Bordetella pertussis - Vaccination and Strain Variation

Pertussis or whooping cough is a highly contagious vaccine-preventable disease of the human respiratory tract caused by the Bordetella pertussis bacteria. In Finland, pertussis vaccinations were started in 1952 leading to a dramatic decrease in the morbidity and mortality. In the late 1990s, the incidence of pertussis increased despite the high vaccination coverage. Strain variation has been connected to the re-emergence of pertussis in countries with long history of pertussis vaccination. In 2005, the pertussis vaccine and the vaccination schedule were changed in Finland. The molecular epidemiology and the strain variation of the B. pertussis isolates were examined in Finland and in countries with similar (France) and different (Sweden) vaccination history. Continuous evolution of the B. pertussis population in Finland was observed since the 1950s, and the recently circulating isolates were antigenically different from the vaccine strains. Comparison of the circulating isolates from Finland, France and Sweden did not refer to significant differences. Certain type of strains noticed in France already in 1994 mainly caused the recent epidemics in Sweden (1999) and in Finland (2003-4). On several occasions, a new type of strains first appeared in Sweden and some years later in Finland. The B. pertussis isolates from the infants were shown to be similar to those from the other age groups. It is suggested that the strains originate from the same reservoir among adolescents and adults. The strain variation does not seem to have a major effect on the morbidity among recently vaccinated individuals, but it might play a role among those who are in the waning phase of immunity. The incidence of pertussis in Finland has remained low since the change of the vaccination programme. This might be related to the epidemic nature of pertussis and the near future will show the real effectiveness of the new vaccination programme. At present, many infants are infected because they are too young to be immunised with the current schedule. New strategies or vaccines are needed to protect those who are the most vulnerable.Hinkuyskä on erittäin tarttuva Bordetella pertussis -bakteerin aiheuttama ja rokottein torjuttavissa oleva tauti, jota esiintyy ainoastaan ihmisillä. Suomessa hinkuyskän sairastuvuus ja kuolleisuus laskivat huomattavasti vuonna 1952 tapahtuneen hinkuyskärokotusten aloittamisen jälkeen. Hyvästä rokotuskattavuudesta huolimatta hinkuyskän esiintyvyys lisääntyi 1990-luvun lopussa. Hinkuyskän lisääntyminen maissa, joissa hinkuyskärokotteet ovat olleet käytössä pitkään, on liitetty B. pertussis -bakteerin kantavaihteluun. Suomen rokotusohjelma ja käytettävä hinkuyskärokote vaihdettiin vuonna 2005. B. pertussis -bakteerin kantavaihtelua ja molekyylitason epidemiologiaa tutkittiin Suomessa sekä samankaltaisen (Ranska) ja poikkeavan (Ruotsi) rokotushistorian maissa. Suomen B. pertussis -populaation jatkuva ja etenevä evoluutio havaittiin 1950-luvulta alkaen. Viime vuosina kiertäneet bakteerikannat poikkeavat rokotekannoista. Suomen, Ruotsin ja Ranskan bakteeripopulaatiot eivät poikenneet selvästi toisistaan. Sekä Ruotsin (1999) että Suomen (2003-4) edellisen epidemian aiheutti etupäässä eräs Ranskassa jo vuonna 1994 havaittu bakteerikanta. Useissa tapauksissa uudet bakteerikannat havaittiin Suomessa joitakin vuosia myöhemmin kuin Ruotsissa. Tulokset osoittivat, että eri ikäryhmistä eristetyt B. pertussis -bakteerikannat ovat samankaltaisia. Näin ollen kaikissa ikäryhmissä tautia aiheuttavien bakteerikantojen oletetaan olevan lähtöisin samasta säilymöstä (reservuaarista) nuorten ja aikuisten keskuudessa. Kantavaihtelu ei näyttäisi paljonkaan vaikuttavan hiljattain rokotettujen sairastuvuuteen, mutta vaikutus saattaa ilmetä niillä, joiden immuniteetti hinkuyskää vastaan on heikentynyt. Hinkuyskää on esiintynyt Suomessa vähän rokotusohjelman vaihdon jälkeen. Tämä saattaa kuitenkin johtua taudin luontaisesta epidemiasyklistä, joten uuden rokotusohjelman todellinen tehokkuus selviää vasta lähitulevaisuudessa. Nykyisellä rokotusaikataululla useat vastasyntyneet sairastuvat hinkuyskään, koska ovat vielä liian nuoria saamaan rokotusohjelman mukaisen ensimmäisen hinkuyskärokotuksensa. Heidän suojaamisekseen tarvitaan uusia rokotusstrategioita tai rokotteita.Siirretty Doriast

Bordetella pertussis, Finland and France

We used pulsed-field gel electrophoresis analysis and genotyping to compare clinical isolates of Bordetella pertussis recovered since the early 1990s in Finland and France, 2 countries with similar histories of long-term mass vaccination with whole-cell pertussis vaccines. Isolates from both countries were similar genetically but varied temporally

Intracellular signalling pathways and cytoskeletal functions converge on the psoriasis candidate gene CCHCR1 expressed at P-bodies and centrosomes

Background: CCHCR1 (Coiled Coil alpha-Helical Rod protein 1) is a putative psoriasis candidate gene with the risk alleles CCHCR1*WWCC and *Iso3, the latter inhibiting the translation of isoform 1. CCHCR1 was recently shown to be a centiosomal piotein, as well as a component of cytoplasmic piocessmg bodies (P-bodies) that regulate mRNA turnovel. The function of CCHCR1 has remained unsettled, partly because of the inconsistent findings, it has been shown to play a wide variety of roles in divergent processes, e.g., cell proliferation and steroidogenesis. Here we utilized RNA sequencing (RNAseq) using HEK293 cells overexpressing isoforms 1 or 3 (Iso1, Iso3 cells), in combination with the coding non-risk or risk (*WWCC haplotype of CCHCR1. Our aim was to study the overall role of CCHCR1 and the effects of its variants. Results: The overexpression of CCHCR1 variants in HEK293 cells resulted in cell line-specific expression profiles though seveial similarities were observable. Overall the Iso1 and Iso3 cells showed a clear isoform-specific clustering as two separate groups, and the Non-risk and Risk cells often exhibited opposite effects. The RNAseq supported a role for CCHCR1 in the centrosomes and P-bodies; the most highlighted pathways included regulation of cytoskeleton, adherens and tight junctions, mRNA surveillance and RNA transport. Interestingly, both the RNAseq and immunofluorescent localization revealed variant-specific differences for CCHCR1 within the P-bodies. Conclusions: CCHCR1 influenced a wide variety of signaling pathways, which could reflect its active role in the P-bodies and centrosomes that both are linked to the cytoskeleton; as a centrosomal P-body protein CCHCR1 may regulate diverse cytoskeleton-mediated functions, such as cell adhesion and division. The piesent findings may explain the previous inconsistent obseivations about the functions of CCHCR1.Peer reviewe

Centrosomal Localization of the Psoriasis Candidate Gene Product, CCHCR1, Supports a Role in Cytoskeletal Organization

Peer reviewe

NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis

Psoriatic skin differs distinctly from normal skin by its thickened epidermis. Most gene expression comparisons utilize full-thickness biopsies, with substantial amount of dermis. We assayed the transcriptomes of normal, lesional, and non-lesional psoriatic epidermis, sampled as split-thickness skin grafts, with 5'-end RNA sequencing. We found that psoriatic epidermis contains more mRNA per total RNA than controls, and took this into account in the bioinformatic analysis. The approach highlighted innate immunity-related pathways in psoriasis, including NOD-like receptor (NLR) signaling and inflammasome activation. We demonstrated that the NLR signaling genes NOD2, PYCARD, CARD6, and IFI16 are upregulated in psoriatic epidermis, and strengthened these findings by protein expression. Interestingly, PYCARD, the key component of the inflammasome, showed an altered expression pattern in the lesional epidermis. The profiling of non-lesional skin highlighted PSORS4 and mitochondrially encoded transcripts, suggesting that their gene expression is altered already before the development of lesions. Our data suggest that all components needed for the active inflammasome are present in the keratinocytes of psoriatic skin. The characterization of inflammasome pathways provides further opportunities for therapy. Complementing previous transcriptome studies, our approach gives deeper insight into the gene regulation in psoriatic epidermis.Peer reviewe

Gene expression analysis of skin grafts and cultured keratinocytes using synthetic RNA normalization reveals insights into differentiation and growth control

Background: Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs' lifecycle has been omitted. Results: We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. Conclusions: The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.Peer reviewe

Rauman kaupungin vammaispalvelutoimiston asiakkaiden tyytyväisyys saamaansa palveluun

Tämän opinnäytetyön tarkoituksena oli suorittaa asiakastyytyväisyyskysely Rauman kaupungin vammaispalvelutoimiston asiakkaille sekä saada tietoa asiakkaiden tyytyväisyydestä saaminsa palveluihin. Tutkimuksen tavoitteena oli, että vammaispalvelutoimiston henkilökunta pystyy saatavan tutkitun tiedon perusteella kehittämään palvelujaan asiakkaidensa toivomaan suuntaan. Aineiston keruuseen käytettiin toimeksiantajalta saatua valmista kyselylomaketta. Tutkimuksen perusjoukon muodostivat Rauman kaupungin vammaispalvelutoimiston asiakkaat. Asiakkaiden kokonaislukumäärä on noin 1400. Asiakas voi saada useampaa palvelua. Tutkimusotos oli 300 asiakasta. Aineisto analysoitiin Excel-taulukkolaskentaohjelman avulla. Tulokset esitetään sanallisesti sekä taulukoiden avulla. Lähetettyjä kyselylomakkeita palautui 78 kappaletta, jolloin vastausprosentiksi muodostui 26 %. Tutkimukseen osallistuneet olivat pääsääntöisesti tyytyväisiä saamiinsa palveluihin. Erityisen tyytyväisiä oltiin myönnettyihin palveluihin sekä vaikutusmahdollisuuksiin palvelusuunnitelmaa tehtäessä. Vastaajat arvostivat myös asiakaspalvelun laatua. Erityisesti vammaispalvelutoimiston työntekijöiden ystä-vällisyyttä korostettiin. Vastaajat olivat tyytymättömimpiä vammaispalvelutoimiston päivittäiseen puhelinaikaan (arkisin klo 9-10). Puhelinajan koettiin olevan liian lyhyt kestoltaan, ja asioimiseen puhelimitse pitäisi olla mahdollisuus myös iltapäivällä. Lisäksi tiedonsaanti saatavilla olevista palveluista koettiin puutteelliseksi. Tutkimustulosten mukaan vastaajat eivät tiedä omasta mielestään tarpeeksi saatavilla olevista palveluista. Seuraavan opinnäytetyön aihe voisi olla esite, jossa kerrottaisiin, mitä palveluja voi saada esimerkiksi näkövammainen tai liikuntavammainen henkilö. Jokainen voisi ottaa esitteen, joka koskettaa omaa elämäntilannettaan. Vammaispalvelutoimiston asiakkaiden tyytyväisyyttä saamiinsa palveluihin tulisi myös tutkia jatkossakin.The purpose of this thesis was first to carry out a customer satisfaction survey for the clients of the Rauma Office for Disability Services. Secondly, the results of the survey were used in order to acquire information about how satisfied the clients are with the services they have received. The objective of this study was to generate necessary information for the staff of the Rauma Office for Disability so that their services can be improved in accordance with the customers’ feedback. The research material for this study was collected using the ready-made questionnaire given by the orderer of this thesis. Target audience of this study was all the customers of the Rauma Office for Disability Services. The total number of the clients is approximately 1400. The client can have several services simultaneously. Research sample size was 300 clients. The research material was analysed with Excel spreadsheet software. The results are presented in both verbal and tabular form. In total, 78 questionnares were returned to the author and thus the response rate was 26 %. According to the results of the customer satisfaction survey the clients were mainly satisfied with the services they have received. The clients were especially satisfied with the services admitted to them as well as with the possibility to influence the content of the personal service plan. The respondents also appreciated the quality of the customer service. Especially the kindness of the staff was underlined. The respondents were most dissatisfied with the daily telephone customer service (from 9 am to 10 am on working days) that the Office for Disability Services offers. According to the customers the daily telephone customer service time is too short and it takes place too early. The customers also pointed out that it is difficult to find out information about the available services. According to the results of the customer satisfaction survey the respondents are not well enough informated about the available services. A further study could be made about how to deliver information about the available services more effectively. One way could be to make brochures where the available services are be listed for persons with different needs, for example visually impaired person or physically disabled person. Every client could take a brochure that is suitable for his or her personal needs. It is also important in future to keep studying how satisfied the clients of Rauma Office for Disability Services are

Bordetella pertussis vaccine strains and circulating isolates in Serbia

Available online 27 November 2009

Strain Variation among Bordetella pertussis Isolates in Finland, Where the Whole-Cell Pertussis Vaccine Has Been Used for 50 Years

Pertussis is an infectious disease of the respiratory tract caused by Bordetella pertussis. Despite the introduction of mass vaccination against pertussis in Finland in 1952, pertussis has remained an endemic disease with regular epidemics. To monitor changes in the Finnish B. pertussis population, 101 isolates selected from 1991 to 2003 and 21 isolates selected from 1953 to 1982 were studied together with two Finnish vaccine strains. The analyses included serotyping of fimbriae (Fim), genotyping of the pertussis toxin S1 subunit (ptxA) and pertactin (prn), and pulsed-field gel electrophoresis (PFGE) after digestion of B. pertussis genomic DNA with XbaI restriction enzyme. Strains isolated before 1977 were found to harbor the same ptxA as the strains used in the Finnish whole-cell pertussis vaccine, and strains isolated before 1982 harbored the same prn as the strains used in the Finnish whole-cell pertussis vaccine. All recent isolates, however, represented genotypes distinct from those of the two vaccine strains. A marked shift of predominant serotype from Fim serotype 2 (Fim2) to Fim3 has been observed since the late 1990s. Temporal changes were seen in the genome of B. pertussis by PFGE analysis. Three PFGE profiles (BpSR1, BpSR11, and BpSR147) were distinguished by their prevalence between 1991 and 2003. The yearly emergence of the three profiles was distributed periodically. Our study stresses the importance of the continuous monitoring of emerging strains of B. pertussis and the need to obtain a better understanding of the relationship of the evolution of B. pertussis in vaccinated populations