Background and objective Since 2013, a biennial rotavirus pattern has emerged in the Netherlands with alternating high and low endemic years and a nearly 50% reduction in rotavirus hospitalization rates overall, while infant rotavirus vaccination has remained below 1% throughout. As the rotavirus vaccination cost-effectiveness and risk-benefit ratio in high-income settings is highly influenced by the total rotavirus disease burden, we re-evaluated two infant vaccination strategies, taking into account this recent change in rotavirus epidemiology. Methods We used updated rotavirus disease burden estimates derived from (active) surveillance to evaluate (1) a targeted strategy with selective vaccination of infants with medical risk conditions (prematurity, low birth weight, or congenital conditions) and (2) universal vaccination including all infants. In addition, we added herd protection as well as vaccine-induced intussusception risk to our previous cost-effectiveness model. An age- and risk-group structured, discrete-time event, stochastic multi-cohort model of the Dutch pediatric population was used to estimate the costs and effects of each vaccination strategy. Results The targeted vaccination was cost-saving under all scenarios tested from both the healthcare payer and societal perspective at rotavirus vaccine market prices (€135/child).

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The cost-effectiveness ratio for universal vaccination was €51,277 at the assumed vaccine price of €75/child, using a societal perspective and 3% discount rates. Universal vaccination became cost-neutral at €32/child. At an assumed vaccine-induced intussusception rate of 1/50,000, an estimated 1707 hospitalizations and 21 fatal rotavirus cases were averted by targeted vaccination per vaccine-induced intussusception case.

Fungilab inc. Applying universal vaccination, an additional 571 hospitalizations. In recent years, the Netherlands has seen an unexpected change in rotavirus epidemiology, while infant rotavirus vaccination coverage (the vaccine has been licensed since 2006) has remained below 1%. Annual epidemics were observed until 2013; thereafter, an alternating pattern of high- and low epidemic years emerged (Fig. During low endemic years, rotavirus detections in virological surveillance decreased by 58% (2014) and 52% (2016) compared to an average of the years before 2013, and a delayed start of rotavirus seasons was observed [, ]. Similarly, general practice (GP) consultation rates for acute gastroenteritis (AGE) during the winter months in children under 5 years old were reduced [ ], and the prevalence of asymptomatic rotavirus observed in daycare attendees was significantly lower in 2014 (prevalence rate 0.6%) compared to 2011–2013 (prevalence rate 6.8–11.2%) [ ].

Rotavirus detections and seasonal GP consultation rates during the alternating years 2015 and 2017 were comparable to pre-2014 numbers [, ]. Due to this changing epidemiology, the overall incidence of rotavirus disease in the Dutch pediatric population has reduced substantially. To our knowledge, a similar change in epidemic pattern has not been observed in any other European country without a national infant rotavirus vaccination program. 1 Weekly number of rotavirus detections in sentinel laboratory surveillance (for 2017 only up to week 40) Although the driving factors for this change in epidemic pattern are currently unknown, it has been suggested that, apart from a declining birth rate and temperature fluctuations, rotavirus dynamics in the Netherlands may also be influenced by vaccination policies in neighboring countries [ ]. Universal rotavirus vaccination programs have been implemented in all three neighboring countries of the Netherlands (Belgium in 2006, Germany in 2013, the UK in 2013), with coverage varying between 78% and 94% [ – ]. Implementation in these countries was followed by a sustained reduction in rotavirus detections of 44–75% [ ]. This reduced circulation of rotavirus may have influenced the number of rotavirus introductions into the Netherlands.