Shalom Ben-Shimol, M.D. Pediatric Infectious Disease Unit Invasive pneumococcal disease in young children in Israel after sequential Soroka University Medical Center Beer-Sheva, Israel introduction of PCV7 followed by PCV13 [email protected] 1S. Ben-Shimol, 1D. Greenberg, 1N. Givon-Lavi, 2Y. Schlesinger, 3E. Somekh, 4S. Aviner, 5D. Miron 1R. Dagan on behalf of the Israeli Bacteremia and Meningitis Active Surveillance Group* 1The Pediatric Infectious Disease Unit, Soroka University Medical Center, Ben-Gurion University, Beer-Sheva, 2Shaare Zedek Medical Center, Jerusalem, 3Wolfson Medical Center, Holon, 4The Barzilai Medical Center, Ashkelon, 5 The Pediatric Infectious Disease Service, HaEmek Medical Center, Afula Vaccine uptake evaluation Figure 2. Monthly IPD rates in children <2 and 2-4 years old, Israel • Vaccine uptake was measured in the Beer-Sheva district, since traditionally the figure in this district represent the average figures Figure 1. Annual IPD rates in Israeli children <2 years old and 2-4 Years old (July 2004 – June 2013) Abstract in Israel. • Each working day, the first 4 Jewish children and the first 4 Bedouin children seen at the Pediatric Emergency Room (PER) of the Soroka Medical Center in Beer-Sheva, whose parents signed an informed consent were chosen for vaccine uptake study. Their • Background: The 7-valent pneumococcal conjugated vaccine (PCV7) was introduced to the Israeli national immunization plan Maternal Child Health Centers and their Clinics were contacted to receive all vaccination details (which PCV, date of all doses) (NIP) in July 2009 [2, 4, 12 months with a catch-up program] with a rapid reduction of PCV7 serotypes invasive pneumococcal • In June 2009, 2010, 2011 and 2012, the proportion of children 12-23 months old who received ≥2 PCV doses in was 20%, 71%, disease (IPD). In November 2010, PCV13 was introduced to the Israeli NIP without any catch-up and gradually replaced PCV7. 96%, and 96%, respectively. The respective figures for children 18-23 months old receiving ≥3 doses were 10%, 25%, 83% and • Aim: To report the impact of PCV7→PCV13 introduction to NIP on IPD in children <5 years in Israel. 83%. In December 2011, June 2012 and December 2012 the proportion of children 12-23 months old who received ≥2 PCV13 • Methods: An ongoing, nationwide, prospective, population-based, active surveillance, initiated in 1989. All children <5 years doses were 33%, 84.8% and 95%. The respective figures for children 18-23 months old who received PCV13 was 0%, 30% and 74%. with IPD episode (S. pneumoniae isolated from blood, CSF or both) were included. Data analysis • Data are recorded as continuous rates (monthly and annually) in the various age groups. In addition, we chose 3 representative • Results: Total IPD incidence (per 100,000) declined from a mean of 92.7±5.0, 21.5±1.1 and 50.6±2.3 in the pre-PCV period sub-periods and 2 interim periods as our reference periods. (July 2004 through June 2008) by 48%, -2% and 35% in 2010-2011 (PCV7 period), and by 69%, 47% and 63% in 2012-2013 - Pre-PCV period: July 2004 – June 2008 (PCV13 period) in children <2 years, 2-4 years and <5 years, respectively. In all age groups, PCV7 and 6A serotypes IPD - PCV7 period: July 2010 – June 2011 (>70% of children 12-23 months old vaccinated with ≥ 2 PCV7 doses, but not with PCV13) incidence declined by >75% and >90% comparing the pre-PCV with the PCV7 and PCV13 periods, respectively. In children <5 - PCV13 period: July 2012-June 2013 (>70% of 12-23 months old vaccinated with ≥ 2 PCV13 doses) years old, serotypes 1, 3, 5, 7F and 19A (grouped) disease rates increased by 47% in the PCV7 period and decreased by 70% in • To evaluate changes in IPD incidence, we have used full years (July through June) rates. Rates reductions and ratios with 95% the PCV13 period, compared with the pre-PCV period. Non-PCV13 serotypes disease rates increased by 53% and 140% in the confidence interval were calculated PCV7 and the PCV13 periods, compared with the pre-PCV period, respectively. Statistical Analysis • Conclusions: Substantial reduction of PCV13 serotypes IPD in children <5 years was observed shortly after PCV13 introduction • Annual incidence rates were calculated as the number of IPD episodes divided by the total population at risk during each year of to NIP, while maintaining PCV7 impact. A continuous surveillance is needed to determine PCV13 effect on IPD caused by non- the study. The age-specific population at risk was estimated according to the Israeli Central Bureau of Statistics reports vaccine serotypes. • P value of <0.05 was considered statistically significant Introduction Results Figure 3. Annual 7VT (+6A), 13VT and non-13VT IPD rates in children <2 and 2-4 Figure 4. Annual serotype-specific IPD rates in children <5 Years old, Israel (July 2004 – June 2013) • Overall (all serotypes) IPD rates declined by 42% in children < 5 years in Israel, in the first 18 months after the introduction • From July 2004 through June 2013, 2,670 IPD episodes were recorded in children <5 years in Israel years old, Israel (July 2004 – June 2013) of PCV7 to the NIP in July 2009. This reduction was similar to rates observed in other countries following rapid PCV7 uptake, • The demographic characteristics of the study IPD episodes are presented in Table 1 and was mainly derived from the >80% reduction of IPD caused by the 7 vaccine serotypes (7VST) and the related serotype • The diagnoses distribution was 48.5%, 35.5%, 9.4%, 1.3%, 1.6% and 3.7% for sepsis, pneumonia, meningitis, cellulitis, other 6A and missing diagnoses, respectively • In November 2010, PCV13 was introduced to the Israeli NIP, gradually replacing PCV7, without a catch-up program • The serotype distribution of IPD episodes are presented in Table 2 • Only limited data are currently available in regard to the impact of PCV13 on pneumococcal disease caused by the • Total IPD dynamics are presented in Table 3, Figure 1 and Figure 2 additional PCV13 serotypes, due to the relatively short time since the licensure of PCV13 (2010) • Total IPD rates decreased by 48% and 69% in children <2 years, and by -2% and 47% in children 2-4 years, comparing the pre- PCV period with the PCV7 and the PCV13 periods, respectively. • Serotype-specific IPD dynamics are presented in Figure 3 and Figure 4 Objectives Table 1. Age and gender distribution of IPD episodes in children <5 years in Israel by ethnic group • To assess the impact of PCV7→PCV13 introduction to the Israeli NIP on IPD in children <5 years old, 4 years after initiation Jewish children (n, %) Non-Jewish children (n, %) Total (n, %) • To assess the additional impact of PCV13 over PCV7, 31 months after the gradual replacement of Gender Males (n, %) 1,269 (58.6%) 294 (58.1%) 1,563 (58.5%) PCV7 by PCV13 Age (months) Mean ± SD 19.8 ± 13.9 18.2 ± 14.6 19.5 ± 14.0 Materials & Methods Median 16.1 14.4 16.0 Age <24 months 1,535 (80.5%) 372 (19.5%) 1,907 (100.0%) Conclusions Study design Age 24-59 months 629 (82.4%) 134 (17.6%) 763 (100.0%) • An ongoing, nationwide, prospective, population-based, active surveillance, initiated in 1989 • Period - July 2004 through June 2013 Age <60 months 2,164 (81.0%) 506 (19.0%) 2,670 (100.0%) • Shortly after introduction of PCV13, a substantial additional reduction in IPD in children <5 years • The detailed description of data collection, vaccine uptake evaluation methods and bacteriology were previously published was observed in Israel [Ben-Shimol et al. Vaccine. 2012 Oct 12;30(46):6600-7]. Table 2. Serotype-specific number of IPD episodes in children <5 Years Table 3. Serotype-specific IPD Incidence per 100,000 children <5 Years, Israel, • This reduction was mainly of IPD caused by the additional PCV13 serotypes • Study population - all children <5 years old in Israel. Israel had a population of 794,300 children <5 years, as of 2011; of Serotype Groups July 2004 – June 2013 • A continuous surveillance is needed to determine PCV13 effect on IPD caused by non-vaccine these, 76% were Jewish, and most of the non-Jewish children were Moslem Arabs. • The study has been conducted in all 27 medical health centers routinely obtaining CSF and blood cultures from children 7VT+6A 1, 3, 5, 7F, 19A (grouped) non 13VT Total Serotypes serotypes • Local investigators in each center responded to a monthly distributed questionnaire sent by the principal investigator, Pre-PCV period jul04-jun05 216 92 45 353 7VT 6A 19A 1,3,5,7F Non-13VT Total IPD *The Israeli Pediatric Bacteremia and Meningitis Group: Ron Dagan, principal investigator, Beer Sheva; Jacob Amir, located at the Pediatric Infectious Disease Unit (PIDU), the Soroka University Medical Center (SUMC), which served as the jul05-jun06 232 126 27 384 Pre-PCV7 period 27.2 ± 0.8 3.3 ± 0.9 5.1 ± 0.7 9.7 ± 2.6 5.3 ± 1.4 50.6 ± 2.3 Study headquarters jul06-jun07 210 111 48 369 (July 2004 – June 2008) Petah-Tikva; Galia Barkai, Tel Hashomer; Diana Averbuch, Jerusalem; Shraga Aviner, Ashkelon; Ahuva Bachinski, Hadera; • Completed reports included the following data: Isolate source (blood/CSF), culture date, birthdate, gender, ethnicity 225 98 33 355 Maskit Bar-Meir, Jerusalem; Avihu Bar-Yochai, Zerifin; Ilana Benedikt, Jerusalem; Rita Bernstein, Rehovot; Nael Elias, jul07-jun08 PCV7 period 2.5 0.7 5.0 16.7 8.1 33.0 (Jewish/non- Jewish), main diagnoses, outcome (mortality) and hospitalization duration jul08-jun09 191 128 41 360 Nazareth; Dan Engelhard, Jerusalem; Moshe Ephros, Haifa; Daniel Glikman, Nahariya; Giora Gottesman, Kfar-Saba; Galia Case definition (July 2010 – June 2011) jul09-jun10 87 104 50 241 • An IPD episode was defined as an illness episode during which S.