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.

Cutaneous Manifestations of Potential Chemical, Biological, and Radiological Agents and Their Clinical Management / 대한피부과학회지

The level of terrorist threats using chemical, biological, and radiological agents has been continuously increasing, and it is an undeniable truth that these agents are actually in use today. The fact that most chemical, biological, and radiological agents cause skin-related symptoms, and that the skin symptoms are observed at a relatively early stage of the condition, leads to the conclusion that dermatologists could be the first point of contact for potential victims of these agents. It is highly important that first responders are able to recognize symptoms caused by these agents early and react quickly. Therefore, dermatologists do have a responsibility to take on a role in dealing with chemical, biological, and radiological attacks, and pre-equip themselves with professional knowledge in this field. Among the various types of chemical agents, typical examples of agents causing skin-related symptoms are blistering agents, which lead to bullae and necrosis on the skin. Biological agents are classified from Category A to C according to their respective risk factors. The most dangerous Category A agents include anthrax, smallpox, plague, tularemia, and viral hemorrhagic fever, all of which are known to show characteristic skin-related symptoms. Upon exposure to a certain level of radiation, radiological agents can also lead to erythema on the skin. In this article, we will discuss various characteristics and up-to-date treatment methods of potential chemical, biological, and radiological agents to help dermatologists advance their knowledge in this field.

Cutaneous Manifestations of Potential Chemical, Biological, and Radiological Agents and Their Clinical Management / 대한피부과학회지

The level of terrorist threats using chemical, biological, and radiological agents has been continuously increasing, and it is an undeniable truth that these agents are actually in use today. The fact that most chemical, biological, and radiological agents cause skin-related symptoms, and that the skin symptoms are observed at a relatively early stage of the condition, leads to the conclusion that dermatologists could be the first point of contact for potential victims of these agents. It is highly important that first responders are able to recognize symptoms caused by these agents early and react quickly. Therefore, dermatologists do have a responsibility to take on a role in dealing with chemical, biological, and radiological attacks, and pre-equip themselves with professional knowledge in this field. Among the various types of chemical agents, typical examples of agents causing skin-related symptoms are blistering agents, which lead to bullae and necrosis on the skin. Biological agents are classified from Category A to C according to their respective risk factors. The most dangerous Category A agents include anthrax, smallpox, plague, tularemia, and viral hemorrhagic fever, all of which are known to show characteristic skin-related symptoms. Upon exposure to a certain level of radiation, radiological agents can also lead to erythema on the skin. In this article, we will discuss various characteristics and up-to-date treatment methods of potential chemical, biological, and radiological agents to help dermatologists advance their knowledge in this field.

The first pediatric case of tularemia in Korea: manifested with pneumonia and possible infective endocarditis / 소아과

Tularemia is a potentially severe zoonotic disease caused by Francisella tularensis. A lack of awareness about tularemia can be embarrassing and could result in delayed treatment because of improper diagnosis. The diagnosis of tularemia is difficult, because the infections are rare and the clinical spectrum is broad. As only 1 adult case has been reported in Korea thus far, pediatricians in Korea may be unfamiliar with tularemia. We report our experience with a 14-year-old male adolescent with tularemia who presented with atypical pneumonia and possible infective endocarditis. Although the infectivity and mortality rates for tularemia are very high if left untreated, we did not suspect tularemia in this case until the incidental isolation of F. tularensis. The present case suggests that clinicians in Korea should be more aware of tularemia. This case also suggests that tularemia should be considered in undetermined cases of atypical pneumonia or acute febrile illness without local signs.

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.

Discovery and tracking source of the new subgroup of Chinese Francisella tularensis type B / 中华预防医学杂志

<p><b>OBJECTIVE</b>To perform laboratory diagnosis and tracking source of a suspected tularemia patient in Beijing.</p><p><b>METHODS</b>A suspected tularemia patient was reported in Beijing city on July 19, 2012. Genomic DNA was extracted from the blood sample of the patient, then general PCR and sequencing of amplicons were conducted using 3 specific genes (fopA, tul4 and 16S rRNA) Francisella tularensis (F.tularensis), and 2 genotyping primers (C1C4 and RD1). Two other laboratories repeated the PCR and sequencing of the fopA in parallel. At the same time, real-time PCR fluorescent ration was performed using 4 targets (fopA, ISFtul2, 23kDa, and tul4), and phylogenetic analysis was carried out using 11 canonical single nucleotide polymorphisms (SNPs) and 4 insertions or deletions.</p><p><b>RESULTS</b>All the 3 specific genes were amplified positively, and sequenced fragments were 409, 407 and 1 053 bp, respectively. The patient was infected by F. tularensis comparing with the whole genome published. Next, amplicons of 151 and 924 bp were obtained by the 2 typing primers after sequencing, respectively. The segment lengths suggested that the patient was infected by the subsp. holarctica. All of the two other laboratories obtained positive data for the PCR and sequencing of the fopA. In addition, all the 4 targets tested positive by real-time PCR for F. tularensis. The Ct value of the fopA, ISFtul2, 23kDa and tul4 were 30, 25, 28, and 30, respectively. The phylogenetic analysis indicated that the whole genome of this case was assigned to a known clade from Russia, which was subgroup B3.</p><p><b>CONCLUSION</b>This case was confirmed to be a tularemia patient, and a new subgroup of F. tularensis type B was found in China.</p>

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.

Tularemia in children.

OBJECTIVE: Tularemia, an infection caused by the coccobacilus Francisella tularensis, can be a difficult disease process to diagnose and treat. The aim of this study was to evaluate an epidemic of tularemia in Bursa. METHODS: In this study, we included only pediatric cases. All the cases were diagnosed on clinical and serological grounds. RESULTS: During an epidemic of tularemia in a village of Bursa on December 2004, 70 people (60 adults, 10 children) fell ill. In children with tularemia, the oropharyngeal form predominated which was diagnosed 70% of cases. Most of the patients (80%) who had older than 10 years old, were treated with doxycycline. All patients recovered without complications. CONCLUSION: The epidemic was thought to be waterborne. The vehicle of the infections was inadequately treated water which was used by the patient in the village.

Cytokine response in Balb/c mice infected with Francisella tularensis LVS and the Pohang isolate

We investigated the immune response induced by the Francisella (F.) tularensis live vaccine strain (LVS) and the Pohang isolate. After the Balb/c mice were infected intradermally (i.d) with 2 x 10(4) cfu of F. tularensis LVS and Pohang, respectively, their blood and organs were collected at different times; 0, 3, 6, 24, 72, 96, 120 and 168 h after infection. Using these samples, RT-PCR and ELISA analysis were carried out for the comparative study of the cytokines, including TNF-alpha, INF-gamma, IL-2, IL-4, IL-10 and IL-12. In the Pohang-infected mice at 120 h, the liver showed a 53 times higher level of TNF-alpha and a 42 times higher level of IFN-gamma than the respective levels at the early time points after infection. The levels of TNF-alpha and IFN-gamma induced by LVS were 5 times lower than those induced by the Pohang isolate. Also, the organs from the Pohang-infected mice showed higher levels of TNF-alpha, IFN-gamma, IL-10 and IL-12 than the levels in the LVS-infected mice. The blood from the Pohang-infected mice at 120 h revealed about a 40 times increased level of IFN-gamma, and IL-10 was also increased by 4 times at 96 h compared to an early infection time point, while IL-4 was not induced during the whole infection period. These results suggest that F. tularensis may induce a Th1-mediated immune response to in vivo infection and the Pohang isolate has a higher capacity than the LVS to induce an acute immune response in Blab/c mice.

Amenaza bioterrorista en Argentina / Bioterrorist threatening in Argentina

This report describes present concepts related to biological terrorism with special reference to he factibility of bioterrorist' attack in Argenina

Trends of Bacterial Zoonoses in Humans in Korea

Out of 60 national communicable diseases in Korea, 23 are zoonoses, diseases transmissible from animals to humans. Among the bacterial zoonoses, plague, brucellosis, anthrax, Q fever, tularemia, glanders, and melioidosis are categorized as a high-level threat of bioterrorism and biowarfare in the world. In this paper, the trends of notifiable bacterial zoonoses recently occurring or recurring in Korea and other potential pathogens for bioterrorism or biowarfare are reviewed. Notifiable bacterial zoonoses recently occurring in Korea are enterohemorrhagic Escherichia coli (EHEC) infection, tetanus, tuberculosis, scrub typhus, leptospirosis, brucellosis, and anthrax. Other bacterial diseases recently emerging are tularemia, ehrlichiosis, and Q fever. However, no human case of plague, glanders, and melioidosis has been reported yet.

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.

Papel del laboratorio clínico ante el bioterrorismo / The role of the clinical laboratory facing bioterrorism

Con el creciente reto de que los agentes biológicos se utilicen afectando a toda la población, el impacto para los laboratorios clínicos es más directo. Si ocurriera un evento bioterrorista el laboratorio clínico promedio podría ser fundamental para ayudar a detectar e identificar al agente biológico utilizado y alertar a las autoridades. Aunque Bacillus anthracis y el virus de la viruela han recibido la mayor publicidad como agentes de guerra biológica, el término de agente biológico se aplica a un diverso grupo de microorganismos, así como a toxinas, plantas y animales.Esta revisión traza los orígenes de los agentes de guerra biológica y describe la percepción actual del reto que suponen tales agentes, el papel que podrían jugar los laboratorios clínicos, y los aspectos clínicos y microbiológicos de los agentes que tienen las mayores posibilidades de ser utilizados con este propósito.

Bioterrorismo / Bioterrorism

Esta rápida revisión tiene por objeto actualizar los conocimientos actuales acerca de los principales agentes biológicos y químicos disponibles, con los que eventualmente podría contar el bioterrorismo. Es necesario conocer las bases de la sospecha diagnóstica clínica: las medidas de protección y los recursos terapéuticos disponibles (antídotos, vacunas, antitoxinas, antibióticos, etc.). Por último, los acontecimientos recientes inducen no sólo a adjuntar conocimientos y recursos profilácticos y curativos, sino que también a meditar acerca del destino de la humanidad, promovido por los inmensos progresos científicos y tecnológicos de las últimas décadas

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 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.