Since the introduction of 10-valent pneumococcal conjugate vaccine (PCV10) into the Finnish national vaccination program in September 2010, the incidence of invasive pneumococcal disease in children ...has decreased steeply in Finland. We studied the antimicrobial susceptibility of invasive and non-invasive
Streptococcus pneumoniae
(pneumococcus) isolated in the Helsinki Metropolitan Area during 2009–2014. We divided the data into two age groups: isolates from patients <5 years old and ≥5 years old. We also studied the serotype distribution of invasive isolates and of a subset of non-invasive multidrug-resistant isolates. The invasive isolate numbers recovered from patients aged <5 years old declined from 33/228 (15%) in 2009 to 8/208 (4%) in 2014 (
p
< 0.001) and non-invasive isolate numbers declined during the same time period from 221/595 (37%) to 119/432 (28%) (
p
< 0.001). At the same time, the proportion of penicillin non-susceptible non-invasive isolates in this age group decreased from 25% (56/220) to 13% (15/119) (
p
= 0.001) and multidrug-resistant isolates from 22% (49/220) to 6% (7/119) (
p
< 0.001), respectively. The number of PCV10 serotype isolates also decreased among the serotyped multidrug-resistant non-invasive isolates. Among patients aged ≥5 years old, the isolate numbers did not show a similar decreasing trend compared to the younger group and, further, the number of non-PCV10 serotype isolates increased in invasive cases. To conclude, the antimicrobial non-susceptibility of pneumococcus has decreased markedly, especially among young patients (<5 years old), following PCV10 implementation in Finland.
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.
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.
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.
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.
Background. Bacterial, nonnecrotizing cellulitis is a localized and often recurrent infection of the skin. The aim of this study was to identify the β-hemolytic streptococci that cause acute ...nonnecrotizing cellulitis infection in Finland. Methods. A case-control study of 90 patients hospitalized for acute cellulitis and 90 control subjects was conducted during the period of April 2004–March 2005. Bacterial swab samples were obtained from skin lesions or any abrasion or fissured toe web. Blood culture samples were taken for detection of bacteremia. The patients, their household members, and control subjects were assessed for pharyngeal carrier status. β-Hemolytic streptococci and Staphylococcus aureus were isolated and identified, and group A and G streptococcal isolates were further analyzed by T serotyping and emm and pulsed-field gel electrophoresis typing. Results. β-Hemolytic streptococci were isolated from 26 (29%) of 90 patients, 2 isolates of which were blood-culture positive for group G streptococci, and 24 patients had culture-positive skin lesions. Group G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis) was found most often and was isolated from 22% of patient samples of either skin lesions or blood, followed by group A Streptococcus, which was found in 7% of patients. Group G streptococci were also carried in the pharynx of 7% of patients and 13% of household members but was missing from control subjects. Several emm and pulsed-field gel electrophoresis types were present among the isolates. Six patients (7%) had recurrent infections during the study. In 2 patients, the group G streptococcal isolates recovered from skin lesions during 2 consecutive episodes had identical emm and pulsed-field gel electrophoresis types. Conclusions. Group G streptococci, instead of group A streptococci, predominated in bacterial cellulitis. No clear predominance of a specific emm type was seen. The recurrent nature of cellulitis became evident during this study.
The expression of insulin-like growth factor II (IGF-II) was analysed immunohistochemically in a series of 211 breast cancers with special reference to standard prognostic factors and patient ...survival. IGF-II was expressed both in the cancer cells and in stromal cells, in 84% and 50% of cases, respectively. IGF-II expression in cancer cells was related to a non-metastatic disease at diagnosis (p = 0.03), low tumour grade (p = 0.02), DNA diploidy (p = 0.02) and S-phase fraction under 7% (p = 0.001). IGF-II negativity was positively correlated to morphometric SD of nuclear area (p = 0.0003), nuclear perimetry (p = 0.002), SD of nuclear perimetry (p = 0.02), minimum nuclear diameter (p = 0.005) and maximum nuclear diameter (p = 0.003). The expression of IGF-II in stromal cells was related to low histological grade (p = 0.02), mitotic index under 10/mm2 (p = 0.01), mild nuclear pleomorphism (p = 0.03), DNA diploidy (p = 0.08), SD of nuclear area (p = 0.006), mean nuclear perimeter (p = 0.05), minimum nuclear diameter (p = 0.005) and maximum nuclear diameter (p = 0.007) in that the nuclear factor values were higher in tumours without stromal IGF-II expression. In univariate and multivariate survival analysis, immunohisto-chemically detected expression of IGF-II had no independent prognostic value over standard prognostic factors. Despite the fact that expression of IGF-II was inversely related to several histopathological features of malignancy, the clinical behaviour of breast cancer seemed to be independent of IGF-II expression.
Neisseria meningitidis, an important cause of bacterial meningitis and septicemia worldwide, is associated with high mortality and serious sequelae. Natural immunity against meningococcal disease ...develops with age, but the specificity and functional activity of natural antibodies associated with protection are poorly understood. We addressed this question by using a selected subset of prevaccination sera (n = 26) with convergent or discrepant serum bactericidal activity (SBA) and infant rat protective activity (IRPA) against the serogroup B meningococcal strain 44/76-SL (B:15:P1.7,16) from Icelandic teenagers (B. A. Perkins et al., J. Infect. Dis. 177:683-691, 1998). The sera were analyzed by opsonophagocytic activity (OPA) assay, immunoblotting, immunoglobulin G (IgG) quantitation against live meningococcal cells by flow cytometry, and enzyme immunosorbent assay (EIA). High levels of SBA and OPA were reflected in distinct IgG binding to major outer membrane proteins and/or lipopolysaccharide in immunoblots. However, we could not detect any specific antibody patterns on blots that could explain IRPA. Only IgM antibody to group B capsular polysaccharide (B-PS), measured by EIA, correlated positively (r = 0.76, P < 0.001) with IRPA. Normal human sera (NHS; n = 20) from healthy Finnish children of different ages (7, 14, and 24 months and 10 years) supported this finding and showed an age-related increase in IRPA that coincided with the acquisition of B-PS specific IgM antibody. The protection was independent of complement-mediated bacterial lysis, as detected by the inability of NHS to augment SBA in the presence of human or infant rat complement and the equal protective activity of NHS in rat strains with fully functional or C6-deficient complement.
A total of 985 group A streptococcus (GAS) bacteraemia isolates collected in Finland during 1995-2004 were T-serotyped, and of these, 336 isolates of serotype T28 were subjected to further emm ...typing. The total number of isolates referred per year showed an increase within the study period, from 43 in 1995 to 130 in 2004. The annual incidence of invasive GAS (iGAS) bacteraemia showed a general increase during the study period, from 1.1 to 2.5 per 100 000 population. Serotype T28 remained among the most common serotypes, in addition to serotypes TB3264 and T1. The serotype T28 isolates were found to be distributed across six distinct emm types: emm28, emm77, emm53 (including subtypes 53.2 and 53.4), emm87, emm2 and emm4. The serotype distribution and the emm type distribution of serotype T28 fluctuated over time. Within the study period, the proportion of T28/emm28 isolates became the most prominent. During periods of low emm28 incidence, emm types 77 and 53 seemed to show a resurgence. emm typing revealed T28 isolates to be a genetically heterogeneous group harbouring a variety of distinct M proteins. This study confirms that T serotyping alone is not a sufficient method for epidemiological surveillance of iGAS.
The role of the N‐methyl‐d‐aspartate (NMDA) receptors in differential ethanol sensitivity of the alcohol‐insensitive alcohol‐tolerant (AT) and alcohol‐sensitive alcohol‐nontolerant (ANT) rat lines ...selected for low and high sensitivity to ethanol‐induced (2 g/kg) motor impairment was studied in behavioral and neurochemical experiments. A noncompetitive antagonist of the NMDA receptor, dirocilpine mal‐eate (MK‐801; 0.2 mg/kg), impaired motor function in ANT rats, but not in AT rats, in a tilting plane test. The impairment was further potentiated by a dose (0.75 glkg) of ethanol, which alone was inactive. This effect was apparently not associated with the locomotor stimulation produced by MK‐801 (0.1 and 0.2 mg/kg), because stimulation did not differ between the rat lines. Locomotor stimulation was potentiated by the low ethanol dose in both rat lines. Ethanol treatment decreased the cerebellar and hippocampal cGMP concentrations both with and without MK‐801 pretreatment in both rat lines. In situ hybridization using oligonucleotide probes specific for NMDA receptor subunit mRNAs NR1 and NR2A, B, C, and D revealed no clear differences in brain regional expression between ANT and AT rats. These results indicate that the alcohol‐sensitive ANT rats are very sensitive to a low dose of ethanol in the presence of NMDA receptor antagonism, consistent with the hypothesis that this receptor system is involved in acute ethanol intoxication.
From a previous published clinical trial among teenagers in Iceland Perkins BA, Jonsdottir K, Briem H, Griffiths E, Plikaytis BD, Høiby EA, et al. J Infect Dis 1998;177:683–91, we evaluated a 25% ...stratified subset of sera, collected before vaccination and 6 weeks after the second vaccination with either the Norwegian (
n
=
37) or the Cuban (
n
=
35) serogroup B meningococcal outer membrane vesicle (OMV) vaccine or the control serogroup A/C capsular polysaccharide vaccine (
n
=
20), for protective activity in an infant rat protection assay (IRPA). Protection was assessed with both the Norwegian (44/76-SL, B:15:P1.7,16:L3,7) and the Cuban (Cu385, B:4:P1.19,15:L3,7) vaccine strain, and the results compared with serum bactericidal assay (SBA) titres and anti-OMV IgG antibody concentrations. An IRPA response was defined as a ≥10-fold rise in protective activity compared to pre-vaccination level. Forty-six percent (42/92) of the pre-vaccination sera showed protection with strain 44/76-SL compared to only 12% (11/92) with strain Cu385. After the second dose, 22% (8/37) of those given the Norwegian vaccine showed IRPA responses with the homologous strain compared to 65% (24/37) in SBA. The corresponding numbers with the homologous strain for the Cuban vaccinees were 14% (5/35) and 29% (10/35), respectively. Among the controls, 15% (3/20) showed IRPA responses to 44/76-SL but none to Cu385. Correlation between IRPA activity and SBA titres or anti-OMV IgG was low, especially for pre-vaccination sera against strain 44/76-SL. We conclude that the sensitivity of IRPA described herein may not be sufficient to evaluate serogroup B OMV vaccine responses from clinical samples.
Bacteriophage PRD1 is an icosahedral dsDNA virus with a diameter of 740 Å and an outer protein shell composed of 720 copies of major coat protein P3. Spike complexes at the vertices are composed of a ...pentameric base (protein P31) and a spike structure (proteins P5 and P2) where the N-terminal region of the trimeric P5 is associated with the base and the C-terminal region of P5 is associated with receptor-binding protein P2. The functionality of proteins P3 and P5 was investigated using insertions and deletions. It was observed that P3 did not tolerate changes whereas P5 tolerated changes much more freely. These properties support the hypothesis that viruses have core structures and functions, which remain stable over time, as well as other elements, responsible for host interactions, which are evolutionally more fluid. The insertional probe used was the apex of exposed loop 4 of group B meningococcal outer membrane protein PorA, a medically important subunit vaccine candidate. It was demonstrated that the epitope could be displayed on the virus surface as part of spike protein P5.
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