The effect of pneumococcal conjugate vaccines on otitis media from 2005 to 2013 in children aged ≤5 years: a retrospective cohort study in two Swedish regions

Figures & data

Table 1. Assignment of children to vaccination cohorts according to date and region of birth

Cohort	Region of birth	Date of birth range*
pre-PCV	Either	1 January 1999–31 December 2008
PCV7	VGR	1 April 2009–31 December 2009
	Skåne	1 April 2009–31 May 2010
PCV13	VGR	1 April 2010–31 December 2013
PHiD-CV	Skåne	1 September 2010–31 December 2013

PCV = pneumococcal conjugate vaccine, PCV7/PCV13 = 7-valent/13-valent pneumococcal conjugate vaccine, PHiD-CV = pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine, VGR = Västra Götalandsregionen

*the assignment of children to each cohort includes a 3-month washout period following vaccine implementation

Table 2. Yearly incidence (per 100,000 person-years) of otitis media/acute otitis media among all children according to age*

Age	2005	2006	2007	2008	2009	2010	2011	2012	2013
Skåne Incidence rate (95% CI)
≤2 years	37,124 (36,507; 37,752)	39,868 (39,233; 40,513)	42,452 (41,808; 43,106)	42,135 (41,508; 42,772)	37,810 (37,230; 38,400)	37,041 (36,477; 37,614)	30,544 (30,038; 31,059)	37,124 (36,507; 37,752)	39,868 (39,233; 40,513)
3–5 years	24,009 (23,491; 24,538)	24,342 (23,828; 24,866)	25,369 (24,853; 25,897)	24,142 (23,645; 24,650)	21,717 (21,250; 22,195)	21,545 (21,088; 22,012)	20,109 (19,677; 20,551)	19,491 (19,075; 19,916)	16,454 (16,079; 16,837)
≤5 years	30,859 (30,451; 31,272)	32,396 (31,983; 32,814)	34,256 (33,838; 34,679)	33,573 (33,166; 33,984)	30,745 (30,355; 31,140)	29,317 (28,937; 29,701)	24,837 (24,490; 25,190)	23,918 (23,582; 24,259)	20,207 (19,901; 20,518)
VGR Incidence rate (95% CI)
≤2 years	29,283 (28,811; 29,763)	30,836 (30,357; 31,324)	34,945 (34,441; 35,458)	34,316 (33,822; 34,817)	32,014 (31,542; 32,492)	38,730 (38,217; 39,249)	31,800 (31,338; 32,268)	29,432 (28,989; 29,882)	25,914 (25,496; 26,338)
3–5 years	19,280 (18,883; 19,686)	21,357 (20,944; 21,779)	22,990 (22,567; 23,422)	21,841 (21,434; 22,257)	19,539 (19,158; 19,928)	23,601 (23,187; 24,023)	21,320 (20,932; 21,716)	19,143 (18,779; 19,514)	16,317 (15,985; 16,655)
≤5 years	24,473 (24,161; 24,788)	26,275 (25,955; 26,598)	29,183 (28,851; 29,520)	28,304 (27,981; 28,631)	26,452 (26,137; 26,771)	31,171 (30,824; 31,521)	25,671 (25,359; 25,986)	24,227 (23,927; 24,532)	21,411 (21,130; 21,696)

CI = confidence interval, VGR = Västra Götalandsregionen

*each study year contains a different blend of unvaccinated children, versus children vaccinated with either the 7-valent pneumococcal conjugate vaccine, the 13-valent pneumococcal conjugate vaccine, or the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine

Table 3. Overall incidence per 100,000 person-years of otitis media/acute otitis media in the pre-PCV, PCV7, and PHiD-CV/PCV13 cohorts*

Cohort	≤2 years	3–5 years	≤5 years
Skåne Incidence rate (95% CI)
pre-PCV	40,843 (40,574; 41,113)	22,034 (21,871; 22,199)	29,721 (29,574; 29,868)
PCV7	31,469 (30,996; 31,949)	17,623 (17,061; 18,203)	27,583  (27,208; 27,964)
PHiD-CV	23,697 (23,367; 24,032)	17,994 (15,325; 21,128)	23,640 (23,312; 23,973)
VGR Incidence rate (95% CI)
pre-PCV	34,501 (34,287; 34,717)	20,819 (20,682; 20,958)	26,376 (26,257; 26,497)
PCV7	33,099 (32,559; 33,648)	17,848 (17,269; 18,445)	28,275 (27,861; 28,694)
PCV13	25,710 (25,433; 25,990)	15,270 (14,283; 16,325)	25,268 (24,999; 25,539)

CI = confidence interval, PCV = pneumococcal conjugate vaccine, PCV7/PCV13 = 7-valent/13-valent pneumococcal conjugate vaccine, PHiD-CV = pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine, VGR = Västra Götalandsregionen

*the PCV7 era was short in VGR and Skåne and any change detected vs the PCV7 cohort in the incidence of otitis media/acute otitis media should be considered with caution

Figure 1. Time-series showing monthly incidence of otitis media/acute otitis media (OM) in the pre-PCV, PCV7, and PHiD-CV eras in Skåne

PCV = pneumococcal conjugate vaccine, PCV7 = 7-valent pneumococcal conjugate vaccine, PHiD-CV = pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine

Figure 2. Time-series showing monthly incidence of otitis media/acute otitis media (OM) in the pre-PCV, PCV7, and PHiD-CV eras in VGR

PCV = pneumococcal conjugate vaccine, PCV7/PCV13 = 7-valent/13-valent pneumococcal conjugate vaccine, VGR = Västra Götalandsregionen

Table 4. Incidence rate ratios of otitis media/acute otitis media diagnoses between vaccine cohorts adjusted for confounding variables, according to the age-period-cohort Poisson model

	Skåne			VGR
PCV Cohorts	IRR	95% CI	p-value	IRR	95% CI	p-value
≤5 years of age
PHiD-CV/PCV13 relative to pre-PCV	0.901	0.849; 0.956	<0.001	0.977	0.924; 1.032	0.401
PHiD-CV/PCV13 relative to PCV7	0.926	0.884; 0.970	0.001	1.017	0.969; 1.067	0.493
PCV7 relative to pre-PCV	0.973	0.932; 1.015	0.207	0.961	0.917; 1.006	0.087
≤2 years of age
PHiD-CV/PCV13 relative to pre-PCV	0.952	0.866; 1.047	0.310	0.952	0.874; 1.037	0.263
PHiD-CV/PCV13 relative to PCV7	0.967	0.904; 1.035	0.330	0.994	0.930; 1.063	0.871
PCV7 relative to pre-PCV	0.985	0.927; 1.046	0.614	0.958	0.901; 1.018	0.164

CI = confidence interval, IRR = incidence rate ratio, PCV = pneumococcal conjugate vaccine, PCV7/PCV13 = 7-valent/13-valent pneumococcal conjugate vaccine, PHiD-CV = pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine, VGR = Västra Götalandsregionen

Table

APC	age-period-cohort
CI	confidence interval
ICD-10	10^th revision of the International Classification of Diseases
IRR	incidence rate ratio
NBHW	Swedish National Board of Health and Welfare
NTHi	non-typeable Haemophilus influenzae
OM	otitis media/acute otitis media
PCV	pneumococcal conjugate vaccine
PCV7/PCV13	7-valent/13-valent pneumococcal conjugate vaccine
PHiD-CV	pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine
UTI	urinary tract infection
VGR	Västra Götalandsregionen