HOW PREGNANT WOMEN IN THE UNITED STATES PERCEIVE VACCINES FOR THEMSELVES, THEIR CLOSE CONTACTS AND THEIR CHILDREN by Matthew Z. Dudley, MSPH A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland December, 2018 © Matthew Z. Dudley 2018 All rights reserved Abstract Vaccine hesitancy has grown in recent decades [1-4], leading to the clustering of vaccine refusal and associated outbreaks of vaccine preventable diseases (VPDs) [5-11]. Vaccination rates of pregnant women in particular are suboptimal [12]. This dissertation contains three manuscripts discussing research performed as part of an NIH- funded large randomized controlled trial of a comprehensive prenatal intervention to increase uptake of maternal and infant vaccines (referred to as P3+) and its add-on study sponsored by Walgreen Co to increase knowledge and uptake of cocooning vaccines among close friends and family of participating P3+ pregnant women. As part of the P3+ provider-level intervention package, we performed a systematic review to update and succinctly summarize the scientific evidence assessing possible causal associations of adverse events following immunization (AEFI), with refined causality conclusions intended for health care providers. Although for 12 of the 47 AEFI studied a causal relationship was established with at least one vaccine currently routinely recommended to the general population in the United States, most of these were rare or mild, and no causal relationship was established for the other 35 AEFI studied. As part of the P3+ patient-level intervention package, we developed an application called MomsTalkShots for smartphones, tablets and computers that delivers patient-tailored education materials to pregnant women and collects survey data to monitor vaccine knowledge, attitudes and beliefs. As part of the add-on study, the MomsTalkShots app encouraged P3+ pregnant women to ii refer their close friends and family to the app. Baseline survey data showed suboptimal maternal vaccine knowledge and intentions among P3+ pregnant women, especially among first-time pregnant women. In addition, pregnant women who valued vaccination and perceived their social network to value vaccination were more likely to refer their close friends and family to the app. This research demonstrates the opportunity for individually-tailored vaccine education of pregnant women and their social networks to increase vaccine confidence and informed decision making at this stage of life. Thesis Readers Advisor: Daniel Salmon, PhD, Professor (International Health) Rupali J. Limaye, PhD, Assistant Scientist (International Health) Janice V. Bowie, PhD, Professor (Health, Behavior and Society) Marie Diener-West, PhD, Professor (Biostatistics) Non-voting member: Michael Taitel, PhD, Senior Director (Walgreens) Alternate: Lawrence H. Moulton, PhD, Professor (International Health) Alternate: David W. Dowdy, MD, Associate Professor (Epidemiology) iii Preface This dissertation is dedicated to my grandfather, Herman Stone, and his brother, Henry Stone. After escaping Nazi Germany for the U.S. as teenagers in 1939, Herman earned a PhD in Physical Organic Chemistry, and Henry a Master’s of Science degree in Engineering and Physics, and both had long and successful careers in science and industry. Their achievements in science and their resolve to succeed in the face of adversity have been an inspiration to me in my own academic pursuits. Herman lives in Buffalo, NY with his wife Peggy and will receive a full copy of this dissertation upon finalization. Henry sadly passed away on December 1, 2018, shortly before this dissertation’s completion, but will be remembered fondly by his many family and friends. Thank you to the National Institutes of Health and Walgreen Co for their funding support. Thank you as well to everyone who contributed to or reviewed some or all of the content of our book discussed in manuscript 1, as well as everyone who contributed to survey design and/or participant recruitment in the studies providing data for manuscripts 2 and 3. A final and special thank you to my soon-to-be wife, Emily, for her unyielding support of my elongated student status, and to my parents for emphasizing and supporting education and learning from my earliest years of life. iv Table of Contents Abstract ........................................................................................................................................... ii Preface............................................................................................................................................ iv List of Tables .................................................................................................................................. x List of Figures ............................................................................................................................... xii Abbreviations ............................................................................................................................... xiii Introduction ..................................................................................................................................... 1 Research Questions and Hypotheses .............................................................................................. 4 Background and Significance ......................................................................................................... 9 The Importance of Vaccines ....................................................................................................... 9 Vaccine Hesitancy ..................................................................................................................... 10 What is Vaccine Hesitancy? .................................................................................................. 10 Measuring Vaccine Hesitancy and Refusal ........................................................................... 11 The Origins of Vaccine Hesitancy and Refusal ..................................................................... 13 The Modern Reemergence of the Anti-Vaccination Movement ........................................... 14 Causes of Vaccine Hesitancy ................................................................................................ 16 Surveys of Vaccine Intentions, Knowledge, Attitudes and Beliefs .......................................... 18 Childhood and Adolescent Vaccines ..................................................................................... 18 Maternal Vaccines ................................................................................................................. 19 Identifying Homogeneous Groups of Parents Based on Their Vaccine Intentions, Knowledge, Attitudes and Beliefs ......................................................................................... 20 Providers Need Better and More Accessible Vaccine Safety Information ............................... 23 Vaccines Recommended During Childhood ............................................................................. 25 Haemophilus influenzae type b (Hib) .................................................................................... 26 Hepatitis A ............................................................................................................................. 29 Hepatitis B ............................................................................................................................. 32 Human Papillomavirus (HPV) ............................................................................................... 36 Influenza ................................................................................................................................ 40 Measles, Mumps and Rubella ................................................................................................ 46 Meningococcal ....................................................................................................................... 50 Pneumococcal ........................................................................................................................ 54 v Polio ....................................................................................................................................... 58 Rotavirus ................................................................................................................................ 61 Tetanus, Diphtheria and Pertussis ......................................................................................... 64 Varicella ................................................................................................................................. 69 Vaccines Recommended During Pregnancy ............................................................................. 74 ACIP Recommendations in Pregnancy ................................................................................. 74 Vaccine Coverage in Pregnancy ............................................................................................ 75 Influenza in Pregnancy and Infancy ...................................................................................... 76 Pertussis in Pregnancy and Infancy ....................................................................................... 79 Cocooning Vaccination Strategy ..............................................................................................