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      BMC Infectious Diseases

      Systematic Literature Review–Sybil Pinchinat, Ana M Cebrián-Cuenca, Hélène Bricout, Robert W JohnsonDisclosures
      BMC Infect Dis. 2013;13(170)

      The present literature review of HZ incidence in Europe showed similar HZ incidence across the included countries for which data was available. Overall annual HZ incidence varied from 2.0–4.6/1 000 PY depending on the country, which is consistent with previous published estimates,[43] and similar to those published in North America (1.25–3.7/1 000 PY[44,45]).

      Our review confirms that HZ incidence increases sharply with age, from around 1/1 000 children <10 years up to 10/1 000 people over 80 years of age. These results are consistent with recent published estimates by Volpi et al.[43] Annual HZ incidence in Europe has been reported as 0.3–0.74/1 000 children <10 years, 1.6/1 000 adults aged <40 years, 2.5/1 000 adults aged 20–50 years, 7.8/1 000 adults aged 60 years or over, and 10/1 000 in elderly adults over 80 years of age.[43]

      As expected, the same increase in incidence rates with age was observed in the studies included in this review that reported age-specific incidence (Figure 3). The correlation between age and HZ incidence may be related to a decreased cellular-mediated immune response to VZV as result of immunosenescence.[44,46] It has been suggested that exposure to varicella reduces the risk of VZV reactivation by boosting specific immunity to the virus.[38,47] This hypothesis is supported by some studies which showed that repeated familial or occupational exposure is associated with a reduced risk of HZ,[48–51] but others did not confirm this.[46,52]

      This review showed that incidence rates are systematically higher among women than men (male/female ratio around 1.4), and this difference increases with age, which has also been found in other studies.[41,53] Women over 50 years of age seem to be particularly at risk. However, it is unclear whether the risk of HZ is increased in all women. Women might simply be more likely to seek medical advice, thereby causing a higher reporting rate, or there may be some biological mechanism by which women are more susceptible to VZV reactivation.[54]

      Our review excluded studies limited to immunocompromised populations, or individuals with primary or acquired immunodeficiency status. Nevertheless, as included studies were population-based, some of them made a distinction between the total study population and the immunocompetent population.[25,29] This review confirms that immunocompetent patients are at lower risk of developing HZ than the general population.[25,29] The control of VZV reactivation depends on the maintenance of adequate levels of cellular-mediated immunity to VZV, which explains why cellular-mediated immune deficiency is a risk factor for developing HZ.[54]

      In Europe, not all countries have some form of surveillance in place for HZ[55,56] and there is marked heterogeneity in the type of HZ surveillance systems that do exist (national mandatory or sentinel), the type of data collected (case-based or aggregated) and the reported case classification (clinical and/or laboratory).[57] Most surveillance systems operate using reports of clinical cases.[57]

      This review highlights the need to identify standardized surveillance methods in order to improve data comparability within European Union Member States and, in the framework of introducing HZ vaccination, to monitor the impact of immunization on the epidemiology of HZ.

      Since most of the European studies in this review were performed and published in the last 10 years, it was difficult to look at a time trend variation in the risk of HZ. The only country (the UK) with two incidence rate estimates, which were about 30 years apart, provided two close figures: 3.40/1 000 people in 1975 vs. 3.73/1 000 people in 2000.[38,40] However, this comparison is delicate since the first study was retrospective [38] and the second prospective.[40]

      In the literature, there are conflicting data with regard to whether age-adjusted HZ incidence is changing over time.[7,58] Indeed, the literature fails to show evidence of any change of HZ incidence over time, notably in relation to varicella vaccination. Longitudinal data, including a few years of baseline before possible routine use of the varicella vaccine in children or adolescents, and a sufficient number of years of data to detect a trend (at least 3, preferably more) after the implementation of the vaccine will be needed to assess the impact of varicella vaccination on HZ incidence.[59] Such data are available from the US where varicella vaccination has been used routinely since 1995; however no clear conclusions were drawn on the impact on HZ incidence. Some authors did not observe any impact of varicella vaccination on HZ incidence [7,58] and others observed an increase.[60] Moreover, looking at a potential HZ incidence trend overtime is challenging and depends on the availability of baseline data collected using comparable study methods in populations with comparable health care behavior. Comparing results across studies and time periods must take into account different study methods and must adjust for changes in the age structure of the population over time. As the proportion of older people grows in Europe [61], HZ is likely to become a more important public health issue in the future. The apparently increasing proportion of immunocompromised persons due to medical conditions or medication in the population, and the effect this may have on HZ, must also be considered.

      This literature review has various limitations. First of all, this review included studies with different designs: direct prospective recruitment of patients with HZ in health care settings during a defined study period, and retrospective identification through medical files from a number of practitioners. In general, prospective recruitment methods are considered to be preferable, whereas retrospective recruitment poses some methodological problems regarding data quality and missing data. However, this was taken into account in the reading grid, which assigned a higher quality score to prospective studies than retrospective studies.

      Moreover, in spite of their potential shortcomings, some studies based on large databases (UK, Italy, Spain, Germany) were included in this review. It is true that in the past the methods used in population-based studies, such as those used to extrapolate results obtained from a single database to the entire North American population, have been criticized.[62] Indeed, in this case the fact that the denominator used was the total number of persons registered in the national health care system and was presented as exhaustive raised a methodological problem linked to the calculation of the HZ incidence rate. This was questionable since no information was given on the number of persons who were not registered, compared to the national census. In that case, the denominator was a surrogate for the true number and the calculated rate could have been over-estimated. Recently, Yawn et al. showed that administrative data use alone appears to overestimate the number of HZ cases,[53] and the potential coding error of HZ diagnosis in administrative data has also been investigated.[63]

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