Hepatology Hepatitis
Table 1: Properties of Commonly Available Monovalent Hepatitis A Virus Vaccines HAV
Strain HM-175 CR-326 GBM RG-SB TZ84
Vaccine (Months)
Manufacturer
HAVRIX™ GlaxoSmithKline Biologicals Rixensart, Belgium
VAQTA™ MSD Whitehouse City, NJ, US AVAXIM™ Sanofi Pasteur Marcy l’Etolle, France EPAXAL™ Crucell Berne, Switzerland
HEALIVE™ Sinovac Biotech Ltd Bejing, China
Figure 1: Global Patterns of Hepatitis A Virus Endemicity
250 U 500 U 0.5 †Enzyme-linked immunosorbent assay (ELISA) units; ‡International units. HAV = hepatitis A virus; U = units; NA = not applicable.
Preliminary results of a recent World Health Organization (WHO) survey suggest a global increase in HAV infections from 117 million in 1990 to 121 million infections in 2005. An increase of incidence was observed in those between two and 14 years of age and those >30 years of age. Death increased from 30,283 in 1990 to 35,245 in 2005.2
Hepatitis A Vaccines
Passive immunisation against HAV via the administration of human immunoglobulin has been used for more than 60 years,1,3,4
while
active immunisation by HAV vaccination has been available since the early 1990s (see Tables 1 and 2).7,8,16–20
High Intermediate Low Adapted with permission from Jacobsen and Wiersma, 2010.2
HAV vaccines currently available and describe the impact of universal childhood immunisation in preventing HAV infection.
Hepatitis A Epidemiology Global HAV incidence is heterogeneous (see Figure 1),1,2
and variation
may exist even within distinct geographical regions of the same country.8
In areas with high endemicity of HAV infection (annual incidence >150 cases/100,000 population confirmed by the presence of anti-HAV antibodies),7
Very low Each vaccine is generated nearly all children become infected at an early
age and typically before five years of age, when the majority of infections are asymptomatic and lifelong immunity is induced. In areas of low (<15 cases/100,000/year) or very low (less than five cases/100,000/year) endemicity,7
most adults have never encountered
the virus and are therefore susceptible to infection and clinically relevant disease. Importantly, socioeconomic development is associated with decreasing HAV prevalence, causing countries to shift from high endemicity to intermediate endemicity (15–150 cases/100,000/year).3,7,11
Whereas industrialised countries have already
undergone this transition, this epidemiological shift currently affects many regions of the world, for example Central and South America and the Middle East, and may affect other developing countries in the future. Paradoxically, HAV infection is likely to become an increasing problem in these areas in transition. Since most of the paediatric population in these regions escapes infection, the subsequent absence of lifelong immunity results in an increasingly large population that is susceptible to HAV outbreaks.12–14
78
from a tissue culture-adapted strain of HAV that is concentrated, purified and then inactivated with formaldehyde. Monovalent HAV vaccines containing tissue-culture derived HAV include HAVRIX™ (GlaxoSmithKline Biologicals, Rixensart, Belgium), VAQTA™ (MSD, Whitehouse City, NJ, US), AVAXIM™ (Sanofi Pasteur, Marcy l’Etoile, France), EPAXAL™ (Crucell, Berne, Switzerland) and HEALIVE™ (Sinovac Biotech Ltd, Beijing, China) (see Table 1). Combination vaccines are also available, including the combined HAV and hepatitis B vaccines TWINRIX™ (GlaxoSmithKline Biologicals, Rixensart, Belgium) and AMBIRIX™ (GlaxoSmithKline Biologicals, Rixensart, Belgium) and the HAV/typhoid vaccines HEPATYRIX™ (GlaxoSmithKline Biologicals, Rixensart, Belgium) and VIATIM™/VIVAXIM™ (Sanofi Pasteur, Marcy l’Etoile, France) (see Table 2). The majority of vaccines contain aluminium as an adjuvant, with the exception of EPAXAL, which utilises a liposomal adjuvant. Live-attenuated monovalent vaccines that provide a similar level of immunity to natural HAV are also available in China.21
In children, vaccination is currently recommended only from 12 months of age and above, as passive acquisition of maternally derived HAV antibodies may blunt the immune response to the vaccine.22,23
The
degree and duration of immunity can also be affected by conditions that cause immunosuppression, such as HIV infection and chronic liver disease, passive immunisation by human immunoglobulin, age (>40 years), weight and body mass index.24–26
recommended vaccination course for monovalent vaccines consists of two doses given intramuscularly at least six months apart, but this may be extended to 18 months (see Table 1). The time course of vaccination for combination vaccines is more variable and depends on the additional antigens present (see Table 2). In immunocompetent
EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW
Furthermore, the shift in morbidity from younger to older people results in increased clinical severity with associated healthcare costs.15
1.0 2 0, 6 24 IU‡ 24 IU 0.5 0.5 2 0, 6–12 NA 160 U NA 0.5 2 0, 6–12 Antigen Dose
(Manufacturer’s Guidelines) Paediatric 720 EI.U†
Adult 1440 EI.U 25 U 50 U Volume (ml)
Paediatric 0.5
0.5
Adult 1.0
1.0
Number of Doses
2 2
Schedule (Months)
0, 6–12 0, 6–18
The principal and
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