RESUMEN
Duration of fever and virus persistence after baloxavir administration were investigated in 81 outpatients, 16 with A(H1N1)pdm09 and 65 with A(H3N2) in the Japanese 2018-2019 influenza season. Only eight cases of A(H3N2) viruses were detected post-dose. PA/I38T-substituted viruses were detected in four (6.2%) of 65 A(H3N2) patients, at days 3 and 4, constituting 50% (4/8) of A(H3N2) detected post-dose. The median duration of fever was 26.0 h for A(H1N1)pdm09 and 20.3 h for A(H3N2). The median duration of fever for patients with PA/I38T-substituted viruses was 22.0 h, without significant difference to that of the patients in whom the mutated virus was not detected. Emergence of PA/I38T-substituted viruses after treatment with baloxavir was confirmed, but no significant prolongation of fever was observed in the four patients with PA/I38T-substituted virus emergence.
Asunto(s)
Antivirales/uso terapéutico , Dibenzotiepinas/uso terapéutico , Gripe Humana/tratamiento farmacológico , Morfolinas/uso terapéutico , Piridonas/uso terapéutico , Triazinas/uso terapéutico , Adulto , Farmacorresistencia Viral/efectos de los fármacos , Fiebre , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/inmunología , Persona de Mediana Edad , Adulto JovenRESUMEN
Comparison of the viral persistence of pandemic H1N1 (H1N1pdm) and seasonal H1N1 with or without H275Y mutation after oseltamivir therapy has not been adequately done. Virus was isolated before and on days 4-6 from the start of oseltamivir treatment for 158 cases of seasonal (2007-2008 and 2008-2009 seasons) or pandemic (2009-2010 season) H1N1 influenza. Sequence analysis was done for each season and NA inhibition assay (IC(50)) was done in the 2009-2010 season. H275Y mutation before therapy was 0% in the 2007-2008 and 2009-2010 seasons, but 100% in the 2008-2009 season. Fever and other symptoms were noticeably prolonged after oseltamivir therapy for children with H275Y mutated seasonal H1N1 (2008-2009 season), but not in patients with seasonal H1N1 without mutation (2007-2008) or H1N1pdm (2009-2010). The viral persistence rate was significantly higher for patients 15 years or younger than for those 16 years and older with H275Y mutated seasonal H1N1 (46.2% and 10.5%, respectively) or with H1N1pdm (43.3% and 11.5%, respectively). The H275Y mutation emerged after oseltamivir treatment in 2.4% (2/82) of all patients with H1N1pdm. In two children, the H275Y mutation emerged after therapy and the IC(50) increased more than 200 fold; however, the prolongation of fever was not so prominent. In conclusion, oseltamivir was effective for fever and other clinical symptoms; however, the virus persisted longer than expected after treatment in H1N1pdm influenza-infected children in the 2009-2010 season, similar to seasonal H1N1 with H275Y mutation in the 2008-2009 season.
Asunto(s)
Antivirales/uso terapéutico , Farmacorresistencia Viral/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/tratamiento farmacológico , Mutación , Oseltamivir/uso terapéutico , Pandemias , Adolescente , Adulto , Antivirales/farmacología , Niño , Farmacorresistencia Viral/genética , Femenino , Fiebre/tratamiento farmacológico , Fiebre/virología , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/fisiopatología , Gripe Humana/virología , Concentración 50 Inhibidora , Japón , Masculino , Oseltamivir/farmacología , Estaciones del Año , Análisis de Secuencia de ADN , Resultado del Tratamiento , Esparcimiento de Virus , Adulto JovenRESUMEN
The clinical symptoms and effectiveness of neuraminidase inhibitors (NAI) have not been adequately compared among pandemic H1N1 2009 patients, seasonal H1N1 patients, and patients with H1N1 with the H275Y mutation. The data of 68 seasonal H1N1 patients in 2007-2008, 193 seasonal H1N1 patients in 2008-2009, and 361 pandemic H1N1 2009 patients diagnosed by PCR who received an NAI were analyzed. The duration of fever (body temperature ≥ 37.5 ºC) after the first dose of NAI and from onset was calculated. The H275Y neuraminidase mutation status was determined for 166 patients. Significantly lower mean age (18.4 ± 13.2 years) and a higher percentage of teenagers (53.7%) were found for pandemic 2009 influenza than for seasonal influenza (P < 0.001). The peak body temperature was equivalent (mean, 39.0 ºC) in the three seasons, and the frequency of symptoms was the same or lower for pandemic influenza compared with seasonal H1N1. None of the 34 analyzed pandemic H1N1 virus isolates contained the H275Y mutation, which was commonly detected in the 2008-2009 season. The duration of fever after the start of oseltamivir therapy was significantly shorter for patients with pandemic (23.0 ± 11.6 h) than with seasonal H1N1 in both the 2008-2009 (49.7 ± 32.3 h) and 2007-2008 seasons (32.0 ± 18.9 h). The mean duration of fever after the first dose of zanamivir was not different among the three seasons (26.9-31.5 h). Clinical symptoms were the same or somewhat milder, and oseltamivir was more effective, for pandemic 2009 than for seasonal H1N1 influenza with or without H275Y mutation.
Asunto(s)
Antivirales/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/tratamiento farmacológico , Gripe Humana/fisiopatología , Neuraminidasa/antagonistas & inhibidores , Pandemias , Adolescente , Adulto , Femenino , Fiebre/tratamiento farmacológico , Fiebre/genética , Fiebre/virología , Humanos , Subtipo H1N1 del Virus de la Influenza A/enzimología , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Neuraminidasa/genética , Oseltamivir/uso terapéutico , Estaciones del Año , Adulto Joven , Zanamivir/uso terapéuticoRESUMEN
BACKGROUND: Influenza A virus subtype H1N1 with the H274Y mutation emerged and spread worldwide. However, the clinical effectiveness of the neuraminidase inhibitors, oseltamivir and zanamivir, has not been adequately reevaluated. METHODS: Data from 164 patients with H1N1 virus infection and 59 patients with H3N2 virus infection during the 2008-2009 influenza season and 68 patients with H1N1 virus infection during the 2007-2008 influenza season who received a neuraminidase inhibitor were analyzed. The duration of fever (body temperature 37.5 degrees C) after the first dose of oseltamivir or zanamivir and from onset of symptoms was calculated from patient reports. The influenza virus was isolated, and its subtype was determined by hemagglutinin inhibition assay and polymerase chain reaction. The H274Y neuraminidase mutation status was determined by sequencing the neuraminidase segment. RESULTS: Of 68 patients with H1N1 virus infection during the 2007-2008 season, 41 were treated with oseltamivir, and 27 were treated with zanamivir. During the 2008-2009 season, 77 patients with H1N1 virus infection were treated with oseltamivir, and 87 were treated with zanamivir; 31 and 28 patients with H3N2 virus infection were treated with oseltamivir and zanamivir, respectively. All 49 analyzed H1N1 virus isolates obtained during the 2008-2009 season, but none of the isolates obtained during the 2007-2008 season, contained the H274Y mutation. The mean +/- standard deviation duration of fever after the start of oseltamivir therapy was significantly longer for patients with H1N1 virus infection (49.1+/-30.2 h) than it was for patients with H3N2 virus infection (33.7+/-20.1 h; P < .01) during the 2008-2009 season and patients with H1N1 virus infection during the 2007-2008 season (32.0+/-18.9 h; P < .001). The duration of fever was significantly longer after the first dose of oseltamivir than it was after the first dose of zanamivir for patients with H1N1 virus infection during the 2008-2009 season (P <.001). The duration of fever from onset of H1N1 virus infection was significantly longer for children 15 years of age during 2008-2009 (70.6+/-34.5 h) than it was for such children during 2007-2008 (48.4+/-21.2). CONCLUSION: The effectiveness of oseltamivir, but not that of zanamivir, decreased significantly for H1N1 virus infection during the 2008-2009 season.
Asunto(s)
Antivirales/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/tratamiento farmacológico , Mutación , Neuraminidasa/genética , Oseltamivir/uso terapéutico , Zanamivir/uso terapéutico , Adulto , Farmacorresistencia Viral , Femenino , Fiebre/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neuraminidasa/antagonistas & inhibidores , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the clinical effectiveness of oseltamivir therapy started within 48h of the onset for influenza A(H1N1) virus with H274Y neuraminidase (NA) mutation. METHODS: Virus was isolated before and four to six days after starting oseltamivir treatment from 73 outpatients with influenza A(H1N1) virus in the 2007-2008 and 2008-2009 seasons. NA inhibition assays (IC(50)) and sequence analyses were done using influenza viruses isolated from these patients. Body temperature was evaluated before and on the second, third, and fourth days after starting treatment. RESULTS: H274Y mutation was not shown in the 2007-2008 season (44 patients) and shown in all 29 patients in the 2008-2009 season by NA sequence analyses. The mean IC(50) before oseltamivir treatment was significantly higher in 2008-2009 (319.3+/-185.4 nM) than in 2007-2008 (1.5+/-0.8 nM; p<.001). Patients < or =15 years with oseltamivir-resistant virus infection had a higher ratio of patients persisted virus after oseltamivir treatment than patients >15 years (50% and 11.8%, respectively, p=0.038), and a significant higher body temperature during oseltamivir treatment, compared to patients < or =15 years treated for oseltamivir-sensitive virus infection. CONCLUSION: The clinical effectiveness of oseltamivir for the A(H1N1) virus was reduced in the 2008-2009 season compared with the previous season, especially in children, probably due to the H274Y mutation. Oseltamivir seems to be not recommended for children and patients with high-risk underlying diseases infected with H274Y mutated A(H1N1) virus.
Asunto(s)
Antivirales/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Neuraminidasa/genética , Oseltamivir/uso terapéutico , Adolescente , Adulto , Sustitución de Aminoácidos , Temperatura Corporal , Niño , Preescolar , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Persona de Mediana Edad , Mutación , Neuraminidasa/antagonistas & inhibidores , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To compare the effectiveness of zanamivir with oseltamivir for influenza A and B. METHODS: 1113 patients with influenza A or B were enrolled in the 2006-2007 influenza season. The duration of fever (temperature, >or=37.5 degrees C) and the percentage of patients afebrile at 24 and 48 h after the first dose of zanamivir or oseltamivir were calculated. Virus persistence after zanamivir therapy was also evaluated. RESULTS: There were marginally significant differences between the duration of fever after the first dose of zanamivir (31.8+/-18.4h) and oseltamivir (35.5+/-23.9h) for influenza A (p<0.05). The duration of fever after starting zanamivir therapy (35.8+/-22.4h) was significantly shorter than that of oseltamivir (52.7+/-31.3h) for influenza B (p<0.001). There were no significant differences between influenza A and B in the percentage of patients afebrile at 24 or 48 h after the first inhalation of zanamivir. The reisolation rate after zanamivir therapy showed marginally significant differences between influenza A and B (<0.05). By multiple regression analysis, therapy (zanamivir or oseltamivir) was the major determinant affecting the duration of fever for influenza B. CONCLUSION: Zanamivir therapy is more effective than oseltamivir for the treatment of influenza B infection.