In June 2008, the Collaborative Pediatric Critical Care Research Network (CPCCRN) began enrolling subjects in a descriptive, prospective cohort study of critical pertussis. Specific aims are to characterize the acute course of pertussis critical illness admission, assess health and demographic characteristics of the children who develop critical pertussis, and to assess health status and family impact following PICU discharge via assessment of developmental sequelae, and quality of life in survivors. Support is provided from the National Vaccine Program Office in the Office of the Secretary, Department of Health and Human Services, as well as the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health.
The study is a trans-Federal project: a co-investigator at the CDC provides collaboration with the laboratory, epidemiology and public health expertise available at CDC, and a basic scientist (Eric Harvill), supported by the National Institute of General Medical Sciences, is utilizing the scientific opportunity afforded by the study to elucidate B. pertussis pathogenesis as a factor of microbial ecology and adaptive characteristics. CPCCRN investigators plan to enroll 200 children with critical pertussis at the 7 CPCCRN sites across the United States. To date, 84 children have been enrolled, over a period of 2 years. Currently, there are about 17,000 annual PICU admissions at 7 CPCCRN sites where surveillance for critical pertussis is ongoing. In addition, investigators and staff at 17 outside sites at academic medical centers with PICUs have been recruited and trained to complete the study within 2 years. With the addition of the outside sites, nearly 33,000 annual PICU admissions are being screened for critical pertussis illness.
Developmental sequelae and quality of life will be assessed in infants who were < 12 months gestational age at PICU admission. That is, children who were premature with a gestational age <40 weeks at enrollment, are included in developmental evaluation if they were enrolled at any time prior to being 12 months old after accounting for their gestational age at birth. Investigators are seeking evidence suggestive of association patterns linking characteristics of the critical illness (support required, evidence of organ failure) to longer term outcomes in survivors.
Laboratory testing for B. pertussis at the CPCCRN sites will facilitate future hypothesis formation. B. pertussis isolates will be collected and shipped to a research laboratory that is conducting research in strain genetics. Researchers hope to identify the types of B. pertussis that causes lethal disease in United States infants and children.
There are several lines of evidence suggesting that groups of organisms with different and characteristic dynamics may reflect independent epidemiology of pertussis infections in various child populations (52
). For example, it is possible that the seasonal peak in the incidence of B. pertussis
in infants (hospitalized and not hospitalized) precedes the seasonal peak in adolescents. This might indicate that seasonal epidemics in adolescents are probably not the main source infecting infants. Parents with pertussis, including new mothers, are the identified source of B. pertussis
infection in about 25% of cases in early infancy, when rates for complications and fatalities are highest (53
). The ability to distinguish the strains that cause severe disease in infants from other strains circulating in various populations will enable more exact understanding of the likely source of the infections.
The laboratory will use the Golden Gate platform to definitively characterize each isolate obtained from the study subjects by SNP (single nucleotide polymorphism) type. The SNP types identified will be related to those present worldwide and to that present in other age groups in survey populations in Massachusetts. These studies will address pressing questions: Is there a subset of strains that are most dangerous to young infants? Are these the same strains that cause the strong cyclical epidemics in adolescents, or the strains that percolate at lower levels in vaccinated children or in adults or elderly? The finding that a subset of B. pertussis lineages is associated with severe disease in infants will inform epidemiologic and therapeutic interventions and generate hypothesis-driven research.
The NICHD CPCCRN sites are geographically diverse, and the populations available to study are representative of the socio-demographic characteristics of children in the United States (56
) (). Translational hypotheses will be generated and understanding of how organ failure might be triggered in critical illness and injury will be enhanced. Detailed studies of critical pertussis illness among children in cohorts with specific demographic description, high acuity and survivor follow-up assessment are largely absent from the literature (22
CPCCRN Patient Population 2008