![]() The gold standard serotyping method, the Quellung reaction, was developed in the early 1900s and is performed by testing colonies with a set of type-specific antisera ( 12). Unfortunately, work in resource-poor settings too often limits the number of these parameters that can be achieved. Additional desirable parameters include detection of most or all serotypes, the ability to detect multiple serotypes in carriage (common in high-burden settings ), in-depth information on genotype, suitability for scale-up to large projects, and practicality for resource-poor settings. Given these differences, accurate assessment of the serotype distribution associated with both pneumococcal colonization and pneumococcal disease is needed in the evaluation, formulation, and delivery of pneumococcal vaccines.Ī pneumococcal serotyping method suitable for use in robust carriage and surveillance studies should therefore, at minimum, be accurate in its serotype assignment, particularly in relation to VT. Serotype distribution differs among continents as well as among individual countries ( 9). This phenomenon, known as serotype replacement, may be more pronounced in low-income settings because of the higher prevalence, density, and diversity of pneumococcal carriage, and it represents a considerable risk to the global pneumococcal immunization strategy ( 8). However, nonvaccine serotypes (NVT) have the potential to fill the ecological niche, becoming more common in carriage and disease ( 5, – 7). ![]() ![]() With reduced carriage among the vaccinated, there is then a reduced risk of VT-IPD (direct protection) and reduced transmission, leading to a reduced risk of VT-IPD among those not vaccinated with PCV (indirect protection). PCV reduce nasopharyngeal carriage of the subset of pneumococcal serotypes they contain, known as vaccine serotypes (VT). Evidence also shows that HIV-infected children and adults are at significantly higher risk of invasive pneumococcal disease (IPD) than their non-HIV-infected counterparts ( 3, 4).Ĭurrent multivalent pneumococcal conjugate vaccines (PCV) target subsets of the 100 capsular serotypes known to be expressed by the pneumococcus. The pneumococcus is estimated to be responsible for >318,000 (uncertainty ratio, 207,000 to 395,000) deaths every year in children aged 1 to 59 months, with the highest mortality burden among African children ( 2). Although carriage is usually asymptomatic, nasopharyngeal (NP) colonization is a prerequisite for diseases including otitis media, sinusitis, pneumonia, bacteremia, and meningitis ( 1). Streptococcus pneumoniae colonizes the nasopharynx of healthy individuals. 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. Latex serotyping is accurate in identifying vaccine serotypes and requires the least expertise and resources for field implementation and analysis. To conclude, all three serotyping methods were highly concordant in identifying dominant serotypes. 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. Concordance was 90.7% (95% confidence interval, 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. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut, Denmark). Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine as part of the Expanded Program on Immunization ), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). Nasopharyngeal swabs were collected according to WHO recommendations between 20 by using stratified random sampling among study populations. 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. ![]() ![]() 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. ![]()
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