• Burden of rotavirus disease in young children in Iceland - Time to vaccinate?

      Kristinsdottir, Iris; Haraldsson, Asgeir; Löve, Arthur; Asgeirsdottir, Tinna Laufey; Thors, Valtyr; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Children's Hospital Iceland, Landspitali University Hospital, Reykjavik, Iceland. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Clinical Microbiology, Division of Virology, Landspitali University Hospital, Reykjavik, Iceland. 3Faculty of Economics, University of Iceland, Reykjavik, Iceland. 4Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Children's Hospital Iceland, Landspitali University Hospital, Reykjavik, Iceland. Electronic address: valtyr@landspitali.is. (Elsevier, 2021-08-09)
      Background: Acute gastroenteritis poses a significant burden on young children, families, health care facilities and societies. Rotavirus is the most common pathogen, but rotavirus infections are vaccine preventable. Information on the epidemiology of gastroenteritis in Icelandic children has until now not been available and rotavirus vaccination is currently not offered to Icelandic infants. The objective of this study was to assess the burden of rotavirus acute gastroenteritis in young children in Iceland and determine the potential benefit of adding rotavirus vaccine to the Icelandic childhood immunization schedule. Methods: For a two-year period, children < 6 years old attending a children's emergency department for acute gastroenteritis were recruited at the Children's Hospital in Reykjavík, Iceland. Demographic information and Vesikari scores were registered. Stool samples were analyzed for pathogens. Duration of symptoms, treatment given, and secondary household infections were among the collected information. Annual cost of the infections in young children was estimated based on health care expenditures and lost days of parental work. Results: 325 children were included in the study, 75% of which were ≤ 24 months old. A pathogen was identified in 80% of cases, of which rotavirus was identified in 54%. Rotavirus caused a more severe disease than other pathogens, more often leading to fluid treatment in the emergency department and admissions. Median duration of rotavirus-illness was six days and caused a median of four days lost from work by parents. The estimated annual cost of rotavirus acute gastroenteritis was €2.9 million. Conclusions: Rotavirus causes significant disease burden in young children. Although rarely life-threatening in high income countries, the costs for society are substantial. The inclusion of rotavirus vaccine in the national immunization schedule will reduce the disease burden and would be cost-saving in Iceland.
    • Challenges in early clinical development of adjuvanted vaccines.

      Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David; [ 1 ] GlaxoSmithKline, I-53100 Siena, Italy [ 2 ] Natl Univ Hosp Reykjavik, Landspitali, IS-101 Reykjavik, Iceland [ 3 ] Univ Iceland, IS-101 Reykjavik, Iceland [ 4 ] Univ Surrey, Clin Res Ctr, Guildford CU2 7XP, Surrey, England (Elsevier, 2015-06-08)
      A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.
    • Decreased immune response to pneumococcal conjugate vaccine after 23-valent pneumococcal polysaccharide vaccine in children.

      Sigurdardottir, Sigurveig Th; Center, Kimberly J; Davidsdottir, Katrin; Arason, Vilhjalmur A; Hjalmarsson, Bjorn; Elisdottir, Ragnheidur; Ingolfsdottir, Gunnhildur; Northington, Robert; Scott, Daniel A; Jonsdottir, Ingileif; et al. (Elsevier Science Ltd., 2014-01-09)
      Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series.
    • Impact of the 10-valent pneumococcal conjugate vaccine on hospital admissions in children under three years of age in Iceland.

      Sigurdsson, Samuel; Eythorsson, Elias; Erlendsdóttir, Helga; Hrafnkelsson, Birgir; Kristinsson, Karl G; Haraldsson, Ásgeir; 1University of Iceland, Faculty of Medicine, Iceland. 2University of Iceland, Faculty of Medicine, Iceland; Department of Clinical Microbiology, Landspítali University Hospital, Iceland. 3Department of Mathematics, University of Iceland, Iceland. 4University of Iceland, Faculty of Medicine, Iceland; Children's Hospital Iceland, Landspítali University Hospital, Iceland. Electronic address: asgeir@lsh.is. (Elsevier, 2020-02-13)
      Introduction: Pneumococcus is an important respiratory pathogen. The 10-valent pneumococcal vaccine (PHiD-CV) was introduced into the Icelandic vaccination programme in 2011. The aim was to estimate the impact of PHiD-CV on paediatric hospitalisations for respiratory tract infections and invasive disease. Methods: The 2005-2015 birth-cohorts were followed until three years of age and hospitalisations were recorded for invasive pneumococcal disease (IPD), meningitis, sepsis, pneumonia and otitis media. Hospitalisations for upper- and lower respiratory tract infections (URTI, LRTI) were used as comparators. The 2005-2010 birth-cohorts were defined as vaccine non-eligible cohorts (VNEC) and 2011-2015 birth-cohorts as vaccine eligible cohorts (VEC). Incidence rates (IR) were estimated for diagnoses, birth-cohorts and age groups, and incidence rate ratios (IRR) between VNEC and VEC were calculated assuming Poisson variance. Cox regression was used to estimate the hazard ratio (HR) of hospitalisation between VNEC and VEC. Results: 51,264 children were followed for 142,315 person-years, accumulating 1,703 hospitalisations for the respective study diagnoses. Hospitalisations for pneumonia decreased by 20% (HR 0.80, 95%CI:0.67-0.95) despite a 32% increase in admissions for LRTI (HR 1.32, 95%CI:1.14-1.53). Hospital admissions for culture-confirmed IPD decreased by 93% (HR 0.07, 95%CI:0.01-0.50) and no hospitalisations for IPD with vaccine-type pneumococci were observed in the VEC. Hospitalisations for meningitis and sepsis did not change. A decrease in hospital admissions for otitis media was observed, but did not coincide with PHiD-CV introduction. Conclusion: Following the introduction of PHiD-CV in Iceland, hospitalisations for pneumonia and culture confirmed IPD decreased. Admissions for other LRTIs and URTIs increased during this period.
    • International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease.

      Gladstone, R A; Siira, L; Brynildsrud, O B; Vestrheim, D F; Turner, P; Clarke, S C; Srifuengfung, S; Ford, R; Lehmann, D; Egorova, E; et al. (Elsevier, 2022-01-05)
      Background: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. Methods: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. Results: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017. Conclusion: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination. Keywords: Molecular epidemiology; Outbreak; PCVs; PPV23; Pneumococcal; ST801; Serotype 4; Streptococcus pneumoniae; Whole genome sequencing.
    • Meningococcal serogroup C polysaccharide specific memory B cells, directly enumerated by labeled polysaccharide, are not affected by age at vaccination

      Henneken, Maren; Burdin, Nicolas; Thoroddsen, Einar; Sigurdardottir, Sigurveig Th; Trannoy, Emanuelle; Jonsdottir, Ingileif; Department of Immunology, Landspitali-University Hospital, Reykjavik, Iceland. (2010-02-25)
      The influence of age on the generation and persistence of specific memory B cells after vaccination with Neisseria meningitidis type C polysaccharide (MenC-PS) conjugate is unknown. MenC-PS-specific B cells could be directly enumerated by fluorochrome-labeled MenC-PS and flow cytometry in blood up to at least 4 years after vaccination, ranging from 0.01% to 0.78% of total B cells and did not correlate with age at vaccination. The percentage of MenC-specific memory B cells out of total memory B cells correlated with total MenC-specific B-cells and with frequencies of IgA(+) plus IgG(+) MenC-specific AbSC, but not with MenC-specific Ab.
    • Neonatal immune response and serum bactericidal activity induced by a meningococcal conjugate vaccine is enhanced by LT-K63 and CpG2006

      Brynjolfsson, Siggeir F; Bjarnarson, Stefania P; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif; Landspitali, Department of Immunology, Reykjavik, Iceland; University of Iceland, Faculty of Medicine, Reykjavik, Iceland. (Elsevier Science, 2008-08-18)
      Neonates have a poorly developed immune system. Therefore it is important to develop vaccination strategies that induce protective immunity and immunological memory against pathogens early in life. The immunogenicity of a meningococcal serogroup C polysaccharide conjugate (MenC-CRM(197)) was assessed in neonatal mice, and effects of LT-K63 and CpG2006 and immunisation routes were compared. Neonatal mice were primed subcutaneously (s.c.) or intranasally (i.n.) with MenC-CRM(197) with or without LT-K63 or CpG2006 and re-immunised 16 and 30 days later by the same route and formulation. Antibody levels were measured and generation of immunological memory assessed by affinity maturation and kinetics of the Ab response. Serum bactericidal activity (SBA) was measured to evaluate protective efficacy. The second and third dose of MenC-CRM(197) mixed with either LT-K63 or CpG2006 induced a rapid increase in MenC-specific IgG antibodies, to levels higher than elicited by MenC-CRM(197) alone (P<0.01) and in unimmunised mice (P<0.001), indicating efficient generation of memory by priming through both s.c. and i.n. routes. SBA was detected after three s.c. immunisations with MenC-CRM(197) s.c. alone. However, only two doses of MenC-CRM(197)+LT-K63 or MenC-CRM(197)+CpG2006 were needed to induce SBA levels>16. LT-K63 and CpG2006 enhanced neonatal antibody responses, affinity maturation, immunological memory to the conjugate MenC-CRM(197) and protective immunity. These results encourage the development of neonatal vaccination strategies to induce protective immunity and immunological memory against meningococcal disease.
    • Pneumococcal vaccination: Direct and herd effect on carriage of vaccine types and antibiotic resistance in Icelandic children.

      Sigurdsson, Samuel; Erlendsdóttir, Helga; Quirk, Sigríður Júlía; Kristjánsson, Júlíus; Hauksson, Kristján; Andrésdóttir, Birta Dögg Ingudóttir; Jónsson, Arnar Jan; Halldórsson, Kolbeinn Hans; Sæmundsson, Árni; Ólason, Óli Hilmar; et al. (Elsevier Science Ltd., 2017-09-18)
      Since the introduction of pneumococcal conjugate vaccines, vaccine type pneumococcal carriage and disease has decreased world-wide. The aim was to monitor changes in the nasopharyngeal carriage of pneumococci, the distribution of serotypes and antimicrobial resistance in children before and after initiation of the 10-valent pneumococcal vaccination in 2011, in a previously unvaccinated population.
    • Public opinion on childhood immunisations in Iceland.

      Óskarsson, Ýmir; Guðnason, Þórólfur; Jónsdóttir, Guðbjörg A; Kristinsson, Karl G; Briem, Haraldur; Haraldsson, Ásgeir; [ 1 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 2 ] Directorate Hlth Chief Epidemiologist, Reykjavik, Iceland [ 3 ] Univ Iceland, Social Sci Res Inst, Reykjavik, Iceland [ 4 ] Landspitali Univ Hosp, Dept Microbiol, IS-101 Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 5 ] Landspitali Univ Hosp, Childrens Hosp Iceland, IS-101 Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital (Elsevier SCI, 2015-12-16)
      In recent years, vaccine preventable diseases such as measles and pertussis have been re-emerging in Western countries, maybe because of decreasing participation in childhood vaccination programs in some countries. There is clear evidence for vaccine efficacy and the risk of adverse effects is low. This needs to be communicated to the general public. The aim of the study was to evaluate the public opinion on childhood vaccinations in Iceland.
    • Safety and immunogenicity of CRM197-conjugated pneumococcal-meningococcal C combination vaccine (9vPnC-MnCC) whether given in two or three primary doses

      Sigurdardottir, Sigurveig Th; Davidsdottir, Katrin; Arason, Vilhjalmur A; Jonsdottir, Olof; Laudat, France; Gruber, William C; Jonsdottir, Ingileif; Department of Immunology, Landspitali University Hospital, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Elsevier Science, 2008-08-05)
      This randomized trial compares safety and immunogenicity when vaccinating infants with a pneumococcal-meningococcal conjugate vaccine in two doses vs. three doses. Infants (N=223) received 9vPnC-MnCC (CRM197-conjugated pneumococcal serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F and meningococcal C polysaccharides) either at 3 and 5 or 3, 4 and 5 months and a booster with either 9vPnC-MnCC or 23-valent pneumococcal-polysaccharide vaccine (23vPPS) and CRM197-MnCC, at 12 months. Safety was monitored and IgG measured at 3, 6, 12 and 13 months in all subjects and serum bactericidal activity (SBA) in half. The 9vPnC-MnCC vaccine was safe and induced significant IgG to all components. Three doses induced higher antibody GMCs (geometric mean concentrations) at 6 months to seven of nine pneumococcal serotypes. This was most significant for 6B and 23F (p<0.001), that also showed lower rate of responders >0.35 (6B, 23F) and >0.5mug/mL (6B). Antibody GMCs remained lower following 9vPnC-MnCC booster in subjects primed with two doses although only significant for serotype 18C. Significant memory responses were observed 1 week after the 23vPPS toddler dose. MnCC-IgG GMC was lower after two doses, however with comparable SBA. This study shows that the 9vPnC-MnCC vaccine is safe and induces successful immunological memory, whether given in two or three primary doses.