PREVALENCE OF HEPATITIS VIRUS INFECTION AND IMMUNOGENICITY OF HBV VACCINE IN CHILDREN WITH DOWN'S SYNDROME

Al Rawi F., Al Marri A., Al Musailhy S., Jaber M., Al Dabbagh and Tawfiq F.A.
Hamad Medical Corporation, Doha, Qatar

Abstract:

The prevalence of Hepatitis A, B and C infection was assessed in sixty children with Down’s syndrome (DS) and compared with sixty children with normal mentality by screening for HBsAg, HBeAg, anti-HBe, anti-HBc, anti-HBs and anti-HCV and HAV-Ig. Both groups had received three doses of recombinant DNA hepatitis vaccine at 0,1 and 6 months of age.

None of the children in either group were found to have any hepatitis viral antiginaemia, hepatitis marker or to have chronic viral hepatitis.

Hepatitis B vaccine protective efficacy which was established by the presence of anti-HBs >= 10 mIU, was significantly lower in the DS than the control group (28.3% Vs 85%, p < 0.001).

None of the children in the DS group, after the age of seven years, had protective anti-HBs level as compared to 79% of the children in the control group.

Booster doses are not recommended for normal children even if they lose their antibody to HBV vaccine because of the presence of immune memory. However, in children with DS, because of their immune deficiency, low vaccination response, and their predisposition to chronic hepatitis infection especially at school age, we recommend booster HBV vaccination for them at school entry.

Introduction:

Multiple Immunological disturbances are observed commonly in individuals with Down’s syndrome (DS), including abnormal proportions of peripheral blood lymphoid subsets, cellular, and autoimmune phenomena(1, 2, 3).

It has been observed that children with DS more frequently acquire HBV infection. They are also more likely to become HBV chronic carriers and maintain HBV replication(4, 5, 6, 7). This occurs after they enter school regardless of the type, whether it is a closed institution or a day school(8).

There is also controversy regarding the efficacy of HBV vaccination in patients with DS(1,6). Following three doses of immunization with a recombinant DNA Hepatitis B Vaccine, protective level of Anti-HBs (ž 10 milli international unit-mIU) are demonstrated in > 90% of adults and > 95% of normal children(9), while the response is much lower in DS patients (16.6%)(1).

At present Hepatitis B immunization is the only promising way to eradicate chronic HBV carriage from the world, and to decrease HBV complications such as chronic hepatitis, cirrhosis and primary hepatocellular carcinomaronic hepatitis, cirrhosis and primary hepatocellular carcinoma(10, 11, 12, 13). Therefore early vaccination is advisable for all children and particularly children with DS(4, 7).

The aim of this study was to evaluate the prevalence of HBV and other types of hepatitis in children with DS, and also to assess the immunological response to recombinant HBV vaccination amongst the previously vaccinated children.

Subjects and Methods:

This was a prospective study during the period January 1997 to the end of December 1999, which involved 60 children with DS aged 18 months to 10 years attending the Day Care Unit program at the Children’s Rehabilitation Unit at Rumailah Hospital, Doha, Qatar compared with 60 control children of comparable age and sex of normal intelligence attending the Pediatrics Outpatient Department of Hamad General Hospital, Doha, for acute illnesses with no history of liver disease.

All the children in the study had received three doses of recombinant HBV vaccine (Engerix B- Smith Kline Beecham), 0.5 ml (10 micrograms) intramuscularly in the anterolateral aspect of the thigh as part of the routine childhood vaccination program at birth, one and six months of age.

A thorough clinical history was obtained, paying special attention to maternal HBV infection, past history of jaundice or hepatitis, family history of hepatitis, hepatitis B vaccination, and its dates, history of past or recent admission to specific institutions, history of nursery or special school attendance, history of blood or blood products transfusion. Telephone numbers were recorded to recall positive cases for further investigations. Informed consent was obtained from the parents of all children.

A medical examination was carried out, with particular attention to the presence or absence of jaundice, size and texture of the liver or any other signs of hepatic dysfunction. Liver function tests included serum bilirubin, ALT, AST, and alkaline phosphatase.

Hepatitis serology was tested by commercially available Micro particles Enzyme Immunoassay (MEIA) technology by Axsym System (ABBOT, USA).

The Auzyme kit (monoclonal) was used to test for HBsAg, USAB for antibodies to HBsAg (anti-HBs) and Coryme for antibodies to core antigen (anti-HBc). Axsym HAV-M & Axsym HCV were used to test for HAV and HCV respectively and were run according to the manufacturer’s instructions.

HBV vaccine protective efficacy was established by anti-HBs antigen titer. Levels of anti-HBs of 10 mIU or more were considered as a marker of immunity.

Results:

Age:

The age of both groups ranged between 18 months (i.e. one year after the 3rd shot of HBV vaccine) and 10 years. Mean DS group age was 5.03 yrs, and mean controls age was 5.23 yrs as shown in Figure 1.

Gender:

In DS, 38 patients were male (63.3%), 22 were female (36.7%).

In the control group 35 were male (58.3%) and 25 were female (41.7%) as shown in Figure 2.

Nationality:

In the DS group, 33 patients were Qatari nationals (55%), 3 were GCC nationals (5%), 24 were from other nationalities (40%).

In the control group, 30 were Qatari nationals (50%), 2 were G.C.C nationals (3.3%) and 28 were from other nationalities (46.7%) as shown in Figure 3.

Consanguinity:

The parents of 25 DS children were first cousins (42%), they were not first cousins in the remaining 35 DS children (58%).

The parents of 29 children in the control group were first cousins (49%), while those of 31 (51%) were not (p> 0.05), as is shown in Figure 4.

Liver Function:

All DS children and controls showed normal values for serum bilirubin, ALT, AST and alkaline phosphatase.

Prevalence of Hepatitis viral infection:

None of the DS patients or the controls had evidence of previous or active HAV, HBV or HCV infection.

Presence of Protective anti HBs level (>10 mIU):

Seventeen DS patients had a protective level (28.3%), while it was negative in 46 patients (71.7%).

In the control group, protective level was present in 51 children (85%) and negative in 9 (15%), p < 0.001 as shown in Figure 5.

The mean anti-HBs antibody level was 147.39 + 132.98 for DS children, while in the control group it was 164.09 + 217.65 (p > 0.1).

None of the DS children above the age of seven years had protective level, while it was present in of controls.

The immune response to HBV vaccine in different age groups of DS patients vs the control group is shown in Figure 6.

Discussion:

The epidemiology of infection with Hepatitis B virus (HBV) displays very marked geographical variation. In Canada, the USA and other developed countries, the prevalence of chronic carriage of Hepatitis B is about 0.5%(14). In China, South East Asia and parts of Africa, chronic carrier rates are over 10% (10,15). There is good evidence to support the recommendation of routine immunization for all children with HBV vaccine including randomized, placebo-controlled trials(16-18). Epidemiological evidence shows a decline in disease incidence in all countries within a short period of introduction of mass immunization(19). The decision to recommend vaccination of all children was based on the facts that the vaccine is safe, effective and the vaccination program is affordable. It costs more to treat chronic liver disease caused by HBV than to vaccinate all children(13,20). HBV vaccine has now been used extensively throughout the world and is currently being incorporated into the expanded program on immunization of the World Health Organization(21).

To control HBV infection, medical authorities in both Canada and the USA now recommend HBV immunization for all children(22-24). In USA, babies receive HBV vaccine at 0, 1 and 6 months or during any childhood visit thereafter. Those who have not previously received the three doses should initiate or complete the series during the 11 to 12 year old visit(25). In Canada, routine vaccination of school age children is recommended. This program has been shown to be very successful reaching over 90% of eligible children with three doses of vaccine(26). Italy, New Zealand and several Asian countries have already introduced routine vaccination to all infants. In Qatar, routine immunization for HBV at 0, 1 and 6 months was introduced in 1989.

Universal HBV immunization is not a policy in the UK. HBV vaccine is given at 0, 1 and 6 months only to babies at risk such as babies born to mothers who are carriers of HBV or who have had acute hepatitis during pregnancy(27).

Surveys in the past have shown a high incidence of carriage of HBV in residential institutions for severe learning disabilities. Thus consideration should be given to immunizing all new residents(7 ,8, 27). Staff of non-residential, childcare programs for the developmentally disabled (e.g. schools and other group settings) attended by known HBV carriers have a risk of infection comparable to that of health care workers and should be vaccinated(28).

Depending on local assessment, it may be appropriate to immunize children in day care settings and special schools for those with severe learning disabilities(27). especially before they begin to attend school(8).

Our survey in our Day Care training program setting for DS children showed that none of our DS patients had any hepatitis viral marker. This may mean that they have no risk factor for acquiring or conveying hepatitis virus infection in this setting in spite of their low rate of antibody response to HBV vaccination (only 28.3% Anti-HBs positive Vs 85% in the control group: p < 0.001). This is comparable to other studies(1, 6).

DS children starting special education schools for the mentally disabled after the age of 6-7 years who have no detectable antibodies to HBV might be at risk of acquiring HBV infection as is seen in studies carried out in other countries(7, 8, 27). Therefore, for children with DS at school entry we recommend re-vaccination with up to three doses of HBV vaccine in an attempt to achieve a protective anti-HBs level. As for DS children already attending SE schools for the mentally disabled (age 6-15 years), viral hepatitis screen should be done and HBV vaccination should be offered to susceptible persons with non-protective levels of anti-HBs and negative HBV markers(29).

Acknowledgements:

We would like to thank Dr. Abdul Latif Al Khal for his support and help with the revision of this paper.

Special thanks are also extended to Mrs. Nada Al Kadi and Miss Huda Al Kadi for their help and technical support in the preparation of this work.

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