• Pediatric Infection and Vaccine
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• v.25 no.2
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• pp.101-106
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• 2018

A 6-year-old boy with underlying hemolytic anemia of unknown etiology, atopic dermatitis, and recurrent urticaria visited our hospital because of acute respiratory failure induced by influenza A. Despite mechanical ventilation after endotracheal intubation along with inhalation of nitric oxide, respiratory acidosis and hypoxemia persisted. Veno-venous extracorporeal membrane oxygenation (VV ECMO) insertion was performed to provide respiratory support. After performing flexible bronchoscopy, we found that thick mucus plugs were obstructing the right bronchus intermedius and the upper lobe orifice. After bronchial washing and removal of the plugs, we were able to wean the patient off VV ECMO and transfer him to the general ward. He was discharged without any neurologic or pulmonary sequelae.

• Molecules and Cells
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• v.43 no.3
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• pp.251-263
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• 2020

Flagellin, a major structural protein of the flagellum found in all motile bacteria, activates the TLR5- or NLRC4 inflammasome-dependent signaling pathway to induce innate immune responses. Flagellin can also serve as a specific antigen for the adaptive immune system and stimulate anti-flagellin antibody responses. Failure to recognize commensal-derived flagellin in TLR5-deficient mice leads to the reduction in anti-flagellin IgA antibodies at steady state and causes microbial dysbiosis and mucosal barrier breach by flagellated bacteria to promote chronic intestinal inflammation. Despite the important role of anti-flagellin antibodies in maintaining the intestinal homeostasis, regulatory mechanisms underlying the flagellin-specific antibody responses are not well understood. In this study, we show that flagellin induces interferon-β (IFN-β) production and subsequently activates type I IFN receptor signaling in a TLR5- and MyD88-dependent manner in vitro and in vivo. Internalization of TLR5 from the plasma membrane to the acidic environment of endolysosomes was required for the production of IFN-β, but not for other pro-inflammatory cytokines. In addition, we found that anti-flagellin IgG2c and IgA responses were severely impaired in interferon-alpha receptor 1 (IFNAR1)-deficient mice, suggesting that IFN-β produced by the flagellin stimulation regulates anti-flagellin antibody class switching. Our findings shed a new light on the regulation of flagellin-mediated immune activation and may help find new strategies to promote the intestinal health and develop mucosal vaccines.

• Pediatric Infection and Vaccine
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• v.5 no.2
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• pp.215-220
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• 1998

Purpose : Asymptomatic infections with positive throat culture for group A beta-hemolytic streptococci(GABHS) and high antistreptolysin O(ASO) concentration may lead to sequelae such as rheumatic fever or acute poststreptococcal glomerulonephritis. Children with asymptomatic infections were treated with oral penicillin V to evaluate the effectiveness of penicillin treatment on the asymptomatic infections. Methods : Throat culture and ASO concentration analysis were performed against healthy elementary school children. Thirty-six children with positive throat culture for GABHS and ASO concentrations of 400 IU/mL or more were divided into two groups. Twenty-two children were treated with oral penicillin V for 10 days, and the others were not treated. Eradication rate of GABHS and the change of ASO concentration between the two groups were compared after one month later. Results : Eradication rates of GABHS between treated and untreated children were 91%(20/22) and 50%(7/14) respectively(P<0.05). Children showing elevation of ASO levels more than 100IU/mL were 22%(4/18) in the treated group and 30%(3/10) in the untreated group, while children showing a decrease of more than 200IU/mL in the ASO level were 44%(8/18) and 40%(4/10) respectively. Conclusion : We confirmed the validity of penicillin treatment, because when we treated the asymptomatic children with penicillin V, the GABHS was eradicated effectively. But there was no significant difference of decrease in the ASO levels between the two groups due to long half-life of ASO or poor compliance. Treatment failure was 22% in terms of elevated ASO levels after penicillin treatment.

• Pediatric Infection and Vaccine
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• v.3 no.2
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• pp.185-193
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• 1996

Purpose : The incidence of measles was gradually decreased since 1963 when measles vaccination was firstly developed and liscenced in the world. But, recently the outbreaks of measles in infants and school children have been reported despite of wide spread use of measles vaccination. This study was performed to evaluate the efficacy of measles vaccination and the necessity of revaccination in Korean infants and children. Methods : 168 subjects of mothers and neonates, infants and children were enrolled in this study during the periods of 10 months from March to December in 1995. Measles specific IgG in the sera of mothers and children was measured using EIA kit (Sigma Co., MO, USA). Antibody titer of over or equal to 110 AU/ml was considered positive. Results : The results obtained were as follows. 1) Values of measles specific IgG in the sera of mother and neonate were 82.9 AU/ml and 89.3 AU/ml respectively and were rapidly decreased within 6 month after birth. Positive antibody levels (${\geq}$ 110 AU/ml) were observed in only 25 % of neonates. 2) In vaccinated children, values of measles specific IgG were 117.4 AU/ml in 9~15 month group, 76.9 AU/ml in 3~6 year group and 79.5 AU/ml in 10~15 year group after either one or two times of measles vaccination. Positive antibody levels in vaccinated children were observed in 57.7% of 9~15 month group, 38.4% of 3~6 year group and 34.7% of 10~15 year group. Conclusion : These results suggest that primary measles vaccination before 6 months of age can be considered and revaccination of measles should be recommended before 3~6 years of age. Further studies will be needed to clarify the reasons of high proportion of primary measles vaccination failure and to established the appropriate schedule of measles vaccination in korean infants and children.

• Korean Journal of Veterinary Research
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• v.41 no.2
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• pp.211-218
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• 2001

The $M_r$ 63,000 glycoprotein (GP63) and lipophosphoglycan (LPG) of Leishmania donovani were evaluated as vaccine candidates against visceral leishmaniasis. Mice were immunized with liposomeencapsulated GP63 and/or LPG that were purified from the soluble extract of L. donovani promastigotes, and were challenged with virulent amastigotes. Mice immunized with GP63/LPG in liposomes plus BCG resulted in a 27.4% reduction of amastigotes in the liver compared to the control group (liposomes plus BCG), and mice immunized with liposome-GP63 plus BCG failed to induce a protective immune response against the challenge infection. Immunization of mice with GP63 fused to the Schistosoma japonicum glutathione S-transferase (GP63-GST) plus BCG also failed to elicit protective immunity. To analyze the cause of failure to induce protection, cytokine release from the spleen cells of immunized mice and Leishmania-specific serum antibodies were analyzed. Spleen cells from mice immunized with GP63-GST plus BCG that were exposed to soluble extract of L. donovani in vitro produced 10-fold greater quantities of IFN-gamma and 3-fold greater quantities of IL-5 than cells from mice receiving BCG only or saline. Western blot analysis revealed that sera from these mice had Leishmania-specific antibodies recognizing 1 to 3 antigens of L. donovani with M. W. of 60-65 kDa. Although immunization of mice with GP63-GST induced a strong Th1 response, this study indicated that GP63-GST simultaneously elicited the Th2 response of the CD4+ T-cell, which was known to abrogate the protective immune response conferred by the Th1 effector function.

• Pediatric Infection and Vaccine
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• v.29 no.2
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• pp.96-104
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• 2022

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disorder presenting with sterile osteomyelitis, most often presenting in childhood. Although the etiology is understood incompletely, its association with other auto-inflammatory diseases including inflammatory bowel disease (IBD); psoriasis; Wegener's disease; arthritis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome suggests that dysregulated innate immunity may play an important role in the pathogenesis. We report a case of a 13-year-old boy with CRMO associated with Crohn's disease (CD) successfully treated with infliximab after failure of non-steroidal anti-inflammatory drug (NSAID) treatment. He initially was diagnosed with CRMO based on symmetric and aseptic bone lesions with no fever, lack of response to antibiotic treatment, vertebral involvement, and normal blood cell counts. Despite five months of NSAID treatment, his musculoskeletal symptoms were aggravated, and he developed gastrointestinal symptoms. Finally, he was diagnosed with CRMO associated with CD. Due to the severity of symptoms, infliximab was initiated and produced symptom improvement. This case supports infliximab as another choice for treatment of bowel symptoms in addition to the bone and joint symptoms of CRMO when other first-line treatments are ineffective.

• Journal of Life Science
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• v.32 no.2
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• pp.94-100
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• 2022

Chronic infection by hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype, adaptive mutations, and environmental factors. The pregenomic RNA transcription of HBV for their replication is regulated by the core promoter activation. Core promoter mutations have been the reason for acute liver failure and are associated with HCC development. We obtained HBV genes from a patient in Myanmar who was infected with HBV and identified gene variations in the core promoter region. For measuring the relative transactivation activity of the core promoter, we prepared the core-promoter reporter construct. Among the gene variations of the core promoter, the mutations of C1731T and G1806A were associated with increase in the transactivation of the HBV core promoter. Through computer analysis for searching for a tentative transcription factor binding site, we showed that the mutations of C1713T and G1806A newly created C/EBPβ and XBP1-responsive elements of the core promoter, respectively. The ectopic expression of C/EBPβ largely increased the HBV core promoter containing the C1713T mutation and that of XBP1 activated the M95 promoter containing the G1806A mutation. Our efforts to treat and prevent HBV infections are hampered by the emergence of drug-resistant mutations and vaccine-escape mutations. Our results provide the biological properties and clinical significance of specific HBV core promoter mutations.

• Pediatric Infection and Vaccine
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• v.29 no.3
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• pp.147-154
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• 2022

The clinical severity of coronavirus disease 2019 (COVID-19) in children is usually mild. Most of the affected patients completely recovered from COVID-19 before being released from approximately 7-day quarantine. However, children with comorbidities are at risk of more severe disease and adverse outcomes. We report three cases of COVID-19-affected adolescents with underlying chronic respiratory difficulty due to neurologic diseases who showed sudden clinical aggravations at the time of discharge, even after full clinical improvement. Patient 1 is a 17-year-old boy with Ullrich congenital muscular dystrophy who had cardiopulmonary arrest 9 days after the initial COVID-19 symptoms. Patient 2 is a 17-year-old girl with intracerebral hemorrhage with infarction in bed-ridden status who had cardiopulmonary arrest 11 days after the initial symptoms. Patient 3 is a 12-year-old boy with intraventricular hemorrhage with hydrocephalus in bed-ridden status who showed multiorgan failure 10 days after the initial symptoms. Remdesivir, dexamethasone, and empirical antibiotics were administered with mechanical ventilation and intensive unit care. Among the three patients, two (patients 1 and 3) were alive, and one (patient 2) expired. Clinicians caring for adolescents with chronic neurologic and/or pulmonary disease should keep in mind that these patients could have sudden deterioration after recovery from the acute phase of COVID-19 around or after the time of discharge.

• Clinical and Experimental Pediatrics
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• v.45 no.8
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• pp.980-986
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• 2002

Purpose : Although the number of patients with measles have dramatically decreased since the introduction of measles vaccines in 1965, measles outbreaks have occurred periodically every 4-6 years during the 1990s(1989-1990 and 1993-1994). During 2000-2001, measles prevailed all over the country again. A characteristic of current epidemics is that the majority of affected population was infants and school-aged children. This study was designed to analyze the epidemic and clinical features of measles prevalence during 2000-2001 and to find ways to overcome vaccination failure. Methods : We reviewed the records of 59 patients with mealses admitted in the Pediatric Department of Pusan National University Hospital from January 2000 to October 2001 for patient's age, month of admission, history of vaccination, clinical features and complications. Antibody titers of measles-specific IgM and IgG were measured by enzyme immunoassay. Results : The epidemic show two peaks in the age distribution. Forty three patients(72.9%) were under 2-years of age and 14 patients(23.7%) were over 5-years of age. Outbreaks had high incidence in July to August, 2000 and March to April, 2001, then faded away after July, 2001. Vaccinated group comprised 30.5% and unvaccinated group comprised 69.5% and their mean age was $9.25{\pm}4.27$ years old and $0.95{\pm}0.30$ years old respectively. Positive rate of IgM was 86.7% in vaccinated group and 90.3% in unvaccinated group. This means there was primary vaccine failure; 13 cases of 15 vaccinated patients were positive in IgM antibody. During the prevalence, two patients died with mealses complication. One of them was immunocompromised. Conclusion : To prevent another prevalence of measles in the future, we must enhance revaccination at ages 4-6 and check vaccination status when children enter elementary school. These will produce over 95% of herd immunity, with catch-up MMR vaccination which has been completed already.

• Pediatric Infection and Vaccine
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• v.5 no.2
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• pp.258-266
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• 1998

Purpose : Cases of adenoviral penumonia with rapidly progressive clinical course were experienced. We reviewed these patients in viewpoint of clinical manifestation and adenoviral serotypes. Methods : Culture and indirect immunofluorescence for respiratory viruses including respiratory syncytial virus, influenza virus, parainfluenza virus, adenovirus was done with nasopharyngeal aspirates from patients who admitted due to respiratory infections in Fatima Hospital, Masan from Nov. 1996 to Jul. 1997. Cultured adenovirus was serotyped by both neutralization and hemagglutination inhibition test. Medical records were reviewed for 5 patients with respiratory failure from adenovirus was isolated and serotyped. Results : The total number of examined patients was 460 patients. We isolated respiratory viruses in 143(30.9%) patients. Adenovirus was isolated from 66 out of 143(46.2%) patients. During Jan 1997 to May 1997, five patients with ages of 18 days to 11 months who were infected by adenovirus and had high fever with dyspnea and required assisted mechanical ventilation. One patients discharged against doctor's advice then died. Two of four patients had complications of disseminated intravascular coagulation; two had bronchiolitis obliterans. Two isolates were serotype 7, and one was serotype 5, and two were untyped. Conclusion : Severe pneumonia caused by serotype 7 continued to occur in 1997 following the epidemic in 1996, and severe pneumonia may also be caused by serotype 5 and other serotypes.