Effectiveness of 13-valent pneumococcal conjugate vaccine on radiological primary end-point pneumonia among cases of severe community acquired pneumonia in children: A prospective multi-site hospital-based test-negative study in Northern India

Introduction Community acquired pneumonia (CAP) is a leading cause of under-five mortality in India and Streptococcus pneumoniae is the main bacterial pathogen for it. Pneumococcal Conjugate Vaccine 13 (PCV13) has been introduced in a phased manner, in the national immunization program of India since 2017/2018. The primary objective of this study was to evaluate the effectiveness of PCV13 on chest radiograph (CXR)-confirmed pneumonia, in children hospitalized with WHO-defined severe CAP. Methods This prospective, multi-site test-negative study was conducted in a hospital-network situated in three districts of Northern India where PCV13 had been introduced. Children aged 2-23 months, hospitalized with severe CAP and with interpretable CXR were included after parental consent. Clinical data was extracted from hospital records. CXRs were interpreted by a panel of three independent blinded trained radiologists. Exposure to PCV13 was defined as >= 2 doses of PCV13 in children aged <= 12 months and >= 1 dose(s) in children > 12 months of age. Our outcome measures were CXR finding of primary endpoint pneumonia with or without other infiltrates (PEPOI); vaccine effectiveness (VE) and hospital mortality. Results From 1(st) June 2017-30(th) April 2021, among 2711 children included, 678 (25.0%) were exposed to PCV1. CXR positive for PEP +/- OI on CXR was found in 579 (21.4%), of which 103 (17.8%) were exposed to PCV. Adjusted odds ratio (AOR) for PEP +/- OI among the exposed group was 0.69 (95% CI, 0.54-0.89, p = 0.004). Adjusted VE was 31.0% (95% CI: 11.0-44.0) for PEP +/- OI. AOR for hospital mortality with PEP +/- OI was 2.65 (95% CI: 1.27-5.53, p = 0.01). Conclusion In severe CAP, children exposed to PCV13 had significantly reduced odds of having PEP +/- OI. Since PEP +/- OI had increased odds of hospital mortality due to CAP, countrywide coverage with PCV13 is an essential priority.