title: A randomized, double-blind, placebo-controlled trial evaluating the safety of early oseltamivir treatment among children 0-9 years of age hospitalized with influenza in El Salvador and Panama.
abstract: Oseltamivir reduces symptom duration among children with uncomplicated influenza, but few data exist on treatment efficacy and tolerability among hospitalized children, particularly among infants aged <1 year. We evaluated tolerability and efficacy of oseltamivir treatment of children aged 0-9 years hospitalized with influenza.
  
  
  
  We conducted a double-blind, randomized, placebo-controlled trial at tertiary care hospitals in El Salvador and Panama. Primary outcomes were length of hospitalization and increased work of breathing. Children were eligible if hospitalized <7 days after symptom onset with cough or sore throat plus tachypnea. Children were randomized 1:1 to receive oseltamivir or placebo; had swabs collected at enrollment for influenza RT-PCR testing; were assessed at enrollment and every 12 h for work of breathing; and were followed for adverse events through 7 days after discharge. Analyses were intention-to-treat.
  
  
  
  Overall, 683 children were randomized (oseltamivir, n = 341, placebo n = 342). Fifty-three percent were aged <1 year and 30 had influenza (oseltamivir, n = 19; placebo, n = 11). The study was terminated early after enrollment of 21% of the sample size due to lower than anticipated participant accrual. Using Kaplan-Meier analysis, there was no significant difference in median length of hospitalization (3 days, IQR 2-4 vs. 5 days, IQR 3-7, p = 0.22) and increased work of breathing (36 h, IQR 24-72 vs. 96 h, IQR 13-108, p = 0.14) between oseltamivir versus placebo recipients. There was no difference in adverse events between groups.
  
  
  
  Oseltamivir treatment was well tolerated among hospitalized children, including among infants aged <1 year.
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA. Electronic address: fdawood@cdc.gov.
authors.forename: Fatimah S
authors.initials: FS
authors.lastname: Dawood
authors.affiliation: Centro de Estudios en Salud, Universidad del Valle de Guatemala, Guatemala City, Guatemala.
authors.forename: Jorge
authors.initials: J
authors.lastname: Jara
authors.affiliation: Gorgas Memorial Institute for Health Studies, Panama City, Panama.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Hospital San Juan De Dios, Santa Ana, El Salvador.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Castillo
authors.affiliation: Hospital Materno Infantil José Domingo De Obaldía, David, Panama.
authors.forename: Tirza
authors.initials: T
authors.lastname: De León
authors.affiliation: Hospital Del Niño, Panama City, Panama.
authors.forename: Dora
authors.initials: D
authors.lastname: Estripeaut
authors.affiliation: Hospital De Especialidades Pediátricas Omar Torrijos, Panama City, Panama.
authors.forename: Kathia
authors.initials: K
authors.lastname: Luciani
authors.affiliation: Hospital San Juan De Dios, San Miguel, El Salvador.
authors.forename: Yarisa
authors.initials: Y
authors.lastname: Sujey Brizuela
authors.affiliation: Hospital Materno Infantil José Domingo De Obaldía, David, Panama.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Barahona
authors.affiliation: Hospital San Juan De Dios, San Miguel, El Salvador.
authors.forename: Rafael Antonio
authors.initials: RA
authors.lastname: Cazares
authors.affiliation: Hospital De Especialidades Pediátricas Omar Torrijos, Panama City, Panama.
authors.forename: Aracelis M
authors.initials: AM
authors.lastname: Lawson
authors.affiliation: Hospital Del Niño, Panama City, Panama.
authors.forename: Mariana
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: Hospital San Juan De Dios, Santa Ana, El Salvador.
authors.forename: Dinora
authors.initials: D
authors.lastname: de Viana
authors.affiliation: Gorgas Memorial Institute for Health Studies, Panama City, Panama.
authors.forename: Danilo
authors.initials: D
authors.lastname: Franco
authors.affiliation: Gorgas Memorial Institute for Health Studies, Panama City, Panama.
authors.forename: Marlene
authors.initials: M
authors.lastname: Castillo
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Fry
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Gubareva
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tamura
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hughes
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Gargiullo
authors.affiliation: CDC-Central American Regional Office, San Salvador, El Salvador.
authors.forename: Wilfrido
authors.initials: W
authors.lastname: Clara
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Azziz-Baumgartner
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: Marc-Alain
authors.initials: MA
authors.lastname: Widdowson
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D004544:El Salvador; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007251:Influenza, Human / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D007902:Length of Stay; D008297:Male; D053139:Oseltamivir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010176:Panama; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir
keywords: Antiviral agents; Children; Hospitalized; Human; Influenza; Oseltamivir