Acute hepatic failure among hospitalized Thai children.

We conducted a hospital-based study from June 2002 to December 2006 of Thai children aged 1-15 years with acute hepatic failure (AHF) to determine the causes and outcomes. Eleven children were included in the study. Hepatitis B virus was the cause of AHF in one child, infection-associated hemophagocytic syndrome was the cause in 1 child, Wilson's disease was the cause in 1 child and dengue fever was suspected to be the cause in 2 children. In 6 children the cause of AHF was unknown. Jaundice was reported in 9 of 11 children. Ten of 11 children had mild to moderate encephalopathy on admission. Five of 11 children died due to AHF. No liver transplantations were performed among the children in this study. Further studies into the relationship between dengue infection and AHF are needed.

Immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Taiwan.

BACKGROUND/PURPOSE: The immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae (H. Influenzae) protein D conjugate vaccine (PHiD-CV), co-administered with routine childhood vaccines, were assessed in Taiwanese infants. METHODS: In this open study, 230 healthy infants were primed with three doses of PHiD-CV (Synflorix) and diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine (DTPa-HBV-IPV/Hib vaccine) at 1.5, 3 and 6 months of age and two doses of oral human rotavirus vaccine at 1.5 and 3 months. Pneumococcal immune responses were assessed 1 month post-dose three, by 22F-inhibition ELISA and opsonophagocytic activity (OPA) assay. Local and general solicited/unsolicited symptoms and serious adverse events (SAEs) were recorded. RESULTS: At least 95.4% of participants had an antibody concentration ≥ 0.2 µg/mL against each vaccine serotype. At least 96.1% of participants had an OPA titer ≥ 8 against each vaccine serotype except 6B (87.3%). All infants, but one, were seropositive for antibodies against nontypeable H. influenzae protein D. Immune responses to the co-administered vaccines were good and in line with previous reports. PHiD-CV was well tolerated, with low (≤ 6.3%) incidences of grade 3 solicited local symptoms. The frequencies of general symptoms were in line with other pneumococcal conjugate vaccine studies. There were no systematic increases in incidences of solicited general or local symptoms with successive doses. There were no reports of grade 3 fever (rectal temperature > 40 °C) or SAEs considered to be causally related to vaccination. CONCLUSION: PHiD-CV co-administered with routine childhood vaccines within the first 6 months of life, was highly immunogenic, and well tolerated in Taiwanese infants.

Etiology, incidence and outcomes of acute hepatic failure in 0-18 year old Filipino children.

Data on the epidemiology of acute hepatic failure (AHF) among pediatric Filipinos is limited. This study investigated the etiology, outcomes and incidence of AHF among 0-18 year old Filipino children. A hospital-based retrospective and prospective surveillance study was conducted at Philippine General Hospital between January 2000 and December 2006. AHF was defined as onset of coagulopathy and/or encephalopathy < or = 28 days after the onset of symptoms, a patient/ laboratory prothrombin time >2, an elevated bilirubin level and evidence of liver failure complicated by encephalopathy. Blood samples were tested for viral hepatitis antibodies using ELISA (Abbott Lab). AHF incidence rates were calculated with 95% confidence intervals (CI). Twenty-seven subjects were recruited and 26 included in the analysis. The mean age of AHF subjects at the time of hospital admission was 6.9 years (SD:6.09 years). The most frequent etiological agents for AHF were hepatitis A virus (HAV) (19.2%; 5/26) and hepatitis B virus (3.8%; 1/26). Incidence of AHF was 11.05 per 100,000 subject years (95% CI 6.81-15.30). Jaundice was observed in 84.6% (22/26) of subjects and encephalopathy on admission (any grade) was reported in 72.0% of subjects: AHF was fatal in 84.6% (22/26) of subjects. HAV was the most common etiological agent for AHF. Indeterminate causes for AHF indicate the need for further investigation.

Immunogenicity and reactogenicity of DTPa-IPV/Hib vaccine co-administered with hepatitis B vaccine for primary and booster vaccination of Taiwanese infants.

Immunogenicity and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (Hib) conjugate vaccine (DTPa-IPV/Hib, Infanrix™-IPV + Hib) was assessed when co-administered with hepatitis B (HBV) vaccine. Seventy healthy infants received DTPa-IPV/Hib at 1.5, 3.5, 6 and 15-18 months, and HBV at birth, 1.5, 6 and 15-18 months of age. Serological responses were assessed. Diphtheria, tetanus, Hib and pertussis seroprotection/seropositivity rates were 100% after primary vaccination. Post-primary immune responses to poliovirus could not be evaluated for technical reasons. However, after the booster dose, seroprotection/seropositivity rates, including poliovirus, were 100%. Over 95% were seroprotected against HBV. Post-booster geometric mean antibody concentrations/titers (GMC/GMTs) rose from 14-fold to 45-fold, indicating effective priming against all antigens, including polioviruses. DTPa-IPV/Hib was well tolerated alone or co-administered with HBV. No serious adverse events were considered related to vaccination. Primary and booster vaccination with combined DTPa-IPV/Hib and HBV was immunogenic and well tolerated. Combination vaccines enable vaccine providers to conveniently provide routine pediatric immunizations, with minimal discomfort.

Immunogenicity and reactogenicity of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus and Haemophilus influenzae type B.

Immunogenicity and reactogenicity of primary vaccination with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) vaccine when co-administered with Haemophilus influenzae (Hib) conjugate vaccine were assessed in 60 healthy infants. Infants received HBV vaccine at birth, then DTPa-HBV-IPV and Hib vaccines at age 1.5 months, 3.5 months and 6 months. Blood samples were collected before the first DTPa-HBV-IPV and Hib vaccine doses and 1 month after dose 3. Reactogenicity was assessed using diary cards. One month after primary vaccination, all infants were seroprotected/seropositive against all vaccine antigens evaluated. The poliovirus antigen could not be evaluated. The vaccines were well tolerated. No case of fever > 39.0 °C was reported. No serious adverse events were considered related to vaccination. Primary vaccination with DTPa-HBV-IPV and Hib vaccines was immunogenic and well tolerated. Combined vaccines, such as this pentavalent vaccine, minimize the number of injections and vaccination visits required to complete primary vaccination, and provide choice and flexibility for physicians and vaccine providers.

Immunogenicity and safety of an AS03(A)-adjuvanted H5N1 influenza vaccine in a Taiwanese population.

BACKGROUND/PURPOSE: A multicenter study (NCT00449670) conducted across Taiwan, Singapore, Hong Kong and Thailand evaluated the safety and manufacturing consistency of four formulations of an AS03(A)-adjuvanted H5N1 vaccine in terms of immune response against the vaccine-homologous strain (A/Vietnam/1194/2004). This manuscript presents data from the Taiwanese population. METHODS: A total of 400 individuals, aged 18-60 years, were randomized into six groups (2:2:2:2:1:1 ratio) to receive two doses (21 days apart) of one of the four adjuvanted formulations (H5N1-AS03(A)-groups) or one of the two nonadjuvanted formulations (H5N1-DIL-groups). Blood samples collected before vaccination (Day 0) and 21 days after each vaccine dose were analyzed using hemagglutination inhibition (HI) assay. Adverse events were recorded. RESULTS: All four AS03(A)-adjuvanted formulations induced comparable immune responses against the A/Vietnam/1194/2004 strain; following the second dose, immune response in terms of HI antibodies was higher in the H5N1-AS03(A)-groups {seroprotection rate=91.6% [95% confidence interval (CI): 87.9-94.4]; geometric mean titer (GMT)=177.6 (95% CI: 153.2-206.0)} compared with the H5N1-DIL-groups [seroprotection rates=5.0% (95% CI: 1.4-12.3); GMT=6.3 (95% CI: 5.4-7.4)]. Immune response against the heterologous A/Indonesia/05/2005 strain was also stronger in the H5N1-AS03(A)-groups [seroprotection rate=45.6% (95% CI: 40.0-51.4); GMT=20.5 (95% CI: 17.8-23.7)] compared with the H5N1-DIL groups [seroprotection rate=0.0% (95% CI: 0.0-4.5); GMT=5.0 (95% CI: 5.0-5.0)]. The overall reactogenicity profile of the adjuvanted formulations was clinically acceptable. CONCLUSION: The AS03(A)-adjuvanted H5N1 influenza vaccine formulations induced stronger immune response against the vaccine-homologous and heterologous strains than the nonadjuvanted formulations. The AS03(A)-adjuvanted H5N1 vaccine demonstrated a good immunogenicity and an acceptable safety profile in the Taiwanese population.

Safety and reactogenicity of DTPa-HBV-IPV/Hib and DTPa-IPV/I-Hib vaccines in a post-marketing surveillance setting.

Combination vaccines have been shown to improve the timeliness of vaccination and vaccine coverage. Safety and reactogenicity of combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib, Infanrix IPV+Hib, GlaxoSmithKline Biologicals) was assessed in two clinical studies. In Study A, 2,590 subjects received DTPa-IPV/Hib at 3, 4 and 5 months of age with a booster at 18 months. In Study B, 702 subjects received the same schedule but with DTPa-hepatitis B-IPV/Hib (DTPa-HBV-IPV/Hib, Infanrix hexa, GlaxoSmithKline Biologicals) vaccine administered at 5 months of age. Reactogenicity was assessed for four days after each dose using diary cards. Serious adverse events (SAEs) were assessed until 24 months of age. The vaccines were well tolerated. After primary vaccination, irritability was the most frequently reported grade 3 general symptom (0.8% of doses in both studies). Fever (axillary) > 39 degrees C was infrequent (0.3% of doses in Study A; 0.5% of doses in Study B). After the booster dose, the most frequently reported grade 3 symptom was redness (5%) in Study A and pain (0.5%) in Study B. An axillary temperature > 39 degrees C was reported in 1.1% of subjects. Throughout the study period, 646 SAEs were reported, of which 6 SAEs were considered to be vaccination-related. The reactogenicity and safety profile of the combined DTPa-IPV/Hib vaccine was good when used for primary and booster vaccinations in over 3,000 Singaporean infants. Substitution of DTPa-IPV/Hib with DTPa-HBV-IPV/Hib at Month 5 reduced the number of injections required at this age by one.

Cross-clade immunogenicity and antigen-sparing with an AS03(A)-adjuvanted prepandemic influenza vaccine in a Thai population.

OBJECTIVE: The present study (NCT00449670) in Asian subjects (18-60 years) evaluated the manufacturing consistency of four formulations of 3.75 mg AS03(A)-adjuvanted H5N1 influenza vaccine, in terms of post-immunization Hemagglutination Inhibition (HI) titers against the A/Vietnam/1194/2004 and A/Indonesia/05/2005 strains. The immunogenicity and safety of the vaccine in the Thai population are reported herein. MATERIAL AND METHOD: Subjects were randomized (2:2:2:2.:1:1) between four vaccine groups and two control groups to receive two doses of either the AS03(A)-adjuvanted or non-adjuvanted H5N1 vaccine formulations, 21 days apart. Sera were assayed for HI antibody titers against the two strains. RESULTS: After the second dose of AS03(A)-adjuvanted vaccine, 94.2% subjects in the H5N1-AS03(A) groups seroconverted and 94.9% subjects were seroprotected against the A/Vietnam/1194/2004 strain. Cross-clade immune response against the A/Indonesia/05/2005 strain was observed. All vaccine formulations had an acceptable safety profile. CONCLUSION: This antigen-sparing AS03(A)-adjuvanted influenza vaccine could be a suitable candidate for combating and mitigating future influenza pandemics.

Immunogenicity, reactogenicity and safety of three-dose primary and booster vaccination with combined diphtheria-tetanus-whole-cell pertussis-hepatitis B-reduced antigen content Haemophilus influenzae type b vaccine in Filipino children.

OBJECTIVES: To evaluate the immunogenicity, reactogenicity and safety of primary and booster vaccination with DTPw-HBVLT/Hib2.5 vaccine containing low thiomersal and reduced quantities of Hib polysaccharide (PRP). BACKGROUND: Combined DTP vaccines have high global coverage. Thus, the addition of new antigens to existing DTP vaccines is the most effective way to ensure high coverage. METHODS: 192 healthy infants were randomized to receive the investigational DTPw-HBVLT/Hib2.5 vaccine or licensed DTPw-HBV/Hib10 at 6, 10, 14 weeks. Immune memory to the Hib antigen was assessed through administration of plain PRP challenge at 10 months in 50% of subjects. Challenged and unchallenged subjects respectively received a DTP-HBV or DTPa-HBV/Hib booster at 15-18 months of age. Antibody responses were measured using enzyme-linked immunosorbent assay (ELISA) and reactogenicity was assessed using diary cards. RESULTS: One month post-primary vaccination, 100% and ≥ 93.7% of subjects in both groups had anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL, respectively. Robust responses to PRP were observed after the 10 month plain PRP challenge and booster responses were observed in unchallenged subjects after the booster dose at 15-18 months of age. Post-primary and post-booster responses to the other vaccine antigens were at least as high in the DTPw-HBVLT/Hib2.5 group versus the DTPw-HBV/Hib10 group. The reactogenicity profile of the DTPw-HBVLT/Hib2.5 vaccine was acceptable. CONCLUSION: The DTPw-HBVLT/Hib2.5 combination vaccine with reduced thiomersal and Hib content had equivalent immunogenicity and tolerability versus the full standard DTPw-HBV/Hib10 vaccine. DTPw-HBVLT/Hib2.5 or DTPw-HBV/Hib10 vaccines can contribute to reducing childhood diseases through ensuring high vaccine coverage in mass vaccination programs. ClinicalTrials.gov identifiers: NCT 01061541, NCT00158808.

Vaccination with a human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in Korean girls aged 10-14 years.

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Indian women.

AIM: India has the highest number of annual incident cases and mortality rates for cervical cancer worldwide. This study was conducted to assess the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Indian women aged 18-35 years old. METHODS: This double-blind, randomized (1:1), controlled and multicenter trial with two parallel groups, the Vaccine and Placebo groups, included 354 subjects in four centers across India. Subjects were given GlaxoSmithKline's HPV-16/18 AS04-adjuvanted cervical cancer vaccine or aluminum hydroxide placebo according to a 0, 1 and 6 month schedule and followed up until month 7. Serum samples were drawn at pre-vaccination and at month 7. Safety data were collected throughout the study. RESULTS: A total of 330 subjects completed the study. One month post-Dose 3, all initially seronegative subjects in the Vaccine group had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titer levels of 10226.5 EL.U/ml (95% confidence interval: 8847.1-11821.0) and 3953.0 EL.U/ml (95% confidence interval: 3421.8-4566.8), respectively. Initially seropositive subjects also showed an increase to similar geometric mean titer levels. Six serious adverse events (two in the Vaccine group and four in the Placebo group), all unrelated to vaccination, were reported. Commonly reported solicited local (injection-site pain) and general (fatigue, headache and fever) symptoms were similar in both groups. Compliance to the three-dose vaccination course was >97%. CONCLUSIONS: The AS04-adjuvanted HPV-16/18 cervical cancer vaccine was highly immunogenic and generally well-tolerated making it a potential tool for prevention and control of cervical cancer in India.

Human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in healthy Chinese women from Hong Kong.

OBJECTIVE: To assess the immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine in Chinese women aged 18 to 35 years enrolled from Hong Kong. DESIGN: Double-blind, randomised controlled trial with vaccine and placebo groups. SETTING: Single-centre study in Hong Kong. PARTICIPANTS: Three hundred women enrolled (150 per group) between March 2006 and June 2007. INTERVENTIONS: Subjects received three doses of human papillomavirus-16/18 vaccine or placebo (aluminium hydroxide), administered intramuscularly at 0, 1, and 6 months. MAIN OUTCOME MEASURES: Human papillomavirus-16/18 seroconversion rates and geometric mean titres at month 7 (in human papillomavirus-16/18 recipients); reactogenicity and safety (in all subjects). RESULTS: A total of 294 women completed the study (148 in the vaccine group, 146 in placebo group). All initially seronegative subjects in the vaccine group had seroconverted for human papillomavirus-16/18 antibodies by month 7. Anti-human papillomavirus-16 and anti-human papillomavirus-18 antibody geometric mean titres were 10 422 (95% confidence interval, 8730-12 442) EL.U/mL and 4649 (3975-5437) EL.U/mL, respectively. High compliance (99% in both groups) was observed for the three-vaccination course. The frequencies of local injection site reactions were higher in the vaccine than placebo group; pain being the most common symptom in both groups. Regarding solicited symptoms, fatigue and myalgia were the most frequent in both groups. Five serious adverse events (four in vaccine group, one in placebo group) were reported, but all were considered unrelated to the vaccinations. CONCLUSION: The human papillomavirus-16/18 AS04-adjuvanted vaccine was highly immunogenic, safe, and generally well tolerated in Chinese women from Hong Kong.

Immunogenicity of HBV vaccine during stated shelf-life.

Thiomersal has been used as preservative in multi-dose vials of hepatitis B vaccine (Engerix-B). Due to safety concerns, thiomersal was replaced with 2-phenoxyethanol (2PE) as preservative in multi-dose vials. The potency of 2PE preserved hepatitis B vaccine multiple use vials was measured over the shelf-life in terms of immunogenicity, reactogenicity and safety. This single-blind, randomized study was conducted with the assistance of employees of GlaxoSmithKline Biologicals, makers of the Engerix-B vaccine. Four hundred twenty subjects aged > or =18 years were randomized to receive three doses (0, 1, 6 months) of 2PE preserved hepatitis B vaccine kept on the shelf <12 months (2PE New group), 2PE preserved hepatitis B vaccine kept on the shelf >18 months (2PE Old group), or thiomersal preserved hepatitis B vaccine [HBV(Thio) group]. Anti-HBs was measured by GlaxoSmithKline Biologicals post-vaccination; the reactogenicity and safety of the vaccines were assessed. Protective anti-HBs levels (> or =10 mIU/ml) were measured one month after dose 3. The results showed protective levels in 86.8% (2PE New), 89% (2PE Old) and 95.3% [HBV(Thio)]. There was no difference detected between the 2PE New and 2PE Old groups in terms of anti-HBs seroprotection rates and geometric mean concentrations one month after dose 3. However, both 2PE groups had significantly lower seroprotection rates than the HBV(Thio) group and the number of non-responders was higher in the 2PE groups than in the Thio group. A antibody response rates over time were similar between the 2PE New and Old groups. The reactogenicity profiles were acceptable and the ranges were similar for each group. The shelf-life of the vaccines had no impact on immunogenicity or reactogenicity and 2PE preserved hepatitis B vaccine can be considered stable over time.

Retrospective surveillance for intussusception in children aged less than five years in a South Indian tertiary-care hospital.

To facilitate the assessment of the safety profile of rotavirus vaccines effectively, baseline data on intussusception are important for comparison with intussusception rates following the introduction of vaccine. The aim of the study was to describe epidemiological and clinical features of intussusception in children aged less than five years in an Indian medical facility. Hospital data on intussusception for children discharged during 1 January 2001-30 June 2004 from the Christian Medical College Hospital, Vellore, India, were reviewed. Relevant information was extracted from medical records to classify cases according to the criteria of the Brighton Collaboration Intussusception Working Group. Complete review of medical records for clinical and demographic information was only performed for those cases fulfilling level 1 diagnostic certainty (definite intussusception) (Study ID 101245). During the surveillance period, 31 infants and children with definite intussusception were identified. The majority (61.2%) of the cases occurred in the first year of life. The male : female ratio was 3.4 : 1. Intussusception cases occurred round the year with no distinct seasonality. No intussusception-associated death was recorded. This study provides baseline data on intussusception in South India. Cases identified in the study were similar in presentation and demographics as those observed in other Asian settings. Prospective surveillance systems, using standardized case definitions will further increase the understanding of the aetiology and epidemiology of intussusception, especially as new rotavirus vaccines are made available.

Safety and immunogenicity of a tetravalent polysaccharide vaccine against meningococcal disease.

BACKGROUND/PURPOSE: Meningococcal disease, including meningitis and sepsis, usually follows an invasive infection by Neisseria meningitidis, and is a major cause of death and morbidity worldwide. Currently available meningococcal vaccines that consist of pure capsular polysaccharides (serogroups A, C, W-135 and Y) are generally safe and efficacious in adults and children aged > 2 years. The purpose of this study was to evaluate the immunogenicity, safety and reactogenicity of a single dose of GlaxoSmithKline Biologicals' Mencevax ACWY vaccine in healthy Taiwanese subjects aged 2-30 years. METHODS: This open, single center, Phase III study was conducted in Taiwan. A single dose of the Mencevax ACWY vaccine was administered to subjects aged 2-30 years. Immunogenicity and safety of the vaccine were evaluated after vaccination. RESULTS: The immunogenicity results obtained 1 month after vaccination with Mencevax ACWY vaccine indicated that the vaccine elicited a good immune response in vaccinees aged 2-30 years. This was both in terms of functional activity directed against meningococcal polysaccharide (A, C, W-135 and Y) as measured by serum bactericidal assay (> 93% activity against all serogroups), and specific IgG concentrations measured by ELISA (> 96% seropositivity to all serogroups). CONCLUSION: The tetravalent polysaccharide Mencevax ACWY meningococcal vaccine was well tolerated and immunogenic in subjects aged 2-30 years in Taiwan.

Priorities and challenges for hepatitis B control in the Philippines and the importance of a vaccine dose at birth.

The Philippines annual birth cohort of over 2 million is the second largest in the Western Pacific Region; 44% of births occur outside health facilities. With third dose infant hepatitis B (HB) vaccine coverage of 43% in 2006, erratic vaccine supply, and lack of policies or processes for universal HB vaccine birth dose delivery, a substantial burden of preventable chronic HB infection continues to occur. Funding, policy, technical and immunization delivery developments now make substantial progress in HB control in the Philippines possible. These developments can help expand access to trained birth care and essential postnatal care for mothers and their newborn.

Survey of childhood empyema in Asia: implications for detecting the unmeasured burden of culture-negative bacterial disease.

BACKGROUND: Parapneumonic empyema continues to be a disease of significant morbidity and mortality among children despite recent advances in medical management. To date, only a limited number of studies have assessed the burden of empyema in Asia. METHODS: We surveyed medical records of four representative large pediatric hospitals in China, Korea, Taiwan and Vietnam using ICD-10 diagnostic codes to identify children <16 years of age hospitalized with empyema or pleural effusion from 1995 to 2005. We also accessed microbiology records of cultured empyema and pleural effusion specimens to describe the trends in the epidemiology and microbiology of empyema. RESULTS: During the study period, we identified 1,379 children diagnosed with empyema or pleural effusion (China, n = 461; Korea, n = 134; Taiwan, n = 119; Vietnam, n = 665). Diagnoses of pleural effusion (n = 1,074) were 3.5 times more common than of empyema (n = 305), although the relative proportions of empyema and pleural effusion noted in hospital records varied widely between the four sites, most likely because of marked differences in coding practices. Although pleural effusions were reported more often than empyema, children with empyema were more likely to have a cultured pathogen. In addition, we found that median age and gender distribution of children with these conditions were similar across the four countries. Among 1,379 empyema and pleural effusion specimens, 401 (29%) were culture positive. Staphylococcus aureus (n = 126) was the most common organism isolated, followed by Streptococcus pneumoniae (n = 83), Pseudomonas aeruginosa (n = 37) and Klebsiella (n = 35) and Acinetobacter species (n = 34). CONCLUSION: The age and gender distribution of empyema and pleural effusion in children in these countries are similar to the US and Western Europe. S. pneumoniae was the second leading bacterial cause of empyema and pleural effusion among Asian children. The high proportion of culture-negative specimens among patients with pleural effusion or empyema suggests that culture may not be a sufficiently sensitive diagnostic method to determine etiology in the majority of cases. Future prospective studies in different countries would benefit from standardized case definitions and coding practices for empyema. In addition, more sensitive diagnostic methods would improve detection of pathogens and could result in better prevention, treatment and outcomes of this severe disease.

A new DTPw-HBV/Hib vaccine: immune memory after primary vaccination and booster dosing in the second year of life.

The response to booster vaccination at 15-18 months of age and the presence of immune memory in 10-month old children, primed with a new combined diphtheria-tetanus-hepatitis B-whole cell pertussis vaccine extemporaneously mixed with Haemophilus influenzae type b-tetanus toxoid conjugate (DTPw-HBV/Hib) from new antigen sources and containing 2.5 microg polyribosyl-ribitol-phosphate (PRP) was assessed. Primary vaccination with the new DTPw-HBV/Hib vaccine was immunogenic and of comparable tolerability to commercially available Tritanrix HepB/Hiberix. Children were boosted with DTPw-HBV, DTPw-HBV/Hib or separate DTPw-HBV+Hiberix. Immune memory was assessed through administration of 10 microg PRP polysaccharide. Anti-PRP antibody GMCs increased substantially after the challenge in DTPw-HBV/Hib-primed subjects indicating the presence of immune memory. One month after the booster dose, 100% of subjects had seroprotective antibody concentrations against PRP, diphtheria and tetanus, >95% were seroprotected against hepatitis B, > or =94.0% had a pertussis booster response. Substantial increases in antibody GMCs against all antigens were observed. Swelling >20 mm was the most common Grade 3 solicited symptom reported (up to 26.0% of subjects). Fever >39.5 degrees C was uncommon (>2.5%). Eleven large swelling reactions were reported; none involved an adjacent joint. One serious adverse event occurred that was considered unrelated to vaccination. This new DTPw-HBV/Hib vaccine with new vaccine components and 2.5 microg PRP induced effective priming against Hib evidenced by a vigorous anamnestic response on exposure to PRP polysaccharide. The booster dose was immunogenic and the safety profile was acceptable. Combined DTPw-HBV and DTPw-HBV/Hib vaccines using new vaccine antigen sources will promote continued supply of combined DTPw-based vaccines to global mass vaccination campaigns.

Booster vaccination at 6-8 years of age with a reduced antigen content dTpa-IPV vaccine is immunogenic and safe after priming with whole-cell pertussis vaccine.

Pertussis vaccines containing reduced amounts of antigen have been considered primarily for use in adolescents and adults to date. We evaluated a reduced antigen content combined diphtheria tetanus acellular pertussis and inactivated polio vaccine (dTpa-IPV) in 6-8 years old children in Taiwan, who had received 4 doses of DTPw (combined diphtheria, tetanus, whole cell pertussis vaccine) and OPV (oral polio vaccine). One month after the booster dose, seroprotection rates and vaccine response rates to all antigens were at least 98.8%, and significant increases in antibody concentrations were observed. Booster vaccination was associated with minor local reactions and systemic symptoms. Symptoms of severe intensity did not occur, with the exception of local pain. The dTpa-IPV vaccine was immunogenic and well tolerated in 6-8 years old children and offers an alternative to the current use of tetanus and diphtheria vaccine and OPV in Taiwan, addressing the established need for repeated booster vaccinations against pertussis at the same time.

Human papillomavirus (HPV) type distribution in Korean women: a meta-analysis.

The aim of the present study is to estimate the overall prevalence and type distribution of human papillomavirus (HPV) in Korean women, through literature review and meta-analysis. We searched published data for the period between 1995 and 2007 using the following inclusion criteria; (1) studies using type-specific HPV tests, (2) data from Korean female, (3) with cytologic or pathologic results, (4) having more than 20 cases for each subgroup classified by cytologic results, and (5) HPV detection including types 16, 18, and at least one other type. In total, 18 studies (13,842 cases) published up to April 2007 were identified and selected. Adjusted overall HPV prevalence was 23.9% (95% CI: 23.8-24.1%) in women with normal cytology and 95.8% (95% CI: 95.4-96.2%) in women with cervical cancer. Type 16 was predominant regardless of cervical disease status, and type 58 occupied a significantly larger proportion in high-grade cervical intraepithelial lesions and cervical cancer in Korean women. HPV types 58, 33, and 52 together accounted for about 20% of infections in cervical cancer and high-grade intraepithelial lesions. After introduction of HPV prophylactic vaccines, extended protection, especially against types 58, 33, and 52, will be an important issue for cervical cancer prevention in Korea. The future dominant genotypes will require follow-up epidemiological studies with a large-scale, multicentered, and prospective design.