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.

中文翻译：

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来自印度人群的肺炎链球菌基因组数据集，使用全基因组测序方法描述疫苗前进化流行病学

在全球范围内，印度的肺炎球菌疾病负担较重，自 2017 年 5 月以来，肺炎球菌结合疫苗 (PCV) 已在全国婴儿免疫计划 (NIP) 的不同阶段推出。为了提供评估疫苗对印度循环肺炎球菌影响的基线，在引入 PCV 之前检测到的肺炎球菌分离株的遗传特征将是有帮助的。在这里，我们介绍了 480株肺炎链球菌的群体基因组研究 在疫苗引入之前（2009-2017 年）从印度各地和所有年龄组收集的分离株，包括 294 株肺炎球菌病分离株和 186 株通过鼻咽调查收集的分离株。从全基因组测序数据中表征和预测群体遗传结构、血清型和抗菌药物敏感性谱。我们的研究结果揭示了由 110 个全球肺炎球菌序列簇 (GPSC) 和 54 种血清型所代表的高水平遗传多样性。血清型 19F 和 GPSC1 (CC320) 分别是最常见的血清型和肺炎球菌谱系。PCV13（辉瑞）和 10 价 Pneumosil（印度血清研究所）血清型在≤2 岁和 3-5 岁年龄组中的覆盖率分别为 63-75% 和 60-69%。≥50 岁年龄组中 PPV23 (Merck) 血清型的覆盖率为 62% (98/158)。在引起疾病的前五个谱系中，排名第二的 GPSC10（CC230）是唯一同时表达 PCV13（血清型 3、6A、14、19A 和 19F）和非 PCV13（7B、13、10A、11A、 13、15B/C、22F、24F) 血清型。它表现出多药耐药性，是致病人群中 NVT 的最大贡献者（17%，18/103）。总体而言，42% (202/480) 的分离株对青霉素耐药（最低抑菌浓度≥0.12 µg ml-1 ) 和 45% (217/480) 具有多重耐药性。9个GPSC（GPSC1、6、9、10、13、16、43、91、376）对青霉素具有耐药性，其中6个具有多重耐药性。表达 PCV13 血清型的肺炎球菌具有较高的抗生素耐药性。肺炎球菌基因组测序显着提高了我们对这些细菌生物学的理解。本研究描述了 PCV 引入前的肺炎球菌疾病和携带流行病学，表明 PCV13 和 Pneumosil 涵盖了 ≤5 岁儿童中 60-75% 的肺炎球菌血清型。接种肺炎球菌疫苗很可能会降低抗生素耐药性。耐多药肺炎球菌谱系 GPSC10 (CC230) 是一种可介导血清型替代的高风险克隆。