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

Abstract

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

Dose-specific effectiveness of 7- and 13-valent pneumococcal conjugate vaccines against vaccine-serotype Streptococcus pneumoniae colonization: a matched, case-control study

“…Elsewhere, 3+0 and a 2+1 series have been estimated to confer 60-69% protection against vaccineserotype carriage in the second year of life. [20][21][22] These findings are in agreement with our point estimates of 50-77% PCV effectiveness against vaccine-serotype carriage after three doses at age 13-24 months.…”

Within-host competition modulates pneumococcal antibiotic resistance in the pre-vaccination era

“…As illustrated in Figures 3A-B , reproduction of pre-vaccination resistance levels while respecting priors related to observed NVT versus VT prevalence and strain co-infection identified particular competition parameter regions. The latter are characterized by a combination of low immunological ( ) and low to intermediate ecological competition ( .25 γ < 0 ), which are compatible with observations of recurrent pneumococcal .2, ψ .7 ψ > 0 < 0 infection [56][57][58] , co-circulation of NVT and VT serotypes [10,55,56,59,60] as well as frequent co-infection [54,55] .…”

“…In particular, carriage levels of VT and NVT serotypes tended to be similar ( Figure 2A ), there was no host co-infection ( Figure 2B ), and strains resistant to antibiotics dominated the population ( Figures 2C ). Such epidemiological dynamics are incompatible with what is observed for the pneumococcus, which ubiquitously include high co-infection [54,55] , reinfection [56][57][58] , and co-circulation of NVT and VT serotypes with dominance of VT [10,55,56,59,60] .…”

“…Pneumococci are characterized by a polysaccharide capsule comprising over 90 distinct antigenic types, termed serotypes [5,6] . Since the introduction of the pneumococcal conjugate vaccines, targeting seven (PCV7), ten (PCV10) or thirteen (PCV13) serotypes, there has been a rapid decrease in pneumococcal carriage and disease of the targeted serotypes across ages [7][8][9][10][11] . Concomitantly, increases in the frequencies of non-targeted serotypes have been recorded both in carriage and disease in a number of countries worldwide [12][13][14][15][16][17][18][19][20] .…”