Investigation of a Human Case of Francisella tularensis Infection, United Kingdom, 2023.

Tularemia, caused by Francisella tularensis, is not known to occur in the United Kingdom. We report a case of tularemia diagnosed in July 2023 in a UK patient with no travel in the 6 weeks before symptom onset. We describe the subsequent multiagency investigation into possible routes of acquisition.

Tularemia: a case series from an endemic area in Hajnówka County, Norteast Poland. / Opis serii przypadków tularemii z obszaru endemicznego na terenie powiatu hajnowskiego.

BACKGROUND: Tularemia is a zoonotic disease caused by the bacterium Francisella tularensis. It may manifest itself in various clinical forms, but in Poland the ulcerative-glandular or glandular forms of tularemia predominate. One of the routes of infection with F. tularensis is through a tick or insect bite. A patient may show no symptoms or report flu-like symptoms and painful lumps adjacent to the bite site. The differential diagnosis of localized lymphadenopathy accompanied by flu-like symptoms should include tularemia, especially in endemic areas. Lymphadenitis usually requires surgical intervention and is often unsuccessfully treated with beta-lactam antibiotics before the diagnosis of tularemia is established. OBJECTIVE: The aim of the study was to analyze and present the epidemiology and clinical presentation of tularemia in a highly endemic area, in which ticks are an important vector of F. tularensis. MATERIAL AND METHODS: We have analyzed epidemiological and medical reports on the confirmed tularemia cases from Hajnówka County in 2014-2022. We describe three patients from the specific endemic area who were diagnosed with granular tularemia in 2022. RESULTS: We have found high local exposition to Francisella tularensis infection in the Narewka community, generally consistent with the seasonality of tick activity and human activity outdoors. CONCLUSIONS: The medical practitioner in such endemic areas must be aware that tularemia should be considered when diagnosing of flu-like symptoms accompanied by lymphadenopathy in patients bitten by ticks or insects in the summer and early autumn months. Early diagnosis and targeted antibiotic therapy are the basis for effective treatment of tularemia.

[Erythema and flu symptoms of a hunter with pre-existing conditions]. / Erythem und grippale Symptome bei einem Jäger mit Vorerkrankungen.

INTRODUCTION: A hunter with a history of oncology, flu-like symptoms and ring-shaped erythema was treated with doxycycline in an outpatient setting on suspicion of a tick-borne disease. After obtaining a positive Francisella tularensis serology, antibiotic treatment was continued for a total of 21 days, followed by freedom of symptoms and falling CRP, but without prompt serological follow-up. In contrast to the previously described tularemia cases in Switzerland, the article shows less pronounced local finding without palpable lymphadenopathy.

Oropharyngeal tularemia outbreak linked to drinking contaminated tap water in North-Western Iran.

Tularemia is a widespread bacterial disease caused by Francisella tularensis. Iran is an endemic country for this zoonosis. In this report, we present a 2020 tularemia outbreak in a village in northwestern Iran involving 15 patients with the oropharyngeal form of the disease. This outbreak was probably linked to the consumption of contaminated drinking water.

Tick abundance and infection with three zoonotic bacteria are heterogeneous in a Belgian peri-urban forest.

Ixodes ricinus is a vector of several pathogens of public health interest. While forests are the primary habitat for I. ricinus, its abundance and infection prevalence are expected to vary within forest stands. This study assesses the spatio-temporal variations in tick abundance and infection prevalence with three pathogens in and around a peri-urban forest where human exposure is high. Ticks were sampled multiple times in 2016 and 2018 in multiple locations with a diversity of undergrowth, using the consecutive drags method. Three zoonotic pathogens were screened for, Borrelia burgdorferi s.l., Coxiella burnetii, and Francisella tularensis. The influence of season, type of site and micro-environmental factors on tick abundance were assessed with negative binomial generalized linear mixed-effects models. We collected 1642 nymphs and 181 adult ticks. Ticks were most abundant in the spring, in warmer temperatures, and where undergrowth was higher. Sites with vegetation unaffected by human presence had higher abundance of ticks. Forest undergrowth type and height were significant predictors of the level of tick abundance in a forest. The consecutive drags method is expected to provide more precise estimates of tick abundance, presumably through more varied contacts with foliage. Borrelia burgdorferi s.l. prevalence was estimated from pooled ticks at 5.33%, C. burnetii was detected in six pools and F. tularensis was not detected. Borrelia afzelii was the dominant B. burgdorferi genospecies. Tick abundance and B. burgdorferi s.l. infection prevalence were lower than other estimates in Belgian forests.

Francisella tularensis Infection Causing Parinaud Oculoglandular Syndrome.

BACKGROUND Parinaud oculoglandular syndrome is a unilateral granulomatous palpebral conjunctivitis associated with preauricular, submandibular, and cervical lymphadenopathies. Several infectious diseases can cause Parinaud oculoglandular syndrome, usually with a conjunctival entry. The most common underlying pathology is cat scratch disease, followed by the oculoglandular form of tularemia. Diagnosis is usually a serious challenge as these infections are themselves rare. On the other hand, Parinaud oculoglandular syndrome may be a rare manifestation of more common disorders (eg, tuberculosis, syphilis, mumps, herpes simplex and Epstein-Barr virus, adenovirus, Rickettsia, Sporothrix, Chlamydia infections). CASE REPORT We present the case of a 66-year-old man with granulomatous conjunctivitis and ipsilateral preauricular, submandibular, and upper cervical lymphadenopathies following a superficial corneal injury. Although the systematic amoxicillin/clavulanic acid and metronidazole antibiotic therapy started immediately at admission, the suppuration of the lymph nodes required surgical drainage. Based on his anamnesis (sheep breeding; a twig scratching his eye 2 days before the initial attendance) and symptoms, a zoonosis, namely the oculoglandular form of tularemia, was suspected, empiric ciprofloxacin therapy was administered, and the patient recovered without sequelae. The Francisella tularensis infection was eventually confirmed by microagglutination serologic assay. CONCLUSIONS If Parinaud oculoglandular syndrome is diagnosed and cat scratch fever as the most common etiology is not likely, other zoonoses, especially the oculoglandular form of tularemia, should be suspected. Serology is the most common laboratory method of diagnosing tularemia. Empiric fluoroquinolone (ciprofloxacin) or aminoglycoside (gentamicin or streptomycin) antibiotic therapy should be started immediately at the slightest suspicion of oculoglandular tularemia.

The geographic distribution, and the biotic and abiotic predictors of select zoonotic pathogen detections in Canadian polar bears.

Increasing Arctic temperatures are facilitating the northward expansion of more southerly hosts, vectors, and pathogens, exposing naïve populations to pathogens not typical at northern latitudes. To understand such rapidly changing host-pathogen dynamics, we need sensitive and robust surveillance tools. Here, we use a novel multiplexed magnetic-capture and droplet digital PCR (ddPCR) tool to assess a sentinel Arctic species, the polar bear (Ursus maritimus; n = 68), for the presence of five zoonotic pathogens (Erysipelothrix rhusiopathiae, Francisella tularensis, Mycobacterium tuberculosis complex, Toxoplasma gondii and Trichinella spp.), and observe associations between pathogen presence and biotic and abiotic predictors. We made two novel detections: the first detection of a Mycobacterium tuberculosis complex member in Arctic wildlife and the first of E. rhusiopathiae in a polar bear. We found a prevalence of 37% for E. rhusiopathiae, 16% for F. tularensis, 29% for Mycobacterium tuberculosis complex, 18% for T. gondii, and 75% for Trichinella spp. We also identify associations with bear age (Trichinella spp.), harvest season (F. tularensis and MTBC), and human settlements (E. rhusiopathiae, F. tularensis, MTBC, and Trichinella spp.). We demonstrate that monitoring a sentinel species, the polar bear, could be a powerful tool in disease surveillance and highlight the need to better characterize pathogen distributions and diversity in the Arctic.

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.

Epidemiology of tularemia in the countries of the WHO Eastern Mediterranean Region (EMRO): A systematic review and meta-analysis.

BACKGROUND: Francisella tularensis, the bacterium that causes tularemia, has been a persistent and widespread pathogen in various regions of the world for centuries. Francisella tularensis can affect humans and various domestic and wild animals. The current study aimed to determine the epidemiological status of tularemia in countries of the WHO Eastern Mediterranean Region (EMRO) through a systematic review and meta-analysis. METHODS: All included studies were identified through a systematic search of online databases, including Scopus, PubMed, Web of Science, and EMBASE, through July 26, 2022, using keywords and suitable combinations. We focused on cross-sectional studies investigating the prevalence of F. tularensis. The weighted pooled prevalence was calculated using a random-effects model. RESULTS: A total of 206 studies were identified, of which 20 were finally included in the analysis. The human seroprevalence of tularemia in WHO-EMRO countries was 6.2% (95% CI, 4.2 9.2). In the subgroup analysis, anti-F. tularensis antibodies were found in 6.92% and 5.5% of the high-risk individuals and Iran, respectively. The pooled prevalence of F. tularensis in environmental samples (water and soil) from the WHO-EMRO countries was 5.8% (9.4% by PCR and 0.5% by culture). In addition, 2.5% (95% CI, 0.2 0.22.7) of ticks in WHO-EMRO countries were positive for F. tularensis. The pooled prevalence of F. tularensis in rodents is 2.0% (1.1% by PCR and 3.7% by serology). In addition, 0.6% of domestic ruminants (0.4% by PCR and 2.4% by serology) were positive for F. tularensis in WHO-EMRO countries. CONCLUSION: According to the results of the present study, tularemia is an endemic but neglected disease in the WHO-EMRO region. However, most studies on tularemia are limited to a few countries in this region. Studies on tularemia in human populations, reservoirs, and vectors have been conducted in all countries in the WHO-EMRO region to obtain more detailed information about the epidemiology of tularemia in these regions.

Thoracic manifestations of tularaemia: a case series.

BACKGROUND: Tularaemia is a zoonotic disease caused by Francisella tularensis, a highly virulent bacterium that affects humans and small wild animals. It is transmitted through direct contact with infected animals or indirectly through contaminated soil, water or arthropod bites (e.g. ticks). Primary thoracic manifestations of tularaemia are infrequent and, therefore, a diagnostic challenge for clinicians. METHODS: We report six tularaemia cases with exclusively thoracic involvement diagnosed in a clinic for pulmonary diseases in Bavaria between 10/2020 and 02/2022. RESULTS: All patients lived or were active in rural areas, four reported a recent tick bite. All patients presented with thoracic lymphadenopathy and pulmonary tumours or consolidations; all underwent bronchoscopy with EBUS-TBNA of lymph nodes, three lung biopsies as well. Five patients showed inflammatory changes in the endobronchial mucosa. The main histological findings were necrotic epithelioid granulomas with remarkable granulocyte infiltration. All cases were identified by positive serology, five by PCR (here identification of F.t. ssp. Holarctica) from biopsy as well. As first-line therapy, oral ciprofloxacin was given (5/6); in 2/6 cases, a combination of quinolone-rifampicin was given. CONCLUSIONS: Pulmonary tularaemia may occur after tick bites and without extrathoracic manifestations. In patients who present with thoracic lymphadenopathy and pulmonary consolidations and who are exposed to increased outdoor activities, tularaemia should be included in the diagnostic pathway. Histologically, the presence of neutrophil-granulocyte infiltrations might help to distinguish tularaemia from other granulomatous infections, e.g. tuberculosis. The combination of quinolone-rifampicin rather than i.v. gentamicin reduced length of hospital stay in two patients.

Targeting Tularemia: Clinical, Laboratory, and Treatment Outcomes From an 11-year Retrospective Observational Cohort in Northern Sweden.

BACKGROUND: Tularemia is an important reemerging disease with a multimodal transmission pattern. Treatment outcomes of current recommended antibiotic regimens (including ciprofloxacin and doxycycline) remain unclear. In this retrospective cohort study, we report clinical, laboratory, geographical, and treatment outcomes of laboratory-confirmed tularemia cases over an 11-year period in Northern Sweden. METHODS: Data from reported tularemia cases (aged >10 years at time of study) in Norrbotten county between 2011 and 2021 were collected through review of electronic medical records and participant questionnaires; 415 of 784 accepted participation (52.9%). Of these, 327 were laboratory-confirmed cases (serology and/or polymerase chain reaction). A multivariable logistic regression model was used to investigate variables associated with retreatment. RESULTS: Median age of participants was 54 years (interquartile range [IQR], 41.5-65) and 49.2% were female. Although ulceroglandular tularemia was the predominant form (n = 215, 65.7%), there were several cases of pulmonary tularemia (n = 40; 12.2%). Inflammatory markers were largely nonspecific, with monocytosis frequently observed (n = 36/75; 48%). Tularemia was often misdiagnosed on presentation (n = 158, 48.3%), with 65 (19.9%) receiving initial inappropriate antibiotics and 102 (31.2%) retreated. Persistent lymphadenopathy was infrequent (n = 22, 6.7%), with 10 undergoing surgical interventions. In multivariable analysis of variables associated with retreatment, we highlight differences in time until receiving appropriate antibiotics (8 [IQR, 3.25-20.75] vs 7 [IQR, 4-11.25] days; adjusted P = .076), and doxycycline-based treatment regimen (vs ciprofloxacin; adjusted P = .084), although this was not significant after correction for multiple comparisons. CONCLUSIONS: We comprehensively summarize clinical, laboratory, and treatment outcomes of type B tularemia. Targeting tularemia requires clinical awareness, early diagnosis, and timely commencement of treatment for an appropriate duration.

Successful treatment of glandular tularemia with azithromycin in a pregnant woman in Austria.

Treatment of tularemia during pregnancy is challenging due to toxicity of standard treatment regimens. Here, we report a 31-year-old woman with glandular tularemia who was successfully treated with intravenous azithromycin. Follow-up examinations over a 6-month period showed a sustained response to treatment. She later gave birth to a healthy child.

Surveillance for diseases, pathogens, and toxicants of muskrat (Ondatra zibethicus) in Pennsylvania and surrounding regions.

Using diagnostic data and contemporary sampling efforts, we conducted surveillance for a diversity of pathogens, toxicants, and diseases of muskrats (Ondatra zibethicus). Between 1977 and 2019, 26 diagnostic cases were examined from Kansas and throughout the Southeast and Mid-Atlantic, USA. We identified multiple causes of mortality in muskrats, but trauma (8/26), Tyzzer's disease (5/6), and cysticercosis (5/26) were the most common. We also conducted necropsies, during November 2018-January 2019 Pennsylvania muskrat trapping season, on 380 trapper-harvested muskrat carcasses after the pelt was removed. Tissue samples and exudate were tested for presence of or exposure to a suite of pathogens and contaminants. Gastrointestinal tracts were examined for helminths. Intestinal helminths were present in 39.2% of necropsied muskrats, with Hymenolepis spp. (62%) and echinostome spp. (44%) being the most common Molecular testing identified a low prevalence of infection with Clostridium piliforme in the feces and Sarcocystis spp. in the heart. We detected a low seroprevalence to Toxoplasma gondii (1/380). No muskrats were positive for Francisella tularensis or Babesia spp. Cysticercosis was detected in 20% (5/26) of diagnostic cases and 15% (57/380) of our trapper-harvested muskrats. Toxic concentrations of arsenic, cadmium, lead, or mercury were not detected in tested liver samples. Copper, molybdenum, and zinc concentrations were detected at acceptable levels comparative to previous studies. Parasite intensity and abundance were typical of historic reports; however, younger muskrats had higher intensity of infection than older muskrats which is contradictory to what has been previously reported. A diversity of pathogens and contaminants have been reported from muskrats, but the associated disease impacts are poorly understood. Our data are consistent with historic reports and highlight the wide range of parasites, pathogens and contaminants harbored by muskrats in Pennsylvania. The data collected are a critical component in assessing overall muskrat health and serve as a basis for understanding the impacts of disease on recent muskrat population declines.

Detection and Genotyping of Francisella tularensis in Animal Hosts and Vectors from Six Different Natural Landscape Areas, Gansu Province, China.

OBJECTIVE: Tularemia, also known as hare fever, is caused by the bacterium Francisella tularensis (F. tularensis) transmitted through diseased wild animals, blood sucking insects, or contaminated water or food, which is distributed worldwide. The purpose of this study was to investigate F. tularensis infection in animal hosts and vectors from six different natural landscape areas in Gansu Province and to identify the genotypes of the detected F. tularensis. METHODS: Rodents were captured by snap traps, and ticks were collected by dragging a cloth over the vegetation or from domestic animals. After species identification, DNA was isolated from the captured animals and detected by nested PCR assays targeting the F. tularensis fopA gene. The positive samples were further amplified to discriminate the species, and another two short-sequence tandem repeat regions (SSTR) were amplified to identify their genotypes. All positive fragments were sequenced and analyzed by ClustalX (5.0) and DNAClub software. RESULTS: A total of 407 rodents of 12 species were captured, among which six rodent species were positive for F. tularensis, with an overall prevalence of 3.93%. The geographical difference in infection rate was statistically significant. At the SSTR9 locus, there were 7 genotypes among positive rodent samples. A total of 1864 ticks were tested for evidence of tularemia by nested PCR assays, 69 of which were positive, with an average positive rate of 3.70% for F. tularensis in ticks. The positive rates were significantly different among different regions. Seven genotypes were identified at the SSTR9 locus, one of which seemed dominant in positive tick samples. All positive samples had the same genotype at the SSTR16 locus. CONCLUSION: There is natural infection of F. tularensis among animal vectors and hosts in Gansu Province, with diverse genotypes.

An outbreak of tularemia in southwestern Turkey.

INTRODUCTION: Tularemia has reemerged and spread throughout Turkey, and the number of cases has increased. In this study, we report on a waterborne outbreak of tularemia in the spring of 2013 in a region which was previously disease-free, and we investigated the reasons for the outbreak. METHODOLOGY: The index case, a 17-year-old male, was diagnosed with oropharyngeal tularemia. An outbreak investigation was initiated after receiving information from other patients with similar symptoms from the same village along with Balkica, Tavas, and Denizli. An epidemiological and environmental investigation was conducted. Tonsil swab specimens/lymph node aspirates collected from patients, and water samples collected from unchlorinated drinking water sources, were cultured. Additionally, a real-time polymerase chain reaction (RT-PCR) was performed on these samples. Serum samples from patients were analyzed for antibody response. RESULTS: A total of 7 patients were found in this outbreak investigation. The attack rate was found to be 1% among the people of the village and 25% among patients' family members. The drinking-water system was contaminated with F. tularensis during this outbreak. CONCLUSIONS: Lack of appropriate water infrastructure and sanitation was the primary reason for this tularemia outbreak in Turkey. Improving the water source infrastructure and sanitation should be the primary approach to preventing tularemia outbreaks.

Francisella tularensis human infections in a village of northwest Iran.

BACKGROUND: Recent seroepidemiological studies have suggested that tularemia could be an endemic bacterial zoonosis in Iran. METHODS: From January 2016 to June 2018, disease cases characterized by fever, cervical lymphadenopathy and ocular involvement were reported in Youzband Village of Kaleybar County, in the East Azerbaijan Province, northwestern Iran. Diagnostic tests included Francisella tularensis serology (including tube agglutination test and ELISA), PCR, and culture. RESULTS: Among 11 examined case-patients, the tularemia tube agglutination test was positive in ten and borderline in one. PCR detected the F. tularensis ISFtu2 elements and fopA gene in one rodent and a spring water sample from the same geographic area. CONCLUSIONS: Based on the clinical manifestations of the disease suggesting an oropharyngeal form of tularemia, serology results in case patients, and F. tularensis detection in the local fauna and aquatic environment, the water supply of the village was the likely source of the tularemia outbreak. Intervention such as dredging and chlorination of the main water storage tank of the village and training of villagers and health care workers in preventive measures and treatment of the illness helped control the infection.

High-resolution melting PCR assay as a powerful tool for the epidemiological surveillance of tularemia in Western Europe.

In Europe, tularemia is caused by Francisella tularensis subsp. holarctica and is a sporadic disease affecting mainly wildlife animals and humans. Classification of this species relies on canonical single nucleotide polymorphisms (canSNPs). Four main clades have been described for F. tularensis subsp. holarctica: B.4, B.6, B.12 and B.16. Phylogeographic studies have shown that clade B.6 is predominant in Western Europe and B.12 in Eastern and Central Europe. Based on this global phylogeny, we aimed to design a molecular typing assay for all genetic subclades of subclade B.11, which is the predominant subclade in clade B.6. We designed high-resolution melting (HRM) primers for the screening of 109 canSNPs divided in seven orders of discrimination for the molecular epidemiology analysis and tracking of Francisella tularensis subsp. holarctica in Western Europe.

Reevaluating limits of detection of 12 lateral flow immunoassays for the detection of Yersinia pestis, Francisella tularensis, and Bacillus anthracis spores using viable risk group-3 strains.

AIM: Rapid detection of biological agents in biodefense is critical for operational, tactical and strategic levels as well as for medical countermeasures. Yersinia pestis, Francisella tularensis, and Bacillus anthracis are high priority agents of biological warfare or bioterrorism and many response forces use lateral flow assays (LFAs) for their detection. Several companies produce these assays, which offer results in short time and are easy to use. Despite their importance, only few publications on the limits of detection (LOD) for LFAs are available. Most of these studies used inactivated bacteria or risk group-2 strains. As the inactivation process in previous studies might have affected the tests' performances, it was our aim in this study to determine and compare the LOD of several commercially available LFAs using viable risk group-3 strains. METHODS AND RESULTS: Lateral flow assays from four different companies for the detection of following bacteria were evaluated: Y. pestis, F. tularensis and B. anthracis spores. Two independent quantification methods for each target organism were applied, in order to ensure high quantification accuracy. LODs varied greatly between tests and organisms and ranged between 104 for Y. pestis-tests and as high as >109 for one B. anthracis-test. CONCLUSION: This work precisely determined the LODs of LFAs from four commercial suppliers. The herein determined LODs differed from results of previous studies. This illustrates the need for using accurately quantified viable risk group 3-strains for determining such LODs. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work bridges an important knowledge gap with regard to LFA LOD. The LODs determined in this study will facilitate better assessment of LFA-results. They illustrate that a negative LFA result is not suited to exclude the presence of the respective agent in the analyzed sample.