The introduction of rotavirus vaccine in Sweden : setting the scene and short term outcomes

Sammanfattning: Background: The rotavirus causes the most severe cases of viral gastroenteritis in small children worldwide, resulting in both high morbidity and mortality. The World Health Organization has recommended vaccination against the rotavirus since 2009 and the vaccine had been introduced by more than 90 countries in 2017. Since 2014, the vaccine has been offered to all newborn infants in Stockholm and Jönköping counties and it will be introduced into the national Swedish immunization program in September 2019. The aim of this thesis is to create a platform for the national implementation of the rotavirus vaccine in Sweden. It studies parental attitudes to the vaccine, examines the rare, but serious, adverse event of intussusception and looks at how the vaccine affects the burden of disease. The thesis also looks at social disparities in hospital use due to gastroenteritis. Methods and Results: Different methods have been used to illustrate different aspects of the introduction of the rotavirus vaccine in Sweden in the five studies included in this thesis. The thesis highlights the importance of good relationships between child health care nurses and parents, sets the scene for safety surveillance, shows how paediatric care for gastroenteritis has been reduced by the rotavirus vaccine and also shows social differences in the utilization of paediatric care for gastroenteritis in small children. Studies I and II focused on parental attitudes, conceptions and knowledge of the rotavirus vaccine during the implementation of the vaccine in Stockholm. Both studies included parents of newborn infants before the first dose of the rotavirus vaccine was offered. Study I was a cross-sectional questionnaire study of 1,063 parents. The analyses were carried out using Pearson´s chi-square test and stepwise logistic regression in order to find the main predictors for vaccination or not. Most parents (81%) intended to vaccinate their child, 8% did not want to vaccinate and 11% were uncertain. Poor knowledge about the vaccine and the rotavirus infection, less trust in the child health care nurse, lower levels of education and having a child of up to five weeks of age were associated with being hesitant or unwilling to vaccinate. Study II was a qualitative study of 10 in-depth interviews with parents. We identified four main categories that showed different conceptions of the rotavirus vaccine: to vaccinate without doubt, hesitant to vaccinate, risky to vaccinate and unnecessary to vaccinate. Study III was a validation study of the diagnosis of intussusception in children under three years of age and it used data from the Swedish National Patient Register for the period 1987-2013. The aim of this study was to create a platform for further register-based follow-up studies of this rare, but serious, adverse event of the rotavirus vaccine. We manually reviewed 392 medical records that were randomly selected by The National Board of Health and Welfare from both pediatric and surgery care in Sweden, by using accepted international criteria of case definitions. A positive predictive value (PPV) of 89% was reached for the total study population and the PPV for the 240 children under one year of age was 88%. Studies IV and V were register-based studies of national birth cohorts. In both studies the children were linked to their parents and the outcome was viral gastroenteritis for paediatric inpatient and outpatient care. In study IV the outpatient care was defined as visits at emergency departments (ED). In study V the outpatient care included both paediatric hospital care in the EDs as well as publically funded paediatric care outside of the hospital. The adjusted hazard ratios (HR) for a diagnosis of viral gastroenteritis were estimated by Cox regression. Study IV consisted of 752,048 children below five years of age in Sweden from 2006-2012. Socioeconomic risk factors for the outcomes and national differences in geographical incidences of the outcomes were investigated. In total 3.1% children were admitted for inpatient care and 9.4% children received paediatric outpatient care at EDs. The adjusted HRs for both outcomes were increased when the mother was under 25 years of age, had a lower level of education, any parent had a psychiatric disorder, and/or when parents were born outside Europe. All these factors were associated with a lower level of health literacy. There were also considerable differences between the incidences of the outcomes between Swedish counties. Study V consisted of 518,500 children aged two months to two years who were born alive between 1 March 2011 and 31 December 2015. The observation period ended in 31 March 2017. Children in Stockholm and Jönköping counties were compared with the rest of Sweden in order to study the effect that the rotavirus vaccine had on outcomes and on the social gradient. After adjustments for time trends and social indicators, reductions of 37% and 24% for inpatient care and 11% and 21% for outpatient care were shown in the Stockholm and Jönköping counties, respectively, compared to the rest of Sweden. The social gradient was maintained for inpatient care, but increased for paediatric outpatient care in Stockholm after the vaccine was introduced. Conclusions This thesis showed reductions of paediatric care of gastroenteritis in small children by the rotavirus vaccine in two Swedish counties. The thesis also showed that it is important to maintain our child health care organization built around child health care centers if we are to achieve high and socially equitable vaccine coverages for the rotavirus vaccine when it is nationally implemented. In addition, other interventions may be needed to support the introduction of the rotavirus vaccine so that we can reduce the impact that social factors have on its potential uptake. Such supportive interventions would include both targeted information and overall policy changes that focus on parents with low health literacy. The thesis also presented that the quality of the diagnosis of intussusception in children under three years of age in the Swedish Patient Register is high, as a prerequisite for further studies. A robust safety surveillance of the newly introduced rotavirus vaccine will also be important so that we can maintain the high levels of trust that the public already have in Swedish child health care nurses and the country’s preventive health care program.