The Pediatric Infectious Disease Journal

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Invasive Streptococcus pneumoniae Infections and Vaccine Failures in Children in Ireland From the Postvaccine Era From 2007 to 2018

imageBackground:
Invasive pneumococcal disease (IPD) causes life-threatening illnesses including meningitis and bloodstream infection. Here, we report the impact of 7- and 13-valent pneumococcal conjugate vaccines (PCV7/PCV13) after introduction into the Irish pediatric immunization schedule in 2008 and 2010, respectively, and the clinical details surrounding suspected PCV vaccine failures.
Methods:
Serotyping and antimicrobial susceptibility testing of all culture-confirmed cases referred from children <16 years of age from July 2007 to June 2018 were assessed. Surveillance data were assessed to identify any potential vaccine failures.
Results:
The number of IPD cases has decreased by >50% since the introduction of PCVs. The most significant decline PCV serotypes in children <2 years of age, with a 97% decline in PCV7 serotypes, incidence rate ratio (IRR) 0.03, 95% confidence interval (CI): 0.00–0.21; and a 78% decline PCV13-only (PCV13-7) serotypes, IRR 0.22, 95% CI: 0.05–1.04, respectively. However, there has been an increase in non-PCV13 serotypes in children <2 years during the same period (IRR: 2.82, 95% CI: 1.02–7.84; P = 0.0463), with similar serotype trends observed for those 2–4 and 5–15 years of age. There were no clear vaccine replacement serotypes, instead a number of different serotypes emerged. Sixteen vaccine failures were identified, 10 of which were postbooster vaccine failures. Most failures were serotype 19A and resistant to antimicrobials.
Conclusions:
Further reducing the incidence of IPD is more challenging as the number of non-PCV13 serotypes has expanded and is now less susceptible to antimicrobials. Consequently, higher valency or broader target vaccines are now required to further prevent IPD in children.

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https://journals.lww.com/pidj/Fulltext/2020/04000/Invasive_Streptococcus_pneumoniae_Infections_and.17.aspx

New Strategy Is Needed to Prevent Pneumococcal Meningitis

imageBackground:
Polysaccharide conjugate vaccines (PCVs) target the pneumococcal capsular types that most commonly cause fatal pneumonia and sepsis. Because these types were eliminated by the vaccines, it became apparent that in immunized populations, most invasive pneumococcal diseases, including bacteremia, sepsis and complicated pneumonia, were greatly reduced. However, the protective effects of PCVs against another invasive disease, meningitis, has shown much less or no decrease in disease incidence.
Methods:
References were identified through searches of PubMed for articles published from January 1930 to the present by use of specific search terms. Relevant articles were also identified through searches in Google and Google Scholar. Relevant references cited in those articles were also reviewed.
Results:
Even in the presence of the PCVs, meningitis rates in children have been reported globally to be as high as 13 per 100,000 annually. Widespread use of vaccines resulted in the emergence of a broad diversity of replacement non-PCV type strains. These strains generally failed to cause sepsis, but caused meningitis of comparable severity and levels similar to, or in excess of, prior pneumococcal meningitis rates. This is probably because these non-PCV type strains do not survive well in the blood, therefore possibly entering the brain through nonhematogenous routes.
Conclusions:
Because virtually all cases of pneumococcal meningitis lead to either permanent neurologic sequelae or death, it would be well worth the effort to develop a new vaccine capable of preventing pneumococcal meningitis regardless of capsular type. Such a vaccine would need to protect against colonization with most, if not all, pneumococci.

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https://journals.lww.com/pidj/Fulltext/2020/04000/New_Strategy_Is_Needed_to_Prevent_Pneumococcal.8.aspx

Amount of Brain Edema Correlates With Neurologic Recovery in Pediatric Cerebral Malaria

imageBackground:
Cerebral malaria (CM) remains a leading cause of mortality and morbidity in children in sub-Saharan Africa. Recent studies using brain magnetic resonance imaging have revealed increased brain volume as a major predictor of death. Similar morphometric predictors of morbidity at discharge are lacking. The aim of this study was to investigate the utility of serial cranial cisternal cerebrospinal fluid (CSF) volume measurements in predicting morbidity at discharge in pediatric CM survivors.
Methods:
In this case–control study, 54 Malawian pediatric CM survivors with neurologic sequelae evident at discharge who underwent serial magnetic resonance imaging scans while comatose were matched to concurrently admitted children with serial imaging who made full recoveries. Serial cranial cisternal CSF volume quantified by radiologists blinded to outcome was evaluated as a predictor of neurologic deficits at discharge. The probability of neurologic sequelae was determined using a model that included coma duration and changes in cisternal CSF volume over time.
Results:
Coma duration before admission was similar between cases and controls (16.1 vs. 15.3; P = 0.81), but overall coma was longer among children with sequelae (60 vs. 38 hours; P < 0.01). Lower initial CSF volumes and decreased volumes over time were both associated with a higher probability of neurologic sequelae at discharge.
Conclusions:
Among pediatric CM survivors with prolonged coma, lower initial CSF volume and decreasing volume during coma is associated with neurologic sequelae at discharge. These findings suggest that cerebral edema is an underlying contributor to both morbidity and mortality in pediatric CM.

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https://journals.lww.com/pidj/Fulltext/2020/04000/Amount_of_Brain_Edema_Correlates_With_Neurologic.4.aspx

Epidemiology and Etiology of Severe Childhood Encephalitis in The Netherlands

imageBackground:
Limited data are available on childhood encephalitis. Our study aimed to increase insight on clinical presentation, etiology, and clinical outcome of children with severe encephalitis in the Netherlands.
Methods:
We identified patients through the Dutch Pediatric Intensive Care Evaluation database and included children diagnosed with encephalitis <18 years of age admitted to 1 of the 8 pediatric intensive care units (PICU) in the Netherlands between January 2003 and December 2013. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality.
Results:
We included 121 children with a median age of 4.6 years (IQR 1.3–9.8). The most frequently described clinical features were headache (82.1%), decreased consciousness (79.8%) and seizures (69.8%). In 44.6% of the children, no causative agent was identified. Viral- and immune-mediated encephalitis were diagnosed in 33.1% and 10.7% of the patients. A herpes simplex virus infection (13.2%) was mainly seen in children <5 years of age, median age, 1.73 years (IQR 0.77–5.01), while immune-mediated encephalitis mostly affected older children, median age of 10.4 years (IQR, 3.72–14.18). An age of ≥ 5 years at initial presentation was associated with a lower mortality (OR 0.2 [CI 0.08–0.78]). The detection of a bacterial (OR 9.4 [CI 2.18–40.46]) or viral (OR 3.7 [CI 1.16–11.73]) pathogen was associated with a higher mortality.
Conclusions:
In almost half of the Dutch children presenting with severe encephalitis, a causative pathogen could not be identified, underlining the need for enhancement of microbiologic diagnostics. The detection of a bacterial or viral pathogen was associated with a higher mortality.

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https://journals.lww.com/pidj/Fulltext/2020/04000/Epidemiology_and_Etiology_of_Severe_Childhood.2.aspx

Paraplegia in a Teenage Girl

imageNo abstract available

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https://journals.lww.com/pidj/Fulltext/2020/04000/Paraplegia_in_a_Teenage_Girl.24.aspx

Low Use of Vitamin A in Children Hospitalized for Measles in the United States

imageVitamin A reduces measles morbidity/mortality and and is recommended for management. We studied 142 patients hospitalized at US Children’s hospitals for measles between January 1, 2004, and March 31, 2019, and found only 47 (33%) received vitamin A. Patients with complex chronic conditions were less likely to be treated. This study highlights a concerning gap between recommendations and practice for hospital management of measles.

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https://journals.lww.com/pidj/Fulltext/2020/04000/Low_Use_of_Vitamin_A_in_Children_Hospitalized_for.23.aspx

Enterococcal Bacteremia in Children With Malignancies and Following Hematopoietic Stem Cell Transplantation: A 15-Year Single-Center Experience

imageBackground:
Data on enterococcal bacteremia (EB) in immunocompromised children are scarce. We aimed to describe EB in children with hematologic malignancies (HM), solid tumors and/or following allogeneic hematopoietic stem cell transplantation (HSCT) and analyze their ampicillin and vancomycin resistance.
Methods:
We conducted an observational retrospective study in the tertiary-care Hadassah University Medical Center (2001-2015). We collected demographic, clinical and laboratory data on EB and compared ampicillin and vancomycin sensitive with resistant episodes.
Results:
Fifty-six of 1123 children developed 74 episodes of EB; 62.1% Enterococcus faecium, 36.5% Enterococcus faecalis; and 1.4% Enterococcus gallinarum. EB developed in 12.1% of HSCT patients, 5.1% of HM, 6.3% of neuroblastoma and 1.0% of other solid tumors patients. Of these episodes, 85.1% were nosocomial, and 71.6% developed while on antibiotic therapy. Resistance rates were: to ampicillin, 57.6%; to vancomycin (vancomycin-resistant enterococci), 21.6%; and higher rates among E. faecium. Among vancomycin-resistant enterococci, 1 of 16 was linezolid and 2 of 10 daptomycin resistant. Overall 7- and 30-day mortality rates were 2.7% and 5.4%, respectively. Thirty-day mortality was 18.2% in recurrent episodes and 0% in the first-time EB episodes (P = 0.006). In multivariate analysis, high treatment intensity was associated with ampicillin resistance [odds ratio (OR) = 3.18, 95% confidence interval (CI): 1.31–9.12], prior penicillin exposure (OR = 7.50, 95% CI: 1.41–39.81) and breakthrough on vancomycin (OR = 18.83, 95% CI: 3.31–101.14) with vancomycin resistance.
Conclusions:
EB occurs mainly as a nosocomial infection in children receiving high-intensity chemotherapy, especially in those with neuroblastoma, HM and following HSCT. Antibiotic resistance is common. Vancomycin resistance can occur regardless of previous vancomycin use. Prognosis in immunocompromised children with EB is better than previously reported. Recurrent EB is associated with increased mortality.

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https://journals.lww.com/pidj/Fulltext/2020/04000/Enterococcal_Bacteremia_in_Children_With.13.aspx

A Phase 1 Randomized, Placebo-controlled, Observer-blinded Trial to Evaluate the Safety and Immunogenicity of Inactivated Streptococcus pneumoniae Whole-cell Vaccine in Adults

imageBackground:
Broadly protective pneumococcal vaccines that are affordable for low-resource countries are needed. Streptococcus pneumoniae whole cell vaccine (wSp) is an investigational vaccine that contains killed cells from a nonencapsulated strain of S. pneumoniae (SPn) with aluminum hydroxide adjuvant. Studies in mice demonstrated protection against nasopharyngeal carriage (T-cell-mediated) and invasive pneumococcal disease (antibody-mediated). The aim of this randomized, double-blind, placebo-controlled Phase 1 study was to assess safety, tolerability and immunogenicity of wSp in healthy adults.
Methods:
Forty-two participants were randomized into 3 dose cohorts to receive 0.1, 0.3, or 0.6 mg of wSp or saline intramuscularly. Participants received a 3-dose vaccination schedule spaced by 4-week intervals. Postvaccination assessments included solicited reactogenicity events through day 7, blood chemistry and hematology assessments at day 7, and adverse events (AEs) through day 84. Participants were monitored for serum antibody and peripheral blood mononuclear cell cytokine responses to pneumococcal antigens. A 6-month telephone follow-up was completed to assess for any additional AEs.
Results:
wSp was safe and well tolerated. Reactogenicity was acceptable and no untoward safety signals were observed. wSp elicited potentially clinically significant rises (defined arbitrarily as at least a 2-fold rise) in immunoglobulin G responses to multiple pneumococcal antigens, including pneumococcal surface protein A and pneumolysin. Functional antibody responses were observed with the highest dose of wSp (0.6 mg). Increases in T-cell cytokine responses, including interleukin 17A, were also seen among wSp vaccines.
Conclusions:
wSp was safe and well tolerated in healthy US adults, eliciting pneumococcal antigen-specific antibody and T-cell cytokine responses.

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https://journals.lww.com/pidj/Fulltext/2020/04000/A_Phase_1_Randomized,_Placebo_controlled,.18.aspx

Safety, Efficacy and Pharmacokinetics of Anidulafungin in Patients 1 Month to <2 Years of Age With Invasive Candidiasis, Including Candidemia

imageNineteen patients 1 month to <2 years of age with (n = 16) or at high risk of (n = 3) invasive candidiasis received anidulafungin for 5–35 days (3 mg/kg day 1, 1.5 mg/kg daily thereafter) followed by optional fluconazole (NCT00761267). Most treatment-emergent adverse events were mild/moderate, and no treatment-related deaths occurred. End of intravenous therapy global response success rate was 68.8%. Pharmacokinetics were similar to adult patients.

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https://journals.lww.com/pidj/Fulltext/2020/04000/Safety,_Efficacy_and_Pharmacokinetics_of.9.aspx

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