Vaccination can drive an increase in frequencies of antibiotic resistance among nonvaccine serotypes of<i>Streptococcus pneumoniae</i>

Obolski, Uri; Lourenço, José; Thompson, Craig; Thompson, Robin N; Gori, Andrea; Gupta, Sunetra

doi:10.1073/pnas.1718712115

Cited by 44 publications

(51 citation statements)

References 69 publications

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“…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%

“…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. For example, models have successfully yielded estimates of VT and non-VT pneumococci transmission potentials 26,[29][30][31] , pneumococcal competition factors 8,9,23,28,32,33 and measures of vaccine-induced protection from carriage at the individual level 11,17,28,34,35 , none of which are readily observed or quantified in crosssectional observational studies.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

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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“…61 Although incompletely understood, the association of serotype replacement with antibiotic resistance has been attributed to elimination of competition by antibiotic-susceptible vaccine serotypes in the nasopharynx, enabling emergence of previously suppressed, resistant nonvaccine serotypes. 62 In this setting, antibiotic resistance comes at the expense of reduced fitness of these nonvaccine serotypes. 63 This may be overcome, however, via genetic transfer of metabolic and virulence components from vaccine to nonvaccine serotypes of the pathogen, conferring both fitness and persistence on the latter serotypes.…”

Section: Causes and Mechanisms Of Antibiotic Resistancementioning

confidence: 99%

The Role of Streptococcus pneumoniae in Community-Acquired Pneumonia

Feldman

Anderson

2020

Semin Respir Crit Care Med

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AbstractWith the notable exceptions of the United States and Canada in particular, the global burden of disease in adults due to invasive infection with the dangerous respiratory, bacterial pathogen, Streptococcus pneumoniae (pneumococcus) remains. This situation prevails despite the major successes of inclusion of polysaccharide conjugate vaccines (PCVs) in many national childhood immunization programs and associated herd protection in adults, as well as the availability of effective antimicrobial agents. Accurate assessment of the geographic variations in the prevalence of invasive pneumococcal disease (IPD) has, however, been somewhat impeded by the limitations imposed on the acquisition of reliable epidemiological data due to reliance on often insensitive, laboratory-based, pathogen identification procedures. This, in turn, may result in underestimation of the true burden of IPD and represents a primary focus of this review. Other priority topics include the role of PCVs in the changing epidemiology of IPD in adults worldwide, smoking as a risk factor not only in respect of increasing susceptibility for development of IPD, but also in promoting pneumococcal antibiotic resistance. The theme of pneumococcal antibiotic resistance has been expanded to include mechanisms of resistance to commonly used classes of antibiotics, specifically β-lactams, macrolides and fluoroquinolones, and, perhaps somewhat contentiously, the impact of resistance on treatment outcome. Finally, but no less importantly, the role of persistent antigenemia as a driver of a chronic, subclinical, systemic proinflammatory/procoagulant phenotype that may underpin the long-term sequelae and premature mortality of those adults who have recovered from an episode of IPD, is considered.

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“…However, it is unclear how universal vaccination may itself impact upon the evolution of antibiotic resistance in S. pneumoniae. While mathematical models are a useful tool for generating predictions from nonlinear transmission dynamics (15,16), existing models focus on serotype-specific vaccines and, even then, disagree over the expected impact of vaccination on resistance evolution (17)(18)(19)(20)(21)(22)(23). Comparing and interpreting the results of these models is hampered by the fact that none starts from a position of recapitulating contemporary, large-scale patterns of antibiotic resistance.…”

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confidence: 99%

Stabilising effects of competition and diversity determine vaccine impact on antibiotic resistance evolution

Davies

Jit

Atkins

2019

Preprint

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One sentence summary: Competition and diversity are key to antibiotic resistance 17 evolution and determine whether vaccines will prevent or increase resistant infections. 18Bacterial vaccines can protect recipients from contracting potentially antibiotic-19 resistant infections. But by altering the selective balance between sensitive and 20 resistant strains, vaccines may also help suppress-or spread-antibiotic 21 resistance among unvaccinated individuals. Predicting the outcome requires 22 knowing the drivers of resistance evolution. Using mathematical modelling, we 23 identify competition and diversity as key mediators of resistance evolution. 24Specifically, we show that the frequency of penicillin resistance in Streptococcus 25 pneumoniae (pneumococcus) across 27 European countries can be explained by 26 between-host diversity in antibiotic use, heritable diversity in pneumococcal 27 carriage duration, or within-host competition. We use our calibrated model to 28 predict the impact of universal pneumococcal vaccination upon the prevalence of 29 carriage, incidence of disease, and frequency of resistance for S. pneumoniae. The 30 relative strength and directionality of competition between resistant and 31 sensitive pneumococcal strains determines whether vaccination promotes, 32 inhibits, or has little effect on the evolution of antibiotic resistance. Finally, we 33 find that differences in overall bacterial transmission and carriage alter 34 predictions, suggesting that evidence-based policies for managing resistance with 35 vaccines must be tailored to both pathogen and setting. 36 37In an age of widespread antibiotic resistance, there is growing interest in using vaccines 38 to prevent bacterial infections that would otherwise call for treatment with antibiotics 39(1-4). This interest arises for two main reasons: first, vaccines are effective against both 40 antibiotic-resistant and antibiotic-sensitive bacteria; and second, successful prophylaxis 41 removes the need for a course of antibiotic therapy that might promote more resistance 42(2-5). Over the past two decades, the use of pneumococcal conjugate vaccines (PCVs) 43 has seemingly borne out these advantages. Administering PCVs to young children has 44 substantially reduced disease caused by S. pneumoniae (5-8)-a common asymptomatic 45 coloniser of the nasopharynx which can cause pneumonia, meningitis and other 46 infections when invasive-and has decreased demand for antibiotic therapy, largely by 47 reducing cases of otitis media (5, 9). But because PCV formulations target only a fraction 48 of the ~100 known pneumococcal serotypes, the niche vacated by PCV-targeted 49 serotypes has been filled by non-vaccine serotypes, and overall pneumococcal carriage 50 has rebounded to pre-vaccine levels (10, 11). Concomitantly, the incidence of infections 51 attributed to non-vaccine serotypes (12) and the proportion of non-vaccine-type 52 infections exhibiting antibiotic resistance (5, 13) have risen in many settings. Concern 53 over serotype replacement-along ...

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Vaccination can drive an increase in frequencies of antibiotic resistance among nonvaccine serotypes ofStreptococcus pneumoniae

Cited by 44 publications

References 69 publications

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

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

The Role of Streptococcus pneumoniae in Community-Acquired Pneumonia

Stabilising effects of competition and diversity determine vaccine impact on antibiotic resistance evolution

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