Human Metapneumovirus Infections in Children

描述(申请人提供)：下呼吸道感染是儿童早期发病和死亡的主要原因。这些感染主要由病毒引起，如呼吸道合胞病毒(RSV)、副流感病毒(PIV)和流感。最近，荷兰和澳大利亚的研究人员描述了副粘病毒家族的一种新成员，暂定命名为人偏肺病毒(HMPV)。该病毒与上呼吸道和下呼吸道疾病(LRI)有关，但其流行病学尚未得到研究。本研究将调查儿童hMPV感染的发生率和临床特征。范德比尔特疫苗诊所为一大群儿童提供初级医疗保健，这些儿童经常接受呼吸道分泌物和血液样本的监测培养，以进行血清学研究。数百个鼻腔冲洗和血清样本可供研究，以及研究护士以盲目方式前瞻性收集的临床数据。在小规模的初步研究中，我们使用RT-PCR在许多冷冻鼻腔冲洗标本中鉴定出hMPV，这些标本来自以前其他已知呼吸道病原体检测为阴性的儿童。这些分离株与荷兰株有同源性，但显示出遗传多样性的证据。与这些感染相关的临床症状类似于RSV感染，特征是发热、咳嗽、喘息和严重的呼吸道疾病。需要一项更大规模的全面研究。本研究的具体目的是明确儿童hMPV感染的流行情况，全面描述临床疾病谱，并确定血清转换的血清学标志和免疫相关因素。

DESCRIPTION (provided by applicant): Lower respiratory tract infection is a leading cause of morbidity and mortality in early childhood. These infections are primarily caused by viruses, such as respiratory syncytial virus (RSV), parainfluenzavirus (PIV) and influenza. Recently investigators in the Netherlands and Australia have described a new member of the Paramyxovirus family, tentatively named human Metapneumovirus (hMPV). The virus was associated with both upper and lower tract respiratory illness (LRI) but the epidemiology has not been studied. This study will investigate the incidence and clinical features of hMPV infection in children. The Vanderbilt Vaccine Clinic provides primary medical care to a large cohort of children who routinely have surveillance cultures of respiratory secretions and blood samples banked for serological studies. Hundreds of nasal wash and serum specimens are available for study, along with clinical data that has been prospectively collected in a blinded fashion by the study nurses. In small preliminary studies, we have used RT-PCR to identify hMPV in numerous frozen nasal wash specimens from children who previously tested negative for other known respiratory pathogens. The isolates share homology with the Netherlands strains, but show evidence of genetic diversity. Clinical symptoms associated with these infections were similar to RSV infection, characterized by fever, cough, wheezing and significant respiratory illness. A larger comprehensive study is needed. The specific aims of this study are to define the prevalence of hMPV infection in children, describe fully the spectrum of clinical illness and identify serologic markers of seroconversion and correlates of immunity.