Frits R Mooi

..pertussis that may have driven this adaptation. Our results underline the importance of Ptx in transmission, suggest that vaccination may select for increased virulence, and indicate ways to control pertussis more effectively...

..pertussis populations has not only increased our understanding of pathogen evolution, but also suggests way to improve pertussis vaccines, underlining the public health significance of population-based studies of pathogens...

..To elucidate how B. pertussis has adapted to vaccination, we compared genome sequences of two ptxP3 strains with four strains isolated before and after the introduction vaccination...

..All isolates contained a locus involved in iron uptake, previously suggested to originate from B. pertussis. The causes for the apparent increase in the isolation of B. holmesii are discussed...

..In the Netherlands, the resurgence of pertussis is associated with the rise of B. pertussis strains with an altered promoter region for pertussis toxin (ptxP3)...

..Further, this work shows that small mutations, even single SNPs, can drive large changes in the populations of bacterial pathogens within a time span of six to 19 years...

..Further, we show that MLVA and fimbrial serotyping of strains can be used as early warning for pertussis epidemics...

..In summary, after challenge vaccination increased lung pathology, TNF-alpha expression (only WCV), and IH parameters. Th1 cells were critical for clearance...

..Here we analyze the effects of wP and aP vaccination and B. pertussis challenge, in Tlr4-deficient C3H/HeJ and wild-type C3H/HeOuJ mice. aP consists of Ptx, filamentous hemagglutinin (FHA), and pertactin (Prn)...

..Using this genotyping, we have been able to show that B. pertussis is much more dynamic than expected...

..69 Prn. The results presented here provide a better understanding of the structure and function of variable loops and their role in the persistence of pathogens in immunologically primed populations...

..Here, we describe the procedure to clone, express, and purify up to 0.1mg P.69 pertactin and its derivatives per 1 ml Escherichia coli culture...

..It also suggests that the amount of pertactin type-specific antibodies will not be very large and that the variation in pertactin probably will not constitute a problem in highly immune individuals...

..This adaptation had very little, if any, effect on mortality, however...

..We determined whether the increase in reported pertussis in the last decade is associated with an increase in the number of infections...

..2%). Given the methodology of this study, estimates of sensitivity probably are overrated (because pertussis patients without IgG-Ptx response are not detected), but estimates of specificities can be considered very accurate...

..Despite >50 years of universal vaccination, pertussis remains the most prevalent vaccine-preventable infectious disease in developed countries. Pertussis is often mild in adults, but can run a severe course in young infants...

..Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis...

..These types may represent newly emerged, successful clones. The identification of highly successful clones may shed light on the question of how B. pertussis is able to maintain itself in vaccinated populations...

..The effectiveness of universal adolescent or adult booster strategies -- to prevent pertussis in infants -- should also be considered from an economical point of view before being implemented...

..Therefore other factors may have contributed to the predominance of Prn2 in vaccinated populations. The mouse model may be useful to assess and predict changes in the B. pertussis population due to vaccination...

..Targeting vaccination at adults and health care workers who are in close contact with infants may prevent transmission of pertussis to infants...

..69 pertactin. This may explain why the variation in P.69 pertactin is so effective, despite the fact that it is limited to only two small segments of the molecule...

..This approach opens up the possibility to the design of new and fully synthetic vaccines that can induce protective antibodies...

..Irreversible and reversible loss occurred, respectively, by recombination between repeats leading to deletion of the tcfA gene and by mutations in a polymorphic G-track. These phenomena may reflect adaptation to distinct niches...

..An acellular preschool booster vaccination against pertussis has been included in the National Immunization Programme in The Netherlands, since November 2001. We studied the impact of this preschool booster on the epidemiology of pertussis...

..pertussis inoculation. Twelve and a half percent of the genomes of these mice are from a different genetic background...

..Vaccination failed to modulate these parameters. In conclusion, although DTaP vaccination may affect the LLNA response, we found no evidence of an effect on lung allergy...

..We found an association between severe pertussis in infancy and respiratory symptoms on toddler age. The mechanisms that may underlie this association require further investigation...

..Maternal vaccination might be an effective way to decrease morbidity and mortality caused by pertussis in newborn babies...

..These results suggest that Fim does not affect bacterial localisation in the mouse lung, but does influence host immune mechanisms. Possibly, Fim may exert an anti-inflammatory function and thereby inhibit killing by macrophages...

..We conclude that the potential risks of DNA vaccines are minimal. However, their safety issues may differ case-by-case, and they should be treated accordingly...