RESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in children. Palivizumab (PZ) is the only RSV-specific immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations leading to amino acid substitutions in the PZ binding site of the RSV F protein have been associated with breakthrough RSV infections in patients receiving PZ. OBJECTIVE: To detect PZ resistance conferring mutations in RSV strains from children who received PZ. STUDY DESIGN: Children aged ≤ 24 months on October 31 who were hospitalized or had outpatient visits for respiratory illness and/or fever during October-May 2001-2008 in 3 US counties were included. PZ receipt was obtained from parent interviews and medical records among children subsequently infected with RSV. Archived nasal/throat swab specimens were tested for RSV by real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein was sequenced using both Sanger and pyrosequencing methods. RESULTS: Of 8762 enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available archived specimens. Molecular typing identified 42 partial F gene sequences in specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children, of which one had documented PZ receipt. CONCLUSIONS: Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance.
Asunto(s)
Antivirales/uso terapéutico , Palivizumab/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/efectos de los fármacos , Virus Sincitiales Respiratorios/genética , Antivirales/farmacología , Niño , Preescolar , Farmacorresistencia Viral/genética , Femenino , Humanos , Masculino , Mutación , Palivizumab/farmacología , Análisis de Secuencia de ADN , Factores de Tiempo , Estados UnidosRESUMEN
OBJECTIVE: To determine the population-based inpatient disease burden of parainfluenza virus in children <5 years of age. STUDY DESIGN: The New Vaccine Surveillance Network (NVSN) enrolled children <5 years of age who were hospitalized with febrile or acute respiratory illnesses. Surveillance hospitals admitted >95% of all hospitalized children from each county. Combined nasal turbinate/throat swabs were tested for parainfluenza virus (PIV), respiratory syncytial virus, and influenza virus with culture and reverse-transcription-polymerase chain reaction. Both parental interviews and medical chart reviews were conducted. Age-specific population-based hospitalization rates were calculated. RESULTS: From October 2000 through September 2004, 2798 children were enrolled. A total of 191 PIVs were identified from 189 children (6.8% of enrolled: 73 PIV type 1, 23 PIV type 2, and 95 PIV type 3), compared with 521 respiratory syncytial viruses and 159 influenza viruses. Mean PIV hospitalization rates were 3.01, 1.73, 1.53, 0.39, and 1.02 per 1000 children per year for ages 0 to 5 months, 6 to 11 months, 12 to 23 months, 24 to 59 months, and 0 to 59 months, respectively. CONCLUSIONS: PIV accounted for 6.8% of all hospitalizations for fever, acute respiratory illnesses, or both in children <5 years of age. The pediatric PIV inpatient burden is substantial and highlights the need to find an effective vaccine candidate.
Asunto(s)
Crup/epidemiología , Hospitalización/estadística & datos numéricos , Vigilancia de la Población , Infecciones por Respirovirus/epidemiología , Enfermedad Aguda , Apnea/epidemiología , Apnea/virología , Asma/epidemiología , Bronquiolitis/epidemiología , Bronquiolitis/virología , Preescolar , Femenino , Fiebre/virología , Humanos , Lactante , Recién Nacido , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Paramyxovirinae/aislamiento & purificación , Estudios Prospectivos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Estaciones del Año , Sepsis/epidemiología , Sepsis/virología , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To determine in healthy children after primary infection the persistence of human herpesvirus 6 (HHV6) DNA, the presence and frequency of HHV6 re-activation or re-infection, and the relationship of both to illness and the presence of human herpesvirus 7 (HHV7) infection. STUDY DESIGN: Children 1 to 12 years of age with previous HHV6 infection were prospectively evaluated by HHV6 and HHV7 DNA polymerase chain reaction (PCR) and reverse transcription (RT)-PCR for HHV6. HHV6 plasma antibody titers were measured. Illnesses were recorded by diary, and physician records were reviewed. RESULTS: HHV6 DNA was detected in >or=1 peripheral blood mononuclear cell (PBMC) samples in 89% of children. HHV6 reactivation and re-infection were detected by RT-PCR in 1.1% of samples. Detection of HHV6 DNA was intermittent in 76% of children and was not associated with cumulative rates of illness. Illness at a study visit was significantly associated with the absence of HHV6 and HHV7 DNA in PBMC samples and was not associated with HHV6 antibody titer or the presence of HHV6 DNA in saliva. CONCLUSIONS: HHV6 DNA persists in most children intermittently following primary infection and is unrelated to illness. Reactivation of HHV6 occurs in healthy children without apparent illness.