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The standard treatment for patients with chronic hepatitis C is a 6–12-month combination therapy with interferon alpha and ribavirin. Induction treatment could result in a faster early decline of the hepatitis C virus (HCV) load and a better response rate. Naive chronically infected HCV patients ( n = 454) were randomized into two arms to receive either induction treatment with interferon alpha 2b 5 million units (MU) subcutaneously (s.c.) daily during a period of 8 weeks (arm A); or treatment with interferon alpha 2b 5 MU s.c. three times a week (TIW) for a period of 8 weeks (arm B). After week 8, interferon treatment in both arms was 3 MU s.c. TIW for a total period of 12 months. In both arms, ribavirin (1000–1200 mg orally per day) was added at week 4. Induction treatment resulted in a higher virological response at week 8 of treatment (66% vs 47%; P < 0.01). However, response at the end of treatment and at 6 months follow-up was not different (53% vs 50%, 41% vs 33%). The occurrence of adverse events and the drop-out rate were similar in both arms. Although an early virological response is observed more frequently in the induction treatment, end of treatment response and sustained responses did not differ. [ABSTRACT FROM AUTHOR]

A weakness of the hu-PBL–SCID model for the study of human immune functions is the appearance of anergy and the consequent loss of T cell function. We demonstrate here that human T cells retain normal functions during the early stage of chimerism. At 1 and 2 weeks post-engraftment, T cells isolated from the peritoneal cavity of hu-PBL chimeras could be activated and proliferated upon stimulation with phytohaemagglutinin (PHA) or specific antigens to which the cell donor was known to be immune. T cells derived from hu-PBL–SCID and hu-PBL–NOD/LtSz-scid (NOD/SCID) mice not only proliferated but also produced interferon-gamma (IFN-γ) and IL-5 following in vitro stimulation with tetanus toxoid (TT) or hepatitis B surface antigen (HBsAg). These antigen-specific T cells could only be demonstrated when cognate antigen was administered together with or immediately following the PBL transfer. Without an early rechallenge with antigen in vivo, no TT- or HBsAg-specific T cell responses could be elicited, showing the vulnerability and antigen-dependence of the T cell response. Vigorous anti-TT or anti-HBs responses could be observed in all chimeras. Administration of antigen together with the PBL graft enhanced the humoral anti-TT response in SCID and NOD/SCID mice but had little effect on the anti-HBs antibody response in NOD/SCID mice. These data confirm the observation that the B cell compartment in hu-PBL–SCID chimera is largely antigen-independent and extend this to SCID/NOD. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on an article about tumor necrosis factor in sepsis.

Abstract: The chimeric uPA+/+-SCID mouse model, transplanted with human hepatocytes, was previously validated as an alternative tool to study in vivo the human steroid metabolism. This humanized mouse model was now applied, in the framework of anti-doping research, to test different nutritional supplements containing steroids. These steroids, intentionally or accidentally added to a nutritional supplement, usually are derivatives of testosterone. Information about the metabolism of these derivatives, which is important to assure their detection, is quite limited. However, due to ethical constraints, human volunteers cannot be used to perform experimental excretion studies. Therefore the chimeric mice were selected to perform three separated excretion studies with superdrol (methasterone), promagnon and also methylclostebol. The urine of the humanized mice was collected 24h after a single dose administration and analyzed by gas chromatography–mass spectrometry (GC–MS). The results indicated the presence of several metabolites including a 3-keto reduced metabolite and numerous hydroxylated metabolites. Also phase 2 metabolism was investigated to update the complete picture of their metabolism. [Copyright &y& Elsevier]

Successful transplantation of xenogeneic hepatocytes into uPA-transgenic SCID mice depends on the zygosity of the recipient mice. Normally, the difference between homozygous and heterozygous animals is determined via a quantitative Southern blot. We sequenced a part of the mouse genome that is eliminated upon integration of the transgene in the genome. Based on that sequence we developed a multiplex PCR that allows the unambiguous discrimination of negative, heterozygous, and homozygous uPA-transgenic SCID mice in a single day procedure. The speed of the procedure is an essential quality because transplantation of xenogeneic hepatocytes into uPA-SCID mice should be done as soon as possible after birth. [Copyright &y& Elsevier]

Vaccination against hepatitis B virus (HBV) immediately after birth prevents neonatal infection by vertical transmission from HBV carrier mothers. There is an ongoing debate whether infant vaccination is sufficient to protect against infection when exposed to HBV later in life. We studied 222 Thai infants born to HBsAg −/+ and HBeAg −/+ mothers who were vaccinated with recombinant hepatitis B vaccine at 0-1-2-12 months of age. A subset of 100 subjects received a booster dose at age 5 years. Blood samples collected yearly for 20 years were examined for anti-HBs antibodies and serological markers of hepatitis B infection (anti-HBc, HBsAg, and in selected cases HBeAg, anti-HBe, HBV DNA). During the 20-year follow-up, no subject acquired new chronic HBV infection or clinical hepatitis B disease. During the first decade, possible subclinical breakthrough HBV infection (anti-HBc seroconversion) was only observed in subjects born to HBsAg +/HBeAg + mothers (6/49 [12.2%]). During the second decade, breakthrough HBV infections were detected in all groups (18/140 [12.8%]). Increases in anti-HBs concentrations that were unrelated to additional HBV vaccination or infection were detected in approximately 10% of subjects in each decade. Primary infant vaccination with a recombinant hepatitis B vaccine confers long-term protection against clinical disease and new chronic hepatitis B infection despite confirmed hepatitis B exposure. ( NCT00240500 and NCT00456625) [ABSTRACT FROM AUTHOR]

In order to study the hepatitis C virus (HCV) epidemiology in Flanders, Belgium, the HCV genotype of 2,301 patients diagnosed with HCV between 2001 and 2009 was determined. HCV genotyping was conducted using the Versant LiPA 1.0 or Versant LiPA 2.0 assay. To explore the transmission history of a remarkable cluster of the rarely found HCV genotype 5a, face-to-face interviews based on detailed questionnaires and maximum likelihood phylogenetic analysis were performed. HCV genotype 1 was the most prevalent genotype in all provinces, followed by HCV genotype 3 in East Flanders, Antwerp, Flemish Brabant and Limburg. In Brussels, HCV genotype 4 was the second most prevalent genotype. This observation is due to the immigration of patients from the Middle East and Africa. Remarkably, a cluster of HCV genotype 5a was found in West Flanders, where it represents the second most prevalent genotype, accounting for 26.2% of HCV infections. We could not identify one major transmission source explaining the whole HCV genotype 5a epidemic. Instead, several smaller possible transmission chains were identified and confirmed phylogenetically. Overall, the HCV genotype 5a epidemic in West Flanders seems to be mainly associated with blood transfusion and unsafe medical practices. [ABSTRACT FROM AUTHOR]

Abstract: A quantitative method based on gas chromatography–mass spectrometry (GC–MS) has been developed for the detection of 16 endogenous androgens in the urine of mice. The substances are extracted from 100μL urine with freshly distilled diethyl ether after alkalinisation. The substances are derivatised with a mixture of N-methyl-N-trimethylsilyltrifluoroacetamide/NH4I/ethanethiol (383/1/2, v/w/v) and detected by GC–MS in the selected ion monitoring mode. The results of the method validation indicate good linearity, accuracy and precision, making the method suitable for the quantification of endogenous androgens in mouse urine. The selectivity of the method showed that no interfering peaks were observed at the retention times of the analytes. The method allows for the direct quantification and identification of testosterone and 15 other endogenous androgens at low concentrations (ng/mL) in mouse urine. The applicability of the method is shown by the analysis of a mouse urine. Several endogenous steroids could be detected. [Copyright &y& Elsevier]

BACKGROUND: Antigen sparing is regarded as crucial for pandemic vaccine development because worldwide influenza vaccine production capacity is limited. Adjuvantation is an important antigen-sparing strategy. We assessed the safety and immunogenicity of a recombinant H5N1 split-virion vaccine formulated with a proprietary adjuvant system and investigated whether it can induce cross-reactive immunity. METHODS: Two doses of an inactivated split A/Vietnam/1194/2004 NIBRG-14 (recombinant H5N1 engineered by reverse genetics) vaccine were administered 21 days apart to eight groups of 50 volunteers aged 18-60 years. We studied four antigen doses (3.8 microg, 7.5 microg, 15 microg, and 30 microg haemagglutinin) given with or without adjuvant. Blood samples were collected to analyse humoral immune response. Adverse events were recorded up through study day 51. Safety analyses were of the whole vaccinated cohort and immunogenicity analyses per protocol. This trial is registered with the ClinicalTrials.gov, number NCT00309634. FINDINGS: All eight vaccine formulations had a good safety profile. No serious adverse events were reported. The adjuvanted vaccines induced more injection-site symptoms and general symptoms than did the non-adjuvanted vaccines, but most were mild to moderate in intensity and transient in nature. The adjuvanted formulations were significantly more immunogenic than the non-adjuvanted formulations at all antigen doses. At the lowest antigenic dose (3.8 microg), immune responses for the adjuvanted vaccine against the recombinant homologous vaccine strain (A/Vietnam/1194/2004 NIBRG-14, clade 1) met or exceeded all US Food and Drug Administration and European Union licensure criteria. Furthermore, 37 of 48 (77%) participants receiving 3.8 microg of the adjuvanted vaccine seroconverted for neutralising antibodies against a strain derived by reverse genetics from a drifted H5N1 isolate (A/Indonesia/5/2005, clade 2). INTERPRETATION: Adjuvantation conferred significant antigen sparing that could increase the production capacity of pandemic influenza vaccine. Moreover, the cross-clade neutralising antibody responses recorded imply that such a vaccine could be deployed for immunisation before a pandemic. [ABSTRACT FROM AUTHOR]

Abstract: Analyses of cellular immune responses during natural infections and following vaccination with established or candidate vaccines are becoming increasingly important and so are the research tools used to achieve this goal. During a recent evaluation of the analytical performance characteristics of one of these techniques, the interferon-γ secretion assay, we noticed that following overnight incubation of PBMC with recall antigens (varicella-zoster antigen, Candida albicans antigen or hepatitis B surface antigen) NK cells are frequently the most predominant interferon-γ-producing cell population. In this study, we monitored the subset distribution of interferon-γ-producing cells following more extended in vitro culture periods and found that, irrespective of the antigen applied, the contribution of NK cells decreased whereas the importance of T cells and NKT cells rose. Analysis of the subset distribution showed that HBsAg stimulated CD4 cells predominantly whereas Candida antigen and varicella-zoster antigen were better inducers of CD8 responses. No correlation was found between the kinetics of total number of interferon-γ-producing cells and the changes of concentrations of interferon-γ in the culture supernatants. Interferon-γ levels in culture supernatants correlated strongly with the kinetics of TH lymphocytes (CD3+, CD4+), CTL (CD3+, CD8+), and NKT cells (CD3+, CD56+). These observations lead us to conclude that methods that enumerate cytokine-secreting cells without determining their phenotype should be interpreted with great care and that an ‘elispot’ should not be directly considered as the footprint of a T lymphocyte. [Copyright &y& Elsevier]

Burnett RJ, François G, Kew MC, Leroux-Roels G, Meheus A, Hoosen AA, Mphahlele MJ. Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: a call for further investigation.Liver International DOI: 10.1111/j.1478-3231.2005.01054x.© Blackwell Munksgaard 2005A growing body of evidence indicates that human immunodeficiency virus (HIV)-positive individuals are more likely to be infected with hepatitis B virus (HBV) than HIV-negative individuals, possibly as a result of shared risk factors. There is also evidence that HIV-positive individuals who are subsequently infected with HBV are more likely to become HBV chronic carriers, have a high HBV replication rate, and remain hepatitis Be antigen positive for a much longer period. In addition, it is evident that immunosuppression brought about by HIV infection may cause reactivation or reinfection in those previously exposed to HBV. Furthermore, HIV infection exacerbates liver disease in HBV co-infected individuals, and there is an even greater risk of liver disease when HIV and HBV co-infected patients are treated with highly active anti-retroviral therapy (HAART). Complicating matters further, there have been several reports linking HIV infection to‘sero-silent’ HBV infections, which presents serious problems for diagnosis, prevention, and control. In sub-Saharan Africa, where both HIV and HBV are endemic, little is known about the burden of co-infection and the interaction between these two viruses. This paper reviews studies that have investigated HIV and HBV co-infection in sub-Saharan Africa, against a backdrop of what is currently known about the interactions between these two viruses. [ABSTRACT FROM AUTHOR]

The mechanisms causing non-responsiveness to hepatitis B surface antigen (HBsAg) vaccines in man remain elusive. The increased incidence of non-responsiveness in subjects with HLA-DR3+ or -DR7+ haplotypes suggests that immune response mechanisms governed by genes of the MHC are involved. Homozygotes for these two haplotypes are found almost exclusively in the non-responder (NR) population. It is conceivable that antigen-presenting cells (APC) of NR are defective in the uptake of HBsAg and that they are unable to present this Ag adequately. Previously, we demonstrated thatDR2+,DR7+ andDP4+ NR were able to present HBsAg. In the present paper we demonstrate that six DR0301+ NR, five of which are homozygous for this marker, were able to take up, process and present HBsAg to HBsAg-specific, DR0301-restricted T cell lines. Non-fractionated peripheral blood mononuclear cells (PBMC) from the DR0301+ NR did not proliferate to HBsAgin vitro, whereas they proliferated vigorously upon stimulation with tetanus toxoid, thus ruling out the presence of a generalized immunodeficiency. We therefore conclude that HLA-DR0301+ NR vaccinees are not deficient in their HBsAg-presentation. Because it was demonstrated that recently activated T cells can apparently bypass the requirement for B7, we may have overlooked the role of the B7-co-stimulation in our set-up that used HBsAg-specific T cell lines. Therefore we examined the expression of B7 co-stimulatory molecules on NR-APC. CD86 was normally present on these cells and was not down-regulated after culturing the PBMC in the presence of HBsAg. We conclude that CD86 expression on CD14+ monocytes of DR0301- and DR07-homozygous poor responders is not deficient and cannot be the mechanism underlying the non-responsiveness of these subjects. [ABSTRACT FROM AUTHOR]

Hepatitis B surface antigen, when produced in yeast (rHBsAg), is capable of binding to cells that express the lipopolysaccharide coreceptor CD14. This interaction is enhanced by a serum protein, the lipopolysaccharide binding protein (LBP). Here we report that most of the rHBsAg particles that attached to monocytes at 0?°C, were not endocytosed but were released back into the serum-containing binding buffer at 37?°C. Additionally, serum-dependent binding at 37?°C was weak when compared to the serum-dependent attachment at 0?°C. Pre-incubation at 37?°C of cells together with serum did not abolish binding of freshly added rHBsAg at 0?°C. However, pre-incubation of rHBsAg with serum at 37?°C reduced attachment to cells following incubation at 0?°C. Soluble CD14 and LBP, two serum proteins which can act as phospholipid transfer molecules, were shown not to be responsible for the inhibitory effect. Pre-incubation at 37?°C of rHBsAg in serum-free hepatoma cell line-conditioned media resulted in a pronounced reduction in subsequent binding to cells at 0?°C. These observations suggest that the temperature-dependent inhibitory effect is caused by serum factors that are probably secreted by hepatocytes. [ABSTRACT FROM AUTHOR]

In spite of advances made in our understanding of the biology of the hepatitis C virus (HCV), the epidemiology and natural history of HCV infection, and the treatment of chronic hepatitis C, the development and worldwide implementation of a comprehensive prevention and control strategy remains necessary. A World Health Organization informal consultation with the Viral Hepatitis Prevention Board was convened and met in Geneva, Switzerland, 13-14 May 2002, to review epidemiological and public health aspects of HCV infection, and the various prevention and control strategies that are currently in place. Based on the presentations and discussions, a number of specific recommendations were made, which should be considered in conjunction with previously published recommendations. [ABSTRACT FROM AUTHOR]

Different single-cell analyses for the detection of antigen-specific T cells based on antigen-triggered induction of cytokine production (elispot, intracellular cytokine staining, cytokine secretion assay, etc.) have been analyzed. In this paper we present the data of a thorough validation of the IFNγ Secretion Assay (ISA, Miltenyi Biotec, Bergisch Gladbach, Germany). In this assay the secreted IFNγ is bound to the cell surface and is then stained as an artificial surface molecule and analyzed by flow-cytometry. The introduction of five quality criteria markedly improved the reproducibility of this assay and made it very reliable (intra-assay variability<5%; inter-assay variability<20%). Recovery experiments further demonstrated that almost 100% of IFNγ+ labeled cells could be detected by this technology. In order to analyze which cell subsets contribute to IFNγ-production, we compared the results obtained in different individuals after VZAg-stimulation. Three different IFNγ-secretion patterns could be discerned. In Pattern 1 there is a predominant and almost equal contribution of T cells and NK cells with a minor contribution of CD3+CD56+ and B cells. Pattern 2, which is most abundant, is characterized by a predominance of NK cells (60–70%). Pattern 3 differs from the previous one in its minor contribution of NK cells. Here T cells predominate the IFNγ secretion. These results clearly demonstrate that the IFNγ+ subset distribution after VZAg-stimulation is not uniform and differs individually. Furthermore, the ISA-technology proves to be very useful in vaccine research. This was demonstrated by testing the IFNγ+ secretion pattern after HBsAg-stimulation in PBMC from HBsAg-vaccinated individuals. [Copyright &y& Elsevier]

Hepatitis A is one of the most common vaccine-preventable infectious diseases in the world. Effective vaccines against hepatitis A have been available since 1992, and they provide long-term immunity against the infection. However, there is no worldwide consensus on how long protection will last or whether there will be a need for hepatitis A virus (HAV) booster vaccinations in the future. In most countries, booster-vaccination policy is guided by manufacturers' recommendations, national authorities, or both. In June, 2002, a panel of international experts met to review the long-term immunogenicity and protection conferred by HAV vaccine in different population groups. Data have shown that after a full primary vaccination course, protective antibody amounts persist beyond 10 years in healthy individuals, and underlying immune memory provides protection far beyond the duration of anti-HAV antibodies. The group concluded that there is no evidence to lend support to HAV booster vaccination after a full primary vaccination course in a healthy individual. However, further investigations are needed before deciding if boosters can be omitted in special patient-groups. [ABSTRACT FROM AUTHOR]

Approximately 5% of vaccinees display an inadequate response after the administration of the standard three dose hepatitis B vaccine. A new hepatitis B vaccine (HBsAg/AS04) formulated with the adjuvant AS04 which contains 3′-deacylated monophosphoryl lipid A (3D-MPL) and alum has been developed. AS04 enhances the immune response which may be beneficial to non-responders. In a single-blind, randomised study, we tested the immunogenicity and reactogenicity of the new vaccine with that of commercially established hepatitis B vaccine, both on a 0, 1, 6 months schedule in 20–60 years old non-responders (titre <10 mIU/ml after four doses of hepatitis B vaccine). One month after the first dose the seroprotection rate was 44% for group 1 (58 subjects) receiving the established vaccine versus 66% for group 2 receiving HBsAg/AS04 (57 subjects) (P=0.03). One month after the second dose this was 58 and 81%, respectively (P<0.005) and 1 month after the third dose this was 68 and 98%, respectively (P<0.001). One month after each dose, GMTs were 34, 56 and 111 mIU/ml for group 1 versus 123, 222 and 1937 mIU/ml for the HBsAg/AS04 group (P<0.05, <0.01 and 0.0001, respectively). Pain at the injection site was the most commonly reported local symptom and very few symptoms were scored as severe. In this group of adult non-responders to previous hepatitis vaccination, the HBsAg/AS04 vaccine was well tolerated and induced, at all time-points, a superior immune response compared to the licensed hepatitis B vaccine. [Copyright &y& Elsevier]

Summary Background : In patients with chronic hepatitis C, elevations in serum iron levels, hepatic iron content and oxidative stress-related molecules have been reported. Treatment with ribavirin induces an increase in hepatic iron concentration. In situations of iron overload, non-transferrin-bound iron can appear. Therefore, we determined non-transferrin-bound iron levels in untreated chronic hepatitis C patients and in patients during interferon–ribavirin treatment. Materials and methods : In 10 untreated and 19 interferon–ribavirin-treated chronic hepatitis C patients, we examined non-transferrin-bound iron levels by a colorimetric method using nitrilotriacetic acid as a ligand and sodium triscarbonatecobalt(iii) to block free iron binding sites on transferrin. Results : Despite the presence of high serum iron saturation and ferritin levels, non-transferrin-bound iron was absent in the majority of hepatitis C virus patients (25/29, 86%). There was no difference in non-transferrin-bound iron levels between untreated and treated patients. Four patients with high non-transferrin-bound iron levels were distinguished by higher serum iron levels. In two of these patients, hepatocytic iron was present on liver biopsy. Conclusions : In the majority of chronic hepatitis C patients, non-transferrin-bound iron levels are normal. Treatment with ribavirin does not induce high non-transferrin-bound iron levels. Non-transferrin-bound iron levels are only higher than normal in hepatitis C patients with higher serum iron levels. [ABSTRACT FROM AUTHOR]

To study the regulation of the human cellular immune response to HBsAg we produced a series of HBsAg-specific T cell lines from good and poor responders to the hepatitis B vaccine. All T cell lines expressed CD4 on their membrane and could therefore be considered of the helper/inducer phenotype. The different HBsAg-specific T cell lines were restricted by HLA-DRB5*0101, DRB1*1201, -DRB1*0701, -DRB1*0301, -DPB1*0201, -DPB1*0402, and -DPB1*0901. In good responders to the hepatitis B vaccine different HLA molecules could act as restricting element. In poor responders the diversity of HLA class II restriction determinants was more limited. This leads us to conclude that the immune response to HBsAg is multispecific and polyclonal in good responders and paucispecific and oligoclonal in poor responders to the hepatitis B vaccine. By using a panel of synthetic peptides representing selected sequences of the HBsAg, the fine specificities of each of these T cell lines could be determined. Strikingly, the majority of the identified T cell epitopes was located in and around the first hydrophobic transmembranous region of the HBsAg. This was observed in T cell lines from good and poor vaccine responders, without distinction. The remarkable T cell immunogenicity of this region may reside in its richness in binding motifs for a variety of HLA class II determinants. [ABSTRACT FROM AUTHOR]

In the rat model of heterotopic auxiliary liver transplantation, graft re-arterialization may influence the outcome of inter-liver competition. This was investigated in the current study using two transplanted groups with or without graft re-arterialization. Immediately after reperfusion, the re-arterialized grafts showed significantly higher bile flow rate and bilirubin excretion than the grafts without re-arterialization. DNA synthesis rate was also increased more drastically in the re-arterialized group following the transplantation. Without re-arterialization, the rats developed more pronounced cytolysis and cholestasis. Among the long-term survivors, all healthy re-arterialized grafts regenerated, whereas 5/6 non-re-arterialized grafts atrophied. These data demonstrate that the re-arterialization increases graft survival by improving early hepatic function, enhancing regenerative response and preventing post-transplant biliary complications in this rat model.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In vitro tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-2 (IL-2) production, serum neopterin levels, and T-lymphocyte subpopulations were determined on a monthly basis in 22 MS patients. We found increased in vitro TNF-α production from 4 weeks on prior to the day of an exacerbation. There was a significant correlation with in vitro IFN-γ release, the absolute blood monocyte count and the serum neopterin levels, suggesting that monocytes stimulated by IFN-γ play an important role in the TNF-α production. Serial analysis of in vitro TNF-α production proved to be a helpful tool in predicting relapses in MS patients. Furthermore, elevated levels of IFN-γ and IL-2 after stimulation with OKT3 during exacerbations were demonstrated. These increases were not reflected by changes in T-lymphocyte subpopulations. However, significant differences in T-cell subsets were observed between controls and relapsing progressive patients. [ABSTRACT FROM AUTHOR]

Quantifying IgG antibodies to pertussis toxin (PT) is the most specific and sensitive method for the serodiagnosis of a Bordetella pertussis infection. Since PT is a component of acellular pertussis vaccines, anti-PT IgG is also induced by vaccination, precluding pertussis serodiagnosis based exclusively on anti-PT IgG in recently vaccinated subjects. Here, we aim to identify additional B. pertussis- specific serological markers that can discriminate between infection and recent vaccination. The clinical usefulness of measuring IgA directed to the vaccine antigen PT and IgG directed to non-vaccine antigens (Fim2/3, LPS, ACT, CatACT) was evaluated in nine well characterized subject groups, aged 10–89 years (n = 390). Serum anti-PT IgG levels (>125 IU/mL) served as an indicator for a recent B. pertussis infection. Comparing symptomatic pertussis-infected subjects (n = 140) with recently vaccinated, non-infected subjects (n = 100) revealed the optimal cut-off, accuracy, sensitivity and specificity for each single parameter. For pertussis diagnosis in recently vaccinated subjects, the measurement of anti-PT IgA (cut-off 15 IU/mL) and anti-ACT IgG (cut-off 15 U/mL) resulted in accuracies of 95% (91.5–97.1) and 87.5% (82.7–91.1), sensitivities of 92.9% (87.4–96.0) and 83.6% (76.5–88.8) and specificities of 98% (93.0–99.4) and 93% (86.3–96.6), respectively. Comparing anti-PT IgA levels between the youngest (10–19 years, n = 38) and oldest (70–89 years, n = 17) age groups revealed an age-dependent increase in antibody levels in pertussis-infected subjects (p < 0.0001). Reflex testing of anti-PT IgA and anti-ACT IgG improves pertussis serodiagnosis in recently vaccinated symptomatic subjects with elevated anti-PT IgG levels. Furthermore, both markers can discriminate between vaccination and recent infection in pertussis serosurveillance studies. [ABSTRACT FROM AUTHOR]

Objectives: To assess to what extent hepatitis B vaccination of sex workers in Ghent, Belgium, is successful within the context of the existing health services and to compare this with alternative approaches such as outreach programmes; to compare two hepatitis B vaccination schemes in the outreach programme for sex workers.Methods: Testing all first contacts (n = 1096) in the outreach programme for hepatitis B virus (HBV) markers assessed success of hepatitis B vaccination in routine services. The performance of the outreach service was measured by counting the number of sex workers who started hepatitis B vaccination in the programme. The hepatitis B vaccination schemes were assessed by analysing the number of people completing the vaccination.Results: Naturally acquired HBV was found in 11.9% of 1096 sex workers (0.6% HBsAg), and 7% were vaccinated in existing services. In contrast, hepatitis B vaccination using outreach methodology was able to achieve higher vaccination rates: among non-immune sex workers 82.8% received the first dose of vaccine, and 71.5% the second. If given 1 month later, 67.9% received the third dose, in contrast with 47.9%, when given 6 months later.Conclusions: Existing services are not successful in vaccinating sex workers for HBV, in contrast with specifically targeted outreach services. Shorter intervals between vaccine doses gave better compliance. [ABSTRACT FROM AUTHOR]