Vaccination, Underlying Comorbidities, and Risk of Invasive Pneumococcal Disease

Yıldırım, İnci; Shea, Kimberly M.; Little, Brent A.; Silverio, Amy L.; Pelton, Stephen I.

doi:10.1542/peds.2014-2426

Cited by 49 publications

(43 citation statements)

References 20 publications

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“…33 IPD risk is highest among children and adults with immunocompromised immune systems due to congenital or acquired immunodeficiency, immunosuppressive therapy, functional (e.g., sickle cell disease) or anatomic asplenia, chronic renal failure, or nephrotic syndrome. 7,32,34 In immunocompromised adults 18–64 years of age, the incidence of IPD is 100–400 cases per 100,000 30,33 compared with approximately 9 cases per 1000,000 in otherwise healthy adults in that age group. 31 Similarly, the risk of IPD in children under 5 years of age and 5 to 17 years of age with immunocompromising medical conditions is ~4-fold to ~40-fold higher compared with otherwise healthy children of the same age.…”

Section: Pneumococcal Disease In Children With Comorbid Conditionsmentioning

confidence: 99%

“…Van Hoek et al reported increased case fatality rates, specifically in children with asplenia and chronic cardiac, pulmonary, and liver disease. 32,35 …”

Section: Pneumococcal Disease In Children With Comorbid Conditionsmentioning

confidence: 99%

“…Several studies have identified an increased proportion of IPD due to non-vaccine serotypes in children with comorbid conditions. 32,39 Ladhani et al 40 reported that children with comorbid conditions have a broader spectrum of serotypes including those with a lower likelihood of causing disease after colonization (Figure 5). These observations have important implications and provide support for the ACIP recommendations for immunization with 23-valent pneumococcal polysaccharide vaccine in children with specified at-risk conditions.…”

Section: Pneumococcal Disease In Children With Comorbid Conditionsmentioning

confidence: 99%

“…55 We continue to use this combination despite the decline in serotype 19A prevalence in the community as most recent data continues to identify cases of 19A disease in children. 32 As vancomycin penetrates the CNS poorly, especially when administered with dexamethasone, higher dosing (70 mg/kg/day) is recommended initially (Table 1) specifically in children < 12 years of age. 56 Once the etiology is established and susceptibility determined, cefotaxime or ceftriaxone alone is adequate when susceptible pneumococci are causative.…”

Section: Treatmentmentioning

confidence: 99%

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Pneumococcal Disease in the Era of Pneumococcal Conjugate Vaccine

Yıldırım

Shea

Pelton

2015

Infectious Disease Clinics of North America

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SYNOPSIS Universal immunization of infants and toddlers with PCVs over the past 15 years has dramatically altered the landscape of pneumococcal disease. Decreases in IPD, all cause pneumonia, empyema, mastoiditis, acute otitis media and complicated otitis media have been reported from multiple countries where universal immunization has been implemented. The introduction of the vaccine has also led to expanded understanding of pneumococcal disease; observations have confirmed that most pneumococci are transmitted from children to adults, not all pneumococcal serotypes are equal in terms of common clinical syndromes, likelihood of antibiotic resistance, or likelihood of progression to disease once colonization occurs. Children with comorbid conditions have higher rates of pneumococcal disease and increased case fatality rates compared to otherwise healthy children, and protection for the most vulnerable pediatric patients will require new strategies to address the underlying host susceptibility and the expanded spectrum of serotypes observed.

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Section: Pneumococcal Disease In Children With Comorbid Conditionsmentioning

confidence: 99%

“…Van Hoek et al reported increased case fatality rates, specifically in children with asplenia and chronic cardiac, pulmonary, and liver disease. 32,35 …”

Section: Pneumococcal Disease In Children With Comorbid Conditionsmentioning

confidence: 99%

Section: Pneumococcal Disease In Children With Comorbid Conditionsmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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Pneumococcal Disease in the Era of Pneumococcal Conjugate Vaccine

Yıldırım

Shea

Pelton

2015

Infectious Disease Clinics of North America

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“…A more recent study from Massachusetts showed no change in serotype 3 carriage rate after PCV13 introduction, although the numbers of serotype 3 cases overall admittedly were quite small (21).…”

Section: Discussionmentioning

confidence: 90%

Capsular Polysaccharide (CPS) Release by Serotype 3 Pneumococcal Strains Reduces the Protective Effect of Anti-Type 3 CPS Antibodies

Choi

Zhang

et al. 2016

Clin Vaccine Immunol

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The efficacy of the serotype 3 (ST3) pneumococcal conjugate vaccine (PCV) remains unclear. While the synthesis of capsular polysaccharide (CPS) of most serotypes is wzy dependent, the strains of two serotypes, 3 and 37, synthesize CPS by the synthasedependent pathway, resulting in a polysaccharide that is not covalently linked to peptidoglycan and can be released during growth. We hypothesized that the release of CPS during growth reduces anti-type 3 CPS antibody-mediated protection and may explain the lower efficacy of the type 3 component of PCV than that of other PCVs. The in vitro-released CPS concentrations per 10 7 CFU of ST3 and ST37 strains were significantly higher than those for the ST1, ST4, ST6B, and ST14 strains. Following intraperitoneal (i.p.) injection in mice, blood concentrations of CPS were significantly higher for the ST3 than for the ST4/5 strains. The opsonophagocytic killing assay (OPKA) titer of anti-type 3 CPS antibody was significantly reduced by type 3 CPS, culture supernatant, or serum from Streptococcus pneumoniae ST3 strain WU2-infected mice. Mice were injected with capsule-specific antibodies and challenged i.p. with or without the addition of sterile culture supernatant containing type-specific CPS. The addition of 0.2 l of culture supernatant from WU2 inhibited passive protection, whereas 100-fold-more culture supernatant from S. pneumoniae ST4 strain TIGR4 was required for the inhibition of protection. We conclude that released type 3 CPS interferes with antibody-mediated killing and protection by anti-CPS antibodies. The relative failure of ST3 PCV may be due to CPS release, suggesting that alternative immunization approaches for ST3 may be necessary. Streptococcus pneumoniae remains a major cause of bacteremia, meningitis, pneumonia, and acute otitis media worldwide (1). For the 94 pneumococcal serotypes (ST) that have been identified, the synthetic mechanisms of capsular polysaccharide (CPS) can be classified into two pathways: a synthase-dependent and a wzydependent pathway (2-5). A major difference between the two pathways is that wzy-dependent synthesis results in CPS that is covalently linked to the peptidoglycan on the bacterial cell wall, whereas the synthase-dependent CPS is bound on phosphatidylglycerol or the synthase on the membrane (2). Therefore, synthase-dependent serotypes can release CPS either by dissociation from phosphatidylglycerol or by ejection from the synthase (6); this release can be detected in vitro, as shown in reference 7.While the CPS synthesis of most serotypes is wzy dependent, strains of two serotypes, 3 and 37, synthesize CPS by the synthasedependent pathway (3, 8). Whereas ST37 strains are rarely isolated from humans, ST3 isolates are an important cause of invasive pneumococcal disease, particularly pneumonia in both children and adults (9). With the expansion of the 7-valent to the currently used 13-valent pneumococcal conjugate vaccine (PCV13), serotype 3 conjugate was added to the formulation. The immunogenicity of the type 3 conjugate led...

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