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

Abstract

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 (PEP±OI); vaccine effectiveness (VE) and hospital mortality.

Results: From 1st June 2017-30th 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.

Fig 1. Flow diagram of hospitalized children (2–23 months) with community acquired pneumonia recruited from Darbhanga (1^st June 2017-30^th April 2021), Patna (1^st June 2018 to 30^th April 2021) and Lucknow (1^st June 2018 to 30^th April 2021).