Pertussis among the youngest infants in California: Evaluating the effectiveness of prenatal Tdap vaccination and identifying infants at greatest risk of disease

Pertussis (whooping cough) is a respiratory infection caused by the bacterium Bordetella pertussis that results in prolonged cough illness often characterized by paroxysms, followed by an inspiratory “whoop”. Nearly all severe and fatal cases of pertussis occur in infants younger than three months of age, who are too young to be protected through active immunization. To help protect infants from pertussis during this vulnerable period in their first few weeks of life, women are recommended to receive a pertussis vaccine booster (Tdap) at the start of the third trimester of each pregnancy to optimize transplacental transfer of antibodies to the fetus. This recommendation was made by the Advisory Committee on Immunization Practices in 2013 based on immunogenicity data, and no studies in the United States have yet evaluated the effectiveness of this strategy in reducing pertussis incidence among infants./nThe objectives of this research are to evaluate the effectiveness of prenatal Tdap vaccination in both preventing pertussis and reducing severity of illness in infants, characterize infants at greatest risk of pertussis in California, and identify risk factors for pertussis among Hispanic and non-Hispanic infants./nChapter 1 summarizes the current literature and presents background information for pertussis and pertussis vaccines to provide the context for this research./nChapter 2 evaluates the impact of prenatal Tdap vaccination on the risk of pertussis in infants within the first few weeks of life among the cohort of women who gave birth in California from January 1, 2013 through December 31, 2014. I demonstrate that Tdap vaccination received during pregnancy is 85% effective at preventing pertussis in infants younger than eight weeks of age compared to Tdap vaccination received postpartum. Additionally, I present data to support the current ACIP recommendation to administer Tdap between 27-36 weeks gestation./nChapter 3 includes a retrospective evaluation of the cohort of infants in California who were reported with pertussis before three months of age from January 1, 2013 through December 31, 2014. I determine that infants whose mothers received Tdap vaccine during pregnancy had a lower risk of hospitalization or intensive care unit admission and had shorter hospital stays compared to infants born to unvaccinated mothers, indicating an impact of prenatal Tdap vaccination on pertussis severity. Tdap vaccination during pregnancy was determined to be 58% effective at preventing hospitalization among infants with pertussis./nChapter 4 presents a case-control study in which I describe pertussis cases in infants younger than four months of age and evaluate maternal and infant characteristics associated with pertussis among Hispanic and non-Hispanic infants. Additionally, I evaluate the relationship between maternal parity, a proxy for the number of siblings, and risk of pertussis and determine that infants of all racial/ethnic groups whose mothers are of higher parity are more likely to be reported with pertussis in the first four months of life compared to first-born infants, with the odds of pertussis increasing with higher maternal parity. Case-infants of all racial/ethnic groups were also more likely to have younger mothers who were born in 1997 and later and who likely only ever received DTaP vaccines during childhood. Maternal age and parity largely explain the increased risk of pertussis observed among Hispanic infants./nFinally, chapter 5 summarizes the major findings of each chapter, provides a conclusion and suggests future directions./nThe data used in this dissertation are both unique and robust as the dissertation includes matched surveillance, immunization and vital records data from the entire state of California for multiple years, capturing a peak in disease incidence. More pertussis hospitalizations and deaths have occurred in California in recent years than in any other state, so this is an ideal setting in which to evaluate severe cases of pertussis. Ultimately, this research will assist in targeting vaccination policies to prevent severe disease in the most vulnerable populations.

Advisor: Reingold, Arthur