Parainfluenza virus infection of young children: estimates of the population-based burden of hospitalization.
ABSTRACT To determine the population-based inpatient disease burden of parainfluenza virus in children <5 years of age.
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.
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.
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.
Article: Epidemiology of respiratory viral infections in two long-term refugee camps in Kenya, 2007-2010.[show abstract] [hide abstract]
ABSTRACT: Refugees are at risk for poor outcomes from acute respiratory infections (ARI) because of overcrowding, suboptimal living conditions, and malnutrition. We implemented surveillance for respiratory viruses in Dadaab and Kakuma refugee camps in Kenya to characterize their role in the epidemiology of ARI among refugees. From 1 September 2007 through 31 August 2010, we obtained nasopharyngeal (NP) and oropharyngeal (OP) specimens from patients with influenza-like illness (ILI) or severe acute respiratory infections (SARI) and tested them by RT-PCR for adenovirus (AdV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza viruses (PIV), and influenza A and B viruses. Definitions for ILI and SARI were adapted from those of the World Health Organization. Proportions of cases associated with viral aetiology were calculated by camp and by clinical case definition. In addition, for children < 5 years only, crude estimates of rates due to SARI per 1000 were obtained. We tested specimens from 1815 ILI and 4449 SARI patients (median age = 1 year). Proportion positive for virus were AdV, 21.7%; RSV, 12.5%; hMPV, 5.7%; PIV, 9.4%; influenza A, 9.7%; and influenza B, 2.6%; 49.8% were positive for at least one virus. The annual rate of SARI hospitalisation for 2007-2010 was 57 per 1000 children per year. Virus-positive hospitalisation rates were 14 for AdV; 9 for RSV; 6 for PIV; 4 for hMPV; 5 for influenza A; and 1 for influenza B. The rate of SARI hospitalisation was highest in children < 1 year old (156 per 1000 child-years). The ratio of rates for children < 1 year and 1 to < 5 years old was 3.7:1 for AdV, 5.5:1 for RSV, 4.4:1 for PIV, 5.1:1 for hMPV, 3.2:1 for influenza A, and 2.2:1 for influenza B. While SARI hospitalisation rates peaked from November to February in Dadaab, no distinct seasonality was observed in Kakuma. Respiratory viral infections, particularly RSV and AdV, were associated with high rates of illness and make up a substantial portion of respiratory infection in these two refugee settings.BMC Infectious Diseases 01/2012; 12:7. · 3.12 Impact Factor
Article: The C proteins of human parainfluenza virus type 1 block IFN signaling by binding and retaining Stat1 in perinuclear aggregates at the late endosome.[show abstract] [hide abstract]
ABSTRACT: Interferons (IFNs) play a crucial role in the antiviral immune response. Whereas the C proteins of wild-type human parainfluenza virus type 1 (WT HPIV1) inhibit both IFN-β induction and signaling, a HPIV1 mutant encoding a single amino acid substitution (F170S) in the C proteins is unable to block either host response. Here, signaling downstream of the type 1 IFN receptor was examined in Vero cells to define at what stage WT HPIV1 can block, and F170S HPIV1 fails to block, IFN signaling. WT HPIV1 inhibited phosphorylation of both Stat1 and Stat2, and this inhibition was only slightly reduced for F170S HPIV1. Degradation of Stat1 or Stat2 was not observed. The HPIV1 C proteins were found to accumulate in the perinuclear space, often forming large granules, and co-localized with Stat1 and the cation-independent mannose 6-phosphate receptor (M6PR) that is a marker for late endosomes. Upon stimulation with IFN-β, both the WT and F170S C proteins remained in the perinuclear space, but only the WT C proteins prevented Stat1 translocation to the nucleus. In addition, WT HPIV1 C proteins, but not F170S C proteins, co-immunoprecipitated both phosphorylated and unphosphorylated Stat1. Our findings suggest that the WT HPIV1 C proteins form a stable complex with Stat1 in perinuclear granules that co-localize with M6PR, and that this direct interaction between the WT HPIV1 C proteins and Stat1 is the basis for the ability of HPIV1 to inhibit IFN signaling. The F170S mutation in HPIV1 C did not prevent perinuclear co-localization with Stat1, but apparently weakened this interaction such that, upon IFN stimulation, Stat1 was translocated to the nucleus to induce an antiviral response.PLoS ONE 01/2012; 7(2):e28382. · 4.09 Impact Factor
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ABSTRACT: BACKGROUND: Human parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China. METHODS: Throat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients' clinical presentations were recorded for further analysis. RESULTS: Of 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more "hoarseness" (p=0.015), "abnormal pulmonary breathing sound" (p<0.001), "dyspnoea" (p<0.001), "pneumonia" (p=0.01), and "diarrhoea" (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (>=14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was "Expectoration" (p<0.001). Co-infections were common, with 33.3%--63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens. CONCLUSIONS: HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.BMC Infectious Diseases 01/2013; 13(1):28. · 3.12 Impact Factor