RESUMEN
BACKGROUND: The limited treatment options for children with severe respiratory syncytial virus (RSV) infection highlights the need for a comprehensive understanding of the host cellular response during infection. We aimed to identify host genes that are associated with severe RSV disease and to identify drugs that can be repurposed for the treatment of severe RSV infection. METHODS: We examined clinical data and blood samples from 37 hospitalized children (29 mild and 8 severe) with RSV infection. We tested RNA from blood samples using next-generation sequencing to profile global mRNA expression and identify cellular processes. RESULTS: Retractions, decreased breath sounds, and tachypnea were associated with disease severity. We observed upregulation of genes related to neutrophil, inflammatory response, blood coagulation, and downregulation of genes related to T cell response in children with severe RSV. Using network-based approach, 43 drugs were identified that are predicted to interact with the gene products of these differentially expressed genes. CONCLUSIONS: These results suggest that the changes in the expression pattern in the innate and adaptive immune responses may be associated with RSV clinical severity. Compounds that target these cellular processes can be repositioned as candidate drugs in the treatment of severe RSV. IMPACT: Neutrophil, inflammation, and blood coagulation genes are upregulated in children with severe RSV infection. Expression of T cell response genes are suppressed in cases of severe RSV. Genes identified in this study can contribute in understanding the pathogenesis of RSV disease severity. Drugs that target cellular processes associated with severe RSV can be repositioned as potential therapeutic options.
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Infecciones por Virus Sincitial Respiratorio/genética , Infecciones por Virus Sincitial Respiratorio/patología , Índice de Severidad de la Enfermedad , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/genéticaRESUMEN
Background: Human respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes. Methods: We conducted a cohort study of children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between initial and subsequent RSV infections. Results: We examined 1802 children from May 2014 to January 2016 and collected 3471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein. Conclusions: Amino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.
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Antígenos Virales/inmunología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/genética , Infecciones del Sistema Respiratorio/virología , Enfermedad Aguda , Sustitución de Aminoácidos , Preescolar , Estudios de Cohortes , Epítopos , Femenino , Proteínas de Unión al GTP/genética , Humanos , Lactante , Masculino , Filipinas/epidemiología , Filogenia , Infecciones por Virus Sincitial Respiratorio/patología , Virus Sincitial Respiratorio Humano/inmunología , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Infecciones del Sistema Respiratorio/patología , Proteínas Virales de Fusión/genéticaRESUMEN
During 2011-2013, a nationwide outbreak of chikungunya virus infection occurred in the Philippines. The Asian genotype was identified as the predominant genotype; sporadic cases of the East/Central/South African genotype were detected in Mindanao. Further monitoring is needed to define the transmission pattern of this virus in the Philippines.
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Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/virología , Virus Chikungunya/clasificación , Virus Chikungunya/genética , Anticuerpos Antivirales/inmunología , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/historia , Brotes de Enfermedades , Ensayo de Inmunoadsorción Enzimática , Genes Virales , Genotipo , Geografía , Historia del Siglo XXI , Humanos , Inmunoglobulina M/inmunología , Filipinas/epidemiología , Filogenia , Filogeografía , Vigilancia de la PoblaciónRESUMEN
BACKGROUND: Human respiratory syncytial virus (HRSV) is a leading viral etiologic agent of pediatric lower respiratory infections, including bronchiolitis and pneumonia. Two antigenic subgroups, HRSV-A and B, each contain several genotypes. While viral load may vary among HRSV genotypes and affect the clinical course of disease, data are scarce regarding the actual differences among genotypes. Therefore, this study estimated and compared viral load among NA1 and ON1 genotypes of HRSV-A and BA9 of HRSV-B. ON1 is a newly emerged genotype with a 72-nucleotide duplication in the G gene as observed previously with BA genotypes in HRSV-B. FINDINGS: Children <5 years of age with an initial diagnosis of severe or very severe pneumonia at a hospital in the Philippines from September 2012 to December 2013 were enrolled. HRSV genotypes were determined and the viral load measured from nasopharyngeal swabs (NPS). The viral load of HRSV genotype NA1 were significantly higher than those of ON1 and BA9. Regression analysis showed that both genotype NA1 and younger age were significantly associated with high HRSV viral load. CONCLUSIONS: The viral load of NA1 was higher than that of ON1 and BA9 in NPS samples. HRSV genotypes may be associated with HRSV viral load. The reasons and clinical impacts of these differences in viral load among HRSV genotypes require further evaluation.
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Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Carga Viral , Adolescente , Niño , Preescolar , Femenino , Genotipo , Hospitalización , Humanos , Masculino , Filipinas/epidemiología , Filogenia , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/clasificación , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/fisiologíaRESUMEN
The current School Health and Safety Act in Japan states that children with influenza infection should stay home until day 6(th) after symptoms onset. This was an amendment of a previous version recommending school return on day 3 after defervescence. Here, we investigated the duration of fever and virus shedding after laninamivir treatment in 7 children infected with influenza A(H3N2) virus and 21 children with influenza B virus in relation to the school return timing recommended by the School Health and Safety Act during the 2011-2012 influenza season. Nasal discharge was collected on the first, second, and third hospital visits and virus titers were assessed by virus culture and real-time PCR. Duration of fever after laninamivir treatment was 1 day longer for influenza B than for influenza A(H3N2). Virus detection rates with 50% tissue culture infectious dose and viral RNA were highest at the first visit and gradually decreased at subsequent visits. Virus positivity rates were detectable at the time of defervescence in less than half of the enrolled patients (14.3-42.9%). Virus shedding rates were similarly low (0.0-19.0%) on day 3 or later from defervescence and on day 6 or later from fever onset (school return dates per the old and current School Health and Safety Act) regardless of the influenza type. In conclusion, despite the higher efficacy of laninamivir against A(H3N2) viruses than B viruses, viral shedding is low after return to school for both types, regardless of the version of the School Health and Safety Act.
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Salud , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Instituciones Académicas , Esparcimiento de Virus/efectos de los fármacos , Zanamivir/análogos & derivados , Antivirales/farmacología , Antivirales/uso terapéutico , Niño , Demografía , Femenino , Guanidinas , Humanos , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Masculino , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/metabolismo , Piranos , ARN Viral/genética , Ácidos Siálicos , Zanamivir/farmacología , Zanamivir/uso terapéuticoRESUMEN
Two novel G3P[4] rotavirus strains were detected from children with acute diarrhea in Sendai, Japan, identified as a G3-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation by whole-genome sequence analysis. The VP7 gene of the two strains displayed the highest nucleotide sequence identity (91 %) and showed a close genetic relationship (99 % bootstrap value) to an equine rotavirus reported in India. The other gene segments were related to human group A rotaviruses. This report suggests a possible reassortment event between human and equine rotaviruses.
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ARN Viral/genética , Virus Reordenados/genética , Virus Reordenados/aislamiento & purificación , Infecciones por Rotavirus/virología , Rotavirus/genética , Rotavirus/aislamiento & purificación , Animales , Antígenos Virales/genética , Proteínas de la Cápside/genética , Preescolar , Análisis por Conglomerados , Diarrea/epidemiología , Diarrea/virología , Femenino , Caballos , Humanos , Lactante , Japón/epidemiología , Masculino , Datos de Secuencia Molecular , Filogenia , Infecciones por Rotavirus/epidemiología , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVE: To genetically characterize human influenza viruses and their susceptibilities to antivirals during two post-pandemic seasons in Lebanon. METHODS: Influenza virus was isolated from nasopharyngeal swabs that were obtained from patients with influenza-like illness during 2010-2012 and further analyzed both phenotypically and genotypically. RESULTS: During the 2010-2011 season, both 2009 pandemic H1N1 (H1N1p) and B viruses co-circulated with equal prevalence, while the H3N2 virus predominated during the 2011-2012 season. All H3N2 and H1N1 viruses were resistant to amantadine. Importantly, all viruses of the influenza A and B types were susceptible to the neuraminidase (NA) inhibitors oseltamivir, zanamivir, peramivir, and laninamivir. Nonetheless, all 2011-2012 H1N1p isolates had three mutations (V241I, N369K, and N386S) in the NA gene that were suggested to be permissive of the H275Y mutation, which confers resistance to oseltamivir. We also detected one H1N1p virus during the 2010-2011 season with a 4-fold decrease in susceptibility to oseltamivir due to an NA-S247N mutation. This isolate was phylogenetically distinct from other H1N1p viruses that were isolated in other regions. CONCLUSIONS: Influenza A viruses with reduced susceptibility to oseltamivir and mutations permissive for acquiring NA resistance-conferring mutation with minimal burden on their fitness were isolated in Lebanon.
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Antivirales/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Gripe Humana/virología , Ácidos Carbocíclicos , Amantadina/farmacología , Ciclopentanos/farmacología , Farmacorresistencia Viral , Guanidinas/farmacología , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/efectos de los fármacos , Virus de la Influenza B/aislamiento & purificación , Líbano/epidemiología , Pruebas de Sensibilidad Microbiana , Mutación , Neuraminidasa/genética , Oseltamivir/farmacología , Pandemias , Filogenia , Piranos , Ácidos Siálicos , Zanamivir/análogos & derivados , Zanamivir/farmacologíaRESUMEN
Influenza vaccination is considered the single most important medical intervention for the prevention of influenza. The dose of trivalent influenza vaccine in children was increased almost double since 2011/12 season in Japan. We estimated the influenza vaccine effectiveness for children 1-11 years of age using rapid test kits in Isahaya City, involving 28,884 children-years, over two consecutive influenza seasons (2011/12 and 2012/13). Children were divided into two groups, vaccinated and unvaccinated, according to their vaccination record, which was obtained from an influenza registration program organized by the Isahaya Medical Association for all pediatric facilities in the city. There were 14,562 and 14,282 children aged from 1-11 years in the city in 2011 and 2012 respectively. In the 2011/12 season, the overall vaccine effectiveness in children from 1-11 years of age, against influenza A and B were 23% [95% confidence interval (CI): 14%-31%] and 20% [95% CI: 8%-31%], respectively. In the 2012/13 season, vaccine effectiveness against influenza A and B was 13% (95% CI: 4%-20%) and 9% (95% CI: -4%-21%), respectively. The vaccine effectiveness was estimated using the rapid diagnosis test kits. Age-stratified estimation showed that vaccine effectiveness was superior in younger children over both seasons and for both virus types. In conclusion, the trivalent influenza vaccine has a significant protective effect for children 1-11 years of age against influenza A and B infection in the 2011/12 season and against influenza A infection in the 2012/13 season in a community in Japan.
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Virus de la Influenza A , Virus de la Influenza B , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Animales , Niño , Preescolar , Perros , Humanos , Incidencia , Lactante , Japón/epidemiología , Células de Riñón Canino Madin Darby , Reacción en Cadena en Tiempo Real de la Polimerasa , Resultado del TratamientoRESUMEN
New cases of coronavirus disease 2019 (COVID-19) are continually being recorded worldwide, despite global efforts in implementing non-pharmaceutical interventions and establishing vaccination programs. This trend highlights the need to identify the factors associated with the continued spread of COVID-19. The World Health Organization recommends hand washing as a cost-effective intervention for preventing COVID-19, indicating that water, sanitation, and hygiene (WaSH) are central to the prevention of the disease. However, low- and middle-income countries lack adequate access to WaSH, which increases the risk of contracting COVID-19. The aim of this study was to identify the WaSH factors associated with the incidence of COVID-19 and quantitatively estimate the effects of improvements in WaSH on reducing the incidence of COVID-19 during the peak of the pandemic. Lasso regression and extreme gradient boosting models were used to identify the WaSH factors. Distinct estimation models were developed to assess the effect of WaSH in rural regions under two assumptions: increasing regional basic sanitation coverage up to 25 % and 50%. The reduction in the incidence of COVID-19 during the peak of the pandemic was calculated for each rural region. The results of the analyses indicated that basic sanitation is important for reducing the incidence of COVID-19 in rural regions compared to urban regions in the Philippines. In addition, the results suggested that increasing basic sanitation coverage could reduce the incidence of COVID-19 by 2-66 %, alleviating the burden on healthcare facilities. This study indicates that improved basic sanitation infrastructure are needed in rural Philippines. The results of this study emphasise the significance of WaSH as an indicator of COVID-19 incidence, highlighting the need for its enhancement to enable the achievement of sustainable disease prevention and pandemic preparedness goals.
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COVID-19 , Higiene , Saneamiento , COVID-19/prevención & control , COVID-19/epidemiología , Filipinas/epidemiología , Humanos , Abastecimiento de Agua , Pandemias/prevención & control , Incidencia , SARS-CoV-2RESUMEN
Objectives: Annual outbreaks of human respiratory syncytial virus (HRSV) are caused by newly introduced and locally persistent strains. During the COVID-19 pandemic, global and local circulation of HRSV significantly decreased. This study was conducted to characterize HRSV in 2018-2022 and to analyze the impact of COVID-19 on the evolution of HRSV. Design/methods: Combined oropharyngeal and nasopharyngeal swabs were collected from children hospitalized with severe acute respiratory infection at two hospitals in Zambia. The second hypervariable region of the attachment gene G was targeted for phylogenetic analysis. Results: Of 3113 specimens, 504 (16.2%) were positive for HRSV, of which 131 (26.0%) and 66 (13.1%) were identified as HRSVA and HRSVB, respectively. In early 2021, an increase in HRSV was detected, caused by multiple distinct clades of HRSVA and HRSVB. Some were newly introduced, whereas others resulted from local persistence. Conclusions: This study provides insights into the evolution of HRSV, driven by global and local circulation. The COVID-19 pandemic had a temporal impact on the evolution pattern of HRSV. Understanding the evolution of HRSV is vital for developing strategies for its control.
RESUMEN
Despite the implementation of non-pharmaceutical interventions, the threat of coronavirus disease 2019 (COVID-19) remains significant on a global scale. Identifying external factors contributing to its spread is crucial, especially given the World Health Organization's recommendation emphasizing access to water, sanitation, and hygiene as essential in curbing COVID-19. There is a notable discrepancy in access to sanitation facilities, particularly evident in low- and middle-income countries. However, there is a lack of quantitative assessments regarding these factors. This study examines various environmental, socioeconomic, water, sanitation, and hygiene factors and their associations with COVID-19 incidence. All regions in the Philippines were categorized into clusters based on socioeconomic factors. A conceptual structural equation model (SEM) was developed using domain knowledge. The best-fitting SEM for each cluster was determined, and associations between factors and COVID-19 incidence were estimated. The correlation analysis revealed that rainfall, minimum temperature, and relative humidity were positively correlated with weekly COVID-19 incidence in urban regions. Maximum temperature, mean temperature, wind speed, and wind direction were negatively correlated with weekly COVID-19 incidence in rural regions, with time lags of 0, 3, and 7 weeks. In urban regions (Cluster 1), factors such as urbanization rate (1.00), area (-0.93), and population (0.54) were found to be associated with weekly COVID-19 incidence. Conversely, in rural regions (Cluster 2), factors including area (0.17), basic sanitation (0.84), and wind direction (0.83) showed associations with weekly COVID-19 incidence. These factors were causally associated with a latent variable reflecting the hidden confounders associated with COVID-19 incidence. It is important to note that sanitation factors were associated only in rural regions. Improving access to sanitation facilities in rural regions of the Philippines is imperative to effectively mitigate disease transmission in future pandemics. Identification of the causal effect of unobserved confounders with COVID-19 incidence is recommended for future research.
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COVID-19 , Higiene , Saneamiento , Factores Socioeconómicos , Filipinas/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Incidencia , Abastecimiento de Agua/estadística & datos numéricos , SARS-CoV-2RESUMEN
BACKGROUND: Viral recombination that occurs by exchanging genetic materials between two viral genomes coinfecting the same host cells is associated with the emergence of new viruses with different virulence. Herein, we detected a patient coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants and identified various recombinants in the SARS-CoV-2 full-length spike gene using long-read and Sanger sequencing. METHODS: Samples from five patients in Japan with household transmission of coronavirus disease 2019 (COVID-19) were analyzed using molecular assays for detection and identification of SARS-CoV-2. Whole-genome sequencing was conducted using multiplex PCR with short-read sequencing. RESULTS: Among the five SARS-CoV-2-positive patients, the mutation-specific assay identified the Delta variant in three, the Omicron variant in one, and an undetermined in one. The undermined patient was identified as Delta using whole-genome sequencing, but samples showed a mixed population of Delta and Omicron variants. This patient was analyzed for viral quasispecies by long-read and Sanger sequencing using a full-length spike gene amplicon. In addition to the Delta and Omicron sequences, the viral quasispecies analysis identified nine different genetic recombinant sequences with various breakpoints between Delta and Omicron sequences. The nine detected recombinant sequences in the spike gene showed over 99% identity with viruses that were detected during the Delta and Omicron cocirculation period from the United States and Europe. CONCLUSIONS: This study demonstrates that patients coinfected with different SARS-CoV-2 variants can generate various viral recombinants and that various recombinant viruses may be produced during the cocirculation of different variants.
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COVID-19 , Coinfección , Genoma Viral , Recombinación Genética , SARS-CoV-2 , Secuenciación Completa del Genoma , Humanos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , COVID-19/virología , COVID-19/complicaciones , Coinfección/virología , Genoma Viral/genética , Glicoproteína de la Espiga del Coronavirus/genética , Masculino , Japón , Femenino , Filogenia , Mutación , Persona de Mediana EdadRESUMEN
As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a record total of 12,073 human influenza positive samples during 2022. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hen's eggs for potential use in seasonal influenza virus vaccines. In 2022, influenza A(H3N2) viruses predominated over influenza A(H1N1)pdm09 and B viruses, accounting for 77% of all viruses analysed. The majority of A(H1N1)pdm09, A(H3N2) and influenza B viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the southern hemisphere in 2022. Of 3,372 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, two A(H1N1)pdm09 viruses showed highly reduced inhibition against oseltamivir.
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Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Animales , Femenino , Humanos , Australia/epidemiología , Pollos , Farmacorresistencia Viral/genética , Farmacorresistencia Viral/inmunología , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/genética , Virus de la Influenza A/inmunología , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Vacunas contra la Influenza/genética , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/epidemiología , Gripe Humana/genética , Gripe Humana/inmunología , Gripe Humana/prevención & control , Oseltamivir/farmacología , Organización Mundial de la Salud , Zanamivir/farmacología , Antivirales/farmacologíaRESUMEN
Rapid molecular testing for severe acute respiratory coronavirus 2 (SARS-CoV-2) variants may contribute to the development of public health measures, particularly in resource-limited areas. Reverse transcription recombinase polymerase amplification using a lateral flow assay (RT-RPA-LF) allows rapid RNA detection without thermal cyclers. In this study, we developed two assays to detect SARS-CoV-2 nucleocapsid (N) gene and Omicron BA.1 spike (S) gene-specific deletion-insertion mutations (del211/ins214). Both tests had a detection limit of 10 copies/µL in vitro and the detection time was approximately 35 min from incubation to detection. The sensitivities of SARS-CoV-2 (N) RT-RPA-LF by viral load categories were 100% for clinical samples with high (>9015.7 copies/µL, cycle quantification (Cq): < 25) and moderate (385.5-9015.7 copies/µL, Cq: 25-29.9) viral load, 83.3% for low (16.5-385.5 copies/µL, Cq: 30-34.9), and 14.3% for very low (<16.5 copies/µL, Cq: 35-40). The sensitivities of the Omicron BA.1 (S) RT-RPA-LF were 94.9%, 78%, 23.8%, and 0%, respectively, and the specificity against non-BA.1 SARS-CoV-2-positive samples was 96%. The assays seemed more sensitive than rapid antigen detection in moderate viral load samples. Although implementation in resource-limited settings requires additional improvements, deletion-insertion mutations were successfully detected by the RT-RPA-LF technique.
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COVID-19 , Transcripción Reversa , Humanos , Recombinasas/genética , ARN Viral/genética , SARS-CoV-2/genética , Sensibilidad y Especificidad , Mutagénesis Insercional , COVID-19/diagnóstico , COVID-19/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Nucleotidiltransferasas/genéticaRESUMEN
The clinical effectiveness of the newly released neuraminidase inhibitors (NAIs) laninamivir and peramivir has not been sufficiently evaluated in influenza-infected patients in clinical and practical settings. In this study, we analyzed the clinical data of 211 patients infected with influenza A virus subtype H3N2 (A(H3N2)) and 45 patients infected with influenza A virus subtype H1N1pdm (A(H1N1)pdm09) who received the NAIs oseltamivir, zanamivir, laninamivir, or peramivir during the 2010-2011 influenza season. The duration of fever from the first dose of the NAI to fever alleviation to <37.5 °C was evaluated as an indicator of the clinical effectiveness of the NAIs in the influenza-infected patients. For the A(H3N2)-infected patients, Kaplan-Meier analysis showed the peramivir treatment group had the fastest time of fever alleviation to <37.5 °C (median 17.0 h, 95 % confidence interval [CI] 7.2-26.8 h) of the four treatment groups. No significant difference was found in the time to fever alleviation among the other antivirals, oseltamivir, zanamivir, and laninamivir. Results of multivariate analysis, using a Cox proportional-hazards model (hazard ratio 3.321) adjusted for the factors age, sex, body weight, vaccination status, time from onset to the clinic visit, and body temperature showed significantly faster fever alleviation in the peramivir treatment group compared with the oseltamivir treatment group. For the A(H1N1)pdm09-infected patients, only the oseltamivir and zanamivir treatment groups were compared, and no significant difference in time to alleviation of fever was observed between the two groups. Based on a cycling probe real-time polymerase chain reaction (PCR) assay, none of the A(H1N1)pdm09 strains in this study had the H275Y mutation conferring oseltamivir resistance. Further evaluation of the clinical effectiveness of the newly released NAIs for influenza-infected patients, including those infected with A(H1N1)pdm09, is needed.
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Antivirales/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/tratamiento farmacológico , Neuraminidasa/antagonistas & inhibidores , Ácidos Carbocíclicos , Niño , Preescolar , Ciclopentanos/uso terapéutico , Brotes de Enfermedades , Femenino , Guanidinas/uso terapéutico , Humanos , Gripe Humana/epidemiología , Gripe Humana/virología , Japón/epidemiología , Masculino , Oseltamivir/uso terapéutico , Resultado del Tratamiento , Zanamivir/uso terapéuticoRESUMEN
OBJECTIVE: Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory infection, and therefore, a major threat to global health. This study determined the epidemiological and molecular characteristics of RSV among cases of influenza-like illness (ILI) and severe acute respiratory infection (SARI) among children in the Philippines. METHOD: The study included archived nasopharyngeal swab and oropharyngeal swab samples collected from patients under the age of five who are presented with ILI or SARI for the period of 2006-2016. Swabs were examined for RSV subgroup by multiplex real-time qRT-PCR. Partial genome sequencing and phylogenetic analyses of the second hypervariable region (HVR) of the G gene were used to determine the genotype of RSV isolates. RESULTS: A total of 1036 representative samples from all sites were selected and tested. Of these samples, 122 were RSV-positive at 11.8% prevalence rate, and 58.2% (71/122) were classified as RSV-A. Six genotypes were identified, which include NA1 (27/122, 22.1%), ON1 (5/122, 4.1%), GA2 (1/122, 0.8%), and GA5 (1/122, 0.8%) for RSV-A; and BA2 (13/122, 10.7%) and BA9 (1/122, 0.8%) for RSV-B. Most RSV-related cases were significantly associated with clinical characteristics such as runny nose (88.1% RSV vs. 11.9% non-RSV: p value = 0.021), pneumonia (80.6% RSV vs. 19.4% non-RSV; p value = 0.015), and bronchitis (71.7% RSV vs. 28.3% non-RSV; p value < 0.001). Increased RSV-related cases were observed among children below 24 months old. CONCLUSION: The RSV trend and genetic variability in the Philippines resembles a similar pattern of transmission globally.
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Gripe Humana , Neumonía , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Virosis , Niño , Preescolar , Genotipo , Humanos , Lactante , Gripe Humana/epidemiología , Filipinas/epidemiología , Filogenia , Infecciones por Virus Sincitial Respiratorio/epidemiologíaRESUMEN
OBJECTIVES: Human adenoviruses (HAdV) are known to cause a wide range of diseases including acute respiratory infections, conjunctivitis, and acute gastroenteritis. In this study, we aimed to determine the serotypes of HAdV in patients with influenza-like illness (ILI) in the Philippines from 2006-2012 and to describe the demographic and epidemiological characteristics of patients who tested positive for HAdV. METHODS: Between 2006 and 2012, the Philippine National Influenza Centre detected HAdV in 1294 samples of patients with ILI. Serotype determination was done in select samples using microneutralization, polymerase chain reaction (PCR), and sequencing methods. RESULTS: A total of 8 serotypes were identified (HAdV 1-7 and 11), with HAdV-2 (27.8%), and HAdV-3 (27.8%) being the most prevalent. The majority of HAdV infections were found in children below 5 years of age (79.9%). CONCLUSIONS: The identification of HAdV circulating serotypes may serve as guide for designing disease intervention and control strategies and will provide important information regarding the contribution of this virus to respiratory infections, particularly in children, which remain a public health burden in the Philippines.
Asunto(s)
Infecciones por Adenovirus Humanos , Adenovirus Humanos , Gripe Humana , Infecciones del Sistema Respiratorio , Infecciones por Adenovirus Humanos/epidemiología , Adenovirus Humanos/genética , Niño , Genotipo , Humanos , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Filipinas/epidemiología , Filogenia , SerogrupoRESUMEN
In eight successive seasons (2001 to 2009), a total of 726 human respiratory syncytial virus (HRSV) infections from a total of 1,560 children with acute lower respiratory tract illness were identified. Molecular analysis of the attachment (G) protein gene confirmed that 52 (7.8%) children were infected more than once with any of the 3 genotypes of HRSV-A (genotypes GA5, NA1, and NA2) and/or 6 genotypes of HRSV-B (genotypes BA4, BA5, and BA7 to BA10). Repeated infections in 46 cases (82.1%) occurred in the next season, and only one case occurred in the same season (10-day interval). First infections were 33 (63.5%) HRSV-A cases and 19 (36.5%) HRSV-B cases, whereas second infections occurred in 35 (67.3%) HRSV-A cases and 17 (32.7%) HRSV-B cases. Third infections were attributed to 4 (100.0%) HRSV-A cases. Homologous subgroup reinfections were detected in 28 cases, 23 HRSV-A cases and 5 HRSV-B cases (P = 0.005), whereas homologous genotype reinfections were detected only for 5 HRSV-A cases (2GA5 and 3NA2) but not any HRSV-B case. Heterologous subgroup reinfections were detected in 28 cases, 12 cases from HRSV-A-to-HRSV-B reinfections and 16 cases from HRSV-B-to-HRSV-A reinfections. Genotypes NA1 and NA2 had higher numbers of heterologous genotype infections than did other genotypes. Our observations suggest that repeated infections occur more frequently in HRSV-A strains than in HRSV-B strains, and heterologous genotype reinfections occur more frequently than homologous genotype reinfections, especially in the case of the emerging genotypes NA1 and NA2 of HRSV-A strains that circulated in the community during our study period.
Asunto(s)
Polimorfismo Genético , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/clasificación , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Preescolar , Femenino , Genotipo , Humanos , Lactante , Japón/epidemiología , Masculino , Datos de Secuencia Molecular , ARN Viral/genética , Recurrencia , Virus Sincitial Respiratorio Humano/genética , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Análisis de Secuencia de ADN , Proteínas del Envoltorio Viral/genéticaRESUMEN
Neuraminidase inhibitors are agents used against influenza viruses; however, the emergence of drug-resistant strains is a major concern. Recently, the prevalence of oseltamivir-resistant seasonal influenza A (H1N1) virus increased globally and the emergence of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses was reported. In this study, we developed a cycling probe real-time PCR method for the detection of oseltamivir-resistant seasonal influenza A (H1N1) and pandemic influenza A (H1N1) 2009 viruses. We designed two sets of primers and probes that were labeled with 6-carboxyfluorescein or 6-carboxy-X-rhodamine to identify single nucleotide polymorphisms (SNPs) that correspond to a histidine and a tyrosine at position 275 in the neuraminidase protein, respectively. These SNPs confer susceptibility and resistance to oseltamivir, respectively. In the 2007-2008 season, the prevalence of oseltamivir-resistant H1N1 viruses was 0% (0/72), but in the 2008-2009 season, it increased to 100% (282/282). In the 2009-2010 season, all of the pandemic influenza A (H1N1) 2009 viruses were susceptible to oseltamivir (0/73, 0%). This method is sensitive and specific for the screening of oseltamivir-resistant influenza A (H1N1) viruses. This method is applicable to routine laboratory-based monitoring of drug resistance and patient management during antiviral therapy.
Asunto(s)
Sustitución de Aminoácidos/genética , Antivirales/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/virología , Tipificación Molecular/métodos , Neuraminidasa/genética , Oseltamivir/farmacología , Proteínas Virales/genética , Genotipo , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Pruebas de Sensibilidad Microbiana/métodos , Polimorfismo de Nucleótido Simple , Sensibilidad y EspecificidadRESUMEN
Complete genome sequences were determined for 4 clade A and 12 clade D enterovirus D68 strains detected in nasopharyngeal swabs from children with acute respiratory illness in the Philippines. These sequence data will be useful for future epidemiological monitoring, including watching for viral evolution.