[Show abstract][Hide abstract] ABSTRACT: Background
Although mouse brain-derived, inactivated Japanese encephalitis vaccines (JE-MBs) have been successfully used for a long time, potential rare neurological complications have prompted the development of a Vero cell culture-derived inactivated vaccine (JE-VC). In a phase III clinical study, we aimed to compare the safety and immunogenicity of a JE-VC, KD-287 with a JE-MB, JEV-GCC, in children.Methods
In this multicenter, double-blinded, randomized controlled trial, the study population consisted of 205 healthy Korean children aged 12¿23 months. Each subject was subcutaneously vaccinated with either KD-287 or JEV-GCC twice at an interval of 2 weeks and then vaccinated once 12 months after the second vaccination. Neutralizing antibodies were measured by the plaque reduction neutralization test using the homologous and heterologous, as a post hoc analysis, challenge virus strains.ResultsThe three-dose regimen of KD-287 showed a comparable safety profile with JEV-GCC except higher incidence of fever after the first dose (30.4% and 14.7%, respectively). Most of the fever was mild degree (61.3% and 66.7%, respectively). KD-287 fulfilled the non-inferiority criteria for seroconversion rate (SCR) and geometric mean titer (GMT) of the neutralizing antibody, which were the primary endpoints, at 4 weeks after the third vaccination (95% CI: ¿1.00, 3.10 for the SCR difference and 10.8, 17.6 for the GMT ratio). The SCRs of KD-287 were all 100% and the GMTs were higher in the KD-287 group than in the JEV-GCC group after the second vaccination and before and after the third vaccination (GMT ratio: 5.59, 20.13, and 13.79, respectively, p¿<¿0.001 in all). GMTs were higher in the KD-287 group in the heterologous analysis also (GMT ratio: 4.05, 5.15, and 4.19, respectively, p¿<¿0.001 in all).Conclusions
This study suggests that the KD287, a JE-VC is as safe as and may be more effective than the licensed MB-derived vaccine. KD-287 could thus be useful as a second-generation vaccine and substitute for the current JE-MB vaccine in Korean children.Trial registrationClinicalTrials.gov: NCT01150942.
[Show abstract][Hide abstract] ABSTRACT: Chronic granulomatous disease (CGD) is a rare immunodeficiency disease, which is characterized by the lack of a functional nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. The disease presents leukocytosis, anemia, hypergammaglobulinemia, and granuloma formation of the skin, lung, or lymph nodes. The mutation of the CYBB gene encoding gp91phox, located on chromosome Xp21.1 is one of the causes of CGD. We report a patient with X-linked CGD who carried a novel mutation, a c.1133A>G (paAsp378Gly) missense mutation, in the CYBB gene.
[Show abstract][Hide abstract] ABSTRACT: This study examined the serotype distribution and antimicrobial resistance of pneumococcal isolates from invasive infections in children between 2006 and 2010, when the 7-valent pneumococcal conjugate vaccine (PCV7) was offered as an optional vaccine in Korea. Among 140 isolates collected from 8 centers, the common serotypes were 19A (22.9%), 19 F (12.1%), and 6B (8.6%). Between 2006 and 2010, PCV7 serotypes decreased from 62.5% to 21.4% (P = 0.002), whereas 3 PCV13-specific serotypes (3, 6A, and 19A) increased from 18.8% to 42.9% (P = 0.016). Among 102 multidrug-resistant isolates, the proportion of PCV7 serotypes decreased from 65.2% to 21.7% (P = 0.001), and 3 PCV13-specific serotypes increased from 17.4% to 47.8% (P = 0.008). Optional PCV7 vaccination has influenced the proportion of PCV7 serotypes in Korea, resulting in a decrease, whereas the proportions of 3 PCV13-specific serotypes, particularly 19A, have increased.
Diagnostic microbiology and infectious disease 04/2014; · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:QuantiFERON-TB Gold In-Tube (QFT-G IT; Cellestis Inc., Valencia, CA, USA) is one of the Interferon-gamma Release Assays (IGRAs) that are promising tools for diagnosing active or latent Mycobacterium tuberculosis infection. We investigated the clinical and laboratory factors that affect the rate of indeterminate QFT-G IT test results. We also suggest the workflow strategy to achieve optimized test results using QFT-G IT for the diagnosis of active TB or LTBI.Methods:We performed statistical analysis using data from review of medical records, retrospectively. The first phase included 683 QFT-G IT test results from 676 patients tested from January 2008 to May 2008, and the second phase included additional 663 QFT-G IT test results from 653 patients tested from January 2008 to December 2008 at Samsung Medical Center, a tertiary care hospital in South Korea.Results:Immunosuppressive drug therapy, underlying diseases, bed-ridden status, and hypoalbuminemia were significantly associated with an indeterminate QFT-G IT test result. With the reduction in incubation delay from an average of 9.82 hours to an average of 2.70 hours during the test procedure by making changes in the workflow, the frequency of indeterminate QFT-G IT test results was significantly reduced from 11.4% to 2.7%. However, if there was a more than 6 hours of incubation delay, the frequency of indeterminate QFT-G IT test results was increased in a statistically significant manner.Conclusion:This study demonstrates that not only the clinicopathological factors, but also the laboratory factor such as incubation delay affects significantly on the rate of indeterminate QFT-G IT test results, and hence optimization of the test procedure may contribute to the reduction in the rate of indeterminate QFT-G IT test results that delay the diagnosis of TB.
Journal of clinical microbiology 10/2013; · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Ventilator-associated pneumonia (VAP) is a serious threat in critically ill pediatric patients. Data regarding associated VAP caused by Stenotrophomonas maltophilia in pediatric population is limited.
Methods: A retrospective chart review was performed in pediatric patients 18 years old or younger who developed the first episode of S. maltophilia associated VAP at Samsung Medical Center, Seoul Korea from January 2008 to December 2012.
Results: A total of 45 patients were identified with VAP caused by S. maltophilia. Median age was 1.9 years (range, 0.1 to 18.8 years) and 24 patients were male (53.3%). Underlying illnesses were hematologic oncologic malignancy (n=14, 31.1%28.9%), cardiologic diseases (n=13, 28.97%), neurologic diseases (n=9, 20.0%), pulmonary diseases (n=5, 11.1%), and others (n=4, 8.9%). The median duration of ventilator treatment before VAP was 21 days (range, 3-255 days). Two patients also developed S. maltophilia bacteremia (4.4%). Overall mortality at 30 days was 6.7%.
Conclusion: S. maltophilia should be also considered as a possible pathogen for VAP in critically ill pediatric patients. Empiric antibiotic choice should include agents that are active against S. maltophila in patients who are deteriorating on broad spectrum beta-lactam antimicrobial agents.
IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
[Show abstract][Hide abstract] ABSTRACT: Background:
Ciprofloxacin is not approved in children under 18 years old due to its potential musculoskeletal adverse effects. However, it is widely prescribed in the pediatric patients. We conducted a retrospective multicenter study to evaluate the prescription pattern of ciprofloxacin and to review any reported adverse events in Korean children.
A retrospective review was performed in patients younger than 18 years old who received ciprofloxacin in 7 university hospitals in Korea from January 2006 to December 2011.
A total of 729 patients were identified. The median age was 15.9 years (range, 0.1-17.9); 18 patients (2.5%) were under 2 years old, 77 (10.6%) 2-9 years, 143 (19.6%) 10-14 years, and 491 (67.4%) 15-17 years. Two-hundred sixty-nine (36.9%) patients had comorbid medical conditions. Ciprofloxacin was given as the first-line antimicrobial agent in 480 (65.8%) patients. Clinical diagnoses at the time of ciprofloxacin prescription were gastroenteritis (325, 44.6%), urinary tract infections (159, 21.8%), abscess or skin and soft tissue infections (65, 8.9%) and pneumonia (55, 7.5%). There were 22 bacteremia cases (3.0%). Ciprofloxacin was prescribed mostly by emergency care physicians (207, 28.4%), internal medicine physicians (187, 25.7%) and pediatricians (153, 21.0%). The use of ciprofloxacin based on culture results was observed in only 26.1% of total patients (190/729); 43.8% by pediatricians vs. 21.4% by non-pediatric physicians (P<0.0001). Adverse events after use of ciprofloxacin were observed in 15 patients (2.1%): four with hypersensitivity, six with gastrointestinal complaints, one with headache, one with EKG abnormality and three others. There was no musculoskeletal complication reported.
This is the first multicenter study to evaluate the prescription pattern and safety of ciprofloxacin in Korean children. We found that ciprofloxacin was frequently prescribed in children as an empiric antibiotic choice in many unapproved indications and musculoskeletal adverse event was not reported in any of these patients. There is a need for systematic monitoring for the appropriate use of ciprofloxacin and development of musculoskeletal complication in Korean children.
IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
[Show abstract][Hide abstract] ABSTRACT: We describe three children with urinary tract abnormalities and large numbers of S. pneumoniae in their urine, along with a brief review of previously reported cases. These findings strongly suggest that S. pneumoniae is a uropathogen, especially in children with urinary tract abnormalities.
The Pediatric Infectious Disease Journal 08/2013; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This article contains the recommended immunization schedule by the Committee on Infectious Diseases of the Korean Pediatric Society, updated in March 2013, when Haemophilus influenzae type b vaccine is now included in the National Immunization Program in Korea. It also includes catch-up immunization schedule for children and adolescents who are behind the recommended schedule. These schedules are a minor revision of the corresponding parts of Immunization Guideline, 7th edition, of the Korean Pediatric Society, released in 2012. Pediatricians should be aware of these schedules to provide adequate immunization to Korean children and adolescents.
Korean Journal of Pediatrics 06/2013; 56(6):231-234.
[Show abstract][Hide abstract] ABSTRACT: Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children.
Korean Journal of Pediatrics 05/2013; 56(5):196-201.
[Show abstract][Hide abstract] ABSTRACT: We compared the 16S rRNA gene sequencing results analyzed with the GenBank, EzTaxon, and BIBI databases for blood culture specimens for which identifications were incomplete, conflicting, or unidentifiable using conventional methods. Analyses performed using GenBank combined with EzTaxon (kappa = 0.79) were more discriminative than those using other databases alone or in combination with a second database.
Journal of clinical microbiology 03/2012; 50(5):1792-5. · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Respiratory viruses (RVs) are a known cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). In this retrospective study, we focused on the first 28 d after transplantation in pediatric HSCT recipients and showed that a multiplex PCR assay significantly increased RV detection compared with a viral culture method. Among 176 pediatric HSCT recipients, 84 with respiratory symptoms within one yr after HSCT were tested by viral culture or multiplex PCR. Within 28 d after HSCT, nine patients were infected with RVs; the incidence of a first episode of RV infection within 28 d after HSCT was 5.1%. Eight patients recovered without complications. However, one patient died of adenovirus (AdV) pneumonia with pulmonary hemorrhage; the mortality rate of RV infection within 28 d after HSCT was 0.57%. In the nine patients with RV infection, five different types of RV were identified, either alone or with another RV. These were corona virus (CoV), rhinovirus (RhV) and respiratory syncytial virus combined with CoV; AdV combined with RhV; and parainfluenza virus. Viral culture detected only one case of RV infection, while multiplex PCR detected eight, suggesting that screening of respiratory infections using multiplex PCR is better than the conventional culture method.
[Show abstract][Hide abstract] ABSTRACT: This study was performed in order to evaluate the incidence and characteristics of cytomegalovirus (CMV) infection in children with acute leukemia according to donor source and graft type.
We retrospectively identified children with acute leukemia who had received allogeneic hematopoietic cell transplantation at Samsung Medical Center in Korea from October 1998 to December 2009.
In total, 134 recipients were identified. The patients were classified into the following three groups: unrelated cord blood (CB, n=36), related bone marrow or peripheral blood stem cells (RD, n=41), and unrelated bone marrow or peripheral blood stem cells (UD, n=57). The 365-day cumulative incidence of CMV antigenemia was not significantly different among the three groups (CB 67% vs. RD 49% vs. UD 65%, p=0.17). However, CB recipients had the highest median value of peak antigenemia (CB 160/2×10⁵ leukocytes vs. RD 7/2×10⁵ leukocytes vs. UD 19/2×10⁵ leukocytes, p<0.01) and the longest duration of CMV antigenemia than the other stem cell source recipients (CB 87 days vs. RD 17 days vs. UD 28 days, p<0.01). In addition, the 730-day cumulative incidence of CMV disease was the highest in the CB recipients (CB 36% vs. RD 2% vs. UD 5%, p<0.01). Thirteen CB recipients developed CMV disease, in which five of them had more than one organ involvement. Two patients, who were CB recipients, died of CMV pneumonia.
This study suggests that CB recipients had both longer and higher cumulative incidences of CMV infection. Therefore, a more aggressive and effective strategy of CMV management should be considered in CB recipients.
Yonsei medical journal 03/2012; 53(2):393-400. · 0.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Respiratory virus (RV) infection can cause significant morbidity and mortality in pediatric cancer patients. Parainfluenza virus (PIV) is a common pathogen in childhood among the respiratory viruses. The objective of this study is to evaluate the impact of parainfluenza virus infection in pediatric cancer patients.
A retrospective review of medical records of 1,554 children diagnosed with cancer from January 2000 through July 2008 was analyzed at Samsung Medical Center.
A total of 6.4% (137/1,554) had respiratory virus infection and 54% (74/137) of patients with RV infection had PIV infection. PIV type 3 was the predominant subtype. Among patients with PIV infection, 59 children (79.7%) had upper respiratory tract infection (URI) whereas 15 children (20.3%) had lower respiratory tract infection (LRI) at initial presentation. Among patients with URI, 12 (20.3%) progressed to pneumonia with the median interval of 4 days from URI to LRI. Mortality associated with PIV infection was 18.5% (5/27) in patients with LRI. Among patients with PIV infection, 80% (59/74) had nosocomial infection, which shows the difficulty and importance of infection control at pediatric cancer ward.
PIV infection was most commonly diagnosed among pediatric cancer patients with RV infection and PIV infection led to significant pulmonary complications and direct mortality in immunocompromised children. Since there are no effective antiviral agents for PIV infection, precautionary infection control and early diagnosis are the only methods available to prevent the infection spread.
Pediatric Blood & Cancer 11/2011; 59(4):708-10. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised children. We investigated the usefulness of Aspergillus galactomannan (GM) antigen assay as a diagnostic tool for IA in pediatric cancer patients and hematopoietic cell transplantation (HCT) recipients.
Methods: GM antigen assay results were analysed in 902 blood samples from 180 pediatric cancer patients at Samsung Medical Center, Seoul, Korea from July 2007 to September 2010. Blood samples with GM index ≥0.5 at least twice in a patient were considered positive. A review of clinical data was performed on subjects with proven or probable IA defined by the European Organization for Research and Treatment of Cancer-Mycoses Study Group criteria (EORTC/MSG).
Results: Twenty-one of 23 patients with proven or probable IA had positive GM antigen test results (91.3% sensitivity, 95% confidence interval (CI) 0.7194-0.9893; 81.7% specificity, 95% CI 0.6958-0.9048; P< 0.0001). False positive rate was 18.3% (11/60); the patient age (<3 year), having solid tumor and receiving HCT within 4 weeks were statistically significant factors for false positive result (P < 0.05). Among 23 patients with IA (six with proven IA and 17 with probable IA), 16 had hematological malignancies (69.6%), 5 had solid tumors (21.7%) and 2 had primary immune deficiency (8.7%). Nineteen patients (82.6%) received HCT (16 allogeneic and 3 autologous). Most patients had several immunocompromised risk factors; steroid therapy (12, 52.2%), immunosuppressive therapy (16, 69.6%) and GVHD (13, 56.5%). The most common clinical site of IA was the lungs (21, 91.3%) and consolidation was the most frequent finding on chest CT (11, 37.9%). Before the diagnosis of IA, 60.9% of patients received antifungal agents (itraconazole 57.1%, fluconazole 42.9%). Amphotericin B deoxycholate was given as the first choice for antifungal agent (15, 65.2%). Six patients received more than two antifungal agents concurrently. The overall mortality was 56.5% and IA attributable mortality was 43.5% despite aggressive antifungal managements.
Conclusion: The GM antigen assay appears to be useful to diagnose IA in pediatric cancer patients and clinical correlation is imperative.
Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
[Show abstract][Hide abstract] ABSTRACT: A 3-year-old girl with acute respiratory distress syndrome due to a H1N1 2009 influenza virus infection was complicated by necrotizing pneumonia was successfully treated with extracorporeal membrane oxygenation (ECMO). This is the first reported case in which a pediatric patient was rescued with ECMO during the H1N1 influenza epidemic in Korea in 2009.
Korean Journal of Pediatrics 08/2011; 54(8):345-9.
[Show abstract][Hide abstract] ABSTRACT: Pertussis is an acute respiratory infection characterized by paroxysmal cough and inspiratory whoop for over 2 weeks. The incidence of pertussis has decreased markedly after the introduction of DTwP/DTaP vaccine, but the incidence of pertussis has increased steadily among young infant and among adolescents and adults in many countries. Td vaccine was used in this age group but the increase in pertussis has lead to the development of a Tdap vaccine. The Tdap vaccine is a Td vaccine with a pertussis vaccine added and is thought to decrease the incidence and transmission of pertussis in the respective age group. In Korea, two products are approved by the KOREA FOOD & DRUG ADMINISTRATION, which are ADACEL™ (Sanofi-Pasteur, Totonto, Ontario, Canada) and BOOSTRIX® (GlaxoSmithKline Biologicals, Rixensart, Belgium) for those aged between 11-64. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.
Korean Journal of Pediatrics 04/2011; 54(4):141-5.
[Show abstract][Hide abstract] ABSTRACT: The risk of invasive fungal infection is greater for allogeneic hematopoietic stem cell transplantation (HSCT) than for autologous transplantation. Therefore, many transplantation centers use antifungal prophylaxis for allogeneic HSCT, however, there exists no standard guidelines or consensus regarding autologous HSCT.
A prospective double-blind randomized study was conducted in autologous HSCT recipients who were divided into prophylaxis and empirical treatment groups, and we investigated the efficacy of itraconazole prophylaxis in pediatric autologous HSCT.
Total 87 autologous HSCT episodes in 55 children with high-risk solid tumors were studied. No invasive fungal infections occurred in either group. However, patients in the prophylaxis group had a significantly shorter duration of fever (p < 0.05) and received antibacterial treatment of shorter duration (p < 0.05) with fewer numbers of antibiotics (p < 0.05 for the use of second line antibiotics) than those in the empirical group. No significant additional adverse events were found with itraconazole prophylaxis.
Although beneficial effects such as a shorter duration of fever and reduced need for antibiotic use were observed in the prophylaxis group, the results were not sufficient to draw a definite recommendation about the routine use of antifungal prophylaxis in pediatric autologous HSCT recipients with high-risk solid tumors (Trial registration: NCT00336531).
Yonsei medical journal 03/2011; 52(2):293-300. · 0.77 Impact Factor