[Show abstract][Hide abstract] ABSTRACT: Seven-valent pneumococcal conjugate vaccine (PCV7) was included in the UK national immunisation program in 2006, and this was replaced by thirteen-valent PCV in 2010. During this time, the carriage of vaccine-type
decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type
. Carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive disease. There has been less focus on how conjugate vaccines indirectly affect colonization of other nasopharyngeal bacteria. If the nasopharynx is treated as a niche, then bacterial dynamics are accepted to occur. Alterations in these dynamics have been shown due to seasonal changes, antibiotic use, and sibling/day care interaction. It has been shown that, following PCV7 introduction, an eradication of pneumococcal vaccine types has resulted in increases in the abundance of other respiratory pathogens including
. These changes are difficult to attribute to PCV7 introduction alone and these studies do not account for further changes due to PCV13 implementation. This review aims to describe nasopharyngeal cocarriage of respiratory pathogens in the PCV era.
Journal of Immunology Research 09/2015; 2015(3):394368. DOI:10.1155/2015/394368 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives Bacterial carriage in the upper respiratory tract is usually asymptomatic but can lead to respiratory tract infection (RTI), meningitis and septicaemia. We aimed to provide a baseline measure of Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Neisseria meningitidis carriage within the community. Self-swabbing and healthcare professional (HCP) swabbing were compared.
Design Cross-sectional study.
Setting Individuals registered at 20 general practitioner practices within the Wessex Primary Care Research Network South West, UK.
Participants 10 448 individuals were invited to participate; 5394 within a self-swabbing group and 5054 within a HCP swabbing group. Self-swabbing invitees included 2405 individuals aged 0–4 years and 3349 individuals aged ≥5 years. HCP swabbing invitees included 1908 individuals aged 0–4 years and 3146 individuals aged ≥5 years.
Results 1574 (15.1%) individuals participated, 1260 (23.4%, 95% CI 22.3% to 24.5%) undertaking self-swabbing and 314 (6.2%, 95% CI 5.5% to 6.9%) undertaking HCP-led swabbing. Participation was lower in young children and more deprived practice locations. Swab positivity rates were 34.8% (95% CI 32.2% to 37.4%) for self-taken nose swabs (NS), 19% (95% CI 16.8% to 21.2%) for self-taken whole mouth swabs (WMS), 25.2% (95% CI 20.4% to 30%) for nasopharyngeal swabs (NPS) and 33.4% (95% CI 28.2% to 38.6%) for HCP-taken WMS. Carriage rates of S. aureus were highest in NS (21.3%). S. pneumoniae carriage was highest in NS (11%) and NPS (7.4%). M. catarrhalis carriage was highest in HCP-taken WMS (28.8%). H. influenzae and P. aeruginosa carriage were similar between swab types. N. meningitidis was not detected in any swab. Age and recent RTI affected carriage of S. pneumoniae and H. influenzae. Participant costs were lower for self-swabbing (£41.21) versus HCP swabbing (£69.66).
Conclusions Higher participation and lower costs of self-swabbing as well as sensitivity of self-swabbing favour this method for use in large population-based respiratory carriage studies.
BMJ Open 10/2014; 4(10):e005341. DOI:10.1136/bmjopen-2014-005341 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST). Here we describe serotype, multilocus sequence type (ST), and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST), (11 of which were not previously described) were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy.
PLoS ONE 06/2014; 9(6):e97912. DOI:10.1371/journal.pone.0097912 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Streptococcus pneumoniae is a major cause of sepsis, meningitis and respiratory disease worldwide. Pneumococcal conjugate vaccines (PCVs) have now been implemented in many countries worldwide, including Singapore. To evaluate the effectiveness of these vaccines, pneumococcal surveillance studies are required. Detailed and unified pneumococcal epidemiology data are currently scarce in South East Asia. Thus, we present data on invasive pneumococcal (IPD) isolates from Singapore that could assist in evaluating the effectiveness of pneumococcal vaccine in Singapore. One hundred and fifty-nine invasive pneumococcal disease isolates were received by the National Public Health Laboratory in Singapore between June 2009 and August 2010. Isolates were characterized using serotyping and multilocus sequence typing. Twenty-four different serotypes were found, the most common of which were 19A, 3, 7F, 23F, 6B, 14, 8 and 19F (in rank order). One hundred and two sequence types were observed, of which 38 were novel due to new alleles or new combinations of already existing alleles. Based on the Simpson’s Index of Diversity, serotypes 3, 6B and 19A were the most genetically diverse. Novel sequence types were more prevalent among conjugate vaccine serotypes 3, 19F and 23F and non-conjugate vaccine serotype 8, serogroup 15 and in non-typable isolates. We have demonstrated considerable genetic diversity among invasive pneumococci before and during the widespread use of conjugate vaccines in Singapore. Approximately half of all novel IPD clones identified in this study were non-conjugate vaccine serotypes. Although PCVs would target the most common serotypes, the high genetic diversity in non-vaccine serotypes would require further surveillance studies.
Emerging Microbes and Infections 06/2014; DOI:10.1038/emi.2014.37 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective To systematically review the literature for evidence of smoking and alcohol intake as independent risk factors for invasive pneumococcal disease (IPD).
Design Systematic review.
Methods MEDLINE (1946—May 2012) and EMBASE (1947—May 2012) were searched for studies investigating alcohol or smoking as risk factors for acquiring IPD and which reported results as relative risk. Studies conducted exclusively in clinical risk groups, those assessing risk factors for outcomes other than acquisition of IPD and studies describing risk factors without quantifying a relative risk were excluded.
Results Seven observational studies were identified and reviewed; owing to the heterogeneity of study design, meta-analysis was not attempted. Five of six studies investigating smoking reported an increased risk of IPD in the range 2.2–4.1. Four of the six studies investigating alcohol intake reported a significant increased risk for IPD ranging from 2.9 to 11.4, while one reported a significant protective effect.
Conclusions Overall, these observational data suggest that smoking and alcohol misuse may increase the risk of IPD in adults, but the magnitude of this risk remains unclear and should be explored with further research. The findings of this review will contribute to the debate on whether pneumococcal vaccine should be offered to smokers and people who misuse alcohol in addition to other clinically defined risk groups.
BMJ Open 06/2014; 4(6):e005224. DOI:10.1136/bmjopen-2014-005224 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pneumococcal disease remains a global problem despite the availability of effective conjugate vaccines. The 13-valent pneumococcal conjugate vaccine (PCV13) extends the valency of PCV7 by including six additional serotypes highly associated with invasive pneumococcal disease (IPD). Comparisons between PCV13 and PCV7 or the pneumococcal polysaccharide vaccine have established noninferiority of PCV13 for both safety and immunogenicity profiles for use in children and adults, respectively. At the end of 2011, PCV13 had been approved and launched in 104 countries worldwide, with 54 including the vaccine in their pediatric national immunization program. Surveillance data from early adopters of PCV13 has indicated reductions are occurring in both overall IPD and IPD caused by the six non-PCV7 serotypes; early reports of serotype replacement in carriage are also emerging. While serotype replacement for PCV7 was observed to varying degrees for both carriage and disease, the extent to which this will occur for PCV13 is yet to be determined.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15) and disease (n = 4) states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST) clonal complex 395 (CC395). A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design.
PLoS ONE 05/2013; 8(5):e64731. DOI:10.1371/journal.pone.0064731 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The success of Streptococcus pneumoniae (pneumococcus) in both colonisation and disease is associated with the increased prevalence of genetic clones expressing virulence factors that assist host invasion. We studied the distribution of pneumococcal clones in paediatric carriage as part of an ongoing longitudinal study of pneumococcal carriage in children less than 5 years of age. Across three years, 87 different sequence types (STs) were found amongst 310 pneumococci. A decline in PCV-7 related STs was observed during the study period. STs 62, 199, 433 and 1692 increased after the implementation of PCV-7 and were related to increases in serotypes 11A, 19A, 22F, and to serotype 6C, respectively. Overall, a strong correlation was observed between ST and serotype. Thirteen STs contained multiple serotypes and 74 STs were associated with only one serotype. On-going molecular epidemiological surveillance of pneumococcal carriage is warranted during the implementation of pneumococcal conjugate vaccines.
[Show abstract][Hide abstract] ABSTRACT: Staphylococcus aureus remains a significant cause of morbidity and mortality and therefore a burden on healthcare systems. Our aim was to estimate the current rate of nasal S. aureus carriage in the general population and to determine the feasibility of nasal self-swabbing. Two thousand people (1200 adults and 800 children) from a single NHS general practice in Southampton UK were randomly selected from a GP age sex register, stratified by age and sex, and invited to undertake nasal self-swabbing in their own home. Overall, 362 (32.5%) adult and 168 (22%) child swabs were returned. Responses were greater for adults, increased age, female gender and decreasing socio-economic deprivation. The overall estimated practice carriage rate of S. aureus directly standardised for age sex was 28% (95% CI 26.1% to 30.2%). Carriage of meticillin-susceptible S. aureus was 27% (95% CI 26.1% to 30.2%) whilst that of meticillin resistant S. aureus was 1.9% (95% CI 0.7% to 3.1%). Although nasal self-swabbing rates were relatively low, they are comparable to other studies and may allow large population-based carriage studies to be undertaken at relatively low cost. Importantly, this study updates prevalence data for S. aureus carriage in the community.
Journal of Medical Microbiology 12/2012; 62(Pt_3). DOI:10.1099/jmm.0.051854-0 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Respiratory infections cause 7% of deaths globally. Microbial upper respiratory tract (URT) carriage is a precursor to respiratory disease, meningitis, and septicaemia. Understanding carriage of URT pathogens is crucial to understanding the spread of respiratory disease. Vaccination against respiratory pathogens has reduced invasive disease rates but also profoundly modified carriage. Previous work shows the importance of individual URT pathogens, especially Streptococcus pneumoniae, and the effects of vaccination on carriage and disease. We aimed to assess carriage of multiple respiratory pathogens within a population benefitting from pneumococcal, Haemophilus influenzae b and meningitis C vaccines. This assessment will enable us to decipher the role of URT community dynamics.
The Lancet 11/2012; 380:S31. DOI:10.1016/S0140-6736(13)60387-6 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Streptococcus pneumoniae is an important pathogen worldwide. Accurate sampling of S. pneumoniae carriage is central to surveillance studies before and following conjugate vaccination programmes to combat pneumococcal disease. Any bias introduced during sampling will affect downstream recovery and typing. Many variables exist for the method of collection and initial processing, which can make inter-laboratory or international comparisons of data complex. In February 2003, a World Health Organisation working group published a standard method for the detection of pneumococcal carriage for vaccine trials to reduce or eliminate variability. We sought to describe the variables associated with the sampling of S. pneumoniae from collection to storage in the context of the methods recommended by the WHO and those used in pneumococcal carriage studies since its publication. A search of published literature in the online PubMed database was performed on the 1st June 2012, to identify published studies that collected pneumococcal carriage isolates, conducted after the publication of the WHO standard method. After undertaking a systematic analysis of the literature, we show that a number of differences in pneumococcal sampling protocol continue to exist between studies since the WHO publication. The majority of studies sample from the nasopharynx, but the choice of swab and swab transport media is more variable between studies. At present there is insufficient experimental data that supports the optimal sensitivity of any standard method. This may have contributed to incomplete adoption of the primary stages of the WHO detection protocol, alongside pragmatic or logistical issues associated with study design. Consequently studies may not provide a true estimate of pneumococcal carriage. Optimal sampling of carriage could lead to improvements in downstream analysis and the evaluation of pneumococcal vaccine impact and extrapolation to pneumococcal disease control therefore further in depth comparisons would be of value.
[Show abstract][Hide abstract] ABSTRACT: Pseudomonas aeruginosa is a Gram-negative bacterium commonly occurring in soil and water. It is an opportunistic pathogen and an important cause of healthcare-associated infections, particularly among infants in neonatal intensive care units (NICUs). Several reports regarding outbreaks of P. aeruginosa in NICUs have been published. MEDLINE and EMBASE databases were searched using the MeSH terms [Pseudomonas aeruginosa], [Outbreak OR Infection OR bacteraemia, OR sepsis OR disease] and [Neonat* OR baby OR babies OR newborn*]. Fifteen studies describing a total of 414 infants colonized or infected with P. aeruginosa were reviewed. The mean percentage of infections occurring in the populations that had been colonized by the organism (calculated as n(infected)/n(infected)+n(colonized)) was 22%. Environmental sampling was performed in 14 studies, nine of which detected P. aeruginosa. The risk factors identified were antimicrobial drug use and the number of days of antimicrobial therapy prescribed before positive blood culture, exposure to particular healthcare workers (HCW), transfusion of blood products, and intravenous delivery of nutrients/electrolytes. Exposure to umbilical venous catheters was associated with bloodstream infections. Increasing age and use of artificial fingernails were risk factors for colonization of hands of HCWs. Low birth weight pre-term infants were at greater risk of mortality from P. aeruginosa infection than older infants.
Journal of Medical Microbiology 06/2012; 61(Pt 8):1052-61. DOI:10.1099/jmm.0.044818-0 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.
[Show abstract][Hide abstract] ABSTRACT: Streptococcus pneumoniae is a major cause of bacterial infections resulting in significant morbidity and mortality worldwide. Currently, up to 13 serotypes are included in pneumococcal conjugate vaccines (PCVs). However, the serotype formulation of these vaccines was initially designed to protect children against serotypes most commonly causing invasive disease in North America, and may not reflect the serotype distribution across the world. Data regarding pneumococcal epidemiology from the other parts of the world, in particular South East Asia, has not been reviewed.
This systematic literature review analyses published serotype data regarding S. pneumoniae isolates from South East Asian countries (defined as countries belonging to the Association of South East Asian Nations, ASEAN): Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam up to 3rd of March 2012.
Analysis of data from six ASEAN countries, from which information on pneumococcal serotypes was available, showed that the most common disease causing serotypes (in rank order) were 19F, 23F, 14, 6B, 1, 19A and 3. Serotype distribution of pneumococcal isolates was similar across the ASEAN region. Serotype level data was more commonly reported for pneumococcal isolates causing invasive pneumococcal disease than for those from non-invasive disease. Studies from Malaysia, Thailand and Singapore contributed the largest proportion of pneumococcal isolates, and serotype data, when compared to other ASEAN countries.
This review demonstrates that the majority of IPD causing serotypes in SE Asia are included in currently licensed PCVs. However, PCV's are included in the routine childhood immunisation schedule of only one of the ten countries included in this analysis. Our findings demonstrate the scarcity of information available on serotype prevalence and distribution of pneumococci in SE Asia.
[Show abstract][Hide abstract] ABSTRACT: The thirteen valent pneumococcal conjugate vaccine (PCV13, Prevenar 13(TM)) is the broader coverage successor to the highly effective seven valent vaccine (PCV7, Prevenar(TM)) which has reduced rates of pneumococcal disease in many countries. Despite the success of PCV7, pneumococcal disease due to non-PCV7 serotypes remains a threat in many settings, in particular many developing countries with a high burden of pneumococcal disease where serotype 1 and 5 are among the most common serotypes. Disease due to certain non-PCV7 serotypes, in particular serotype 19A has also begun to increase in incidence in countries with widespread use of PCV7. PCV13 consists of thirteen pneumococcal capsular polysaccharides individually conjugated to the diphtheria-derived protein carrier CRM(197). In addition to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F included in PCV7, PCV13 also includes serotypes 1, 3, 5, 6A, 7F and 19A. PCV13 was licensed on the basis of non-inferiority trials and has proved to be at least as safe and effective as PCV7. PCV13 replaced PCV7 in the childhood immunisation schedules of the USA and UK in 2010 and is being rolled out to an increasing number of developing countries during 2011. Here we review the current literature regarding this vaccine, describing safety, efficacy, global serotype coverage and use and future directions.
Human vaccines 10/2011; 7(10):1012-8. DOI:10.4161/hv.7.10.16794 · 3.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pathogens increasingly evade current vaccines, and new strategies to control them are needed. There is mounting evidence that replacement of vaccine serotypes of Streptococcus pneumoniae with non-vaccine serotypes has taken place following widespread use of limited-serotype conjugate vaccines. New strategies to control vaccine evasion are needed and understanding evolutionary theory is important for the development of such approaches. Hosts are under selection pressure to evolve resistance against pathogens whereas pathogens are under selection pressure to evolve counter-resistance against the resistance mechanism of their host. Evolutionary changes in both host and pathogen lead to a continuous turnover of host and pathogen genotypes; this is known as Red Queen dynamics. We argue that integrating evolutionary thinking into pneumococcal vaccine design will lead to the avoidance of Red Queen dynamics and improved interventions against pneumococci.
Trends in Microbiology 08/2011; 19(8):377-81. DOI:10.1016/j.tim.2011.06.001 · 9.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Asymptomatic carriage of the opportunistic pathogen Streptococcus pneumoniae is known to precede the development of invasive disease. Young children are one of the major reservoirs for pneumococci and worldwide over 700,000 children under two years old die due to invasive pneumococcal disease each year. Heptavalent conjugate vaccine (PCV-7) was introduced into the UK childhood immunisation schedule in September 2006. Our objective was to assess the emergence of colonising serotypes in young children in the three years following PCV-7 implementation.
Time-series prevalence survey set in the paediatric outpatients department of a large UK teaching hospital. Participants were children aged four years and under attending the outpatients department during PCV-7 introduction (October 2006-February 2007) and in the same months of the two subsequent years. The main outcome measure was prevalence of pneumococcal carriage by serotype.
The rate of pneumococcal nasopharyngeal carriage remained stable during the three year period. We observed a significant 69% (95% CI, -40% to -118%, p<0.0001) decrease in carriage of PCV-7 serotypes during PCV-7 implementation and a concomitant increase in the proportion of non PCV-7 serotypes. The most prevalent emerging non-vaccine serotypes were 6C, 11A, 19A and 22F. By March 2009, PCV-13 was predicted to cover only 33.3% (95% CI, 24.2-42.5%) of strains carried in the study population.
Although the overall pneumococcal carriage rate remained stable between 2006 and 2009, we observed a significant decrease in the serotype coverage of PCV-7 and PCV-13. PCV-7 was highly successful in reducing carriage of vaccine serotypes. However, the increase in the proportion of non-vaccine serotypes found both in our study and causing invasive disease currently in the UK, underlines the importance of continued surveillance of carriage and disease.