Analyses of tularemia cases and their long-term results

@#Tularemia is a zoonotic disease and endemic in the northern hemisphere. The aim of this study was to evaluate the epidemiological, clinical and laboratory characteristics of tularemia patients, and to re-analyze their lymphadenopathy during the follow-up. The patients who were diagnosed with tularemia were reviewed. They were invited for the long term, physical and radiological evaluations. 69.8% patients had lived in rural areas. 54.7% patients were associated with animal husbandry, the 18.9% had contact with rodents. The most common form was the glandular type (62.3%). The frequency of granulomatous lymphadenitis was significantly higher in patients diagnosed later than 30 days from the onset of symptoms. Lymphadenopathy was undetectable in 61.5% patients, its severity was reduced in 38.4% patients compared to its state at the admission. In rural areas, avoiding contact with wild animals can ensure the protection from the pathogen. Public communities should be made aware of the disease.

Treatment-failure tularemia in children / 소아과

PURPOSE: Tularemia is an infection caused by Francisella tularensis. Its diagnosis and treatment may be difficult in many cases. The aim of this study was to evaluate treatment modalities for pediatric tularemia patients who do not respond to medical treatment. METHODS: A single-center, retrospective study was performed. A total of 19 children with oropharyngeal tularemia were included. RESULTS: Before diagnosis, the duration of symptoms in patients was 32.15±17.8 days. The most common lymph node localization was the cervical chain. All patients received medical treatment (e.g., streptomycin, gentamicin, ciprofloxacin, and doxycycline). Patients who had been given streptomycin, gentamicin, or doxycycline as initial therapy for 10–14 days showed no response to treatment, and recovery was only achieved after administration of oral ciprofloxacin. Response to treatment was delayed in 5 patients who had been given ciprofloxacin as initial therapy. Surgical incision and drainage were performed in 9 patients (47.5%) who were unresponsive to medical treatment and were experiencing abcess formation and suppuration. Five patients (26.3%) underwent total mass excision, and 2 patients (10.5%) underwent fine-needle aspiration to reach a conclusive differential diagnosis and inform treatment. CONCLUSION: The causes of treatment failure in tularemia include delay in effective treatment and the development of suppurating lymph nodes.

Tularemia, a re-emerging infectious disease in Iran and neighboring countries / 한국역학회지

OBJECTIVES: Tularemia is a zoonotic disease transmitted by direct contact with infected animals and through arthropod bites, inhalation of contaminated aerosols, ingestion of contaminated meat or water, and skin contact with any infected material. It is widespread throughout the northern hemisphere, including Iran and its neighbors to the north, northeast, and northwest. METHODS: In this paper, the epidemiology of tularemia as a re-emerging infectious disease in the world with a focus on Iran and the neighboring countries is reviewed. RESULTS: In Iran, positive serological tests were first reported in 1973, in wildlife and domestic livestock in the northwestern and southeastern parts of the country. The first human case was reported in 1980 in the southwest of Iran, and recent studies conducted among at-risk populations in the western, southeastern, and southwestern parts of Iran revealed seroprevalences of 14.4, 6.52, and 6%, respectively. CONCLUSIONS: Several factors may explain the absence of reported tularemia cases in Iran since 1980. Tularemia may be underdiagnosed in Iran because Francisella tularensis subspecies holarctica is likely to be the major etiological agent and usually causes mild to moderately severe disease. Furthermore, tularemia is not a disease extensively studied in the medical educational system in Iran, and empirical therapy may be effective in many cases. Finally, it should be noted that laboratories capable of diagnosing tularemia have only been established in the last few years. Since both recent and older studies have consistently found tularemia antibodies in humans and animals, the surveillance of this disease should receive more attention. In particular, it would be worthwhile for clinical researchers to confirm tularemia cases more often by isolating F. tularensis from infected humans and animals.

Tularemia and plague survey in rodents in an earthquake zone in southeastern Iran / 한국역학회지

OBJECTIVES: Earthquakes are one the most common natural disasters that lead to increased mortality and morbidity from transmissible diseases, partially because the rodents displaced by an earthquake can lead to an increased rate of disease transmission. The aim of this study was to evaluate the prevalence of plague and tularemia in rodents in the earthquake zones in southeastern Iran. METHODS: In April 2013, a research team was dispatched to explore the possible presence of diseases in rodents displaced by a recent earthquake magnitude 7.7 around the cities of Khash and Saravan in Sistan and Baluchestan Province. Rodents were trapped near and in the earthquake zone, in a location where an outbreak of tularemia was reported in 2007. Rodent serums were tested for a serological survey using an enzyme-linked immunosorbent assay. RESULTS: In the 13 areas that were studied, nine rodents were caught over a total of 200 trap-days. Forty-eight fleas and 10 ticks were obtained from the rodents. The ticks were from the Hyalomma genus and the fleas were from the Xenopsylla genus. All the trapped rodents were Tatera indica. Serological results were negative for plague, but the serum agglutination test was positive for tularemia in one of the rodents. Tatera indica has never been previously documented to be involved in the transmission of tularemia. CONCLUSIONS: No evidence of the plague cycle was found in the rodents of the area, but evidence was found of tularemia infection in rodents, as demonstrated by a positive serological test for tularemia in one rodent.

Genetic diversity of Francisella tularensis subsp.holarctica in China / 中华流行病学杂志

Objective To explore the genetic relationship between the Chinese and the foreign species of Francisella tularensis.Methods Based on our own findings and from the literature,17 SNP,4 INDEL,and 12 VNTR were selected for phylogenetic analysis on 39 strains of F.tularensis,including 10 strains of Chinese F.tularensis and 29 strains of foreign F.tularensis that had been sequenced and published.SNP-INDEL and MLVA were used for the separation and combination.Results Data from the combined analysis indicated that 3 strains of Chinese F.tularensis with Japanese FSC022 were assigned to B5;3 strains,with Swedish FSC200 to B1;3 strains with American OSU18 to B2 and 1 strain with French FTNF002-00,German F92,and American OR96246 to B4,respectively.10 strains of Chinese F.tularensis were assigned to 4 clades and the result demonstrated a wide diversity of F.tularensis subsp.holarctica in China.Conclusion A set of simple and robust typing tools for F.tularensis subsp.holarctica were established in this study.Based on the results,F.tularensis subsp.holarctica might have had its origins in Asia.

Differential diagnosis of cervical lymphadenitis mimicking malignancy due to tularemia: Our experiences.

Background: Tularemia is a disease caused by a Gram-negative coccobaci llus Francisella tularensis. This bacterium may cause different types of clinical pictures owing to acquisition route and entrance site, such as ulceroglandular, oropharyngeal, glandular, pneumonic, typhoid and ocular forms. Oropharyngeal tularemia (OPT) is the most common form of tularemia in some regions. OPT may cause tonsillopharyngitis followed by cervical lymphadenopathies (LAPs). Without treatment LAP may p ersist for several months and may mimic other diseases causing cervical LAPs. Materials and Methods: A total of six cases of OPT, fi ve male and one female, between 21 and 31 years old, diagnosed serologically and clinically recorded in GATA Haydarpasa Training Hospital were included in this study. Detailed story including the region they lived for last 6 months, their occupation, family and neighborhood story with similar complaints were obtained. Patient data were also obtained from manually written patients fi les and electronical patient fi le system. Formalin fi xed paraffi n embedded tissue blocks of all biopsy material were submitted for polymerase chain reaction (PCR) study for F. tularensis. Results: A total of six cases with head and neck mass following a story of tonsillopharyngitis admitted to different clinics including infectious diseases, ear-nose-throat and internal medicine in our tertiary care hospital. Physical examination revealed immobile, hard, conglomerated unilateral cervical lymphadenopathy in all cases. Histopathological examination revealed granulomatous infl ammation in four cases. Acute suppurative infl ammatory changes were also seen in two cases. Large necrotic areas mimicking casseifying necrosis were seen in two cases. PCR amplifi cation of F. tularensis genom from isolated deoxyribonucleic acids was successful in fi ve cases. Conclusion: Tularemia should be kept in mind in patients with tonsillopharyngitis not responding to penicillins and beta lactam antibiotics. Furthermore, persisting LAPs mimicking tumor with or without the story of previously experienced sore throat or tonsillopharyngitis in past few days or weeks should be evaluated for glandular or OPT. At this point, easily applicable serological tests such as tularemia micro-agglutination tests will confi rm the diagnosis of OPT. However, if lymph node were already sampled to exclude especially malignancy or T cell lymphoma, tularemia PCR test may be used to make a certain diagnosis.

Current status of vaccine development for tularemia preparedness

Tularemia is a high-risk infectious disease caused by Gram-negative bacterium Francisella tularensis. Due to its high fatality at very low colony-forming units (less than 10), F. tularensis is considered as a powerful potential bioterrorism agent. Vaccine could be the most efficient way to prevent the citizen from infection of F. tularensis when the bioterrorism happens, but officially approved vaccine with both efficacy and safety is not developed yet. Research for the development of tularemia vaccine has been focusing on the live attenuated vaccine strain (LVS) for long history, still there are no LVS confirmed for the safety which should be an essential factor for general vaccination program. Furthermore the LVS did not show protection efficacy against high-risk subspecies tularensis (type A) as high as the level against subspecies holarctica (type B) in human. Though the subunit or recombinant vaccine candidates have been considered for better safety, any results did not show better prevention efficacy than the LVS candidate against F. tularensis infection. Currently there are some more trials to develop vaccine using mutant strains or nonpathogenic F. novicida strain, but it did not reveal effective candidates overwhelming the LVS either. Difference in the protection efficacy of LVS against type A strain in human and the low level protection of many subunit or recombinant vaccine candidates lead the scientists to consider the live vaccine development using type A strain could be ultimate answer for the tularemia vaccine development.

Tularemia and the oculoglandular syndrome of Parinaud

An 18-year-old female came to our clinic with complaints of a tender lump just under her jaw on the left side and another lump in front of her left ear, ecchymosis around the eye and some redness in the eye at the same side. After administering antibiotic therapy for two days we suspected of tularemia and referred the patient to the Infectious Diseases Department. A serum sample was taken and a fine needle aspiration biopsy was performed. The patient was diagnosed with tularemia, the oculoglandular syndrome of Parinaud. Tularemia should also be kept in mind for differential diagnosis in patients with both ocular and glandular symptoms in endemic regions like Turkey and the appropriate therapy should be initiated immediately.

An Outbreak of Oropharyngeal Tularemia with Cervical Adenopathy Predominantly in the Left Side

PURPOSE: We describe the epidemiological and clinical characteristics and the efficacy of a delayed initiation to therapy in an oropharyngeal tularemia outbreak in Duzce, Turkey. MATERIALS AND METHODS: Between March and June 2000, 22 patients with tularemia were diagnosed by microagglutination tests. RESULTS: Oropharyngeal and ulceroglandular forms of the disease were discovered. Most of the cases were oropharyngeal (19 cases). The most common symptoms were sore throat (95.4%) and fever (90.9%). Lymphadenopathy (95.4%) and pharyngeal hyperemia (81.8%) were usually observed signs. The lymphadenopathies were localized especially in the left cervical region (66.7%), a finding that has not been previously reported in the literature. The time between the onset of the symptoms and diagnosis was 40.7 +/- 22.8 (10 - 90) days. The patients were treated with streptomycin plus doxycycline and ciprofloxacin. The patients' recoveries took up to 120 days. CONCLUSION: This report describes the first outbreak of tularemia in northwest Turkey. Tularemia may occur in any region where appropriate epidemiological conditions are found and should be kept in mind for differential diagnosis in oropharyngeal symptoms. Late initiation of therapy may delay complete recovery. In this outbreak, cervical lymph nodes predominantly localized on the 1eft side were found, which had not been previously reported.

An Outbreak of Tularemia in Western Black Sea Region of Turkey

The aim of this study was to investigate the source and the size of a tularemia outbreak in a village located in a non-endemic area. Five patients from the same village were admitted to hospital with the same complaints all within one week of September 2001. Tularemia was suspected and a diagnosis was made after physical and anamnesis examinations. The village was visited the same week that the patients were admitted to the hospital, in the January and April 2002. The villagers were examined and screened serologically by microagglutination method and the water sources were investigated bacteriologically. A total of 14 people were found to be infected from the outbreak and the oropharyngeal form was the only clinical presentation. Antibody titers ranged between 1 : 80 and 1 : 640. The patients responded well to the aminoglycoside plus tetracycline therapy. Examination of the pipewater and three springs revealed that all the water sources were contaminated by coliforms, however, Francisella tularensis could not be isolated in glucose-cystine medium. Antibody levels stayed stable or decreased seven months after. Tularemia had not been reported in this area before, so the first patients were misdiagnosed. In conclusion tularemia should be considered in differential diagnosis of patients with fever, sore throat and cervical lymphadenopaties.

A Case of Ulceroglandular Tularemia

Tularemia is a zoonosis caused by Francisella tularensis. It is primarily a disease of wild animals. Human infection is incidental and usually results from interaction with biting or blood-sucking insects, wild or domestic animals, or the environment. An increasing number of cases have been reported in several countries. However, in Korea it has not been reported until now. A 40-year old male patient visited our department on Jan 13, 1997, complaining of multiple swollen lymph-nodes on his axillae and reddish swollen left upper arm which contained an abscess at its central portion for about ten days. On Dec 25, 1996, he found a dead wild rabbit on a nearby mountainside, ate it after cooking it by himself with his hands injured. His abscess was drained and microbiologic examination was done. However no microorganism was isolated. His lymph nodes were surgically removed from both axillae, and we investigated them microbiologically and pathologically. On microbiologic examination, small aerobic gram negative coccobacilli were grown on a chocolate agar plate in an aerobic condition with 5% CO2 at 37 degrees centigrade. On H & E staining, the lymph node showed chronic granulomatous inflammation. We sent the microorganism and lymph nodes to the Centers for Disease Control and Prevention in the United States of America for the definitive diagnosis. Finally the microorganism was identified as F. tularensis by culture morphology, biological tests and immunohistochemical staining. We report the first case of F. tularensis in Korea.

A Case of Tularemia Caused by Francisella Tularensis / 대한임상병리학회지

Tularemia is a major laboratory acquired zoonoses caused by Francisella tularensis that have high virulence, and usually transmitted to humans from direct contact with infected wild animals like rabbits or insect vectors like ticks. Clinical tularemia can be divided with 6 major syndromes that are delineated by the mode of organism aquisition, in which ulceroglandular type is the most common. F. tularensis have 3 different biogroups which have homogeneous antigenecity, type A (biogroup tularensis), type B (biogroup palearctica) and biogroup novicida, and can be confirmed by serology most frequently. In the domestic area, there was no reports of tularemia in humans or presence of bacteria in the reservoirs. Authers experienced a case of tularemia which is suspected as F. tularensis type B, ulceroglandular type. A healthy 40-year-old man admitted the hospital for lymph node swelling in both axillary and upper arm area and for furuncles in both forearm and palm. He contacted with dead rabbit and eated it after cooking before 20 days from admission day. In laboratory cultures, F. tularensis did not grow in any of the routine or anaerobic culture media except for one blood agar plate at 5 days. After subculturing that to cystine containing chocolate agar plate at 37C degree, 5% CO2 incubator, we could see the accelerating growth of colony. In microbiological test, it was oxidase and urease negative. In acid production in cystine trypticase agar base, it was glucose positive and sucrose, maltose, glycerol negative. In agglutinating test, F. tularensis antiserum titer (Difco, USA) with isolates was 1:160 or over and antibody titer to F. tularensis antigen (Difco, USA) was 1:320 or over. Anti-F. tularensis-IF assay and Anti-F. tularensis-indirect-EIA with isolates were positive.

A Case of Ulceroglandular Tularemia Occurred In Korea / 한국역학회지

Tularemia is a zoonosis caused by Francisella tularensis. It is primarily a disease of wild animals. Human infection is incidental and usually results from interaction with biting or blood-sucking insect, wild or domestic animals or the environment. It is common in United States. An increasing number of cases have been reported from the Scandinavian countries, eastern Europe, Siberia, and Japan. But In Korea it has not been reported. A 40-year old male visited the department of Surgery on Jan 13, 1997 complaining multiple swollen lymph-nodes on his axillae and upper right arm for about ten days. On Dec 25, 1996, he found a dead wild rabbit at mountainside nearby, cooked it himself and ate it with his friends. He informed us that he got light injury on both hands while he was walking on the mountainside. On Dec 28, he started to suffer from high fever, fatigue and loss of appetite lasting for a day. After medication at a local clinic for several day, symptoms were somewhat relieved. A week later(Jan 4, 1997), several erythematous lesions developed on his both hands, which left ulcerations on the skin. Both axillary lymph nodes were swollen at both sides, but not tender. He visited the department of surgery on Jan 13 and he admitted on Jan 15. During hospitalization, the lymph nodes were surgically removed from both axillae and upper left arm. On microbiologic examination, small aerobic gram negative coccobacilli were grown on the chocolate agar plate in aerobic condition with 5% CO2 at 37 degrees centigrade. On Feb 10, fine needle aspiration from the liver abscess was done, drawing 3 ml of yellowish thick pustular material, but the microorganism was not isolated at the smear and culture of this material in the same condition as described above. After admission, he was treated with antibiotics(cefazole and marocin). His general conditions and laboratory results, including liver function, were markedly improved. He was discharged on Feb 12 and appears well on subsequent follow-ups. The microorganism and lymph nodes were sent to Centers for Disease Control and Prevention in the United States for further evaluation. A twostep indirect immunoalkaline phosphatase technique using an anti-F. tularensis antibody was performed on the lyph nodes having a positive reaction. The immunohistochemical stain demonstrated intense positivity in the stellate abscesses and fine granular reaction in some of the vessels in the paracortical region. Also F. tularensis was identified in the agar plug by culture morphology and immunofluorescence antibody test. We report a case of F. tularensis in Korea for the first time. Further studies were recommened for epidemiological characteristics and prevention of the disease.