Abstract
Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations. Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine [PCV13] as part of the Expanded Program on Immunization [EPI]), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut [SSI], Denmark). For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. A total of 1,347 samples were analyzed. Concordance was 90.7% (95% confidence interval [CI], 89.0 to 92.2%) between latex agglutination and PneumoCaT, 95.2% (95% CI, 93.9 to 96.3%) between latex agglutination and the microarray, and 96.6% (95% CI, 95.5 to 97.5%) between the microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococci carried at low relative abundances (median, 8%), the microarray increased VT detection by 31.5% over that by latex serotyping. To conclude, all 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 for investigating the importance of vaccine serotypes at low relative abundances in transmission and disease.
Highlights
Sentinel sites should be considered for regional nonvaccine serotypes (NVT) and vaccine serotype (VT)
Estimation aAMR, antimicrobial resistance; NT, nontypeable; VE, vaccine effectiveness. bThe estimated costs and feasibility of implementation and maintenance are specific to the study requirements and laboratory capacity at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme in Blantyre, Malawi. cNVT and NT isolates are reported as NVT
The use of both commercial products and latex serotyping reagents produced in-house can significantly increase the number of NVT serotypes that can be differentiated by latex agglutination. dAn AMR profile cannot be assigned to a single strain in a sample with multiple-serotype or multiple-pathogen carriage
Summary
Blantyre is located in southern Malawi with an urban population of approximately 1.3 million. Samples were collected as part of a larger 3.5-year pneumococcal carriage surveillance project, as described elsewhere [14]. This was a prospective rolling cross-sectional observational study using stratified random sampling to measure nasopharyngeal pneumococcal carriage in Blantyre, Malawi. The samples used in this analysis were collected during the first 2 years of twice-annual cross-sectional surveys, from June 2015 to April 2017. Recruitment included three groups: (i) healthy children 3 to 6 years old who received the 13-valent pneumococcal conjugate vaccine (PCV13) as part of routine EPI [Expanded Program on Immunization] activities, (ii) healthy children 5 to 10 years old who were age-ineligible to receive PCV13 as part of EPI, and (iii) HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART)
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