Immunization has proven to be one of the most cost-effective public health interventions to date. Not only has immunization saved millions of lives, but it has also protected children from severe illness and life-changing disability. Measles, which had once been a significant childhood killer, is now targeted for elimination. Worldwide measles vaccination has led to a 71% decrease in measles-related deaths and an 88% reduction the World Health Organization African Region (WHO-AFRO) alone. In the Democratic Republic of Congo (DRC), measles immunization has had a profound effect on reducing childhood mortality; however, beginning in 2010 large-scale measles outbreaks threatened past successes. Suspected case counts increased dramatically. This was mainly attributed to a weak routine immunization system and missed supplementary immunization activities. This dissertation aims to inform the improvement and further development of the immunization program in DRC by assessing measles immunization effects, vaccine effectiveness, and compares the cost-effectiveness of different immunization strategies. Chapter 1 is a brief introduction to measles immunization worldwide and in DRC. Chapter 2 is based on measles surveillance data from the Integrated Disease Surveillance and Response (IDSR) and demonstrated that measles immunization, in particular mass campaigns are extremely effective in DRC. Chapter 3 utilized case-based surveillance data with laboratory confirmation to estimate measles vaccine effectiveness. Finally, chapter 4 further solidifies the importance of mass campaigns in DRC until routine immunization is further strengthened through a cost-effectiveness analysis of three different vaccination strategies.

Measles is a highly contagious viral disease, and infection can result in severe symptoms, complications, and both acute and prolonged immunologic effects. The Democratic Republic of the Congo (DRC) is a resource poor and measles endemic country. Limited health care services, poor nutrition, and high levels of infectious disease, as found in the DRC, make host immune function of crucial public health importance. In addition to assessing vaccination coverage and seroprotective antibody levels, identifying and quantifying the immunologic impact of measles vaccination and disease on child health outcomes can provide valuable recommendations for public health policy and practice. The overall aim of this dissertation is twofold. First, this dissertation seeks to describe measles vaccination coverage and seroprotective levels of measles antibody in DRC and examine factors that may contribute to the large proportion of children with inadequate immunity. Second, it aims to assess associations of both measles vaccination and disease with markers of infectious disease (acute fever, cough, and diarrhea outcomes). Chapter 1 is a brief overview of measles vaccination and disease pathogenesis. Chapter 2 examines predictors of measles vaccination coverage in the DRC and describes characteristics of children who are least reached by routine measles immunization efforts. Chapter 3 utilizes a causal mediation model to quantify the impact of measles vaccination on acute fever, cough, and diarrhea outcomes. Chapter 4 describes measles antibody seroprevalence among vaccinated and unvaccinated children and identifies trends in inadequate immunization. Finally, Chapter 5 explores the immunologic impact of measles on child health outcomes by examining the association of previous measles infection with acute fever, cough, and diarrhea episodes.

Background

Methods

Results

Conclusions

Introduction: Local outbreaks of measles infection are primarily mediated by international travel of persons from endemic areas, with subsequent spread of the virus via undervaccinated populations. Recent resurgences of measles in communities where vaccination rates are non-ideal secondary to philosophical objections require the emergency physician to more routinely consider the diagnosis. In cases of measles complicated by acute encephalitis or encephalopathy, the diagnosis can be especially difficult to make due to lack of a reliable primary historian.

Case report: Here we present a case of altered mental status and new-onset bilateral lower extremity weakness in a fully vaccinated young woman diagnosed with measles infection caused by acute disseminated encephalomyelitis in the setting of vaccine failure.

Conclusion: Despite a documented history of immunization, acute measles infection and its uncommon sequelae are possible. Recognizing vaccine failure and appropriately isolating patients are of paramount importance.

Rates of non-medical vaccine exemptions have been increasing in the U.S. since the early 1990s. These exemptions tend to be spatially clustered rather than randomly occurring in the population. In contrast to long-standing public health findings, under-vaccination due to non-medical exemptions tends to be found among children with educated, affluent, non-Hispanic white parents rather than those with relatively disadvantaged backgrounds. This dissertation uses data on Personal Beliefs Exemptions (PBEs) in schools in California from 1998-2014 and an empirically-calibrated large-scale simulation experiment to understand how spatial clusters of these exemptions form and their potential consequences for measles transmission.

This dissertation emphasizes the importance of interaction in social networks in structuring both the local context surrounding parents’ vaccine decisions and the patterns of physical contact through which disease spreads. Major findings show that residential sorting of parents into neighborhoods and schools based on socio-demographic characteristics associated with school-level PBE rates provides only a partial explanation for broader patterns of clustering. Additional analyses provide evidence of spillover effects between PBE rates and socio-demographic characteristics, particularly percent non-Hispanic white children, on PBE rates in nearby schools.

A large-scale simulation of measles transmission using a synthetic population of youth in California in 2014 is then used to examine the potential consequences of PBEs for disease spread. Schools serve as hotspots for measles transmission regardless of the spatial locations of PBEs, although clustering of these exemptions within households and charter schools increase the opportunities for infections. Surprisingly, spatial pockets of PBEs may provide slight protection against measles transmission when outbreak sizes are small and the disease is introduced randomly into the population. Yet, clustering of exemptions can reduce protective effects of herd immunity to large measles epidemics, even when overall vaccination coverage in the population is high.

This dissertation concludes by drawing connections between findings in the empirical chapters and linking the results to the larger theoretical context of social interaction in networks. Practical implications for vaccine policy and efforts to control vaccine-preventable disease are discussed. Overall, this project seeks to illustrate how decisions perceived as personal by parents contribute to collective health outcomes.