Rapid Decrease in Rates of Hospitalization Resulting From Invasive Pneumococcal Disease and Community-Acquired Pneumonia in Children Aged <60 Months After 13-Valent Pneumococcal Conjugate Vaccine Introduction in Argentina.

BACKGROUND: In January 2012, Argentina included universal pneumococcal vaccination in the routine childhood vaccination program using a 13-valent pneumococcal conjugate vaccine (PCV13). A 2 + 1 schedule (2 doses in the first year of life and a booster dose at 12 months of age) in children aged <2 years and 2-dose catch-up immunization in children aged 13 to 24 months was administered during the first year of vaccine introduction. The purpose of this study was to assess the burdens of invasive pneumococcal disease (IPD) and/or community-acquired pneumonia (CAP) in hospitalized children younger than 5 years during the first 2 years of the program compared to those in the prevaccination period in our setting. METHODS: This was a multicenter, prospective, and descriptive study. Rates of hospitalization resulting from IPD and/or CAP in 5 pediatric reference centers across the country were analyzed (every 10 000 admissions). Clinical, epidemiologic, and microbiological data were recorded. Statistical analysis using Stata 8.0 was performed. RESULTS: A comparison of rates of hospitalization resulting from global IPD and/or CAP in the prevaccine (2009-2011) and postvaccine (2012-2013) periods revealed significant decreases of 50% (P = .003) and 51% (P < .0001), respectively. Significant decreases were also observed in number of hospitalizations resulting from empyema (39%; P = .03) and pneumococcal empyema (67.8%; P = .007); the reduction was not statistically significant for pneumococcal CAP (58%; P = .18). Hospital stays for IPD and/or CAP decreased by 56%. CONCLUSION: Rapid and significant decreases in the rates of hospitalization resulting from IPD and/or CAP during the first 2 years after PCV13 introduction were observed. A longer surveillance period is required to confirm these results and the effectiveness of the vaccination program.

An epidemiologic surveillance of Shiga-like toxin-producing Escherichia coli infection in Argentinean children: risk factors and serum Shiga-like toxin 2 values.

BACKGROUND AND AIMS: Shiga-like toxin (Stx)-producing Escherichia coli (STEC) infection is an ongoing health issue that can lead to serious complications, including hemolytic uremic syndrome (HUS) and death. This study assessed demographic and epidemiologic information of STEC infection among Argentinean children. METHODS: A prospective surveillance of 2435 screened children (age, 0.5-15 years) presenting with watery diarrhea and/or bloody diarrhea was undertaken to evaluate the clinical course of STEC infection. RESULTS: Prevalence of STEC infection was 4.1% among subjects presenting with watery diarrhea for ≤ 5 days' duration, bloody diarrhea for ≤ 36 hours' duration, or both. Incidence of STEC infection was significantly higher in the subjects with bloody diarrhea. Ninety-three STEC+ children underwent further evaluation, of whom 8 (8.6%) developed HUS. White blood cells, particularly neutrophils, were abnormally elevated at screening in 5 of 8 HUS subjects. Quantifiable serum Stx-2 values were noted within 24 to 48 hours after the onset of bloody diarrhea in 3 HUS subjects using a validated chemiluminescence assay, with levels quickly dissipating by HUS onset. CONCLUSIONS: Results suggest that young STEC-positive children with bloody diarrhea and exhibiting neutrophilic leukocytosis in the early course of their diarrhea are at risk for HUS progression. The observation of measurable concentrations of Stx-2 levels in the early post-bloody-diarrhea period and rapid dissipation at the time of HUS onset requires further evaluation.

Safety and pharmacokinetics of urtoxazumab, a humanized monoclonal antibody, against Shiga-like toxin 2 in healthy adults and in pediatric patients infected with Shiga-like toxin-producing Escherichia coli.

Shiga-like toxin-producing Escherichia coli (STEC) infection causes diarrhea, which is often bloody and which can result in potentially life-threatening hemolytic-uremic syndrome (HUS). Urtoxazumab, a humanized monoclonal antibody directed against the Shiga-like toxin 2 (Stx2) produced by STEC, has been developed as a promising agent for the prevention of HUS. Single randomized, intravenous, double-blind, placebo-controlled doses of urtoxazumab were administered to assess its safety and pharmacokinetics in healthy adults (0.1 to 3.0 mg/kg of body weight) and STEC-infected pediatric patients (1.0 and 3.0 mg/kg). No dose-related safety trends were noted, nor were antiurtoxazumab antibodies detected. The disposition of urtoxazumab showed a biexponential decline, regardless of the dose. In healthy adults, the mean terminal elimination half-life was consistent across the dose groups and ranged from 24.6 days (3.0-mg/kg dose group) to 28.9 days (0.3-mg/kg dose group). The mean maximum serum drug concentration (C(max)) ranged from 2.6 microg/ml at 0.1 mg/kg to 71.7 microg/ml at 3.0 mg/kg. The disposition of urtoxazumab following the administration of doses of 1.0 and 3.0 mg/kg in pediatric patients showed mean C(max)s of 19.6 and 56.1 microg/ml, respectively. Urtoxazumab was well tolerated, appears to be safe at doses of up to 3.0 mg/kg, and is a potential candidate for the prevention of HUS in pediatric patients.