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"de Blasio, Birgitte Freiesleben"
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Pertussis epidemiology including direct and indirect effects of the childhood pertussis booster vaccinations, Norway, 1998–2019
by
Greve-Isdahl, Margrethe
,
Bøås, Håkon
,
Steens, Anneke
in
Adolescent booster
,
Adults
,
Age groups
2022
•School-age and adolescent boosters protect targeted age groups against pertussis.•Pertussis incidence among infants remained unchanged since introduction of boosters.•Boosters may have offered indirect protection among adults.•Recent increases in incidence among children warrant evaluation of vaccination schedule.
The acellular pertussis vaccine has been used in the Norwegian national immunisation program since 1998. Following an increase in pertussis incidence in all age groups, booster doses were introduced for 7–8-year-olds in 2006, and for 15–16-year-olds in 2013. We assessed the effects of the booster doses on pertussis incidence in different age groups to inform potential changes in vaccination policy.
We included all pertussis cases notified to the Norwegian Surveillance System for Communicable Diseases in 1998–2019. We calculated annual incidence rates (IR, per 100,000 inhabitants) by age group. We estimated average annual changes in IRs (incidence rate ratios, IRR) for each age group for 2006–2012 and 2013–2019 using Poisson regression.
In 1998–2019, 74,675 cases of pertussis were notified. Coinciding with booster introduction, between 2006 and 2012 the IR decreased among 8–15-year-olds (from 433 to 199/100,000, IRR 0.89 [95% confidence interval 0.88–0.90]). A similar decrease was seen between 2013 and 2019 among 16–19-year-olds (from 171 to 77/100,000, IRR 0.84 [0.82–0.86]). There was no significant change in IRs among children < 1 year of age between 2006 and 2012 (IRR 0.99 [0.95–1.04]) or 2013–2019 (IRR 0.96 [0.91–1.02]). The IR decreased in both periods among adults aged 20–39 and 40+ (IRR 0.94 [0.93–0.95] and 0.92 [0.91–0.92] in 2006–2012; IRR 0.97 [0.96–0.99] and 0.97 [0.96–0.99] in 2013–2019, respectively). Despite steady, high vaccination coverage, in 2013–2019, there was an increase in the IR among children aged 1–7 (63 to 86/100,000, IRR 1.05 [1.03–1.07]) and 8–15 years (88 to 122/100,000, IRR 1.08 [1.06–1.10]).
Pertussis booster doses have offered direct protection in the targeted age groups. Our findings suggest indirect protection in adults, while the incidence in infants hasn’t changed. The recent increase in IRs among 1–15-year-olds warrants close monitoring and further evaluation of the vaccination schedule.
Journal Article
Effect of Vaccines and Antivirals during the Major 2009 A(H1N1) Pandemic Wave in Norway – And the Influence of Vaccination Timing
by
Scalia Tomba, Gianpaolo
,
Freiesleben de Blasio, Birgitte
,
Iversen, Bjørn G.
in
Adjuvants, Immunologic - administration & dosage
,
Adolescent
,
Adult
2012
To evaluate the impact of mass vaccination with adjuvanted vaccines (eventually 40% population coverage) and antivirals during the 2009 influenza pandemic in Norway, we fitted an age-structured SEIR model using data on vaccinations and sales of antivirals in 2009/10 in Norway to Norwegian ILI surveillance data from 5 October 2009 to 4 January 2010. We estimate a clinical attack rate of approximately 30% (28.7-29.8%), with highest disease rates among children 0-14 years (43-44%). Vaccination started in week 43 and came too late to have a strong influence on the pandemic in Norway. Our results indicate that the countermeasures prevented approximately 11-12% of potential cases relative to an unmitigated pandemic. Vaccination was found responsible for roughly 3 in 4 of the avoided infections. An estimated 50% reduction in the clinical attack rate would have resulted from vaccination alone, had the campaign started 6 weeks earlier. Had vaccination been prioritized for children first, the intervention should have commenced approximately 5 weeks earlier in order to achieve the same 50% reduction. In comparison, we estimate that a non-adjuvanted vaccination program should have started 8 weeks earlier to lower the clinical attack rate by 50%. In conclusion, vaccination timing was a critical factor in relation to the spread of the 2009 A(H1N1) influenza. Our results also corroborate the central role of children for the transmission of A(H1N1) pandemic influenza.
Journal Article
The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster
by
Mirinaviciute, Grazina
,
Marangi, Luigi
,
Scalia Tomba, Gianpaolo
in
Activation
,
Adolescent
,
Adult
2017
We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3-5 yrs) and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation.
Journal Article
Short-lived immunity against pertussis, age-specific routes of transmission, and the utility of a teenage booster vaccine
by
de Blasio, Birgitte Freiesleben
,
Storsaeter, Jann
,
Bjørnstad, Ottar N.
in
Adolescent
,
adolescents
,
Adult
2012
► Immunity against pertussis is relatively short-lived and heterogeneous. ► Vaccination prevents both disease and transmission. ► The age-mixing patterns lead to little contact between teenagers and infants. ► A teenage booster vaccine will not likely indirectly protect infants.
Pertussis incidence has been increasing for the past two decades in Norway, as in much of the highly vaccinated world. The greatest increase is in teenagers, although the most severe cases occur in infants. A teenage booster is recommended globally, largely with the aim of reducing infant incidence. However few countries have implemented the booster, and almost no data have been published on its utility in preventing infant cases. We aim to assess the duration of vaccine-induced immunity, and the possibility for a teenage-booster vaccine to protect infants in Norway.
We used a unique data set that merged case reports with a national vaccine registry from Norway, 1996–2010, to assess age- and cohort-specific hazards of infection. We also developed and implemented a likelihood-based method for estimating the duration of immunity, taking into account age-contact data relevant for pertussis transmission. The risk of infection in thirteen-year olds increased nearly four-fold, however the hazard in infants did not significantly change. The seasonality of cases in pre-school-aged children differed from that of school-aged children. The introduction of a childhood booster vaccine provided indirect protection for unvaccinated members of the cohort, but little protection to neighboring cohorts. Additionally, we found evidence for increasingly rapid infection after three doses of vaccine, potentially caused by significant and heterogeneous loss of immunity. An estimated 15% of vaccinated individuals lost their immunity within five years after vaccination.
Immunity induced by the acellular pertussis vaccine prevents both disease and transmission, but is short-lived and heterogeneous. The age-mixing patterns lead to little contact between teenagers and infants. Therefore, while a teenage booster vaccine campaign would likely provide strong protection for cohorts of teenagers, it would provide little protection for infants.
Journal Article
A theoretical single-parameter model for urbanisation to study infectious disease spread and interventions
by
Freiesleben de Blasio, Birgitte
,
Engebretsen, Solveig
,
Engø-Monsen, Kenth
in
Algorithms
,
Biology and Life Sciences
,
Cluster Analysis
2019
The world is continuously urbanising, resulting in clusters of densely populated urban areas and more sparsely populated rural areas. We propose a method for generating spatial fields with controllable levels of clustering of the population. We build a synthetic country, and use this method to generate versions of the country with different clustering levels. Combined with a metapopulation model for infectious disease spread, this allows us to in silico explore how urbanisation affects infectious disease spread. In a baseline scenario with no interventions, the underlying population clustering seems to have little effect on the final size and timing of the epidemic. Under within-country restrictions on non-commuting travel, the final size decreases with increased population clustering. The effect of travel restrictions on reducing the final size is larger with higher clustering. The reduction is larger in the more rural areas. Within-country travel restrictions delay the epidemic, and the delay is largest for lower clustering levels. We implemented three different vaccination strategies-uniform vaccination (in space), preferentially vaccinating urban locations and preferentially vaccinating rural locations. The urban and uniform vaccination strategies were most effective in reducing the final size, while the rural vaccination strategy was clearly inferior. Visual inspection of some European countries shows that many countries already have high population clustering. In the future, they will likely become even more clustered. Hence, according to our model, within-country travel restrictions are likely to be less and less effective in delaying epidemics, while they will be more effective in decreasing final sizes. In addition, to minimise final sizes, it is important not to neglect urban locations when distributing vaccines. To our knowledge, this is the first study to systematically investigate the effect of urbanisation on infectious disease spread and in particular, to examine effectiveness of prevention measures as a function of urbanisation.
Journal Article
Modeling geographic vaccination strategies for COVID-19 in Norway
by
Rø, Gunnar
,
Chan, Louis Yat Hin
,
Kristoffersen, Anja Bråthen
in
Aged
,
Biology and Life Sciences
,
Computer industry
2024
Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.
Journal Article
Analysis of multi-level spatial data reveals strong synchrony in seasonal influenza epidemics across Norway, Sweden, and Denmark
by
Viboud, Cécile
,
Freiesleben de Blasio, Birgitte
,
Wesolowski, Amy
in
Analysis
,
Archives & records
,
Climate
2018
Population structure, spatial diffusion, and climatic conditions mediate the spatiotemporal spread of seasonal influenza in temperate regions. However, much of our knowledge of these dynamics stems from a few well-studied countries, such as the United States (US), and the extent to which this applies in different demographic and climatic environments is not fully understood. Using novel data from Norway, Sweden, and Denmark, we applied wavelet analysis and non-parametric spatial statistics to explore the spatiotemporal dynamics of influenza transmission at regional and international scales. We found the timing and amplitude of epidemics were highly synchronized both within and between countries, despite the geographical isolation of many areas in our study. Within Norway, this synchrony was most strongly modulated by population size, confirming previous findings that hierarchical spread between larger populations underlies seasonal influenza dynamics at regional levels. However, we found no such association when comparing across countries, suggesting that other factors become important at the international scale. Finally, to frame our results within a wider global context, we compared our findings from Norway to those from the US. After correcting for differences in geographic scale, we unexpectedly found higher levels of synchrony in Norway, despite its smaller population size. We hypothesize that this greater synchrony may be driven by more favorable and spatially uniform climatic conditions, although there are other likely factors we were unable to consider (such as reduced variation in school term times and differences in population movements). Overall, our results highlight the importance of comparing influenza spread at different spatial scales and across diverse geographic regions in order to better understand the complex mechanisms underlying disease dynamics.
Journal Article
Estimating Age-Specific Immunity and Force of Infection of Varicella Zoster Virus in Norway Using Mixture Models
by
Freiesleben de Blasio, Birgitte
,
Manfredi, Piero
,
Scalia Tomba, Gianpaolo
in
Adults
,
Analysis
,
Biology and life sciences
2016
This study applies mixture modelling to examine age-specific immunity to varicella zoster virus (VZV) infection in Norway based on the first large-scale serological study in the general population. We estimated the seropositive proportions at different ages and calculated the underlying force of infection by using a sample of 2103 residual sera obtained from patients seeking primary and hospital care. A rapid increase in the VZV-associated immunity is observed in the first years of life with 63% of children being immune by age 5. The increase in the immunity levels slows down thereafter, with a large proportion of adults still susceptible by age 20 (around 14.5%), thus at risk of serious sequelae of varicella infection. The corresponding force of infection peaks during the preschool period, subsequently declines to a minimum between ages 10 and 20 years, and afterwards moderately increases to reach a plateau lasting throughout the childbearing period. In comparison with the traditional cut-off approach, mixture modelling used the whole data without producing any inconclusive cases, led to an unbiased classification of individuals between susceptible and immune, and provided a smoother immune profile by age. These findings represent an important step towards any decision about the introduction of varicella vaccination in Norway, as they are a primary input for mathematical transmission models aimed at evaluating potential vaccination scenarios.
Journal Article
Assessment of Coronavirus Disease 2019 Intervention Strategies in the Nordic Countries Using Genomic Epidemiology
by
Pettersson, John H O
,
Freiesleben de Blasio, Birgitte
,
Holmes, Edward C
in
Brief Report
,
COVID-19
,
Editor's Choice
2022
Abstract
We explored how the duration, size, and number of virus transmission clusters, defined as country-specific monophyletic groups in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogenetic tree, differed among the Nordic countries of Norway, Sweden, Denmark, Finland, and Iceland. Our results suggest that although geographical connectivity, population density, and openness influence the spread and the size of SARS-CoV-2 transmission clusters, the different country-specific intervention strategies had the largest impact. We also found a significant positive association between the size and duration of transmission clusters in the Nordic countries, suggesting that the rapid deployment of contact tracing is a key response measure in reducing virus transmission.
Genomic epidemiology of COVID-19 in the Nordic countries reveal substantial effect of country-specific intervention policies on SARS-CoV-2 evolution and transmission.
Journal Article
The Role of Polymorphonuclear Leukocyte Counts from Urethra, Cervix, and Vaginal Wet Mount in Diagnosis of Nongonococcal Lower Genital Tract Infection
by
Freiesleben de Blasio, Birgitte
,
Moghaddam, Amir
,
Randjelovic, Ivana
in
Adolescent
,
Adult
,
Antibiotics
2018
Objective. The aim of this study was to evaluate whether the polymorphonuclear leukocyte (PMNL) inflammatory response in women with nongonococcal lower genital tract infection (LGTI) can be used to optimize criteria for syndromic treatment. Methods. A cross-sectional study of 375 women attending the STI clinic in Oslo. Urethral, cervical, and vaginal specimens underwent microscopy for PMNLs. Chlamydia trachomatis (Ct) and other STIs were detected in the cervical/vaginal swabs and urine, using nucleic acid amplification test (NAAT). After excluding vulvovaginal candidiasis, genital herpes, and trichomoniasis, we correlated clinical and microscopic signs of inflammation with positive NAAT for Ct, mycoplasma genitalium (Mg), and Ureaplasma urealyticum (Uu) in a subgroup of 293 women. Results. To predict a positive Ct, the combination of high cut-off urethritis (≥10 PMNLs/HPF) and microscopic cervicitis had a high specificity of 0.93, a PPV of 0.37, and a sensitivity of 0.35. LGTI criteria had low predicting values for Mg and Uu. Conclusion. Including microscopic criteria for the diagnosis of LGTI gives better indication for presumptive antibiotic treatment than anamnestic and clinical diagnosis alone.
Journal Article