Morrow Ardythe L, Staat Mary A, DeFranco Emily A, McNeal Monica M, Cline Allison R, Conrey Shannon C, Schlaudecker Elizabeth P, Piasecki Alexandra M, Burke Rachel M, Niu Liang, Hall Aron J, Bowen Michael D, Gerber Susan I, Langley Gayle E, Thornburg Natalie J, Campbell Angela P, Vinjé Jan, Parashar Umesh D, Payne Daniel C
Department of Environmental and Public Health Sciences, Division of Epidemiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
JMIR Res Protoc. 2021 Feb 12;10(2):e22222. doi: 10.2196/22222.
Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development.
The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children.
Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody.
Of the 245 enrolled mother-child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother-child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized.
The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/22222.
急性胃肠炎（AGE）和急性呼吸道感染（ARIs）导致大量儿童发病和死亡。研发针对主要肠道和呼吸道病原体的儿童疫苗应以感染自然史和获得性免疫为指导。美国目前缺乏当代出生队列数据来指导疫苗研发。
开展PREVAIL（儿科呼吸道和肠道病毒感染与免疫发生纵向）队列研究，以明确美国儿童感染主要导致AGE和ARI的病原体的自然史及免疫反应。
俄亥俄州辛辛那提市的母亲在妊娠晚期入组，对其子女进行密集随访至2岁。在出生时（脐带血）、6周、6、12、18和24个月时采集儿童血样。每周收集全粪便标本和中鼻甲鼻拭子，并通过多病原体分子检测进行检测。还收集唾液、胎粪、母亲血液和乳汁样本。通过每周自动短信向母亲进行手机调查并查阅病历，记录AGE（24小时内≥3次稀便或水样便或≥1次呕吐发作）和ARI（咳嗽或发热）病例。从登记处和医疗机构获取免疫接种记录。随访于2020年10月结束。病原体特异性感染通过PCR阳性样本或血清抗体升高来定义。
在245对入组的母婴对中，51.8%（n = 127）为白人，43.3%（n = 106）为黑人，55.9%（n = 137）有公共保险，86.5%（n = 212）开始母乳喂养。母亲血样采集率为100.0%（n = 245），脐带血样采集率为85.7%（n = 210）。基于至少70%（≥71/102个研究周）的儿童周参与度以及在此期间提供70%或更多的每周样本，或在18或24个月时提供血样，共有194/245（79.2%）对母婴对符合要求。符合要求的参与者（n = 194）中鼻拭子采集的中位数为71.0%（四分位间距30.0% - 90.5%），其中98.5%（191/194）提供了18或24个月时的血样；每周短信调查的中位数回复率为95.1%（四分位间距76.5% - 100%）。符合要求的母亲报告每个儿童年有2.0例AGE病例和4.5例ARI病例，其中分别有25.5%（分别为160/627）和38.06%（486/1277）的病例接受了医疗护理；0.5%的AGE病例（3/627）和0.55%的ARI病例（7/1277）住院治疗。
PREVAIL队列展示了对美国0至2岁儿童肠道和呼吸道感染及免疫自然史的密集随访，并将为指导疫苗推荐提供独特数据。病原体和抗体检测正在进行中。
国际注册报告标识符（IRRID）：RR1 - 10.2196/22222。
