Direct and Indirect Effects of Rotavirus Vaccination Upon Childhood Hospitalizations in 3 US Counties, 2006-2009

Epidemiology Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 06/2011; 53(3):245-53. DOI: 10.1093/cid/cir307
Source: PubMed


Routine rotavirus vaccination of US infants began in 2006. We conducted active, population-based surveillance for rotavirus gastroenteritis hospitalizations in 3 US counties to assess vaccine impact.
Children <36 months old hospitalized with diarrhea and/or vomiting were enrolled from January through June each year during the period 2006-2009 and tested for rotavirus. Age-stratified rates of hospitalization for rotavirus infection were compared with corresponding vaccination coverage among a control group of children with acute respiratory illness. To assess direct and indirect benefits, vaccination coverage rates in the control group were multiplied by vaccine effectiveness estimates to calculate expected reductions in the rate of hospitalization for rotavirus infection. Rotavirus serotypes were compared across years.
Compared with 2006, a significant reduction in rates of hospitalization for rotavirus infection (P < .001) was observed in 2008 among all age groups. There was an 87% reduction in the 6-11-month-old age group (coverage, 77%), a 96% reduction in the 12-23-months-old age group (coverage, 46%), and a 92% reduction in the 24-35-month-old age group (coverage, 1%), which exceeded reductions expected on the basis of coverage and vaccine effectiveness estimates. Age-specific rate reductions were nearly equivalent to those expected on the basis of age-specific vaccine coverage in 2009. Predominant strains varied annually: G1P[8] (91%) in 2006; G1P[8] (45%) and G12P[8] (36%) in 2007; G1P[8] (89%) in 2008; and G3P[8] (43%), G2P[4] (34%), and G9P[8] (27%) in 2009.
Rotavirus vaccination has dramatically decreased rates of hospitalization for rotavirus infection among children in these US counties. In 2008, reductions were prominent among both vaccine-eligible age groups and older, largely unvaccinated children; the latter likely resulted from indirect protection. Although rates among age groups eligible for vaccination remained low in 2009, indirect benefits disappeared.

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Available from: Ben A Lopman, Jun 18, 2014
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    • "The low detection rate among healthy controls in our study also might be partially attributable to the eligibility criteria for healthy controls that required a child to be 14 days without AGE before enrollment and the fecal specimen obtained within 5 days enrollment. In addition, unlike the previous studies, our study was conducted after the introduction of rotavirus vaccine into the US immunization program at a time when rotavirus activity had declined substantially (22–24). The lower detection rate of rotavirus in healthy children in our study may reflect this decrease in rotavirus activity after vaccine introduction; that is, fewer children may have been shedding virus from a previous infection, some may have had an asymptomatic infection, and infected children who had been vaccinated were possibly clearing the virus more quickly. "
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    ABSTRACT: We compared rotavirus detection rates in children with acute gastroenteritis (AGE) and in healthy controls using enzyme immunoassays (EIAs) and semiquantitative real-time reverse transcription PCR (qRT-PCR). We calculated rotavirus vaccine effectiveness using different laboratory-based case definitions to determine which best identified the proportion of disease that was vaccine preventable. Of 648 AGE patients, 158 (24%) were EIA positive, and 157 were also qRT-PCR positive. An additional 65 (10%) were qRT-PCR positive but EIA negative. Of 500 healthy controls, 1 was EIA positive and 24 (5%) were qRT-PCR positive. Rotavirus vaccine was highly effective (84% [95% CI 71%-91%]) in EIA-positive children but offered no significant protection (14% [95% CI -105% to 64%]) in EIA-negative children for whom virus was detected by qRT-PCR alone. Children with rotavirus detected by qRT-PCR but not by EIA were not protected by vaccination, suggesting that rotavirus detected by qRT-PCR alone might not be causally associated with AGE in all patients.
    Full-text · Article · Aug 2013 · Emerging Infectious Diseases
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    • "Other discount rates, including those recommended for Dutch health economic evaluations, were used in sensitivity analysis [39]. Although there is no consensus on a cut-off point for good value for resources, we present our results in the context of commonly cited thresholds per QALY of $50,000 equivalent to €35,000 [67,68]. This amount is approximately equal to the Dutch Gross Domestic Product per capita in 2011, the recommended threshold for highly cost-effective interventions by the WHO [66]. "
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    ABSTRACT: Background The cost-effectiveness of universal rotavirus (RV) vaccination is controversial in developed countries. As a result, RV vaccination programs do not currently exist in most European countries. Hospitalization is the main driver of RV disease costs, and prematurity, low birth weight (LBW) and underlying medical conditions have been associated with RV hospitalization and complications. We investigated the cost-effectiveness of targeted RV vaccination of high-risk infants and universal RV vaccination versus no vaccination. Methods Disease burden, mortality and healthcare costs of RV hospitalization for children with and without prematurity, LBW and congenital pathology were quantified in two hospital-based observational studies in the Netherlands. Cost-effectiveness analysis was based on an age-structured stochastic multi-cohort model of the Dutch population comparing universal RV vaccination and targeted vaccination of high-risk infants to no vaccination. The primary endpoint was the incremental cost-effectiveness ratio (ICER), with a threshold of €35,000/quality-adjusted life year (QALY) from the healthcare provider perspective. Sensitivity analyses included vaccine price and coverage, herd-immunity and QALY losses. Results A total of 936 children with RV infection were included. Prematurity, LBW and congenital pathology were associated with increased risks of RV hospitalization (relative risks (RR) ranging from 1.6 to 4.4), ICU admission (RR ranging from 4.2 to 7.9), prolonged hospital stay (1.5 to 3.0 excess days) and higher healthcare costs (€648 to €1,533 excess costs). Seven children succumbed due to RV complications, all belonging to the high-risk population. Targeted RV vaccination was highly cost-effective and potentially cost-saving from the healthcare provider perspective with ICERs below €20,000/QALY in all scenarios with total (undiscounted) annual healthcare costs between -€0.1 and €0.5 million/year. Results were most sensitive to mortality rates, but targeted vaccination remained highly cost-effective up to reductions of 90% compared to observed mortality. Universal RV vaccination was not considered cost-effective (mean ICER: €60,200/QALY) unless herd-immunity and caretaker QALY losses were included and vaccine prices were €60 at most (mean ICER: €21,309/QALY). Conclusion We recommend targeted RV vaccination for high-risk infants in developed countries.
    Full-text · Article · Apr 2013 · BMC Medicine
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    • "In addition to epidemiological studies of rotavirus-related disease, studies on the observed indirect protection (herd immunity) have been carried out either through observing the actual change in RVGE hospitalized cases in the US [8,12] between pre and post- rotavirus vaccination eras or through projecting the impacts of rotavirus vaccination by applying mathematical transmission models in England and Wales [13] or in five other countries in the European Union [14]. The results from these studies have reinforced results of other studies on the topic [8,15-20]. It is important to emphasize that the US-study on herd protection reported the observation of an actual decrease in the annual RVGE hospitalized cases for all age groups after rotavirus vaccination was introduced in the US in 2006 [8,12,21]. "
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    ABSTRACT: Background To update a cost-effectiveness analysis of rotavirus vaccination in the Netherlands previously published in 2011. Methods The rotavirus burden of disease and the indirect protection of older children and young adults (herd protection) were updated. Results When updated data was used, routine infant rotavirus vaccination in the Netherlands would potentially become an even more cost-effective strategy than previously estimated with the incremental cost per QALY at only €3,000-4,000. Break-even total vaccination costs were indicated at €92–122, depending on the applied threshold. Conclusions We concluded that the results on potentially favourable cost-effectiveness in the previous study remained valid, however, the new data suggested that previous results might represent an underestimation of the economic attractiveness of rotavirus vaccination.
    Full-text · Article · Jan 2013 · BMC Infectious Diseases
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