The 13-Valent Pneumococcal Conjugate Vaccine Is Effective Against Hypoxic Pneumonia in Children in Lao PDR: A Novel Method Using a Hospital-Based Observational Study

Background: Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no 13-valent PCV (PCV13) vaccine effectiveness (VE) studies on hypoxic pneumonia from Asia. We describe a novel approach to determine the effectiveness of PCV13 against hypoxic pneumonia in children admitted with pneumonia in the Lao People's Democratic Republic, a low-resource setting. Methods: A prospective hospital-based observational study of children up to 59 months old admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as an oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. PCV13 status was determined by written record. VE was calculated using logistic regression comparing the odds of hypoxia between vaccinated and undervaccinated pneumonia cases. To handle potential confounders a propensity score (PS) analysis using inverse probability of treatment weighting was used; for missing data, multiple imputation (MI) analysis was undertaken. Findings: There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, PS adjusted and MI adjusted VE against hypoxic pneumonia were 23% (95% confidence interval [CI]: -9, 46%; p=0·14); 37% ([CI]: 6, 57%; p=0·02) and 35% ([CI]: 7, 55%; p=0·02) respectively. Interpretation: This is the first apparent study to show PCV13 is effective against hypoxic pneumonia in Asia. This single hospital-based approach will enable other similar settings to test for VE. Funding Statement: This study received funding from the Bill & Melinda Gates Foundation (OPP1115490). Declaration of Interests: KM and CN receive grants from Pfizer, outside the submitted work. The Institute of Research for Development (IRD) and Aix-Marseille University funds both ADP and the HRSV testing. PN receives grants from the Wellcome Trust. JL receives funding from Bill and Melinda Gates foundation. All other authors declare no competing interests. The opinion presented in this paper is that of the authors and does not reflect Pfizer. We have not been paid by a pharmaceutical company to write this article. Ethics Approval Statement: This study was conducted according to the study protocol approved by the Oxford Tropical Research Ethics Committee (OxTREC reference:1050-13), Laos Ministry of Health National Ethics Committee for Health Research (No 061NECHR), the Ethics Review Committee of the WHO Regional Office for the Western Pacific Region (WPRO-ERC) (reference ID:2013.30.LAO.2.EPI) and by The Royal Children’s Hospital Human Resources Ethics Committee (HREC) (reference number:33177B).