, including the description of tularemia outbreaks, the clinical picture, and the source of infection, transmission factors, and geographical coordinates of outbreak registration. Sampling was carried out by trapping rodents on snap traps and collecting ticks by rodent combing and by "flagging" methods. For the last 20 years, 85 human cases of tularemia have been reported. During the period from 2000 to 2020, more than 600 strains of F. tularensis were isolated from field rodents and ticks in the natural foci of tularemia. MLVA typing of F. tularensis strains isolated from natural foci of tularemia in Kazakhstan over the past 20 years. The results of retrospective monitoring indicate that currently active foci of tularemia include the Aktobe, West Kazakhstan, Almaty, East Kazakhstan, and Pavlodar regions. Low-activity natural foci are located in the territory of the Akmola, Karaganda, North Kazakhstan, Kostanay, Atyrau, Zhambyl, and Kyzylorda regions. There are no active natural foci of tularemia in the Mangystau and Turkestan regions. The widespread occurrence of tularemia in the country is associated with landscape and geographical features that contribute to the circulation of the pathogen in the natural focus. An analysis of natural foci of tularemia showed that it is necessary to continue monitoring studies of carriers and vectors for the presence of the causative agent of the F. tularensis, in order to prevent mass cases of human disease.

Functional characterization of Francisella tularensis subspecies holarctica genotypes during tick cell and macrophage infections using a proteogenomic approach.

Tularemia is a vector-borne disease caused by the Gram-negative bacterium Francisella tularensis. Known hosts and vectors in Europe are hare and ticks. F. tularensis is transmitted from ticks and animals, but also from the hydrotelluric environment and the consumption of contaminated water or food. A changing climate expands the range in which ticks can live and consequently might contribute to increasing case numbers of tularemia. Two subspecies of F. tularensis are human pathogenic. Francisella tularensis tularensis (Ftt) is endemic in North America, while Francisella tularensis holarctica (Fth) is the only subspecies causing tularemia in Europe. Ft is classified as a category A bioterrorism agent due to its low infectious dose, multiple modes of transmission, high infectivity and potential for airborne transmission and has become a global public health concern. In line with the European survey and previous phylogenetic studies, Switzerland shows the co-distribution of B.6 and B.12 strains with different geographical distribution and prevalence within the country. To establish itself in different host environments of ticks and mammals, F. tularensis presumably undergoes substantial changes on the transcriptomics and proteomic level. Here we investigate the transcriptomic and proteomic differences of five strains of Fth upon infection of rabbit macrophages and tick cells.

Current vaccine strategies and novel approaches to combatting Francisella infection.

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.

Water and mosquitoes as key components of the infective cycle of Francisella tularensis in Europe: a review.

Francisella tularensis is the pathogen of tularemia, a zoonotic disease that have a broad range of hosts. Its epidemiology is related to aquatic environments, particularly in the subspecies holarctica. In this review, we explore the role of water and mosquitoes in the epidemiology of Francisella in Europe. F. tularensis epidemiology has been linked to natural waters, where its persistence has been associated with biofilm and amebas. In Sweden and Finland, the European countries where most human cases have been reported, mosquito bites are a main route of transmission. F. tularensis is present in other European countries, but to date positive mosquitoes have not been found. Biofilm and amebas are potential sources of Francisella for mosquito larvae, however, mosquito vector capacity has not been demonstrated experimentally, with the need to be studied using local species to uncover a potential transmission adaptation. Transstadial, for persistence through life stages, and mechanical transmission, suggesting contaminated media as a source for infection, have been studied experimentally for mosquitoes, but their natural occurrence needs to be evaluated. It is important to clear up the role of different local mosquito species in the epidemiology of F. tularensis and their importance in all areas where tularemia is present.

Seroepidemiology of Human Tularemia-Systematic Review and Meta-analysis of Seroprevalence Studies.

Background: Seroepidemiologic studies of human tularemia have been conducted throughout the northern hemisphere. The purposes of this study were (1) to provide an overview of Francisella tularensis seroprevalence data, and (2) to generate an estimate of the proportion of study participants whose infection remained subclinical. Methods: We conducted a systematic review of F tularensis seroprevalence studies according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched PubMed, Embase, and Web of Science covering the period from 1951 to 2023. Results: The weighted pooled seroprevalence among 44 486 participants recruited in 52 studies was 3.7% (95% confidence interval [CI], 2.7-5.1). Reported seroprevalences ranged between 0.2% and 31.3%. Occupational activities associated with an increased likelihood of exposure (risk ratio, 3.51 [95% CI, 3.2-3.86]) and studies from North America versus Europe and Asia (4.53 [4.15-4.94]) were associated with significantly increased seropositive rates. Twenty-eight data sets (47%) reported clinical information on a total of 965 seropositive participants. The weighted pooled estimate for subclinical seropositivity was 84.4% (95% CI, 72.9%-991.7%). Studies from F tularensis type A areas (risk ratio, 0.37 [95% CI, .27-.51) and studies from sites where pulmonary tularemia prevailed (0.38 [.28-.51]) reported lower subclinical seropositivity rates than studies from type B areas and from areas of predominance of (ulcero)glandular or oropharyngeal tularemia, respectively. Conclusions: Throughout the northern hemisphere, only a small proportion of study participants showed serologic evidence of exposure to F tularensis. Eight of 10 seropositive participants had no historical evidence of past clinical tularemia.

An Unusual Etiology of Fluorodeoxyglucose Avid Intrathoracic Lymph Nodes.

A middle-aged man in his 50s, active smoker, presented to the pulmonary office for lung cancer evaluation. On a low-dose computed tomography for lung cancer screening, he was found to have an 8 mm endobronchial lesion in the right main stem bronchus. A PET-CT revealed no endobronchial lesion, but incidentally, fluorodeoxyglucose (FDG) avidity was present in the right hilar (SUV 13.2) and paratracheal lymph nodes (LNs). He underwent bronchoscopy and EBUS-TBNA of station 7 and 10 R LNs. The fine needle aspiration (FNA) revealed necrotizing epithelioid granuloma. The acid-fast bacilli (AFB) and Grocott methenamine silver (GMS) stains were negative. He had suffered from pneumonic tularemia 13 months ago and immunohistochemical staining for Francisella tularensis on FNA samples at Center for Disease Control and Prevention was negative. The intense positron emission tomography (PET) avidity was attributed to prior tularemic intrathoracic lymphadenitis without active tularemia, a rare occurrence. To the best of our knowledge, PET-positive intrathoracic lymph node beyond one year without evidence of active tularemia has not been previously reported.

Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularemia, 1993-2023.

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.

Efficacy of Doxycycline and Ciprofloxacin for Treatment of Pneumonic Tularemia in Cynomolgus Macaques.

BACKGROUND: The incidence of pneumonic tularemia is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCMs) in humans. The US Food and Drug Administration's Animal Model Qualification Program under the Drug Development Tools Program is a regulatory pathway for animal models used in MCM efficacy testing and approval under the Animal Rule. The National Institute of Allergy and Infectious Diseases and Biomedical Advanced Research and Development Authority worked together to qualify the cynomolgus macaque model of pneumonic tularemia. METHODS: Using the model parameters and end points defined in the qualified model, efficacy of the antibiotics doxycycline and ciprofloxacin was evaluated in separate studies. Antibiotic administration, aimed to model approved human dosing, was initiated at time points of 24 hours or 48 hours after onset of fever as an indicator of disease. RESULTS: Upon aerosol exposure (target dose of 1000 colony-forming units) to Francisella tularensis SchuS4, 80% of vehicle-treated macaques succumbed or were euthanized. Ciprofloxacin treatment led to 10 of 10 animals surviving irrespective of treatment time. Doxycycline administered at 48 hours post-fever led to 10 of 10 animals surviving, while 9/10 animals survived in the group treated with doxycycline 24 hours after fever. Selected surviving animals in both the placebo and doxycycline 48-hour group showed residual live bacteria in peripheral tissues, while there were no bacteria in tissues from ciprofloxacin-treated macaques. CONCLUSIONS: Both doxycycline and ciprofloxacin were efficacious in treatment of pneumonic tularemia, although clearance of bacteria may be different between the 2 drugs.

Systematic Review of Tularemia During Pregnancy.

BACKGROUND: Tularemia is caused by the gram-negative bacterium Francisella tularensis. Although rare, tularemia during pregnancy has been associated with pregnancy complications; data on efficacy of recommended antimicrobials for treatment are limited. We performed a systematic literature review to characterize clinical manifestations of tularemia during pregnancy and examine maternal, fetal, and neonatal outcomes with and without antimicrobial treatment. METHODS: We searched 9 databases, including Medline, Embase, Global Health, and PubMed Central, using terms related to tularemia and pregnancy. Articles reporting cases of tularemia with ≥1 maternal or fetal outcome were included. RESULTS: Of 5891 articles identified, 30 articles describing 52 cases of tularemia in pregnant patients met inclusion criteria. Cases were reported from 9 countries, and oropharyngeal and ulceroglandular tularemia were the most common presenting forms. A plurality (46%) of infections occurred in the second trimester. Six complications were observed: lymph node aspiration, lymph node excision, maternal bleeding, spontaneous abortion, intrauterine fetal demise, and preterm birth. No deaths among mothers were reported. Of 28 patients who received antimicrobial treatment, 1 pregnancy loss and 1 fetal death were reported. Among 24 untreated patients, 1 pregnancy loss and 3 fetal deaths were reported, including one where F. tularensis was detected in placental and fetal tissues. CONCLUSIONS: Pregnancy loss and other complications have been reported among cases of tularemia during pregnancy. However, risk of adverse outcomes may be lower when antimicrobials known to be effective are used. Without treatment, transplacental transmission appears possible. These data underscore the importance of prompt recognition and treatment of tularemia during pregnancy.