• Korean Journal of Veterinary Research
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• v.25 no.1
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• pp.7-17
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• 1985

Many investigators have been pursuing various attempts so far to produce hepatitis B surface antigen(HBsAg) vaccines using the techniques such as isolation from plasma of chronic HBsAg carrier, recombinant DNA technique or preparation of synthetic peptides specific for immunogenic determinants. Hepatitis B virus can not grow on any cell lines by the tissue culture technique at the present time. The plasma of chronic HBsAg carrier is expensive and its source is limited. The HBsAg from the recombinant DNA technique gave still very low yield. Another approach, therefore, has been initiated to develop a synthetic hepatitis B virus vaccine. The possible use of several distinct synthetic vaccines in prophylaxis can be facilitated by availability of full synthetic immunogens. Peptides synthesized for potential application as antiviral vaccines have been mostly tested in the form of conjugates with carrier proteins, although the free synthetic peptide can be immunogenic. To understand basic knowledges on the antigenicity and immunogenicity of a synthetic peptide specific for major immunogenic determinant of HBsAg, a nonapeptide, $H_2N^{139}Cys-Thr-Lys-Pro-Thr-Asp-Gly-^{146}Asn-Aba$ COOH, which corresponds to HBsAg amino acid residues 139 to 147, was synthesized by the Merrifield's solid-phase method with a slight modification. The antigenicity and immunogenicity of this specific synthetic peptide were examined comparing with purified plasma-derived natural HBsAg. The results obtained are as follows; 1. The peptide synthesized showed the identical amino acid composition to the theoretical value. The degree of purification and molecular weight were acertained by methods of high performance liquid chromatography and mass spectrometry. 2. Using m-maleimidobenzoyl-N-hydroxysuccinimide ester as a conjugating agent, the synthetic peptide was conjugated to rabbit albumin and ${\gamma}$-globulin, tetanus and diphtheria toxoids, and keyhole limpet hemocyanin. Their conjugation yields were 8.3, 9.5, 15.8, 13.5, and 11.2%, respectively. 3. The natural HBsAg was purified from plasma of chronic HBsAg carrier. By the electron microscopic observation of the purified natural HBsAg preparation, no Dane particles were observed and the preparation showed negative DNA polymerase activity. 4. Antigenicity of the synthetic peptide and the plasma-derived natural HBsAg was determined by competition radioimmunoassay using $^{125}I$-natural HBsAg. Their 50% inhibitions appeared as $90{\mu}g/ml$ and $0.12{\mu}g/ml$ for the synthetic peptide and the natural HBsAg, respectively. This indicates that the former was about 750-fold less antigenic than the latter. 5. Immunogenicity of the synthetic peptide was determined by administering the peptide-carrier conjugates into rabbits with and without Freund's complete adjuvant. Regardless the carrier proteins and adjuvant, positive immune responses to the synthetic peptide were observed. The higher antibody titers, however, were shown in the groups administered with Freund's complete adjuvant. 6. Immunizing dose 50% in mice of the various peptide-carrier conjugates was 5.47, 6.00, 65.16, 31.25 and $13.03{\mu}g/dose$ for rabbit albumin and ${\gamma}$-globulin, tetanus and diphtheria toxoids, and keyhole limpet hemocyanin, respectively, while the natural HBsAg showed $0.65{\mu}g/dose$. 7. It was postulated that homologous proteins prefer to heterologous ones as the carriers.

• Pediatric Infection and Vaccine
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• v.4 no.2
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• pp.232-239
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• 1997

Purpose: The incidence of hepatitis A virus(HAV) infection has markedly decreased in the last 20 years due to industrialization and improvements in the standard of living and hygiene in Korea. The reduction in seroprevalence rates indicates infection potential for young adult population, and a need for vaccinations in high-risk adults and children groups has been suggested. In this study we evaluated the seroprevalence rates and natural infection rates of hepatitis A in children and adolescent to obtain the basic data for vaccination of hepatitis A. Methods: A total of 334 children and adolescent subjects below 20 years old in Kyonggi-do province were examined for HAV antibody and seroprevalence rates in each age group was investigated. In 584 elementary school students residing in Kyonggi-do province, serum samples collected in 1993 and 1996 from the same subjects for investigation of natural seroconversion rates. Method of testing antibody was enzyme immunoassay. Results: 1) The seropositive rate of HAV in 334 subjects aged below 20 years old was 5.4%. According to age, the seropositive rates were 27.3% in infant group, 0.0% in 1~4 year-old group, 0.0% in 5~9 year-old group, 2.9% in 10~14 year-old group and 15.0% in 15~19 year-old group. 2) In the study of 584 elementary school children, only one subject showed seropositive in 1993, and in 1996 three different subjects showed seropositive results(0.5%); the natural seroconversion rate during 3 years was 0.5%. 3) The seroprevalence rates of below 20 year-old subjects reported in previous studies were 63.8% in 1979 and 47.3% in 1989 while the present study showed the rate at 5.4%. Conclusion: Since natural antibody formation is rarely occurring, there is a high risk for apparent hepatitis A infection in adults. Therefore vaccination in high risk groups is essential at present, and in order to reduce the chance for hepatitis A infection in adults, vaccination in children may be needed.

• Pediatric Infection and Vaccine
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• v.28 no.2
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• pp.101-109
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• 2021

Purpose: Common human coronaviruses (HCoVs) are relatively understudied due to the mild nature of HCoV infection. Given the lack of local epidemiology data on common HCoVs, we aimed to describe clinical and epidemiological characteristics of common HCoVs in children. Methods: Respiratory viral test results from 9,589 respiratory samples from Seoul National University Children's Hospital were analyzed from January 2015 to December 2019. Viral detection was done by the multiplex reverse transcription polymerase chain reaction. Demographics and clinical diagnosis were collected for previously healthy children tested positive for HCoVs. Results: Of the 9,589 samples tested, 1 or more respiratory viruses were detected from 5,017 (52.3%) samples and 463 (4.8%) samples were positive for HCoVs (OC43 2.8%, NL63 1.4%, 229E 0.7%). All 3 types co-circulated during winter months (November to February) with some variation by type. HCoV-OC43 was the most prevalent every winter season. HCoV-NL63 showed alternate peaks in late winter (January to March) and early winter (November to February). HCoV-229E had smaller peaks every other winter. Forty-one percent of HCoV-positive samples were co-detected with additional viruses; human rhinovirus 13.2%, respiratory syncytial virus 13.0%, influenza virus 4.3%. Common clinical diagnosis was upper respiratory tract infection (60.0%) followed by pneumonia (14.8%), croup (8.1%), and bronchiolitis (6.7%). Croup accounted for 17.0% of HCoV-NL63-positive children. Conclusions: This study described clinical and epidemiological characteristics of common HCoVs (OC43, NL63, 229E) in children. Continuing surveillance, perhaps by adding HKU1 in the diagnostic panel can further elucidate the spectrum of common HCoV infections in children.

• Pediatric Infection and Vaccine
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• v.28 no.2
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• pp.92-100
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• 2021

Purpose: Rapid detection of etiologic organisms is crucial for initiating appropriate therapy in patients with central nervous system (CNS) infection. This study aimed to evaluate the diagnostic value of the BioFire^® Meningitis/Encephalitis (ME) panel in detecting etiologic organisms in cerebrospinal fluid (CSF) samples from febrile infants. Methods: CSF samples from infants aged <90 days who were evaluated for fever were collected between January 2016 and July 2019 at the Seoul National University Children's Hospital. We performed BioFire^® ME panel testing of CSF samples that had been used for CSF analysis and conventional tests (bacterial culture, Xpert^® enterovirus assay, and herpes simplex virus-1 and -2 polymerase chain reaction) and stored at -70℃ until further use. Results: In total, 72 (24 pathogen-identified and 48 pathogen-unidentified) CSF samples were included. Using BioFire^® ME panel testing, 41 (85.4%) of the 48 pathogen-unidentified CSF samples yielded negative results and 22 (91.7%) of the 24 pathogen-identified CSF samples yielded the same results (enterovirus in 19, Streptococcus agalactiae in 2, and Streptococcus pneumoniae in 1) as those obtained using the conventional tests, thereby resulting in an overall agreement of 87.5% (63/72). Six of the 7 pathogen-unidentified samples were positive for human parechovirus (HPeV) via BioFire^® ME panel testing. Conclusions: Compared with the currently available etiologic tests for CNS infection, BioFire^® ME panel testing demonstrated a high agreement score for pathogen-identified samples and enabled HPeV detection in young infants. The clinical utility and cost-effectiveness of BioFire^® ME panel testing in children must be evaluated for its wider application.

• Pediatric Infection and Vaccine
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• v.30 no.2
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• pp.73-83
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• 2023

Purpose: This study aimed to investigate the viral load dynamics in children with underlying malignancies diagnosed with symptomatic coronavirus disease 2019 (COVID-19). Methods: This was a retrospective longitudinal cohort study of patients <19 years old with underlying hemato-oncologic malignancies that were diagnosed with their first symptomatic severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)-confirmed COVID-19 infection during March 1 to August 30, 2022. Review of electronic medical records and telephone surveys were undertaken to assess the clinical presentations and transmission route of the patients. Thresholds of negligible likelihood of infectious virus was defined as E gene reverse transcription (RT)-PCR cycle threshold (Ct) value ≥25. Results: During the 6-month study period, a total of 43 children with 44 episodes of COVID-19 were included. Of the 44 episodes, the median age of the patients included was 8 years old (interquartile range [IQR], 4.9-10.5), and the most common underlying disease was acute lymphoid leukemia (n=30, 68.2%), followed by patients post-hematopoietic stem cell transplantation (n=8, 18.2%). Majority of the patients had mild COVID-19 (n=32, 72.7%), and three patients (7.0%) had severe/critical COVID-19. Furthermore, 2.3% (n=1) died of COVID-19 associated acute respiratory distress syndrome. The largest percentage of the patients showed E gene RT-PCR Ct value ≥25 between 15-21 days (n=13, 39.4%), followed by 22-28 days (n=10, 30.3%). In 15.2% (n=5), E gene RT-PCR Ct value remained <25 beyond 28 days after initial positive PCR. Refractory malignancy status (β, 67.0; 95% confidence interval, 7.0-17.0; P=0.030) was significantly associated with prolonged duration of E gene RT-PCR <25. A patient with prolonged duration of E gene RT-PCR Ct value <25 was suspected to have infectivity shown by the transmission of the virus to his mother at day 86 after his initial positive test. Conclusions: Children that acquire symptomatic COVID-19 during refractory malignancy state are at a high risk for prolonged shedding warranting PCR-based transmission precautions in this cohort of patients.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.129-138
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• 2023

Purpose: Cancer incidence is known to be higher in patients with inborn errors of immunity (IEI) compared to the general population in addition to traditionally well-known infection susceptibility. We aimed to investigate cancer occurrence in patients with IEI in a single center. Methods: Medical records of IEI patients treated at Samsung Medical Center, Seoul, Korea were retrospectively reviewed from November 1994 to September 2023. Patients with IEI and cancer were identified. Results: Among 194 patients with IEI, seven patients (3.6%) were diagnosed with cancer. Five cases were lymphomas, 4 of which were Epstein-Barr virus (EBV)-associated lymphomas. The remaining cases included gastric cancer and multiple myeloma. The median age at cancer diagnosis was 18 years (range, 1-75 years). Among patients with cancer, underlying IEIs included X-linked lymphoproliferative disease-1 (XLP-1, n=3), activated phosphoinositide 3-kinase delta syndrome (APDS, n=2), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) haploinsufficiency (n=2). Seventy-five percent (3/4) of XLP-1 patients, 40.0% (2/5) of APDS patients, and 50.0% (2/4) of CTLA-4 haplo-insufficiency patients developed cancer. Patients with XLP-1 developed cancer at earlier age (median age 5 years) compared to those with APDS and CTLA-4 (P<0.001). One patient with APDS died during hematopoietic cell transplantation. Conclusions: Cancer occurred in 3.6% of IEI patients at a single center in Korea. In addition to infectious complications and inflammation, physicians caring for IEI patients should be aware of the potential risk of cancer, especially in association with EBV infection.

• Pediatric Infection and Vaccine
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• v.14 no.1
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• pp.75-82
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• 2007

Purpose : Human metapneumovirus (hMPV) is a newly identified paramyxovirus that causes a variety of clinical syndromes in children, including upper and lower respiratory tract illnesses. hMPV is considered an ubiquitous virus causing respiratory tract diseases among children especially during late winter and spring seasons. We report clinical features of human metapneumovirus infection in Korean children. Methods : hMPV infection was diagnosed by reverse transcriptase-polymerase chain reaction (RT-PCR) in respiratory specimens obtained from patients with acute respiratory tract infections from October, 2004 to May, 2005. Medical records of all hMPV-positive patients were reviewed, retrospectively. Results : A total of 15 hMPV were identified from 443 nasopharyngeal aspirations by RT-PCR (3.4%). The range of age of the patients with hMPV infection was from 1 month to 62 months (median age, 31.5 months), with similar numbers of females (8/15) and males (7/15). Among hMPV-positive children, 53.3% (8/15) were aged less than 24 months. Fever, cough, rhinorrhea, vomiting, diarrhea, tachypnea, and chest wall retractions were common findings. Most common clinical diagnosis was pneumonia (60%). Two of the 15 hMPV-positive patients were also positive for adenovirus. Fever persisted from 0 to 10 days (mean 4.9 days). The duration of hospitalization ranged from 4 to 7 days (mean 5.6 days). Conclusion : hMPV accounted for a small but significant proportion of respiratory tract infection in infants and children. Future development and application of diagnostic tools will determine the burden of disease caused by this newly discovered pathogen.

• Pediatric Infection and Vaccine
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• v.19 no.3
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• pp.121-130
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• 2012

Purpose : The purpose of this study is to investigate clinical features and causative organisms in febrile infants younger than three months, to help identification of high risk patients for serious bacterial infection (SBI). Methods : A total of 313 febrile infants younger than three months, who had visited Seoul National University Children's Hospital from January 2008 to December 2010 were included. Clinical features, laboratory findings, causative organisms, and risk factors of SBI were analyzed by retrospective chart review. Causative bacterial or viral pathogens were identified by gram stain and cultures, rapid antigen tests, or the polymerase chain reaction from clinically reliable sources. Results : Among 313 infants, etiologic organisms were identified in 127 cases (40.6%). Among 39 cases of bacterial infections, Escherichia coli (66.7%) and Streptococcus agalactiae (12.8%) were common. Enterovirus (33.7%), respiratory syncytial virus (19.8%), and rhinovirus (18.8%) were frequently detected in 88 cases of viral infection. Patients with SBI (39 cases) showed significantly higher values of the white blood cell count ($14,473{\pm}6,824/mm^3$ vs. $11,254{\pm}5,775/mm^3$, P=0.002) and the C-reactive protein ($6.32{\pm}8.51mg/L$ vs. $1.28{\pm}2.35mg/L$, P<0.001) than those without SBI (274 cases). The clinical risk factors for SBI were the male (OR 3.7, 95% CI 1.5-8.9), the presence of neurologic symptoms (OR 4.8, 95% CI 1.4-16.8), and the absence of family members with respiratory symptoms (OR 3.6, 95% CI 1.2-11.3). Conclusion : This study identified common pathogens and risk factors for SBI in febrile infants younger than three months. These findings may be useful to guide management of febrile young infants.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.40-47
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• 2011

Purpose : Norovirus infection, a common cause of community-acquired gastroenteritis, can also lead to severe illness in immunocompromised patients. We investigated clinical manifestations of norovirus infection in pediatric cancer patients. Methods : Stool specimens were collected from pediatric patients with gastrointestinal symptoms between November 2008 and September 2009 at Samsung Medical Center, Seoul, Korea. Norovirus infection was identified by reverse-transcription polymerase chain reaction (RT-PCR). A retrospective chart review was performed in pediatric cancer patients who were diagnosed with norovirus infection. Results : Ten patients were diagnosed with norovirus infection by RT-PCR in stool samples. The median age was 0.83 years (range 0.25-5.5 years) and the male to female ratio was 1.5:1 (6 males and 4 females). Underlying diseases were hematologic malignancies (4/10, 40%), neuroblastoma (4/10, 40%), and brain tumors (2/10, 20%). Three patients were infected before hematopoietic cell transplantation (HCT) and four patients after HCT. All patients had diarrhea (10/10, 100%), with a median frequency of diarrhea of 8.5 times/day (range 4-22 times/day). Median virus shedding duration was 72.5 days (range 19-299 days). Four patients with pneumatosis intestinalis were conservatively treated with bowel rest and total parenteral nutrition. One patient with severe diarrhea and bloody stool had concomitant chronic gut graft-versus-host disease (GVHD). Norovirus infection-related mortality was not observed. Conclusion : Norovirus infection can cause significant clinical manifestations with prolonged viral shedding in immunocompromised patients. Norovirus should be considered in pediatric cancer patients with severe gastrointestinal symptoms.

• Pediatric Infection and Vaccine
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• v.27 no.2
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• pp.102-110
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• 2020

Purpose: This study aimed to investigate the clinical characteristics of human parechovirus (HPeV) infection in sepsis-like syndrome in infants aged under 3 months. Methods: Medical records of infants aged under 3 months with sepsis-like symptoms who were admitted between July 1, 2018 and August 31, 2018 were reviewed. A multiplex reverse transcription-polymerase chain reaction panel test was performed on the cerebrospinal fluid (CSF). Thirty-nine enrolled infants were categorized into three groups: 11 in group 1 (HPeV detected in the CSF), 13 in group 2 (enterovirus detected in the CSF), and 15 in group 3 (no virus detected in the CSF). Results: Compared with groups 2 and 3, a higher proportion of group 1 had tachycardia, tachypnea, apnea, and hypotension (P<0.05). A significantly lower white blood cell (WBC) count was noted in group 1 than in groups 2 and 3 (5,622±2,355/μL, 9,397±2,282/μL, and 12,312±7,452/μL, respectively; P=0.005). The CSF WBC count was lower in group 1 than in groups 2 and 3 (0.9±1.7/μL, 85.1±163.6/μL, and 3.7±6.9/μL, respectively; P=0.068). The proportion of patients requiring inotrope support (36.6% vs. 0% and 6.6%), mechanical ventilation (18.1% vs. 0% and 0%), and high flow nasal cannula (45.4% vs. 15.3% and 6.6%) was higher in group 1 than in groups 2 and 3. All patients recovered completely without complications. Conclusions: HPeV infection shows a severe clinical course and can cause a severe sepsis-like syndrome in infants aged under 3 months. Early diagnosis and proper treatment of HPeV infection are required.