Burden of RSV and Influenza Virus in Children in Pakistan

说明（由申请人提供）：巴基斯坦是世界上儿童死亡率第四高的国家，每年有50多万5岁以下儿童死亡。近四分之一的死亡是由于下呼吸道感染（LRTI）。呼吸道病毒在巴基斯坦儿童下呼吸道感染中作为主要病原体或与细菌共病原体的作用尚未确定。我们推测呼吸道合胞病毒（RSV）和流感病毒在巴基斯坦5岁以下儿童下呼吸道感染的病因学中起重要作用。本提案的目的是确定巴基斯坦儿童因呼吸道合胞病毒和流感病毒造成的疾病负担。具体目的是：1)提高巴基斯坦的病毒诊断能力；2)确定在巴基斯坦卡拉奇两家三级医院因发烧或呼吸道疾病住院的5岁以下儿童中RSV和流感病毒的流行情况；3)确定巴基斯坦卡拉奇Bilal Colony（一个城市贫民窟）5岁以下儿童中与RSV和流感病毒相关的LRTI的社区发病率。由于目前已有流感疫苗，而呼吸道合流病毒疫苗正处于后期开发阶段，这些研究将确定基线发病率，并对在巴基斯坦引进这些疫苗的必要性进行客观评估。在研究的第一年，阿里博士将在美国范德比尔特大学的导师的帮助下，领导在巴基斯坦阿迦汗大学建立的病毒培养。随后将进行2年以医院为基础的监测，然后进行2年以社区为基础的主动监测，以发现巴基斯坦卡拉奇住院和门诊环境中5岁以下儿童的呼吸道合胞病毒和流感病毒负担。如果确认存在重大负担，则可以向其他供资机构提出使用病毒疫苗减轻这一负担的研究。公共卫生相关性：肺炎是巴基斯坦儿童死亡的主要原因。呼吸道合胞病毒和流感病毒在巴基斯坦儿童肺炎病因学中的作用尚不清楚，这将是本次调查的重点。如果发现这些病毒是重要的病原体，那么针对这些病毒的疫苗可能会降低巴基斯坦与肺炎相关的儿童死亡率。

DESCRIPTION (provided by applicant): Pakistan has the fourth highest number of child deaths in the world with more than 500,000 children dying annually before the age of 5 years. Nearly one quarter of this mortality is due to lower respiratory tract infections (LRTI). The role of respiratory viruses as primary pathogens, or co-pathogens with bacteria in childhood LRTI in Pakistan has not been determined. We hypothesize that respiratory syncytial virus (RSV) and influenza virus play an important role in the etiology of LRTI in children <5 year old in Pakistan. The objective of this proposal is to determine the disease burden due to RSV and influenza virus in children in Pakistan. The specific aims are 1) to advance viral diagnostic capacity in Pakistan 2) to determine the prevalence of RSV and influenza virus in < 5 year old children hospitalized with fever or respiratory illness at two tertiary care hospitals in Karachi, Pakistan and 3) To determine the community based incidence of LRTI associated with RSV and influenza virus in < 5 year old children at Bilal Colony (an urban slum) in Karachi, Pakistan. Since influenza vaccines are currently available and RSV vaccines are in advanced development, these studies will establish baseline disease rates and present objective assessment of the need for introducing these vaccines in Pakistan. In the first year of the study, Dr. Ali will lead the establishment of viral culture set up at Aga Khan University in Pakistan, with the help of mentors at Vanderbilt University in United States. This will be followed by 2 years of hospital based surveillance and then 2 years of community based active surveillance to find the burden of RSV and influenza virus in < 5 year old children in inpatient and outpatient settings in Karachi, Pakistan. If a significant burden is confirmed, then a study to use viral vaccines to reduce this burden can be proposed to other funding agencies. PUBLIC HEALTH RELEVANCE: Pneumonia is the leading cause of child mortality in Pakistan. Role of respiratory syncytial virus and influenza virus in the etiology of childhood pneumonia in Pakistan is not known, and will be the focus of this investigation. If these viruses are found to be significant pathogens, then vaccines against these viruses may reduce the pneumonia associated child mortality in Pakistan.