Hepatitis B Virus , Hepatitis C Virus and Human T Lymphotropic Type I Among Institutionalized Mentally Retarded Patients in Okinawa , Japan

During the period 1986-1991 in Okinawa, Japan, serologic markers of hepatitis B virus infection (hepatitis B surface antigen : HBsAg, antibody to hepatitis B core antigen : anti-HBc), hepatitis C virus infection (antibody to HCV : anti-HCV) and human T lymphotropic virus type I (antibody to HTLV-I: anti-HTLV-I) were investigated in institutionalized mentally retarded patients. In 1986, HBsAg was detected in 34(9.1%), anti-HBc in 179(48.0%), anti-HCV in 5(1. 3%) and anti-HTLV-I in 34(9.1%) of 373 patients. HBsAg and anti-HBc were more prevalent in patients than in the 400 controls (3.8%, p<0.05, 25.5%, p<0.001, respectively). However, there was no significant difference in the prevalence of either anti-HCV or anti-HTLV-I between patients and controls (1.0%, 9.0%, respectively). Eight (12.5%) of 64 seronegative patients not given hepatitis B vaccine were infected with hepatitis B virus (one became an HBsAg carrier) over five years of observation, whereas none were infected with hepatitis C virus or HTLV-I. Hepatitis B virus was the most transmissible of the three viruses among the mentally retarded patients in these institutions.

During the period 1986-1991 in Okinawa, Japan, serologic markers of hepatitis B virus infection (hepatitis B surface antigen : HBsAg, antibody to hepatitis B core antigen : anti-HBc), hepatitis C virus infection (antibody to HCV : anti-HCV) and human T lymphotropic virus type I (antibody to HTLV-I: anti-HTLV-I) were investigated in institutionalized mentally retarded patients.
HBsAg and anti-HBc were more prevalent in patients than in the 400 controls (3.8%, p<0.05, 25.5%, p<0.001, respectively).However, there was no significant difference in the prevalence of either anti-HCV or anti-HTLV-I between patients and controls (1.0%, 9.0%, respectively).
Eight (12.5%) of 64 seronegative patients not given hepatitis B vaccine were infected with hepatitis B virus (one became an HBsAg carrier) over five years of observation, whereas none were infected with hepatitis C virus or HTLV-I.Hepatitis B virus was the most transmissible of the three viruses among the mentally retarded patients in these institutions.hepatitis B virus, hepatitis C virus, human T lymphotropic virus type I, institution, mentally retarded patients Hepatitis B virus 1,2), hepatitis C virus3-5) and human T lymphotropic virus type I6,7) are spread via infected blood and by sexual intercourse.
Moreover, it is well known that hepatitis B virus8) and HTLV-I7) are transmitted from mother to child.Recently, Thaler et a19).also reported the maternal transmission of hepatitis C virus.Blumberg et a110).reported a high prevalence of hepatitis B surface antigen (HBsAg) in sera from patients with Down's syndrome and Krugman et al11).were apparently the first to draw attention to the high incidence of hepatitis B among institutionalized mentally retarded patients.The reservoir of infection is maintained in such institutions by HBsAg-positive residents, Down's syndrome patients particularly prone to persistent antigenemia12).However, little is known of the the rates of infection of hepatitis C virus and HTLV-I in institutions for the mentally retarded.
The present study was undertaken to determine the frequency and distribution of HBsAg, antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis C virus (anti-HCV) and antibody to HTLV-I (anti-HTLV-I) among institutionalized patients with various neurological disorders and to investigate the rate of infection of the three viruses.

MATERIALS AND METHODS
Patients in six institutions for the mentally retarded in Okinawa, Japan were surveyed for hepatitis B virus markers, since 198613).These institutions have patients with Down's syndrome and other forms of mental retardation housed together according to their sex and IQ levels.The conditions were little different among six institutions.
The wards were not overcrowded and sanitary conditions were good.These patients were allowed home leave twice a year.They were trained together in classrooms and in workshops.No patients from a different institution was included.measured by first-generation enzyme-linked immunosorbent assay (ELISA ; Ortho Diagnostics Systems, Raritan, New Jersey, USA).All sera that were repeatedly reactive by ELISA were tested means of recombinant immunoblot assay (RIBA, Ortho Diagnostics Systems).Only sera with reactivity to recombinant antigen 5-1-1 and c100-3, but without any nonspecific reactivity, were defined as positive.Anti-HTLV-I was tested using ELISA (model E-0733; Eisai Co, Tokyo, Japan) 14).Absorbance at 0.100 was considered to be the cut-off value.To evaluate the specificity for this method, samples that were judged to be positive but had absorbance values less than 0.300 were assayed by the ELISA inhibition test and by western blot analysis, using antigens prepared from MT-2 cells.
The chi-squared test was used to determine the statistical significance.
The prevalence of HBsAg and anti-HBc in these patients was significantly higher than in the controls (p<0.05,p< 0.001 respectively).However, the prevalence of anti-HCV and anti-HTLV-I did not differ between patients and controls.
The prevalence of HBsAg in patients from different institutions ranged from 4.3 percent to 18.6 percent and anti-HBc from 27.6 percent to 68.6 percent.HBeAg was found in the sera of 10(29.4percent) of 34 HBsAg carriers.There were several HBsAg carriers with HBeAg, in every institution.
In Institution C, in which only male adult patients resided, the prevalence of HBsAg (18.6 percent) and anti-HBc (68.6 percent) was the highest.There was only one institution in which more than two anti-HCV-positive patients resided.Anti-HTLV-I-positive patients were found in every institution, the prevalence ranging from 3.4 percent to 11.4 percent.Age specific prevalences of HBsAg, anti-HBc, anti-HCV and anti-HTLV-I among the 373 patients are shown in Table 3.The prevalence of HBsAg was the highest in the 30-39 age group (11.3 percent), the prevalences of anti-HBc increased with age up to the over 40 age group (64.7 percent), the prevalence of anti-HCV increased with age group to the over 40 age group (2.9 percent) and the prevalence of anti-HTLV-I was the highest in the over 40 age group (14.7 percent).
There were no significant differences between the sexes with regard to the prevalence of viral markers.HBsAg was more prevalent in patients with Down's syndrome (24.0 percent) than those with other forms of mental retardation (5.4 percent) (p<0.001), and other markers showing no significant differences (Table 4).
Three hundred and fifty-eight of the 373 institutionalized patients were followed for viral markers for five years of whom 186 were negative for anti-HBc initially.One hundred and seventeen of them were given hepatitis B vaccine from 1986.Of the 117 vaccinated patients, 110(94.0%)aquired antibodies to HBsAg (anti-HBs) and one was infected with hepatitis B during the period of this study.He became anti- HBs-positive (RIA < 10 mIU/ml) without anti-HBc within I month after the first dose of vaccine and became positive for anti-HBc, in the 5 months between the second and third injections.
None of the remaining 116 vaccinated patients became HBsAg and/or anti-HBc-positive15-17) and we excluded them from the follow up study for hepatitis B virus infection.Finally, 64 patients were analyzed with respect to hepatitis B virus infection.Eight (12.5 percent) of these anti-HBc-negative patients seroconverted to positive.One of the eight patients became an HBsAg carrier, he was in Institution C, was 29 years old, and had Down's syndrome.
Three hundred and fifty-three of 368 patients who were initially negative for anti-HCV remained negative and 326 of 336 patients who were negative for anti-HTLV-I initially also remained negative through 1991(Table 5).In no patient with HBsAg, anti-HBc, anti-HCV and anti-HTLV-I these viral markers were eliminated from their sera during observation period.

DISCUSSION
We have surveyed for serum markers of hepatitis B virus infection since 197618,19) and for HTLV-I infection since 19807.20).The prevalence of these markers in the inhabitants of Okinawa is the highest in the Japanese.The prevalence of HBsAg was 7.5 percent and that of anti-HBc was 65.5 percent in the period from 1979-81.The prevalence of anti-HTLV-I was 15.3 percent from 1980-84.The lower prevalence of hepatitis B virus markers in the controls studied are because of the marked decrease of hepatitis B virus infection in Okinawa2 ).The prevalence of anti-HTLV-I increased with advancing age to 30.1 percent in individuals over 7020).People over age 70 years were excluded from our control group to match the ages of patients.
Hepatitis B virus infection is a particular problem in institutions for the mentally handicapped because of aberrant social behavior of the patients, unique medical problems such as bleeding gums and drooling, and crowded conditions22, 23).The patients in this study sometimes used razors and toothbrushes which had been previously used by HBsAg carriers13).Our data revealed that hepatitis B virus markers in institutionalized patients were more prevalent than those in controls.Moreover, it was found that eight (12.5 percent) of 64 patients were newly infected with hepatitis B virus during the five year period.The annual rate of hepatitis B virus infection was 2.5 percent in the institutions studied.By contrast, there was no significant difference in either anti-HCV or anti-HTLV-I between patients and controls.
We found no institutionalized patient newly infected with hepatitis C virus or HTLV-I over the five years of our study.Hepatitis B virus was the most transmissible of the three viruses studied.In hospital personnel the prevalence of hepatitis B virus markers was higher than in the controls24) whereas the prevalences of anti-HTLV-I25) and anti-HCV26) was the same as in controls.
Horizontal transmission of hepatitis C virus and HTLV-I seems to be difficult.
Despite similar routes of transmission of these three viruses (e.g.blood, sexual intercourse, maternal), the infective events differed.There are three likely reasons for the transmission of hepatitis B virus but not of hepatitis C virus and HTLV-I, in these institutions.Firstly, details on the mechanism of infection differ : hepatitis B virus is transmitted by serum, whereas HTLV-I is transmitted by lymphocytes6).Secondly, there are few virions in serum infected with hepatitis C virus27).Viremia during the course of hepatitis C virus infection may occur at a lower level than hepatitis B virus infection.Experimental transmission studies in chimpanzees suggest that most hepatitis C virus-infected blood contains only 100 to 1000 chimpanzee infectious units per ml, wheareas hepatitis B virus-infected blood often has levels of transmissible virus two to three logs higher28).Finally , the infectivity of hepatitis B virus may be the strongest among the three viruses studied.These differences in mode of transmission perhaps account for the apparent differences in infectivity in the institutionalized patients we studied.
Although RNA viruses are generally more infectious than DNA viruses, hepatitis C virus is an RNA virus and hepatitis B virus is a DNA virus .Hepatitis C virus was detected in saliva29) as was hepatitis B virus30).Both hepatitis B virus and hepatitis C virus may be transmitted by parenteral exposure by means of blood transfusion or intravenous drug use31) .Sexual transmission of hepatitis C virus may also occur, although it is probably less frequent than with hepatitis B virus5).It may be that hepatitis C virus infection did not spread because there were few hepatitis C virus carriers in the institutions studied.In conclusion, the results of this study show that institutionalized patients are at a low risk for transmission of hepatitis C virus and HTLV-I, whereas they are at a high risk for hepatitis B virus infection.

Table 1 .
Profile of mentally retarded patients from six institutions in Okinawa, Japan, in 1986.

Table 2 .
Prevalence of hepatitis B surface antigen, antibody to hepatitis B core antigen, antibody to hepatitis C virus and antibody to human T lymphotropic virus type I in 373 mentally retarded patients in six institutions and controls in Okinawa, Japan, in 1986.

Table 3 .
Distribution of hepatitis B surface antigen, antibody to hepatitis B core antigen, antibody to hepatitis C virus and antibody to human T lymphotropic virus type I, by age, in 373 mentally retarded patients in institutions in Okinawa, Japan, in 1986.