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Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Humanos , Ratones , Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Interleucina-15 , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
Although classical swine fever occurred in September 2018 for the first time in 26 years, its virulence is thought to be moderate based on field observations by veterinary authorities and our previous experimental infections. We quantified viremia and viral shedding in pigs infected with recent Japanese classical swine fever virus isolates, as well as a highly virulent strain. The results show that pigs infected with the Japanese strains exhibited lower viremia and viral shedding than those infected with the highly virulent strain. However, horizontal transmission occurred in pigs infected with the Japanese strains, similar to those infected with the highly virulent strain. Additionally, viremia and neuralization antibodies coexisted in pigs infected with the Japanese strains, presenting challenges for control measures.
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Virus de la Fiebre Porcina Clásica , Enfermedades de los Porcinos , Animales , Porcinos , Japón/epidemiología , Esparcimiento de Virus , Viremia/veterinaria , Brotes de Enfermedades/veterinaria , Enfermedades de los Porcinos/epidemiologíaRESUMEN
Understanding of disease dynamics and viral shedding in wild boar and of the potential for disease spreading within wild boar and domestic pig populations is critical for developing effective control and eradication measures for foot-and-mouth disease (FMD). Accordingly, we infected experimentally wild boar and domestic pigs with FMD virus (FMDV) strains O/TAI/315/2016 and A/MOG/2013, and studied their susceptibility and viral transmissibility in both populations. Similar to FMDV-infected pigs, wild boar inoculated with both viruses exhibited vesicular lesions on their feet, snout, tongue and lip, although they did not show lameness. Further, inoculated wild boar were equally capable of transmitting the virus to all of their contact animals. While all contact pigs developed vesicular lesions after contact with inoculated animals, in contrast, no wild boar when exposed to the same infected animals showed obvious clinical signs. These results will be useful for further understanding of the critical roles in occurring and sustaining an FMD outbreak, and will be useful for establishing epidemiological surveillance programs and effective countermeasures for wild boar.
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Virus de la Fiebre Aftosa , Fiebre Aftosa , Enfermedades de los Porcinos , Porcinos , Animales , Fiebre Aftosa/epidemiología , Japón/epidemiología , Sus scrofaRESUMEN
We analyzed the pathogenicity of a recent Japanese classical swine fever virus (CSFV) to wild boars via an experimental infection using boar-pig hybrids as an alternative to wild boars. We also investigated the effectiveness of a bait vaccine against the CSFV. Naïve boar-pig hybrids and pigs showed clinical signs such as fever, leucopenia, anorexia and conjunctivitis following the experimental infection. In contrast, the boar-pig hybrids administered the bait vaccine did not show any clinical signs. Our data indicated that boar-pig hybrids and domestic pigs have similar susceptibility to the recent Japanese CSFV. Additionally, the bait vaccine is effective against the CSFV.
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Virus de la Fiebre Porcina Clásica/inmunología , Peste Porcina Clásica/prevención & control , Vacunación/veterinaria , Vacunas Virales/inmunología , Animales , Cruzamientos Genéticos , Hibridación Genética , Japón , Sus scrofa , PorcinosRESUMEN
Structural modification of a 1,4-benzodiazepin-2-one-based PTHR1 antagonist 5, a novel type of PTHR1 antagonist previously synthesized in our laboratories, yielded compound 10, which had better chemical stability than compound 5. Successive optimization of the lead 10 improved aqueous solubility, metabolic stability, and animal pharmacokinetics, culminating in the identification of DS37571084 (12). Our study paves the way for the discovery of novel and orally bioavailable PTHR1 antagonists.
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Descubrimiento de Drogas , Receptor de Hormona Paratiroídea Tipo 1/antagonistas & inhibidores , Administración Oral , Animales , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Relación Estructura-ActividadRESUMEN
In September 2018, classical swine fever reemerged in Japan after 26 years, affecting domestic pigs and wild boars. The causative virus belongs to the 2.1 subgenotype, which caused repeated outbreaks in eastern and Southeast Asia. Intensive surveillance of swine and vaccination of wild boars will help control and eradicate this disease in Japan.
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Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica/epidemiología , Peste Porcina Clásica/virología , Animales , Peste Porcina Clásica/historia , Virus de la Fiebre Porcina Clásica/clasificación , Virus de la Fiebre Porcina Clásica/genética , Virus de la Fiebre Porcina Clásica/aislamiento & purificación , Genes Virales , Historia del Siglo XXI , Japón/epidemiología , Filogenia , Vigilancia en Salud Pública , ARN Viral , PorcinosRESUMEN
BACKGROUND: A clear survival benefit has been reported for lung metastasectomy for colorectal cancer, and several clinicopathological prognostic factors have been proposed in the past. However, clinical advances, such as chemotherapy and radiographic imaging, should have improved patient outcome and may have altered prognosticators. This study aimed to assess patient survival and determine prognostic factors for survival and recurrence in patients who underwent initial lung metastasectomy for colorectal cancer in the modern clinical era. METHODS: Clinicopathological data and outcomes of 59 patients who underwent curative initial lung metastasectomy for colorectal cancer from 2004 to 2012 at a single institution in Japan were retrospectively investigated. Survival was estimated using the Kaplan - Meier method, and Cox proportional hazards regression models were used to estimate the prognostic impacts of each variable in univariate and multivariate analysis. RESULTS: The 5-years overall and disease-free survival rates were 54.3 and 40.6%, respectively. A disease-free interval < 24 months after colorectal cancer resection (P = 0.004) and a serum carcinoembryonic antigen ≥ 5.0 ng/mL before initial lung metastasectomy (P = 0.015) were independent predictors for poor overall survival. Moreover, the disease-free interval after colorectal cancer resection < 24 months (P = 0.010) and a colorectal cancer with N2 stage disease (P = 0.018) were independently associated with poor disease-free survival. On the other hand, the number of lung metastasis was not identified as a poor prognostic factor for both overall and disease-free survival. CONCLUSIONS: Our findings demonstrated similar or slightly better overall survival, and substantially favorable disease-free survival as compared with past reports. Poor prognostic factors for overall survival appeared not to differ from those of past studies, although this modern series did not determine the number of lung metastasis as a poor prognostic factor, which should be investigated in future studies. Moreover, initial lung metastasectomy is not expected to be a curable treatment for patients with both a short disease-free survival after colorectal cancer resection and colorectal cancers with N2 stage disease.
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Neoplasias Colorrectales/patología , Neoplasias Pulmonares/cirugía , Metastasectomía/métodos , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Neoplasias Pulmonares/secundario , Masculino , Análisis Multivariante , Recurrencia Local de Neoplasia/cirugía , Neumonectomía/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
A 64-year-old man was admitted because of dyspnea. He was diagnosed with rectal cancer with lymphangiosis carcinomatosa and metastases in the liver and lymph nodes. The patient was treated with cetuximab and modified FOLFOX6 (mFOLFOX6). After treatment, the primary rectal cancer and metastases were considered to have achieved a partial response (PR) and the lymphangiosis carcinomatosa remarkably improved. However, anaphylactic shock occurred in the 6 courses of treatment, 5 minutes after the infusion of oxaliplatin, and the patient was treated.
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Anafilaxia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfangitis/etiología , Compuestos Organoplatinos/efectos adversos , Neoplasias del Recto/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias del Recto/patologíaRESUMEN
H6 influenza viruses are prevalent in domestic and wild birds in Eurasian countries and have been isolated from pigs and a human. To prepare for an influenza pandemic, we have established an influenza virus library consisting of more than 1,300 influenza virus strains, including 144 combinations of 16 hemagglutinin and 9 neuraminidase subtypes. H6 viruses in the library were classified into Early, Group II, Group III, and W312 sublineages and the North America lineage on the basis of their phylogenetic features. Chicken antisera to A/duck/Hong Kong/960/1980 (H6N2) of the Early sublineage broadly reacted with viruses of different sublineages in a hemagglutinin inhibition test. A whole inactivated virus particle vaccine was prepared from A/duck/Hong Kong/960/1980 (H6N2) which was stocked in the influenza virus library. The potency of this vaccine against A/duck/Vietnam/OIE-0033/2012 (H6N2), which belongs to a different sublineage, was evaluated in mice. The test vaccine was sufficiently potent to induce an immune response that reduced the impact of disease caused by a challenge with A/duck/Vietnam/OIE-0033/2012 (H6N2) in mice. The present results indicate that the whole inactivated virus particle vaccine prepared from a virus strain in the influenza virus library is useful as a vaccine against pandemic influenza.
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Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Virus de la Influenza A/genética , Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/inmunología , Animales , Anticuerpos Antivirales/inmunología , Secuencia de Bases , Línea Celular , Embrión de Pollo , Perros , Femenino , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/virología , Filogenia , Análisis de Secuencia de ADN , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Vaccination is a feasible approach for controlling foot-and-mouth disease (FMD). In FMD-free countries, vaccines are stored as a precautionary measure to control potential outbreaks. However, the challenge lies in pre-stocking optimal vaccines against the newly emerging strains. This study examined the potency of pre-stocked vaccines administered at elevated doses during emergencies. We vaccinated the cows with either a single or double trivalent vaccine dose containing two serotype O and one serotype A strains. Subsequently, vaccinated and unvaccinated cows were exposed to virulent strains of serotype O (O/JPN/2010; topotype Southeast Asia/Mya-98 lineage) or A (A/IRN/2016; topotype ASIA/G-VII lineage), which were genetically and antigenically distinct from the vaccine strains. Following challenge infections, all cows that received a single dose vaccination exhibited vesicular lesions with excreted viruses in the oral and nasal discharges. However, a substantial reduction was observed in the total clinical scores and virus titers in the sera and nasal discharges compared to those in the unvaccinated group. Cows receiving a doubled dose vaccination were completely protected from infection with O/JPN/2010 or demonstrated a significant decrease in viral shedding and clinical scores against A/IRN/2016. To note, vesicular lesions harbor significant amounts of viruses; thus, by mitigating their formation, viral transmission can be impeded, thereby slowing viral spread in the field. Furthermore, increasing the vaccine dose induced higher neutralizing antibody titers against heterologous strains. These findings suggest an alternative strategy for the effective management of future epidemics using pre-stocked vaccines.
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Enfermedades de los Bovinos , Virus de la Fiebre Aftosa , Fiebre Aftosa , Vacunas Virales , Animales , Bovinos , Fiebre Aftosa/prevención & control , Fiebre Aftosa/inmunología , Fiebre Aftosa/virología , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/virología , Enfermedades de los Bovinos/inmunología , Virus de la Fiebre Aftosa/inmunología , Femenino , Vacunación/veterinaria , Anticuerpos Antivirales/sangre , Esparcimiento de Virus , SerogrupoRESUMEN
To estimate the prevalence of avian influenza virus infection in Vietnam, surveillance was conducted in domestic and wild birds from households, live-bird markets, slaughtering sites, and bird sanctuaries in Vietnam between October 2010 and October 2012. Of the 4,550 samples collected, 226 influenza A virus isolates were obtained from domestic ducks, muscovy ducks, and chickens. Of these, 25 and 22 H5N1 highly pathogenic avian influenza viruses (HPAIVs) were isolated from apparently healthy domestic ducks in live-bird markets and slaughtering sites in northern and southern Vietnam, respectively. The HA genes of H5 viruses isolated from birds in northern Vietnam phylogenetically belonged to the genetic clade 2.3.2.1 and those in southern Vietnam belonged to the genetic clade 1.1. In addition, 39 H3, 12 H4, 1 H5, 93 H6, 2 H7, 18 H9, 3 H10, and 11 H11 viruses were isolated. Phylogenetic and antigenic analyses of the H6 and H9 viruses revealed that they were closely related to the isolates obtained from domestic poultry in China. Phylogenetic analyses of internal gene segments of these isolates revealed that these viruses were circulating in both domestic and wild birds in Asia and reassortment events had occurred frequently. Therefore, it will be important to continue the surveillance and strict controls over the movement and trade of poultry and poultry products in order to eradicate H5N1 HPAIV from Asia.
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Variación Antigénica , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Virus de la Influenza A/genética , Virus de la Influenza A/inmunología , Gripe Aviar/virología , Animales , Pollos , Análisis por Conglomerados , Patos , Gripe Aviar/epidemiología , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , ARN Viral/genética , Análisis de Secuencia de ADN , Homología de Secuencia , Vietnam/epidemiologíaRESUMEN
Here, we report near-complete genome sequences of three foot-and-mouth disease viruses isolated in 2016 from bovine and porcine epithelial tissue samples collected in Nonthaburi, Songkhla, and Ratchaburi provinces, Thailand. These viruses were classified as serotype O, topotype ME-SA, and sublineage Ind-2001e.
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PURPOSE: We examined the association of gross motor function and activities of daily living (ADL) with muscle mass of the trunk and lower extremity muscles in children and adults with cerebral palsy (CP). METHODS: The subjects were 32 children and adults with CP. Muscle thickness of the trunk and lower extremity muscles was measured using an ultrasound imaging device. RESULTS: Stepwise regression analysis revealed that the thoracic erector spinae muscle thickness was a significant and independent factor of gross motor function. Stepwise regression analysis also showed that the thickness of the rectus abdominis and vastus lateralis muscles were significant and independent factors of ADL. CONCLUSIONS: Our findings suggest that declined gross motor function is associated with decreased thoracic erector spinae muscle mass in children and adults with CP. The results also indicate that declined ADL is associated with decreased muscle mass of the rectus abdominis and vastus lateralis muscles.
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Actividades Cotidianas , Parálisis Cerebral , Humanos , Niño , Adulto , Espasticidad Muscular , Músculo Esquelético , Extremidad Inferior , Rango del Movimiento ArticularRESUMEN
BACKGROUND: Preoperative computed tomography-guided marking can help identify small non-palpable pulmonary nodules during surgery. However, this technique is associated with the risk of air embolism. We retrospectively evaluated whether small pulmonary nodules could be intraoperatively localized using cone-beam computed tomography (CBCT). METHODS: A hybrid operating room permitting stable lateral positioning and scanning from the pulmonary apex to the base was used in all patients. CBCT images were obtained using a 10-s protocol with 180º rotation of the C-arm flat panel detector around the patient. Clips were placed on the visceral pleura to help guide pulmonary nodule localization. Partial pulmonary resection was performed using video-assisted thoracoscopic surgery at the predicted nodule site. RESULTS: Between July 2013 and June 2019, 132 patients with 145 lesions underwent this procedure at our center. The detection rate of lesions on CBCT was 100%. The pathological diagnoses were primary lung cancer, metastatic pulmonary tumors, and benign lesions. The average consolidation-to-tumor ratio was 0.65 for all nodules, with ratios of 0.33, 0.96, and 0.70 for primary lung cancer, metastatic pulmonary tumors, and benign lesions, respectively. No complications related to this localization method were observed. CONCLUSIONS: CBCT-guided intraoperative localization is safe and feasible for non-palpable small pulmonary nodules. This technique may eliminate the risk of serious complications such as air embolism.
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Embolia Aérea , Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Humanos , Estudios Retrospectivos , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Tomografía Computarizada de Haz Cónico , Instrumentos QuirúrgicosRESUMEN
A previous study proved that vGPE- mainly maintains the properties of classical swine fever (CSF) virus, which is comparable to the GPE- vaccine seed and is a potentially valuable backbone for developing a CSF marker vaccine. Chimeric viruses were constructed based on an infectious cDNA clone derived from the live attenuated GPE- vaccine strain as novel CSF vaccine candidates that potentially meet the concept of differentiating infected from vaccinated animals (DIVA) by substituting the glycoprotein Erns of the GPE- vaccine strain with the corresponding region of non-CSF pestiviruses, either pronghorn antelope pestivirus (PAPeV) or Phocoena pestivirus (PhoPeV). High viral growth and genetic stability after serial passages of the chimeric viruses, namely vGPE-/PAPeV Erns and vGPE-/PhoPeV Erns, were confirmed in vitro. In vivo investigation revealed that two chimeric viruses had comparable immunogenicity and safety profiles to the vGPE- vaccine strain. Vaccination at a dose of 104.0 TCID50 with either vGPE-/PAPeV Erns or vGPE-/PhoPeV Erns conferred complete protection for pigs against the CSF virus challenge in the early stage of immunization. In conclusion, the characteristics of vGPE-/PAPeV Erns and vGPE-/PhoPeV Erns affirmed their properties, as the vGPE- vaccine strain, positioning them as ideal candidates for future development of a CSF marker vaccine.
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Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Pestivirus , Vacunas Virales , Porcinos , Animales , Vacunas Marcadoras , Anticuerpos Antivirales , Vacunas Atenuadas , Virus de la Fiebre Porcina Clásica/genética , Pestivirus/genéticaRESUMEN
Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance. Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC. Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation. Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.
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We detected the classical swine fever virus (CSFV) antigen in three boar-pig hybrids (hybrids) and three pigs. All animals were experimentally infected with CSFV strain JPN/27/2019 to optimize diagnostic sampling and risk assessment of virus dissemination. Two hybrids died 17- and 19-days post-inoculation (dpi). The other animals were euthanized at 28 dpi. The detection of CSFV antigen at 28 dpi in epithelial cells of the apocrine sweat and sebaceous glands in the skin, salivary glands, mucosal epithelial cells in the rectum, and epithelial cells in the kidney and urinary bladder, suggests that CSFV persists in these tissues and spreads via sweat, saliva, feces, and urine for at least 4 weeks. These findings reveal that hybrids and pigs represent a high risk of virus dissemination four weeks after infection with CSFV strain JPN/27/2019. Prominent CSFV antigens were also detected in hair follicles of the skin. These results suggest that postmortem sampling of animal skin may be effective for CSF diagnosis and can be used to develop a rapid and easy diagnostic method using hair follicles.
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Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Enfermedades de los Porcinos , Animales , Antígenos Virales , Masculino , Saliva , Porcinos , Vacunación/veterinariaRESUMEN
African swine fever (ASF) and classical swine fever (CSF) are contagious swine diseases that are clinically indistinguishable from each other; hence, reliable test methods for accurate diagnosis and differentiation are highly demanded. By employing a buffer system suitable for crude extraction of nucleic acids together with an impurity-tolerant enzyme, we established a multiplex assay of real-time reverse-transcription polymerase chain reaction (rRT-PCR) for simultaneous detection of ASF virus (ASFV), CSF virus (CSFV) and swine internal control derived genes in a sample without the need for prior purification of viral nucleic acids. We applied this method to test serum and tissue samples of infected pigs and wild boars and compared the statistical sensitivities and specificities with those of standard molecular diagnostic methods. When a serum was used as a test material, the newly established assay showed 94.4% sensitivity for both and 97.9 and 91.9% specificity for ASFV and CSFV detection, respectively. In contrast, the results were 100% identical with those obtained by the standard methods when a crude tissue homogenate was used as a test material. The present data indicate that this new assay offers a practical, quick, and reliable technique for differential diagnosis of ASF and CSF where geographical occurrences are increasingly overlapping.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Ácidos Nucleicos , Fiebre Porcina Africana/diagnóstico , Virus de la Fiebre Porcina Africana/genética , Animales , Virus de la Fiebre Porcina Clásica/genética , Diagnóstico Diferencial , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Sensibilidad y Especificidad , PorcinosRESUMEN
After 26 years, another classical swine fever virus (CSFV) outbreak in domestic pigs and wild boars occurred in Japan 2018. Herein, we investigated the entry and the spatial dynamics of the CSFV outbreak in Japan using the nearly complete genomes of strains isolated from both wild boars and domestic pigs during this epidemic. Phylogenetic analysis showed that the most recent common ancestor (MRCA) of the Japanese lineage emerged 146 days (95% highest posterior density (HPD): 85-216 days) before the index case was detected. Based on epidemiological analysis, the period for the 95% HPD was 1 month earlier than the time of virus introduction into the index farm. The disease mainly spreads to the adjoining regions during the epidemic, with no spread to the nonadjacent regions. This result indicates that human activities, such as the movement of vehicles, contributed to the infection spread. As cases occurred in nonadjacent regions, the MRCA for the epidemic in the Saitama prefecture was estimated to have emerged 93 days before the date of detection in the initial farm in this region. Similarly, the MRCA for the epidemic in Okinawa prefecture, more than 1,300 km away from the other infected regions, was estimated to have emerged 34 days before the date of detection in the region's primary farm. Therefore, our results indicate that if exotic diseases emerge after a long period of absence or in a disease-free country, a longer period of time will elapse before detection, resulting in further spread. Additionally, subsequent infections occurring in regions distant from the original infected region will require less time for detection than in the original region. This study provides valuable insights into a CSFV outbreak that occurred in a previously CSFV-free country and thus beneficial in enhancing producers' awareness and allow for better preparation for infections.
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Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Enfermedades de los Porcinos , Animales , Peste Porcina Clásica/epidemiología , Virus de la Fiebre Porcina Clásica/genética , Brotes de Enfermedades/veterinaria , Japón/epidemiología , Filogenia , Sus scrofa , Porcinos , Enfermedades de los Porcinos/epidemiologíaRESUMEN
Classical swine fever (CSF) is a worldwide devastating disease of the pig industry caused by classical swine fever virus (CSFV). In September 2018, an outbreak of CSF occurred in Japan where the disease had been eradicated and was officially designated a CSF-free country since 2015. Following the detection of the first 2018 case on a farm in Gifu Prefecture, the disease spread among both farm pigs and wild boars and still continues. Epigenome analysis using whole-genome information is helpful in identifying the infection route, but the current approaches provide an insufficient resolution. In this study, a novel method of using single-nucleotide variants (SNVs) was employed to identify the associations among 158 isolates (65 from farms and 93 from wild boars). The identified groups of CSFV strains were plotted in different colours on a map, identifying the location where each strain was collected. The lack of an SNV set shared between the index case and the other strains suggested the first infection in Japan during the outbreak occurred in wild boars, not at the index farm. For the Atsumi Peninsula outbreaks, where nine farms were found infected within a 10-km radius area, the farm strains were assembled into three groups, suggesting these outbreaks resulted from at least three different infection events in this area. For the infections in the area around Saitama Prefecture, an area remote from the epicentre, strains from both the farms and wild boars were identified as being in the same group, suggesting they resulted from one viral introduction. Likewise, seven infected farms in Okinawa Prefecture, almost 1,500 km from Gifu Prefecture, were identified as being in a common, but separate group. By demonstrating the variety of transmission routes and possibility of long-distance infection, these results will help improve disease control measures.