Hepatitis: Szenborn L

Knuf M, Szenborn L, Moro M, Petit C, Bermal N, Bernard L, Dieussaert I, Schuerman L. · Zentrum für Kinder- und Jugendmedizin, Johannes Gutenberg Universität Mainz, Mainz, Germany. · Pediatr Infect Dis J. · Pubmed #19325452 No free full text.

Abstract: BACKGROUND: The choice of non-typeable Haemophilus influenzae Protein D as main carrier protein in the candidate 10-valent pneumococcal conjugate vaccine (PHiD-CV, GlaxoSmithKline Biologicals), was driven in part to avoid carrier-mediated suppression and possible bystander interference with coadministered vaccines. Immunogenicity data from 3 primary and 2 booster vaccination studies were assessed for possible impacts of PHiD-CV coadministration on immune responses to routinely administered childhood vaccines, in comparison to 7-valent pneumococcal conjugate vaccine (7vCRM) coadministration. METHODS: Randomized, controlled studies in which PHiD-CV or 7vCRM vaccines were coadministered with DTPa-[HBV]-IPV/Hib, DTPa-[HBV]-IPV, DTPw-HBV/Hib, IPV, and OPV, combined Hib-Neisseria meningitidis serogroup C vaccine (Hib-MenC-TT), standalone MenC-TT or MenC-CRM vaccines. RESULTS: One month after primary vaccination, >96% of PHiD-CV recipients had seroprotective antibody concentrations against diphtheria, tetanus, poliovirus types 1 and 3, Hib (>or=0.15 microg/mL), SBA-MenC (>or=1:8), and >94% were seropositive for antibodies against pertussis antigens. Somewhat lower responses against poliovirus type 2 in study A (compared with poliovirus type 1 and 2 responses) and hepatitis B in the 6-, 10-, and 14-week schedule in the Philippines (compared with hepatitis B responses in the other studies) were observed after coadministration of both PHiD-CV and 7vCRM vaccines. Antitetanus and anti-PRP antibody geometric mean concentrations (GMCs) tended to be higher after PHiD-CV coadministration, probably because of the TT carrier protein for serotype 18C in PHiD-CV. Booster vaccination induced substantial increases in antibody GMCs for all coadministered antigens. These responses were generally within the same range in PHiD-CV and 7vCRM groups. Observed anti-PRP responses remained higher in PHiD-CV recipients after the booster dose. CONCLUSIONS: Coadministration of PHiD-CV with commonly used childhood vaccines induced high levels of seroprotection/seropositivity against all targeted diseases. No evidence of negative interference on the immune response to any of the coadministered vaccine antigens was observed when compared with the current routine practice of 7vCRM coadministration.

Bermal N, Szenborn L, Chrobot A, Alberto E, Lommel P, Gatchalian S, Dieussaert I, Schuerman L. · Research Institute for Tropical Medicine, Filinvest Corporate City, Alabang, Muntinlupa City, The Philippines. · Pediatr Infect Dis J. · Pubmed #19325451 No free full text.

Abstract: BACKGROUND: Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was evaluated when coadministered with DTPw-HBV/Hib and OPV at 6, 10, and 14 weeks of age in the Philippines, or with DTPw-HBV/Hib and IPV at 2, 4, and 6 months of age in Poland. METHODS: In this double-blind, controlled study (107007/NCT00344318), 400 Filipino and 406 Polish infants 6 to 12 weeks of age were randomized (3:1) to receive either PHiD-CV or the 7-valent pneumococcal conjugate vaccine (7vCRM). Immune responses were assessed 1 month post-dose III. RESULTS: Percentages of infants with anti-pneumococcal antibody concentrations >or=0.2 microg/mL (GSK's 22F-inhibition ELISA) were within the same range for both pneumococcal conjugate vaccine groups, with the exception of serotypes 6B and 23F for which lower percentages were observed in the PHiD-CV group in Poland. At least 98.2% of PHiD-CV vaccinees had antibody concentrations >or=0.2 microg/mL against pneumococcal serotypes 1, 5, and 7F. In both countries, anti-pneumococcal antibody geometric mean concentrations against serotypes 18C and 19F were higher in the PHiD-CV group than in the 7vCRM group. Antibody geometric mean concentrations for most of the other common serotypes were within the same range for both groups in the Philippines and were lower in the PHiD-CV group in Poland. Functional responses (opsonophagocytic activity [OPA]) were observed for all vaccine serotypes in both countries. CONCLUSIONS: PHiD-CV was immunogenic against each of the 10 pneumococcal vaccine serotypes when coadministered with DTPw-HBV/Hib and poliovirus vaccines.

Kawashima H, Kato N, Ioi H, Nishimata S, Watanabe C, Kashiwagi Y, Takekuma K, Hoshika A, Szenborn L, Bergman K. · Department of Pediatrics, Tokyo Medical University, Tokyo, Japan. · Pediatr Int. · Pubmed #18533937 No free full text.

Abstract: BACKGROUND: In the pathology of autoimmune hepatitis the immunity mechanism of T-helper 1 (Th1) and Th2 cells was recently evaluated. The purpose of the present study was to measure the mRNA levels in peripheral mononuclear cells and serum cytokines obtained from children with autoimmune hepatitis for a better understanding of the mechanism. METHODS: Twenty-five patients with autoimmune hepatitis and seven controls were enrolled. mRNA levels in peripheral mononuclear cells and serum cytokines were measured using real-time polymerase chain reaction and immunoassay. RESULTS: Serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were rarely detected. In contrast the IFN-gamma/beta-actin mRNA levels were high. CONCLUSION: Autoimmune hepatitis is a Th1-predominant state, therefore immune modulation therapies that target the control of Th1 cytokines should be used.

Szenborn L, Kacprzak-Bergman I, Zaleska I, Gruszka J. · Katedra i Klinika Chorób Zakaznych Dzieci Akademii Medycznej we Wrocławiu. · Pol Merkur Lekarski. · Pubmed #15690693 No free full text.

Abstract: Etiology and pathogenesis of autoimmune hepatitis (AIH) is still unknown. In several studies significantly increased antibody titers to measles virus in the sera of patients with AIH and chronic active hepatitis as compared to healthy people were observed. Aim of the study was to evaluate the humoral immunity against measles in children and adolescent with AIH after measles vaccination. MATERIAL AND METHODS: 110 subjects of both sexes aged 6-22 year (19 patients with AIH, 41 children with chronic hepatitis B and C (CH) and 50 healthy persons (HP) were tested to measles antibodies. Moreover mumps antibodies were examined for humoral immunity defects exclusion. All subjects were vaccinated against measles but none of them with mumps vaccine. Antibody were tested by enzyme immunoassays (EIA) and standardized by calibration against the International Standard. Geometrical mean concentration (GMC) of antibodies and the number of seropositive patients were calculated. RESULTS: Measles antibodies were found in all AIH patients (GMC 1.33 IU/ml (range 0.5-21.1 IU/ml)), in 85.4% of patients with CH (GMC 1.68 IU/ml (0.5-4.9 IU/ml)) and in 78% of HP (GMC 1.62 IU/ml (0.41-10 IU/ml)). The differences between the number of seropositive patients and between antibody concentrations in three groups were not significant. Mumps antibodies were detected in 82% AIH patients, 70% patients with CH and 76% HP. In AIH group higher antibody titer was observed than in patients with CH (p=0.047). CONCLUSIONS: The vaccination with measles vaccine does not lead to immunoregulation disturbances in AIH patients in contrary to natural measles infection.

Szenborn L, Hoehne M, Zalewska I, Gruszka J, Kacprzak-Bergman I, Schreier E. · Department of Pediatric Infectious Diseases, Medical University, Wrocłow, Poland. · Med Sci Monit. · Pubmed #12552247 No free full text.

Abstract: BACKGROUND: TTV is a newly discovered virus and little is known about the frequency of TTV infection in children in Poland. The aim of our study was to investigate the frequency of TTV infection in children with chronic viral hepatitis B and C. MATERIAL/METHODS: Two patient groups were tested: 74 patients with chronic hepatitis B aged 4 to 20 years, and 13 patients with chronic hepatitis C aged 10 to 18 years. Nucleic acids were extracted from serum using the spin column technique (QIAGEN(r), Hilden, Germany), and TTV DNA sequences were amplified by nested PCR. RESULTS: TTV DNA was found in 47.3% of patients with chronic hepatitis B and in 53.8% of patients with hepatitis C. Among those patients with chronic B hepatitis there was no statistical difference between the frequency of coinfection with TTV and clinical-histopathological diagnosis, activity of aminotransaminases, frequency of seroconversion of HBeAg to antiHBe, or interferon alpha therapy. CONCLUSIONS: In Poland, TTV viremia is frequent in patients with chronic viral hepatitis B and C. TTV coinfection did not modify the course and activity of chronic hepatitis B or influence the outcome of interferon therapy.