The sequences reported in this paper have been deposited in the National Center for Biotechnology Information (NCBI) Sequence Read Archive (see URLs) with the Bioproject accession number PRJNA434389 and the NCBI Gene Expression Omnibus (GEO) under accession number GSE113058.
ETHICS STATEMENTAll mouse studies were performed in accordance with a protocol (AUP-0318-0016) approved by the Institutional Animal Care and Use Committee at Houston Methodist Research Institute. All studies with human blood and blood components were performed in accordance with a protocol (01-I-N055) approved by the Institutional Review Board for human subjects, National Institute of Allergy and Infectious Diseases. All study volunteers gave written informed consent.
Bordetella pertussis is a pathogen-causing whooping cough (pertussis) in humans. Although vaccination against the disease is effective, the bacterium is still circulating among population and can even cause death. Especially young infants, who lack protection, are vulnerable. The laboratory diagnostic methods to detect B. pertussis are culture, PCR and ELISA serology. Reported cases of the disease vary among countries but usually the incidence rates are low, <1 to 10/100 000. However, pertussis often goes unrecognized among patients as it presents itself like the common cold, especially in adults and elders who are often the source of the infection. This makes pertussis difficult to monitor and control. Serological surveillance is an easy manner to estimate the real burden of the disease among population. Furthermore, to have reliable results, anti-PT IgG antibodies should be measured, as PT is the only specific antigen to B. pertussis. This review aims to evaluate available pertussis seroprevalence studies throughout the world, and to compare the findings from countries with different vaccination histories and strategies. Estimation of the real burden of pertussis is compared to reported numbers. In addition, future aspects in seroprevalence studies are considered.
Recently, two related Streptococcus pyogenes strains with reduced susceptibility to ampicillin, amoxicillin, and cefotaxime, antibiotics commonly used to treat S. pyogenes infections, were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the pbp2x gene, encoding penicillin-binding protein 2X (PBP2X). This concerning report led us to investigate our library of 7,025 genome sequences of type emm1, emm28, and emm89 S. pyogenes clinical strains recovered from intercontinental sources for mutations in pbp2x. We identified 137 strains that, combined, had 37 nonsynonymous mutations in 36 codons in pbp2x. Although to a lesser magnitude than the two previously published isolates, many of our strains had decreased susceptibility in vitro to multiple beta-lactam antibiotics. Many pbp2x mutations were found only in single strains, but 16 groups of two or more isolates of the same emm type had an identical amino acid replacement. Phylogenetic analysis showed that, with one exception, strains of the same emm type with the same amino acid replacement were clonally related by descent. This finding indicates that strains with some amino acid changes in PBP2X can successfully spread to new human hosts and cause invasive infections. Mapping of the amino acid changes onto a three-dimensional structure of the related Streptococcus pneumoniae PBP2X suggests that some substitutions are located in regions functionally important in related pathogenic bacterial species. Decreased beta-lactam susceptibility is geographically widespread in strains of numerically common emm gene subtypes. Enhanced surveillance and further epidemiological and molecular genetic study of this potential emergent antimicrobial problem are warranted.
Despite more than 50 years of vaccination, pertussis is still an endemic disease, with regular epidemic outbreaks. With the exception of Poland, European countries have replaced whole-cell vaccines (WCVs) by acellular vaccines (ACVs) in the 1990s. Worldwide, antigenic divergence in vaccine antigens has been found between vaccine strains and circulating strains. In this work, 466 Bordetella pertussis isolates collected in the period 1998–2012 from 13 European countries were characterised by multi-locus antigen sequence typing (MAST) of the pertussis toxin promoter (ptxP) and of the genes coding for proteins used in the ACVs: pertussis toxin (Ptx), pertactin (Prn), type 2 fimbriae (Fim2) and type 3 fimbriae (Fim3). Isolates were further characterised by fimbrial serotyping, multi-locus variable-number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). The results showed a very similar B. pertussis population for 12 countries using ACVs, while Poland, which uses a WCV, was quite distinct, suggesting that ACVs and WCVs select for different B. pertussis populations. This study forms a baseline for future studies on the effect of vaccination programmes on B. pertussis populations.Electronic supplementary materialThe online version of this article (doi:10.1007/s10096-014-2297-2) contains supplementary material, which is available to authorized users.
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