Content
Available Vaccines
Hepatitis A
Introduction
Hepatitis A is an acute infectious disease of the liver caused by hepatitis A virus (HAV). HAV is classified in the genus enterovirus of the family Picornaviridae, based on its biophysical and biochemical characteristics.
HAV is transmitted by the faecal-oral route. Person-to-person spread is the most common method of transmission in developed countries. Infections occur readily under condition of poor sanitation, hygiene and overcrowding. Subclinical infection is common in children and severity tends to increase with age. Occasional cases of fulminant hepatitis may occur but there is no chronicity.
Hepatitis A occurs endemically in all parts of the world with frequent reports of minor and major outbreaks. The exact incidence is difficult to estimate because of the high proportions of subclinical infection and infections without jaundice, differences in surveillance systems and differing patterns of disease. The degree of under-reporting is very high.
Hepatitis A has been a notifiable disease in Malaysia since 1988. The overall incidence of hepatitis A has decreased significantly from 11.65 (1988), 9.16 (1991), 4.72 (1997), 0.41 (2013) to 0.30 (2018) per 100,000 population. On the other hand, the seroprevalance rate has also decreased from 67% (1986) to 54.9% (1993) and 48.4% (2000).
In terms of age-related seroprevalence of HAV infection, Malaysia portrays a pattern typical of declining endemicity (i.e. from intermediate to low endemicity). The proportion of seroconverted children and adolescents has decreased in line with socioeconomic development. However, a relatively high seroprevalence still occurs in older adults (76.1% among those aged 41-60 years) although this is expected to decline as younger adults replace the current cohort.
There is an obvious shift of the seroprevalence curve in Malaysia to the right and downwards from 1986 to year 2000, similar to the one shown by developed countries like Singapore and the United States.
Vaccines
All available inactivated hepatitis A vaccines contain HAV antigen. Most will have aluminium hydroxide or aluminium hydroxyphosphate as adjuvant. They are available in paediatric and adult formulations.
Vaccines Available in Malaysia
1. Avaxim® (Hepatitis A)
Sanofi Aventis (M) Sdn Bhd/Sanofi Pasteur, France
2. Havrix® (Hepatitis A)
GlaxoSmithKline Pharmaceuticals (M) Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium
3. Twinrix® (Hepatitis A and B)
GlaxoSmithKline Pharmaceuticals (M) Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium
Mode of Administration
- The primary vaccination consists of 1 single dose of vaccine followed by a booster injection preferably 6-12 months after the first vaccination. The booster dose is extended up to 36 months for some vaccines.
- For combined hepatitis A and hepatitis B vaccine, a 3-dose series is required at 0, 1, 6 months; minimum intervals: 4 weeks between first and second doses, 5 months between second and third doses.
- The vaccine should be given intramuscularly in the deltoid region. In exceptional circumstances (in patients with thrombocytopenia or in patients at risk of haemorrhage), the vaccine may be injected by the subcutaneous route; however, this may be associated with a higher risk of local reaction including injection site nodule.
- The vaccine should not be administered into the gluteal muscles of the buttocks (due to the presence of varying amounts of adipose tissue) or intradermally since these modes of administration may induce a lesser degree of immune response.
Co-administration with Other Vaccines
- Combination inactivated hepatitis A and hepatitis B vaccine (Twinrix®) is also available. In some countries, combination vaccines for the prevention of hepatitis A and typhoid fever are available, incorporating Salmonella typhi Vi capsular polysaccharide antigen packaged in a dual-chamber bypass syringe (Vivaxim®).
Contraindications and Adverse Effects
- Immunisation should be postponed in individuals suffering from severe febrile illness. Since it is an inactivated vaccine, the risks of adverse effects to the foetus are likely to be negligible but it should NOT be given in pregnancy unless there is a definite risk of infection.
- Adverse effects are usually mild and confined to the first few days after immunisation. The most common reactions are mild transient soreness, erythema and induration at the injection site. General symptoms such as fever, malaise, fatigue, headache, nausea and loss of appetite are also reported, though less frequently.
- To date, the most frequently reported adverse events for hepatitis A vaccines received by the National Pharmaceutical Regulatory Agency (NPRA) are local site reactions such as injection site pain, swelling and rash. Systemic reactions such as pruritus and urticaria have also been reported.
Target Groups in Malaysia
- Travelers to countries where hepatitis A endemicity is high.
- Patients with chronic liver disease.
- Haemophiliacs.
- Occupational exposure: healthcare workers, food handlers and laboratory personnel.
- Men who have sex with men.
- Injection drug users.
- Individuals at risk during outbreaks.
Implications for Healthcare Workers (HCWs)
Outbreaks of hepatitis A among hospital staff occur occasionally, usually in association with an unsuspected index patient who is faecally incontinent. In most outbreaks, nurses accounted for the majority of personnel infected. However, HCWs were not found to have an increased prevalence of anti-HAV compared to control populations in serologic surveys.
Evidence for Effectiveness
- The vaccines are highly immunogenic in persons aged ≥18 years when administered according to the recommended schedules. Protective antibody levels developed in 94-100% of adults, 1 month after the 1st dose. After the 2nd dose, all persons had protective levels of antibody, with high geometric mean antibody concentrations (GMCs).
- Protective levels of anti-HAV were still observed in 99% of 549 children evaluated 5-6 years after receiving the vaccine. Estimates of antibody persistence indicate that protective levels of anti-HAV could be present for ≥20 years. Whether other mechanisms (cellular memory) also contribute to long-term protection is unknown.
References
- Doebbeling, B. N., Li, N., & Wenzel, R. P. (1993). An outbreak of hepatitis A among health care workers: risk factors for transmission. American Journal of Public Health, 83(12),1679-1684.
- Favero, M. S., Maynard, J. E., Leger, R. T., Graham, D. R. & Dixon, R. E. (1979). Guidelines for the care of patients hospitalised with viral hepatitis. Annals of Internal Medicine, 91,872-876.
- Gibas, A., Blewett, D. R., Schoeneld, D. A. & Dienstag, J. L. (1992). Prevalence and incidence of viral hepatitis in health workers in the prehepatitis B vaccination era. American Journal of Epidemiology, 136,603-610.
- The Malaysian National Centre of Adverse Drug Reactions Database [Accessed: 10 October 2019]
- McMahon, B. J., Williams, J., Bulkow, L., Snowball, M., Wainwright, R., Kennedy, M. & Krause, D. (1995). Immunogenicity of an inactivated hepatitis A vaccine in Alaska Native children and native and non-native adults. Journal of Infectious Diseases, 171,676-679.
- Ministry of Health (2020, October 15) Malaysia Health Facts 2019. https://www.moh.gov. my/moh/resources/Penerbitan/Penerbitan%20Utama/HEALTH%20FACTS/Health%20 Facts%202019_Booklet.pdf
- National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia. Senarai Produk Vaksin Berdaftar Dengan Pihak Berkuasa Kawalan Dadah. Received on 5 September 2019.
- Wiedermann, G., Kindi, M. & Ambrosch, F. (1998). Estimated persistence of anti-HAV antibodies after single dose and booster hepatitis A vaccination (0–6 schedule). Acta Tropica 69,12-125.
- Wiens, B., Bohidar, N., Pigeon, J. G., Egan, J., Hurni, W., Brown, L, Kuter, B. J. & Nalin D. R. (1996).Duration of protection from clinical hepatitis A disease after vaccination with VAQTA. Journalof Medical Virology,49,235–241.