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.
Biopsy, Fine-Needle ; Child ; Ciprofloxacin ; Diagnosis ; Diagnosis, Differential ; Doxycycline ; Drainage ; Francisella tularensis ; Gentamicins ; Humans ; Lymph Nodes ; Retrospective Studies ; Streptomycin ; Suppuration ; Treatment Failure ; Tularemia

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.
Anthrax ; Biological Factors ; Blister ; Erythema ; Hemorrhagic Fevers, Viral ; Necrosis ; Plague ; Risk Factors ; Skin ; Smallpox ; Terrorism ; Tularemia ; Weapons

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.
Anthrax ; Biological Factors ; Blister ; Erythema ; Hemorrhagic Fevers, Viral ; Necrosis ; Plague ; Risk Factors ; Skin ; Smallpox ; Terrorism ; Tularemia ; Weapons

OBJECTIVETo perform laboratory diagnosis and tracking source of a suspected tularemia patient in Beijing.

METHODSA 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.

RESULTSAll 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.

CONCLUSIONThis case was confirmed to be a tularemia patient, and a new subgroup of F. tularensis type B was found in China.

Beijing ; DNA Primers ; DNA, Bacterial ; genetics ; Francisella tularensis ; classification ; Genes, Bacterial ; Genotype ; Humans ; Phylogeny ; Polymorphism, Single Nucleotide ; RNA, Ribosomal, 16S ; genetics ; Real-Time Polymerase Chain Reaction ; Russia ; Tularemia ; epidemiology ; microbiology

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.
Adolescent ; Adult ; Diagnosis ; Endocarditis* ; Francisella tularensis ; Humans ; Korea* ; Mortality ; Pediatrics ; Pneumonia* ; Tularemia* ; Zoonoses

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.
Agglutination Tests ; Disasters ; Earthquakes* ; Enzyme-Linked Immunosorbent Assay ; Iran* ; Mortality ; Plague* ; Prevalence ; Rodentia* ; Serologic Tests ; Siphonaptera ; Ticks ; Tularemia* ; Xenopsylla

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.
Aerosols ; Animals ; Antibodies ; Arthropods ; Bacterial Infections ; Communicable Diseases, Emerging* ; Eating ; Epidemiology ; Francisella tularensis ; Humans ; Inhalation ; Iran* ; Livestock ; Meat ; Rodentia ; Seroepidemiologic Studies ; Serologic Tests ; Skin ; Tularemia* ; Water ; Zoonoses

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.
Bioterrorism ; Communicable Diseases ; Francisella tularensis ; Humans ; Sprains and Strains ; Stem Cells ; Tularemia ; Vaccination ; Vaccines

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.
Adolescent ; Adult ; Aged ; Child ; Diagnosis, Differential ; Disease Outbreaks/*statistics & numerical data ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Diseases/*microbiology/*pathology ; Male ; Middle Aged ; Oropharynx ; Tularemia/*epidemiology/*pathology ; Turkey/epidemiology ; Water ; Young Adult

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.
Animals ; *Bacterial Vaccines ; Cytokines/*biosynthesis ; Francisella tularensis/immunology/isolation & purification/*pathogenicity ; Humans ; Interferon-gamma/genetics/metabolism ; Interleukins/genetics/metabolism ; Korea ; Liver/microbiology/pathology ; Mice ; Mice, Inbred BALB C ; Polymerase Chain Reaction ; Tularemia/*diagnosis/*immunology ; Tumor Necrosis Factor-alpha/genetics/metabolism