Identifying transmission routes of <i>Streptococcus pneumoniae</i> and sources of acquisitions in high transmission communities

Althouse, Benjamin M.; Hammitt, Laura L.; Grant, Lindsay R.; Wagner, Bradley G.; Reid, Raymond; Larzelere-Hinton, Francene; Weatherholtz, Robert; Klugman, Keith P.; Rodgers, Gail L.; O'Brien, Katherine L.; Hu, Hao

doi:10.1017/s095026881700125x

Cited by 53 publications

(60 citation statements)

References 27 publications

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“…Our results are consistent with previous epidemiological and modelling studies of pneumococcal colonization that suggest that toddlers and young school-aged children, rather than infants, drive transmission of pneumococcus in the population (11)(12)(13)(14). (27).…”

Section: Discussionsupporting

confidence: 92%

“…To consider this issue, it is critical to determine which groups of young children contribute most to the indirect benefit of the vaccine for unimmunized adults. Epidemiological and modeling studies of transmission focused on households and daycare centers suggest that toddlers and older children, rather than infants, drive transmission in the population (11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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Decline in pneumococcal disease in unimmunized adults is associated with vaccine-associated protection against colonization in toddlers and preschool-aged children

Pitzer

Regev‐Yochay

Givon-Lavi

et al. 2018

Preprint

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Conflicts of Interest: Within the last two years, DMW has received consulting fees from Affinivax and Pfizer. RD has received grants and consulting and speaker fees from Pfizer; grant and consulting fees from MSD and consulting fees from MeMed. GRY has received consulting fees from Pfizer and research support from Pfizer and MSD. ABSTRACTVaccinating children with pneumococcal conjugate vaccines disrupts transmission, reducing disease rates in unvaccinated adults. When considering changes in vaccine dosing strategies (e.g., removing doses), it is critical to understand which groups of children contribute most to transmission to adults. We used data from children and adults in Israel to evaluate how the buildup of vaccine-associated immunity in children was associated with declines in IPD due to vaccine-targeted serotypes in unimmunized adults. Data on vaccine uptake and prevalence of colonization with PCV-targeted serotypes were obtained from a unique study conducted among children visiting an emergency department in southern Israel and from surveys of colonization from central Israel. Data on invasive pneumococcal disease in adults were obtained from a nationwide surveillance study. We compared the trajectory of decline of IPD due to PCVtargeted serotypes in adults with the trajectory of decline of colonization prevalence and trajectory of increase in vaccine-derived protection against pneumococcal carriage among different age groupings of children. The declines in IPD in adults were most closely associated with the declines in colonization and increased vaccination coverage in children in the range of 36-59 months of age. This suggests that preschool-aged children, rather than infants and young toddlers, are responsible for maintaining the indirect benefits of PCVs.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Decline in pneumococcal disease in unimmunized adults is associated with vaccine-associated protection against colonization in toddlers and preschool-aged children

Pitzer

Regev‐Yochay

Givon-Lavi

et al. 2018

Preprint

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“…Therefore, the success of a 1 + 1 PCV schedule relies on the timely provision of a booster dose and the schedule's ability to sustain indirect protection in a mature PCV programme. Toddlers and older children between the age of 12 and 36 months of age 18 rather than infants 19 , are thought to be the major spreaders of pneumococci to their siblings and parents. Vaccinating this age group is therefore thought to be critical in establishing and sustaining indirect protection, hence reassurance is required that the booster response following a single priming dose would sustain vaccine efficacy against acquisition of carriage.…”

Section: Discussionmentioning

confidence: 99%

Pneumococcal conjugate vaccine 13 delivered as one primary and one booster dose (1 + 1) compared with two primary doses and a booster (2 + 1) in UK infants: a multicentre, parallel group randomised controlled trial

Green

Southern

Andrews

et al. 2018

The Lancet Infectious Diseases

101

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SummaryBackgroundInfants in the UK were first offered a pneumococcal conjugate vaccine (PCV7) in 2006, given at 2 and 4 months of age and a booster dose at 13 months (2 + 1 schedule). A 13-valent vaccine (PCV13) replaced PCV7 in 2010. We aimed to compare the post-booster antibody response in UK infants given a reduced priming schedule of PCV13 (ie, a 1 + 1 schedule) versus the current 2 + 1 schedule and to assess the potential effect on population protection.MethodsIn this multicentre, parallel group, randomised controlled trial, we recuited infants due to receive their primary immunisations aged up to 13 weeks on first vaccinations by information booklets mailed out via the NHS Child Health Information Service and the UK National Health Application and Infrastructure Services. Eligible infants were randomly assigned (1:1) to receive PCV13 at 2, 4, and 12 months (2 + 1 schedule) or 3 and 12 months of age (1 + 1 schedule) delivered with other routine vaccinations. Randomisation was done by computer-generated permuted block randomisation, with a block size of six. Participants and clinical trial staff were not masked to treatment allocation. The primary endpoint was serotype-specific immunoglobulin G concentrations values (geometric mean concentrations [GMC] in μg/mL) measured in blood samples collected at 13 months of age. Analysis was by modified intention to treat with all individuals included by randomised group if they had a laboratory result. This trial is registered on the EudraCT clinical trial database, number 2015-000817-32, and ClinicalTrials.gov, number NCT02482636.FindingsBetween September, 2015, and June, 2016, 376 infants were assessed for eligibility. 81 infants were excluded for not meeting the inclusion criteria (n=50) or for other reasons (n=31). 213 eligible infants were enrolled and randomly allocated to group 1 (n=106; 2 + 1 schedule) or to group 2 (n=107; 1 + 1 schedule). In group 1, 91 serum samples were available for analysis 1 month after booster immunisation versus 86 in group 2. At month 13, post-booster, GMCs were equivalent between schedules for serotypes 3 (0·61 μg/mL in group 1 vs 0·62 μg/mL in group 2), 5 (1·74 μg/mL vs 2·11 μg/mL), 7F (3·98 μg/mL vs 3·36 μg/mL), 9V (2·34 μg/mL vs 2·50 μg/mL), and 19A (8·38 μg/mL vs 8·83 μg/mL). Infants given the 1 + 1 schedule had significantly greater immunogenicity post-booster than those given the 2 + 1 schedule for serotypes 1 (8·92 μg/mL vs 3·07 μg/mL), 4 (3·43 μg/mL vs 2·55 μg/mL), 14 (16·9 μg/mL vs 10·49 μg/mL), and 19F (14·76 μg/mL vs 11·12 μg/mL; adjusted p value range <0·001 to 0·047). The 2 + 1 schedule was superior for serotypes 6A, 6B, 18C and 23F (adjusted p value range <0·0001 to 0·017). In a predefined numerical subset of all of the infants recruited to the study (n=40 [20%]), functional serotype-specific antibody was similar between schedules. 26 serious adverse events were recorded in 21 (10%) infants across the study period; 18 (n=13) were in the 2 + 1 group and eight (n=8) in the 1 + 1 group. Only one serious adverse event, a hi...

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“…The inhomogeneous transmission matrix presented in Figure 1c overperformed the others and was used for the results presented in the main text. Its structure is based on epidemiological studies conducted in American, European and African populations reporting typical, strong, intrinsic variation in frequency, efficiency and environmental risk of transmission between age-groups 10,31,[42][43][44][45][46][47] . In summary, the transmission matrix is generally populated with a baseline coefficient β, and a different coefficient θ assigned to transmission occurring within and between ages 0-5 years, and within 6-7 and 8-9 years of age independently.…”

Section: Force Of Infectionmentioning

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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Identifying transmission routes of Streptococcus pneumoniae and sources of acquisitions in high transmission communities

Cited by 53 publications

References 27 publications

Decline in pneumococcal disease in unimmunized adults is associated with vaccine-associated protection against colonization in toddlers and preschool-aged children

Decline in pneumococcal disease in unimmunized adults is associated with vaccine-associated protection against colonization in toddlers and preschool-aged children

Pneumococcal conjugate vaccine 13 delivered as one primary and one booster dose (1 + 1) compared with two primary doses and a booster (2 + 1) in UK infants: a multicentre, parallel group randomised controlled trial

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

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