Rapid reduction in invasive pneumococcal disease after introduction of PCV7 into the National Immunization Plan in Israel
Highlights
► A prospective nationwide IPD surveillance has been conducted in Israeli children for >20 years. ► IPD incidence rapidly declined in children <5 years old following PCV7 introduction. ► No serotype replacement was observed so far. ► Our results compare favorably with other programs, using either 3 + 1 or 2 + 1 regimens. ► PCV13 introduction into the NIP could lead to a further decrease in IPD rates.
Introduction
Streptococcus pneumoniae is a major cause of morbidity and mortality in children, causing ∼11% of all deaths in children <5 years globally [1]. The highest incidence of invasive pneumococcal disease (IPD) is seen in children <2 years old [2], [3], [4]. In 2000, the 7-valent pneumococcal CRM197 conjugated vaccine (PCV7; serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) was first licensed, and has increasingly been used globally. During the pre-pneumococcal conjugate vaccine (PCV) era, most IPD in developed regions was caused by PCV7 serotypes (7VST); however, in developing countries larger proportions were caused by non-7VST [5], [6].
Reports from sites having introduced PCV7 clearly show reduction in 7VST IPD in all ages, but replacement with non-7VST is usually apparent [6]. However, in contrast to the uniformity in 7VST IPD reduction, replacement rates by non-7VST vary significantly between reports [3], [6]. One important potential cause of such variability could be the absence of long-term surveillance before PCV7 introduction, resulting in instability of the surveillance system [6].
PCV7 was licensed in Israel in 2007, with sporadic use until 2009. The vaccine was introduced into the Israeli National Immunization Plan (NIP) in July 2009 (administered at age 2, 4 and 12 months) with a catch-up campaign in all children <2 years. In November 2010, the 13-valent CRM197 PCV (PCV13; additional serotypes 1, 3, 5, 6A, 7F, 19A) replaced PCV7 in the Israeli NIP, without a further catch-up.
In 2010, the population in Israel was 7.2 million (80% Jews; most of the non-Jews being Moslem-Arabs) [7]. In general, the non-Jewish population lives under lower socioeconomic conditions than the Jewish population, crowded living conditions, a greater proportion of children <15 years, and a lower proportion of elderly persons, as well as more rapid population growth [8]. Higher incidences of pneumococcal carriage [9], respiratory infections [10], [11], and IPD [12] were reported in the non-Jewish population, compared with the Jewish population.
We now report: (1) a 20-year pre-PCV7 IPD incidence dynamics in children <5 years old; (2) IPD dynamics in the first 18 months after PCV7 introduction; and (3) the residual disease at the time of PCV13 introduction.
Section snippets
Study design
This is an ongoing, nationwide, prospective, population-based, active surveillance, initiated in 1989, conducted by the Israeli Pediatric Bacteremia and Meningitis Group (IPBMG). This report presents data spanning over a 22-year period, 1989–2010.
The study has been conducted in 27 medical centers routinely obtaining blood cultures from children: All 26 hospitals admitting children and one major outpatient health maintenance organization (HMO, Maccabi Healthcare Services) central laboratory.
Results
From January 1989 through December 2010, 6022 IPD episodes were recorded in children <5 years in Israel, of which ∼50% were sepsis, ∼35% were pneumonia, ∼9% were cellulitis and ∼6% other diagnoses. IPD diagnoses distribution in the pre-PCV7 era was similar to that in the post-PCV7 era (Supplemental Table 1). Serotype was determined in 2891 (48%) episodes, and in an additional 361 episodes (6%), serogroup only was determined. The proportion of isolates with serotype determination increased from
Discussion
Since PCV7 introduction into the NIP in July 2009, childhood IPD in Israel has decreased substantially. In children <2 years old, the primary vaccine target population, the 7VST IPD incidence decreased by 81%. Furthermore, IPD caused by the cross-reacting serotype 6A was reduced by 78% in this age group. These led to a respective overall IPD reduction of 42%, compared to the mean incidence during the 5 pre-NIP years. Since PCV7 was introduced to the Israeli NIP as a 2 + 1 schedule with a catch-up
Funding
The study was supported in part by Wyeth (Pfizer) Grant No. 0887X1-4603.
Conflict of interest
Shalom Ben Shimol: None. David Greenberg has received a grant from MSD. Noga Givon Lavi: None. Nael Elias: None. Uri Rubinstein: None. Daniel. Glikman: None. Ron Dagan: In the last five years, Prof. Ron Dagan has received grants/research support from Berna/Crucell, Wyeth/Pfizer, MSD, Protea; has been a scientific consultant for Berna/Crucell, GlaxoSmithKline, Novartis, Wyeth/Pfizer, Protea, MSD and a speaker for Berna/Crucell, GlaxoSmithKline, Wyeth/Pfizer; he is a shareholder of Protea/NASVAX.
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2019, International Journal of Infectious DiseasesCitation Excerpt :By June 2014, 91% of 24–35-month-old children had received three or more PCV13 doses (Regev-Yochay et al., 2017). This resulted in a marked overall decrease in IPD incidence in children (Ben-Shimol et al., 2012; Greenberg et al., 2015). Moreover, in adults, an approximate 20% decrease in all-serotype IPD incidence and an approximate 70% decrease in PCV7/13 serotype (vaccine type (VT)7/13) IPD was observed, due to an indirect effect (herd effect) (Cabaj et al., 2016; Regev-Yochay et al., 2017).
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See Appendix A.