A waterborne tularemia outbreak in eastern of Turkiye: Evaluation of Adult and Pediatric patients

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Abstract Purpose Tularemia is a zoonotic disease that can cause outbreaks as well as sporadic cases. This study assessed to analyze patients identified in a waterborne tuaremia outbreak in a village in eastern Turkiye and to evaluate the adult and pediatric populations. Methods The study included patients who presented to the Infectious Diseases and Clinical Microbiology and Pediatrics outpatient clinics of Malazgirt State Hospital during the tularemia outbreak in January and February 2025 and were diagnosed with tularemia. Data on age, gender, clinical and laboratory findings, antibiotic regimens and durations, and complications were collected and analyzed. Results The study included 56 participants (mean age 24.6 ± 20.5 years, 44% female, 51% adult). No significant difference was found in the distribution of tularemia type between adult and pediatric patients (p = 0.198); the predominant type in both groups was the oropharyngeal form. Lymphadenopathy (LAP) was more frequent in adult patients (p < 0.05), abdominal pain was more frequent in pediatric patients (p < 0.001), and no significant differences were found in other clinical findings. Leukocytosis was significantly more frequent in pediatric patients compared to adults (p = 0.016). Treatment duration was statistically significantly longer in adult patients compared to pediatric patients (p < 0.001). One of the patients was pregnant who was treated with azithromycin and a healthy delivery was achieved. There were no cases resulting in sepsis or death. Conclusions Waterborne tularemia outbreaks can have different outcomes in different patient populations despite sharing a common causative pathogen. Therefore, individual patient assessments can be beneficial when managing an epidemic.
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A waterborne tularemia outbreak in eastern of Turkiye: Evaluation of Adult and Pediatric patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A waterborne tularemia outbreak in eastern of Turkiye: Evaluation of Adult and Pediatric patients Kamil MERT, Furkan ÖZTÜRK This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9212550/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Purpose Tularemia is a zoonotic disease that can cause outbreaks as well as sporadic cases. This study assessed to analyze patients identified in a waterborne tuaremia outbreak in a village in eastern Turkiye and to evaluate the adult and pediatric populations. Methods The study included patients who presented to the Infectious Diseases and Clinical Microbiology and Pediatrics outpatient clinics of Malazgirt State Hospital during the tularemia outbreak in January and February 2025 and were diagnosed with tularemia. Data on age, gender, clinical and laboratory findings, antibiotic regimens and durations, and complications were collected and analyzed. Results The study included 56 participants (mean age 24.6 ± 20.5 years, 44% female, 51% adult). No significant difference was found in the distribution of tularemia type between adult and pediatric patients (p = 0.198); the predominant type in both groups was the oropharyngeal form. Lymphadenopathy (LAP) was more frequent in adult patients (p < 0.05), abdominal pain was more frequent in pediatric patients (p < 0.001), and no significant differences were found in other clinical findings. Leukocytosis was significantly more frequent in pediatric patients compared to adults (p = 0.016). Treatment duration was statistically significantly longer in adult patients compared to pediatric patients (p < 0.001). One of the patients was pregnant who was treated with azithromycin and a healthy delivery was achieved. There were no cases resulting in sepsis or death. Conclusions Waterborne tularemia outbreaks can have different outcomes in different patient populations despite sharing a common causative pathogen. Therefore, individual patient assessments can be beneficial when managing an epidemic. Lymphadenopathy Outbrake Treatment Tularemia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Tularemia is a zoonotic disease caused by Francisella tularensis , a gram-negative coccobacillus. The majority of infections in humans are caused by the Tularensis and Holarctica subspecies[ 1 ]. The disease can be transmitted to humans through arthropod bites, animal contact, consumption of contaminated water and food, or through the respiratory tract. It can present in different clinical forms, including glandular, oculoglandular, ulceroglandular, oropharyngeal, pneumonic, and typhoid forms[ 2 ]. Diagnosis can be made using culture, serological, and molecular methods. Parenteral aminoglycosides such as gentamicin and streptomycin are recommended for cases requiring hospitalization, while ciprofloxacin and doxycycline are recommended for outpatients[ 3 ]. The first tularemia outbreak in Turkiye was reported in 1936, and since then, outbreaks have occurred in different regions of the country, primarily in Marmara, Western Black Sea, and Central Anatolia[ 4 ]. Although various studies on tularemia have been published in the Eastern Anatolia region in recent years, studies presenting and analyzing outbreaks from this region are limited[ 5 – 7 ]. In this study, the tularemia outbreak observed in Malazgirt district of Mus in January and February 2025 was evaluated, and the clinical and laboratory findings of 56 patients were analyzed. Methods Patients and Study Design The study included 56 patients (29 adults, 27 children) who presented to the Infectious Diseases and Clinical Microbiology and Pediatrics outpatient clinics of Malazgirt State Hospital during the tularemia outbreak in January and February 2025 and were diagnosed with tularemia. Patients aged ≥ 16 were considered adults, and those aged < 16 were considered children. All patients resided in Bescatak village, Malazgirt district, Mus. Patients whose serum samples sent to the National High-Risk Pathogens Reference Laboratory of the General Directorate of Public Health showed a positive Francisella Tularensis microagglutination result at a titer of ≥ 1/160 were included in the study.Eight pediatric patients with positive microagglutination results at titers < 1/160, but whose clinical findings were consistent with tularemia and who were unable to attend hospital for control testing, were also considered to have tularemia and included in the study. Patients with exudative tonsillopharyngitis were considered to have oropharyngeal tularemia, those with conjunctivitis were considered to have oculoglandular tularemia, those with isolated LAP were considered to have glandular tularemia, and those with systemic infection findings without LAP were considered to have typhoid tularemia. Data on age, gender, clinical and laboratory findings, antibiotic regimens and durations, and complications such as abscess/suppuration were collected and analyzed. Statistical Analysis Statistical analyses were performed using IBM SPSS Statistics (or equivalent statistical software). The distribution characteristics of continuous variables were evaluated using visualization methods and the Shapiro–Wilk test. Non-parametric tests were preferred for comparing continuous variables that did not exhibit a normal distribution or had unbalanced group sizes. The Mann–Whitney U test was used for comparing continuous variables between two independent groups, and the Kruskal–Wallis test was used for comparing more than two groups. For variables showing a statistically significant difference in the Kruskal–Wallis test results, post-hoc Mann–Whitney U tests with Bonferroni correction were applied to determine which groups showed the difference. Categorical variables were presented as numbers and percentages. For comparing categorical variables between groups, the Pearson chi-square test was used when expected cell counts were ≥ 5, while the Fisher exact test or the Fisher–Freeman–Haltonexact test was preferred for multi-category tables when expected cell counts were < 5. Some variables, such as leukocyte count, were analyzed both numerically and categorically (yes/no) to strengthen the clinical significance of the findings. No imputation method was applied for missing data; analyses were performed on cases with available data for the relevant variable (complete-case analysis). Two-sided p-tests were used in all statistical tests, and p < 0.05 was considered statistically significant. Epidemic Management Bescatak is a village located on the Malazgirt-Karacoban road and near the Murat River, with a population of 838 according to 2024 data. Following the identification of tularemia patients residing in the village, contact was made with the relevant public health units. Francisella Tularensis was detected in samples taken from the water reservoir supplying the village. It was learned that the reservoir was open at the top, the water flow was not constant, and the water in the reservoir may have been contaminated by rodents. After identifying the source, chlorination was carried out in the reservoir by the relevant public health units, and the source was controlled. Results The study included 56 patients. 29 (51%) of the patients were adults and 27 (48%) were children. 31 (55%) of the patients were male and 25 (44%) were female. No significant difference was found in gender distribution between adult and child patients (p = 0.81). The mean age was 24.6 ± 20.5 (3–78, median 17, IQR 9-39.3) years. 23 (41%) patients were diagnosed with oropharyngeal tularemia, 19 (33%) with glandular tularemia, 8 (14%) with oculoglandular tularemia, and 6 (10%) with typhoid tularemia. Ulceroglandular tularemia and tularemia pneumonia were not detected. No significant difference was found in tularemia type distribution between adult and pediatric patients (p = 0.198). While 11 (19%) patients showed no LAP, 43 (76%) had cervical LAP, 3 (5%) had periauricular LAP, and one each (1%) had inguinal and axillary LAP. The presence of LAP was significantly higher in adult patients compared to pediatric (p < 0.05). Skin manifestations were observed in 13 (23%) patients, and abdominal pain in 14 (25%) patients (Figs. 1 , 2 , 3 ). While erythrocyte sedimentation rates (ESR) were significantly higher in patients with skin involvement (p = 0.030); no statistically significant difference was observed between the groups in terms of leukocytosis, C-reactive protein (CRP), platelet, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Conjunctivitis was observed in 9 (16%) patients, and exudative tonsillopharyngitis in 23 (41%) patients. It was found that conjunctivitis was more frequent in patients with skin lesions (p = 0.003). Abdominal pain was significantly more frequent in pediatric patients compared to adults (p < 0.001); however, no statistically significant differences were found between the groups in terms of other clinical findings (Table 1 ). Table 1 Comparison of clinical characteristics of adult and pediatric patients Parameter Pediatric (n = 27) Adult (n = 29) p-value * Gender (Male), n (%) 14 (%51.8) 17 (%58.6) 0.810 Clinical form, n (%) 0.198 - Oropharyngeal 9 (%33.3) 14 (%48.3) - Glandular 8 (%29.6) 11 (%37.9) - Oculoglandular 5 (%18.5) 3 (%10.3) - Typhoidal Tularemia 5 (%18.5) 1 (%3.4) Clinical findings, n (%) - LAP 17 (%63.0) 28 (%96.6) 0.002 - Abdominal pain 13 (%48.1) 1 (%3.4) < 0.001 - Abscess/Suppuration 2 (%7.4) 8 (%27.6) 0.079 - Tonsillopharyngitis 9 (%33.3) 14 (%48.3) 0.288 - Conjunctivitis 5 (%18.5) 4 (%13.8) 0.724 Seconder skin findings, n (%) 0.064 - None 22 (%81.5) 21 (%72.4) - Erythema Nodosum 5 (%18.5) 2 (%6.9) - Dermatitis 0 (%0) 5 (%17.2) - Sweet Syndrom 0 (%0) 1 (%3.4) * p < 0.05 was considered statistically significant Microagglutination titers were positive in 19 (33%) patients (≥ 1/1280), 29 (51%) patients (1/160–640), and 8 (14%) patients (< 1/160). Complete blood counts at initial presentation showed leukocytosis in 27 (48%) patients, the mean leukocyte count was 10.4 ± 3.4 ×10³/µL, with a median value of 10.0 ×10³/µL (IQR: 8.2–12.5). Only one patient had leukopenia. Leukocytosis was significantly more frequent in pediatric patients compared to adults (p = 0.016). Thrombocytosis was observed in 12 (21%) patients, the mean platelet count was 319.8 ± 119.6 ×10³/µL, and the median platelet count was 319×10³/µL (IQR: 217.5–393.8). Only three patients had thrombocytopenia. ESR was elevated in 38 (86%) patients, the mean ESR was 41.3 ± 17.7 mm/hour, with a median value of 42 mm/hour (IQR: 28.5–55.5). CRP was elevated in 55 (98%) patients, the mean CRP level was 57.8 ± 41.4 mg/L, with a median CRP value of 54.0 mg/L (IQR: 23.0–81.5). No patients had acute renal failure, elevated total bilirubin, or hypernatremia. Six (10%) patients had elevated ALT, and five (8%) had elevated AST. ALT levels were significantly higher in adult patients (p < 0.001); however, the mean ALT level in both groups was lower than the reference value. Hyperkalemia was observed in only one patient, hypokalemia in four (7%) patients, and hyponatremia in eighteen (32%) patients. Table 2 Laboratory findings and treatment durations of adult and pediatric patients Parameter Pediatric (n = 27) Adult (n = 29) p-value * Leukocytosis, n (%) 18 (%66.7) 9 (%31.0) 0.015 Leukocyte (10 3 /mm 3 ), Mean ± SD 11.6 ± 3.5 9.3 ± 3.0 0.010 Platelet (10 3 /mm 3 ), Mean ± SD 352 ± 105 290 ± 126 0.051 Sedimantation (mm/hour), Mean ± SD 41.4 ± 16.0 41.3 ± 18.8 0.978 CRP (mg/L), Median (IQR) 45.0 (52) 57.0 (66) 0.915 ALT (U/L), Mean ± SD 15.5 ± 5.6 29.5 ± 15.2 < 0.001 AST (U/L), Median (IQR) 26.0 (11) 24.0 (17) 0.767 Agglutination Titer, Median 320 640 0.062 Treatment duration (Day), Median (IQR) 14 (7) 21 (7) < 0.001 * p < 0.05 was considered statistically significant Six (10%) of the patients received inadequate and/or irregular antibiotic treatment, while the mean treatment duration was 16.6 ± 7.5 days, with a median value of 14 days (IQR: 14–21). Treatment duration was statistically significantly longer in adult patients compared to pediatric patients (Table 2 ). The median treatment duration was 21 days (mean 19.2 ± 6.6 days) in adult patients, while the median treatment duration was 14 days (mean 14.0 ± 7.6 days) in pediatric patients (p < 0.001). Of the patients, 52 (92%) received ciprofloxacin, 8 (14%) received doxycycline, 3 (5%) received gentamicin, 2 (3) received azithromycin, and 1 (1%) received streptomycin. One patient using ciprofloxacin developed peripheral neuropathy, resulting in a switch to doxycycline. No significant difference was found in antibiotic selection between adult and pediatric patients. No significant difference was found in the types of antibiotics used among tularemia types. Drainage was performed in 10 (17%) patients who developed abscess and/or suppuration, and lymphadenopathy excision was performed in 2 (3%) patients. Two of the patients were lactating, and one was pregnant (Figs. 4 , 5 ). The pregnant patient was treated with azithromycin and a healthy delivery was achieved. There were no cases resulting in sepsis or death. Discussion First identified in the United States of America (USA), tularemia is a zoonotic disease frequently seen in the Northern Hemisphere[ 8 ]. A recent review analyzed articles published between 1993 and 2023 concerning human tularemia and found that Turkiye had the highest number of cases[ 9 ]. The first tularemia outbreak in Turkiye was reported in 1936, and since then, outbreaks have occurred in various regions of the country, primarily in Marmara, Western Black Sea, and Central Anatolia[ 4 ]. Articles analyzing outbreaks from the Eastern Anatolia region are rare; most recently, Benli evaluated two tularemia outbreaks in Mus between 2017 and 2019[ 5 ]. This study examines a tularemia outbreak in the Malazgirt district of Mus in 2025. It is known that tularemia outbreaks in Turkiye are waterborne and occur during the autumn and winter months[ 4 ]. It is thought that outbreaks occur as a result of the increase in the rodent population after rainy periods and the contact of these animals with water sources[ 10 ]. In our study, the outbreak occurred in January and February, consistent with the literature, and originated from the reservoir that supplies water to the villagers. In the review presented by Nelson et al., it was determined that 61.7% of tularemia cases were male, and similarly, the number of male cases (55%) was higher in our study[ 9 ]. In waterborne outbreaks, in addition to adult cases, child cases can also be seen[ 11 ]. 48% of the cases in our study were children. In European countries and the USA, arthropod-associated ulceroglandular form is the most common type of tularemia; however, in outbreaks seen in Turkiye, the majority of cases are oropharyngeal tularemia due to waterborne transmission[ 12 ]. In line with Turkish data, the dominant form in our study was oropharyngeal tularemia (42%). In a multicenter study by Erdem et al., the dominant oropharyngeal form was followed by glandular, oculoglandular, and ulceroglandular forms, respectively, with only one patient each having typhoid form and tularemia pneumonia[ 13 ]. This study included patients treated for tularemia from 41 different centers, and epidemiological risk factors were not included. In our study, the predominant oropharyngeal form was similarly followed by glandular (33%) and oculoglandular (14%) forms, but unlike others, the ulceroglandular form was not observed. No significant difference was found in tularemia form distribution between adult and pediatric patients (p = 0.198). In an article compiling tularemia cases seen in Bursa, Turkiye over a ten-year period, LAP was observed in 85% of the 205 tularemia cases evaluated[ 14 ]. The location of LAP in the cases was mostly cervical, with periauricular and axillary locations in a small number of cases. In our study, LAP was observed in 81% of the cases, with the predominant location being the cervical region; axillary and inguinal LAP were observed in one patient each. The presence of LAP was significantly higher in adult patients compared to pediatric (p < 0.05). Tularemia can present with a skin rash in any form of the disease. In an article published by Senel et al., 151 cases of tularemia were evaluated, and skin rash was detected in 36 (23%) patients[ 15 ]. In our study, skin rash was detected in 13 (23%) patients, and no ulcerative lesions were found. In a study by Helvacı et al., tonsillitis was detected in 29% and conjunctivitis in 8% of tularemia cases[ 14 ]. In our study, conjunctivitis was observed at higher rates (16%) and exudative tonsillopharyngitis at 42%. The lower rates observed in a similar study may be due to the inclusion of sporadic cases with suspected different routes of transmission, in addition to waterborne epidemic patients. In a study conducted by Gozel et al., which evaluated 68 tularemia patients, similar to our study, no significant difference was found between adult and pediatric patient groups in terms of conjunctivitis, tonsillopharyngitis, and skin lesions[ 16 ]. It is noteworthy that abdominal pain was observed in 14 (25%) of the cases in our study, and all but one of these cases were children. The gold standard serological method used in the diagnosis of tularemia is the microagglutination test[ 3 ]. In the study conducted by Helvacı et al., the microagglutination test titer was found to be < 1/160 in 13% of the diagnosed patients and ≥ 1/1280 in 56%[ 14 ]. Similarly, in our study, the titer was < 1/160 in 14% of the patients and ≥ 1/1280 in 51%. There is no specific laboratory finding for tularemia. In a study evaluating 145 tularemia cases, the mean leukocyte count was found to be 9,200/mm 3 , while in a similar study, leukocytosis was detected in 41% of tularemia patients, with an average leukocyte count of 9,610/mm 3 [ 17 , 18 ]. In our study, leukocytosis was observed in 48% of the patients, while the mean leukocyte count was 10.4 ± 3.4 ×10³/µL. In the study conducted by Gozel et al., no significant difference was found in the presence of leukocytosis between adult and pediatric patient groups. [ 16 ]. In contrast to that study, in our study, leukocytosis was significantly more frequent in pediatric patients compared to adults (p = 0.016). Leukopenia was observed in only one patient. There is insufficient data in the literature regarding the effect of tularemia on platelet count; in our study, thrombocytosis was observed in 21% of patients, the mean platelet count was 319.8 ± 119.6 ×10³/µL, and thrombocytopenia was observed in only three patients. In the study by Cakır Kıymaz et al., ALT elevation was detected in 5% of patients and AST elevation in 9%, while in our study these rates were 10% and 8%, respectively[ 18 ]. In the study by Meric et al., ESR elevation was detected in all patients[ 17 ]. In a similar study, ESR elevation was detected in 60% of patients and CRP elevation in 76%[ 18 ]. In our study, CRP elevation was detected in all patients except one, and ESR elevation was detected in 86%. Currently, agents such as gentamicin, streptomycin, doxycycline, and ciprofloxacin are recommended for the treatment of tularemia. In a study evaluating 1.163 tularemia patients diagnosed in the USA between 2006 and 2021, it was found that 62.8% of patients receiving high-potency antibiotic therapy were treated with tetracycline, 39.6% with fluoroquinolone, and 23.8% with aminoglycoside therapy[ 19 ].The same study showed that tetracycline use was less common in the pediatric patient group. In another study evaluating 327 tularemia patients diagnosed in Northern Sweden between 2011 and 2021, ciprofloxacin was the most frequently initiated antibiotic (68.2%)[ 20 ]. The majority of cases in our study received ciprofloxacin treatment (92%). Aminoglycoside use was limited due to concerns about nephrotoxicity/ototoxicity and the lack of audiometric evaluation facilities in our hospital. Data on the use of doxycycline in the treatment of pediatric tularemia cases are limited, and some experts therefore recommend against using doxycycline in treatment[ 21 ]. Of the 8 cases treated with doxycycline in our study, only one was a child. In our study, mean treatment duration was 16.6 ± 7.5 days; adult patients received treatment for a longer period (p < 0.001). No significant difference was found in antibiotic selection between adult and pediatric patients. The use of gentamicin and ciprofloxacin is recommended in the treatment of pregnant patients[ 22 ]. However, the use of these antibiotics in pregnant patients is not licensed in many countries due to the risk of fetal toxicity[ 22 ]. Although azithromycin, an alternative agent, is considered safe for fetal health, there are limitations regarding its use in the treatment of tularemia. The dominant subspecies in North America, Tularensis , is susceptible to erythromycin; however, the subspecies Holarctica , which is dominant in Asia, Europe, and Turkiye, is generally resistant to erythromycin[ 22 ]. In recent years, pregnant tularemia cases treated with azithromycin have been reported in Europe[ 23 , 24 ]. A pregnant oropharyngeal tularemia case reported from Turkey by Arslan et al. was successfully treated with azithromycin for 6 weeks[ 25 ]. In our follow-up case of pregnant woman with oropharyngeal tularemia, the patient was informed about the potential risks of the infection and first-line antibiotic regimens to fetal health, as well as alternative antibiotic regimens. Following a decision made with the patient, azithromycin 500 mg/day was initiated for three consecutive days within a week, and clinical improvement was achieved at the end of the four-week treatment period. Although studies suggest that tularemia infections in Central and Eastern Europe are frequently caused by macrolide-resistant strains, there are cases successfully treated in Turkiye[ 26 ]. In our follow-up case, subspecies determination was not possible. Our study has some limitations. First, some patients with positive microagglutination titers but below the diagnostic cut-off and for whom control testing was not available were included in the study. Secondly, tularemia was diagnosed solely by serological methods, subspecies identification and susceptibility analysis could not be performed. Finally, the study did not include an analysis of treatment outcomes and success. Conclusion Waterborne tularemia outbreaks can have different outcomes in different patient populations despite sharing a common causative pathogen. Therefore, individual patient assessments can be beneficial when managing an epidemic. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript . Competing Interests: The authors have no relevant financial or non-financial interests to disclose . Author Contributions: All authors contributed to the conceptualization, design of the study and the data collection. FÖ, analyzed the data. KM, drafted the manuscript. All authors reviewed and approved the final manuscript. Data Availability: Data from the nationwide Turkish administrative health registries are subject to Turkish legislation and can only be made available to a third party under certain conditions. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. This study was approved by the institutional review board and the research and ethics committee at Mus Alparslan University (11.04.2025 and numbered 189789). Consent to Participate: Informed consent was obtained from all individual participants included in the study. Written informed consent was obtained from the parents. Consent to Publish: The authors affirm that human research participants provided informed consent for publication of the images in Figures 1-5 . Acknowledgements: We wish to thanks all personnel at Malazgirt State Hospital, especially former chief physician Esma Söylemez. References Petersen JM, Molins CR. Subpopulations of Francisella tularensis ssp. tularensis and holarctica: identification and associated epidemiology. Future Microbiol. 2010;5(4):649–61. 10.2217/fmb.10.17 . Penn RL. Francisella tularensis (tularemia). In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 6th ed. 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Erdem H, Ozturk-Engin D, Yesilyurt M, Karabay O, Elaldi N, Celebi G, et al. Evaluation of tularaemia courses: a multicentre study from Turkey. Clin Microbiol Infect. 2014;20(12):O1042–51. 10.1111/1469-0691.12741 . Helvaci S, Gedikoğlu S, Akalin H, Oral HB. Tularemia in Bursa, Turkey: 205 cases in ten years. Eur J Epidemiol. 2000;16(3):271–6. 10.1023/a:1007610724801 . Şenel E, Satılmış Ö, Acar B. Dermatologic manifestations of tularemia: a study of 151 cases in the mid-Anatolian region of Turkey. Int J Dermatol. 2015;54(1):e33–7. 10.1111/ijd.12431 . Gozel MG, Engin A, Altuntas EE, Salk İ, Kaya A, Celik C, et al. Evaluation of clinical and laboratory findings of pediatric and adult patients with oropharyngeal tularemia in Turkey: a combination of surgical drainage and antibiotic therapy increases treatment success. Jpn J Infect Dis. 2014;67(4):295–9. 10.7883/yoken.67.295 . Meric M, Willke A, Finke EJ, Grunow R, Sayan M, Erdogan S, et al. Evaluation of clinical, laboratory, and therapeutic features of 145 tularemia cases: the role of quinolones in oropharyngeal tularemia. APMIS. 2008;116(1):66–73. 10.1111/j.1600-0463.2008.00901 . Çakır Kıymaz Y, Bolat S, Katırcı B, Aldemir O, Altınkaya I, Ozcan MM, et al. Evaluation of the clinical characteristics, laboratory parameters, and antibiotic treatment in patients diagnosed with tularemia. J Infect Chemother. 2025;31(2):102546. Wu HJ, Bostic TD, Horiuchi K, Kugeler KJ, Mead PS, Nelson CA. Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006–2021. Clin Infect Dis. 2024;78(Suppl 1):S29–37. 10.1093/cid/ciad689 . Plymoth M, Lundqvist R, Nystedt A, Sjöstedt A, Gustafsson TN. Targeting Tularemia: Clinical, Laboratory, and Treatment Outcomes From an 11-year Retrospective Observational Cohort in Northern Sweden. Clin Infect Dis. 2024;78(5):1222–31. 10.1093/cid/ciae098 . American Academy of Pediatrics. Tularemia. In: Red Book: 2024–2027 Report of the Committee on Infectious Diseases, 33rd Edition, Kimberlin DW, Banerjee R, Barnett E, et a, editors, American Academy of Pediatrics, 2024. Kılıc S, Yesilyurt M, Tularemia. A General Overview on Current Treatment Options. Klimik J. 2011;24(1):2–10. Dentan C, Pavese P, Pelloux I, Boisset S, Brion JP, Stahl JP, et al. Treatment of tularemia in pregnant woman, France. Emerg Infect Dis. 2013;19(6):996–8. 10.3201/eid1906.130138 . Schubert L, Koelz M, Kussmann M, et al. Successful treatment of glandular tularemia with azithromycin in a pregnant woman in Austria. Infection. 2024;52(3):1181–4. 10.1007/s15010-023-02160-2 . Arslan M, Cavnar AM, Turan M. Successful Treatment of Glandular Tularemia with Azithromycin in a Pregnant Patient and Literature Review. Microbiol Bul. 2025;59(2):242–9. 10.5578/mb.202502133 . Gyuranecz M, Birdsell DN, Splettstoesser W, Seibold E, Beckstrom-Sternberg SM, Makrai L, et al. Phylogeography of Francisella tularensis subsp. holarctica, Europe. Emerg Infect Dis. 2012;18(2):290–3. 10.3201/eid1802.111305 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 May, 2026 Reviews received at journal 03 May, 2026 Reviewers agreed at journal 27 Apr, 2026 Reviews received at journal 25 Apr, 2026 Reviewers agreed at journal 06 Apr, 2026 Reviewers invited by journal 05 Apr, 2026 Editor invited by journal 30 Mar, 2026 Editor assigned by journal 27 Mar, 2026 Submission checks completed at journal 27 Mar, 2026 First submitted to journal 24 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9212550","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":618374866,"identity":"835e43a3-9025-4552-948d-0d7d58471600","order_by":0,"name":"Kamil MERT","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBACCSA+8ADEYu8BC/DwEaUlAaSU5wyQBaTZiNHCANYikQPWwkBQi2T76cQDiTk2+faSbw8+/phjJ8PGwPzw0Q08WqR5cjccSNyWZtkjnZdscHBbMtBhbMbGOXi0yDGAtRw24JHOMZM4uI0ZqIWHTRqvFv63IC3/DXgkz4C01BPWIi0BtuWAAY8ED0jLYcJaJGeAbUk24DmTY2xwdttxHjZmAn6ROJ+7+cPHbXYG7O1nDB9Ubqu252dvfvgYnxYsgJk05aNgFIyCUTAKsAAAgw9Hh6TYhkEAAAAASUVORK5CYII=","orcid":"","institution":"Istanbul Medipol Mega Hospital","correspondingAuthor":true,"prefix":"","firstName":"Kamil","middleName":"","lastName":"MERT","suffix":""},{"id":618374882,"identity":"0e46e9a0-02a9-4e57-a557-2e9ec6d13ad8","order_by":1,"name":"Furkan ÖZTÜRK","email":"","orcid":"","institution":"Ankara City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Furkan","middleName":"","lastName":"ÖZTÜRK","suffix":""}],"badges":[],"createdAt":"2026-03-24 13:26:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9212550/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9212550/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106545015,"identity":"b4fbf582-b599-40f9-ad1a-0cb64b943cb1","added_by":"auto","created_at":"2026-04-09 16:43:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":865029,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSkin rash on the hands of a male tularemia patient\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9212550/v1/1ef574116cb2667b2867118b.png"},{"id":106725029,"identity":"3ba54d5b-0525-42e0-b1e7-89b3209f897c","added_by":"auto","created_at":"2026-04-12 18:31:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":700286,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSkin rash on the legs of a female tularemia patient\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9212550/v1/43b9206616c3d52d6f4d3833.png"},{"id":106545017,"identity":"6e6974c5-769f-43f7-bc53-699ae5bac069","added_by":"auto","created_at":"2026-04-09 16:43:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":395253,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in tularemia rash with antibiotic treatment\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9212550/v1/263a3ac2915c7a807745f880.png"},{"id":106725305,"identity":"f242fe3b-3692-41c2-93c5-da2488c55651","added_by":"auto","created_at":"2026-04-12 18:32:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":761604,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCervical lymphadenopathy in pregnant tularemia patient\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-9212550/v1/6dbfdbd0de3872ecf0effe16.png"},{"id":106545019,"identity":"3a4b1ad4-8f62-464e-aeef-77cc729c2018","added_by":"auto","created_at":"2026-04-09 16:43:25","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":954030,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLymphadenopathy with suppurative symptoms during lactation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-9212550/v1/9f4c664f530cadea677ea2f7.png"},{"id":106726935,"identity":"8be2e597-5a23-4fa0-bca3-5e657666c447","added_by":"auto","created_at":"2026-04-12 18:37:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4731561,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9212550/v1/f43f9b74-a6c4-4418-97b3-8e1b156c6264.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A waterborne tularemia outbreak in eastern of Turkiye: Evaluation of Adult and Pediatric patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTularemia is a zoonotic disease caused by \u003cem\u003eFrancisella tularensis\u003c/em\u003e, a gram-negative coccobacillus. The majority of infections in humans are caused by the \u003cem\u003eTularensis\u003c/em\u003e and \u003cem\u003eHolarctica\u003c/em\u003e subspecies[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The disease can be transmitted to humans through arthropod bites, animal contact, consumption of contaminated water and food, or through the respiratory tract. It can present in different clinical forms, including glandular, oculoglandular, ulceroglandular, oropharyngeal, pneumonic, and typhoid forms[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Diagnosis can be made using culture, serological, and molecular methods. Parenteral aminoglycosides such as gentamicin and streptomycin are recommended for cases requiring hospitalization, while ciprofloxacin and doxycycline are recommended for outpatients[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe first tularemia outbreak in Turkiye was reported in 1936, and since then, outbreaks have occurred in different regions of the country, primarily in Marmara, Western Black Sea, and Central Anatolia[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although various studies on tularemia have been published in the Eastern Anatolia region in recent years, studies presenting and analyzing outbreaks from this region are limited[\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In this study, the tularemia outbreak observed in Malazgirt district of Mus in January and February 2025 was evaluated, and the clinical and laboratory findings of 56 patients were analyzed.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003ePatients and Study Design\u003c/p\u003e \u003cp\u003eThe study included 56 patients (29 adults, 27 children) who presented to the Infectious Diseases and Clinical Microbiology and Pediatrics outpatient clinics of Malazgirt State Hospital during the tularemia outbreak in January and February 2025 and were diagnosed with tularemia. Patients aged\u0026thinsp;\u0026ge;\u0026thinsp;16 were considered adults, and those aged\u0026thinsp;\u0026lt;\u0026thinsp;16 were considered children. All patients resided in Bescatak village, Malazgirt district, Mus. Patients whose serum samples sent to the National High-Risk Pathogens Reference Laboratory of the General Directorate of Public Health showed a positive \u003cem\u003eFrancisella Tularensis\u003c/em\u003e microagglutination result at a titer of \u0026ge;\u0026thinsp;1/160 were included in the study.Eight pediatric patients with positive microagglutination results at titers\u0026thinsp;\u0026lt;\u0026thinsp;1/160, but whose clinical findings were consistent with tularemia and who were unable to attend hospital for control testing, were also considered to have tularemia and included in the study. Patients with exudative tonsillopharyngitis were considered to have oropharyngeal tularemia, those with conjunctivitis were considered to have oculoglandular tularemia, those with isolated LAP were considered to have glandular tularemia, and those with systemic infection findings without LAP were considered to have typhoid tularemia. Data on age, gender, clinical and laboratory findings, antibiotic regimens and durations, and complications such as abscess/suppuration were collected and analyzed.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics (or equivalent statistical software). The distribution characteristics of continuous variables were evaluated using visualization methods and the Shapiro\u0026ndash;Wilk test. Non-parametric tests were preferred for comparing continuous variables that did not exhibit a normal distribution or had unbalanced group sizes. The Mann\u0026ndash;Whitney U test was used for comparing continuous variables between two independent groups, and the Kruskal\u0026ndash;Wallis test was used for comparing more than two groups. For variables showing a statistically significant difference in the Kruskal\u0026ndash;Wallis test results, post-hoc Mann\u0026ndash;Whitney U tests with Bonferroni correction were applied to determine which groups showed the difference. Categorical variables were presented as numbers and percentages. For comparing categorical variables between groups, the Pearson chi-square test was used when expected cell counts were \u0026ge;\u0026thinsp;5, while the Fisher exact test or the Fisher\u0026ndash;Freeman\u0026ndash;Haltonexact test was preferred for multi-category tables when expected cell counts were \u0026lt;\u0026thinsp;5. Some variables, such as leukocyte count, were analyzed both numerically and categorically (yes/no) to strengthen the clinical significance of the findings. No imputation method was applied for missing data; analyses were performed on cases with available data for the relevant variable (complete-case analysis). Two-sided p-tests were used in all statistical tests, and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003eEpidemic Management\u003c/p\u003e \u003cp\u003eBescatak is a village located on the Malazgirt-Karacoban road and near the Murat River, with a population of 838 according to 2024 data. Following the identification of tularemia patients residing in the village, contact was made with the relevant public health units. \u003cem\u003eFrancisella Tularensis\u003c/em\u003e was detected in samples taken from the water reservoir supplying the village. It was learned that the reservoir was open at the top, the water flow was not constant, and the water in the reservoir may have been contaminated by rodents. After identifying the source, chlorination was carried out in the reservoir by the relevant public health units, and the source was controlled.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 56 patients. 29 (51%) of the patients were adults and 27 (48%) were children. 31 (55%) of the patients were male and 25 (44%) were female. No significant difference was found in gender distribution between adult and child patients (p\u0026thinsp;=\u0026thinsp;0.81). The mean age was 24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.5 (3\u0026ndash;78, median 17, IQR 9-39.3) years. 23 (41%) patients were diagnosed with oropharyngeal tularemia, 19 (33%) with glandular tularemia, 8 (14%) with oculoglandular tularemia, and 6 (10%) with typhoid tularemia. Ulceroglandular tularemia and tularemia pneumonia were not detected. No significant difference was found in tularemia type distribution between adult and pediatric patients (p\u0026thinsp;=\u0026thinsp;0.198). While 11 (19%) patients showed no LAP, 43 (76%) had cervical LAP, 3 (5%) had periauricular LAP, and one each (1%) had inguinal and axillary LAP. The presence of LAP was significantly higher in adult patients compared to pediatric (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Skin manifestations were observed in 13 (23%) patients, and abdominal pain in 14 (25%) patients (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). While erythrocyte sedimentation rates (ESR) were significantly higher in patients with skin involvement (p\u0026thinsp;=\u0026thinsp;0.030); no statistically significant difference was observed between the groups in terms of leukocytosis, C-reactive protein (CRP), platelet, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Conjunctivitis was observed in 9 (16%) patients, and exudative tonsillopharyngitis in 23 (41%) patients. It was found that conjunctivitis was more frequent in patients with skin lesions (p\u0026thinsp;=\u0026thinsp;0.003). Abdominal pain was significantly more frequent in pediatric patients compared to adults (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001); however, no statistically significant differences were found between the groups in terms of other clinical findings (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical characteristics of adult and pediatric patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePediatric (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAdult (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender (Male), n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (%51.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (%58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.810\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical form, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.198\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Oropharyngeal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (%33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (%48.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Glandular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (%29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (%37.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Oculoglandular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (%18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (%10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Typhoidal Tularemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (%18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (%3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical findings, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- LAP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (%63.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28 (%96.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Abdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (%48.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (%3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Abscess/Suppuration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (%7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (%27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Tonsillopharyngitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (%33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (%48.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Conjunctivitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (%18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (%13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.724\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSeconder skin findings, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- None\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (%81.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21 (%72.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Erythema Nodosum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (%18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (%6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Dermatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (%0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (%17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Sweet Syndrom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (%0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (%3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMicroagglutination titers were positive in 19 (33%) patients (\u0026ge;\u0026thinsp;1/1280), 29 (51%) patients (1/160\u0026ndash;640), and 8 (14%) patients (\u0026lt;\u0026thinsp;1/160). Complete blood counts at initial presentation showed leukocytosis in 27 (48%) patients, the mean leukocyte count was 10.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 \u0026times;10\u0026sup3;/\u0026micro;L, with a median value of 10.0 \u0026times;10\u0026sup3;/\u0026micro;L (IQR: 8.2\u0026ndash;12.5). Only one patient had leukopenia. Leukocytosis was significantly more frequent in pediatric patients compared to adults (p\u0026thinsp;=\u0026thinsp;0.016). Thrombocytosis was observed in 12 (21%) patients, the mean platelet count was 319.8\u0026thinsp;\u0026plusmn;\u0026thinsp;119.6 \u0026times;10\u0026sup3;/\u0026micro;L, and the median platelet count was 319\u0026times;10\u0026sup3;/\u0026micro;L (IQR: 217.5\u0026ndash;393.8). Only three patients had thrombocytopenia. ESR was elevated in 38 (86%) patients, the mean ESR was 41.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.7 mm/hour, with a median value of 42 mm/hour (IQR: 28.5\u0026ndash;55.5). CRP was elevated in 55 (98%) patients, the mean CRP level was 57.8\u0026thinsp;\u0026plusmn;\u0026thinsp;41.4 mg/L, with a median CRP value of 54.0 mg/L (IQR: 23.0\u0026ndash;81.5). No patients had acute renal failure, elevated total bilirubin, or hypernatremia. Six (10%) patients had elevated ALT, and five (8%) had elevated AST. ALT levels were significantly higher in adult patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001); however, the mean ALT level in both groups was lower than the reference value. Hyperkalemia was observed in only one patient, hypokalemia in four (7%) patients, and hyponatremia in eighteen (32%) patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory findings and treatment durations of adult and pediatric patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePediatric (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAdult (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeukocytosis, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (%66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (%31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeukocyte (10\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/mm\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlatelet (10\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e/mm\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e352\u0026thinsp;\u0026plusmn;\u0026thinsp;105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e290\u0026thinsp;\u0026plusmn;\u0026thinsp;126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSedimantation (mm/hour), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.3\u0026thinsp;\u0026plusmn;\u0026thinsp;18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP (mg/L), Median (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.0 (52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.0 (66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.915\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALT (U/L), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAST (U/L), Median (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.0 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.0 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.767\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAgglutination Titer, Median\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e640\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment duration (Day), Median (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSix (10%) of the patients received inadequate and/or irregular antibiotic treatment, while the mean treatment duration was 16.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5 days, with a median value of 14 days (IQR: 14\u0026ndash;21). Treatment duration was statistically significantly longer in adult patients compared to pediatric patients (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median treatment duration was 21 days (mean 19.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6 days) in adult patients, while the median treatment duration was 14 days (mean 14.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6 days) in pediatric patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Of the patients, 52 (92%) received ciprofloxacin, 8 (14%) received doxycycline, 3 (5%) received gentamicin, 2 (3) received azithromycin, and 1 (1%) received streptomycin. One patient using ciprofloxacin developed peripheral neuropathy, resulting in a switch to doxycycline. No significant difference was found in antibiotic selection between adult and pediatric patients. No significant difference was found in the types of antibiotics used among tularemia types. Drainage was performed in 10 (17%) patients who developed abscess and/or suppuration, and lymphadenopathy excision was performed in 2 (3%) patients. Two of the patients were lactating, and one was pregnant (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The pregnant patient was treated with azithromycin and a healthy delivery was achieved. There were no cases resulting in sepsis or death.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFirst identified in the United States of America (USA), tularemia is a zoonotic disease frequently seen in the Northern Hemisphere[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A recent review analyzed articles published between 1993 and 2023 concerning human tularemia and found that Turkiye had the highest number of cases[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The first tularemia outbreak in Turkiye was reported in 1936, and since then, outbreaks have occurred in various regions of the country, primarily in Marmara, Western Black Sea, and Central Anatolia[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Articles analyzing outbreaks from the Eastern Anatolia region are rare; most recently, Benli evaluated two tularemia outbreaks in Mus between 2017 and 2019[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This study examines a tularemia outbreak in the Malazgirt district of Mus in 2025.\u003c/p\u003e \u003cp\u003eIt is known that tularemia outbreaks in Turkiye are waterborne and occur during the autumn and winter months[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It is thought that outbreaks occur as a result of the increase in the rodent population after rainy periods and the contact of these animals with water sources[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In our study, the outbreak occurred in January and February, consistent with the literature, and originated from the reservoir that supplies water to the villagers. In the review presented by Nelson et al., it was determined that 61.7% of tularemia cases were male, and similarly, the number of male cases (55%) was higher in our study[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In waterborne outbreaks, in addition to adult cases, child cases can also be seen[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. 48% of the cases in our study were children.\u003c/p\u003e \u003cp\u003eIn European countries and the USA, arthropod-associated ulceroglandular form is the most common type of tularemia; however, in outbreaks seen in Turkiye, the majority of cases are oropharyngeal tularemia due to waterborne transmission[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In line with Turkish data, the dominant form in our study was oropharyngeal tularemia (42%). In a multicenter study by Erdem et al., the dominant oropharyngeal form was followed by glandular, oculoglandular, and ulceroglandular forms, respectively, with only one patient each having typhoid form and tularemia pneumonia[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This study included patients treated for tularemia from 41 different centers, and epidemiological risk factors were not included. In our study, the predominant oropharyngeal form was similarly followed by glandular (33%) and oculoglandular (14%) forms, but unlike others, the ulceroglandular form was not observed. No significant difference was found in tularemia form distribution between adult and pediatric patients (p\u0026thinsp;=\u0026thinsp;0.198). In an article compiling tularemia cases seen in Bursa, Turkiye over a ten-year period, LAP was observed in 85% of the 205 tularemia cases evaluated[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The location of LAP in the cases was mostly cervical, with periauricular and axillary locations in a small number of cases. In our study, LAP was observed in 81% of the cases, with the predominant location being the cervical region; axillary and inguinal LAP were observed in one patient each. The presence of LAP was significantly higher in adult patients compared to pediatric (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Tularemia can present with a skin rash in any form of the disease. In an article published by Senel et al., 151 cases of tularemia were evaluated, and skin rash was detected in 36 (23%) patients[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our study, skin rash was detected in 13 (23%) patients, and no ulcerative lesions were found. In a study by Helvacı et al., tonsillitis was detected in 29% and conjunctivitis in 8% of tularemia cases[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In our study, conjunctivitis was observed at higher rates (16%) and exudative tonsillopharyngitis at 42%. The lower rates observed in a similar study may be due to the inclusion of sporadic cases with suspected different routes of transmission, in addition to waterborne epidemic patients. In a study conducted by Gozel et al., which evaluated 68 tularemia patients, similar to our study, no significant difference was found between adult and pediatric patient groups in terms of conjunctivitis, tonsillopharyngitis, and skin lesions[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It is noteworthy that abdominal pain was observed in 14 (25%) of the cases in our study, and all but one of these cases were children.\u003c/p\u003e \u003cp\u003eThe gold standard serological method used in the diagnosis of tularemia is the microagglutination test[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In the study conducted by Helvacı et al., the microagglutination test titer was found to be \u0026lt;\u0026thinsp;1/160 in 13% of the diagnosed patients and \u0026ge;\u0026thinsp;1/1280 in 56%[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Similarly, in our study, the titer was \u0026lt;\u0026thinsp;1/160 in 14% of the patients and \u0026ge;\u0026thinsp;1/1280 in 51%. There is no specific laboratory finding for tularemia. In a study evaluating 145 tularemia cases, the mean leukocyte count was found to be 9,200/mm\u003csup\u003e3\u003c/sup\u003e, while in a similar study, leukocytosis was detected in 41% of tularemia patients, with an average leukocyte count of 9,610/mm\u003csup\u003e3\u003c/sup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our study, leukocytosis was observed in 48% of the patients, while the mean leukocyte count was 10.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 \u0026times;10\u0026sup3;/\u0026micro;L. In the study conducted by Gozel et al., no significant difference was found in the presence of leukocytosis between adult and pediatric patient groups. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In contrast to that study, in our study, leukocytosis was significantly more frequent in pediatric patients compared to adults (p\u0026thinsp;=\u0026thinsp;0.016). Leukopenia was observed in only one patient. There is insufficient data in the literature regarding the effect of tularemia on platelet count; in our study, thrombocytosis was observed in 21% of patients, the mean platelet count was 319.8\u0026thinsp;\u0026plusmn;\u0026thinsp;119.6 \u0026times;10\u0026sup3;/\u0026micro;L, and thrombocytopenia was observed in only three patients. In the study by Cakır Kıymaz et al., ALT elevation was detected in 5% of patients and AST elevation in 9%, while in our study these rates were 10% and 8%, respectively[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In the study by Meric et al., ESR elevation was detected in all patients[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In a similar study, ESR elevation was detected in 60% of patients and CRP elevation in 76%[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our study, CRP elevation was detected in all patients except one, and ESR elevation was detected in 86%.\u003c/p\u003e \u003cp\u003eCurrently, agents such as gentamicin, streptomycin, doxycycline, and ciprofloxacin are recommended for the treatment of tularemia. In a study evaluating 1.163 tularemia patients diagnosed in the USA between 2006 and 2021, it was found that 62.8% of patients receiving high-potency antibiotic therapy were treated with tetracycline, 39.6% with fluoroquinolone, and 23.8% with aminoglycoside therapy[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].The same study showed that tetracycline use was less common in the pediatric patient group. In another study evaluating 327 tularemia patients diagnosed in Northern Sweden between 2011 and 2021, ciprofloxacin was the most frequently initiated antibiotic (68.2%)[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The majority of cases in our study received ciprofloxacin treatment (92%). Aminoglycoside use was limited due to concerns about nephrotoxicity/ototoxicity and the lack of audiometric evaluation facilities in our hospital. Data on the use of doxycycline in the treatment of pediatric tularemia cases are limited, and some experts therefore recommend against using doxycycline in treatment[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Of the 8 cases treated with doxycycline in our study, only one was a child. In our study, mean treatment duration was 16.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5 days; adult patients received treatment for a longer period (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant difference was found in antibiotic selection between adult and pediatric patients.\u003c/p\u003e \u003cp\u003eThe use of gentamicin and ciprofloxacin is recommended in the treatment of pregnant patients[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, the use of these antibiotics in pregnant patients is not licensed in many countries due to the risk of fetal toxicity[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although azithromycin, an alternative agent, is considered safe for fetal health, there are limitations regarding its use in the treatment of tularemia. The dominant subspecies in North America, \u003cem\u003eTularensis\u003c/em\u003e, is susceptible to erythromycin; however, the subspecies \u003cem\u003eHolarctica\u003c/em\u003e, which is dominant in Asia, Europe, and Turkiye, is generally resistant to erythromycin[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In recent years, pregnant tularemia cases treated with azithromycin have been reported in Europe[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A pregnant oropharyngeal tularemia case reported from Turkey by Arslan et al. was successfully treated with azithromycin for 6 weeks[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our follow-up case of pregnant woman with oropharyngeal tularemia, the patient was informed about the potential risks of the infection and first-line antibiotic regimens to fetal health, as well as alternative antibiotic regimens. Following a decision made with the patient, azithromycin 500 mg/day was initiated for three consecutive days within a week, and clinical improvement was achieved at the end of the four-week treatment period. Although studies suggest that tularemia infections in Central and Eastern Europe are frequently caused by macrolide-resistant strains, there are cases successfully treated in Turkiye[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In our follow-up case, subspecies determination was not possible.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, some patients with positive microagglutination titers but below the diagnostic cut-off and for whom control testing was not available were included in the study. Secondly, tularemia was diagnosed solely by serological methods, subspecies identification and susceptibility analysis could not be performed. Finally, the study did not include an analysis of treatment outcomes and success.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWaterborne tularemia outbreaks can have different outcomes in different patient populations despite sharing a common causative pathogen. Therefore, individual patient assessments can be beneficial when managing an epidemic.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003cem\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u0026nbsp;\u003c/strong\u003e\u003cem\u003eThe authors have no relevant financial or non-financial interests to disclose\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the conceptualization, design of the study and the data collection. F\u0026Ouml;, analyzed the data. KM, drafted the manuscript. All authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u0026nbsp;\u003c/strong\u003eData from the nationwide Turkish administrative health registries are subject to Turkish legislation and can only be made available to a third party under certain conditions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval:\u0026nbsp;\u003c/strong\u003e\u003cem\u003eThis study was performed in line with the principles of the Declaration of Helsinki.\u0026nbsp;\u003c/em\u003eThis study was approved by the institutional review board and the research and ethics committee at Mus Alparslan University (11.04.2025 and numbered 189789).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate:\u0026nbsp;\u003c/strong\u003e\u003cem\u003eInformed consent was obtained from all individual participants included in the study. Written informed consent was obtained from the parents.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConsent to Publish:\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eThe authors affirm that human research participants provided informed consent for publication of the images in Figures 1-5\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eWe wish to thanks all personnel at Malazgirt State Hospital, especially former chief physician Esma S\u0026ouml;ylemez.\u003c/em\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePetersen JM, Molins CR. Subpopulations of Francisella tularensis ssp. tularensis and holarctica: identification and associated epidemiology. 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Microbiol Bul. 2025;59(2):242\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5578/mb.202502133\u003c/span\u003e\u003cspan address=\"10.5578/mb.202502133\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGyuranecz M, Birdsell DN, Splettstoesser W, Seibold E, Beckstrom-Sternberg SM, Makrai L, et al. Phylogeography of Francisella tularensis subsp. holarctica, Europe. Emerg Infect Dis. 2012;18(2):290\u0026ndash;3. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3201/eid1802.111305\u003c/span\u003e\u003cspan address=\"10.3201/eid1802.111305\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Lymphadenopathy, Outbrake, Treatment, Tularemia","lastPublishedDoi":"10.21203/rs.3.rs-9212550/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9212550/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTularemia is a zoonotic disease that can cause outbreaks as well as sporadic cases. This study assessed to analyze patients identified in a waterborne tuaremia outbreak in a village in eastern Turkiye and to evaluate the adult and pediatric populations.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe study included patients who presented to the Infectious Diseases and Clinical Microbiology and Pediatrics outpatient clinics of Malazgirt State Hospital during the tularemia outbreak in January and February 2025 and were diagnosed with tularemia. Data on age, gender, clinical and laboratory findings, antibiotic regimens and durations, and complications were collected and analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included 56 participants (mean age 24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.5 years, 44% female, 51% adult). No significant difference was found in the distribution of tularemia type between adult and pediatric patients (p\u0026thinsp;=\u0026thinsp;0.198); the predominant type in both groups was the oropharyngeal form. Lymphadenopathy (LAP) was more frequent in adult patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), abdominal pain was more frequent in pediatric patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and no significant differences were found in other clinical findings. Leukocytosis was significantly more frequent in pediatric patients compared to adults (p\u0026thinsp;=\u0026thinsp;0.016). Treatment duration was statistically significantly longer in adult patients compared to pediatric patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). One of the patients was pregnant who was treated with azithromycin and a healthy delivery was achieved. There were no cases resulting in sepsis or death.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eWaterborne tularemia outbreaks can have different outcomes in different patient populations despite sharing a common causative pathogen. Therefore, individual patient assessments can be beneficial when managing an epidemic.\u003c/p\u003e","manuscriptTitle":"A waterborne tularemia outbreak in eastern of Turkiye: Evaluation of Adult and Pediatric patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 16:43:21","doi":"10.21203/rs.3.rs-9212550/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-05T07:46:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-03T18:38:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"335836084286745212337358057501483293809","date":"2026-04-27T06:20:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-25T05:04:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329638425331211783640983469694929372964","date":"2026-04-06T16:37:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-05T08:42:02+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-30T12:36:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-27T12:00:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-27T12:00:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2026-03-24T13:06:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c88e8718-5038-486f-92ae-a98d4c1a270f","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-05T07:46:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-03T18:38:11+00:00","index":39,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T10:53:34+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 16:43:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9212550","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9212550","identity":"rs-9212550","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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