The ribose and phosphorus contents in Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) are two important chemical indexes for the development and quality control of Hib conjugate vaccine. A quantitative ¹H- and ³¹P-NMR method using a single internal standard was developed for simultaneous determination of ribose and phosphorus contents in Hib CPS. Hexamethylphosphoramide (HMPA) was successfully utilized as an internal standard in quantitative ¹H-NMR method for ribose content determination. The ribose and phosphorus contents were found to be affected by the concentration of polysaccharide solution. Thus, 15-20 mg·L^-1 was the optimal concentration range of Hib CPS in D₂O solution for determination of ribose and phosphorus contents by this method. The ribose and phosphorus contents obtained by the quantitative NMR were consistent with those obtained by traditional chemical methods. In conclusion, this quantitative ¹H- and ³¹P-NMR method using a single internal standard shows good specificity, accuracy and precision, providing a valuable approach for the quality control of Hib glycoconjugate vaccines.
Haemophilus Vaccines ; Haemophilus influenzae type b ; Phosphorus ; Polysaccharides, Bacterial ; Ribose

Objective:b> To evaluate the immunity persistence five years later after immunization with Haemophilus influenzae type b (Hib) conjugate vaccine in healthy infants/children aged 3 months to 5 years in China. Methods:b> The children were subjects who completed the whole-schedule immunization in the phase Ⅲ clinical trial in Lianshui county of Jiangsu povince was selected for the collection of blood samples at 5 years after vaccination from November to December, 2019. The enzyme-linked immunosorbent assay (ELISA) was used to detect Hib polyribosyl-ribitol-phosphate antibody (anti-Hib-PRP), and the long-term/short-term protection rate, geometric mean concentration (GMC) and geometric mean concentration increase fold (GMFI) of serum anti-Hib-PRP were calculated. Results:b> A total of 580 children were enrolled in this study, of which 158, 207 and 215 belonged to 3-5 month age group, 6-11 month age group and 1-5 year age group, respectively. The short-term (≥0.15 μg/ml)/long-term (≥1.0 μg/ml) protection rates of serum anti-PRP in the three groups after immunization were 89.24%, 90.34% and 98.60%, respectively; the GMC were 3.95 μg/ml, 3.11 μg/ml and 10.01 μg/ml respectively, and the GMFI were 29.04, 11.01 and 3.26 respectively. Conclusions:b> Hib conjugate vaccine can still have good immunogenicity after 5 years of primary immunization in healthy infants/children aged 3 months to 5 years in China.
Child ; Infant ; Humans ; Vaccines, Conjugate ; Haemophilus influenzae type b ; Immunization ; Vaccination ; Antibodies, Bacterial

Since the implementation of conjugate Haemophilus influenzae serotype b (Hib) vaccine, the rate of infections caused by Hib has dramatically decreased, and the proportion of infections caused by non-type b H. influenzae has increased. Cerebral venous sinus thrombosis (CVST) is rare; however, it should be considered as a potential complication of bacterial meningitis. Herein, we report about a child who developed CVST after being diagnosed with H. influenzae serotype f meningitis.
Bacteremia ; Central Nervous System Infections ; Cerebrospinal Fluid ; Child ; Haemophilus influenzae type b ; Haemophilus influenzae ; Haemophilus ; Humans ; Influenza, Human ; Meningitis ; Meningitis, Bacterial ; Meningitis, Haemophilus ; Sepsis ; Serogroup ; Sinus Thrombosis, Intracranial

PURPOSE: Because children with asplenia have an increased risk of fulminant infection associated with a high fatality, chemoprophylaxis, and vaccinations against encapsulated bacteria are recommended. However, there have been few reports of the burden of severe bacterial infection and the current status of chemoprophylaxis and immunization among children with asplenia in Korea. METHODS: We conducted a retrospective study including children with asplenia who were treated at our institute between January 1997 and December 2016. RESULTS: From a total of 213 children with asplenia, 114 (53.5%) had congenital asplenia and 58 (27.2%) had functional asplenia. The remaining 41 (19.3%) had acquired asplenia with the median age at splenectomy being 12.2 years (range, 5.0 to 16.9 years); the most common cause of splenectomy was hereditary spherocytosis (39.0%). The chemoprophylaxis rate was 16.4%. The immunization rates were 44.1% for pneumococcus, 53.0% for Haemophilus influenzae type B, and 10.7% for meningococcus. The incidence of invasive bacterial infection among children with asplenia was 0.28/100 person-year; a total of six episodes (2.8%) were observed in five patients with congenital asplenia and one patient with functional asplenia. The median age for these infections was 15 months (range, 4 to 68 months). Five of the six episodes were bacteremia, and the other was meningitis. The most common pathogen was Streptococcus pneumoniae (n=3), followed by H.influenzae (n=1). Three of the six patients (50.0%) died, all of whom had pneumococcal bacteremia. None of the six had chemoprophylaxis or proper vaccinations. CONCLUSIONS: Although there is an increased risk of a severe infection proper vaccinations and chemoprophylaxis are still lacking. Physicians should be encouraged to implement appropriate chemoprophylaxis and immunizations for patients with asplenia.
Bacteremia ; Bacteria ; Bacterial Infections* ; Chemoprevention ; Child* ; Haemophilus influenzae type b ; Humans ; Immunization ; Incidence ; Korea ; Meningitis ; Neisseria meningitidis ; Retrospective Studies* ; Splenectomy ; Splenic Diseases ; Streptococcus pneumoniae ; Vaccination

PURPOSE: Because children with asplenia have an increased risk of fulminant infection associated with a high fatality, chemoprophylaxis, and vaccinations against encapsulated bacteria are recommended. However, there have been few reports of the burden of severe bacterial infection and the current status of chemoprophylaxis and immunization among children with asplenia in Korea. METHODS: We conducted a retrospective study including children with asplenia who were treated at our institute between January 1997 and December 2016. RESULTS: From a total of 213 children with asplenia, 114 (53.5%) had congenital asplenia and 58 (27.2%) had functional asplenia. The remaining 41 (19.3%) had acquired asplenia with the median age at splenectomy being 12.2 years (range, 5.0 to 16.9 years); the most common cause of splenectomy was hereditary spherocytosis (39.0%). The chemoprophylaxis rate was 16.4%. The immunization rates were 44.1% for pneumococcus, 53.0% for Haemophilus influenzae type B, and 10.7% for meningococcus. The incidence of invasive bacterial infection among children with asplenia was 0.28/100 person-year; a total of six episodes (2.8%) were observed in five patients with congenital asplenia and one patient with functional asplenia. The median age for these infections was 15 months (range, 4 to 68 months). Five of the six episodes were bacteremia, and the other was meningitis. The most common pathogen was Streptococcus pneumoniae (n=3), followed by H.influenzae (n=1). Three of the six patients (50.0%) died, all of whom had pneumococcal bacteremia. None of the six had chemoprophylaxis or proper vaccinations. CONCLUSIONS: Although there is an increased risk of a severe infection proper vaccinations and chemoprophylaxis are still lacking. Physicians should be encouraged to implement appropriate chemoprophylaxis and immunizations for patients with asplenia.
Bacteremia ; Bacteria ; Bacterial Infections* ; Chemoprevention ; Child* ; Haemophilus influenzae type b ; Humans ; Immunization ; Incidence ; Korea ; Meningitis ; Neisseria meningitidis ; Retrospective Studies* ; Splenectomy ; Splenic Diseases ; Streptococcus pneumoniae ; Vaccination

PURPOSE: After the introduction of Haemophilus influenzae type b (Hib) vaccine in 1995 in Korea, it was included in the national immunization program in 2013. In the post-Hib vaccine era, some studies in other countries reported that invasive Hib disease affects adults, especially the elderly and immunocompromised persons, more often than it affects children. To evaluate disease susceptibility, quantitative and qualitative analysis of anti-polyribosylribitol phosphate (PRP) antibodies were carried out in Korean adults aged 20 to 85 years. METHODS: Sera were collected from 39 healthy adults (20 to 50 years of age) and from 30 elderly adults (75 to 85 years of age) who did not have immune-compromising conditions. The concentration of anti-PRP immunoglobulin G (IgG) and serum bactericidal indices (SBIs) were measured by enzyme-linked immunosorbent assay and serum bactericidal assay. RESULTS: Geometric mean concentrations of anti-PRP IgG and geometric mean SBIs were 0.88 µg/mL (95% confidence interval [CI], 0.17 to 3.85) and 354 (95% CI, 50 to 2,499) in young adults and 1.67 µg/mL (95% CI, 0.53 to 5.24) and 449 (95% CI, 146 to 1,376) in elderly adults, respectively. When the threshold of seropositivity for anti-PRP IgG was applied as 0.15 or 1.0 µg/mL, which is the protective antibody level in children, seropositive rates were 87.2% or 53.8% in young adults and 100% or 60% in elderly adults. The seropositivity rates of the SBI (SBI ≥4) were 82.1% and 100% in the groups, respectively. CONCLUSIONS: Most subjects in the adult and elderly adult groups display immunity to Hib based on quantitative and qualitative antibody levels, but not all. Because high immunization and low Hib circulation rates may reduce the natural Hib immunity in the population, monitoring Hib immunity as well as disease are needed continuously.
Adult* ; Aged ; Antibodies* ; Child ; Disease Susceptibility ; Enzyme-Linked Immunosorbent Assay ; Haemophilus influenzae type b* ; Haemophilus influenzae* ; Haemophilus* ; Humans ; Immunization ; Immunization Programs ; Immunoglobulin G ; Korea ; Young Adult

BACKGROUND: Meningitis is a clinically important disease because of its high mortality and morbidity. The epidemiology of this disease has changed remarkably due to the introduction of pneumococcal vaccines and Haemophilus influenzae type b (Hib) conjugate vaccine. Therefore, it is required to continuously monitor and research the organisms isolated from cerebrospinal fluid (CSF) cultures. METHODS: We analyzed trends of bacteria and fungi isolates obtained from CSF cultures between 1997 and 2016 in a tertiary care hospital according to year, month, gender, and age. RESULTS: Out of a total of 38,450 samples, we identified 504 (1.3%) isolates. The isolation rate in the first tested decade (1997–2006) ranged from 1.3% to 3.1%, while that in the second decade (2007–2016) ranged from 0.4% to 1.5%. The most common organisms was coagulase-negative staphylococci (CoNS) (31.9%), followed by Staphylococcus aureus (9.5%), Streptococcus pneumoniae (7.5%), Acinetobacter baumannii (5.8%), and Mycobacterium tuberculosis (5.8%). Monthly isolation rates were highest in May and July and lowest in February and December. Male to female ratio was 1.5:1. The isolation rates of S. pneumoniae, Enterococcus faecium, and Escherichia coli were similar in children and adults, but those of S. aureus, E. faecalis, A. baumannii, Pseudomonas aeruginosa, M. tuberculosis, and Cryptococcus neoformans were higher in adults than in children. CONCLUSION: During the last two decades, the isolation rate of CSF culture per year has decreased, with monthly isolation rates being highest in May and July. CoNS, S. aureus, and S. pneumoniae were most common in males, whereas CoNS, S. pneumoniae, and M. tuberculosis were most common in females. While Group B Streptococcus was most common in infants younger than 1 year, S. aureus and C. neoformans were more common in adults.
Acinetobacter baumannii ; Adult ; Bacteria* ; Cerebrospinal Fluid* ; Child ; Cryptococcus neoformans ; Enterococcus faecium ; Epidemiology ; Escherichia coli ; Female ; Fungi* ; Haemophilus influenzae type b ; Humans ; Infant ; Male ; Meningitis ; Mortality ; Mycobacterium tuberculosis ; Pneumococcal Vaccines ; Pneumonia ; Pseudomonas aeruginosa ; Staphylococcus aureus ; Streptococcus ; Streptococcus pneumoniae ; Tertiary Healthcare* ; Tuberculosis

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 µg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 µg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).
Antibodies ; Appointments and Schedules ; Haemophilus influenzae type b* ; Humans ; Infant* ; Korea ; Licensure ; Parents ; Vaccination ; Vaccines* ; Whooping Cough

PURPOSE: Vaccine evaluation studies were initiated from 2000 by the Ministry of Food and Drug Safety to produce proper data about the safety and immunogenicity of vaccines. The purpose of this study was to review studies and reports on evaluation of vaccine such as immunogenicity, efficacy, effectiveness, safety and other related topics in order to find and analyze the data on the usefulness of each vaccine. METHODS: From 2000 to 2014, the project "The vaccine evaluation" had been performed by several researchers, and studies and reports of vaccine evaluation. We reviewed the results and outcomes of studies regarding the evaluation of vaccine's usefulness and analyzed the possibilities of applying these data for establishing vaccine policies. For each vaccine, data analysis and organization were done according to evaluation fields. RESULTS: A total of 83 studies were performed on vaccines from 2000 to 2014. For each vaccine, 8 studies were performed on BCG, 14 on DTaP/Td, 1 on poliovirus, 5 on Hib, 3 on pneumococcus, 11 on influenza, 3 on hepatitis A, 11 on MMR, 11 on varicella, and 16 on Japanese encephalitis. All studies were analyzed by the following evaluation area, such as safety, immunogenicity, seroprevalence, persistence of immunity, efficacy, effectiveness, vaccine evaluation methods, quality control product for vaccine, and others. CONCLUSIONS: Vaccine evaluation studies performed in Korea may be useful as references for establishing vaccination strategy and policy and could be used as baseline data for future studies on vaccine evaluation, vaccine policy establishment, and public/expert vaccine education in Korea.
Chickenpox ; Education ; Encephalitis, Japanese ; Haemophilus influenzae type b ; Hepatitis A ; Influenza, Human ; Korea* ; Mycobacterium bovis ; Poliovirus ; Quality Control ; Republic of Korea ; Seroepidemiologic Studies ; Statistics as Topic ; Streptococcus pneumoniae ; Vaccination ; Vaccines

This report includes the recommended immunization schedule table for children and adolescents based on the 8th (2015) and revised 7th (2012) Immunization Guidelines released by the Committee on Infectious Diseases of the Korean Pediatric Society (KPS). Notable revised recommendations include: reorganization of the immunization table with a list of vaccines on the vertical axis and the corresponding age on the horizontal axis; reflecting the inclusion of Haemophilus influenzae type b vaccine, pneumococcal conjugate vaccine, and hepatitis A vaccine into the National Immunization Program since 2012; addition of general recommendations for 2 new Japanese encephalitis (JE) vaccines and their interchangeability with existing JE vaccines; addition of general recommendations for quadrivalent meningococcal conjugate vaccines and scope of the recommended targets for vaccination; and emphasizing catch-up immunization of Tdap vaccine. Detailed recommendations for each vaccine may be obtained from the full KPS 8th Immunization Guidelines.
Adolescent* ; Child* ; Communicable Diseases ; Encephalitis, Japanese ; Haemophilus influenzae type b ; Hepatitis A Vaccines ; Humans ; Immunization Programs ; Immunization Schedule* ; Immunization* ; Infant ; Korea ; Vaccination ; Vaccines ; Vaccines, Conjugate