31 research outputs found
Death or survival from invasive pneumococcal disease in Scotland: associations with serogroups and multilocus sequence types
No full textWe describe associations between death from invasive pneumococcal disease (IPD) and particular serogroups and sequence types (STs) determined by multilocus sequence typing (MLST) using data from Scotland. All IPD episodes where blood or cerebrospinal fluid (CSF) culture isolates were referred to the Scottish Haemophilus, Legionella, Meningococcal and Pneumococcal Reference Laboratory (SHLMPRL) from January 1992 to February 2007 were matched to death certification records by the General Register Office for Scotland. This represented 5959 patients. The median number of IPD cases in Scotland each year was 292. Deaths, from any cause, within 30 days of pneumococcal culture from blood or CSF were considered to have IPD as a contributing factor. Eight hundred and thirty-three patients died within 30 days of culture of Streptococcus pneumoniae from blood or CSF [13.95%; 95% confidence interval (13.10, 14.80)]. The highest death rates were in patients over the age of 75. Serotyping data exist for all years but MLST data were only available from 2001 onward. The risk ratio of dying from infection due to particular serogroups or STs compared to dying from IPD due to all other serogroups or STs was calculated. Fisher's exact test with Bonferroni adjustment for multiple testing was used. Age adjustment was accomplished using the Cochran-Mantel-Haenszel test and 95% confidence intervals were reported. Serogroups 3, 11 and 16 have increased probability of causing fatal IPD in Scotland while serogroup 1 IPD has a reduced probability of causing death. None of the 20 most common STs were significantly associated with death within 30 days of pneumococcal culture, after age adjustment. We conclude that there is a stronger association between a fatal outcome and pneumococcal capsular serogroup than there is between a fatal outcome and ST
Antibiotic resistance in invasive Streptococcus pneumoniae isolates identified in Scotland between 1999 and 2007
No full textData from 4727 invasive isolates of Streptococcus pneumoniae submitted to the Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory between 1999 and 2007 were analysed to establish susceptibility profiles to penicillin, erythromycin and cefotaxime. Pneumococcal resistance to penicillin over the study period remained low, with only 0.2?% (n=7/4727) of isolates falling into this category (MIC ?2?mg l(-1)). These isolates have been sporadic, and have mainly represented serogroup 14 (ST9) and 9 (ST156). In comparison, the 'intermediate sensitivity' group (MIC 0.12-1?mg l(-1)) ranged between 2 and 6?% per year, the majority from serogroup 9 (ST156). Over the study period, we found that 12?% (n=585/4727) of isolates were erythromycin-resistant (MIC >0.5?mg l(-1)), with the majority (n=467; 80?%) of these isolates identified as serogroup 14 (ST9). Cephalosporin resistance (cefotaxime MIC >1?mg l(-1)) was found in only 0.06?% (n=2/3135) of isolates. Internationally recognized clones (Pneumococcal Molecular Epidemiology Network) accounted for 35?% (n=28/81) of the penicillin non-susceptible isolates and 75?% (n=248/330) of the macrolide-resistant isolates, with ST9 and ST306 predominating. Between 1999 and 2007 we found that 11.6?% (n=18/155) of the penicillin non-susceptible isolates and 4.8?% (n=28/585) of the macrolide-resistant isolates were from serogroups not covered by the 7-valent conjugate pneumococcal vaccine in use in the UK since 2006. Susceptibility to first-line antimicrobial agents for invasive pneumococcal disease in Scotland remained high over the period 1999-200
Genomic diversity in naturally transformable Streptococcus pneumoniae
No full textInfections due to Streptococcus pneumoniae (the pneumococcus) remain a substantial source of morbidity and mortality in both developing and developed countries despite a century of research and the development of effective therapeutic interventions (such as antibiotic therapy and vaccination). The ability of the pneumococcus to evade multiple classes of antibiotic through several genetically determined resistance mechanisms and its evasion of capsular polysaccharide based vaccines through serotype replacement and capsular switching, all reflect the extensive diversity and plasticity of the genome of this naturally transformable organism which can readily alter its genome in response to its environment and the pressures placed upon it in order to survive.
The purpose of this thesis is to investigate this diversity from a genome sequence perspective and to relate these observations to pneumococcal molecular epidemiology in a region of high biodiversity, the pathogenesis of certain disease manifestations and assess for a possible bacterial genetic basis for the pneumococcal phenotypes of, “carriage” and, “invasion.”
In order to do this, microarray comparative genomic hybridization (CGH) has been utilized to compare DNA from a variety of pneumococcal isolates chosen from 10 diverse serotypes and Multilocus Sequence Types and from clinically relevant serotypes and sequence types (particularly serotypes 3, 4 and 14 and sequence types ST9, ST246 and ST180)) against a reference, sequenced pneumococcal genome from an extensively investigated serotype 4 isolate – TIGR4.
Microarray comparison of the transcriptional profiles of several isolates has also been undertaken to compare gene expression from isolates of serotype 1 (ST227 and ST306) and serotype 3 (ST180) related to particular disease states and exposure of a multi-resistant pneumococcus to an antimicrobial (clarithromycin) commonly used to treat pneumococcal pneumonia
Trends in serotypes and sequence types among cases of invasive pneumococcal disease in Scotland, 1999-2010.
No full textINTRODUCTION: The 7-valent pneumococcal conjugate vaccine (Prevenar(®), Wyeth; PCV7) was introduced to the UK paediatric immunisation schedule in 2006. This study investigates trends in serotypes and multi locus sequence types (STs) among cases of invasive pneumococcal disease (IPD) in Scotland prior to, and following, the introduction of PCV7. METHODS: Scottish Invasive Pneumococcal Disease Enhanced Surveillance has records of all cases of IPD in Scotland since 1999. Cases diagnosed from blood or cerebrospinal fluid isolates until 2010 were analysed. Logistic and poisson regression modelling was used to assess trends prior to and following the introduction of PCV7. RESULTS: Prior to PCV7 use, on average 650 cases of IPD were reported each year; 12% occurred in those aged <5 years and 35% affected those aged over 65 years. Serotypes in PCV7 represented 47% of cases (68% in <5 year olds). The serotype and ST distribution was relatively stable with only serotype 1 and associated ST 306 showing an increasing trend. PCV7 introduction was associated with a 69% (95% CI: 50%, 80%) reduction in the incidence of IPD among those aged <5 years, a 57% (95% CI: 47%, 66%) reduction among those aged 5-64 years but no significant change among those aged 65 years and over where increases in non-PCV7 serotypes were observed. Serotypes which became more prevalent post-PCV7 are those which were associated with STs related to the PCV7 serotypes. CONCLUSIONS: Routine serotyping and sequence typing in Scotland allowed the assessment of the relationship between the capsule and the clones in the post vaccination era. Changes in the distribution of serotypes post PCV7 introduction appear to be driven by associations between serotypes and STs prior to PCV7 introduction. This has implications for the possible effects of the introduction of higher valency vaccines and could aid in predicting replacement serotypes in IPD
The impact upon mortality due to sepsis following the introduction of a restrictive empirical antibiotic policy in NHS Lanarkshire
No full textA Comparison Of Methods For Identification And Antifungal Susceptibility Testing Of Candida Isolates
No full textThe spectrum of HIV-related disease in rural Central Thailand.
No full textTo determine the spectrum of HIV-related illnesses presenting to a rural primary and secondary healthcare facility in Central Thailand, a cross-sectional study was conducted. Routinely collected data were extracted from outpatient medical notes for all adult HIV-infected new attenders of the Manorom Christian Hospital Infectious Disease Clinic. Data concerning inpatient admissions of HIV-infected individuals were collected from ward admission books and discharge summaries. Complete data were available for 229 outpatients, 70% of whom were men. The median age at presentation was 31 years for men and 30 years for women. The majority of the outpatients were married (69%) and infected heterosexually (91%). The commonest conditions requiring admission were cryptococcal meningitis (15%), bacterial pneumonia (12%), extrapulmonary tuberculosis (12%), Pneumocystis carinii pneumonia (7%), cerebral toxoplasmosis (4%) and pulmonary tuberculosis (3%). Of the patients presenting for the first time, 32% had AIDS-defining illnesses. Presentations with some conditions, such as tuberculosis and septicemia, were fewer than expected. The common opportunistic infections among HIV-infected adults in this rural region are treatable and preventable. Most patients present with advanced disease and earlier diagnosis, through improved access to voluntary counseling and testing, would enable them to receive appropriate preventive therapies and antiretrovirals as they becomes available. The high prevalence of cryptococcal disease suggests that prophylactic anti-fungal therapy may be of value in this area. Septicemia and tuberculosis may be under-diagnosed, highlighting the need for improved diagnostic laboratory facilities or treatment based upon validated clinical algorithms. Community care and palliative care services for HIV-infected individuals will increasingly be required in this region
Dominant Role of Nucleotide Substitution in the Diversification of Serotype 3 Pneumococci over Decades and during a Single Infection
No full textStreptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease associated with high mortality rates relative to other pneumococci. Phylogenetic analysis of a complete reference genome and 81 draft sequences from clonal complex 180, the predominant serotype 3 clone in much of the world, found most sampled isolates belonged to a clade affected by few diversifying recombinations. However, other isolates indicate significant genetic variation has accumulated over the clonal complex’s entire history. Two closely related genomes, one from the blood and another from the cerebrospinal fluid, were obtained from a patient with meningitis. The pair differed in their behaviour in a mouse model of disease and in their susceptibility to antimicrobials, with at least some of these changes attributable to a mutation that upregulated
the patAB efflux pump. This indicates clinically important phenotypic variation can accumulate rapidly through
small alterations to the genotype
Simultaneous Nasopharyngeal Carriage of Two Pneumococcal Multilocus Sequence Types with a Serotype 3 Phenotype
No full textKnowledge of the epidemiology of pneumococcal disease in Bolivia is sparse, and Multilocus Sequence Typing (MLST) of isolates has not been previously possible. Beni state has until recently been a geographically isolated region of the Bolivian Amazon basin and is a region of significant poverty. During June and July 2007, we performed a pneumococcal carriage study recruiting over 600 schoolchildren in two towns in the Beni state. Here, we describe the unique identification of simultaneous nasopharyngeal carriage of two pneumococcal multilocus sequence types with a serotype 3 phenotype within a single subject
