Estimating the incidence of symptomatic rotavirus infections: a systematic review and meta-analysis

Abstract

Background: We conducted for the first time a systematic review, including a meta-analysis, of the incidence of symptomatic rotavirus (RV) infections, because (1) it was shown to be an influential factor in estimating the cost-effectiveness of RV vaccination, (2) multiple community-based studies assessed it prospectively, (3) previous studies indicated, inconclusively, it might be similar around the world.

Methodology: Pubmed (which includes Medline) was searched for surveys assessing prospectively symptomatic (diarrheal) episodes in a general population and situation, which also reported on the number of the episodes being tested RV+ and on the persons and the time period observed. A bias assessment tool was developed and used according to Cochrane guidelines by 4 researchers with different backgrounds. Heterogeneity was explored graphically and by comparing fits of study-homogenous 'fixed effects' and -heterogeneous 'random effects' models. Data were synthesized using these models. Sensitivity analysis for uncertainty regarding data abstraction, bias assessment and included studies was performed.

Principal findings: Variability between the incidences obtained from 20 studies is unlikely to be due to study groups living in different environments (tropical versus temperate climate, slums versus middle-class suburban populations), nor due to the year the study was conducted (from 1967 to 2003). A random effects model was used to incorporate unexplained heterogeneity and resulted in a global incidence estimate of 0.31 [0.19; 0.50] symptomatic RV infections per personyear of observation for children below 2 years of age, and of 0.24 [0.17; 0.34] when excluding the extreme high value of 0.84 reported for Mayan Indians in Guatemala. Apart from the inclusion/exclusion of the latter study, results were robust.

Conclusions/significance: Rather than assumptions based on an ad-hoc selection of one or two studies, these pooled estimates (together with the measure for variability between populations) should be used as an input in future cost-effectiveness analyses of RV vaccination.

Figure 1. Flow diagram of the studies reviewed.

Figure 2. Incidence of symptomatic RV infections in children below age 2 for the 20 eligible studies.

Forest plot showing incidence (number of symptomatic RV infections per personyear of observation; boxes) and 95% credible intervals (horizontal lines), obtained from studies which were evaluated to be at respectively no high risk of bias (‘no bias’), possible high risk of bias (‘possible bias’), and high risk of bias (‘bias’). The size of each box is proportionate to the person-years of observation from each study.

Figure 3. Incidence of symptomatic RV infections by age (in years) obtained from different studies.

Incidence is number of symptomatic RV infections per personyear of observation. Black, grey and white bars represent incidences for children in their first, second and third year of life, respectively.

Figure 4. Impact of excluding any particular study from meta-analysis.

Impact on the pooled estimate for the incidence of symptomatic RV infections in children below 2 years of age. Squares and horizontal lines represent means and 95% credible intervals of the pooled estimates. Only studies without high risk of bias are considered.

Figure 5. Impact of including/excluding studies from meta-analysis with possible high risk of bias, high risk of bias and the Mata et al paper.

Impact on the pooled estimate for incidence of symptomatic RV infections for children below 2 years of age. Squares and horizontal lines represent means and 95% credible intervals of the pooled estimates. Ho = study-homogeneous model, He = study-heterogeneous model, NR = only studies with no high risk of bias included, NPR = studies with no or possible high risk of bias included, ALL = studies with no, possible or high risk of bias included, n = number of studies included in meta-analysis.