Showing papers by "Derrick W. Crook published in 2011"

Clinical Clostridium difficile: clonality and pathogenicity locus diversity.

Abstract: Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings. The major virulence determinants are large clostridial toxins, toxin A (tcdA) and toxin B (tcdB), encoded within the pathogenicity locus (PaLoc). Isolates vary in pathogenicity from hypervirulent PCR-ribotypes 027 and 078 with high mortality, to benign non-toxigenic strains carried asymptomatically. The relative pathogenicity of most toxigenic genotypes is still unclear, but may be influenced by PaLoc genetic variant. This is the largest study of C. difficile molecular epidemiology performed to date, in which a representative collection of recent isolates (n = 1290) from patients with CDI in Oxfordshire, UK, was genotyped by multilocus sequence typing. The population structure was described using NeighborNet and ClonalFrame. Sequence variation within toxin B (tcdB) and its negative regulator (tcdC), was mapped onto the population structure. The 69 Sequence Types (ST) showed evidence for homologous recombination with an effect on genetic diversification four times lower than mutation. Five previously recognised genetic groups or clades persisted, designated 1 to 5, each having a strikingly congruent association with tcdB and tcdC variants. Hypervirulent ST-11 (078) was the only member of clade 5, which was divergent from the other four clades within the MLST loci. However, it was closely related to the other clades within the tcdB and tcdC loci. ST-11 (078) may represent a divergent formerly non-toxigenic strain that acquired the PaLoc (at least) by genetic recombination. This study focused on human clinical isolates collected from a single geographic location, to achieve a uniquely high density of sampling. It sets a baseline of MLST data for future comparative studies investigating genotype virulence potential (using clinical severity data for these isolates), possible reservoirs of human CDI, and the evolutionary origins of hypervirulent strains.

Waves of trouble: MRSA strain dynamics and assessment of the impact of infection control

Abstract: There has been a sustained decline in bloodstream infections due to methicillin-resistant Staphylococcus aureus (MRSA) throughout the UK. The UK MRSA epidemic, which began in the 1990s, has been dominated by two epidemic MRSA (EMRSA) clones {EMRSA-15, of clonal complex (CC) 22 [sequence type (ST) 22], and EMRSA-16, of CC30 (ST36)}. It appears that both these clones followed a wave trajectory (initial expansion, relative stasis, then decline). Three recent studies have shown that ST36 has declined faster than ST22, a change that appears to have begun before the recent intensification of intensive control measures in the UK. The biological basis of infectious disease waves, including those of MRSA, is discussed, as are the implications of such waves for the assessment of the impact of infection control measures.

Decline of meticillin-resistant Staphylococcus aureus in Oxfordshire hospitals is strain-specific and preceded infection-control intensification

Abstract: Background In the past, strains of Staphylococcus aureus have evolved, expanded, made a marked clinical impact and then disappeared over several years. Faced with rising meticillin-resistant S aureus (MRSA) rates, UK government-supported infection control interventions were rolled out in Oxford Radcliffe Hospitals NHS Trust from 2006 onwards. Methods Using an electronic Database, the authors identified isolation of MRS among 611 434 hospital inpatients admitted to acute hospitals in Oxford, UK, 1 April 1998 to 30 June 2010. Isolation rates were modelled using segmented negative binomial regression for three groups of isolates: from blood cultures, from samples suggesting invasion (eg, cerebrospinal fluid, joint fluid, pus samples) and from surface swabs (eg, from wounds). Findings MRSA isolation rates rose rapidly from 1998 to the end of 2003 (annual increase from blood cultures 23%, 95% CI 16% to 30%), and then declined. The decline accelerated from mid-2006 onwards (annual decrease post-2006 38% from blood cultures, 95% CI 29% to 45%, p=0.003 vs previous decline). Rates of meticillin-sensitive S aureus changed little by comparison, with no evidence for declines 2006 onward (p=0.40); by 2010, sensitive S aureus was far more common than MRSA (blood cultures: 2.9 vs 0.25; invasive samples 14.7 vs 2.0 per 10 000 bedstays). Interestingly, trends in isolation of erythromycin-sensitive and resistant MRSA differed. Erythromycin-sensitive strains rose significantly faster (eg, from blood cultures p=0.002), and declined significantly more slowly (p=0.002), than erythromycin-resistant strains (global p<0.0001). Bacterial typing suggests this reflects differential spread of two major UK MRSA strains (ST22/36), ST36 having declined markedly 2006-2010, with ST22 becoming the dominant MRSA strain. Conclusions MRSA isolation rates were falling before recent intensification of infection-control measures. This, together with strain-specific changes in MRSA isolation, strongly suggests that incompletely understood biological factors are responsible for the much recent variation in MRSA isolation. A major, mainly meticillin-sensitive, S aureus burden remains.

Changes in Serogroup and Genotype Prevalence Among Carried Meningococci in the United Kingdom During Vaccine Implementation

Abstract: Background. Herd immunity is important in the effectiveness of conjugate polysaccharide vaccines against encapsulated bacteria. A large multicenter study investigated the effect of meningococcal serogroup C conjugate vaccine introduction on the meningococcal population. Methods. Carried meningococci in individuals aged 15–19 years attending education establishments were investigated before and for 2 years after vaccine introduction. Isolates were characterized by multilocus sequence typing, serogroup, and capsular region genotype and changes in phenotypes and genotypes assessed. Results. A total of 8462 meningococci were isolated from 47 765 participants (17.7%). Serogroup prevalence was similar over the 3 years, except for decreases of 80% for serogroup C and 40% for serogroup 29E. Clonal complexes were associated with particular serogroups and their relative proportions fluctuated, with 12 statistically significant changes (6 up, 6 down). The reduction of ST-11 complex serogroup C meningococci was probably due to vaccine introduction. Reasons for a decrease in serogroup 29E ST-254 meningococci (from 1.8% to 0.7%) and an increase in serogroup B ST-213 complex meningococci (from 6.7% to 10.6%) were less clear. Conclusions. Natural fluctuations in carried meningococcal genotypes and phenotypes a can be affected by the use of conjugate vaccines, and not all of these changes are anticipatable in advance of vaccine introduction.

Reduction in invasive pneumococcal disease following implementation of the conjugate vaccine in the Oxfordshire region, England

Abstract: Pneumococcal conjugate vaccine to seven capsular types has been highly effective in the US since its introduction in 2000. The same vaccine was adopted by the UK in 2006. Ongoing surveillance since 1995 of invasive pneumococcal disease (IPD) in Oxfordshire, UK, allowed assessment of the impact of vaccine intervention. The vaccine significantly reduced IPD among the target group, children under 2 years of age; incidence rate ratio (IRR)=0.62 (95 % CI 0.43-0.90) (P=0.008) comparing the 3 years pre- and post-implementation with a residual incidence of 22.4/100 000 children. The reduction was even greater when comparing 11 years pre- with the 3 years post-implementation of vaccine; IRR=0.53 (0.39-0.70) (P<0.0001). There was a marked direct effect of the vaccine evidenced by substantial reductions in the seven serotypes contained in the vaccine. There was also a clear reduction in IPD for those serotypes contained in the vaccine among those older than 2 years when comparing both the 3 and 11 year pre-PCV7 time periods, with IRR=0.57 (0.47-0.69) (P<0.0001) and IRR=0.50 (0.43-0.58) (P<0.0001), respectively, indicating a strong herd effect. There was a significant, though moderate, rise in the serotypes not contained in the vaccine, with clear evidence for replacement in some serotypes.

Molecular Epidemiology of Clostridium difficile Strains in Children Compared with That of Strains Circulating in Adults with Clostridium difficile-Associated Infection

Abstract: Molecular analysis of Clostridium difficile (28 isolates) from children (n = 128) in Oxfordshire, United Kingdom, identified eight toxigenic genotypes. Six of these were isolated from 27% of concurrent adult C. difficile-associated infections studied (n = 83). No children carried hypervirulent PCR ribotype 027. Children could participate in the transmission of some adult disease-causing genotypes.