Immunogenicity and safety of a pediatric dose of a virosome-adjuvanted hepatitis A vaccine: a controlled trial in children aged 1-16 years.

BACKGROUND: The availability of pediatric formulations of hepatitis A virus (HAV) vaccines would facilitate the introduction of universal mass vaccination against HAV. The objective of this study was to compare a pediatric dose (0.25 mL) of Epaxal, a virosomal, aluminum-free HAV vaccine, to 0.5 mL standard dose, and to alum-adsorbed HAV vaccine. METHODS: Subjects aged 1-16 years, stratified for age, were randomized (2:2:1) into group A (0.25 mL Epaxal), group B (0.5 mL Epaxal), or group C (Havrix Junior). Vaccines were administered at months 0, 6. Seroprotection rates (>or=10 mIU/mL anti-HAV antibodies) were assessed for noninferiority, defined as lower limit of 1-sided 97.5% CI >-10%. Incidence of local solicited adverse events and unsolicited adverse events were recorded. RESULTS: Mean age of 308 enrolled subjects was 8.9 years (range, 1.0-17.0 years). All 3 vaccines were highly immunogenic. Noninferiority of group A versus group B and group C with regard to seroprotection was demonstrated after both vaccine doses for the entire study group and for all age subgroups (11-23 months, 2-4, 5-7, 8-10, 11-13, 14-16 years). One month after first vaccination, geometric mean antibody concentrations were 69.0, 83.5, and 50.5 mIU/mL for the 3 groups, respectively (A versus B, P = 0.0208; A versus C, P = 0.0015). Local injection site pain occurred more frequently in group C than in groups A and B. No subjects withdrew from study or reported any vaccine-related serious adverse event. CONCLUSION: In children aged 1-16 years, 0.25 mL dose of Epaxal is as immunogenic as standard 0.5 mL dose and Havrix Junior. The aluminum-free vaccine compares favorably to comparator vaccine regarding local reactogenicity.

Isolate KAV: a new genotype of the TT-virus family.

A novel DNA sequence belonging to a new genotype of TT virus (TTV) was detected by long-distance PCR in the serum of a chronically HCV-infected patient. The isolate was designated KAV according to the patient's initials. Extending the sequence to full length revealed a 3705-nt viral genome, which is about 100 nucleotides shorter than the other TT-viruses. KAV showed common features with the TTV family, such as the organization of open reading frames and conserved noncoding regions. The largest open reading frame of KAV (ORF 1) was about 40 aa shorter than that of other TT-viruses. Overall sequence homology with known TTV isolates was less than 66%. Phylogenetic analysis poses KAV in one major group with three recently published TTV sequences. So KAV can be considered as a new genotype of the TTV family (provisionally designated genotype 28).

[Detection of antibodies to the nucleocapsid protein of Hepatitis C virus by immunoenzyme analysis using synthetic peptides of nucleocapsid N-terminal part]. / Opredelenie antitel k nucleokapsidnomu belku virusa gepatita C metodom immunofermentnogo analiza na osnove sinteticheskikh peptidov iz N-kontsevoi chastinukleokapsidnogo peptida.

Solid-phase synthesis of 7 linear peptides overlapping the immunodominant N-terminal region of hepatitis C virus (HCV) core protein (aa 7-75) was carried out. Their antigen reactivity was studied by non-competitive ELISA with sera from patients with chronic HCV infection. Three B-epitopes located within aa 7-19, 20-34, and 39-75 appeared to be the most immunoreactive. Use of the set of synthetic peptides in ELISA detected anti-HCV core antibodies with 93% efficiency in comparison with ELISA and commercial anti-HCV Recomblot based on the use of commercial recombinant HCV core protein.

The natural course of hepatitis C virus infection 18 years after an epidemic outbreak of non-A, non-B hepatitis in a plasmapheresis centre.

BACKGROUND: The natural history of hepatitis C virus (HCV) infection is variable and factors determining the course of the illness are unclear. AIMS: To determine the natural course of HCV infection in a well characterised group of patients 18 years after an epidemic outbreak of non-A, non-B hepatitis at a plasmapheresis centre. METHODS: Between 1994 and 1996, 20 of 30 affected individuals were studied. HCV infection was confirmed using second and third generation ELISA test kits. HCV RNA was detected by a polymerase chain reaction (PCR) method and HCV genotyping was performed by analysing amplicons from the conserved 5'-non-translated region generated by nested PCR. Thirty two liver biopsies were carried out in 14 patients. RESULTS: HCV antibodies were detected in all subjects. Eighteen patients had abnormal liver enzymes and 17 were HCV RNA positive, all of whom were infected with genotype 1a. Ninety per cent of this cohort showed evidence of chronic HCV infection with 50% having progressive liver disease and 20% cirrhosis 18 years after acute onset of non-A, non-B hepatitis. Considerable variation in disease outcome occurred between individuals and no correlation with clinical features of the acute illness was found. CONCLUSIONS: Variability in the consequences of HCV infection in cases infected with the same virus suggests that host factors are important in determining disease outcome. The factors which determine differences in the natural history of the disease still remain to be elucidated.

Thunderclap headache caused by Erve virus?

Systematic studies of a possible human neuropathogenicity of the Erve virus have not yet been carried out. In a randomized, blind study 166 patients with viral encephalitis, 46 patients with cerebral hemorrhage, 72 patients with "thunderclap" headache, and 205 healthy blood donors were examined by indirect immunofluorescence for Erve virus antibodies. None of the patients with encephalitis, two patients with cerebral hemorrhage (4.3%), 10 patients with thunderclap headache (13.9%; p < 0.0001), and two blood donors (1.0%) exhibited antibodies against the Erve virus. These results suggest a human pathogenicity of the Erve virus for the first time.

[Hepatitis C virus: results of detection in several high risk groups in the X region of Chile]. / Virus hepatitis C: resultados de detección en algunos grupos de riesgo en la X región de Chile.

The aim of this study was to determine the prevalence of hepatitis C virus antibodies in high risk patients coming from Valdivia, Osorno and Puerto Montt. Fifty-six patients in hemodialysis, 51 renal graft recipients, 42 cirrhotics and 14 patients with acute non A non B hepatitis were studied. Antibodies were detected with a second generation ELISA technique and positive cases were confirmed with RIBA. All hemodialysis patients and renal graft recipients were negative for hepatitis C virus antibodies. In one non alcoholic patient with cirrhosis, a positive ELISA was confirmed with RIBA. Six patients with acute hepatitis had positive ELISA tests but none was confirmed with RIBA. It is concluded that the prevalence of hepatitis C virus antibodies in this region of Chile is very low.

[Acute sporadic hepatitis caused by the E virus in Chile. Clinical case]. / Hepatitis aguda esporádica por virus E en Chile. Caso clínico.

A 53 year old female nurse presenting with malaise, jaundice and pruritus is reported. Physical examination only disclosed jaundice and laboratory values showed an ALT of 445 U/l, ASAT of 179 U/l, alkaline phosphatases of 455 U/l and a total bilirubin of 7.7 mg/dl. Serological markers for hepatitis virus E were positive and negative for hepatitis virus A, B and C, cytomegalovirus and Epstein Barr virus. The patient recovered fully in 10 weeks and is asymptomatic after 5 years of follow up. Health care workers probably have a higher risk for hepatitis E than the general population and this is the first acute sporadic case described in Chile.

[Natural history of viral hepatitis A in Chilean adults: clinical and laboratory aspects]. / Historia natural de la hepatitis viral A en adultos en Chile: clínica y laboratorio.

In many countries, Hepatitis is mainly due to virus. A. When improving life condition in a given population, initially there is a tendency to increase the number of cases in adults. We report clinical and laboratory findings in 87 adults with acute viral Hepatitis A in Chile. The rate man/woman was 1.55/1. Mean age: 23.8 years. Clinical forms: icteric classical (77.01%), cholestatic (10.34%), anicteric (8.05%), biphasic (2.30%) and fulminant (2.30%). From 87 patients in consult 1, 64 were controlled at day 15 (consult 2) and 35 one year later (consult 3). Laboratory (means): ALT (UI/L): 856.8, 111.6 and 20.8 in consult 1, 2 and 3 respectively. Correlation between values of ALT and AST (p < 0.0001). Mean total bilirubin (mg%): 6.6, 2.5 and 0.8 respectively. The evolution of Hepatitis A was favorable with a rapid decrease of clinical signs and normalization of laboratory values within the 3 first weeks of disease.

[Post-transfusion hepatitis iin Chile: the reference parameters]. / Hepatitis postransfusional en Chile: parámetros de referencia.

Most cases of post-transfusion hepatitis correspond to infection by non-A non-B virus. Indirect test (ALT elevation, anti-HBc titers) have been used to detect the presence of this virus. We screened 692 blood donors and health personnel, measuring anti-HBc (n = 572), HBs antigen (340), and ALT serum levels (190). Positive results were obtained for anti-HBc in 1.7% and HBs in 0%. ALT levels were 25 +/- 12 u/l in males and 18 +/- 14 in females (p < 0.01). ALT levels above 45 u/l were found in 6% of subjects. ALT levels were not related to anti-HBc positiveness nor to alcohol intake. The possible risk of posttransfusion hepatitis related to increased ALT levels remains to be clarified by specific markers.

[Determination of hepatitis B E antigens, anti-hepatitis B E and Dane particles in the serum of hepatitis B S carriers and patients with chronic hepatitis B S antigen-positive hepatitis]. / Nachweis von HBeAG, Anti-HBe and Dane-Partikeln im Serum von HBs-Trägern und bei Patienten mit chronischer HBsAg-positiver Hepatitis.

The correlation of HBeAg, anti-HBe, Dane particles and results of light microscopy of liver biopsies have been studied in 109 patients with chronic HBV infection and in 21 HBsAg carriers. The following conclusions may be drawn: 1. There is a good correlation between the presence of HBeAg and Dane particles. 2. Patients with both of these markers often have chronic active or lobular hepatitis. 3. The presence of anti-HBe points in 80% of these cases to a carriership or chronic persistent hepatitis. 4. 60% of patients without an HBe-marker and 20% of patients with anti-HBe exhibit presence of Dane particles.

Prevalance of antibody to hepatitis B surface antigen in various populations.

Sera from individuals with different degrees of exposure to the agent of hepatitis B were tested for antibodies to hepatitis B surface antigen (anti-HB-s) by passive hemagglutination and for hepatitis B surface antigen (HB-s Ag) by radioimmunoassay and immunoelectroosmophoresis. In a plasma fractionation plant, anti-HB-s was detected in 82 percent of workers processing human plasma and 3.3 percent were healthy carriers of the antigen. Fifty-six percent of the workers having only casual contact with plasma processing exhibited anti-HB-s and 24 percent of workers with no contact had anti-HB-s, yet HB-s Ag was not found in either of these two groups of workers. A similar correlation was shown in hospital personnel; 31 percent of employees with direct contact to serum specimens and only 8 percent without direct contact had anti-HB-s. The frequency of HB-s Ag (0.8 percent in patients with disorders not involving the liver; 49.8 percent in patients tentatively diagnosed as viral hepatitis) and anti-HB-s (14.5 percent to 28.5 percent, respectively) in selected groups of hospitalized patients varied greatly. In 508 paid blood donors, anti-HB-s was present in 19.9 percent, whereas it was present in only 6.6 percent of 1,146 volunteer donors. These data demonstrate a correlation between frequency of exposure to human blood or blood products and the prevalence of anti-HB-s.

Evaluation of passive hemagglutination, solid-phase radioimmunoassay, and immunoelectroosmophoresis for the detection of hepatitis B antigen.

Sensitivity and specificity of passive hemagglutination (RCA), solid phase radioimmunoassay (RIA), and immunoelectroosmophoresis (IEOP) were compared under experimental and clinical conditions. In dilution experiments with sera containing hepatitis B antigen (HB Ag) of known subtypes, the sensitivity for an ad subtype serum was RIA (1), RCA (1/2), IEOP (1/256) and for an ay subtype serum RCA (1), RIA (1/8), IEOP (1/128). An evaluation of the National Institutes of Health, Division of Biologics Standards test panel number 2 demonstrated HB Ag in 34 of 60 samples by RIA, in 33 by RCA, and in 25 by IEOP. HB Ag was detected in 57.5% of 200 outpatients with a tentative diagnosis of hepatitis by RIA, in 54% by RCA, and in 42.5% by IEOP. In 1,661 volunteer blood donors, 13 (0.78%) were "positive" for HB Ag by RIA, 11 (0.66%) by RCA, and 3 (0.18%) by IEOP. However, absorption experiments indicated that at least six of the above RIA positive and five of the RCA positive sera exhibited nonspecific positive reactions.