Vol. 20, No. 3 Printed in Great Britain
International Journal of Epidemiology ©International Epidemiological Association 1991
Response to Hepatitis B Vaccine in Relation to the Hepatitis B Status of Family Members H M INSKIP," A J HALL,* I K TEMPLE,t F LOIK,# E HERBAGE.t J CHOTARD* AND H WHITTLEt
In many areas of the world, infection with the hepatitis B virus (HBV) at an early age is widespread and up to 20% of the adult population are carriers of the virus. In parts of Asia many children are infected by their mothers in early infancy, but this does not appear to be the situation in Africa. There is little understanding of mode of transmission in that continent but various mechanisms have been suggested such as poor vaccination techniques, circumcision and scarification practices, infection by contact with an open wound and transmission by arthropods. In The Gambia in West Africa it has been shown that sibling to sibling transmission is common and possibly the major route, though the mechanism of transmission is not clear. u Vaccination programmes against hepatitis B are now being implemented in many countries, but there is little information about what determines a good or a poor response to the vaccine. Given that the hepatitis B serological status of a child seems to be strongly determined by the status of his/her family,u it is possible that response to vaccine is also influenced by the profile of HBV infections in the family into which he/ she is born. This is an important question in the evaluation of the effectiveness of the vaccine. If a child
born into a family containing an HBV carrier is poorly protected by immunization then administration of the vaccine will fail to protect those at greatest risk. Conversely, if the vaccine response of such children is boosted due to the presence of carriers in the family the effect of the vaccine will be enhanced. The present study therefore aims to examine vaccine response in infants in relation to the pattern of HBV infection in their families. METHODS The Gambia Hepatitis Intervention Study was instigated in 1986 and aims to examine the effectiveness of the hepatitis B vaccine in preventing liver cancer. This is a very long term project as the vaccine is administered in infancy but the liver cancers develop in adulthood. The details of this study have been described elsewhere.3'4 All children registering at health centres over a period of four years are being recruited into the study, thus creating a group of 120000 children on whom information is available. The vaccine has been introduced into the Expanded Programme on Immunization (EPI) in The Gambia in a phased manner. Thus initially only one health centre administered the vaccine and all children registering in other health centres contributed to the unvaccinated group. Later a second health centre introduced the vaccine and by February 1990 nationwide coverage was achieved with
'International Agency for Research on Cancer, c/o MRC Laboratories, PO Box 273, Fajara, Banjul, The Gambia, West Africa. tMRC Laboratories, Fajara, Nr Banjul, The Gambia.
770
Downloaded from http://ije.oxfordjournals.org/ at Karolinska Institutet on May 25, 2015
Inskip HM (International Agency for Research on Cancer, c/o MRC Laboratories, Fajara, Nr Banjul, The Gambia), Hall AJ, Temple IK, Loik F, Herbage E, Chotard J and Whittle H. Response to hepatitis B vaccine in relation to the hepatitis B status of family members. Internationa/Journal of Epidemiology, 1991; 20: 770-773. The influence of the hepatitis B status of family members on the response to hepatitis B vaccine of an infant has been examined in 395 families. The presence of one or more HBsAg-positive family members did not appear to have any effect on the vaccine response. This is an encouraging finding as children born into carrier families are at an increased risk of becoming carriers themselves. That the vaccine response of such children is as good as for those born into noncarrier families means that they are likely to be protected against the carrier state by the vaccine.
RESPONSE TO HEPATITIS B VACCINE
RESULTS HBV Infection in Families Some 395 families of 399 index children (including four sets of twins) were recruited into the study although it was not always possible to obtain a blood sample from every family member. Of the original 399 children 293
were traced at one year and a blood sample obtained. Both children in two of the sets of twins were traced and so these 293 children are from 291 families. Of these 293 children, 171 (43%) had received four doses of vaccine, 182 (46%) three doses, 28 (7%) two doses and three children (1%) had received only one dose. The hepatitis B serological status of the family members of these children is presented in Table 1. Only three children had no family members ever infected with HBV. These three children had 0,1, and 2 siblings respectively none of whom had been infected, but for one of these index children the status of the father was unknown. Of the 293 children 88 (30.0%) had at least one family member positive for HBsAg. HBV Infection by Geographical Area No differences were seen in the hepatitis B status of the parents in the two geographical areas, but family size was greater in the Eastern region and thus children in this area tended to have a larger number of siblings who were positive for the two HBV markers. After adjustment for the number of siblings bled there was no difference in the positivity rate for siblings. However, while there were no differences between the areas for positivity of any particular type of family member (mother, father or siblings) there was a significant difference between the proportions of families with at least one HBsAg-positive member when the whole data set of 395 families was examined. The proportions in the two areas were 23% and 37% for Brikama and URD respectively and this effect remained after adjustment for number of siblings bled (p = 0.01). No difference between the areas was observed for HBeAg positivity amongst family members. Anti-HBs Response to Vaccination At one year of age the anti-HBs levels of the index children were found to be high with only four (1.4%) children being non-responders to the vaccine with an antibody level of less than 10 mlU/ml vaccine. Levels of over 1000 mlU/ml were found in 177 (60.4%) of the children. Seventeen index children were positive for anti-HBc at one year of age. Of these, 11 were re-bled at two years of age and only one was still positive for this antibody, thus indicating that maternal antibody was still present at one year of age for most of these children. None of the children were positive for HBsAg which is encouraging as in other data from The Gambia 7% of unvaccinated children aged one to two years were HBsAg carriers.6 This indicates that the vaccine has been successful in preventing the HBsAg carrier state during the first year of life.
Downloaded from http://ije.oxfordjournals.org/ at Karolinska Institutet on May 25, 2015
approximately 60000 of the study group having received the vaccine. Four doses of plasma-derived H-B-Vax (10 ug/dose), produced by Merck, Sharp and Dohme, are given intramuscularly in the deltoid; the first when the child is brought to be registered at the health centre (as soon after birth as possible) and the remaining doses at the ages of two, four and nine months. In each of the first four areas to administer the vaccine, thefirst250 children registering at the clinic were recruited into a cohort to be followed up annually to examine vaccine response in terms of levels of antibody to hepatitis B surface antigen (anti-HBs) and vaccine failures.5 At recruitment a blood sample was obtained from the mothers of all these children and, in two of the areas, Brikama in the Western region and two neighbouring centres in the Upper River Division (URD) at the Eastern end of the country, an attempt was made to obtain blood samples from the fathers of the index children and all the other children of the mother by visiting the family home. At the home visit, information about the house in which the index child lived was also obtained. Only the families of those children living closest to the health centre were recruited with the aim of obtaining information on 200 families in each of the two areas. The index children were given their first dose of hepatitis B vaccine at the time of recruitment and received the remaining doses as and when they attended an EPI clinic for vaccination. The index children were then bled when they were at least one year of age to examine their response to the vaccine. All blood samples were analysed for hepatitis B surface antigen (HBsAg) by reverse passive haemagglutination ('Hepatest', Burroughs Wellcome) and radioimmunoassay ('Sorin', Biomedica) was used to test for hepatitis B surface antibody (anti-HBs), core antibody (anti-HBc) and for 'e' antigen (HBeAg) amongst the HBsAg positives. Anti-HBs was quantitated in mlU/ml with the WHO reference preparation as standard, this being used at nine different levels of dilution. The data were analysed using EPILOG and the Generalized Linear Interactive Modelling (GLIM) program to relate the infants' vaccine response to the hepatitis B status of family members.
771
772
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY TABLE 1
Prevalence of HBV markers in families of vaccinated children
Family member
Number in study
Number bled
No
%
No
%
Mother Father Sibling
291 291 529
290 242 451
39 25 68
(13.4) (10.3) (15.1)
4 2 44
(1.4) (0.8) (9.8)
Vaccine Response and HBV Infection Related to Housing Characteristics Various characteristics associated with the homes of the families were examined. None appeared to have any influence on the child's response to vaccine. However, using the data on all 395 families the presence or Anti-HBs levels in index children at one year by presence or absence of an HBsAg-positive family member HBsAg-positive family member Anti-HBs at 1 year 9999 Total
No 4 (2%) 11 (5%) 67 (33%) 82(40%) 41(20%) 205
0 5 29 43 11 88
Yes (0%) (6%) (33%) (49%) (12%)
Total 4 (1%) 16 (6%) 96 (33%) 125 (43%) 52 (18%) 293
Anti-HBc +ve % No 250 226 249
(86.2) (93.4) (55.2)
absence of an HBsAg-positive family member was examined in relation to the housing characteristics. A surprising finding was that families living in houses made of mud or grass or under a thatched roof were more likely to have an HBsAg-positive person in the family than those living in concrete houses or under corrugated roofs. Of those living in a concrete house, 31/157 (19.7%) had an HBsAg-positive family member as opposed to a 84/240 (35%) of those in a mud or grass house. The corresponding figures for roof type were 73/294 (24.8%) of those with a corrugated roof versus 42/103 (40.8%) of those with a thatched roof. After adjustment for area and number of siblings bled the association was still strong (p9999 mlU/ml) also tended to come from non-carrier families. The geometric mean concentrations of antibody are marginally lower for children born into carrier families with levels of 1645 and 1878 mlU/ml in the carrier and non-carrier families respectively (p = 0.6). These analyses were repeated to examine the effect of HBsAg positivity in the different types of family members separately, namely mothers, fathers and siblings, but no effect was found on the index child's response to vaccination.
TABLE 2
HBeAg +ve
HBsAg +ve
RESPONSE TO HEPATITIS B VACCINE
In conclusion, the hepatitis B profile of the family into which a child is born appears to have little influence in determining that child's response to the vaccine. Thus children at high risk of becoming carriers of the virus should be protected by the vaccine. ACKNOWLEDGEMENTS This study is generously funded by a grant from the Department of Cooperation and Development of the Ministry of Foreign Affairs of Italy. The vaccine for the study was donated by Merck, Sharp and Dohme. We thank Fiona Shenton, Fatou Joof and Maimuna Mendy, MRC Laboratories, Fajara, The Gambia for technical assistance, the health workers of The Gambian Medical and Health Department for their support, and the children and their families in the study for their patience and cooperation. REFERENCES Whittle H C, Bradley A K, McLauchlan K, et al. Hepatitis B infection in two Gambian villages Lancet 1983; i: 1203-6. 2 Whittle H, Inskip H, Bradley A K, et al. The pattern of childhood hepatitis B infection over 4 years in two Gambian villages. 1 Infect Dis 1990; 161: 1112-15. 'The Gambia Hepatitis Intervention Study Group. The Gambia Hepatitis Intervention Study. Can Res 1987; 47: 5782-87. "The Gambia Hepatitis Intervention Study Group. Hepatitis B vaccine in the Expanded Programme of Immunization: The Gambian experience. Lancet 1989; 1: 1057-9. 5 Inskip H M, Hall A J, Chotard J, et al. Hepatitis B vaccine in the Gambian Expanded Programme on Immunization: Factors influencing antibody response. Inl J Epidemiol 1991; 20: 764-69. 'Vail Mayans M, Hall AJ, Inskip HM, et al. Risk factors for transmission of hepatitis B virus to Gambian children. Lancet 1990; 336: 1107-9. 'Smuzness W, Harley EJ, Prince AM. Intrafamilial spread of asymptomatic hepatitis B. AmerJ Mcd Sri 1975; 270:293-304. 1 Tower E A. Postnatal intrafamilial spread of hepatitis B infection in Alaskan Eskimo infants. Alaska Medicine 1985; 27: 92-7. 9 WilliamsS J, Craig P I, Uddle C, Batey R G, Farrell G C. Hepatitis B in Australia: Determinants of intrafamilial spread. Aust NZ J Med\9gl; 17:220-27. M Lok A S, Lai C, Wu P, Ng M M. Response to hepatitis B vaccine in family members of HBsAg carriers. J Mcd Virol 1986; 19: 33-9. "Zahradnik JM, Heiberg D, Hollinger FB. Hepatitis B vaccine: immune responses in children from families with an HBsAg carrier. Vaccine 1985; 3: 407-13. 12 Prince A M, White T, Pollock N, Riddle J, Brotman B, Richardson L. Epidemiology of hepatitis B infection in Liberian infants. Infect lmmun 1981; 32: 148-62. o Coursaget P, Yvonnet B, Chotard J, et al. Age- and sex-related study of hepatitis B virus chronic carrier state in infants from an endemic area (Senegal). J Med Virol 1987; 22: 1-5. "Toukan A U, Sharaiha Z K, Abu-el-rub O A, et al. The epidemiology of hepatitis B virus among family members in the Middle East. Am J Epidemiol 1990; 132: 220-32. 1
(Revised version received March 1991)
Downloaded from http://ije.oxfordjournals.org/ at Karolinska Institutet on May 25, 2015
the mother's HBsAg status and the child's antibody level at one year was observed, in agreement with the findings of this smaller study.5 In West Africa, vertical transmission from mother to child early in life is rare11213 and in these studies the HBsAg status of the mother has had little influence on the child's response to vaccine. Although perhaps disappointing that there is no apparent boosting in children living in infected families it is good that the converse does not occur, namely that children in infected families respond less well. Since such children are at greatest risk of becoming carriers2 this means that the vaccine is effective in the group in which protection is most needed. This is an encouraging finding for those incorporating the hepatitis B vaccine into the EPI. That there is a difference in the HBsAg prevalence rate amongst family members between the two areas is not surprising given the variations seen elsewhere in The Gambia. Notably, Whittle et al.1>2 have shown considerable differences between two neighbouring villages in the centre of the country and these are larger than the differences found in the current study where the distance between the two areas is much greater. It should be noted that the children in this study were not randomly selected and were chosen as those living close to the health centres studied. This may have introduced some bias, though in this group, the antiHBs levels, and effect of the mother's HBsAg status on them, are similar to those from different groups of children chosen randomly from areas covered by the same health centres.5 Thus it appears that the effect of any bias caused by the non-random selection is unlikely to be large. An unexpected finding of this study was the association between HBsAg positivity in family members and the type of house in which the family lived. It is difficult to assess socioeconomic status in The Gambia but it is possible that house type is one indicator. If so then it appears that those at a lower socioeconomic level are more likely to be HBsAg positive. This is in agreement with findings from Toukan et a/14 in a study in Jordan although their assessment of socioeconomic status was based on a variety of factors only one of which was concerned with the structure of the house. Methods of sanitation and type of water supply are also factors which contributed to their assessment of socioeconomic status but are not associated with HBsAg status in this study. Another possible explanation for the association with house type is that houses made of mud or grass or with a thatched roof might be more likely to harbour insects which may transmit infection.9
773
International Journal of Epidemiology ©International Epidemiological Association 1991
Response to Hepatitis B Vaccine in Relation to the Hepatitis B Status of Family Members H M INSKIP," A J HALL,* I K TEMPLE,t F LOIK,# E HERBAGE.t J CHOTARD* AND H WHITTLEt
In many areas of the world, infection with the hepatitis B virus (HBV) at an early age is widespread and up to 20% of the adult population are carriers of the virus. In parts of Asia many children are infected by their mothers in early infancy, but this does not appear to be the situation in Africa. There is little understanding of mode of transmission in that continent but various mechanisms have been suggested such as poor vaccination techniques, circumcision and scarification practices, infection by contact with an open wound and transmission by arthropods. In The Gambia in West Africa it has been shown that sibling to sibling transmission is common and possibly the major route, though the mechanism of transmission is not clear. u Vaccination programmes against hepatitis B are now being implemented in many countries, but there is little information about what determines a good or a poor response to the vaccine. Given that the hepatitis B serological status of a child seems to be strongly determined by the status of his/her family,u it is possible that response to vaccine is also influenced by the profile of HBV infections in the family into which he/ she is born. This is an important question in the evaluation of the effectiveness of the vaccine. If a child
born into a family containing an HBV carrier is poorly protected by immunization then administration of the vaccine will fail to protect those at greatest risk. Conversely, if the vaccine response of such children is boosted due to the presence of carriers in the family the effect of the vaccine will be enhanced. The present study therefore aims to examine vaccine response in infants in relation to the pattern of HBV infection in their families. METHODS The Gambia Hepatitis Intervention Study was instigated in 1986 and aims to examine the effectiveness of the hepatitis B vaccine in preventing liver cancer. This is a very long term project as the vaccine is administered in infancy but the liver cancers develop in adulthood. The details of this study have been described elsewhere.3'4 All children registering at health centres over a period of four years are being recruited into the study, thus creating a group of 120000 children on whom information is available. The vaccine has been introduced into the Expanded Programme on Immunization (EPI) in The Gambia in a phased manner. Thus initially only one health centre administered the vaccine and all children registering in other health centres contributed to the unvaccinated group. Later a second health centre introduced the vaccine and by February 1990 nationwide coverage was achieved with
'International Agency for Research on Cancer, c/o MRC Laboratories, PO Box 273, Fajara, Banjul, The Gambia, West Africa. tMRC Laboratories, Fajara, Nr Banjul, The Gambia.
770
Downloaded from http://ije.oxfordjournals.org/ at Karolinska Institutet on May 25, 2015
Inskip HM (International Agency for Research on Cancer, c/o MRC Laboratories, Fajara, Nr Banjul, The Gambia), Hall AJ, Temple IK, Loik F, Herbage E, Chotard J and Whittle H. Response to hepatitis B vaccine in relation to the hepatitis B status of family members. Internationa/Journal of Epidemiology, 1991; 20: 770-773. The influence of the hepatitis B status of family members on the response to hepatitis B vaccine of an infant has been examined in 395 families. The presence of one or more HBsAg-positive family members did not appear to have any effect on the vaccine response. This is an encouraging finding as children born into carrier families are at an increased risk of becoming carriers themselves. That the vaccine response of such children is as good as for those born into noncarrier families means that they are likely to be protected against the carrier state by the vaccine.
RESPONSE TO HEPATITIS B VACCINE
RESULTS HBV Infection in Families Some 395 families of 399 index children (including four sets of twins) were recruited into the study although it was not always possible to obtain a blood sample from every family member. Of the original 399 children 293
were traced at one year and a blood sample obtained. Both children in two of the sets of twins were traced and so these 293 children are from 291 families. Of these 293 children, 171 (43%) had received four doses of vaccine, 182 (46%) three doses, 28 (7%) two doses and three children (1%) had received only one dose. The hepatitis B serological status of the family members of these children is presented in Table 1. Only three children had no family members ever infected with HBV. These three children had 0,1, and 2 siblings respectively none of whom had been infected, but for one of these index children the status of the father was unknown. Of the 293 children 88 (30.0%) had at least one family member positive for HBsAg. HBV Infection by Geographical Area No differences were seen in the hepatitis B status of the parents in the two geographical areas, but family size was greater in the Eastern region and thus children in this area tended to have a larger number of siblings who were positive for the two HBV markers. After adjustment for the number of siblings bled there was no difference in the positivity rate for siblings. However, while there were no differences between the areas for positivity of any particular type of family member (mother, father or siblings) there was a significant difference between the proportions of families with at least one HBsAg-positive member when the whole data set of 395 families was examined. The proportions in the two areas were 23% and 37% for Brikama and URD respectively and this effect remained after adjustment for number of siblings bled (p = 0.01). No difference between the areas was observed for HBeAg positivity amongst family members. Anti-HBs Response to Vaccination At one year of age the anti-HBs levels of the index children were found to be high with only four (1.4%) children being non-responders to the vaccine with an antibody level of less than 10 mlU/ml vaccine. Levels of over 1000 mlU/ml were found in 177 (60.4%) of the children. Seventeen index children were positive for anti-HBc at one year of age. Of these, 11 were re-bled at two years of age and only one was still positive for this antibody, thus indicating that maternal antibody was still present at one year of age for most of these children. None of the children were positive for HBsAg which is encouraging as in other data from The Gambia 7% of unvaccinated children aged one to two years were HBsAg carriers.6 This indicates that the vaccine has been successful in preventing the HBsAg carrier state during the first year of life.
Downloaded from http://ije.oxfordjournals.org/ at Karolinska Institutet on May 25, 2015
approximately 60000 of the study group having received the vaccine. Four doses of plasma-derived H-B-Vax (10 ug/dose), produced by Merck, Sharp and Dohme, are given intramuscularly in the deltoid; the first when the child is brought to be registered at the health centre (as soon after birth as possible) and the remaining doses at the ages of two, four and nine months. In each of the first four areas to administer the vaccine, thefirst250 children registering at the clinic were recruited into a cohort to be followed up annually to examine vaccine response in terms of levels of antibody to hepatitis B surface antigen (anti-HBs) and vaccine failures.5 At recruitment a blood sample was obtained from the mothers of all these children and, in two of the areas, Brikama in the Western region and two neighbouring centres in the Upper River Division (URD) at the Eastern end of the country, an attempt was made to obtain blood samples from the fathers of the index children and all the other children of the mother by visiting the family home. At the home visit, information about the house in which the index child lived was also obtained. Only the families of those children living closest to the health centre were recruited with the aim of obtaining information on 200 families in each of the two areas. The index children were given their first dose of hepatitis B vaccine at the time of recruitment and received the remaining doses as and when they attended an EPI clinic for vaccination. The index children were then bled when they were at least one year of age to examine their response to the vaccine. All blood samples were analysed for hepatitis B surface antigen (HBsAg) by reverse passive haemagglutination ('Hepatest', Burroughs Wellcome) and radioimmunoassay ('Sorin', Biomedica) was used to test for hepatitis B surface antibody (anti-HBs), core antibody (anti-HBc) and for 'e' antigen (HBeAg) amongst the HBsAg positives. Anti-HBs was quantitated in mlU/ml with the WHO reference preparation as standard, this being used at nine different levels of dilution. The data were analysed using EPILOG and the Generalized Linear Interactive Modelling (GLIM) program to relate the infants' vaccine response to the hepatitis B status of family members.
771
772
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY TABLE 1
Prevalence of HBV markers in families of vaccinated children
Family member
Number in study
Number bled
No
%
No
%
Mother Father Sibling
291 291 529
290 242 451
39 25 68
(13.4) (10.3) (15.1)
4 2 44
(1.4) (0.8) (9.8)
Vaccine Response and HBV Infection Related to Housing Characteristics Various characteristics associated with the homes of the families were examined. None appeared to have any influence on the child's response to vaccine. However, using the data on all 395 families the presence or Anti-HBs levels in index children at one year by presence or absence of an HBsAg-positive family member HBsAg-positive family member Anti-HBs at 1 year 9999 Total
No 4 (2%) 11 (5%) 67 (33%) 82(40%) 41(20%) 205
0 5 29 43 11 88
Yes (0%) (6%) (33%) (49%) (12%)
Total 4 (1%) 16 (6%) 96 (33%) 125 (43%) 52 (18%) 293
Anti-HBc +ve % No 250 226 249
(86.2) (93.4) (55.2)
absence of an HBsAg-positive family member was examined in relation to the housing characteristics. A surprising finding was that families living in houses made of mud or grass or under a thatched roof were more likely to have an HBsAg-positive person in the family than those living in concrete houses or under corrugated roofs. Of those living in a concrete house, 31/157 (19.7%) had an HBsAg-positive family member as opposed to a 84/240 (35%) of those in a mud or grass house. The corresponding figures for roof type were 73/294 (24.8%) of those with a corrugated roof versus 42/103 (40.8%) of those with a thatched roof. After adjustment for area and number of siblings bled the association was still strong (p9999 mlU/ml) also tended to come from non-carrier families. The geometric mean concentrations of antibody are marginally lower for children born into carrier families with levels of 1645 and 1878 mlU/ml in the carrier and non-carrier families respectively (p = 0.6). These analyses were repeated to examine the effect of HBsAg positivity in the different types of family members separately, namely mothers, fathers and siblings, but no effect was found on the index child's response to vaccination.
TABLE 2
HBeAg +ve
HBsAg +ve
RESPONSE TO HEPATITIS B VACCINE
In conclusion, the hepatitis B profile of the family into which a child is born appears to have little influence in determining that child's response to the vaccine. Thus children at high risk of becoming carriers of the virus should be protected by the vaccine. ACKNOWLEDGEMENTS This study is generously funded by a grant from the Department of Cooperation and Development of the Ministry of Foreign Affairs of Italy. The vaccine for the study was donated by Merck, Sharp and Dohme. We thank Fiona Shenton, Fatou Joof and Maimuna Mendy, MRC Laboratories, Fajara, The Gambia for technical assistance, the health workers of The Gambian Medical and Health Department for their support, and the children and their families in the study for their patience and cooperation. REFERENCES Whittle H C, Bradley A K, McLauchlan K, et al. Hepatitis B infection in two Gambian villages Lancet 1983; i: 1203-6. 2 Whittle H, Inskip H, Bradley A K, et al. The pattern of childhood hepatitis B infection over 4 years in two Gambian villages. 1 Infect Dis 1990; 161: 1112-15. 'The Gambia Hepatitis Intervention Study Group. The Gambia Hepatitis Intervention Study. Can Res 1987; 47: 5782-87. "The Gambia Hepatitis Intervention Study Group. Hepatitis B vaccine in the Expanded Programme of Immunization: The Gambian experience. Lancet 1989; 1: 1057-9. 5 Inskip H M, Hall A J, Chotard J, et al. Hepatitis B vaccine in the Gambian Expanded Programme on Immunization: Factors influencing antibody response. Inl J Epidemiol 1991; 20: 764-69. 'Vail Mayans M, Hall AJ, Inskip HM, et al. Risk factors for transmission of hepatitis B virus to Gambian children. Lancet 1990; 336: 1107-9. 'Smuzness W, Harley EJ, Prince AM. Intrafamilial spread of asymptomatic hepatitis B. AmerJ Mcd Sri 1975; 270:293-304. 1 Tower E A. Postnatal intrafamilial spread of hepatitis B infection in Alaskan Eskimo infants. Alaska Medicine 1985; 27: 92-7. 9 WilliamsS J, Craig P I, Uddle C, Batey R G, Farrell G C. Hepatitis B in Australia: Determinants of intrafamilial spread. Aust NZ J Med\9gl; 17:220-27. M Lok A S, Lai C, Wu P, Ng M M. Response to hepatitis B vaccine in family members of HBsAg carriers. J Mcd Virol 1986; 19: 33-9. "Zahradnik JM, Heiberg D, Hollinger FB. Hepatitis B vaccine: immune responses in children from families with an HBsAg carrier. Vaccine 1985; 3: 407-13. 12 Prince A M, White T, Pollock N, Riddle J, Brotman B, Richardson L. Epidemiology of hepatitis B infection in Liberian infants. Infect lmmun 1981; 32: 148-62. o Coursaget P, Yvonnet B, Chotard J, et al. Age- and sex-related study of hepatitis B virus chronic carrier state in infants from an endemic area (Senegal). J Med Virol 1987; 22: 1-5. "Toukan A U, Sharaiha Z K, Abu-el-rub O A, et al. The epidemiology of hepatitis B virus among family members in the Middle East. Am J Epidemiol 1990; 132: 220-32. 1
(Revised version received March 1991)
Downloaded from http://ije.oxfordjournals.org/ at Karolinska Institutet on May 25, 2015
the mother's HBsAg status and the child's antibody level at one year was observed, in agreement with the findings of this smaller study.5 In West Africa, vertical transmission from mother to child early in life is rare11213 and in these studies the HBsAg status of the mother has had little influence on the child's response to vaccine. Although perhaps disappointing that there is no apparent boosting in children living in infected families it is good that the converse does not occur, namely that children in infected families respond less well. Since such children are at greatest risk of becoming carriers2 this means that the vaccine is effective in the group in which protection is most needed. This is an encouraging finding for those incorporating the hepatitis B vaccine into the EPI. That there is a difference in the HBsAg prevalence rate amongst family members between the two areas is not surprising given the variations seen elsewhere in The Gambia. Notably, Whittle et al.1>2 have shown considerable differences between two neighbouring villages in the centre of the country and these are larger than the differences found in the current study where the distance between the two areas is much greater. It should be noted that the children in this study were not randomly selected and were chosen as those living close to the health centres studied. This may have introduced some bias, though in this group, the antiHBs levels, and effect of the mother's HBsAg status on them, are similar to those from different groups of children chosen randomly from areas covered by the same health centres.5 Thus it appears that the effect of any bias caused by the non-random selection is unlikely to be large. An unexpected finding of this study was the association between HBsAg positivity in family members and the type of house in which the family lived. It is difficult to assess socioeconomic status in The Gambia but it is possible that house type is one indicator. If so then it appears that those at a lower socioeconomic level are more likely to be HBsAg positive. This is in agreement with findings from Toukan et a/14 in a study in Jordan although their assessment of socioeconomic status was based on a variety of factors only one of which was concerned with the structure of the house. Methods of sanitation and type of water supply are also factors which contributed to their assessment of socioeconomic status but are not associated with HBsAg status in this study. Another possible explanation for the association with house type is that houses made of mud or grass or with a thatched roof might be more likely to harbour insects which may transmit infection.9
773
