Infections associated with varicella-zoster virus in Norway: disease burden and healthcare resource utilization

Nearly everybody is infected with varicella zoster virus (VZV), which causes varicella (chickenpox) and herpes zoster (shingles) (HZ). Varicella is usually a benign, but very itchy skin disease, predominantly occurring in childhood. HZ is a painful skin disease mainly affecting adults >50 years old. Both diseases can lead to serious complications. The burden of varicella and HZ is substantial and could be prevented by vaccination. Despite the availability of safe and efficacious vaccines, Norway currently does not implement vaccination programs against varicella and HZ. The aims of the thesis were to characterize the healthcare burden of varicella and HZ in Norway in the pre-vaccine era by estimating rates of primary- and hospital care cases and assessing the levels of immunity against VZV in general population and among pregnant women. This aims to inform the national policy decision on the use of varicella and HZ vaccines, and guide current screening policies for varicella in obstetric populations. Only 73% of the Norwegian population had immunity against VZV compared to >90% reported in most European countries. In addition, a small proportion of pregnant Norwegian women who were not immune to VZV got infected during their pregnancies, thereby increasing the risk of unfavourable health outcomes for themselves and for their offspring. The data from national health registries showed that 10,881 varicella patients and 11,181 HZ patients were treated annually in primary care. Moreover, 361 varicella patients and 1,218 HZ patients were hospitalized annually. At least 47% of hospitalized HZ cases had complications. Very few patients were vaccinated against varicella and none against HZ during the study period 2008-2014. Varicella and HZ cause considerable healthcare burden in Norway. There is an urgent need to develop robust knowledge-based national vaccine recommendations for both diseases and revise screening guidelines for VZV susceptibility in pregnancy

The burden of herpes zoster disease in Norway

Background No national vaccination program against herpes zoster (HZ) is currently in place in Norway. We aimed to quantify the burden of medically attended HZ to assess the need for a vaccination program. Methods We linked data from several health registries to identify medically attended HZ cases during 2008–2014 and HZ-associated deaths during1996–2012 in the entire population of Norway. We calculated HZ incidences for primary and hospital care by age, sex, type of health encounter, vaccination status, and co-morbidities among hospital patients. We also estimated HZ-associated mortality and case-fatality. Results The study included 82,064 HZ patients, of whom none were reported as vaccinated against HZ. The crude annual incidence of HZ was 227.1 cases per 100,000 in primary healthcare and 24.8 cases per 100,000 in hospitals. Incidence rates were higher in adults aged ≥50 years (461 per 100,000 in primary care and 57 per 100,000 in hospitals), and women than in men both in primary healthcare (267 vs 188 per 100,000), and hospitals (28 vs 22 per 100,000). Among hospital patients, 47% had complicated zoster and 25% had comorbidities, according to the Charlson comorbidity index. The duration of hospital stay (median 4 days) increased with the severity of comorbidities. The estimated mortality rate was 0.18 per 100,000; and in-hospital case-fatality rate was 1.04%. Conclusions Medically attended HZ poses a substantial burden in the Norwegian healthcare sector. The majority of the zoster cases occurred among adults aged ≥50 years – the group eligible for zoster vaccination – and increased use of zoster vaccination may be warranted, especially among persons with co-morbidities

Modeling the impact of combined vaccination programs against varicella and herpes zoster in Norway

Background: Adoption of varicella immunization in Europe is limited due to a predicted increase in the incidence of herpes zoster (HZ) resulting from a removal of exogenous boosting by varicella vaccination. Most available assessments of immunization strategies only considered universal varicella vaccination (alone or in combination with HZ by the live vaccine). The development of a new subunit recombinant zoster vaccine may provide new perspectives of HZ control. Methods: We used a mathematical model for VZV in Norway based on the progressive immunity formulation of exogenous boosting. We evaluated a complete range of alternative immunization options against varicella and HZ including both universal and targeted varicella vaccination, either alone or with zoster immunization, and zoster immunization alone. We considered all values of the boosting intensity consistent with the Norwegian HZ incidence and compared the performance of the currently available live vaccine vs. a new recombinant vaccine. Results: Universal varicella vaccination alone resulted in a marked increase in the incidence of HZ under all scenarios considered. Even under the most favorable hypotheses on the magnitude of the boosting intensity, this increase could be mitigated only by a parallel HZ immunization with a recombinant vaccine, assuming a long duration of protection. Targeted varicella immunization of adolescents resulted in a modest increase in the HZ incidence which could be counterbalanced by both the live and, especially, the recombinant vaccine. Conclusions: Given current knowledge on HZ pathogenesis and exogenous boosting, targeted varicella vaccination of adolescents was the only strategy that was not predicted to impact the epidemiology of HZ, and therefore it may represent a suitable alternative to universal vaccination. These results are aimed to support vaccine policy decisions in Norway and other countries with a similar VZV epidemiolog

Immunity to varicella zoster virus among pregnant women in the Norwegian Mother and Child Cohort Study

Infection with varicella zoster virus (VZV) in pregnancy may lead to serious outcomes both for the mother and the newborn. Targeted screening and vaccination of non-immune women during reproductive age could prevent varicella infection in pregnancy. Currently, no universal varicella screening of pregnant women is implemented in Norway, but serological testing in pregnancy is recommended in particular situations. We examined seroprevalence of VZV in a national pregnancy cohort in order to help assess a need for VZV screening of women during reproductive age. Methods We determined the susceptibility to VZV and the reliability of self-reported history of VZV infection in the Norwegian obstetric population by using a random sample of 1,184 pregnant women from the Norwegian Mother and Child Cohort study (MoBa). The MoBa study included approximately 95,200 pregnant women in Norway between 1998 and 2009. Blood samples taken at gestational week 17–18 were analysed using a commercial enzyme immunoassay for specific IgG antibodies to Varicella-Zoster virus. Second sample taken at birth was tested if the first sample result was negative or equivocal. Results Of the 1,184 pregnant women, 98.6% (n = 1,167) were seropositive, 0.83% (n = 10) remained seronegative, and four women (0.34%) seroconverted during their pregnancy. No significant associations were found between serological status and women’s age at birth, gestational age, women’s country of birth and year of child’s birth. One woman reported prior history of varicella, whereas 143 (12.1%) women reported a household exposure to childhood diseases with fever and rash, of which 25 reported exposure to varicella, of which all were seropositive. Conclusions The findings support antenatal screening recommendations in Norway advising testing for VZV in pregnant women with unknown immunity to VZV. Further studies are however needed to better identify target groups for screening and vaccination

The natural history of VZV in Norway.

<p>Pattern of the AIC for some alternative models for the reactivation risk, for different levels of the boosting constant z. The underlying transmission model (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176845#pone.0176845.t002" target="_blank">Table 2</a>) is based on the synthetic matrix, hypothesis Q₃, 16.</p

The different hypotheses about the VZV reactivation rate.

<p>The different hypotheses about the VZV reactivation rate.</p

Predicted age-specific varicella incidence.

<p>Predicted age-specific varicella incidence.</p

Estimation of the burden of varicella in Europe before the introduction of universal childhood immunization

Varicella is generally considered a mild disease. Disease burden is not well known and country-level estimation is challenging. As varicella disease is not notifiable, notification criteria and rates vary between countries. In general, existing surveillance systems do not capture cases that do not seek medical care, and most are affected by underreporting and underascertainment. We aimed to estimate the overall varicella disease burden in Europe to provide critical information to support decision-making regarding varicella vaccination

The natural history of VZV in Norway: Fit to seroprevalence data and force of infection.

<p>Top row: results from model Q₃,16 based on the synthetic matrix; bottom row: results from model Q₀ based on the Polymod matrix of close contacts. Left: predicted vs observed varicella age-specific sero-prevalence, with 95% confidence bands. Center: predicted age-specific varicella FOI with 95% confidence bands. Right: best R₀ estimate, related distribution of bootstrap estimates and 95% percentile CI. For sake of comparison between models based on synthetic matrices (based on census data, and therefore lacking an uncertainty evaluation) vs models based on Polymod matrices (based on survey data), the bootstrap was done by re-sampling sero-prevalence data only.</p