Preliminary study on the immunogenicity of a newly developed GCC Tdap vaccine and its protection efficacy against Bordetella pertussis in a murine intranasal challenge model.

PURPOSE: Active reduced dose tetanus-diphtheria-acellular pertussis (Tdap) vaccination for adolescents and adults is necessary because waning immunity after primary diphtheria-tetanus-pertussis vaccination is related to the recent emergence of pertussis. This study was conducted to compare the immunogenicity and protection efficacy against Bordetella pertussis between a new GCC Tdap vaccine and a commercially available Tdap vaccine in a murine model. MATERIALS AND METHODS: BALB/c mice were immunized with two doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccine for priming and a subsequent Tdap booster vaccination. According to the type of booster vaccine, mice were divided into four groups: commercially available Tdap vaccine in group 1 and GCC Tdap vaccines of different combinations of pertussis antigens in groups 2 to 4. Humoral and cell-mediated immune responses and protection efficacy using a murine intranasal challenge model after booster vaccination were compared among the four groups. RESULTS: Every group showed significant increases in antibody titers against pertussis antigens such as pertussis toxin, filamentous hemagglutinin, and pertactin after booster vaccination. Spleen cells showed both Th1 and Th2 cell-mediated immune responses stimulated by pertussis antigens in all groups without any significant difference. In the intranasal B. pertussis infection model, bacteria were eradicated in all groups five days after challenge infection. CONCLUSION: This preliminary study did not show significantly different immunogenicity or protection efficacy of the new GCC Tdap vaccines compared to the commercially available Tdap vaccine, although a more extensive study is necessary to assess the differing efficacies of the new GCC Tdap vaccines.

Varicella and varicella vaccination in South Korea.

With continuing occurrence of varicella despite increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in South Korea. Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea). Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV) antibody was measured before and 6 weeks after immunization. In the case-based study, the median age of the patients was 4 years. Among 152 patients between 1 and 15 years of age, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with increasing varicella vaccine uptake, we illustrate no upward age shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient immunogenicity of domestic varicella vaccine. There is need to improve the varicella vaccine used in South Korea.

Etiology of invasive bacterial infections in immunocompetent children in Korea (1996-2005): a retrospective multicenter study.

The purpose of this study was to identify the major etiological agents responsible for invasive bacterial infections in immunocompetent Korean children. We retrospectively surveyed invasive bacterial infections in immunocompetent children caused by eight major pediatric bacteria, namely Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species that were diagnosed at 18 university hospitals from 1996 to 2005. A total of 768 cases were identified. S. agalactiae (48.1%) and S. aureus (37.2%) were the most common pathogens in infants younger than 3 months. S. agalactiae was a common cause of meningitis (73.0%), bacteremia without localization (34.0%), and arthritis (50%) in this age group. S. pneumoniae (45.3%) and H. influenzae (20.4%) were common in children aged 3 months to 5 yr. S. pneumoniae was a common cause of meningitis (41.6%), bacteremia without localization (40.0%), and bacteremic pneumonia (74.1%) in this age group. S. aureus (50.6%), Salmonella species (16.9%), and S. pneumoniae (16.3%) were common in older children. A significant decline in H. influenzae infections over the last 10 yr was noted. S. agalactiae, S. pneumoniae, and S. aureus are important pathogens responsible for invasive bacterial infections in Korean children.

Current status and clinical presentations of invasive neonatal Group B streptococcal infections in Korea.

BACKGROUND: Group B streptococcus (GBS) is the most common cause of invasive neonatal infections in developed countries. The incidence of early-onset GBS disease in Korea is known to be much lower than that in other developed countries; however neonatal GBS disease has been frequently reported in recent years in Korea. This retrospective study sought to determine the current status and clinical presentation of neonatal GBS disease in Korea. METHODS: From January 1996 through December 2005, GBS cases (n= 157) diagnosed in blood, cerebrospinal fluid, or other sterile body fluids among infants <3 months of age from 14 university hospitals in Korea were identified. Age of onset, diagnosis, underlying medical conditions, and outcomes were investigated by reviewing the medical records. RESULTS: A total of 157 cases were identified during the study period. Of the cases, 32 were early-onset disease (EOD) and 125 were late-onset disease (LOD). Twenty-six of the EOD cases had symptoms during the first 24 h after birth. One hundred of the 157 GBS cases were diagnosed as meningitis. The mortality rate of EOD was 20.7%. The case fatality rate of LOD was 7.2% and 25.2% of LOD cases had sequelae. CONCLUSIONS: GBS is becoming an important cause of invasive neonatal infections in Korea, with LOD being more common. It may not be currently necessary to adopt the prevention guidelines of perinatal GBS disease in Korea. However, studies of maternal GBS carriage rates and neonatal GBS disease will continue.

In vitro antimicrobial activity of cefditoren and other oral antibiotics against Streptococcus pneumoniae, isolated from children with community acquired respiratory tract infections.

The antibacterial susceptibility to frequently prescribed antibiotics of Streptococcus pneumoniae isolated from the pediatric patients with acute respiratory infectious diseases was investigated in a study of three medical institutions in Korea. Total 143 clinical isolates of S. pneumoniae were available for susceptibility tests between May 2003 and July 2007. Antimicrobial susceptibility data for S. pneumoniae were analyzed by using agents of amoxicillin, cefaclor, cefuroxime, cefdinir, and cefditoren as the test antibiotics. The prevalence of each resistance class, penicillin-resistant S. pneumoniae (PRSP) were high with the proportion of MIC range (susceptible = 8.4%, intermediate resistance = 18.2%, resistance = 73.4%). MIC90 and susceptible (S) rate of antimicrobial agents to the strains tested were amoxicillin (MIC90 = 4 microg/ml, S = 76.2%), cefaclor (MIC90 = 128 microg/ml, S=8.4%), cefuroxime (MIC90 = 16 microg/ml, S = 24.5%), cefdinir (MIC90 = 16 microg/ml, S = 21.8%), and cefditoren (MIC90 = 0.5 microg/ml, S=90.2%) respectively. Against clinical isolates including PRSP, cefditoren demonstrated the strongest antibacterial activity intrinsically among the antibiotics tested. Conclusively, the antimicrobial activity of cefditoren to S. pneumoniae strains isolated from pediatric patients with acute respiratory infection is very high. In South Korea, where the antibiotic resistance ofS. pneumoniae is issued, cefditoren is expected to be used as a primary or secondary antibiotic. Moreover, cefditoren may serve as a useful option for secondary antibiotics after failure of amoxicillin treatment, which is most primarily used for acute respiratory S. pneumoniae infection in children.

The causative organisms of bacterial meningitis in Korean children in 1996-2005.

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood, despite the availability of effective vaccines against Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The purpose of this study was to analyze data on bacterial meningitis cases in Korea from 1996 through 2005. The information of all hospitalized bacteria-proven meningitis cases was obtained from 17 university hospitals nationwide. A total of 402 cases were identified. Of these, 125 (29.9%) cases were neonates. Streptococcus agalactiae was the most common bacteria responsible for 99 (24.6%) of all cases regardless of age, followed by S. pneumoniae for 91 (22.6%) and H. influenzae for 67 (16.7%) patients. The common etiology beyond the neonatal period was S. pneumoniae for 91 (33.0%) followed by H. influenzae for 63 (22.8%) patients. The overall case fatality rate was 9.4%, which was similar with that in 1986-1995. In conclusion, S. agalactiae, S. pneumoniae and H. influenzae were important etiologic agents of bacterial meningitis in children in the last 10 yrs. It is required to establish the preventive strategy of the three bacteria. The nationwide epidemiologic study should be continued to evaluate immunization strategy and efficacy.

The changing epidemiology of hospitalized pediatric patients in three measles outbreaks.

OBJECTIVES: To assess the demographic and clinical findings of measles patients during three epidemics from 1989 to 2001. METHODS: A total 520 medical records of measles patients were analyzed retrospectively and divided into three groups; those who were admitted during 1989-1990 (group I, 116 patients), those admitted during 1993-1994 (group II, 127 patients), and those admitted during 2000-2001 (group III, 277 patients). RESULTS: For the age distribution, there was no difference in the proportion of < 2 years of age (61%, 58% and 57%, respectively) for the three groups. However, in each outbreak, there were significant differences in the distribution of > or = 2 years children who had mostly received one-dose measles-mumps-rubella (MMR) vaccination. The age distribution had changed with a significant increase in older children in subsequent outbreaks. In the last 2000-2001 outbreak, there was a pattern for increased attack rates with increasing interval since the initial vaccination. There was no statistical difference between the three groups in gender ratio, MMR vaccination rate in > or = 2 years of age, duration of fever, and complications. No difference was found in all the clinical and laboratory parameters between the anti-measles IgM antibody negative patients and the positive patients. CONCLUSIONS: The age distribution of admitted children with measles in each outbreak has changed over time since the introduction of one-dose MMR vaccination. This finding suggests that the secondary vaccine failure may have played a large role in the last measles outbreak.

Alteration of the influences of HLA classes I and II alleles on the perinatal hepatitis B virus infection after immunoprophylaxis in Korean children.

Some HLA alleles are known to be associated with hepatitis B virus (HBV) persistence. In order to find out the relationship between HLA and perinatal HBV infection after prophylaxis, we typed HLA classes I and II in 38 HBeAg-positive mothers, their children (19 succeeded and 19 failed in prophylaxis) and 198 HBsAg-negative healthy controls. HLA-B35 (RR=2.8, p<0.03), Cw*07 (RR=2.7, p<0.02), DRB1*07 (RR=3.6, p<0.006), DQA1*02 (RR=3.6, p<0.02) and DQB1*02 (RR=2.4, p<0.05) alleles were higher and DRB1*13 (RR=0.3, p<0.03) and DPB1*0401 (RR=0.1, p<0.01) alleles were lower frequencies in HBeAg-positive mothers than in the control. In failed children to the perinatal HBV prophylaxis, HLA-Cw*0303 allele was significantly higher (p<0.05) and DPB1*0202 allele was lower (p<0.03) than in succeeded children. These results suggest the influences of certain HLA alleles on naturally acquired chronic HBV infection may be changed by perinatal HBV prophylaxis.

[The incidence rate of hepatitis B virus surface gene variants in Korean children with immunoprophylaxis failure of perinatal infection].

BACKGROUND/AIMS: Perinatal infection with hepatitis B virus (HBV) may occur despite immunoprophylaxis. One of the important mechanisms for perinatal prophylaxis failure, might include HBV surface gene variants. Therefore, we screened Korean children, in whom perinatal prophylaxis failed, for HBV surface gene variants. METHODS: Thirty-one children with perinatal HBV prophylaxis failure were selected. To amplify the major hydrophilic region of the HBV surface gene, nested PCR with primers targeted to nucleotides 237 to 706 was performed, and then sequencing was done. RESULTS: All cases were shown to be PCR positive for HBV-DNA and genotype C. Nine out of 31 (29%) with perinatal prophylaxis failure had a nucleotide substitution at the major hydrophilic region of the gene; but only two cases (6.5%) had an amino acid substitution. One case was infected by wild type and variants of I126S, and the other by wild type and S114A+I126S, respectively. CONCLUSIONS: In Korea, compared to the previous studies of other nations, gene surface variants such as G145R do not appear to play an important role in perinatal immunoprophylaxis failure.

Clinical features of measles according to age in a measles epidemic.

The purpose of this study was to retrospectively investigate the relationship between age and clinical manifestations and laboratory findings in patients with measles. The study included 216 patients admitted to a hospital in Daejeon, 1 of the largest cities in South Korea, during the 2000-2001 measles outbreak: very young children (<2 y old; 159 patients), school age children (9-11 y old; 34 patients), and young adults (>16 y old; 23 patients). Few of the very young children (9%), but most of the older children (86%) had a history of a prior measles-mumps-rubella vaccination. There were no statistical differences between the 3 groups in terms of the total duration of fever, length of hospitalization, occurrence of complications (defined as hospitalization for more than 7 d) or anti-measles IgM positivity. A reduction in the number of white blood cells and lymphocytes was observed in all age groups. The levels of C-reactive protein were not different between very young children and older children, but hepatic involvement was more prevalent in young adults. In conclusion, the clinical course including the complications experienced was similar in all the measles patients regardless of age.

A Korean family of hypokalemic periodic paralysis with mutation in a voltage-gated calcium channel (R1239G).

Hypokalemic periodic paralysis (HOPP) is a rare disease characterized by reversible attacks of muscle weakness accompanied by episodic hypokalemia. Recent molecular work has revealed that the majority of familial HOPP is due to mutations in a skeletal muscle voltage-dependent calcium-channel: the dihydropyridine receptor. We report a 13-yr old boy with HOPP from a family in which 6 members are affected in three generations. Genetic examination identified a nucleotide 3705 C to G mutation in exon 30 of the calcium channel gene, CACNA1S. This mutation predicts a codon change from arginine to glycine at the amino acid position #1239 (R1239G). Among the three known mutations of the CACNA1S gene, the R1239G mutation was rarely reported. This boy and the other family members who did not respond to acetazolamide, showed a marked improvement of the paralytic symptoms after spironolactone treatment.

Penicillin Resistant Distribution and in-vitro Susceptibility of Oral Antibiotics against Streptococcus pneumoniae, isolated from Pediatric Patients with Community- Acquired Respiratory Infections in Korea / 소아과

PURPOSE: S. pneumoniae is one of major pathogens of community-acquired respiratory infections. The rate of antibiotic resistance to this organism has increased, and resistance to multiple antimicrobial agents in a single strain of S. pneumoniae may compromise the efficacy of empiric antimicrobial treatment commonly used for respiratory infections. We did this study to find out the penicillin resistant distributions and oral antibiotics susceptibility patterns against S. pneumoniae, isolated from pediatric patients with community-acquired respiratory infections in Korea. METHODS: One hundred fifty six pneumococcal isolates obtained from pediatric patients with community-acquired respiratory infections such as acute otitis media(AOM), sinusitis and pneumonia between May 2000 to June 2003. And MICs of penicillin and oral antibiotics(amoxicillin, amoxicillin- clavulanate, cefaclor) were performed by broth microdilution methods according to the NCCLS(2003a). RESULTS: Seventy eight percent of the isolates were resistant to penicillin. The isolates, collected from AOM patients showed the highest penicillin resistance(92.7%). The resistant rates of amoxicillin (16.7%) and amoxicillin-clavulanate(9.6%), based on susceptibility breakpoints established by the NCCLS, were markedly lower than these of penicillin. But, the resistant rate of cefaclor was very high, above 95%. CONCLUSION: We concluded that pneumococci isolated from study cases may be one of the world's highest penicillin resistant rates. But, amoxicillin and amoxicillin-clavulanate can be used as a first- line antibiotics. Finally, we hope that a continuous surveillance study to monitor resistant patterns of pneumococcal respiratory infections will be needed for the standard guidelines of empiric antibiotic treatment.

Roxithromycin treatment of scrub typhus (tsutsugamushi disease) in children.

BACKGROUND: Although chloramphenicol and doxycycline have been used for the treatment of scrub typhus, a difficulty exists in determining which drug to use in treating children because of such potential complications as aplastic anemia or tooth discoloration. We evaluated the effect of roxithromycin, a macrolide antibiotic, on scrub typhus in children. METHODS: A retrospective analysis was conducted on 39 children with scrub typhus who were treated with doxycycline (DC), chloramphenicol (CM) or roxithromycin (RM) between 1991 and 2000. We divided the patients into the DC-treated group (DC group; 16 children), CM-treated group (CM group; 14 children) and RM- treated group (RM group; 9 children) and compared these groups. RESULTS: Most cases (97%) occurred in October and November. Fever and rash were observed in all 39 cases, and an eschar was noted in 36 cases (92%). No statistical differences could be found between the 3 groups in mean age, duration of fever before admission, white blood cell (WBC) count and complications including abnormal liver enzymes. In most cases defervescence after treatment was within 24 h (34 cases, 87%) and during 24 to 48 h in 2 cases in the DC group, 1 case in the CM group and 2 cases in the RM group (no statistical difference). CONCLUSION: Roxithromycin was as effective as conventional doxycycline or chloramphenicol in children with scrub typhus and may be safer to use.