Duration of Hepatitis B Immunity in Low Risk Children Receiving Hepatitis B Vaccinations from Birth - 2 OF 4

[Guest guest]

Materials and Methods

Study Population

We conducted 2 studies in Alaska children. All the children but 1 were

Alaska Natives. Since 1985, all Native children in Alaska have received

hepatitis B vaccine as part of a statewide vaccination program. Hepatitis B

vaccination is initiated within the first 7 days of life, with the second

dose given at 4-6 weeks and the third at 6 months of age. Until 1989, a

plasma-derived hepatitis B vaccine (Heptavax-B, 10 µg; Merck Sharp & Dohme,

West Point, PA) was given. Since 1989, yeast recombinant hepatitis B

vaccines [RecombivaxHB, 2.5 µg (Merck Sharp & Dohme), or Engerix-B, 10 µg

(Kline Beecham, Rixensart, Belgium)] have been used. Study 1 consisted

of children whose initial response to the hepatitis B vaccine series was

unknown (groups 1a and 1b), and study 2 consisted of children with a

documented anti-HBs titer >/=10 mIU/mL after the initial vaccine series

(Groups 2a, 2b and 2c) (Table 1). All booster doses in both studies used

RecombivaxHB.

The institutional review boards of the Alaska Area Native Health Service,

the Indian Health Service and the Centers for Disease Control and Prevention

approved the protocols for both studies. Approval was also obtained from the

Anchorage Native Health Board and Southcentral Foundation. Written informed

consent was obtained from the parents or guardians of the children plus

verbal assents from all children older than 7 years.

Study Design

Study 1. Two groups of children born to HBsAg-negative mothers and

vaccinated in infancy were examined. The initial antibody responses after

the primary vaccination for children in this study were unknown. The first

group consisted of 102 children (Table 1) who had received plasma-derived

vaccine in infancy (group 1a); the second consisted of 208 children who had

received recombinant vaccine (group 1b). Potential participants were

identified by a computer search of immunization records, and they were

invited to participate.

At enrollment, sera were obtained from all children and tested for anti-HBs

and antibody to hepatitis B core antigen (anti-HBc). Children who were

anti-HBc-negative with anti-HBs <10 mIU/mL were randomized by a

computer-generated schedule to receive either a 2.5-µg booster dose at that

time or deferred for 3 years. Serum specimens were obtained 10-14 days after

the booster dose and were tested for anti-HBs.

Those returning in 3 years were retested for anti-HBs and anti-HBc. Children

who were anti-HBc-negative and whose anti-HBs remained <10 mIU/mL then

received a 2.5-µg booster dose. After the study was under way, early results

led to a desire to obtain more immediate data on the booster response of

children who had originally received the plasma vaccine (group 1a). Rather

than wait for 3 years, group 1a children whose booster dose had initially

been deferred were recalled early, and the booster dose was given an average

of 1.5 years after initial recruitment.

Study 2. These children were originally part of a long term follow-up study

of children who had received hepatitis B vaccine from birth and had their

sera tested for anti-HBs after completion of the initial vaccination series.

Only children who responded with anti-HBs titers of >/=10 mIU/mL or >/=10

standard ratio units (used in or before 1986) were included. Group 2a

consisted of 17 children of HBsAg-negative mothers who had received a

plasma-derived vaccine (Table 1) and were boosted with 5 µg of recombinant

vaccine (Recombivax). Group 2b consisted of 36 children of HBsAg-negative

mothers who had received a recombinant vaccine. Approximately one-half of

the children in group 2b were randomly assigned to receive a 2.5-µg dose of

recombinant vaccine, whereas the remaining children received a 5-µg dose.

Group 2c included 16 children who were born of HBsAg-positive mothers and

who had received a plasma-derived vaccine; they were boosted with 5 µg of

recombinant vaccine.

At enrollment, sera were obtained from all children and tested for anti-HBs

and anti-HBc. The children were recalled at ~2 months and 2 years after the

booster dose and tested for anti-HBs. Those who did not respond initially

(at the 2-month visit) to the booster dose with an anti-HBs >/=10 mIU/mL

received additional doses of recombinant vaccine and were retested.

Laboratory Testing

All serologic specimens were tested quantitatively by radioimmunoassay (RIA)

for anti-HBc (CORAB; Abbott Laboratories, Abbott Park, IL) and qualitatively

by RIA for anti-HBs (AUSAB-RIA; Abbott Laboratories). The anti-HBs titers

were reported in milli-International Units (mIU) per mL using the WHO

international reference standard.[13]

Data Analysis

Anti-HBs >/=10 mIU/mL in a child was considered protected against hepatitis

B infection.[6] An anamnestic response to a hepatitis B vaccine booster dose

was defined as a rise of anti-HBs from <10 mIU/mL to >/=10 mIU/mL. Anti-HBs

titers were log-transformed for calculating geometric mean titer (GMT), and

comparisons of GMT over time were made with a paired t test with the

log-transformed values. For analysis, persons with undetectable anti-HBs

were assigned a value of 0.1 mIU/mL. Proportions were compared with the use

of a ?2 or Fisher exact test, as appropriate. All P values were two-sided.

[Guest guest]

Materials and Methods

Study Population

We conducted 2 studies in Alaska children. All the children but 1 were

Alaska Natives. Since 1985, all Native children in Alaska have received

hepatitis B vaccine as part of a statewide vaccination program. Hepatitis B

vaccination is initiated within the first 7 days of life, with the second

dose given at 4-6 weeks and the third at 6 months of age. Until 1989, a

plasma-derived hepatitis B vaccine (Heptavax-B, 10 µg; Merck Sharp & Dohme,

West Point, PA) was given. Since 1989, yeast recombinant hepatitis B

vaccines [RecombivaxHB, 2.5 µg (Merck Sharp & Dohme), or Engerix-B, 10 µg

(Kline Beecham, Rixensart, Belgium)] have been used. Study 1 consisted

of children whose initial response to the hepatitis B vaccine series was

unknown (groups 1a and 1b), and study 2 consisted of children with a

documented anti-HBs titer >/=10 mIU/mL after the initial vaccine series

(Groups 2a, 2b and 2c) (Table 1). All booster doses in both studies used

RecombivaxHB.

The institutional review boards of the Alaska Area Native Health Service,

the Indian Health Service and the Centers for Disease Control and Prevention

approved the protocols for both studies. Approval was also obtained from the

Anchorage Native Health Board and Southcentral Foundation. Written informed

consent was obtained from the parents or guardians of the children plus

verbal assents from all children older than 7 years.

Study Design

Study 1. Two groups of children born to HBsAg-negative mothers and

vaccinated in infancy were examined. The initial antibody responses after

the primary vaccination for children in this study were unknown. The first

group consisted of 102 children (Table 1) who had received plasma-derived

vaccine in infancy (group 1a); the second consisted of 208 children who had

received recombinant vaccine (group 1b). Potential participants were

identified by a computer search of immunization records, and they were

invited to participate.

At enrollment, sera were obtained from all children and tested for anti-HBs

and antibody to hepatitis B core antigen (anti-HBc). Children who were

anti-HBc-negative with anti-HBs <10 mIU/mL were randomized by a

computer-generated schedule to receive either a 2.5-µg booster dose at that

time or deferred for 3 years. Serum specimens were obtained 10-14 days after

the booster dose and were tested for anti-HBs.

Those returning in 3 years were retested for anti-HBs and anti-HBc. Children

who were anti-HBc-negative and whose anti-HBs remained <10 mIU/mL then

received a 2.5-µg booster dose. After the study was under way, early results

led to a desire to obtain more immediate data on the booster response of

children who had originally received the plasma vaccine (group 1a). Rather

than wait for 3 years, group 1a children whose booster dose had initially

been deferred were recalled early, and the booster dose was given an average

of 1.5 years after initial recruitment.

Study 2. These children were originally part of a long term follow-up study

of children who had received hepatitis B vaccine from birth and had their

sera tested for anti-HBs after completion of the initial vaccination series.

Only children who responded with anti-HBs titers of >/=10 mIU/mL or >/=10

standard ratio units (used in or before 1986) were included. Group 2a

consisted of 17 children of HBsAg-negative mothers who had received a

plasma-derived vaccine (Table 1) and were boosted with 5 µg of recombinant

vaccine (Recombivax). Group 2b consisted of 36 children of HBsAg-negative

mothers who had received a recombinant vaccine. Approximately one-half of

the children in group 2b were randomly assigned to receive a 2.5-µg dose of

recombinant vaccine, whereas the remaining children received a 5-µg dose.

Group 2c included 16 children who were born of HBsAg-positive mothers and

who had received a plasma-derived vaccine; they were boosted with 5 µg of

recombinant vaccine.

At enrollment, sera were obtained from all children and tested for anti-HBs

and anti-HBc. The children were recalled at ~2 months and 2 years after the

booster dose and tested for anti-HBs. Those who did not respond initially

(at the 2-month visit) to the booster dose with an anti-HBs >/=10 mIU/mL

received additional doses of recombinant vaccine and were retested.

Laboratory Testing

All serologic specimens were tested quantitatively by radioimmunoassay (RIA)

for anti-HBc (CORAB; Abbott Laboratories, Abbott Park, IL) and qualitatively

by RIA for anti-HBs (AUSAB-RIA; Abbott Laboratories). The anti-HBs titers

were reported in milli-International Units (mIU) per mL using the WHO

international reference standard.[13]

Data Analysis

Anti-HBs >/=10 mIU/mL in a child was considered protected against hepatitis

B infection.[6] An anamnestic response to a hepatitis B vaccine booster dose

was defined as a rise of anti-HBs from <10 mIU/mL to >/=10 mIU/mL. Anti-HBs

titers were log-transformed for calculating geometric mean titer (GMT), and

comparisons of GMT over time were made with a paired t test with the

log-transformed values. For analysis, persons with undetectable anti-HBs

were assigned a value of 0.1 mIU/mL. Proportions were compared with the use

of a ?2 or Fisher exact test, as appropriate. All P values were two-sided.

[Guest guest]

Materials and Methods

Study Population

We conducted 2 studies in Alaska children. All the children but 1 were

Alaska Natives. Since 1985, all Native children in Alaska have received

hepatitis B vaccine as part of a statewide vaccination program. Hepatitis B

vaccination is initiated within the first 7 days of life, with the second

dose given at 4-6 weeks and the third at 6 months of age. Until 1989, a

plasma-derived hepatitis B vaccine (Heptavax-B, 10 µg; Merck Sharp & Dohme,

West Point, PA) was given. Since 1989, yeast recombinant hepatitis B

vaccines [RecombivaxHB, 2.5 µg (Merck Sharp & Dohme), or Engerix-B, 10 µg

(Kline Beecham, Rixensart, Belgium)] have been used. Study 1 consisted

of children whose initial response to the hepatitis B vaccine series was

unknown (groups 1a and 1b), and study 2 consisted of children with a

documented anti-HBs titer >/=10 mIU/mL after the initial vaccine series

(Groups 2a, 2b and 2c) (Table 1). All booster doses in both studies used

RecombivaxHB.

The institutional review boards of the Alaska Area Native Health Service,

the Indian Health Service and the Centers for Disease Control and Prevention

approved the protocols for both studies. Approval was also obtained from the

Anchorage Native Health Board and Southcentral Foundation. Written informed

consent was obtained from the parents or guardians of the children plus

verbal assents from all children older than 7 years.

Study Design

Study 1. Two groups of children born to HBsAg-negative mothers and

vaccinated in infancy were examined. The initial antibody responses after

the primary vaccination for children in this study were unknown. The first

group consisted of 102 children (Table 1) who had received plasma-derived

vaccine in infancy (group 1a); the second consisted of 208 children who had

received recombinant vaccine (group 1b). Potential participants were

identified by a computer search of immunization records, and they were

invited to participate.

At enrollment, sera were obtained from all children and tested for anti-HBs

and antibody to hepatitis B core antigen (anti-HBc). Children who were

anti-HBc-negative with anti-HBs <10 mIU/mL were randomized by a

computer-generated schedule to receive either a 2.5-µg booster dose at that

time or deferred for 3 years. Serum specimens were obtained 10-14 days after

the booster dose and were tested for anti-HBs.

Those returning in 3 years were retested for anti-HBs and anti-HBc. Children

who were anti-HBc-negative and whose anti-HBs remained <10 mIU/mL then

received a 2.5-µg booster dose. After the study was under way, early results

led to a desire to obtain more immediate data on the booster response of

children who had originally received the plasma vaccine (group 1a). Rather

than wait for 3 years, group 1a children whose booster dose had initially

been deferred were recalled early, and the booster dose was given an average

of 1.5 years after initial recruitment.

Study 2. These children were originally part of a long term follow-up study

of children who had received hepatitis B vaccine from birth and had their

sera tested for anti-HBs after completion of the initial vaccination series.

Only children who responded with anti-HBs titers of >/=10 mIU/mL or >/=10

standard ratio units (used in or before 1986) were included. Group 2a

consisted of 17 children of HBsAg-negative mothers who had received a

plasma-derived vaccine (Table 1) and were boosted with 5 µg of recombinant

vaccine (Recombivax). Group 2b consisted of 36 children of HBsAg-negative

mothers who had received a recombinant vaccine. Approximately one-half of

the children in group 2b were randomly assigned to receive a 2.5-µg dose of

recombinant vaccine, whereas the remaining children received a 5-µg dose.

Group 2c included 16 children who were born of HBsAg-positive mothers and

who had received a plasma-derived vaccine; they were boosted with 5 µg of

recombinant vaccine.

At enrollment, sera were obtained from all children and tested for anti-HBs

and anti-HBc. The children were recalled at ~2 months and 2 years after the

booster dose and tested for anti-HBs. Those who did not respond initially

(at the 2-month visit) to the booster dose with an anti-HBs >/=10 mIU/mL

received additional doses of recombinant vaccine and were retested.

Laboratory Testing

All serologic specimens were tested quantitatively by radioimmunoassay (RIA)

for anti-HBc (CORAB; Abbott Laboratories, Abbott Park, IL) and qualitatively

by RIA for anti-HBs (AUSAB-RIA; Abbott Laboratories). The anti-HBs titers

were reported in milli-International Units (mIU) per mL using the WHO

international reference standard.[13]

Data Analysis

Anti-HBs >/=10 mIU/mL in a child was considered protected against hepatitis

B infection.[6] An anamnestic response to a hepatitis B vaccine booster dose

was defined as a rise of anti-HBs from <10 mIU/mL to >/=10 mIU/mL. Anti-HBs

titers were log-transformed for calculating geometric mean titer (GMT), and

comparisons of GMT over time were made with a paired t test with the

log-transformed values. For analysis, persons with undetectable anti-HBs

were assigned a value of 0.1 mIU/mL. Proportions were compared with the use

of a ?2 or Fisher exact test, as appropriate. All P values were two-sided.

[Guest guest]

Materials and Methods

Study Population

We conducted 2 studies in Alaska children. All the children but 1 were

Alaska Natives. Since 1985, all Native children in Alaska have received

hepatitis B vaccine as part of a statewide vaccination program. Hepatitis B

vaccination is initiated within the first 7 days of life, with the second

dose given at 4-6 weeks and the third at 6 months of age. Until 1989, a

plasma-derived hepatitis B vaccine (Heptavax-B, 10 µg; Merck Sharp & Dohme,

West Point, PA) was given. Since 1989, yeast recombinant hepatitis B

vaccines [RecombivaxHB, 2.5 µg (Merck Sharp & Dohme), or Engerix-B, 10 µg

(Kline Beecham, Rixensart, Belgium)] have been used. Study 1 consisted

of children whose initial response to the hepatitis B vaccine series was

unknown (groups 1a and 1b), and study 2 consisted of children with a

documented anti-HBs titer >/=10 mIU/mL after the initial vaccine series

(Groups 2a, 2b and 2c) (Table 1). All booster doses in both studies used

RecombivaxHB.

The institutional review boards of the Alaska Area Native Health Service,

the Indian Health Service and the Centers for Disease Control and Prevention

approved the protocols for both studies. Approval was also obtained from the

Anchorage Native Health Board and Southcentral Foundation. Written informed

consent was obtained from the parents or guardians of the children plus

verbal assents from all children older than 7 years.

Study Design

Study 1. Two groups of children born to HBsAg-negative mothers and

vaccinated in infancy were examined. The initial antibody responses after

the primary vaccination for children in this study were unknown. The first

group consisted of 102 children (Table 1) who had received plasma-derived

vaccine in infancy (group 1a); the second consisted of 208 children who had

received recombinant vaccine (group 1b). Potential participants were

identified by a computer search of immunization records, and they were

invited to participate.

At enrollment, sera were obtained from all children and tested for anti-HBs

and antibody to hepatitis B core antigen (anti-HBc). Children who were

anti-HBc-negative with anti-HBs <10 mIU/mL were randomized by a

computer-generated schedule to receive either a 2.5-µg booster dose at that

time or deferred for 3 years. Serum specimens were obtained 10-14 days after

the booster dose and were tested for anti-HBs.

Those returning in 3 years were retested for anti-HBs and anti-HBc. Children

who were anti-HBc-negative and whose anti-HBs remained <10 mIU/mL then

received a 2.5-µg booster dose. After the study was under way, early results

led to a desire to obtain more immediate data on the booster response of

children who had originally received the plasma vaccine (group 1a). Rather

than wait for 3 years, group 1a children whose booster dose had initially

been deferred were recalled early, and the booster dose was given an average

of 1.5 years after initial recruitment.

Study 2. These children were originally part of a long term follow-up study

of children who had received hepatitis B vaccine from birth and had their

sera tested for anti-HBs after completion of the initial vaccination series.

Only children who responded with anti-HBs titers of >/=10 mIU/mL or >/=10

standard ratio units (used in or before 1986) were included. Group 2a

consisted of 17 children of HBsAg-negative mothers who had received a

plasma-derived vaccine (Table 1) and were boosted with 5 µg of recombinant

vaccine (Recombivax). Group 2b consisted of 36 children of HBsAg-negative

mothers who had received a recombinant vaccine. Approximately one-half of

the children in group 2b were randomly assigned to receive a 2.5-µg dose of

recombinant vaccine, whereas the remaining children received a 5-µg dose.

Group 2c included 16 children who were born of HBsAg-positive mothers and

who had received a plasma-derived vaccine; they were boosted with 5 µg of

recombinant vaccine.

At enrollment, sera were obtained from all children and tested for anti-HBs

and anti-HBc. The children were recalled at ~2 months and 2 years after the

booster dose and tested for anti-HBs. Those who did not respond initially

(at the 2-month visit) to the booster dose with an anti-HBs >/=10 mIU/mL

received additional doses of recombinant vaccine and were retested.

Laboratory Testing

All serologic specimens were tested quantitatively by radioimmunoassay (RIA)

for anti-HBc (CORAB; Abbott Laboratories, Abbott Park, IL) and qualitatively

by RIA for anti-HBs (AUSAB-RIA; Abbott Laboratories). The anti-HBs titers

were reported in milli-International Units (mIU) per mL using the WHO

international reference standard.[13]

Data Analysis

Anti-HBs >/=10 mIU/mL in a child was considered protected against hepatitis

B infection.[6] An anamnestic response to a hepatitis B vaccine booster dose

was defined as a rise of anti-HBs from <10 mIU/mL to >/=10 mIU/mL. Anti-HBs

titers were log-transformed for calculating geometric mean titer (GMT), and

comparisons of GMT over time were made with a paired t test with the

log-transformed values. For analysis, persons with undetectable anti-HBs

were assigned a value of 0.1 mIU/mL. Proportions were compared with the use

of a ?2 or Fisher exact test, as appropriate. All P values were two-sided.