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Background: It has been reported that vaccination against hepatitis B is less effective among people with Down syndrome than in the general population. We aimed to evaluate the rate of seroconversion to hepatitis B vaccine in children with Down syndrome from Brazil., Methods: A total of 120 people with Down syndrome were included. All of them received the vaccine at intervals of 0, 30 and 180 days and serum samples were tested for the presence of antibodies to the hepatitis B surface antigen (anti-HBs) 30 days after the last dose., Results: In the studied group, 58.3% (70/120) were male and 41.7% (50/120) female, with the median age of 5 years (range 2-15 years). Fifty-eight of 120 (48.3%) developed anti-HBs after vaccination. No association was found between gender and/or age and vaccine response., Conclusions: The low rate of seroconversion in response to hepatitis B vaccine suggests that all patients with Down syndrome immunized against hepatitis B should be followed and monitored by clinicians., (© 2013 John Wiley & Sons Ltd.)

The objective of this study was to examine whether the prevalence of hepatitis C, like hepatitis B, is increased among the mentally retarded in Denmark. The prevalence of serological markers of hepatitis B and C was examined in an institution for the mentally retarded. A total of 126 out of 178 inhabitants (71%) with a median age of 49 years (range 23-78) participated. All subjects were anti-HCV-negative by third generation ELISA antibody test. A total of 45 (35.7%) subjects were anti-HBc-positive and 10 (7.9%) were HBsAg-positive. Among subjects with Down's syndrome (n = 20), 55% were anti-HBc-positive and 30% were HBsAg-positive as compared to 32% and 3.8% respectively among others. In conclusion, hepatitis C infection seems to be uncommon among mentally retarded persons in Denmark and the risk of acquiring infection not significantly increased as compared to that of the general population. The prevalence of serological markers for hepatitis B was high and comparable to previous studies in this population.

Although it is well known that viral hepatitis can be complicated by autoimmune phenomena, the evidence for a pathogenetic role of viral hepatitis in the etiology of autoimmune thyroiditis is unclear. Because both hepatitis B and autoimmune thyroiditis occur frequently in Down syndrome, we decided to determine whether a cause-and-effect relationship might exist. Such a relationship might provide insight into basic mechanisms that could generalize to other populations. Accordingly, the frequency of hepatitis B surface antigen (HBsAg) positivity and thyroiditis was determined in 57 adults with Down syndrome and compared with frequencies in 450 age-, sex-, and environmentally matched mentally retarded patients without Down syndrome. We found no relationship of HBsAg positivity and thyroiditis in those mentally retarded patients without Down syndrome. On the other hand, the frequency of thyroiditis in those Down syndrome patients who were also carriers of HBsAg was threefold higher than the frequency of thyroid disease in those patients with Down syndrome who were not carriers of HBsAg (65% vs. 23%, p < 0.01). This relationship of hepatitis B and thyroid disease in Down syndrome might be explained by cytokine and/or cellular immune abnormalities linked to extra genetic material in trisomy 21. Clinically, patients with Down syndrome who are also hepatitis B carriers should be closely monitored for development of thyroid disease.

In order to know in Down's Syndrome (DS) the age of infection by hepatitis B virus (HBV), the incidence of evolution to a chronic carrier status and the optimal age for vaccination against this virus, a study of the prevalence of HBV-markers was carried out in 302 mentally retarded children: Group I, 51 pre-schoolchildren with DS (mean age 2.9 +/- 1.6 years); Group II, 72 schoolchildren with DS (mean age 13.8 +/- 3 years) and Group III, 179 schoolchildren with other types of mental retarded (OMR). Children from group II and III attended the same school as external day-pupils. Fifty eight percent of schoolchildren with SD presented at least one HBV-marker while this percentage was of 25% in schoolchildren with OMR (p > 0.05) or pre-schoolchildren with DS (p > 0.005); DS schoolchildren become also HBV chronic carrier with higher frequency than ORM schoolchildren (40 vs 17) (p > 0.05) and they maintained HBV replication in a higher proportion of cases (36 vs 4) (p > 0.05). In conclusion children with DS acquire easily HBV infection and this occurs when they attend the school independently that the school is a closed or an open institution. They also become more frequently HBV chronic carriers and they maintain HBV replication; so, they must be vaccinated before they begin to attend school and they must be treated with antiviral agents as soon as possible.

Persons with Down's syndrome (DS) constitute a risk group for hepatitis B (HB) and are recommended to be immunized. Of 123 persons with DS in Orebro county screened for markers of HB, 31% had such markers; 16% were potentially contagious. 83 persons without markers participated in a comparative trial of the immunogenicity of a recombinant HB vaccine given either intramuscularly (IM) or in a lower dose intradermally (ID). Immunity developed in 73% after IM vaccination as compared to 29% of those given ID vaccination (p < 0.005). At 3-year follow-up half and two-thirds of the immune persons, respectively, had lost their immunity. Those > 30 years had a poor immunization response compared to the younger ones (p < 0.01). Only 19% of the non-responders developed immunity after an IM booster dose given 10 months after the third injection. Intradermal vaccination is not warranted in persons with DS, especially not in middle aged and older persons. A booster dose of vaccine does not ascertain immunity in those who do not respond with immunity to the ordinary immunization schedule. Post-vaccination immunity should therefore be controlled.

Unlabelled: Hepatitis B virus (HBV) markers are found with high frequency in immunocompromised individuals. In order to find out if this is also true for the hepatitis C virus (HCV), we have analyzed a group (G.1) of 46 patients (pts.) with Down syndrome, situation known to be associated with immunodepression G. 1. We compared them with a G. of 310 mentally retarded pts. without Down syndrome G. 2 and without evidence of immunological disfunction. All of them were studied for infection with HBV. All pts. in G. 1 and G. 2 were also tested for HCV. The pts. have been hospitalized in a specialized medical institution for mentally retarded on a long term basis and were followed during 1 year. Finally G 3 was composed of 5454 voluntary blood donors., Material and Methods: In all pts. search for HBV infection markers (anti-HBc, HBsAg, HBeAg by EIA test and HBV-DNA by nucleic acids hybridization) were performed. Search for HCV markers was done by a second generation EIA kit (Abbott Hepatitis C (rDNA) (Antigen)., Results: HBsAg was found to be positive in 12/46 (26%) of G. I and 25/310 (8%) of G. II (p < 0.001). HBeAg was positive in 8/12 (67%) of G. I and in 2/25 (8%) of G. II (p < 0.001). All HBeAg positive pts. had elevated values of DNA-HBV. In G. I, 4/12 (33%) pts. lost HBeAg during the observation period, one of them remained HBV-DNA positive and none become HBsAg negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-nine healthy HBsAg- and HBsAb-negative children with Down's syndrome who were living at home (mean age 42 months; 19 M, 10 F) were vaccinated against hepatitis B virus either with recombinant DNA or plasma-derived vaccine. Both groups of children responded well to the vaccination schedules, with HBsAb seroconversion rates close to 100%. Vaccination against hepatitis B in preschool children with Down's syndrome is effective in spite of the existing abnormalities of the immune function.

We examined 180 noninstitutionalized persons with Down syndrome for the presence of both hepatitis B surface antigens and antibodies to hepatitis B surface antigen. Two of the 180 subjects with Down syndrome had a positive test. One patient was hepatitis B surface antigen positive and the other was found to have antibodies to hepatitis B surface antigen. Also, 2 of the 155 individuals in the comparison group tested positive for hepatitis B surface antigen. Thus, we did not observe an increased prevalence of hepatitis B surface antigen or antibody in the study group and there was no significant difference between the Down syndrome and comparison groups. This is in contrast to many studies that originated in residential facilities where an increased number of persons with Down syndrome were found to have hepatitis B surface antigenemia. The related public health concerns are discussed.

The resident population in a long-stay hospital for the mentally handicapped was surveyed in order to assess evidence for past and present infection with the Hepatitis B virus. The authors found a 0.5% prevalence of carriage of Hepatitis Be Antigen and do not recommend mass vaccination of staff and residents in this hospital.

Data obtained concerning Hepatitis B as a possible couse of Down's syndrome, neonatal hepatitis, and the occurrence of Hepatitis A and B in institutionalized Down's syndrome and matched non-Down's syndrome retarded patients was summarized. The results of our studies indicated that Hepatitis B infection during pregnancy was not related to the genetic changes associated with Down's syndrome. It was further indicated that in institutionalized patients the incidence of Hepatitis B infection in both Down's syndrome and other mentally retarded patients was similar. Within the institition we studied, the incidence of Hepatitis B varied among wards. This ward variation seemed to be related to age at time of institutionalization and degree of mental retardation. Those patients with most retardation and those institutionalized at an early age were placed on wards with highest incidence of Hepatitis B antigenemia.

Data on prevalence of antibody to hepatitis B surface antigen (anti-HBs) and of hepatitis B surface antigen (HBsAg) among 95 matched pairs of Down's syndrome (DS) and other mentally retarded (OMR) patients in an institution were analyzed by age on admission and by length of residence. Passive hemagglutination test were used to determine anti-HBs. Anti-HBs prevalence increased with admission age among DS patients (26%, 42% and 56% for age groups less than or equal to 5, 6-15 and greater than 15 years, respectively) but decreased among OMR patients (85%, 71% and 78%), giving overall rates of 38% for DS and 77% for OMR which are significantly different (p less than .001). Anti-HBs prevalence increased with length of residence for OMR patients but was unchanged for DS patients. For both groups, the prevalence of hepatitis B (HB) infection (both anti-HBs and HBsAg) increased with length of residence and, overall, was nearly the same for DS and OMR patients. These observations are consistent with the hypothesis that, with respect to response to HB virus, younger DS patients are immunologically immature.

In 1,149 clients of an institution for the mentally retarded, the prevalences of hepatitis B surface antigen (HBsAg) and hepatitis B virus markers were 12 per cent and 66 per cent, respectively. HBsAg prevalence was higher in males, Down syndrome, ambulatory, and older clients, and those with longer institutionalization. Serum alanine aminotransferase levels were abnormal in 31 per cent of HBsAg positive and 10 per cent of HBsAg-negative clients.

A screening of 615 mentally retarded residents in a Finnish institution revealed 22 HBsAg-positive asymptomatic carriers in 1972. Thirteen of them were placed in a special ward and followed up for 12 years. Only one patient had hepatitis eight years later. During the years all 52 staff members of the ward and the laboratory had been HBsAg-negative, but one laboratory nurse and two ward nurses showed antibody production. The seroconversion rate was one per 33 person-years among the staff. The results suggest that the risk of transmitting hepatitis B still exists, even in special wards in such institutions, and isolation of the carriers alone cannot guarantee full protection for hepatitis B infections.

Literature citations show that institutionalized people with Down's syndrome have a significantly higher incidence of positive hepatitis B antigen (HBsAg) than mentally handicapped people who do not have Down's syndrome. A review of 2,136 institutionalized mentally handicapped people in Georgia shows that 27% of residents who have Down's syndrome and 7% of the residents who do not have Down's syndrome tested positive for HBsAg. Forty-nine people with Down's syndrome living in the community were screened for HBsAg. Only one (3%) of 37 of the people who had never lived in an institution tested positive for HBsAg. The implication is that patients with Down's syndrome who have never been institutionalized should be treated no differently than any person in the general population who is not suspected of being a transmitter of an infectious disease.

Institutionalized patients with Down's syndrome (DS) are uniquely predisposed to develop chronic hepatitis B infection following exposure. Therefore vaccination is particularly warranted, but there have been concerns that these individuals may react suboptimally. We examined the immune responses of 62 institutionalized patients with DS to 20 and 40 micrograms of hepatitis B vaccine inactivated (Heptavax-B) over one year. The subjects were matched by weight, age, and sex. Seroconversion rates and levels of antibodies to hepatitis B surface antigen (anti-HBs) were comparable to those found in a normal population and were higher than those found in immunocompromised patients undergoing hemodialysis. The anti-HBs levels were consistently higher in the 40-micrograms vaccine group. In patients with DS who were over 30 years old, age was a significant factor in predicting anti-HBs responses. Conversely, in younger subjects, weight was negatively correlated with anti-HBs levels. These data clearly indicate that patients with DS respond normally to hepatitis B surface antigen vaccination and need not be considered a special group when guidelines for vaccination are recommended.

Screening for HBeAg and anti-HBe was performed on 133 carriers of HBsAg in an institution for the mentally retarded. By radioimmunoassay, the prevalences of HBeAg and anti-HBe were determined to be 16 and 78%, respectively. HBeAg prevalence was significantly different in the following pairs of carriers: 70% in blacks, 10% in whites, and 35% in carriers with Down's syndrome, 8% in carriers without Down's syndrome. Mean age of HBeAg-positive carriers (25.7 years) was lower than HBeAg-negative carriers (29.6 years, p less than 0.05). SGPT levels were abnormal in 66% of HBeAg-positive and 25% of HBeAg-negative carriers (p less than 0.01). This suggests an association between HBeAg positivity and functional liver impairment.

A longitudinal study carried out over 43 months in a residential home for the mentally retarded confirmed the marked propensity of individuals with Down's syndrome (DS) to develop chronic HB antigenaemia. This could not be accounted for by environmental factors, and a genetic basis is postulated. In addition, DS subjects appeared innately more susceptible to hepatitis B virus (HBV) infection, requiring one-third the patient-months of exposure of non-Down's subjects (ND) before showing evidence of infection. The reciprocal geometric mean titre of anti-HBS in DS subjects was 110 compared with 705 in ND subjects, suggesting a deficiency of humoral immunity in the DS subjects. Transmission of HBV was occurring by means other than therapeutic, prophylactic, dental or diagnostic procedures, in the institution, and possible modes of transmission are discussed. These were probably both parenteral and non-parenteral. Eighty-one per cent of HBV infections in the Home were subclinical.

The prevalence of hepatitis B viral (HBV) infection was assessed in 340 patients and 268 staff in a hospital for the mentally subnormal in Wessex. Hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg, e antigen (eAg), and antibody to eAg were used as markers of such infection. Forty patients and 10 staff had evidence of recent or current infection, while 149 patients and 50 staff had evidence of past infection. HBV markers were more common in mongols, epileptics, patients with cerebral palsy, and those of lower mental grades and reached a peak after 5-15 years of hospitalisation. eAg was detected in 12 out of 26 patients with HBsAg but in none of the four staff with HBsAg. Abnormal liver function values were found in 24 (60%) of the patients with recent or current HBV infection but in only 30 (19%) of those without HBV markers. Among the staff the prevalence of HBV markers correlated with the duration of employment and degree of contact with patients. Of those with recent or current infection, 4 (40%) had abnormal liver function values compared with 25 (12%) of those without HBV markers. Despite the high prevalence of markers clinically overt hepatitis B was rare.

The presence of hepatitis B e antigen (HBeAg) and its antibody (anti-HBe) was studied in 249 asymptomatic carriers of hepatitis B surface antigen (HBsAg) of different ethnic origin and clinical course. Among male homosexuals, renal transplant recipients, and hemodialysis patients, > 90% were HBeAg-positive. In contrast, anti-HBe was present in > 85% of HBsAg-positive Danish pregnant women and blood donors. In presumably immunologically intact persons, significantly elevated levels of transaminases were found in the HBeAg-positive group as compared with the anti-BHe group (P < 0.0001). Among persons with Down's syndrome, males showed a tendency toward clearing of HBeAg and development of anti-BHe as compared with females. In Eskimos a correlation was found between presence of hepatitis B e markers, age of the HBsAg carrier, and geographic origin of the carrier. A similar age relationship was found in Vietnamese refugees. It is proposed that in the general population a correlation may exist between the prevalence of HBsAg carriers and the percentage of HBeAg-positive HBsAg carriers.

Sera from patients and employees of the Lynchburg Training School and Hospital were tested for Hepatitis B surface antigen by complement fixation test and antibody against Hepatitis B surface antigen by radioimmunoprecipitation test. Hepatitis B surface antigen was detected in 20% of the Down's syndrome patients and 7 percent of the matched other retarded patients. Antibody against Hepatitis B surface antigen was detected in 40% of the Down's syndrome and 57% of the matched other retarded patients. Hepatitis B virus infection as measured by presence of either Hepatitis B surface antigen or antibody was similar in the Down's syndrome patients (59%) and the matched other retarded patients (63%). Male patients had a higher frequency of Hepatitis B surface antigen chronic carriers and a lower frequency of antibodies to Hepatitis B surface antigen than the female patients. No relationship between age at time of first institutionalization and prevalence of Hepatitis B virus infection was demonstrated. However, it was observed that patients institutionalized at an earlier age were more likely to be housed in wards with a high frequency of Hepatitis B surface antigen. Increased length of institutionalization was associated with increased prevalence of Hepatitis B virus infection. Antibody to Hepatitis B surface antigen was detected in 33% of the employees. Employees who worked on wards with a high frequency of Hepatitis B virus infection had a high frequency of Hepatitis B surface antibody (50%) whereas those working on wards with a low frequency of infection had a low frequency of Hepatitis B surface antibody (9%).

The age specific prevalence of HBsAg and anti-HBs was studied in 855 mentally retarded children and adults living in a large institution. The sera of every HBsAg positive patient was re-tested for the presence of HBeAg and anti-HBe. Overall, 78.2% of subjects showed serological evidence of current or past infection with HBV. The carrier rate was highest in children and young adults and higher amongst subjects with Down's syndrome than with other forms of retardation. HBeAg was detected in 33.9% of carriers and its prevalence also decreased with increasing age and was highest amongst subjects with Down's syndrome.

The immune response after vaccination with H-B-VAX (20 micrograms, Months 0, 1 and 6) was investigated in 23 Down's syndrome patients and compared to that in 30 other mentally retarded patients and 32 staff members. About 90% of Down's syndrome and other mentally retarded patients and 100% of staff members had anti-HBs at Month 9, but anti-HBs less than 10 IU per liter were found in 6/23 (26.1%) of Down's syndrome, 7/30 (23.3%) of other mentally retarded patients, in contrast to 2/32 (6.2%) of staff members. No differences in anti-HBs response with regard to sex and age were observed in staff members, but geometric mean titers of anti-HBs were lower in older Down's syndrome and other mentally retarded patients, and in male Down's syndrome patients. Supplementary vaccination is necessary in these individuals to obtain "protective levels" of anti-HBs.

It is important to establish the stability of Australia antigen subtypes in chronic carriers in order to evaluate the validity of using immunological determinants as long-term epidemiological markers. In this study sequential blood samples containing Australia antigen from 31 chronic carriers were typed for determinants d, y, and w. The subjects included asymptomatic carriers from Rongelap Atoll in the Marshall Islands, Down's syndrome patients, and renal patients receiving hemodialysis treatment. The period of time between blood samples extended from 3 months to 11 years. In no case did the subtype change within any individual. It appears from these data that the Australia antigen subtypes are good long-term markers for epidemiological studies.