Vaccination Drives Changes in Metabolic and Virulence Profiles of Streptococcus pneumoniae

Watkins, Eleanor; Penman, Bridget S.; Lourenço, José; Buckee, Caroline O.; Maiden, Martin; Gupta, Sunetra

doi:10.1371/journal.ppat.1005034

Cited by 52 publications

(106 citation statements)

References 44 publications

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“…These results bear some similarity to previous multistrain models where linkage disequilibrium between loci emerges from the epidemiological properties of strains (21,22). In these models, unlike Number of isolates and serotypes for which carriage duration could be calculated: Massachusetts, 180 and 19; Malawi, 300 (Materials and Methods) and 9; and Maela, 2,923 and 51.…”

Section: Discussionsupporting

confidence: 83%

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

Lehtinen

Blanquart

Croucher

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

130

195

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Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence of antibiotic sensitive and resistant strains are not fully understood. While allelic diversity can be maintained at a locus by direct balancing selection, there is no evidence for such selection acting in the case of resistance. In this work, we propose a mechanism for maintaining coexistence at the resistance locus: linkage to a second locus that is under balancing selection and that modulates the fitness effect of resistance. We show that duration of carriage plays such a role, with long duration of carriage increasing the fitness advantage gained from resistance. We therefore predict that resistance will be more common in strains with a long duration of carriage and that mechanisms maintaining diversity in duration of carriage will also maintain diversity in antibiotic resistance. We test these predictions in S. pneumoniae and find that the duration of carriage of a serotype is indeed positively correlated with the prevalence of resistance in that serotype. These findings suggest heterogeneity in duration of carriage is a partial explanation for the coexistence of sensitive and resistant strains and that factors determining bacterial duration of carriage will also affect the prevalence of resistance.A ntibacterial resistance is a serious threat to public health, with resistant strains emerging in numerous pathogens. Although estimates of resistance levels vary by region, pathogen, and antibiotic type, a common feature is that fixation of resistance is rarely observed: sensitive and resistant strains tend to coexist robustly. For example, according to the European Antimicrobial Resistance Surveillance Network (EARS-Net; available at ecdc.europa.eu) (1), the prevalence of penicillin and macrolide nonsensitivity in Streptococcus pneumoniae has been stable at around 10 and 15% respectively for the past 15 years in Europe. Similarly, EARS-Net estimates of multidrug resistance in Klebsiella pneumoniae have varied around 20% since 2009 and those for methicillin resistance in Staphylococcus aureus have ranged between 15 and 25% from 1999 onwards, with no persisting directional trend.The stable coexistence of sensitive and resistant strains is unexpected: because these strains compete for the same hosts, simple ecological models predict that the fitter strain would dominate and the weaker strain become extinct ("competitive exclusion"). Understanding how coexistence is maintained is therefore important for predicting the prevalence of resistant strains and for explaining the approximately linear relationship between regional antibiotic consumption and resistance (2). Predicting the prevalence of resistance is, in turn, crucial...

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Section: Discussionsupporting

confidence: 83%

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

Lehtinen

Blanquart

Croucher

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

130

195

View full text Add to dashboard Cite

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“…Moreover, a reduction of isolates belonging to ST320 19A has also been detected in a pediatric population from the USA [35] after the PCV13 introduction, even though this reduction was lower than that observed for the susceptible clones. In fact, it seems that the persistence of the ST320 19A over the remaining 19A clones may be due to a combination of factors including an improved colonizing ability [36], a change in their metabolic profile [37] and an enhanced resistance to the antimicrobial stress due its MDR pattern.…”

Section: Discussionmentioning

confidence: 99%

Decrease of invasive pneumococcal disease (IPD) in adults after introduction of pneumococcal 13-valent conjugate vaccine in Spain

et al. 2017

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A prospective laboratory-based multicenter study that collected all adult invasive pneumococcal disease (IPD) episodes from 6 Spanish hospitals before (2008–2009) and after (2012–2013). The 13-valent pneumococcal conjugate vaccine (PCV13) licensure was conducted in order to analyze the impact of PCV13 introduction for children on adult IPD. A total of 1558 IPD episodes were detected. The incidence of IPD decreased significantly in the second period by -33.9% (95% CI, -40.3% to -26.8%). IPD due to PCV7 serotypes (-52.7%; 95% CI, -64.2% to -37.5%) and to PCV13 additional serotypes (-55.0% 95% CI, -62.0% to -46.7%) significantly decreased whereas IPD due to non-PCV13 serotypes remained stable (1.0% 95% CI, -12.9% to 17.2%). IPD due to all PCV13 additional serotypes significantly declined with the exception of serotype 3 (-11.3%; 95%CI -35.0% to 21.1%). IPD due to two non-PCV13 serotypes varied: serotype 6C that rose (301.6%; 95%CI, 92.7% to 733.3%, p<0.001), related to the expansion of ST3866C, and serotype 8 that decreased (-34.9%, 95%CI, -57.1 to -1.2, p = 0.049), related to a decline of the ST638. The recombinant clone ST652111A (variant of ST1569V) increased in frequency. The decrease of serotype 19A IPD was linked to a fall in those antibiotic susceptible clones. In the last period, rates of penicillin- and cefotaxime-resistance remained under 10% and 4%, respectively. Adult IPD decreased after the PCV13 introduction in Spain due to herd protection. The spread of multidrug resistant clones (ST3866C, ST652111A) related to non-PCV13 serotypes needs further surveillance.

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“…All have been demonstrated to be highly protective against 7, 10 or 13 common pneumococcal serotypes associated with carriage and disease (also termed vaccine serotypes, VT). A frequently observed consequence of PCV introduction is the increase in both carriage and disease of non-VT pneumococci (NVT), likely due to increased niche availability and reduction of competition between VT and NVT [4][5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

“…However, recently published data on nasopharyngeal carriage as measured in a cross-sectional observational study in Blantyre (Southern Malawi), four to seven years after PCV13 introduction (2015)(2016)(2017)(2018), has shown that vaccine impact (VT carriage reduction) has been slower than expected and heterogeneous across age-groups 22 . Epidemiological mathematical models have previously been employed successfully to improve our understanding of pneumococcal dynamics 5,9,[23][24][25][26][27] , as well as having contributed to explain, estimate and project PCV impact 8,11,28 . The main advantage of models is their cost-free potential to test hypotheses and gain a mechanistic, ecological and immunological understanding of carriage and disease dynamics, estimating epidemiological parameters which are difficult to otherwise quantify from raw epidemiological data.…”

Section: Introductionmentioning

confidence: 99%

Determinants of high residual post-PCV13 pneumococcal vaccine type carriage in Blantyre, Malawi: a modelling study

Lourenço

Obolski

Swarthout

et al. 2018

Preprint

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Abbreviations:VT -vaccine type NVT -non-vaccine type PCV -pneumococcal conjugate vaccine CI -confidence interval bMCMC -Bayesian Markov chain Monte Carlo ODE -ordinary-differential equations FOI -force of infection dVP -duration of vaccine-induced protection 1 Abstract Background: In November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to seven years after introduction (2015)(2016)(2017)(2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in developed countries, and VT impact was surprisingly asymmetric across age-groups. A dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage.Results: Accumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age-groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49-82.26%), similar to previous estimates.Ten-year projected vaccine impact (VT carriage reduction) among 0-9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02-81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection. Conclusions:We have identified both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by age-related characteristics of the local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.PCV routine vaccination has been a common control strategy for over a decade in developed countries, with past experience showing that both pre-and post-PCV pneumococcal carriage can be highly variable within and between countries 10-16 . PCV vaccines have only recently been introduced (survey 7). In this study, we use the mid-point dates of the surveys for model fitting and presentation of results. A total of 7148 individuals were screened with nasopharyngeal swabs processed following WHO recommendations 36 . Isolates were serotyped by latex agglutination (ImmuLex™ 7-10-13-valent Pneumotest; Statens Serum Institute, Denmark). In this study, we use all the data from three agegroups: 499 vaccinated children 2 years old, 2565 vaccinated children 3-7 years old and 1402

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Vaccination Drives Changes in Metabolic and Virulence Profiles of Streptococcus pneumoniae

Cited by 52 publications

References 44 publications

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

Decrease of invasive pneumococcal disease (IPD) in adults after introduction of pneumococcal 13-valent conjugate vaccine in Spain

Determinants of high residual post-PCV13 pneumococcal vaccine type carriage in Blantyre, Malawi: a modelling study

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