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 (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.

Epidemiology of Hypoxic Community-Acquired Pneumonia in Children Under 5 Years of Age: An Observational Study in Northern India.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of under-five mortality in India. An increased risk of mortality has been reported in cases of hypoxic pneumonia. METHODS: The primary objective of this study was to assess the proportion of children aged 2-59 months, hospitalized with hypoxic CAP, as well as socio-demographic, clinical, and radiological features associated with it. The secondary objective was to determine the risk of mortality among hospitalized cases of hypoxic CAP. This prospective, observational study was conducted in four districts of Northern India, between January 2015 and April 2021. A hospital-based surveillance network was established. Inclusion criteria were as follows: (a) child between 2 and 59 months, (b) hospitalization with symptoms of WHO-defined CAP, (c) resident of project district, (d) illness of <14 days, and (e) child had neither been hospitalized for this illness nor recruited previously. Children whose chest x-rays (CXRs) were either unavailable/un-interpretable and those that received any dose of pneumococcal conjugate vaccine-13 were excluded. Hypoxic pneumonia was defined as oxygen saturation <90% on pulse oximetry or requiring oxygen supplementation during hospital stay. RESULTS: During the study period, 71.9% (7,196/10,006) children of severe pneumonia were eligible for inclusion, of whom 35.9% (2,580/7,196) were having hypoxic pneumonia. Female gender and use of biomass fuel for cooking increased the odds of hypoxic CAP. Clinical factors like wheezing, pallor, tachypnea, low pulse volume, presence of comorbidity, general danger signs, severe malnutrition, and radiological finding of primary end-point pneumonia ± other infiltrates (PEP±OI) also increased the odds of hypoxic CAP in a conditional logistic regression model. Adjusted odds ratio for mortality with hypoxia was 2.36 (95% CI: 1.42-3.92). CONCLUSION: Almost one-third of cases hospitalized with severe CAP had hypoxia, which increased chances of mortality. Besides known danger signs, certain newer clinical signs such as pallor and wheezing as well as PEP+OI were associated with hypoxic CAP. Therefore, objective assessment of oxygen saturation must be done by pulse oximetry in all cases of CAP at the time of diagnosis.