Invasive Pneumococcal Disease in Infants Younger Than 90 Days Before and After Introduction of PCV7

Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, Utah
PEDIATRICS (Impact Factor: 5.47). 06/2013; 132(1). DOI: 10.1542/peds.2012-3900
Source: PubMed


Introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) changed the epidemiology of invasive pneumococcal disease (IPD). We evaluated the changes that occurred after PCV7 introduction among Utah infants aged 1 to 90 days, too young to be fully immunized.

We identified children <18 years with culture-confirmed IPD from 1997-2010. We analyzed demographic, clinical, and serotype data for infants aged 1-90 days. The pre- and post-vaccine introduction periods spanned 1997-2000 and 2001-2010, respectively.

Of 513 children with IPD, 36 were 1 to 90 days and accounted for 7% of IPD cases in both the pre- and post-vaccine introduction period. The pre-vaccine IPD incidence rate was 5.0 per 100 000 live births, and was unchanged in the post-vaccine introduction period. IPD caused by PCV7 serotypes decreased by 74% (from 2.2 to 0.58 per 100 000), whereas non-vaccine serotype IPD increased by 57% (from 2.8 to 4.4 per 100 000). Sixteen infants (44%) required intensive care, and 3 (8%) died. Bacteremia without focus (56%) and meningitis (44%) were the predominant syndromes in the pre- and post-vaccine introduction periods, respectively. In the post-vaccine introduction period, serotype 7F was the most common serotype among infants and was responsible for 50% of meningitis.

The incidence of IPD in Utah infants aged 1 to 90 days caused by PCV7 serotypes decreased after PCV7 introduction, but overall incidence was unchanged. In the post-vaccine introduction period, serotype 7F predominated in this age group and was associated with meningitis.

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    • "These studies ended in 2010 and showed a decrease of IPD caused by PCV-7 serotypes, like our study. Both Olarte et al [12] and Ladhani et al [11] found that a majority of IPD cases in infants were due to the additional six serotypes included in the PCV-13. Therefore, they anticipated that a further decrease would occur after the introduction of PCV-13. "
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    ABSTRACT: Background The seven-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the Danish childhood immunization program (at 3, 5 and 12 months of age) in 2007 and was replaced with PCV-13 in 2010 without changes to the schedule. After the introduction of these vaccines the incidence of invasive pneumococcal disease (IPD) due to vaccine types (VTs) declined markedly in children aged 0–2 years; however, cases among infants too young to be protected by vaccination have not been studied in detail. We present data on IPD in infants less than 90 days from 1943 until 2013. Study design The study included all infants younger than 90 days born from 1943 through 2013, who had not been PCV vaccinated and from whom a pneumococcus isolate from blood or cerebrospinal fluid had been submitted to the Danish national reference laboratory. All isolates were serotyped using Pneumotest Latex and Quellung reaction. Results A total of 216 IPD cases were identified. The age group specific incidence (total number of IPD cases per 100,000 live births) varied from 0 to 16 in the period 1943 to 2007 and from 1.7 to 9.2 in the period 2008 to 2013. IPD cases due to PCV-7 serotypes were not observed later than 2009. Conclusion In Danish infants younger than 90 days, IPD due to PCV-7 serotypes has decreased and has not been observed since 2009, but the total incidence of IPD has not changed.
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    ABSTRACT: Objectives: Clinical data are lacking on optimal levels of specific antipneumococcal antibodies (PnPsAbs) in patients with primary immunodeficiency (PID) receiving intravenous immunoglobulin (IVIG) replacement. Objectives were to conduct a prospective multicenter study providing data on total immunoglobulin G (IgG) and peak/trough levels of PnPsAbs specifically targeting the 16 most prevalent pneumococcal serotypes in IVIG-treated children with PID; to compare trough PnPsAb levels with those measured in healthy adults and the IVIG product; and to evaluate PnPsAb protection correlates with thresholds based on World Health Organization. Methods: Patients received 7 consecutive IVIG infusions. Total IgG and PnPsAb levels were determined on plasma samples obtained before and after infusion. Results: Twenty-two children with PID were treated with IVIG (mean weekly dose: 0.10 g/kg). The mean trough and peak levels of total IgG were 7.77 and 13.93 g/L, respectively. Trough and peak geometric mean concentrations and distribution curves differed between serotypes and showed wide dispersion (0.17-7.96 µg/mL). In patients (89%-100%), antibodies against most serotypes reached trough levels ≥ 0.2 µg/mL, a threshold considered protective against invasive pneumococcal infection. For several serotypes, trough levels reached ≥ 1.0 to 1.3 µg/mL, the level found in adults. Trough geometric mean concentrations correlated well with the PnPsAb contents of the IVIG product. Conclusions: In IVIG-treated children with PID, protective PnPsAb levels for most pathogenic serotypes were obtained. A correlation was observed between PnPsAb levels in patients and in the IVIG product. This offers the potential to improve infection prevention by adapting the IVIG product and dose according to epidemiology.
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