Impact of PCV7/PCV13 introduction on community-acquired alveolar pneumonia in children <5 years
Introduction
The introduction of the 7-valent and the 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) to the National Immunization Plan (NIP) in many countries, including Israel, resulted in major reductions in invasive pneumococcal disease (IPD) [1], [2], [3], pneumonia [4], [5], [6], [7] otitis media [8], and pneumococcal carriage [9] in children.
Radiographically confirmed alveolar pneumonia, as defined by the World Health Organization (WHO), is considered most often a bacterial disease and served therefore as an endpoint for vaccine efficacy studies in several pivotal pneumococcal conjugate vaccine (PCV) pre-licensure studies [10]. In these studies, the efficacy ranged from 20% to 37% in infants and young toddlers [11], [12], [13], [14], [15], [16].
Although several post-PCV7 implementation studies reported vaccine impact on pneumonia, differences in case definition and methodology were significant [4], [7], [17], [18], [19], [20], [21]. Since the 10-valent pneumococcal conjugate vaccine (PCV10) and PCV13 were only recently introduced, only a limited number of impact data are available for these vaccines [22], [23].
In southern Israel, >95% of the children are born at the only medical center in the region, where they also receive medical treatment, enabling prospective population-based studies. PCV7 was introduced to the Israeli NIP in July 2009 (with a catch-up immunization plan) and has been gradually replaced by PCV13 since November 2010, without a catch-up program. This sequential PCV7/PCV13 introduction, together with the unique epidemiological situation in southern Israel, provided the opportunity to observe the impact of these vaccines on hospital pediatric emergency room (PER) visits and hospitalization due to radiologically-confirmed alveolar community-acquired pneumonia (A-CAP).
We recently reported a substantial reduction of bacteremic pneumococcal pneumonia after the introduction of the sequential PCV7/PCV13 program in children <5 years old, using a prospective active nationwide surveillance [24]. However, since in young children only <10% of all pneumonia cases are bacteremic [25], [26], [27], there is a need to study incidence dynamics of all, mostly non bacteremic, alveolar pneumonia after PCV introduction in this age group. Since 2002, a prospective ongoing study is being conducted in southern Israel, in which all PER visits and hospitalizations due to radiologically-proven A-CAP are being recorded. The aims of the current study were: (1) To document the impact of the sequential PCV7/PCV13 introduction on hospital visits and hospitalizations due to A-CAP in young children; and (2) To assess whether the pattern of reduction in A-CAP rates was similar in hospitalized children and outpatients seen at the PER.
Section snippets
Setting
The Soroka University Medical Center (SUMC) is the only hospital in the Negev district of southern Israel, providing primary and referral health services to the entire population of the region (>643,000 inhabitants and 77,000 children under 5 years old in 2012) [28]. Over 95% of the children living in the region are served by the SUMC,enabling incidence figures calculations. Two ethnic populations reside in Southern Israel: The Bedouin Muslim population, resembling a developing population and
Results
From July 2002 through June 2013, a total of 70,483 chest radiographs were obtained in children <5 years, and in 10,142 (14.4%), an A-CAP episode was diagnosed. Of all A-CAP episodes, 7464 occurred in the study-defined pre-PCV, PCV7 and PCV13 periods, and were used for comparison of incidence between these periods; of these, 4570 (61.2%) were in hospitalized children, and 2894 (38.8%) in outpatients.
Of the 10,142 episodes, blood cultures were obtained in 6855 (67.6%) and only 200 (0.3%) were
Discussion
The present population-based prospective study demonstrates, in spite of only a modest reduction of 13% in A-CAP in young children shortly after PCV7, a sharp decline of 47% shortly after PCV13 introduction. The initial reduction in A-CAP rate in the PCV7 period was mainly observed in outpatients and was more marked in children 12–23 months of age, but in the PCV13 period the rates declined significantly in all age groups, in both inpatients and outpatients. Still, the reduction among
Funding
This work was supported in part by a grant from Pfizer [grant no. 0887X1-4603]. The funding source did not play any role in the design and control of the study, collection, management, analysis and interpretation of the data and preparation, review or approval of the manuscript.
Contributors
David Greenberg made substantial contributions to concept and design, participated in acquisition of data, analysis and interpretation of data, drafted the manuscript and revised it critically for important intellectual content and has approved the manuscript as submitted. Noga Givon-Lavi contributed to the concept and design, made substantial contributions to the analysis and interpretation of data, revised the manuscript critically for important intellectual content and has approved the
Conflict of interest statement
Financial disclosure: Ron Dagan has received grants/research support from MSD and Pfizer. He is a scientific consultant to Genocea, MeMed, MSD, and Pfizer and receives speaker's fee from GlaxoSmithKline and Pfizer. David Greenberg is a speaker for Abbvie, Astra Zeneca, GlaxoSmithKline, MSD and Pfizer; a scientific consultant for Abbvie, A.I.T. (Advance Inhalation Therapy), Astra Zeneca, Enox Biopharma, GlaxoSmithKline, MSD and Pfizer; he has received grants from MSD and Abbvie and is a
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