text:
The Australian Immunisation Handbook 10th Edition
PDF printable version of 4.5 Hepatitis B of the 10th edition of the Handbook (PDF 530 KB)
This chapter has been amended on July 2016.
- 4.5.1 - Virology
- 4.5.2 - Clinical features
- 4.5.3 - Epidemiology
- 4.5.4 - Vaccines
- 4.5.5 - Transport, storage and handling
- 4.5.6 - Dosage and administration
- 4.5.7 - Recommendations
- 4.5.8 - Pregnancy and breastfeeding
- 4.5.9 - Contraindications
- 4.5.10 - Adverse events
- 4.5.11 - Public health management of hepatitis B
- 4.5.12 - Variations from product information
- References
4.5.1 Virology
Hepatitis B virus (HBV) contains circular, partially double-stranded DNA. The outer surface of the virus is glycolipid, which contains the hepatitis B surface antigen (HBsAg). Other important antigenic components are the hepatitis B core antigen (HBcAg) and hepatitis B e antigen (HBeAg). HBcAg is not detectable in serum, but can be detected in liver tissue in persons with acute or chronic hepatitis B infection. HBeAg, and antibodies against HBeAg (anti-HBe) or the HBcAg (anti-HBc), are serological markers of HBV infection. Antibodies against HBsAg (anti-HBs) indicate immunity, which may result from either natural infection or immunisation (in which case there would not be any markers of HBV infection). Persistence of HBsAg denotes infectivity, which is greater if HBeAg and/or HBV DNA are also positive.1 Occult hepatitis B infection is characterised by the presence of HBV DNA in the liver (with or without detectable HBV DNA in the serum) and negative HBsAg.2
4.5.2 Clinical features
In approximately 30 to 50% of adults, infection causes symptomatic acute hepatitis, but in neonates and young children, particularly those <1 year of age, initial infection is usually asymptomatic.3,4 The incubation period is usually 45 to 180 days and the period of communicability extends from several weeks before the onset of acute illness usually to the end of the period of acute illness. Acute illness is clinically indistinguishable from other forms of hepatitis, and symptoms include fever, jaundice, malaise, anorexia, nausea and vomiting, abdominal pain (especially in the right upper quadrant), myalgia, and the passage of dark-coloured urine and light-coloured stools. Jaundice may be preceded by an acute febrile illness with arthralgia or arthritis and rash, most typical of hepatitis B. During recovery, malaise and fatigue may persist for many weeks. Fulminant hepatitis occurs in up to 1% of acute cases.1,5
Following acute infection, approximately 1 to 10% of persons infected in adulthood,4,6 but up to 90% of those infected in early infancy,6 become chronically infected with hepatitis B. Persons chronically infected with HBV are identified by the long-term presence (longer than 6 months) of circulating HBsAg.1,5 Those with occult infection may reactivate HBV infection if they become immunocompromised.
Persons with chronic HBV infection are capable of transmitting the disease, including mother-to-child peripartum transmission, though they often remain asymptomatic and may not be aware that they are infected. Most of the serious complications associated with hepatitis B occur in the context of chronic HBV infection, which is associated in up to 25% of cases with premature mortality due to cirrhosis and/or hepatocellular carcinoma.1
4.5.3 Epidemiology
The prevalence of chronic HBV infection differs in different parts of the world, and may be quite variable within countries. The prevalence of chronic HBV infection varies from less than 0.5% among Caucasians in the United States, northern Europe and Australia, 1 to 5% in the Mediterranean countries, parts of eastern Europe, Africa, Central and South America, up to greater than 10% in many sub-Saharan African, East and Southeast Asian and Pacific island populations.7-10 In regions of moderate to high prevalence of HBsAg (where ≥2% of the population is HBsAg-positive), infections are mainly acquired perinatally or in early childhood.1
Chronic infection and its sequelae, including cirrhosis and hepatocellular carcinoma, contribute to the majority of HBV disease burden in Australia. In recent decades, the burden from such disease has been increasing, concurrent with the increasing number of immigrants from regions of high HBV prevalence.11 Aboriginal and Torres Strait Islander people, and migrants born in Asia and Pacific islands, North Africa, Middle Eastern and Mediterranean countries, have a significantly increased prevalence of chronic HBV infection compared with the rest of the Australian-born population.12,13 First-generation immigrants of culturally and linguistically diverse background, who are mostly from countries of high HBV endemicity, usually retain the prevalence of chronic HBV infection of their country of origin. Other population groups with an increased prevalence of markers of HBV infection include patients with HIV infection, persons who used injected drugs between 1980 and 1990, and household contacts of someone diagnosed with hepatitis between 1980 and 1990.13 Notification of chronic HBV infection depends on levels of hepatitis B testing and reporting, and a substantial proportion of persons with chronic HBV infection remain undiagnosed. It has been estimated by mathematical modelling that, in 2010, about 170 000 people were living with HBV infection in Australia, with about 335 deaths due to HBV infection in that year.14
Newly acquired cases of HBV infection in Australia mostly occur in young adults, through injecting drug use, skin penetration procedures or sexual contact.15 Between 2006 and 2010, the notification rate of newly acquired hepatitis B in Australia ranged from 1.0 to 1.4 per 100 000 population. Since 2001, the rate of diagnosis of newly acquired infections has declined substantially among people aged 15–29 years and has remained relatively stable among people aged ≥30 years.14-16 However, some new HBV infections are asymptomatic and may go undetected.
Similar to chronic infection, higher rates of notified cases of newly acquired hepatitis B, or hospitalisation due to acute hepatitis B, have been reported among Aboriginal and Torres Strait Islander people compared with the general Australian population.17,18 In one United States study, adults with diabetes mellitus had a greater chance of developing acute hepatitis B disease than the general population;19 however, there are no published Australian studies examining this.
Transmission of HBV may result from inoculation through broken or penetrated skin, or by mucosal contact with blood or other body fluids (mainly vaginal fluids and semen) from an infectious person. There are four major routes of HBV transmission:
- perinatal transmission from infected mother to neonate (vertical transmission), usually occurring at or around the time of birth
- parenteral or mucosal exposure to infected blood and other bodily fluids; common scenarios include:
- sharing of contaminated equipment that penetrates the skin, such as needles (among persons who inject drugs), tattoo equipment, body-piercing equipment, acupuncture equipment and razor blades
- needle-stick injury, for example, in a healthcare setting
- contact between infective body fluids and mucous membranes
- sexual contact (including vaginal or anal intercourse, although the latter is associated with a higher risk)
- non-sexual contact with an infected person (horizontal transmission), including household transmission, for example, child-to-child transmission through contact between open sores or wounds.
In Australia, screening of blood and organ donors using serological, and subsequently nucleic acid amplification testing, has virtually eliminated the risk of transmission of hepatitis B through blood transfusion and organ transplants.20,21 Saliva may contain levels of virus that are likely to be infective only if inoculated directly into tissue (ocular or mucous membranes). The risk of transmission by inadvertent inoculation by other means, such as by toothbrush, razor etc., or through close personal contact in households in which one or more infected persons reside, is low but not negligible.22-29
The strategy for prevention of hepatitis B through immunisation in Australia commenced in the early 1980s, with vaccination programs targeting individuals with increased risk of HBV exposure, including infants at particular risk of infection at birth. Universal infant vaccination commenced in the Northern Territory in 1990. A universal hepatitis B vaccination program was recommended for infants and adolescents in 1996. The adolescent program commenced in some states and territories in 1997 and the universal infant program, which includes a dose given at birth, began nationally in 2000. The adolescent program will continue until those immunised for hepatitis B in the infant program reach adolescence.
4.5.4 Vaccines
Monovalent hepatitis B vaccines
- Engerix-B – GlaxoSmithKline Australia Pty Ltd (recombinant DNA hepatitis B vaccine). Adult formulation – Each 1.0 mL monodose vial or pre-filled syringe contains 20 �g recombinant hepatitis B surface antigen (HBsAg) protein, adsorbed onto 0.5 mg aluminium as aluminium hydroxide. Paediatric formulation – Each 0.5 mL monodose vial or pre-filled syringe contains 10 �g HBsAg protein, adsorbed onto 0.25 mg aluminium as aluminium hydroxide. Both formulations may contain yeast proteins.
- H-B-Vax II – bioCSL Pty Ltd/Merck Sharp & Dohme (Australia) Pty Ltd (recombinant DNA hepatitis B vaccine). Adult formulation – Each 1.0 mL monodose vial or pre-filled syringe contains 10 �g recombinant HBsAg protein, adsorbed onto 0.5 mg aluminium hydroxide. Paediatric formulation – Each 0.5 mL monodose vial or pre-filled syringe contains 5 �g recombinant HBsAg protein, adsorbed onto 0.25 mg aluminium hydroxide. Dialysis formulation – Each 1.0 mL monodose vial contains 40 �g recombinant HBsAg protein, adsorbed onto 0.5 mg aluminium hydroxide. All formulations may contain yeast proteins.
Combination vaccines that contain hepatitis B
- Hexaxim – Sanofi-Aventis Australia Pty Ltd (DTPa-hepB-IPV-Hib; diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b). Each 0.5 mL pre-filled syringe contains ≥20 IU diphtheria toxoid, ≥40 IU tetanus toxoid, 25 �g pertussis toxoid (PT), 25 �g filamentous haemagglutinin (FHA), 10 �g recombinant HBsAg, 40 D-antigen units inactivated poliovirus type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1), 32 D-antigen units type 3 (Saukett) and 12 �g purified Hib capsular polysaccharide (PRP) conjugated to 22–36 �g tetanus toxoid, adsorbed onto 0.6 mg aluminium as aluminium hydroxide. May contain traces of glutaraldehyde, formaldehyde, neomycin, streptomycin and polymyxin B.
- Infanrix hexa – GlaxoSmithKline Australia Pty Ltd (DTPa-hepB-IPV-Hib; diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b). The vaccine consists of both a 0.5 mL pre-filled syringe containing ≥30 IU diphtheria toxoid, ≥40 U tetanus toxoid, 25 �g PT, 25 g FHA, 8 �g pertactin, 10 �g recombinant HBsAg, 40 D-antigen units inactivated poliovirus type 1 (Mahoney), 8 D-antigen units type 2 (MEF-1) and 32 D-antigen units type 3 (Saukett), adsorbed onto aluminium hydroxide/phosphate; traces of formaldehyde, polysorbate 80, polysorbate 20, polymyxin and neomycin; and a vial containing a lyophilised pellet of 10 �g purified Hib capsular polysaccharide (PRP) conjugated to 20–40 �g tetanus toxoid. May contain yeast proteins.
- Twinrix Junior (360/10) – GlaxoSmithKline (formaldehyde-inactivated hepatitis A virus [HM175 strain] and recombinant hepatitis B vaccine). Each 0.5 mL monodose vial or pre-filled syringe contains 360 ELISA units of HAV antigens, 10 �g recombinant DNA hepatitis B surface antigen protein; 0.225 mg aluminium as aluminium phosphate/hydroxide; traces of formaldehyde, neomycin, trometamol and polysorbate 20. May contain yeast proteins.
- Twinrix (720/20) – GlaxoSmithKline (formaldehyde-inactivated hepatitis A virus [HM175 strain] and recombinant hepatitis B vaccine). Each 1.0 mL monodose vial or pre-filled syringe contains 720 ELISA units of HAV antigens, 20 �g recombinant DNA hepatitis B surface antigen protein; 0.45 mg aluminium as aluminium phosphate/hydroxide; traces of formaldehyde, neomycin, trometamol and polysorbate 20. May contain yeast proteins.
Hepatitis B vaccines are prepared using recombinant technology. After purification, the HBsAg protein is adsorbed onto elemental aluminium (as hydroxide and/or phosphate). Hepatitis B vaccines may contain up to 1% yeast proteins (but no yeast DNA).
The Engerix-B and the H-B-Vax II vaccines are manufactured by different processes, and the HBsAg content of 'equivalent' doses of these two vaccines is different. the HBsAg content of the paediatric formulations of these two vaccines is half that of the corresponding manufacturer's adult formulation. Studies of hepatitis B vaccines have been conducted using different schedules and intervals for different age groups. Acceptable schedules are shown in Table 4.5.1 and are described below.
The standard 3-dose schedule and variations
Neonates, children and young adults aged <20 years
The recommended Australian infant schedule consists of a dose of monovalent hepatitis B vaccine given at birth, followed by 3 doses of a hepatitis B-containing combination vaccine, given at 2, 4 and 6 months of age (refer to 'Infants and young children' in�4.5.7�Recommendations�below). If an infant did not receive the birth dose within the 1st 7 days of life, catch-up of that dose is not necessary. Such infants then only require 3 doses of a hepatitis B-containing vaccine, given at 2, 4 and 6 months of age.
A 3-dose schedule at birth, 1–2 months and 6–18 months of age has been shown to be equally as immunogenic as the recommended Australian schedule above; such schedules are often used overseas.30-32 Children born overseas who have received hepatitis B vaccine in such a 3-dose schedule can also be considered to have completed the primary vaccination course.
For infants, the final dose of the primary hepatitis B vaccine course should preferably be administered at ≥24 weeks of age. However, if the final dose is given at <24 weeks but ≥16 weeks of age, it is not necessary to repeat the dose, provided the minimum intervals between doses in Table 2.1.7 (in 2.1.5�Catch-up.) have been met.
For older children and young adults aged <20 years (who have not received hepatitis B vaccination earlier in life) a 3-dose schedule of the paediatric formulation (0.5 mL) of monovalent hepatitis B vaccine can be used (at times 0, 1 and 6 months), as per Table 4.5.1. Immunogenicity studies suggest there can be some flexibility of the vaccination schedule intervals for monovalent hepatitis B vaccines. The use of longer time intervals between doses does not impair the immunogenicity of hepatitis B vaccine.33,34 The minimum interval between the 1st and 3rd doses of a 3-dose primary schedule is 4 months. This means that a shortened 3-dose schedule provided at either 0, 1, 4 months or 0, 2, 4 months is acceptable.35 More compressed 3-dose schedules (e.g. 0, 1, 3 months) are not recommended. Such compressed schedules are associated with lower peak levels of anti-HBs antibody,36,37 and hence likely shorter duration of antibody persistence (at levels ≥10 mIU/mL),38 although the clinical significance of this is uncertain.39 (Refer also to 'Adults aged ≥20 years' below.)
Adults aged ≥20 years
For adults, monovalent hepatitis B vaccine adult formulation (1.0 mL) is given in a 3-dose schedule at times 0, 1 and 6 months (refer to Table 4.5.1). There is some flexibility regarding the interval between the doses. The proportion of vaccine recipients attaining a seroprotective anti-HBs antibody level (≥10 mIU/mL), generally measured 1–2 months after vaccination, is comparable between adults who received their 3rd dose at 4–6 months after the 1st dose and those who received their 3rd dose 6 months or more after the 1st dose.40 Increasing the interval between the 1st and 2nd doses has little effect on the final antibody level attained, but a longer interval between the 2nd and 3rd doses is associated with a higher final antibody level.37, 41, 42 However, for those who may be exposed to hepatitis B, delaying the 3rd dose may increase the risk of acquiring HBV infection.
For a shortened 3-dose schedule to attain comparable antibody levels to the standard 3-dose schedule, all three of the following minimum interval requirements must be satisfied:
- the minimum interval between the 1st and 2nd doses is 1 month,
- the minimum interval between the 2nd and 3rd doses is 2 months, and
- the minimum interval between the 1st and 3rd doses is 4 months.
That is, either a 0, 1, 4 month or a 0, 2, 4 month interval schedule is an acceptable 3-dose schedule for adults.43
The minimum intervals outlined above should be met where possible. More compressed 3-dose schedules (e.g. 0, 1, 3 months) are not recommended. If a compressed 3-dose schedule that does not meet these minimum intervals has already been administered, it may not be necessary to repeat a dose. Although compressed schedules are associated with lower peak antibody levels41 and hence likely shorter duration of antibody levels ≥10 mIU/mL,38 the significance of this is unclear. The majority of individuals in whom anti-HBs becomes undetectable have been shown to mount an anamnestic response to an additional vaccine dose, which indicates they are likely to be protected if exposed to hepatitis B virus.39
Note that the interval between the 1st and 3rd doses has been shortened to less than 4 months in studies of 4-dose accelerated schedules, with the aim to achieve a higher seroprotective antibody level sooner. However, as antibody levels are substantially lower after 3 accelerated doses than after the standard 3-dose schedule,42 a 4th dose is required to achieve comparable antibody levels to the standard 3-dose schedule (refer to 'Accelerated schedules' below).
The standard 3-dose schedule induces protective levels of neutralising antibody against hepatitis B virus in more than 90% of adults. The frequency of seroconversion increases progressively from approximately 35% after the 1st dose to more than 90% after the 3rd dose. There is evidence of immunity in most vaccine recipients after administration of 2 doses of a 3-dose schedule. However, the 3rd dose is necessary to increase the percentage of responders and to provide long-term protection.
Alternative 2-dose schedule for adolescents
Several studies have demonstrated that adolescents 11–15 years of age who receive 2 doses of adult formulation monovalent hepatitis B vaccine 4 to 6 months apart develop similar protective antibody levels to those vaccinated using paediatric formulations in the standard 3-dose schedule.44-46
Using a 2-dose schedule for the 11–15 years age group may improve compliance and will provide comparable immunogenicity to that of a 3-dose paediatric schedule. Adolescents (11–15 years of age) can be vaccinated with the adult formulation of either H-B-Vax II or Engerix-B in a 2-dose schedule (refer to Table 4.5.1).
|Age of vaccine recipient
|Dose (HBsAg protein)
|Volume per dose (mL)
|Number of doses
|Recommended schedule intervals *†
|Recommended infant schedule
Engerix-B (paediatric formulation)
H-B-Vax II (paediatric formulation)
10 �g
5 �g
(H-B-Vax II)
|Birth (if not given at birth, may be given up to 7 days of age)
Combination hepatitis B-containing vaccine
(e.g. Infanrix hexa DTPa-hepB-IPV-Hib)
|2, 4 and 6 ‡ months
|10 �g
1st dose: 2 months of age�
2nd dose: 4 months of age
(2 months after 1st dose)
3rd dose ‡: 6 months of age
(2 months after 2nd dose)
|Monovalent hepatitis B vaccines – standard 3-dose schedule
|Engerix-B (paediatric formulation)
|<20 years
|10 �g
1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 6 months after 1st dose
|Engerix-B (adult formulation)
|≥20 years
|20 �g
1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 6 months after 1st dose
|H-B-Vax II (paediatric formulation)
|<20 years
|5 �g
1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 6 months after 1st dose
|H-B-Vax II (adult formulation)
|≥20 years
|10 �g
1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 6 months after 1st dose
|H-B-Vax II (dialysis formulation)
|≥20 years
|40 �g
1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 6 months after 1st dose
|Monovalent hepatitis B vaccines – 2-dose schedule ONLY for adolescents aged 11–15 years
|Engerix-B (adult formulation)
|11–15 years
|20 �g
1st dose: day 0 (day of vaccination)
2nd dose: 6 months after 1st dose
|H-B-Vax II (adult formulation)
|11–15 years
|10 �g
1st dose: day 0 (day of vaccination)
2nd dose: between 4 and 6 months after 1st dose
|Combination hepatitis A/hepatitis B vaccines
|Twinrix (720/20) �
|1–<16 years
|20 �g
1st dose: day 0 (day of vaccination)
2nd dose: between 6 and 12 months after 1st dose (2-dose schedule)
|Twinrix Junior (360/10)
|1–<16 years
|10 �g
1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 6 months after 1st dose
|Twinrix (720/20)
|≥16 years
|20 �g
1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 6 months after 1st dose
*�For minimum intervals, refer to text above.
† In these schedules, the 'day 0' dose refers to the day when the 1st dose is given (i.e. day 0 of the vaccination course), not the age of the recipient. For infant vaccination, where the 1st dose is a 'birth dose' it is indicated as so.
‡�The final dose of the primary course for infants should preferably be given at ≥24 weeks of age ; however, if given at <24 weeks but ≥16 weeks of age, it is not necessary to repeat the dose, provided the minimum intervals between doses have been met (refer to Table 2.1.7 in 2.1.5 Catch-up).
� The 2 month dose can be given as early as 6 weeks of age.
��This schedule should not be used for those who require prompt protection against hepatitis B, for example, if there is close contact with a person known to be chronically infected with hepatitis B.
Accelerated schedules
Engerix-B (monovalent hepatitis B vaccine, paediatric and adult) and Twinrix (720/20) (combination hepatitis A/hepatitis B vaccine) are also registered for use in accelerated schedules, which consist of 4 doses in total (refer to Table 4.5.2 below). Accelerated schedules result in a high proportion of vaccine recipients attaining a seroprotective anti-HBs antibody level (≥10 mIU/mL) in the early months following commencement of the schedule. However, multiple studies have consistently shown that antibody levels are substantially lower at month 7, after 3 accelerated doses, than after the standard 3-dose schedule (0, 1, 6 months).42 Also, some studies, in particular among persons who inject drugs and/or inmates of correctional facilities, have shown a lower proportion of subjects attaining the seroprotective antibody level after 3 doses of an accelerated schedule than after the standard 3-dose schedule.42,47,48 After the 4th dose of an accelerated schedule, administered at 12 months, anti-HBs antibody levels are higher or comparable to those after a standard 3-dose schedule. Hence, a 4th dose should be administered at 12 months to complete an accelerated schedule.
Accelerated schedules should only be used for those persons with an imminent risk of exposure, such as those intending to travel to hepatitis B endemic areas with a very limited time before departure. As higher seroprotective rates after the 3rd dose of an accelerated 4-dose schedule are seen after the 0, 1, 2, 12 months schedule than after the 0, 7, 21 days, 12 months schedule, it is recommended that the latter schedule only be used in exceptional circumstances.
|Age of vaccine recipient (years)
|Dose (HBsAg protein)
|Volume (mL)
|Number of doses
| Recommended schedule
minimum interval
|Engerix-B (paediatric formulation)
|10 �g
| 1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 2 months after 1st dose
4th dose: 12 months after 1st dose
|Engerix-B (adult formulation)
|20 �g
| 1st dose: day 0 (day of vaccination)
2nd dose: 1 month after 1st dose
3rd dose: 2 months after 1st dose
4th dose: 12 months after 1st dose
1st dose: day 0 (day of vaccination)
2nd dose: 7 days after 1st dose
3rd dose: 21 days after 1st dose
4th dose: 12 months after 1st dose
|Twinrix (720/20)
|20 �g
| 1st dose: day 0 (day of vaccination)
2nd dose: 7 days after 1st dose
3rd dose: 21 days after 1st dose
4th dose: 12 months after 1st dose
Combination hepatitis A/hepatitis B vaccine schedules
The schedules for combination hepatitis A/hepatitis B vaccines are shown in Table 4.5.1 (and 4.4 Hepatitis A). Three-dose schedules for adults and children aged <16 years are acceptable; however, a 2-dose schedule in children 1–15 years of age, using Twinrix (720/20), also results in protective antibody levels for both hepatitis A and hepatitis B. An accelerated schedule for combination hepatitis A/hepatitis B vaccine in those aged ≥16 years is shown in Table 4.5.2. above. The appropriate use of accelerated schedules is discussed above.
The use of mixed vaccine schedules using both the combination hepatitis A/hepatitis B vaccine and monovalent hepatitis B vaccines is not routinely recommended. Generally, use of the same brand of vaccine is recommended. (Refer also to 'Interchangeability of hepatitis B vaccines' in 4.5.6 Dosage and administration below.)
4.5.5 Transport, storage and handling
Transport according to National vaccine storage guidelines: Strive for 5.46 Store at +2�C to +8�C. Do not freeze.
Infanrix hexa must be reconstituted by adding the entire contents of the syringe to the vial and shaking until the pellet is completely dissolved. Reconstituted vaccine should be used as soon as practicable. If storage is necessary, hold at room temperature for not more than 8 hours.
4.5.6 Dosage and administration
The schedules for hepatitis B vaccines and for combination hepatitis A/hepatitis B vaccines are shown in Table 4.5.1 and 4.5.2. For combination hepatitis A/hepatitis B vaccines, refer also to 4.4 Hepatitis A.
The dose of Engerix-B and H-B-Vax II (paediatric formulations) and Twinrix Junior (360/10) is 0.5 mL, to be given by IM injection.
The dose of Engerix-B and H-B-Vax II (adult formulations) and Twinrix (720/20) is 1.0 mL, to be given by IM injection.
The dose of Infanrix hexa is 0.5 mL, to be given by IM injection.
Hepatitis B and combination hepatitis A/hepatitis B vaccines can generally be co-administered simultaneously with, or at any time before or after, all other vaccines.
Interchangeability of hepatitis B vaccines
The Engerix-B and H-B-Vax II vaccines are manufactured by different processes, and the HBsAg content of an 'equivalent' dose is different. Although switching of vaccine brands is not recommended, in cases where the brand of vaccine used for previous doses is not known, another age-appropriate 'equivalent' dose brand (refer to Table 4.5.1) may be used. For example, a study in healthy neonates demonstrated comparable high levels of immunogenicity between two different mixed regimens that used two monovalent hepatitis B vaccines from different manufacturers.50 As there is only one brand of combination hepatitis A/hepatitis B vaccine, interchangeability is not relevant. (Refer also to 'Combination hepatitis A/hepatitis B vaccine schedules' in 4.5.4 Vaccines above.)
4.5.7 Recommendations
Infants and young children
The recommended hepatitis B vaccine schedule for infants from birth is shown in Table 4.5.1. A birth dose of monovalent paediatric formulation hepatitis B vaccine is recommended for all newborn infants. Following this birth dose, 3 doses of a hepatitis-B-containing vaccine (usually provided as DTPa-hepB-IPV-Hib) are recommended for all children, at 2, 4 and 6 months of age. Thus, a total of 4 doses of hepatitis B vaccine are provided in the 1st year of life. The 1st dose of a hepatitis B-containing vaccine can be given as early as 6 weeks of age. If the 1st dose is given at 6 weeks of age, the next scheduled doses should still be given at 4 months and 6 months of age.
If an infant has not received a birth dose within the 1st 7 days of life, a primary 3-dose course of a hepatitis B-containing combination vaccine should be given, at 2, 4 and 6 months of age; catch-up of the birth dose is not necessary.
The rationale for recommending the birth dose for all newborn infants is not only to prevent vertical transmission from a mother with chronic hepatitis B infection (recognising that there may be errors or delays in maternal testing, reporting, communication or appropriate response), but also to prevent horizontal transmission to the infant in the first months of life from persons with chronic hepatitis B infection who are household or other close contacts.48 The birth dose should be given as soon as the baby is medically stable, and preferably within 24 hours of birth. Every effort should be made to administer the vaccine before discharge from the obstetric hospital or delivery unit. All newborns of mothers known to have chronic hepatitis B infection must be given a birth dose of hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) (refer to 'Management of infants born to mothers who are HBsAg-positive' below).
Although it is not routinely recommended in Australia, infants or toddlers who have received a 3-dose schedule of hepatitis B vaccine (often given overseas) with doses at birth, 1–2 months of age and ≥6 months of age can also be considered fully vaccinated (refer to 4.5.4 Vaccines, 'The standard 3-dose schedule and variations' above).
The final dose of the primary hepatitis B vaccine course in infants should preferably be administered at ≥24 weeks of age. However, if the final dose is given at <24 weeks but ≥16 weeks of age, it is not necessary to repeat the dose, provided the minimum intervals between doses in Table 2.1.7 (in 2.1.5�Catch-up.) have been met.
Management of infants born to mothers who are HBsAg-positive
Routine antenatal screening of pregnant women for HBsAg is recommended to enable appropriate management to prevent newborn infants developing HBV infection (refer to 4.5.2 Clinical features and 4.5.3 Epidemiology above).52-54 It also enables appropriate follow-up and management of mothers who have chronic HBV infection, identification of the HBV immune status of other household members, and protection of those who are susceptible to HBV infection.
Infants born to HBsAg-positive mothers should be given HBIG and a dose of monovalent hepatitis B vaccine on the day of birth, concurrently but in separate thighs. The dose of HBIG is 100 IU, to be given by IM injection. It is preferable to administer HBIG immediately after birth (preferably within 12 hours of birth and certainly within 48 hours) as its efficacy decreases markedly if given more than 48 hours after birth.
The dose of monovalent hepatitis B vaccine should be given to the infant preferably within 24 hours of birth, and definitely within 7 days. This regimen results in seroconversion rates of more than 90% in neonates, even with concurrent administration of HBIG. Vaccination should not be delayed beyond 7 days after birth, as vaccination alone has been shown to be reasonably effective in preventing infection, provided it is given early.52 Three subsequent doses of a hepatitis B-containing vaccine should be given, at 2, 4 and 6 months of age, so that the infant receives a total of 4 doses of hepatitis B-containing vaccines.
Anti-HBs antibody and HBsAg levels should be measured in infants born to mothers with chronic hepatitis B infection 3 to 12 months after completing the primary vaccine course. Testing should not be performed before 9 months of age to avoid detection of anti-HBs antibodies from HBIG given at birth. If anti-HBs antibody levels are adequate (≥10 mIU/mL) and HBsAg is negative, then the infant is considered to be protected35 (refer to 'Serological testing following hepatitis B vaccination' below). If the anti-HBs level is <10 mIU/mL, expert advice regarding revaccination and/or further testing should be sought.
Preterm and low-birth-weight infants
Low-birth-weight preterm newborn infants do not respond as well to hepatitis B-containing vaccines as full-term infants.56-58 Thus, for low-birth-weight infants (<2000 g) and/or infants born at <32 weeks gestation (irrespective of weight), it is recommended to give the vaccine in a 4-dose schedule at 0 (birth), 2, 4 and 6 months of age, followed by either:
- measuring the anti-HBs antibody level at 7 months of age, and if the antibody titre is <10 mIU/mL, giving a booster at 12 months of age (due to a better immunogenic response at this age compared with a younger age); or
- giving a booster of a hepatitis B-containing vaccine at 12 months of age (without measuring the antibody titre).
HIV-positive and immunocompromised children
All HIV-positive and immunocompromised children should be age-appropriately vaccinated against hepatitis B.
HIV-positive children should receive 3 doses of hepatitis B vaccine using an adult formulation (i.e. double the standard recommended dose for children). In a limited number of studies, paediatric haemodialysis patients have demonstrated improved response when given higher doses in a 3-dose schedule.59,60
For specific hepatitis B recommendations for immunocompromised children, refer to 3.3.3 Vaccination of immunocompromised persons.
Vaccination of adolescents 10–13 years of age is recommended for all those in this age group who have not already received a primary course of hepatitis B vaccine. Refer to your state/territory health authority for further information about hepatitis B vaccine for this age group (refer to Appendix 1 Contact details for Australian, state and territory government health authorities and communicable disease control).
As the risk in Australian schools is very low,61 vaccination of classroom contacts of hepatitis B cases is seldom indicated. Nevertheless, vaccination of all children and adolescents should be encouraged.
A 2-dose schedule of hepatitis B vaccine using the adult formulation of either of the available monovalent vaccines should be considered for adolescents aged 11–15 years who are to receive hepatitis B vaccination (refer to Table 4.5.1 and 4.5.4 Vaccines above). A 2-dose schedule increases compliance and thus protection in this age group.
Adolescents who did not receive an age-appropriate completed course of vaccination should be identified and offered catch-up vaccination, particularly if they fall into one of the risk categories for hepatitis B infection, discussed under 'Adults' below.
Hepatitis B vaccination is recommended for the following groups of adults because they are either at a higher risk of acquiring hepatitis B infection and/or at higher risk of severe disease. Refer to Tables 4.5.1 and 4.5.2 Vaccines above for recommended adult vaccination schedules. Serological testing for previous or chronic hepatitis B infection may be indicated in many circumstances (refer to 'Serological testing prior to hepatitis B vaccination' below). Refer also to 3.3 Groups with special vaccination requirements.
When vaccination against both hepatitis B and hepatitis A is indicated, the combination hepatitis A/hepatitis B vaccines may be used. Refer to Tables 4.5.1 and 4.5.2 above and 'Recommendations for the use of combination hepatitis A/hepatitis B vaccines' below.
Household or other close (household-like) contacts of persons with hepatitis B
There is a low, but definite, risk of transmission from a person with acute or chronic hepatitis B to household or other close residential contacts (e.g. students or asylum seekers sharing residential facilities). This can be reduced by avoiding contact with blood or other body fluids and not sharing items that may penetrate the skin (such as combs, nail brushes, toothbrushes and razors). Immunisation of susceptible household-like contacts is strongly recommended. This includes household members of the adoptive family if the adopted child is known to have chronic hepatitis B infection.
Sexual contacts of persons with hepatitis B
Susceptible sexual partners of persons who are HBsAg-positive should be offered post-exposure HBIG and hepatitis B vaccination; both should be initiated within 14 days of the last sexual contact (refer to 4.5.11 Public health management of hepatitis B below and Table 4.5.3).
Hepatitis B is relatively common in clients of sexual health services and vaccination should be offered to susceptible persons at the time of first attendance.
Susceptible, sexually active men who have sex with men should be vaccinated. The combination hepatitis A/hepatitis B vaccine may be appropriate for men who have sex with men, if they are not immune to either disease, as they are at increased risk of both conditions (refer to 'Recommendations for the use of combination hepatitis A/hepatitis B vaccines' below).
Migrants from hepatitis B endemic countries
Migrants from hepatitis B endemic countries have a higher likelihood of having been previously infected with hepatitis B and of having a close household contact with chronic hepatitis B infection. Such persons should be offered testing for hepatitis B, and vaccination if appropriate. (Refer also to 3.3.8 Vaccination of migrants to Australia.) Areas of high endemicity, indicated by high seroprevalence of HBsAg, include most of East and Southeast Asia (except Japan), Pacific island groups, parts of central Asia and the Middle East, the Amazon Basin, and sub-Saharan Africa.62
Aboriginal and Torres Strait Islander people
There is an increased risk of acquiring new HBV infection among Aboriginal and Torres Strait Islander people compared with other Australians.17,18 Although many younger Aboriginal and Torres Strait Islander people, especially children and adolescents, would have been eligible for, and have received, hepatitis B vaccination through population-wide vaccination programs, it is recommended that Aboriginal and Torres Strait Islander people have their risks and vaccination status for hepatitis B reviewed, be offered testing for previous hepatitis B infection, and be offered vaccination if non-immune. (Refer also to 3.1 Vaccination for Aboriginal and Torres Strait Islander people.)
Adult haemodialysis patients and patients with severely impaired renal function in whom dialysis is anticipated
Dialysis patients, and patients with severely impaired renal function in whom dialysis is anticipated, may be at increased risk of acquiring hepatitis B infection and also respond less well to vaccination. These patients should be given a larger than usual dose of hepatitis B vaccine.
Adult haemodialysis or pre-dialysis patients should be given either:
- 1.0 mL of Engerix-B adult formulation (20 �g) in each arm at each schedule point (i.e. effectively giving a double dose on each occasion) in a 4-dose schedule at 0, 1, 2 and 6 months;63 or
- a single dose of H-B-Vax II dialysis formulation (40 �g) on each occasion in a 3-dose schedule at 0, 1 and 6 months.
Solid organ and haematopoietic stem cell transplant recipients
If seronegative for hepatitis B, solid organ transplant recipients should be vaccinated before transplantation as they may be at increased risk of infection from the transplanted organ.64 Haematopoietic stem cell transplant recipients should be revaccinated following transplantation, due to the loss of immune memory that often follows the transplant procedure. (Refer also to 3.3.3 Vaccination of immunocompromised persons.)
HIV-positive adults and other immunocompromised adults
HIV-positive adults, and other immunocompromised adults, may be at increased risk of acquiring hepatitis B infection and also respond less well to vaccination. Limited studies in HIV1-positive adults have demonstrated an improved and accelerated serological response to a schedule that consists of 4 double doses, comprising two injections of the standard adult dose (using Engerix-B) on each occasion, at times 0, 1, 2 and 6 months.65,66
Persons with chronic liver disease and/or hepatitis C
Hepatitis B vaccination is recommended for those in this category who are seronegative for hepatitis B, because of the risk of severe liver disease following infection with hepatitis B.67
Persons who inject drugs
Persons who inject drugs should be tested, and be vaccinated if they have not previously been infected with HBV.
Recipients of certain blood products
Screening of all blood donors for HBV using HBsAg and nucleic acid amplification tests has greatly decreased the incidence of transfusion-related hepatitis B virus infection. Since 2010, nucleic acid testing has been introduced nationally to improve detection of hepatitis B infection in donated blood, mainly through reduction of the infectious window period when acute hepatitis B infection may not be detected using HBsAg, but also through detecting persons with occult hepatitis B infection. This further reduces the residual risk of hepatitis B transmission through transfusion in Australia, to approximately 1 in 982 000 per unit transfused.21 However, persons with clotting disorders who receive blood product concentrates, persons with recurrent transfusion requirements, and persons with underlying immunocompromise68 have an elevated risk of hepatitis B virus infection, and should therefore be vaccinated.
Persons with developmental disabilities
Vaccination is recommended for persons who attend either residential or non-residential day-care facilities for persons with developmental disabilities. This is due to the high prevalence of markers indicating past or current infection in persons in these settings, including an HBsAg prevalence of >10%.69-71
Inmates of correctional facilities
Inmates are at increased risk of hepatitis B infection because of the prevalence of chronic hepatitis B among inmates, and the potential for unprotected sexual intercourse, injecting drug use and amateur tattooing in correctional facilities. Therefore, they should be offered the opportunity to be screened for hepatitis Bupon incarceration, as part of the preventive health program for blood-borne viruses, and vaccinated if susceptible.
Sex industry workers
Sex industry workers are one of the population groups at higher risk of HBV infection. They have been specifically identified as an important population on which to focus for the prevention of hepatitis B transmission.72 They are at a particularly high risk if they engage in unprotected sex.
Persons at occupational risk
The risk to persons in certain occupations differs considerably from setting to setting in different parts of Australia. However, it is recommended that all staff directly involved in patient care and/or the handling of human tissue, blood or body fluids should be vaccinated. In addition, standard precautions against exposure to human tissue, blood or body fluids should be used as a matter of routine.73
Other occupations where the risk of acquiring hepatitis B is increased include:
- police, members of the armed forces, emergency services staff and staff of correctional facilities; these persons should be vaccinated if they are assigned to duties that may involve exposure to human tissue, blood or body fluids
- funeral workers, embalmers and other workers who have regular contact with human tissue, blood or body fluids and/or used needles or syringes
- staff involved in both residential and non-residential care of persons with developmental disabilities, due to the high prevalence of markers of past or current infection in persons in this setting69-71
- workers who perform skin penetration procedures (e.g. tattooists, body-piercers).
Staff of child day-care centres will normally be at minimal risk of hepatitis B. If advice on risk is sought, the enquiry should be directed to the local public health authority.
Contact sports generally carry a low risk of hepatitis B infection. However, age-appropriate hepatitis B vaccination is recommended.
Travellers to hepatitis B endemic areas
Persons travelling to regions of intermediate or high endemicity, either long-term or for frequent short terms, or who are likely to undertake activities that increase their risks of exposure to HBV during travel, should be vaccinated.62 (Refer also to 3.2 Vaccination for international travel.)
Recommendations for the use of combination hepatitis A/hepatitis B vaccines
Combination hepatitis A/hepatitis B vaccines should be considered for susceptible persons in whom both hepatitis A and hepatitis B vaccines are recommended, including:
- travellers to, and expatriates living in, moderately to highly endemic areas for hepatitis A and B
- persons whose lifestyle puts them at increased risk of hepatitis A and hepatitis B (sexually active men who have sex with men, sex industry workers, persons who inject drugs and inmates of correctional facilities)
- persons who attend or work at residential or non-residential facilities for people with developmental disabilities
- persons with occupational risks of exposure to both hepatitis A and hepatitis B
- persons with chronic liver disease and/or hepatitis C
- solid organ transplant liver recipients or solid organ transplant recipients who have chronic liver disease (refer to Table 3.3.2 Recommendations for vaccinations for solid organ transplant (SOT) recipients).
If a combination hepatitis A/hepatitis B vaccine is not available, monovalent hepatitis A and hepatitis B vaccines can be administered simultaneously (in separate syringes at separate sites) (refer to 'Interchangeability of hepatitis B vaccines' above).
Refer to 4.5.7 Recommendations above and 4.4 Hepatitis A for more details. Refer also to 3.3 Groups with special vaccination requirements.
Booster doses
Booster doses of hepatitis B vaccine (after completion of a primary course by using recommended schedule) are not recommended for immunocompetent persons. This applies to children and adults, including healthcare workers and dentists.74-80 This is because there is good evidence that a completed primary course of hepatitis B vaccination provides long-lasting protection. Even though vaccine-induced antibody levels may decline with time and may become undetectable, immune memory persists and is thought to result in a protective immune response on re-exposure.81 However, booster doses are recommended for persons who are immunocompromised, in particular those with either HIV infection or renal failure. The time for boosting in such persons should be decided by regular monitoring of anti-HBs levels at 6- to 12-monthly intervals.74
Serological testing prior to hepatitis B vaccination
Routine antenatal screening of all pregnant women for HBsAg is recommended to allow appropriate measures to be implemented to prevent newborn infants developing chronic HBV infection49-51 (refer to 'Management of infants born to mothers who are HBsAg-positive' above).
Serological testing for evidence of past (or current) hepatitis B infection prior to vaccination may be warranted for certain older children, adolescents and adults. This is particularly so for those at increased risk of acquiring hepatitis B infection, such as persons who inject drugs, sex industry workers, immunocompromised persons, and those living in communities with higher prevalence of HBV, including migrant communities and Aboriginal and Torres Strait Islander people. Serological testing enables identification of persons who were infected by HBV, to facilitate timely appropriate clinical management and prevention of onward transmission, hence reducing population impact of HBV infection. Testing also identifies those who are susceptible to HBV infection and, as such, should be offered vaccination if they continue to have a high exposure risk (refer to 4.5.7 Recommendations above).72 Testing for immunity to hepatitis A infection (and vaccination of susceptible at-risk persons with combination hepatitis A/hepatitis B vaccines) may also be indicated for some population groups at increased risk of hepatitis A exposure (refer to 4.4 Hepatitis A).
Interpretation of the results of serological testing may be enhanced by discussion with the laboratory that performed the test, ensuring that relevant clinical information is provided.
Serological testing following hepatitis B vaccination
Anti-HBs antibody and HBsAg levels should be measured in infants born to mothers with chronic hepatitis B infection 3 to 12 months after completing the primary vaccine course (for more information refer to 'Management of infants born to mothers who are HBsAg-positive' above).
Other than for infants born to mothers with chronic hepatitis B infection, post-vaccination serological testing is recommended 4 to 8 weeks after completion of the primary course for persons in the following categories:
- those at significant occupational risk (e.g. healthcare workers whose work involves frequent exposure to human tissue, blood or body fluids)
- those at risk of severe or complicated HBV disease (e.g. persons who are immunocompromised, and persons with pre-existing liver disease not related to hepatitis B)
- those in whom a poor response to hepatitis B vaccination may occur (e.g. haemodialysis patients, persons with bleeding disorders vaccinated via the SC route)
- sexual partners and household, or other close household-like, contacts of persons who are infected with hepatitis B.35
For these individuals, if adequate anti-HBs levels (≥10 mIU/mL) are not reached on serological testing 4 to 8 weeks after the 3rd dose, the possibility of HBV infection, including chronic HBV infection, should be investigated by testing for serological markers, including HBsAg and anti-HBc antibodies. In select cases in which hepatitis B infection is suspected, HBV nucleic acid testing may also be indicated, and expert advice regarding further management should be sought. If there are no markers of HBV infection, the individual should be managed as a non-responder to hepatitis B vaccination (refer to 'Non-responders to primary vaccination' below).
If persons who are at significant risk of hepatitis B (such as healthcare workers) were not tested for anti-HBs within 4 to 8 weeks after completion of the documented primary course, they should still undergo serological testing to ensure immunity. If, on testing, they have an anti-HBs level of <10 mIU/mL, they should be given a single booster dose (4th dose) of vaccine. Persons with immune memory established from effective prior vaccination should respond to this booster dose. Anti-HBs should be checked 4 weeks later, and if the anti-HBs level remains <10 mIU/mL, the possibility of HBV infection should be investigated (and, if excluded, the person should be managed as a non-responder to vaccination, refer to below). If the anti-HBs level is ≥10 mIU/mL, the person can be regarded as immune.
Non-responders to primary vaccination
A non-responder is a person without HBV infection who has a documented history of an age-appropriate primary course of hepatitis B vaccine, but with a current anti-HBs level <10 mIU/mL. There are a number of potential options for non-responders. Persons who do not respond to the primary vaccination course, and in whom chronic HBV infection has been excluded, should be offered further doses.
As discussed above, in 'Serological testing following hepatitis B vaccination', a single booster dose (4th dose) of vaccine can be given to confirm non-responder status. Persons who are non-responders after being given the booster/4th dose (and in whom HBV infection has been excluded) should have 2 further doses of hepatitis B vaccine at monthly intervals, and be re-tested for anti-HBs levels at least 4 weeks after the last dose. The booster/4th dose that was received could be counted as the 1st of the 3 repeat doses, as recommended for non-responders. A few small studies have reported attainment of seroprotection in non-responders with high-dose formulations or double-dose administration for a 4th, or subsequent, dose of hepatitis B vaccination, but there is no consistent evidence to suggest that a higher proportion of subjects would respond with these higher-dose regimens.82-84
For HBsAg-negative healthcare workers who are non-responders to a primary course of vaccination and to subsequent additional IM doses (≥5 doses in total), some small observational studies report that some individuals may respond to the vaccine administered intradermally.85-87 Engerix-B (0.25 mL [5 μg] per dose) was used in these studies, giving up to 4 doses.85 Younger age and longer duration (≥6 months) since the last IM dose may be associated with greater probability of response.86 If an intradermal dose(s) is given, it is recommended that the anti-HBs levels be measured before each subsequent dose to assess for seroconversion.
Persistent non-responders should be informed that they should be considered not protected against hepatitis B and should minimise exposures. They should also be informed about the need for HBIG within 72 hours of parenteral or mucosal exposure to HBV (refer to Table 4.5.3).
4.5.8 Pregnancy and breastfeeding
Hepatitis B vaccine is not routinely recommended for pregnant or breastfeeding women. However, the WHO states that neither pregnancy nor breastfeeding is a contraindication to the use of this vaccine.88
Refer to 3.3 Groups with special vaccination requirements, Table 3.3.1 Recommendations for vaccination in pregnancy for more information.
4.5.9 Contraindications
The only absolute contraindications to hepatitis B vaccines are:
- anaphylaxis following a previous dose of any hepatitis B vaccine
- anaphylaxis following any vaccine component.
In particular, hepatitis B vaccines are contraindicated in persons with a history of anaphylaxis to yeast.
4.5.10 Adverse events
Extensive experience indicates that the birth dose of hepatitis B vaccine is very well tolerated by newborn infants. It does not interfere with either the establishment or maintenance of breastfeeding, and it is not associated with an increased risk of either fever, medical investigation for sepsis, or serious outcomes in newborns who were vaccinated compared with the unvaccinated.89-91
Adverse events after hepatitis B vaccination are transient and minor, and include soreness at the injection site (5%), fever (usually low grade; 2–3%), nausea, dizziness, malaise, myalgia and arthralgia. Fever can be expected in some neonates following immunisation with hepatitis B vaccine (0.6–3.7%).
Anaphylaxis has been reported very rarely in adults, notably in yeast-sensitive individuals.92 Although various adverse events such as demyelinating diseases, Guillain-Barr� syndrome and arthritis have been reported, there is no evidence of a causal relationship with hepatitis B vaccination.92,93
The World Health Organization Global Advisory Committee on Vaccine Safety states that 'multiple studies and review panels have concluded that there is no link between MS [multiple sclerosis] and hepatitis B vaccination'.94,95
The vaccine produces neither therapeutic effects nor adverse events in persons with chronic HBV infection. It is also safe, though of no additional benefit, in those already immune to hepatitis B through past natural infection.
4.5.11 Public health management of hepatitis B
Acute hepatitis B and newly identified chronic hepatitis B are notifiable diseases in all states and territories in Australia.
Further instructions about the public health management of hepatitis B, including management of cases of acute hepatitis B and newly identified chronic hepatitis B, and their contacts, should be obtained from state/territory public health authorities (refer to Appendix 1 Contact details for Australian, state and territory government health authorities and communicable disease control).
Following significant exposure (percutaneous, ocular or mucous membrane) to blood or to potentially blood-contaminated secretions, where feasible, the source individual should be tested for HBsAg as soon as possible.
If the person exposed has not been previously vaccinated against hepatitis B, their anti-HBs level, and anti-HBc and HBsAg status, should be determined immediately. If the person exposed is anti-HBs and anti-HBc negative (non-immune) and the source is either HBsAg-positive or cannot be identified and tested rapidly, a single dose of HBIG should be administered according to the recommendations in Table 4.5.3. below. The dose of HBIG is 100 IU for children weighing up to 30 kg (about 5 years of age) and 400 IU for all others. Hepatitis Bvaccine must also be given as soon as possible, with further doses as recommended in Table 4.5.3. below.
For previously vaccinated persons exposed to either an HBsAg-positive source or a source whose hepatitis B status cannot be determined, post-exposure prophylaxis is not necessary if there was a documented protective response (anti-HBs level ≥10 mIU/mL) at any time after vaccination. If the response to previous vaccination is unknown, the anti-HBs level should be determined as quickly as possible. If the anti-HBs level is <10 mIU/mL and there is no evidence of HBV infection, HBIG and HBV vaccine should be administered as per Table 4.5.3. below.
All healthcare workers should be immunised against hepatitis B. Completion of a full course of hepatitis B vaccination is strongly recommended for any non-immune healthcare worker who has sustained a needle-stick injury or other potential hepatitis B exposure.
|Type of exposure
|Hepatitis B immunoglobulin
|Perinatal (exposure of babies during and after birth)*
|100 IU, by IM injection
|Single dose immediately after birth (preferably within 12 hours of birth and certainly within 48 hours)
|0.5 mL, by IM injection
|Immediately after birth (preferably within 24 hours, no later than 7 days),† then at 2, 4 and 6 months of age
|Percutaneous, ocular or mucous membrane
| 400 IU, by IM injection
100 IU, if body weight
<30 kg
|Single dose within 72 hours of exposure
|0.5 mL or 1 mL (depending on age), by IM injection
|Within 7 days† of exposure and at 1 and 6 months after 1st dose
| 400 IU, by IM injection
100IU, if body weight <30 kg
|Single dose, preferably within 72 hours of last sexual contact‡
|0.5 mL or 1 mL (depending on age), by IM injection
|Within 14 days† and at 1 and 6 months after 1st dose
* Refer also to 'Management of infants born to mothers who are HBsAg-positive' above.
† The 1st dose can be given at the same time as HBIG, but should be administered at a separate site. Administration as soon as possible after exposure is preferred.
‡ There is limited evidence for efficacy if given within 14 days of contact; however, administration as soon as possible after exposure is preferred.
- Hepatitis B Immunoglobulin-VF – CSL Limited. 160 mg/mL immunoglobulin (mainly IgG) prepared from human plasma containing high levels of antibody to surface antigen of the hepatitis B virus. Single vials contain 100 IU or 400 IU hepatitis B antibody, with the actual volume stated on the label on the vial. Also contains glycine.
Hepatitis B immunoglobulin (HBIG) is prepared from plasma donated through routine blood bank collection. Samples are selected on the basis that they contain high levels of anti-HBs antibodies. As stocks of HBIG are very limited, use should be strictly reserved for those who are at high risk, such as babies born to mothers with chronic HBV infection and non-immune persons who are exposed through occupational exposure to the blood of unidentified persons or to persons who are chronically infected with hepatitis B or whose hepatitis status cannot be ascertained in time.88 Requests should be directed to the Australian Red Cross Blood Service in your state/territory (refer to 5.1.1 Availability of immunoglobulins in Part 5 Passive immunisation).
4.5.12 Variations from product information
The product information for Infanrix hexa states that this vaccine is indicated for primary immunisation of infants from the age of 6 weeks and as a booster dose for children 18 months of age if boosting is required for all antigens. The ATAGI recommends that this vaccine may also be used for catch-up of the primary schedule in children <10 years of age.
The product information for Infanrix hexa states that this vaccine is contraindicated in children with encephalopathy of unknown aetiology or with neurologic complications occurring within 7 days following a vaccine dose. The ATAGI recommends instead that the only contraindication is a history of anaphylaxis to a previous dose or to any of the vaccine components.
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- Cassidy WM, Watson B, Ioli VA, et al. A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatrics 2001;107:626-31.
- Heron L, Selnikova O, Moiseieva A, et al. Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11–15 years: a randomised controlled trial. Vaccine 2007;25:2817-22.
- Van Damme P, Moiseeva A, Marichev I, et al. Five years follow-up following two or three doses of a hepatitis B vaccine in adolescents aged 11–15 years: a randomised controlled study. BMC Infectious Diseases 2010;10:357.
- Quaglio G, Talamini G, Lugoboni F, et al. Compliance with hepatitis B vaccination in 1175 heroin users and risk factors associated with lack of vaccine response. Addiction 2002;97:985-92.
- Christensen PB, Fisker N, Krarup HB, et al. Hepatitis B vaccination in prison with a 3-week schedule is more efficient than the standard 6-month schedule. Vaccine 2004;22:3897-901.
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- Golbiowska M, Kardas-Sobantka D, Chlebna-Sok�l D, Sabanty W. Hepatitis B vaccination in preterm infants. European Journal of Pediatrics 1999;158:293-7.
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- Drachman R, Isacsohn M, Rudensky B, Drukker A. Vaccination against hepatitis B in children and adolescent patients on dialysis. Nephrology Dialysis Transplantation 1989;4:372-4.
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- Danzinger-Isakov L, Kumar D, AST Infectious Diseases Community of Practice. Guidelines for vaccination of solid organ transplant candidates and recipients. American Journal of Transplantation 2009;9 Suppl 4:S258-62.
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- Launay O, van der Vliet D, Rosenberg AR, et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA 2011;305:1432-40.
- Chlabicz S, Grzeszczuk A. Hepatitis B virus vaccine for patients with hepatitis C virus infection. Infection 2000;28:341-5.
- Candotti D, Allain JP. Transfusion-transmitted hepatitis B virus infection. Journal of Hepatology 2009;51:798-809.
- Perrillo RP, Storch GA, Bodicky CJ, Campbell CR, Sanders GE. Survey of hepatitis B viral markers at a public day school and a residential institution sharing mentally handicapped students. Journal of Infectious Diseases 1984;149:796-800.
- Perrillo RP, Strang S, Lowry OH. Different operating conditions affect risk of hepatitis B virus infection at two residential institutions for the mentally disabled. American Journal of Epidemiology 1986;123:690-8.
- Woodruff BA, Vazquez E. Prevalence of hepatitis virus infections in an institution for persons with developmental disabilities. American Journal of Mental Retardation 2002;107:278-92.
- Australian Government Department of Health and Ageing. National hepatitis B strategy 2010–2013. Canberra: Australian Government Department of Health and Ageing, 2010.
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- Williams JL, Christensen CJ, McMahon BJ, et al. Evaluation of the response to a booster dose of hepatitis B vaccine in previously immunized healthcare workers. Vaccine 2001;19:4081-5.
- Watson B, West DJ, Chilkatowsky A, Piercy S, Ioli VA. Persistence of immunologic memory for 13 years in recipients of a recombinant hepatitis B vaccine. Vaccine 2001;19:3164-8.
- Greub G, Zysset F, Genton B, Spertini F, Frei PC. Absence of anti-hepatitis B surface antibody after vaccination does not necessarily mean absence of immune response. Medical Microbiology and Immunology 2001;189:165-8.
- Zanetti AR, Mariano A, Roman� L, et al. Long-term immunogenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study. The Lancet 2005;366:1379-84.
- FitzSimons D, Fran�ois G, Hall A, et al. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine 2005;23:4158-66.
- Petersen KM, Bulkow LR, McMahon BJ, et al. Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth. Pediatric Infectious Disease Journal 2004;23:650-5.
- But DY, Lai CL, Lim WL, et al. Twenty-two years follow-up of a prospective randomized trial of hepatitis B vaccines without booster dose in children: final report. Vaccine 2008;26:6587-91.
- Goldwater PN. Randomized, comparative trial of 20 �g vs 40 �g Engerix B vaccine in hepatitis B vaccine non-responders. Vaccine 1997;15:353-6.
- Bertino JS, Jr., Tirrell P, Greenberg RN, et al. A comparative trial of standard or high-dose S subunit recombinant hepatitis B vaccine versus a vaccine containing S subunit, pre-S1, and pre-S2 particles for revaccination of healthy adult nonresponders. Journal of Infectious Diseases 1997;175:678-81.
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- Playford EG, Hogan PG, Bansal AS, et al. Intradermal recombinant hepatitis B vaccine for healthcare workers who fail to respond to intramuscular vaccine. Infection Control and Hospital Epidemiology 2002;23:87-90.
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- Duclos P. Safety of immunisation and adverse events following vaccination against hepatitis B. Expert Opinion on Drug Safety 2003;2:225-31.
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- Zuckerman JN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. Journal of Medical Virology 2006;78:169-77.


text: Model and apparent muse Annabelle Dexter-Jones recently launched her first ever fashion collection, a capsule for French label Faith Connexion—and now you can buy it online from Net-A-Porter! The collection has a distinct rock 'n' roll vibe, thanks in part to Faith Connexion's signature rocker-chic style and no doubt in part to Annabelle Dexter-Jones family. (Her father is Mick Jones of Foreigner and her half-siblings include both Samantha and Mark Ronson.) Key pieces include a navy blue jumpsuit, a lace blouse with a pink collar, a velvet blazer, an oversized leopard-print fur coat, and a denim newsboy cap. To check out the full collection, head to NetAPorter.com now. Prices start at $120.

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When you've performed some kind of transformation with Free Transform (copy, move, scale, etc.) you can repeat that same operation. After transforming, press Command-Shift-T (PC:...
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Resorts and also the Entrepreneur
People who journey for company really are a various variety of tourist than people who do for its discretion. Than do regular vacationers, company travelers frequently anticipate a greater common of amenities throughout their moves. They're there to function and they'll not be satisfied with support that is regular. And because company vacationers type a significant almost all vacationers every year, resorts have developed to match their requirements that were exact. This is a listing of a few of the greatest resorts for enterprise experts.
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Conwy dog walkers 'intimidated' by enforcement company
A group of dog-walkers have accused a company contracted to enforce Conwy council's dog control bylaws of intimidating behaviour by staff and not providing enough information signs.
Kingdom Security hand out fixed penalty notices for fouling and failing to keep dogs on a lead throughout the county.
The group has collected about 1,000 signatures for a petition which they will hand to councillors later.
Conwy council said it would consider the issue in due course.
The group is also objecting to the nature of the contract, which awards bonuses for each fine delivered.
Tony Costa, who organised the petition, said that whilst nobody objected to attempts to clean-up parks and beaches, Kingdom were targeting the wrong people.
Of around 1,000 fines handed out, 954 were for litter, only three were for dog fouling and 22 were for not controlling dogs or walking them in prohibited areas.
"The areas change constantly, and there's no signs to warn you what is a prohibited area," said Mr Costa.
"It's clearly got nothing to do with making public spaces cleaner or safer, and everything to do with trying to catch out responsible dog owners in order to make money out of them."
In a statement Conwy council said they were aware of a complaint against one of Kingdom's officers, but they stood by their contractor's work.
"Kingdom fulfils a very important function, in partnership with our own enforcement officers who work to a very high and professional standard, and Kingdom staff are trained to operate to the same high standards," a spokesperson said.
Kingdom said they had nothing to add to the council's comments.


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fashion's night out 2010: korres detox bubbles, cupcakes & more!
WHO: Korres Natural Products
WHEN: Friday, September 10, 2010 – 6:00pm – 11:00pm
WHAT: Head to the Korres store in SoHo on Friday, September 10th for an evening of cocktails, cupcakes and makeovers. The event will feature 'Detox Bubbles, Cupcakes & More' for guests to enjoy as they help VOGUE magazine celebrate a night of fashion. The stores will include a detox bar serving complimentary antioxidant-infused cocktails based on the Greek skincare brand's natural ingredients – Wild Rose, Pomegranate, Thyme Honey & Raspberry – along with delicious cupcakes also 'packed' with natural ingredients. Attendees can detox on the outside as well with a complimentary Korres makeover or advice on how to wear VOGUE's hottest color looks of the season using 'green' make-up. All guests will receive a product samples including global bestsellers.
WHERE: KORRES / 110 Wooster Str. [btw Prince & Spring, SoHo, NY] RSVP: To book a complimentary makeover, call: Korres Store 212-219-0683


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What excites me most is seeing a potentially beautiful image, capturing that singular moment, and re-creating it with light, composition and a dynamic point of view. I love using my photography to help promote the vision of a local business. I also have a passion for creating Fine Art with photography. So come along and share with me this beautiful world. Please contact me for questions and to give feedback!
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Eating in FlorencePeople ask me all the time where to eat in Florence, the city I call home. Recently someone blogged about ten places to eat incredibly well in Florence. I disagreed with most choices. And found the list somewhat simplistic, impressed with trendy Michelin-starred places, not really what a visitor needs ...read story
posted on 14 August 2015
Region: Toscana
Il CipressoI don't know what took me so long to get to Ristorante Il Cipresso in Loro Ciuffenna. It's one of those places that flies under the radar, not in most guidebooks, but for me, worth a voyage. Superstar butcher Dario Cecchini, my Tuscan brother, took me there for dinner, along ...read story
posted on 15 July 2015
Region: ToscanaTags: restaurant, chef, meat
HomepageCarissimi, I know. I ignored my website and it got stale. I piled pieces I'd written in disorganized lists in my Italian regional files. Magazines closed and their websites changed. The places that I wrote for with pleasure mostly disappeared. I looked around and wasn't thrilled with the print world. ...read story
posted on 26 May 2014
Region: Toscana
Outside my front doorThe Left Bank of FlorenceI live in the Oltrarno (beyond the Arno, the un-Duomo side of the river--think Left Bank), near piazza Santo Spirito, my favorite piazza in Florence. Unfortunately, restaurants directly in the piazza are a sad story. Caffe' Ricchi has changed hands and although I still love to ...read story
posted on 27 July 2010
Region: ToscanaTags: hotel, restaurant, gelato, pizza, trattoria, atlantic magazine
new season....of tomatoes!Just back to a new season, with tomatoes... I've been away from home, in California for two weeks, and came back to a delivery from my favorite farmers, the Innocenti brothers, featuring a new season of produce. In addition to beets, cucumbers, spring onions, zucchini with flowers and basil, which were ...read story
posted on 02 July 2010
Region: ToscanaTags: tomato, recipe, atlantic magazine
Taste 2010 - Part 2I knew the fair would be impossible to navigate on Sunday and focused on Fuori di Taste events. In the afternoon I visited Carapina's new shop, and tasted gelato made with Mieli Thun's superb honey, then tasted a spoonful of crystallized ivy honey, complex, evolving flavors. I went to an ...read story
posted on 27 April 2010
Region: ToscanaTags: festival, restaurant, chef, seafood, gelato, atlantic magazine
Taste 2010Taste is the one of the most exciting food fairs in Italy. It's in my home town of Florence in the Stazione Leopolda, an ex-railroad station, a most beautiful space. For three days well-chosen producers offer an array of culinary jewels, house wares, books, with round table discussions on important ...read story
posted on 27 April 2010
Region: ToscanaTags: festival, restaurant, chef, atlantic magazine
Superstar Chef LunchIt's a tradition that started a few years ago, with lots of chef friends in town for the presentation of the Espresso restaurant and wine guides. Raffaele Alajmo reserved two places at my table, brought magnums of Champagne, invited a few friends, I made lunch, and everyone had a good ...read story
posted on 03 December 2009
Region: ToscanaTags: recipe, chef, restaurant, menu, Atlantic Magazine
Best New Product at TASTEI love the event Taste, a gastronomic fair with quality food, wine and table products, held in the beautiful "Stazione Leopolda", ex-railway station, with off-site events at restaurants, shops and wine-bars throughout the city of Florence. The fair is small enough to walk through in few hours, and there's a ...read story
posted on 03 December 2009
Region: ToscanaTags: fair, Atlantic Magazine
Biscottificio MatteiThe most famous cookies in Tuscany are called "cantucci" or "cantuccini", golden, crisp, studded with whole almonds, most often served with a glass of Vin Santo dessert wine for sipping or dipping. In the Florence area they're known as "biscotti di Prato", probably since the greatest version of this cookie ...read story
posted on 03 December 2009
Region: ToscanaTags: bakery, biscotti, cookies, dessert, Atlantic Magazine
Agriturismo La PetraiaLa Petraia is one of the most beautiful agriturismo farms in Italy, tucked away in an unspoiled corner of Tuscany in the Chianti Classico area. The stone farm house dates from the 11th century (check out the archival prints in the living room documenting the history of this ancient property) ...read story
posted on 01 December 2009
Region: ToscanaTags: agriturism, restaurant, Atlantic Magazine
'inoI'm wild about 'ino, a gastronomic gem--gourmet grocery meets sandwich shop, in Florence, between the Uffizi gallery and the Arno river. Owner Alessandro Frassica has selected some of Italy's greatest artisanal products. The display case in the front room is packed with choice Italian cheese (many raw milk) including 36-month ...read story
posted on 01 December 2009
Region: ToscanaTags: grocery, gifts, salumi, Atlantic Magazine
Florentine Gelato CrawlBeginning with Bernardo Buontalenti, Mannerist architect, military engineer, theatrical set designer and supposed inventor of churned-over-ice milk-based gelato for the court of Francesco de' Medici in 1565, Florentines have always taken gelato seriously. But there are many inferior shops, with signs declaring "produzione propria" or "produzione artigianale", where gelato is ...read story
posted on 01 December 2009
Region: ToscanaTags: gelato, dessert, artisan, Atlantic Magazine
The Emperor's New ClothesFabio Picchi has always been my favorite chef-restaurateur in Florence and he's created an empire in the Sant'Ambrogio area. His restaurant Cibreo, trattoria Cibreino, bar, and private club, Teatro del Sale serve some the city's best food, at prices that range from expensive (Cibreo) to bargain (Teatro del Sale). Membership ...read story
posted on 01 December 2009
Region: ToscanaTags: restaurant, clothing, chef, Atlantic Magazine,
DarioI love to visit Dario Cecchini, Italy's most famous butcher. His shop in Panzano in Chianti has always been a hang-out for food-lovers from all over the world, who come for a taste of his Chianti "butter" (ground fat-back and herbs), Cosimino (named after the Medici, meatloaf meets huge meatball), Chianti ...read story
posted on 01 December 2009
Region: ToscanaTags: butcher, salumi, trattoria, Atlantic Magazine, meat
Le Chiave dOro and Hotel PatioI've got two new reasons to visit Arezzo, as if one of my favorite frescoes in Italy wasn't enough. The restaurant "Le Chiave d'Oro" is in Palazzo De'Bacci, built by the family who commissioned Piero della Francesca's frescoes "The Legend of the True Cross" in 1452 at the church in ...read story
posted on 01 December 2009
Region: ToscanaTags: hotel, restaurant, Atlantic Magazine
Olympian SeafoodDining at Bagno Olimpia, in Cecina Marina.A friend recommended I try a restaurant on the Tuscan coast that is part of a beach club, and although I was a bit skeptical (after all, bathing facilities are not known for fine food) I fell in love. Ristorante Olimpia doesn't look like ...read story
posted on 27 November 2009
Region: ToscanaTags: restaurant, seafood
Bittersweet in TuscanyTwo Tuscan chocolatiers.Tuscans like their flavors full bodied. Here olive oil is preferred nuovo - fresh from the local mill, peppery, and raw. The everyday wine, Sangiovese, is a red that's austere, earthy, and bold compared to a French Cabernet. And when it comes time for chocolate, Tuscans also crave ...read story
posted on 27 November 2009
Region: Toscana
The Good Lardo of ColonnataLardo from Colonnata and dining at da Venanzio.I've just returned from the village of Colonnata, in the mountains above Carrara near the Tuscan coast, an area well-known for its marble quarries, but worth a gastronomic pilgrimage for those who love lardo.Not to be confused by English speakers with lard (called ...read story
posted on 27 November 2009
Region: ToscanaTags: lard
Springtime Fava RightsSpringtime fava beans and pecorino.I know it's really spring when I spot farmers at the market selling large, lumpy, bright green pods - fava beans, fave in Italian. In most regions Italians cook fava beans. I'm in love when someone makes me a labor-intensive, but delicious, braised vegetable stew, a ...read story
posted on 27 November 2009
Region: Toscana
Fruit Catalogs, c.1700The paintings of Bartolomeo Bimbi, C.1700.I'm crazy about the paintings of Bartolomeo Bimbi. Born in 1648, outside Florence in Settignano, he apprenticed with artists in Florence and Rome, then returned home to work in a studio that turned out flower paintings. The ruling Medici, Cosimo III, hired Bimbi to work ...read story
posted on 27 November 2009
Region: Toscana


text: Michael - PraNAms In simple terms - BMI is body, mind and intellect - Body is gross matter (anna kosham) and mind and intellect together are subtle (manomaya and vijnaanamaya koshas). They can be referred general tern as just mind - which in principle has four subparts - the emotional mind (manas) and discriminative mind (intellect or buddhi), ego (ahankaara - a notional ownership) and memory (chitta). Most of the definitions you can find in Tatva bhoda text by Shankara. That is the classical introductory text in Advaita Vedanta. In Panchadasi - 8th chapter Vidyaranya discusses epistemological aspects. Some of these are being covered in the Knowledge series. The chapter and the whole text have to be studied under guidance since it is somewhat technical. I used the term pool of intellect for intellect in analogy of reflection of the consciousness. Since it is part of subtle body any grossification as pool etc are only for communication, similar to any definition of mind, by psychologists or philosophers. Hari Om! Sadananda --- On Thu, 2/26/09, Michael Shepherd <michael at shepherd87.fsnet.co.uk> wrote: I'm unfamiliar with the terms BMI. I have always taken antahkarana as ahamkara, chitta, buddhi, manas. So my question was, what in the Panchadashi and in your own mind, does 'intellect' and the 'pool of intellect' cover in Sanskrit ?


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A Jumpstart for Entrepreneurs
Intensive course helps students navigate early challenges in starting a company.Read
Entrepreneurship plays a vital role in deploying new ideas and technologies. StartMIT is a two-and-a-half-week January Independent Activities Period course aimed at exposing members of the MIT community to the elements of entrepreneurship. The program is hosted by the Department of Electrical Engineering and Computer Science (EECS), in collaboration with the MIT Innovation Initiative.
Launched in 2014 as Start6 in EECS, or Course 6, the program now includes students from disciplines across the Institute. In 2016, students from all five of MIT's schools had the opportunity to work closely with successful entrepreneurs and innovators, including Ethernet co-inventor and 3Com co-founder Bob Metcalfe, the 2015-2016 Visiting Innovation Fellow. Topics covered include (but are not limited to) equity division, models of funding, marketing, scalability and team building. Additionally, StartMIT highlights some of the campus resources already available to students, including the Sandbox Innovation Fund, Venture Mentoring Service, Technology Licensing Office, and the 100K Challenge.


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Learn About Retirement Planning and the 2018 Investing Landscape in These Webinars View Our Archived Education Events
Roger is founder and semi-retired Managing Partner of Venture Investors LLC, the General Partner of five early stage venture capital funds focused on technology spinning out of Big Ten university research. Venture Investors LLC is headquartered in the University Research Park, Madison, WI with a second office in Ann Arbor, MI. Roger is chairman of the board of directors of the UW-Whitewater Foundation and the World Federation of Investors Corporation, and a member of the NYSE Individual Investor Advisory Committee.
Roger has a Master of Public Administration, Urban Development from the Rockefeller School, State University of New York, Albany and a Bachelor of Education, Broad Field of Social Science from the University of Wisconsin-Whitewater