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Biomedical subjects

W Jilg

Publications and source records attributed to W Jilg.

At least 19 recordsLinked to original sources

[Combined vaccine against tetanus, diphtheria and polio. A randomized controlled study of immunogenicity and tolerance].

UNLABELLED: BACKGROUND, METHOD: Given the worldwide distribution of infection and the mobility of large parts of the population immunizations against tetanus, diphtheria and polio remain a challenge. This is especially true for adolescents and adults since antibodies tend to wane once immunized children enter adolescence and adulthood. A new combination vaccine against tetanus, diphtheria and polio (Td-IPV) for booster immunizations was subjected to a randomized, controlled and single-blind trial. Non-inferiority had to be demonstrated with regard to efficacy (immunogenicity) and safety in comparison to separate Td and IPV injections. RESULTS: Almost 500 subjects from community practices and occupational/immunization clinics took part. Antibody titres were equivalent for all antigens. Local and systemic reactions were equal or even less marked in the intervention group. CONCLUSION: From a public health perspective the new vaccine can make an important contribution to ensure adequate protection against tetanus, diphtheria and polio in adolescent and adult populations.

Adolescent↗

Hepatitis C virus transmission in a pediatric oncology ward: analysis of an outbreak and review of the literature.

Hospital-related hepatitis C virus (HCV) infections continue to occur even after the introduction of blood donor screening. We report an outbreak of HCV in nine patients of a pediatric oncology ward in 1996/1997. Sequencing of the hypervariable genomic region 1 (HVR1) of the E2/NS1 region showed near identity between HCV isolates from these patients as evidence for infection with the same virus. Despite a detailed and careful investigation, the source of infection and the mode of virus transmission could not be established. Based on a review of the current literature about nosocomial HCV infection and HCV infection in children, hypotheses for possible means of transmission in this outbreak are discussed.

Autoimmune Diseases↗

Prevalence of markers of hepatitis B in the adult German population.

The prevalence of hepatitis B virus markers was investigated in 5305 individuals considered to be representative for the adult German population. After adjustment of the data according to the age and sex distribution in the whole German population an anti-HBc prevalence of 8.71% (95% confidence interval, 7.94-9.48%) and an HBsAg carrier rate of 0.62% (95% confidence interval, 0.40-0.84%) were calculated. Anti-HBc prevalence increased with age from 4.12% in the youngest group to 15.66% in the 61-70-year-old. The percentage of HBsAg carriers showed a maximum of 1.12% in the 41-50-year-old individuals and decreased significantly in the older age groups. 1.40% (95% confidence interval, 1.08-1.72%) of individuals had anti-HBc only. There was a trend to higher rates of this pattern in males than in females; a significantly higher percentage of persons with anti-HBc only was found in anti-HBc-positive individuals below 31 years than in older individuals. Five participants with anti-HBc only (7.7%, or about 0.1% of the whole population) showed HBV-DNA despite the absence of HBsAg. 3.1% of anti-HBc positive individuals where also positive for anti-HCV, that was significantly higher than the percentage of anti-HCV-positives among persons without any HBV marker (0.46%). This study provides a comprehensive picture of the current hepatitis B situation in Germany, showing new data especially on the distribution of HBsAg in the general population and on the subgroup of individuals with anti-HBc only.

Adolescent↗

[Liver histology in hepatitis C: correlation with different biochemical and virological parameters].

BACKGROUND AND AIM: According to the German consensus statement, the indication for treatment of HCV-RNA-positive chronic hepatitis C is not derived from histopathology but from elevated aminotransferases. The indication for liver biopsy has been discussed controversely. This study aimed at investigating the correlation between different biochemical and virological parameters and histological scores of inflammation and fibrosis in chronic hepatitis C. PATIENTS AND METHODS: In a retrospective study, data of 126 patients with chronic hepatitis C who had undergone liver biopsy between January 1994 and March 1998 were analyzed. Histology was interpreted according to a defined numerical score of inflammation and fibrosis by a single pathologist. Scores of fibrosis and inflammation were correlated with biochemical and virological parameters. RESULTS: Inflammatory grading showed a moderate but significant correlation with ALT (r = 0.33, p < 0.001), whereas staging of fibrosis did not correlate with ALT (r = 0.15). There was no association between grading or staging and HCV genotype (n = 110) or serum viral load (n = 57). Grading and staging showed a significant association with each other (p < 0.0001). CONCLUSION: Aminotransferases as "surrogate markers" reflect more or less the histological inflammatory activity but do not allow any estimation of the extent of fibrosis. Some patients may have a high inflammatory activity with low aminotransferases or high aminotransferases with low inflammatory activity. Virological parameters such as HCV genotype or viral load do not allow an estimation of histological findings. If prior to treatment of chronic hepatitis C liver biopsy is omitted and the decision for treatment depends solely on the measurement of surrogate markers, considerable misjudgement of the actual status of liver inflammation or fibrosis may result.

Adolescent↗

Can monovalent hepatitis A and B vaccines be replaced by a combined hepatitis A/B vaccine during the primary immunization course?

A combined hepatitis A/B vaccine (Twinrix Adult) has been licensed in Germany since 1997. We investigated possible differences in immunogenicity and safety when changing over from vaccinations with monovalent vaccines made by different manufacturers to vaccinations with the combined hepatitis A/B vaccine in an open, randomized, multicenter trial. We therefore compared four different schemes changing over from concomitant vaccinations with monovalent vaccines against hepatitis A and B (Havrix 1440+Engerix-B or Vaqta+Gen H-B-Vax) to combined vaccination against hepatitis A+B with three injections of the combined hepatitis A/B vaccine (0, 1, and 6 month schedule). Local and general symptoms were mostly mild in all five groups. With complete three-dose course using the combined vaccine or an early changeover from monovalent vaccines to the combined vaccine, higher overall anti-HBs seroprotection rates and geometric mean concentrations (GMCs) against hepatitis B could be achieved as early as after 2 months as compared to those groups switching later to the combined vaccine. This study demonstrated for the first time that switching from monovalent hepatitis A and B vaccinations to the combined hepatitis A and B vaccination has no negative influence on the tolerability and improves the immunogenicity.

Adolescent↗

Immunogenicity of a combined hepatitis A and B vaccine in healthy young adults.

Combining several vaccines in a single formulation can change the potency of the vaccine antigens. Previous studies suggested a higher immunogenicity of a new combined hepatitis A and B vaccine compared with the monovalent hepatitis B vaccine. We investigated the immune response to hepatitis B surface antigen 1 month after the third vaccine dose in 282 healthy adults who had received either a monovalent hepatitis B vaccine (n=148) or the combined hepatitis A/B vaccine (n=134). A slight trend towards higher geometric mean titres of anti HBs was found at this point in time in the group immunised with the combined vaccine, especially in the few vaccinees with preexisting antibodies against hepatitis A virus. However none of these differences was statistically significant, arguing against an advantage of the combined vaccine regarding hepatitis B immunisation.

Adolescent↗

Serological pattern "anti-HBc alone": report on a workshop.

In areas with low hepatitis B virus (HBV) endemicity such as most parts of Europe and the United States "anti-HBc alone" is found in 10-20% of all individuals with HBV markers, i.e., 1-4% of the population. In about 10% of these individuals HBV DNA is detected by PCR, the proportions varying greatly depending on the population studied, being highest in individuals coinfected with hepatitis C virus (HCV) (above 35%) and HIV (above 85%). A small proportion of individuals with "anti-HBc alone" are in the window phase of an HBV infection or in a stage of late HBV immunity. For the large proportion of these individuals this is not the case and they are thought to have an unresolved HBV-infection or a chronic infection in a late or "low grade" productive state. Currently, limited studies have been performed concerning the clinical aspects of individuals with "anti-HBc alone" and suspected chronic HBV infection. The majority of these individuals seem to be healthy. Some chronic carriers with "anti-HBc alone," however, do present signs of chronic hepatitis. Individuals with "anti-HBc alone" are potentially infectious. This is exemplified by a few case reports of HBV transmission to sexual contacts, perinatal transmission between mother and newborns and in blood recipients. Recommendations are given in relation to both the diagnostic and therapeutic procedures in the individuals with "anti-HBc alone" and in the blood banking and transplantation services.

Blood Banks↗

[Epidemiology, diagnosis and prevention of viral hepatitis].

Viral hepatitis is one of the most important infectious diseases worldwide. It is frequent in tropical and subtropical areas, but also plays still a significant role in the industrialized countries of Northern and Western Europe and the USA. In Germany more than 100,000 people are infected by viral hepatitis each year. Whereas hepatitis A and E are transmitted fecal-orally, hepatitis B, C and D are transmitted by the parenteral route. Most hepatitis A infections seen in Germany are acquired abroad. Hepatitis B is still a nosocomial disease; the majority of infections in Germany, however, seems to be transmitted sexually. For the serological diagnosis of viral hepatitis a battery of sensitive tests for specific antibodies and antigens is available; usually testing of one serum sample allows an unambiguous diagnosis. Prophylaxis of hepatitis A and B is possible using safe and efficient vaccines.

Cross-Cultural Comparison↗

Sensitive and accurate quantitation of hepatitis B virus DNA using a kinetic fluorescence detection system (TaqMan PCR).

The laboratory diagnosis of hepatitis B virus (HBV) infection is based mainly on serological assays. Yet the detection and quantitation of viral DNA is necessary when addressing directly the question of infectivity or when monitoring the viral load during therapy. Standard hybridization assays allow for exact quantitation, but their sensitivity is limited to 10(5)-10(6) viral genomes per ml of serum. The most sensitive tests for HBV DNA are nested PCR systems, which recognize virtually one molecule of the target DNA per reaction. However, these assays only provide very coarse quantitative statements. To take advantage of both methods, a new assay for HBV DNA is described based on the commercial TaqMan system. This assay is capable of quantifying HBV DNA from the theoretical lower limit up to 10(10) genome equivalents per ml of serum and, thus, covers the complete range of naturally occurring states of infections. The method was calibrated on the basis of serial plasmid dilutions and compared with a well-established nested PCR system. More than 100 HBV positive sera and serial dilutions of the Eurohep standard for both ad and ay subtypes were analyzed. The assay reliably detected all HBV positive samples. It shows minimal run-to-run deviations, allows for quantitation that covers eight orders of magnitude, and finally, completely avoids the risk of cross-contamination by PCR products. Thus, this technique combines the sensitivity of PCR amplification and the quantitation potential of hybridization tests and it is time efficient and safer.

DNA, Viral↗

The economic burden of hepatitis B in Germany.

Despite the widespread distribution of Hepatitis B virus (HBV) infection and the ongoing controversy about HBV immunization, surprisingly few published studies examined in detail the economic impact of HBV infection in Europe. Therefore, we investigated a cohort of 180 patients throughout Germany to evaluate the economic burden of HBV-associated disease. In 58 patients with acute and 122 patients with chronic HBV infection, cost-consuming events including direct medical costs and work-loss costs were documented. The direct costs were DM 7702 (95% confidence interval (CI): 5473-9931) for each acute HBV infection and DM 4247 (CI: 1601-6893) per patient-year of chronic HBV infection, with marked differences between different stages of HBV disease. The derived overall costs (1997 price levels) per year were DM 10,018 (CI: 7613-12,421) and DM 4860 (CI: 2185-7536), respectively. Based on crude population-based estimates (30,000 acute and 420,000 chronic HBV cases), we calculated the total HBV-related costs in Germany to exceed DM 1200 millions in 1997 (CI: 924.2-1536.7), with the treatment of patients with chronic active HBV disease as the major cost determinant. Previously published data from Germany probably overestimated the financial impact of acute HBV infection. In summary, our results illustrate the ongoing economic importance of this potentially life-threatening, but preventable disease and support the call for more accurate HBV surveillance and control in Germany.

Adult↗

High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum.

Chronic carriers of hepatitis B virus (HBV) usually show hepatitis B surface antigen (HBsAg) in their sera, which is considered the best marker for acute and chronic HBV infection. In some individuals, however, this antigen cannot be detected by routine serological assays despite the presence of virus in liver and peripheral blood. One reason for this lack of HBsAg might be mutations in the part of the molecule recognized by specific antibodies. To test this hypothesis, the HBV S gene sequences were determined of isolates from 33 virus carriers who were negative for HBsAg but showed antibodies against the virus core (anti-HBc) as the only serological marker of hepatitis B. Isolates from 36 HBsAg-positive patients served as controls. In both groups, a considerable number of novel mutations were found. In isolates from individuals with anti-HBc reactivity only, the variability of the major hydrophilic loop of HBsAg, the main target for neutralizing and diagnostic antibodies, was raised significantly when compared with the residual protein (22. 6 vs 9.4 mutations per 1000 amino acids; P<0.001) and with the corresponding region in the controls (22.6 vs 7.5 exchanges per 1000 residues; P<0.001). A similar hypervariable spot was identified in the reverse transcriptase domain of the viral polymerase, encoded by the same nucleotide sequence in an overlapping reading frame. These findings suggest that at least some of the chronic low-level carriers of HBV, where surface antigen is not detected, could be infected by diagnostic escape mutants and/or by variants with impaired replication.

Amino Acid Substitution↗

[Diphtheria antitoxin level 2 years after booster vaccination].

In a prospective, controlled, randomized, multicenter study the immunogenicity of a single (day 0) and two (day 0, 28) booster vaccination against diphtheria were compared in subjects who had received their last diphtheria vaccination more than 10 years ago. Both short-term and long-term immunogenicity was assessed by determining diphtheria antitoxin levels four weeks after vaccination and after one and two years. 102 subjects received the first booster vaccination, and 83 were vaccinated twice. Prior to the first vaccination 27% of the subjects had a diphtheria antitoxin level below 0.01 I.U./ml; after the first booster only 5% were unprotected. The second booster did not show a significant effect, however, in 1 of the 5 subjects who were still unprotected after the first booster the second elicited an antitoxin level of more than 0.01 I.U./ml. After one and two years 7% and 8% of the subjects had diphtheria antitoxin level below 0.01 I.U./ml. A serological effect of a second booster vaccination four weeks after the first one could not be demonstrated neither after one nor after two years.

Adolescent↗

Frequency of CD8(+) T lymphocytes specific for lytic and latent antigens of Epstein-Barr virus in healthy virus carriers.

We investigated CD8(+) T cell frequencies of five different Epstein-Barr virus-specific cytotoxic T lymphocyte epitopes located within proteins of the replicative cycle and the latent state in healthy long-term virus carriers with IFN-gamma enzyme-linked immunospot assay. Frequencies of the HLA-A3-restricted epitope RVRAYTYSK (RVR) whose minimal length was mapped in this study to amino acid position 148-156 of the immediate-early protein BRLF1 were compared with those of a further known HLA-A3-restricted epitope within EBNA3A, RLRAEAQVK (RLR). Determination of frequencies of CD8(+) T lymphocytes directed against lytic antigen epitope RVR revealed that only one of eight donors recognized this epitope. Frequency was calculated to be 65 RVR-specific CD8(+) T lymphocytes per 10(6) PBMC. None of the HLA-A3-positive donors exhibited IFN-gamma release after antigenic stimulation with the EBNA3A-specific peptide epitope RLR. Furthermore, we chose three known HLA-B8-restricted epitopes, RAKFKQLL (RAK), FLRGRAYGL (FLR), and QAKWRLQTL (QAK), of the lytic protein BZLF1 and the latent protein EBNA3A. Examination of eight HLA-B8-positive virus carriers revealed that the BZLF1-specific epitope RAK was recognized by all donors with a median frequency of 233 RAK-specific CD8(+) T lymphocytes per 10(6) PBMC. Only 50% of these donors reacted against EBNA3A-specific epitope FLR and a minority (25%) reacted against EBNA3A-specific epitope QAK.

CD8-Positive T-Lymphocytes↗

Diphtheria booster vaccination: one or two injections?

In a prospective, controlled, randomized, multicenter study the immunogenicity and tolerance of a single vaccination (day 0) and two (day 0, 28) booster vaccinations against diphtheria were compared in subjects who had received their last diphtheria vaccination more than 10 years ago. 415 subjects received the first booster vaccination, and 203 were vaccinated twice. The geometric mean diphtheria antitoxin concentration after the first booster (day 28) was 2.354 I.U./ml, and after the second booster (day 56) 2.238 I.U./ml. Prior to the first vaccination 48.9% of the subjects had a diphtheria antitoxin level below 0.1 I.U./m; after the first and second boosters 95.4% and 97.5% of subjects, respectively, showed a level of at least 0.1 I.U./ml. A clear serological effect of a second booster 4 weeks after the first one could not be demonstrated.

Adolescent↗

A novel deletion mutant of hepatitis B virus surface antigen.

HBsAg is the most important serological marker for acute or chronic hepatitis B. Nevertheless, there are reports of HBsAg-negative virus carriers, either with anti-HBc as the only marker for hepatitis B virus (HBV) infection or even positive for anti-HBs and anti-HBc. We report isolates from a patient, in which a deletion in the HBs-gene was associated with persisting viremia in the presence of anti-HBs. The 62-year-old female, infected most likely by her husband, had detectable markers of chronic active hepatitis B, such as HBsAg, HBeAg, and anti-HBc-IgM, for 2 years. The patient then seroconverted to anti-HBs, although HBeAg and anti-HBc-IgM remained detectable. At this time, semiquantitative polymerase chain reaction showed about 10(4) viral genomes per milliliter of serum. Direct sequencing of the amplified products revealed a major population of DNA molecules with a deletion of nucleotide 31 of the HBs-gene, which up to now has not been described. This deletion led to a frame-shift and introduced a stop-codon after 21 amino acids of the sHBsAg. We suspect that this deletion, and the resulting HBsAg lacking the major epitopes recognized by specific antibodies, could favor ongoing viral replication, despite the presence of anti-HBs. However, because the reading frame of the polymerase was also severely damaged by this deletion, it is assumed that a minor population of intact genomes was present to help in the formation of virus particles.

Amino Acid Sequence↗

Prevalence of antibodies against hepatitis C virus in the adult German population.

OBJECTIVE: The prevalence of anti-HCV in Germany has been determined for blood donors and certain risk groups, but the burden of disease in the general population remains unknown. The aim of this study was to determine the prevalence of anti-HCV in a study group representing the normal adult German population. DESIGN: A total of 5312 individuals aged 18-70 years were randomly selected from small, middle-sized and big cities in five different German states. Sera were tested for anti-HCV by enzyme immunoassay and immuno dot assay, as well as for anti-HBc and, in the case of a positive result, for anti-HBs and HBsAg. Serological typing was performed in anti-HCV-positive persons. RESULTS: Thirty-nine individuals were anti-HCV positive; indeterminate results (with antibodies against the viral core protein only) were obtained in 20. There was a tendency to higher prevalence rates with increasing age as well as to a higher prevalence in women. Serological typing revealed the presence of genotype 1 in the vast majority of participants (82%); only a minority showed genotype 3 (7.2%) or other genotypes (7.2%). Markers of HBV were seen in 43.6% of the anti-HCV positive individuals, with nearly one third (29.4%) of the double-infected showing anti-HBc as the only marker for HBV. CONCLUSIONS: According to our data, an anti-HCV prevalence of 0.63% (95% confidence interval, CI, 0.42-0.84%) can be assumed in the general adult German population, with higher values in older people and women. Nearly half of the anti-HCV positive individuals also show markers of hepatitis B virus.

Adolescent↗