RESUMEN
Japan has reported a relatively small number of COVID-19 cases. Because not all infected persons receive diagnostic tests for COVID-19, the reported number must be lower than the actual number of infections. We assessed SARS-CoV-2 seroprevalence by analyzing >60,000 samples collected in Japan (Tokyo Metropolitan Area and Hokkaido Prefecture) during February 2020-March 2022. The results showed that ≈3.8% of the population had become seropositive by January 2021. The seroprevalence increased with the administration of vaccinations; however, among the elderly, seroprevalence was not as high as the vaccination rate. Among children, who were not eligible for vaccination, infection was spread during the epidemic waves caused by the SARS-CoV-2 Delta and Omicron variants. Nevertheless, seroprevalence for unvaccinated children <5 years of age was as low as 10% as of March 2022. Our study underscores the low incidence of SARS-CoV-2 infection in Japan and the effects of vaccination on immunity at the population level.
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COVID-19 , SARS-CoV-2 , Niño , Humanos , Anciano , COVID-19/epidemiología , COVID-19/prevención & control , Japón/epidemiología , Estudios Seroepidemiológicos , Anticuerpos Antivirales , VacunaciónRESUMEN
INTRODUCTION: Mycoplasma pneumoniae (M. pneumoniae) is the major pathogen involved in community-acquired pneumonia in all age groups. Resistance to macrolides, the first-line treatment for M. pneumoniae infection, is a major global public health concern. However, studies evaluating macrolide-resistant M. pneumoniae infection simultaneously in all ages are limited. This study aimed to determine the prevalence and clinical characteristics of macrolide-resistant M. pneumoniae infection in terms of age distribution. METHODS: We enrolled 292 patients in Tokyo, Japan, who visited Eiju General Hospital or Zama Children's Clinic in 2015-2016. Patients were tested using real-time PCR for M. pneumoniae DNA. PCR-positive patients (n = 151) were further selected and sequentially divided into preschool-aged children (≤5 years, n = 31), school-aged children (6-15 years, n = 101), adolescents (16-19 years, n = 5), and adults (≥20 years, n = 14). We then analyzed the M. pneumoniae infection clinical characteristics, prevalence of macrolide-resistant infection, and 23S rRNA domain V resistance-associated mutation status. RESULTS: We found insignificant differences in the prevalence of macrolide-resistant M. pneumoniae infection among all groups, clinical characteristics, and resistance-associated mutation status in patients with macrolide-resistant M. pneumoniae infection. We also found statistically higher prevalence of mutation-positive (n = 85) M. pneumoniae in patients previously treated with macrolide compared to the mutation-negative group (n = 66); 63.8% vs 11.1% (p < 0.001), respectively. CONCLUSIONS: We found no significant differences in both clinical characteristics and prevalence of macrolide-resistant M. pneumoniae infection among all ages. Also, previous macrolide treatment contributes to drug-resistance.
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Mycoplasma pneumoniae , Neumonía por Mycoplasma , Adolescente , Adulto , Distribución por Edad , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Niño , Preescolar , Farmacorresistencia Bacteriana , Humanos , Japón/epidemiología , Macrólidos/farmacología , Macrólidos/uso terapéutico , Mycoplasma pneumoniae/genética , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/epidemiología , ARN Ribosómico 23S/genética , TokioRESUMEN
INTRODUCTION: ID NOW™ Influenza A & B 2 (ID NOW 2) is a rapid molecular assay that combines two characteristics, namely the rapidness of rapid antigen detection test (RADT) and the high sensitivity of molecular assay. METHODS: The clinical performance of ID NOW 2 compared with real-time RT-PCR was evaluated in adults. RESULTS: The sensitivity of ID NOW 2 over multiple seasons from 2016/2017 to 2019/2020 was 97.3% (95% CI: 90.7-99.7) for Type A, 100% (95% CI: 81.9-100) for Type B, and 97.8% (95% CI: 92.2-99.7) for influenza (Type A + Type B), and it was significantly higher than the sensitivity of RADT, which was 80.0% (95% CI: 69.2-88.4) for Type A, 73.3% (95% CI: 44.9-92.2) for Type B, and 78.9% (95% CI: 69.0-86.8) for influenza. The sensitivity of RADT tended to be lower in patients in the particularly early period, within 12 h from disease onset; however, the sensitivity of ID NOW 2 remained high, increasing the difference between the sensitivity of RADT and ID NOW 2. The viral loads were low within 12 h from onset, and it was considered this affected the sensitivity of RADT due to its low analytical sensitivity. The specificity of ID NOW 2 was 98% or greater in all groups. CONCLUSIONS: Since ID NOW 2 has a high sensitivity and specificity in adults, it is anticipated to be used in clinical practice, particularly in patients who require early and accurate diagnosis.
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Virus de la Influenza A , Gripe Humana , Adulto , Clorofenoles , Humanos , Virus de la Influenza A/genética , Virus de la Influenza B/genética , Gripe Humana/diagnóstico , Sensibilidad y EspecificidadRESUMEN
In this study, we evaluated the performance of ID NOW Influenza A & B 2 (ID NOW 2), a rapid molecular point-of-care test for influenza within 13 min, in comparison with currently available tests. A total of 254 nasopharyngeal swabs (NPS) and 271 nasopharyngeal aspirates (NPA) collected from 373 children and 152 adults with influenza-like illness were tested using ID NOW 2, viral culture, rapid antigen detection test, and loop-mediated isothermal amplification test to evaluate the sensitivity and specificity compared with real-time reverse transcription polymerase chain reaction as the reference method. The sensitivities of ID NOW 2 for influenza A were 95.9% and 95.7% in NPS and NPA, respectively, and for influenza B were 100% and 98.7% in NPS and NPA, respectively. The specificity was 100% for both influenza A and influenza B in NPS and NPA. Sensitivity of each test method reflected the difference of analytical sensitivity among the tests, and ID NOW 2 was not affected by time after illness onset and patient age. In conclusion, ID NOW 2 demonstrated a high sensitivity and specificity that is useful for diagnosis of influenza in the clinical setting and infection control.
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Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Virales/aislamiento & purificación , Niño , Preescolar , Femenino , Humanos , Lactante , Virus de la Influenza A/genética , Virus de la Influenza B/genética , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Adulto JovenRESUMEN
In 2019, influenza A(H3N2) viruses carrying an I38T substitution in the polymerase acidic gene, which confers reduced susceptibility to baloxavir, were detected in Japan in an infant without baloxavir exposure and a baloxavir-treated sibling. These viruses' whole-genome sequences were identical, indicating human-to-human transmission. Influenza virus isolates should be monitored for baloxavir susceptibility.
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Antivirales/farmacología , Susceptibilidad a Enfermedades , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/transmisión , Gripe Humana/virología , Oxazinas/farmacología , Piridinas/farmacología , Tiepinas/farmacología , Triazinas/farmacología , Adolescente , Adulto , Antivirales/uso terapéutico , Niño , Dibenzotiepinas , Humanos , Lactante , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Japón/epidemiología , Persona de Mediana Edad , Morfolinas , Mutación , Oxazinas/uso terapéutico , Piridinas/uso terapéutico , Piridonas , Tiepinas/uso terapéutico , Triazinas/uso terapéutico , Adulto JovenRESUMEN
In January 2019, two influenza A(H3N2) viruses carrying an I38T substitution in the polymerase acidic subunit (PA), which confers reduced susceptibility to baloxavir, were detected from epidemiologically unrelated hospitalised children in Japan. The viruses exhibited reduced susceptibility to baloxavir but were susceptible to neuraminidase inhibitors. Only one of the two children had been treated with baloxavir. An epidemiological analysis suggests possible transmission of the PA I38T mutant A(H3N2) virus among humans.
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Antivirales/farmacología , Farmacorresistencia Viral/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/tratamiento farmacológico , Oxazinas/farmacología , Piridinas/farmacología , Tiepinas/farmacología , Triazinas/farmacología , Adolescente , Adulto , Antivirales/uso terapéutico , Niño , Dibenzotiepinas , Inhibidores Enzimáticos/farmacología , Humanos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/diagnóstico , Pacientes Internos , Japón , Persona de Mediana Edad , Morfolinas , Oxazinas/uso terapéutico , Reacción en Cadena de la Polimerasa , Piridinas/uso terapéutico , Piridonas , Tiepinas/uso terapéutico , Resultado del Tratamiento , Triazinas/uso terapéutico , Adulto JovenRESUMEN
The novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved for the treatment of influenza virus infection in Japan in February 2018. Two influenza A(H3N2) viruses carrying an I38T substitution in the polymerase acidic subunit (PA) were detected in baloxavir-treated children in December 2018. This mutation is known to confer reduced susceptibility to baloxavir, and the two mutant viruses exhibited 76- and 120-fold reduced susceptibility to baloxavir.
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Antivirales/uso terapéutico , Endonucleasas/antagonistas & inhibidores , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/tratamiento farmacológico , Oxazinas/uso terapéutico , Piridinas/uso terapéutico , Tiepinas/uso terapéutico , Triazinas/uso terapéutico , Sustitución de Aminoácidos/genética , Antivirales/administración & dosificación , Dibenzotiepinas , Farmacorresistencia Viral/efectos de los fármacos , Farmacorresistencia Viral/genética , Endonucleasas/genética , Humanos , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/diagnóstico , Japón , Pruebas de Sensibilidad Microbiana , Morfolinas , Piridonas , Resultado del TratamientoRESUMEN
The oxidant and antioxidant equilibrium is known to play an important role in equine medicine and equine exercise physiology. There are abundant findings in this field; however, not many studies have been conducted for reference ranges of oxidative stress biomarkers in horses. This study was conducted to determine the reference values of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) using blood samples from 372 (191 males, 181 females) Thoroughbred racehorse aged 2 to 5 (3.43 ± 1.10 (mean ± SD)) years old. There were obvious gender differences in oxidative biomarkers, and growth/age-related changes were observed especially in females. Gender and age must be considered when interpreting obtained oxidative stress biomarkers for diagnosis of disease or fitness alterations in Thoroughbred racehorses.
RESUMEN
Influenza A viruses cause recurrent outbreaks at local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On 11 June 2009 the World Health Organization declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses. Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) seem to be mild; however, a substantial number of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; hereafter referred to as CA04), as well as several other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04 and other S-OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in non-human primates, causes more severe pathological lesions in the lungs of infected mice, ferrets and non-human primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen-free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting that these compounds could function as a first line of defence against the recently declared S-OIV pandemic.
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Subtipo H1N1 del Virus de la Influenza A/fisiología , Porcinos/virología , Animales , Anticuerpos Antivirales/inmunología , Antivirales/farmacología , Línea Celular , Perros , Femenino , Hurones/virología , Proteína HN/metabolismo , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/enzimología , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Macaca fascicularis/inmunología , Macaca fascicularis/virología , Masculino , Ratones , Ratones Endogámicos BALB C , Pruebas de Neutralización , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/transmisión , Infecciones por Orthomyxoviridae/virología , Enfermedades de los Primates/patología , Enfermedades de los Primates/virología , Enfermedades de los Porcinos/patología , Enfermedades de los Porcinos/virología , Porcinos Enanos/virología , Replicación ViralRESUMEN
Substance P-immunoreactive nerve fiber (SP-IR NF) and calcitonin gene-related peptide-immunoreactive nerve fiber (CGRP-IR NF) are important mediators of neurogenic inflammation and blood supply. SP-IR and CGRP-IR NFs in the tensor tympani muscle (TTM) of the human middle ear have yet to be described. In this study, the TTM, tympanic membrane, malleus in the middle ear and tensor veli palatini muscle (TVPM) were examined by whole-mount immunohistochemistry in tissue from Japanese subjects. Thirteen human cadavers (ranging in age from 46 to 90 years) were used in this study. SP-IR and CGRP-IR NFs were primarily found on vessels at the origin, insertion and belly of the surface of the TTM and on the internal surface of the tympanic membrane. These neural factors were also detected on the surface of the malleus and the insertion of the TVPM. Therefore, our results indicate that existence of the SP-IR and CGRP-IR NFs of the TTM and the TVPM may reflect muscle properties involved in pain or inflammation of the middle ear.
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Péptido Relacionado con Gen de Calcitonina/análisis , Sustancia P/análisis , Tensor del Tímpano/anatomía & histología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Microvasos/inervación , Persona de Mediana Edad , Fibras Nerviosas/ultraestructura , Tensor del Tímpano/irrigación sanguínea , Tensor del Tímpano/inervaciónRESUMEN
It is difficult to differentiate between coronavirus disease 2019 (COVID-19) and influenza based on the symptoms. In the present study, a newly developed antigen rapid diagnostic test (Ag-RDT) called Panbio™ COVID-19/Flu A&B that can simultaneously detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/B virus was evaluated. Its accuracy was evaluated using 235 pairs of nasopharyngeal samples collected from patients with respiratory symptoms and fever (>37.5°C). Reverse transcription polymerase chain reaction was used as a reference method to evaluate the accuracy of the SARS-CoV-2 detection. We confirmed the accuracy of the developed Ag-RDT against the Omicron variant where the sensitivity and specificity were 94.8% and 100%, respectively. In addition, to identify the influenza A virus, a noninferiority test was conducted using a commercial Ag-RDT, which has a sensitivity and specificity in comparison with viral culture of 94.8% and 98.4%, respectively. The positive and negative predictive values for influenza A virus were 98.5% and 98.1%, respectively, for the Panbio COVID-19/Flu A&B test. The evaluation of this newly developed Ag-RDT using clinical samples suggests that it has a high efficacy in clinical settings.
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Antígenos Virales , COVID-19 , Virus de la Influenza A , Virus de la Influenza B , Gripe Humana , SARS-CoV-2 , Sensibilidad y Especificidad , Humanos , Gripe Humana/diagnóstico , Gripe Humana/virología , Gripe Humana/inmunología , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Virus de la Influenza A/inmunología , Virus de la Influenza A/aislamiento & purificación , Persona de Mediana Edad , Adulto , Femenino , Masculino , Anciano , Antígenos Virales/inmunología , Virus de la Influenza B/inmunología , Virus de la Influenza B/aislamiento & purificación , Adulto Joven , Adolescente , Nasofaringe/virología , Anciano de 80 o más Años , Niño , Prueba Serológica para COVID-19/métodos , Preescolar , Prueba de Diagnóstico RápidoRESUMEN
We evaluated Clearline Influenza A/B/(H1N1)2009, a new multi-line immunochromatographic assay for rapid detection of antigens of influenza A (Flu A), B (Flu B), and A(H1N1)2009 viruses. Clearline detected Flu A, Flu B, and A(H1N1)2009 viruses with a detection limit of 4.6 × 10(3) to 7.5 × 10(4) pfu/assay. The sensitivity and specificity of detection of influenza virus by Clearline, using RT-PCR as reference standard, were determined for A(H1N1)2009, Flu A, and Flu B, in nasopharyngeal aspirate, nasopharyngeal swab, and self-blown nasal discharge specimens. Sensitivity for nasopharyngeal aspirate specimens was: A(H1N1)2009 = 97.3 %, Flu A = 94.5 %, and Flu B = 96.8 %, and specificity was Flu A = 99.1 % and Flu B = 100 %. Sensitivity for nasopharyngeal swab specimens was: A(H1N1)2009 = 91.9 %, Flu A = 92.8 %, and Flu B = 100 %, and specificity was Flu A = 98.2 % and Flu B = 100 %. Sensitivity for self-blown nasal discharge specimens was: A(H1N1)2009 = 75.7 %, Flu A = 86.5 %, and Flu B = 76.2 %, and specificity was Flu A = 98.4 % and Flu B = 100 %. Sensitivity and specificity of Clearline were sufficient for nasopharyngeal aspirate and swab specimens. For self-blown nasal discharge specimens, sensitivity was lower than for nasopharyngeal aspirates and nasopharyngeal swabs. The sensitivity of Clearline for A(H1N1)2009 was good even 6 h after the onset of symptoms. These findings suggest that Clearline may be useful for early clinical diagnosis of influenza.
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Cromatografía de Afinidad/métodos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Virus de la Influenza A/clasificación , Virus de la Influenza B/clasificación , Gripe Humana/virología , Virología/métodos , Fiebre/virología , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/inmunología , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/inmunología , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/diagnóstico , Nasofaringe/virología , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: Gas sampling tubes are essential tools for the evaluation of air quality in work environments. It adsorbs toxic gaseous matters onto the surface of various granular adsorbents, such as silica gel or activated carbon packed in a thin glass tube, for quantitative analysis by gas chromatography. Currently, most of the semi-volatile matters are evaluated via aerosol filtration or solid-phase gas adsorption depending on the main phase of the substances; however, only a few substances have a sampling protocol regarding both solid and gaseous phases. Therefore, semi-volatile components evaluated by the solid-phase adsorption may result in the underestimation of the component concentrations due to particulate components passing through and remaining in the adsorbent. To highlight issues on sampling of semi-volatile matters by the solid-phase adsorption method, the collection efficiency of aerosol particles by 17 commercial gas sampling tubes were measured via pressure drop. METHODS: To measure the particle collection efficiency of the gas collection tubes, precise control and dilution of the aerosol particle monitors are essential. However, we cannot apply typical filter test methods at a lower filtration flow rate than that of the aerosol particles monitors. Therefore, we developed a new experimental method that considers flow adjustment between the aerosol monitors. By assuming two specific particle size distributions and five inlet conditions, the collection efficiencies of total mass particles are estimated. From the gas-particle partitioning ratio of 16 polycyclic aromatic hydrocarbons (PAHs) in a coal tar pitch manufacturing industry, the underestimation of the concentration of semi-volatile matters using the gas collection tubes has been discussed. RESULTS: The aerosol particles were collected in all kinds of layers in the gas sampling tubes, such as in the glass wool cap, gas adsorbent granular bed, and polyurethane foam. Furthermore, the collection efficiency curve of all 17 gas sampling tubes tested showed similar trends; a valley around particle sizes ranging from 0.2-0.3 µm between high collection zones below 0.1 µm and above 1 µm was observed. The observations suggested granular bed filters collection mechanisms such as inertial impaction, Brownian diffusion, gravity, and interception as same as air filters. CONCLUSIONS: Solid-phase collection can underestimate the concentrations of multi-phase matters. Thus, we wish to highlight the importance of solid-phase collection methods along with filtration collection methods to collect all phases of semi-volatile matters.
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Polvo , Hidrocarburos Policíclicos Aromáticos , Aerosoles/análisis , Carbón Mineral/análisis , Polvo/análisis , Monitoreo del Ambiente/métodos , Gases/análisis , Gases/química , Humanos , Tamaño de la Partícula , Hidrocarburos Policíclicos Aromáticos/análisisRESUMEN
BACKGROUND: Although influenza virus resistance to the neuraminidase inhibitor zanamivir is reported less frequently than is resistance to the neuraminidase inhibitor oseltamivir in clinical settings, it is unknown whether this difference is due to the limited use of zanamivir or to an inherent property of the drug. We therefore compared the prevalence of drug-resistant viruses and virus shedding in seasonal influenza virus-infected children treated with either oseltamivir or zanamivir. METHODS: Clinical specimens (throat or nasal swab) were collected from a total of 144 pediatric influenza patients during the 2005-2006, 2006-2007, 2007-2008, and 2008-2009 influenza seasons. Neuraminidase inhibitor-resistant mutants were detected among the isolated viruses by sequencing the viral hemagglutinin and neuraminidase genes. Sensitivity of the viruses to neuraminidase inhibitors was tested by neuraminidase inhibition assay. RESULTS: In oseltamivir- or zanamivir-treated influenza patients who were statistically comparable in their age distribution, vaccination history, and type or subtype of virus isolates, the virus-shedding period in zanamivir-treated patients was significantly shorter than that in oseltamivir-treated patients. Furthermore, the frequency of zanamivir-resistant viruses was significantly lower than that of oseltamivir-resistant viruses. CONCLUSION: In comparison with treatment with oseltamivir, treatment of pediatric patients with zanamivir resulted in the emergence of fewer drug-resistant influenza viruses and a shorter virus-shedding period. We conclude that zanamivir shows promise as a better therapy for pediatric influenza patients.
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Farmacorresistencia Viral , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Orthomyxoviridae/efectos de los fármacos , Oseltamivir/uso terapéutico , Esparcimiento de Virus , Zanamivir/uso terapéutico , Adolescente , Antivirales/farmacología , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Mucosa Nasal/virología , Neuraminidasa/antagonistas & inhibidores , Orthomyxoviridae/aislamiento & purificación , Oseltamivir/farmacología , Faringe/virología , ARN Viral/genética , Análisis de Secuencia de ADN , Resultado del Tratamiento , Zanamivir/farmacologíaRESUMEN
Human-to-human transmission of PA I38 mutant influenza A(H3N2) viruses with reduced baloxavir susceptibility has been reported in Japan. In December 2019, we detected a PA E23K mutant A(H1N1)pdm09 virus from a child without baloxavir treatment. The PA E23K mutant virus exhibited reduced baloxavir susceptibility but remained susceptible to neuraminidase inhibitors. Epidemiological data suggest possible transmission of this PA E23K mutant virus among humans, although its growth capability relative to that of the wild-type virus was reduced. Therefore, baloxavir susceptibility monitoring of influenza viruses is essential.
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Antivirales/farmacología , Dibenzotiepinas/farmacología , Farmacorresistencia Viral/genética , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/genética , Morfolinas/farmacología , Piridonas/farmacología , Triazinas/farmacología , Proteínas Virales/genética , Sustitución de Aminoácidos , Animales , Niño , Perros , Humanos , Gripe Humana/transmisión , Gripe Humana/virología , Japón , Células de Riñón Canino Madin DarbyRESUMEN
Surveillance studies of the influenza viruses circulating in Europe and other countries in 2007 and 2008 have revealed rates of resistance to oseltamivir of up to 67% among H1N1 viruses. In the present study, we examined 202 clinical samples obtained from patients infected with H1N1 virus in Japan in 2007 and 2008 for oseltamivir resistance and found that three were oseltamivir resistant (1.5%). The 50% inhibitory concentrations (IC(50)s), as measured by a sialidase inhibition assay with these drug-resistant viruses, were >100-fold higher than those of the nonresistant viruses (median IC(50), 12.6 nmol/liter). The His274Tyr (strain N2 numbering) mutation of the neuraminidase protein, which is known to confer oseltamivir resistance, was detected in these three isolates. Phylogenetic analysis showed that one virus belonged to a lineage that is composed of drug-resistant viruses isolated in Europe and North America and that the other two viruses independently emerged in Japan. Continued surveillance studies are necessary to observe whether these viruses will persist.
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Antivirales/farmacología , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/virología , Oseltamivir/farmacología , Sustitución de Aminoácidos/genética , Análisis por Conglomerados , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Concentración 50 Inhibidora , Japón , Mutación Missense , Neuraminidasa/genética , Filogenia , Homología de Secuencia , Proteínas Virales/genéticaRESUMEN
BACKGROUND: We compared the clinical effectiveness of oseltamivir and zanamivir in children with influenza A (H1N1) virus, influenza A (H3N2) virus, and influenza B virus infections. METHODS: Total febrile period and the duration of fever after the start of treatment were compared between an oseltamivir-treated group (mean age, 8.9 years; range, 4.0-15.9 years) and a zanamivir-treated group (mean age, 10.0 years; range, 4.0-15.7 years) in the pediatric outpatient clinics of our hospitals. Oseltamivir was used to treat 91 children with influenza A (H3N2) infection and 24 children with influenza A (H1N1) infection. Zanamivir was used to treat 35 children with influenza A (H3N2) infection and 12 children with influenza A (H1N1) infection. Oseltamivir was also used to treat 128 children with influenza B virus infection, and zanamivir was used to treat 59 with influenza B virus infection. RESULTS: There was no statistically significant difference in total febrile period or duration of fever after the start of treatment between the oseltamivir-treated group and the zanamivir-treated group of children with influenza A (H3N2) infection (mean duration of febrile period, 2.40 days vs. 2.39 days; mean duration of fever after the start of treatment, 1.35 days vs. 1.40 days), influenza A (H1N1) (mean duration of febrile period, 2.60 days vs. 2.46 days; mean duration of fever after the start of treatment, 1.79 days vs, 1.54 days), or influenza B (mean duration of febrile period, 2.95 days vs. 2.84 days; mean duration of fever after the start of treatment, 1.86 days vs. 1.67 days). Oseltamivir was more effective against influenza A (H3N2) than against influenza A (H1N1) or influenza B. CONCLUSIONS: Oseltamivir and zanamivir were equally effective in reducing the febrile period of children with influenza A (H1N1), influenza A (H3N2), and influenza B virus infection.
Asunto(s)
Antivirales/uso terapéutico , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Oseltamivir/uso terapéutico , Zanamivir/uso terapéutico , Adolescente , Niño , Preescolar , Fiebre/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Mycoplasma pneumoniae infection is conventionally diagnosed using serum antibody testing, microbial culture, and genetic testing. Recently, immunochromatography-based rapid mycoplasma antigen test kits have been developed and commercialised for rapid diagnosis of M. pneumoniae infection. However, as these kits do not provide sufficient sensitivity and specificity, a rapid test kit with improved accuracy is desired. The present prospective study evaluated a rapid M. pneumoniae diagnostic system utilizing a newly developed silver amplification immunochromatography (SAI) system. We performed dilution sensitivity test and the prospective clinical study evaluating the SAI system. The subjects of the clinical study included both children and adults. All patients suspected to have mycoplasma pneumonia (169 patients) were sequentially enrolled. Twelve patients did not agree to participate and 157 patients were enrolled in the study. The results demonstrate excellent performance of this system with 90.4% sensitivity and 100.0% specificity compared with real-time polymerase chain reaction. When compared with loop-mediated isothermal amplification (LAMP) methods, the results also demonstrate a high performance of this system with 93.0% sensitivity and 100.0% specificity. The SAI system uses a dedicated device for automatic analysis and reading, making it highly objective, and requires less human power, supporting its usefulness in clinical settings.
Asunto(s)
Antígenos Bacterianos/análisis , Cromatografía de Afinidad/métodos , Mycoplasma pneumoniae/inmunología , Neumonía por Mycoplasma/diagnóstico , Plata/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía por Mycoplasma/inmunología , Estudios Prospectivos , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Recently, many Japanese physicians have claimed that oseltamivir is less effective in children with influenza B virus infection. This study assesses the effectiveness of oseltamivir against influenza A (H3N2) and influenza B in children on the basis of the duration of febrile illness. METHODS: We used oseltamivir to treat 127 children with influenza A (H3N2; mean age, 6.97 years [range, 1-15 years]) and 362 children with influenza B (mean age, 5.16 years [range, 1-15 years]) in outpatient clinics. The duration of fever after the start of oseltamivir therapy was compared in the influenza A group and the influenza B group. RESULTS: The mean duration of fever after the start of oseltamivir therapy was significantly greater in the influenza B group than in the influenza A (H3N2) group (2.18 days vs. 1.31 days, respectively; P<.001). The difference was marked in young children (1-5 years old; 2.37 days for the influenza B group vs. 1.42 days for the influenza A group) but was not significant among older children (11-15 years old). The 50% inhibitory concentration of oseltamivir against influenza B virus was 75.4+/-41.7 nmol/L and was substantially higher than that for type A (H3N2) virus (0.3+/-0.1 nmol/L). Only 3 (1.6%) of 192 influenza B viruses were resistant to oseltamivir. CONCLUSIONS: Oseltamivir is much less effective against influenza B virus infection in young children, probably because of the low sensitivity of influenza B viruses to oseltamivir. The effectiveness of oseltamivir against influenza B is influenced by age and host immunity. A few oseltamivir-resistant influenza B strains were isolated before the start of oseltamivir therapy.
Asunto(s)
Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Oseltamivir/uso terapéutico , Adolescente , Envejecimiento , Antivirales/uso terapéutico , Niño , Preescolar , Humanos , LactanteRESUMEN
CONTEXT: Very little is known about the frequency of generation and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. Furthermore, transmission of resistant virus, whether influenza A or B, has not been recognized to date. OBJECTIVE: To assess the prevalence and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. DESIGN, SETTING, AND PATIENTS: Investigation of the neuraminidase inhibitor sensitivity of influenza B isolates from 74 children before and after oseltamivir therapy and from 348 untreated patients with influenza (including 66 adults) seen at 4 community hospitals in Japan during the 2004-2005 influenza season. Four hundred twenty-two viruses from untreated patients and 74 samples from patients after oseltamivir therapy were analyzed. MAIN OUTCOME MEASURE: Sialidase inhibition assay was used to test the drug sensitivities of influenza B viruses. The neuraminidase and hemagglutinin genes of viruses showing reduced sensitivity to neuraminidase inhibitors were sequenced to identify mutations that have the potential to confer reduced sensitivity to these drugs. RESULTS: In 1 (1.4%) of the 74 children who had received oseltamivir, we identified a variant with reduced drug sensitivity possessing a Gly402Ser neuraminidase substitution. We also identified variants with reduced sensitivity carrying an Asp198Asn, Ile222Thr, or Ser250Gly mutation in 7 (1.7%) of the 422 viruses from untreated patients. Review of the clinical and viral genetic information available on these 7 patients indicated that 4 were likely infected in a community setting, while the remaining 3 were probably infected through contact with siblings shedding the mutant viruses. CONCLUSIONS: In this population, influenza B viruses with reduced sensitivity to neuraminidase inhibitors do not arise as frequently as resistant influenza A viruses. However, they appear to be transmitted within communities and families, requiring continued close monitoring.