Kamng'ona, A. W. | bioRxiv Science

bioRxiv2020

Evaluation of pneumococcal serotyping in nasopharyngeal carriage isolates by latex agglutination, whole genome sequencing (PneumoCaT) and DNA microarray in a high pneumococcal carriage prevalence population in Malawi

BackgroundAccurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for the evaluation and formulation of pneumococcal vaccines and informing vaccine policy. MethodsWe evaluated pneumococcal serotyping concordance between latex agglutination, PneumoCaT by whole genome sequencing (WGS) and DNA microarray using samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected, following WHO recommendations, between 2015 and 2017, using stratified random sampling among study populations. Participants included healthy children 3-6 years old (PCV13 vaccinated as part of EPI), healthy children 5-10 years (age-ineligible for PCV13), and HIV-infected adults (18-40yrs) on ART. For phenotypic serotyping we used a 13-valent latex kit (SSI, Denmark). For genomic serotyping we applied PneumoCaT pipeline to whole genome sequence libraries. For molecular serotyping by microarray we used the BUGS Bioscience DNA microarray. Results1347 samples were analysed. Concordance was 90.7% (95% CI: 89.0-92.2) between latex and PneumoCaT; 95.2% (93.9-96.3) between latex and microarray; and 96.6% (95.5-97.5) between microarray and PneumoCaT. By detecting carried vaccine serotype (VT) pneumococcus in low relative abundance (median 8%), microarray increased VT detection by 31.5% compared to latex serotyping. ConclusionAll three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine-serotypes and requires the least expertise and resources for field-implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories while investigating the importance of VT in low relative abundance in transmission and disease.

microbiology↗

bioRxiv2018

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

BackgroundIn November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to seven years after introduction (2015-2018), 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.\n\nResultsAccumulation 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.\n\nConclusionsWe 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.

epidemiology↗