[Show abstract][Hide abstract] ABSTRACT: Nicaragua is highly endemic for hepatitis A. We aimed to provide an estimate of the change in the age-specific risk of hepatitis A virus (HAV) infection based on serological data from cross-sectional and longitudinal samples collected in León, Nicaragua, in 1995/96 (n = 979) and 2003 (n = 494).
The observed age-specific prevalence of anti-HAV antibodies was correlated to the age-specific risk of infection by calculating the probability of freedom from infection at a specific age.
The proportion of seropositive children aged 1.5 to 6 years was 42% in 2003 compared to 67% in 1995/96. Estimated annual risk of infection for a 3-year old child was 30% (95% CI: 27.0%, 33.1%) in 1995 and 15.5% (95% CI: 12.4%, 19.0%) in 2003. There was good agreement between estimates based on cross-sectional and longitudinal data. The age-specific geometric mean of the quantified anti-HAV antibody levels assessed in 2003 was highest at age 4 and decreased steadily up to age 40.
The substantially lower risk of HAV infection in 2003 than in 1995 for young children indicates a beginning transition from high to intermediate endemicity in León, Nicaragua. Consecutive age-stratified serosurveys are useful to assess changes in risk of infection following public health interventions. The decreasing age-specific GMC of anti-HAV antibodies during adulthood in a country with endemic HAV indirectly suggests that ongoing HAV exposure in the community has marginal boosting effect on antibody levels once protective immunity has been established by natural infection.
PLoS ONE 02/2014; 9(2):e87643. DOI:10.1371/journal.pone.0087643 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the immunogenicity of the paediatric dose of Epaxal(®) (0.25 mL) and the degrees of seroprotection achieved with the standard dose (0.5 mL) of Epaxal(®) or a dose of Havrix(®) Junior, in children in an open, randomised, controlled, multi-centre, parallel-group study conducted at 2 Chilean study centres. 360 healthy children and adolescents 12 months to <17 years of age not previously vaccinated against hepatitis A were enrolled. Subjects were randomised 2:2:1 to be vaccinated with either Epaxal(®) 0.25 mL [n=146], Epaxal(®) 0.5 mL [n=142] or Havrix(®) Junior [n=72] intramuscularly on Day 1 and after 6 months (26 weeks±14 days). Primary end point was the proportion of subjects seroprotected (anti-HAV antibody concentration ≥10 mIU/mL) in the ATP population at Month 1. All vaccines elicited high seroprotection rates at Month 1: 95.7% with Epaxal(®) 0.25 mL, 99.3% with Epaxal(®) 0.5 mL and 94.0% with Havrix(®) Junior. After the booster vaccination, all subjects demonstrated 100% seroprotection with all vaccines. Antibody concentrations were similarly high in all age groups. The paediatric presentation achieved antibody concentrations similar to those achieved with the 0.5 mL dose across the entire age range, and there were no differences across the range of body weights from 9.0 kg to 82.7 kg. All study vaccines were well tolerated and there were no AEs leading to discontinuation. Thus, the paediatric 0.25 mL dose of Epaxal(®) fulfilled the primary objective of showing non-inferiority to the adult 0.5 mL dose and to Havrix(®) Junior, in terms of seroprotection rates achieved. The results show the paediatric dose of Epaxal(®) to be an attractive option when conducting childhood-vaccination programmes.
[Show abstract][Hide abstract] ABSTRACT: Boosting adult travelers with the virosome-formulated, aluminum-free hepatitis A vaccine Epaxal up to 128 months after a single primary dose confers full protection against hepatitis A, even in travelers aged 50 years and above. Delaying the booster dose did not influence the immune memory response to Epaxal.
[Show abstract][Hide abstract] ABSTRACT: Few studies have examined the duration of protection following vaccination against hepatitis A virus (HAV) with currently licensed HAV vaccines. This study explored the long-term immunogenicity in individuals vaccinated with the virosomal hepatitis A virus, Epaxal. Adult volunteers (N = 130) previously enrolled into four different studies between 1992 and 1994 and who had completed a 0/12-month immunization regimen (primary and booster dose) were asked to participate in this follow-up study. Yearly anti-HAV titers up to 6 years following booster vaccination, and then once 9-11 years after booster were measured using two assays, Enzygnost and AxSYM HAVAB 2.0. Based on the Enzygnost assay, the seroprotection rate 9-11 years after booster was 100%, with a geometric mean concentration (GMC) of anti-HAV antibodies of 526 mIU/ml. Females had markedly higher GMCs than males (741 mIU/ml vs. 332 mIU/ml). Using an anti-HAV cut-off titer of >or=10 mIU/ml, a linear mixed mathematical model predicted a median duration of protection of 52.1 years. A duration of protection >or= 35.7 years was predicted for 95% of subjects. A more stringent cut-off of >or=20 mIU/ml shortened the median predicted duration of protection to 45.0 years. In conclusion, a two-dose Epaxal vaccination regimen confers in healthy adults a real-time protection of at least 9-11 years; this protection is predicted to last at least 30 years in over 95% of individuals. Further studies are necessary to assess the real duration of seroprotection and whether an additional booster is necessary later.
Journal of Medical Virology 10/2010; 82(10):1629-34. DOI:10.1002/jmv.21883 · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Noroviruses are a major cause of viral gastroenteritis and have been detected with increasing prevalence in recent years. Currently, two main genogroups GI and GII with an increasing number of subtypes are differentiated. Because of a high genetic variability new variants emerge constantly allowing epidemiological tracing of viruses from year to year and location to location. A 282 bp sequence at the 5'end of the capsid gene was analyzed in isolates originating from the University hospital, Technische Universität München. Phylogenetic analysis was based on 20 GII positive samples from an outbreak in March/April 2006 and 8 samples from the following winter season 2006-2008. In the initial outbreak two distinct genotypes were identified. The GII.4 strain 2006a found in the majority of outbreaks in 2006 worldwide was isolated from all but two patients. These two individuals were infected with a GII.7 strain clustering mainly with isolates from Asia. Of note, they excreted noroviral RNA for 81 and 27 days, respectively. Longitudinal analysis of an extended 1381 bp sequence revealed positive selection in the P2 domain. The variant was very similar to GII.7 strains isolated in 1990 and 1994 suggesting slow evolution with evidence of recombination according to the SimPlot analysis. Strains found in the following years 2006-2008 clustered around the isolate GII.4 2006b, characterized in the spring of 2006 and reaching a high prevalence in 2006-2007. The results provide an insight into norovirus evolution at a University hospital over 3 years and describe intraindividual evolution within a patient infected chronically.
Journal of Medical Virology 05/2010; 82(6):1058-64. DOI:10.1002/jmv.21755 · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.).
Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded.
Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m.
The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.
Journal of Travel Medicine 11/2009; 16(6):413-9. DOI:10.1111/j.1708-8305.2009.00351.x · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The epidemic outbreak of severe acute respiratory syndrome (SARS) in 2003 was caused by a novel coronavirus (CoV), designated SARS-CoV. The RNA genome of SARS-CoV is complexed by the nucleocapsid protein (N) to form a helical nucleocapsid. Besides this primary function, N seems to be involved in apoptotic scenarios. We show that upon infection of Vero E6 cells with SARS-CoV, which elicits a pronounced cytopathic effect and a high viral titer, N is cleaved by caspases. In contrast, in SARS-CoV-infected Caco-2 cells, which show a moderate cytopathic effect and a low viral titer, this processing of N was not observed. To further verify these observations, we transiently expressed N in different cell lines. Caco-2 and N2a cells served as models for persistent SARS-CoV infection, whereas Vero E6 and A549 cells did as prototype cell lines lytically infected by SARS-CoV. The experiments revealed that N induces the intrinsic apoptotic pathway, resulting in processing of N at residues 400 and 403 by caspase-6 and/or caspase-3. Of note, caspase activation is highly cell type specific in SARS-CoV-infected as well as transiently transfected cells. In Caco-2 and N2a cells, almost no N-processing was detectable. In Vero E6 and A549 cells, a high proportion of N was cleaved by caspases. Moreover, we examined the subcellular localization of SARS-CoV N in these cell lines. In transfected Vero E6 and A549 cells, SARS-CoV N was localized both in the cytoplasm and nucleus, whereas in Caco-2 and N2a cells, nearly no nuclear localization was observed. In addition, our studies indicate that the nuclear localization of N is essential for its caspase-6-mediated cleavage. These data suggest a correlation among the replication cycle of SARS-CoV, subcellular localization of N, induction of apoptosis, and the subsequent activation of caspases leading to cleavage of N.
[Show abstract][Hide abstract] ABSTRACT: The objectives of this trial were to test for noninferiority of a virosomal hepatitis A virus (HAV) vaccine (Epaxal) coadministered with routine childhood vaccines compared with Epaxal given alone and to an alum-adjuvanted HAV vaccine (Havrix Junior) coadministered with routine childhood vaccines.
Healthy children 12- to 15-month-old were randomized to receive either a pediatric dose (0.25 mL) of Epaxal coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 109; group A), or Epaxal given alone (n = 105; group B), or Havrix Junior coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 108; group C). A booster dose was given 6 months later. Anti-HAV antibodies were tested before and 1 month after each vaccination. Safety was assessed for 1 month after each vaccination. Solicited adverse events were assessed for 4 days after each vaccination.
: HAV seroprotection rates (> or =20 mIU/mL) at 1 and 6 months after first dose were: A: 94.2% and 87.5%, B: 92.6% and 80.0%, C: 78.2% and 71.3%, respectively (A versus C: P < 0.001 and P = 0.017 at month 1 and 6, respectively). The respective geometric mean concentrations were: A: 51 and 64 mIU/mL, B: 49 and 59 mIU/mL, C: 33 and 37 mIU/mL (A versus C: P < 0.001 at both time points). All groups achieved 100% seroprotection after the booster dose. The geometric mean concentrations after the booster dose were 1758, 1662, and 1414, for groups A, B and C, respectively (A versus C: P = 0.15). No clinically significant reduction in immune response to all concomitant vaccine antigens was seen. All vaccines were well tolerated.
: Coadministration of pediatric Epaxal with routine childhood vaccines showed immunogenicity and safety equal to Epaxal alone as well as to Havrix Junior. After first dose, Epaxal was significantly more immunogenic than Havrix Junior.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: In this open study, 20 toddlers and 80 schoolchildren received an intramuscular dose of Epaxal® and a booster dose 12 mo later to assess the efficacy and safety of this aluminium-free, virosomal hepatitis A vaccine. Four weeks after primary vaccination, 94% of toddlers and 99% of schoolchildren had seroconverted, and all toddlers and 94% of schoolchildren remained seroprotected for 12 mo.
Conclusion: After vaccination with Epaxal® and booster, all subjects were seroprotected. Epaxal® was very well tolerated by both age groups.
[Show abstract][Hide abstract] ABSTRACT: Immunization of young children could control hepatitis A virus (HAV) infection, but the efficacy of hepatitis A vaccines in early childhood is unknown. In a randomized, double-blind trial of a single dose of a virosome-formulated, aluminum-free inactivated HAV vaccine in Nicaragua, 274 children (age range, 1.5-6 years) received vaccine or placebo injections; 239 children seronegative for hepatitis A were included in the primary efficacy analysis. HAV infection documented by immunoglobulin M antibodies was the primary end point. Among children seronegative for hepatitis A, infection was diagnosed in 4 children in the vaccine group and 22 children in the placebo group (protective efficacy, 84.6%; 95% confidence interval, 54.7%-96.1%). All infections in children in the vaccine group occurred within 6 weeks. After 6 weeks, protective efficacy was 100% (79.8%-100%). In children in the placebo group, the incidence of HAV infection was 17.6 and that of icteric illness was 1.6 cases/100 person-years. Adverse effects were rare in both children in the vaccine group and children in the placebo group. A single dose of a hepatitis A virosome vaccine is safe and protects young children against HAV infection.
The Journal of Infectious Diseases 10/2003; 188(5):671-7. DOI:10.1086/377309 · 5.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As sanitary conditions of a population improve, hepatitis A virus infection occurs at higher ages, thus decreasing the prevalence of antibodies against the virus. In the eighties, the prevalence of antibodies among children was 97% and depended on the socioeconomic level.
To assess the prevalence of antibodies against hepatitis A virus in school age children living in Valdivia.
Two thousand three hundred thirty three school age children were studied. Total antibodies against hepatitis A virus were detected using an ELISA kit from Abbott. Children were stratified in age groups and school were classified as private, subsidized, municipal or foster homes.
Antibodies were positive in 65% of children (59% in children aged 6 to 8 years old, 66% in children aged 9 to 11 years and 69% in children aged 12 to 15 years. In private schools, the prevalence was 26%, in subsidized schools the figure was 54%, in municipal schools 73% and in foster homes 91%.
The general prevalence of antibodies against hepatitis A virus is higher in low socioeconomic level children. There is a global decrease in the prevalence of these antibodies in the last years.
Revista medica de Chile 11/1998; 126(10):1161-4. · 0.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Revista medica de Chile 05/1995; 123(4):439-44. · 0.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Revista medica de Chile 02/1994; 122(1):68-71. · 0.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
G.E.N.: organo oficial de la Sociedad Venezolana de Gastroenterología, Endocrinología y Nutrición 01/1993; 47(1):25-31.
[Show abstract][Hide abstract] ABSTRACT: Accumulation and persistence of hepatitis A virus (HAV) in the mussel Mytilus chilensis was evaluated. Under optimal filtration activity of mussels (temperature 12 degrees C, salinity 3%, feeding twice a day with Dunaliella marina), HAV was concentrated 100-fold from the surrounding water. Similar concentrations of HAV were reached in the filtration apparatus and in the digestive system (hepatopancreas). HAV persisted for about 7 days in mussels. Elimination of HAV from mussels was slower than elimination of poliovirus. Without feeding of mussels (causing low filtration activity), there was no measurable uptake of HAV into mussels, and depuration of HAV from mussels was slower. The ability of mussels to concentrate HAV was used successfully to monitor fecally contaminated river water for the presence of HAV.
Journal of Medical Virology 07/1992; 37(3):174-9. DOI:10.1002/jmv.1890370305 · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A placebo-controlled, double-blind study on the efficacy of a hepatitis A vaccine (SmithKline Beecham Biologicals) was started in a region of Chile in September 1990, using hepatitis B vaccine as control. A total of 260 healthy children, 6-15 years of age, negative for antibody to hepatitis A virus (anti-HAV), antibody to HAV immunoglobulin M (IgM), hepatitis B surface antigen, and antibody to hepatitis B surface and core antigens by ELISA tests within 7 days before vaccination, were randomly assigned to two study groups: 128 children received the vaccine with a yellow label (group 1), and 132 children the vaccine with an orange label (group 2) at months 0, 1 and 6. Blood for serology and transaminase determination was drawn at months 1, 2, 6, 7 and 12. Both vaccines were tolerated equally well and no serious side effects were seen. In group 1 (presumed hepatitis A vaccine group), anti-HAV was detected (20% inhibition was used as the cut-off level) in 122 of 128 children (95.5%) tested at month 1, in 126 of 127 (99.2%) at month 2, in 126 of 127 (99.2%) at month 6 and in 126 of 126 (100%) at month 7. One anti-HAV seroconversion seen at month 1 was associated with presence of anti-HAV IgM and therefore probably represents HAV infection. Geometric mean anti-HAV concentration of the other children was 128, 342, 214 and 2301 mIU/ml at months 1, 2, 6 and 7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
[Show abstract][Hide abstract] ABSTRACT: 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.
Revista medica de Chile 02/1990; 118(2):134-8. · 0.37 Impact Factor