Streptococcus pneumoniae genomic datasets from an Indian population describing pre-vaccine evolutionary epidemiology using a whole genome sequencing approach

Abstract

Globally, India has a high burden of pneumococcal disease, and pneumococcal conjugate vaccine (PCV) has been rolled out in different phases across the country since May 2017 in the national infant immunization programme (NIP). To provide a baseline for assessing the impact of the vaccine on circulating pneumococci in India, genetic characterization of pneumococcal isolates detected prior to introduction of PCV would be helpful. Here we present a population genomic study of 480 Streptococcus pneumoniae isolates collected across India and from all age groups before vaccine introduction (2009-2017), including 294 isolates from pneumococcal disease and 186 collected through nasopharyngeal surveys. Population genetic structure, serotype and antimicrobial susceptibility profile were characterized and predicted from whole-genome sequencing data. Our findings revealed high levels of genetic diversity represented by 110 Global Pneumococcal Sequence Clusters (GPSCs) and 54 serotypes. Serotype 19F and GPSC1 (CC320) was the most common serotype and pneumococcal lineage, respectively. Coverage of PCV13 (Pfizer) and 10-valent Pneumosil (Serum Institute of India) serotypes in age groups of ≤2 and 3-5 years were 63-75 % and 60-69 %, respectively. Coverage of PPV23 (Merck) serotypes in age groups of ≥50 years was 62 % (98/158). Among the top five lineages causing disease, GPSC10 (CC230), which ranked second, is the only lineage that expressed both PCV13 (serotypes 3, 6A, 14, 19A and 19F) and non-PCV13 (7B, 13, 10A, 11A, 13, 15B/C, 22F, 24F) serotypes. It exhibited multidrug resistance and was the largest contributor (17 %, 18/103) of NVTs in the disease-causing population. Overall, 42 % (202/480) of isolates were penicillin-resistant (minimum inhibitory concentration ≥0.12 µg ml^-1) and 45 % (217/480) were multidrug-resistant. Nine GPSCs (GPSC1, 6, 9, 10, 13, 16, 43, 91, 376) were penicillin-resistant and among them six were multidrug-resistant. Pneumococci expressing PCV13 serotypes had a higher prevalence of antibiotic resistance. Sequencing of pneumococcal genomes has significantly improved our understanding of the biology of these bacteria. This study, describing the pneumococcal disease and carriage epidemiology pre-PCV introduction, demonstrates that 60-75 % of pneumococcal serotypes in children ≤5 years are covered by PCV13 and Pneumosil. Vaccination against pneumococci is very likely to reduce antibiotic resistance. A multidrug-resistant pneumococcal lineage, GPSC10 (CC230), is a high-risk clone that could mediate serotype replacement.

Keywords: India; S. pneumoniae; genomic dataset; global pneumococcal sequence cluster; pre-vaccine.

Fig. 1.

The geographical and age distribution of pneumococcal collection in this study. (a) The size of the circle is proportionate to the number of isolates; breakdown is by carriage and disease. (b) Age-wise distribution of disease and carriage pneumococcal isolates.

Fig. 2.

The top ten serotypes among pneumococci from (a) disease-causing and (b) carriage populations, stratified by age groups.

Fig. 3.

(a) Serotype composition and prevalence of antibiotic resistance by Global Pneumococcal Sequence Clusters (GPSCs) among disease (n=294) and (b) carriage (n=186) isolates from India. Lineages with fewer than three isolates are not shown. PCV13 serotypes are indicated in solid colour and non-PCV13 serotypes in colours with patterns. This figure shows that GPSC10 is one of the major pneumococcal lineages in both populations. It expresses a variety of serotypes and is multidrug resistant. Red=resistant; white=sensitive.

Fig. 4.

Maximum-likelihood tree reconstructed with all pneumococcal genomes in this study (n=480). The nodes of the tree are coloured according to the Global Pneumococcal Sequencing Clusters (GPSCs). Multidrug-resistant (MDR) lineages are highlighted and their corresponding in silico serotype, antibiotic-resistance profile and presence of pilus are indicated in the metablock. This figure can be visualized at https://microreactorg/project/GPS_India/2b522af9. PEN, penicillin; AMO, amoxicillin; MER, meropenem; TAX, cefotaxime; CFT, cefotaxime; CFX, cefuroxime; ERY, erythromycin; CLI, clindamycin; TET, tetracycline; DOX, doxycycline; CHL, chloramphenicol; MDR, multidrug-resistant.