Effectiveness of the 10-valent pneumococcal conjugate vaccine on pediatric pneumonia confirmed by ultrasound: a matched case-control study

Abstract

Background: Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) for children aged < 1 year in March 2015. Previous vaccine effectiveness (VE) studies for pneumonia have used invasive pneumococcal disease or chest X-rays. None have used ultrasound. We sought to determine the VE of PCV10 against sonographically-confirmed pneumonia in three subdistrict health complexes in Bangladesh.

Methods: We conducted a matched case-control study between July 2015 and September 2017 in three subdistricts of Sylhet, Bangladesh. Cases were vaccine-eligible children aged 3-35 months with sonographically-confirmed pneumonia, who were matched with two types of controls by age, sex, week of diagnosis, subdistrict health complex (clinic controls) or distance from subdistrict health complex (community controls) and had an illness unlikely due to Streptococcus pneumoniae (clinic controls) or were healthy (community controls). VE was measured using multivariable conditional logistic regression.

Results: We evaluated 8926 children (average age 13.3 months, 58% boys) with clinical pneumonia by ultrasound; 2470 had pneumonia with consolidations ≥ 1 cm; 1893 pneumonia cases were matched with 4238 clinic controls; and 1832 were matched with 3636 community controls. VE increased with the threshold used for consolidation size on ultrasound: the adjusted VE of ≥ 2 doses vs. non-recipients of PCV10 against pneumonia increased from 15.8% (95% CI 1.6-28.0%) for consolidations ≥ 1 cm to 29.6% (12.8-43.2%) for consolidations ≥ 1.5 cm using clinic controls and from 2.7% (- 14.2-17.2%) to 23.5% (4.4-38.8%) using community controls, respectively.

Conclusions: PCV10 was effective at reducing sonographically-confirmed pneumonia in children aged 3-35 months of age when compared to unvaccinated children. VE increased with the threshold used for consolidation size on ultrasound in clinic and community controls alike. This study provides evidence that lung ultrasound is a useful alternative to chest X-ray for case-control studies evaluating the effectiveness of vaccines against pneumonia.

Keywords: Child health; Pneumococcal conjugate vaccine; Pneumonia; South Asia; Ultrasound; Vaccine effectiveness.

Fig. 1

Flow diagram for children screened by ultrasound and those enrolled into the matched case–control study. We include eligibility criteria for cases, the number of matching sets (which is equal to the number of cases) and the number of control children. Only 10 sets (0.5%) had missing data

Fig. 2

Vaccine effectiveness of receiving at least two doses of the 10-valent pneumococcal conjugate vaccine (PCV10) vs. none against ultrasound-confirmed pneumonia when compared with clinic controls in 3 subdistricts in Sylhet, Bangladesh (July 2015–September 2017). A Displays a forest plot of unadjusted vaccine effectiveness of ≥ 2 doses of PCV10 vs. none stratified by consolidation size, laterality, and by age or sex. B Displays a forest plot of vaccine effectiveness adjusted for household characteristics, assets, maternal education, whether the father resides in the household, number of children aged under five years living in the household, whether the family owns the house, family owns a clean stove, whether the mother participates in decision making, and propensity to seek care for the child. We stratified cases by consolidation size and, evaluated for interactions between consolidation size (≥ 1.5 or 1–1.49 cm) and laterality. Vaccine effectiveness is represented with a diamond, and the horizontal line is the corresponding 95% confidence interval. The size of the diamond is proportional to the sample size used for each analysis

Fig. 3

Vaccine effectiveness of receiving at least two doses of the 10-valent pneumococcal conjugate vaccine (PCV10) vs. none against ultrasound-confirmed pneumonia when compared with community controls in 3 subdistricts in Sylhet, Bangladesh (July 2015–September 2017). A Displays a forest plot of unadjusted vaccine effectiveness of ≥ 2 doses of PCV10 vs. none stratified by consolidation size, laterality, and by age or sex. B Displays a forest plot of vaccine effectiveness adjusted for household characteristics, assets, maternal education, whether the father resides in the household, number of children aged under 5 years living in the household, whether the family owns the house, family owns a clean stove, whether the mother participates in decision making, and propensity to seek care for the child. We stratified cases by consolidation size and, evaluated for interactions between consolidation size (≥ 1.5 or 1–1.49 cm) and laterality (unilateral or bilateral). Vaccine effectiveness is represented with a diamond, and the horizontal line is the corresponding 95% confidence interval. The size of the diamond is proportional to the sample size used for each analysis

Fig. 4

Vaccine effectiveness of receiving at least two doses of the 10-valent pneumococcal conjugate vaccine (PCV10) vs. none against ultrasound-confirmed pneumonia when compared with clinic controls in 3 subdistricts in Sylhet, Bangladesh (June 2015–September 2017). A Displays a forest plot of unadjusted vaccine effectiveness of ≥ 2 doses of PCV10 vs. none stratified by consolidation size by age or sex. B Displays a forest plot of vaccine effectiveness adjusted for household characteristics, assets, years of schooling for both mother and father, whether the father resides in the household, number of children aged under 5 years living in the household, whether the family owns the house, family owns a clean stove, whether the mother participates in decision making, and propensity to seek care for the child. We stratified cases by consolidation size and, evaluated for interactions between consolidation size (≥ 1.5 or 1–1.49 cm) and age (< 12 or ≥ 12 months) or consolidation size and sex. Vaccine effectiveness is represented with a diamond, and the horizontal line is the corresponding 95% confidence interval. The size of the diamond is proportional to the sample size used for each analysis

Fig. 5

Vaccine effectiveness of receiving at least two doses of the 10-valent pneumococcal conjugate vaccine (PCV10) vs. none against ultrasound-confirmed pneumonia when compared with community controls in 3 subdistricts in Sylhet, Bangladesh (June 2015–September 2017). A Displays a forest plot of unadjusted vaccine effectiveness of ≥ 2 doses of PCV10 vs. none stratified by consolidation size by age or sex. B Displays a forest plot of vaccine effectiveness adjusted for household characteristics, assets, years of schooling for both mother and father, whether the father resides in the household, number of children aged under 5 years living in the household, whether the family owns the house, family owns a clean stove, whether the mother participates in decision making, and propensity to seek care for the child. We stratified cases by consolidation size and, evaluated for interactions between consolidation size (≥ 1.5 or 1–1.49 cm) and age (< 12 or ≥ 12 months) or consolidation size and sex. Vaccine effectiveness is represented with a diamond, and the horizontal line is the corresponding 95% confidence interval. The size of the diamond is proportional to the sample size used for each analysis