Control of hepatitis A by universal vaccination of children and adolescents: An achieved goal or a deferred appointment?

doi:10.1016/j.vaccine.2010.07.069

Vaccine

Volume 28, Issue 41, 24 September 2010, Pages 6783-6788

https://doi.org/10.1016/j.vaccine.2010.07.069 Get rights and content

Abstract

Temporal trends of Hepatitis A cases and vaccination coverage data against Hepatitis A Virus have been investigated to analyse the impact of the universal routine vaccination strategy more than 10 years from its introduction in Puglia (region of Southern Italy). The basic reproductive number (R₀) before vaccination introduction and the effective reproductive number (R_e) after introduction have been calculated. A progressive decrease in incidence has been recorded in Puglia during last 10 years. Vaccination coverage is actually 64.8% (95% CI: 52.7–76.9%) for children aged 12–24 months and of 67.6% (95% CI: 58.4–76.8%) for 12-year-old adolescents. R₀ estimated in 1996 was 2.01; actually R_e is 0.651. Theoretical age at infection is 31.82 years. Universal routine vaccination aimed at the control of direct transmission remains the milestone in the strategy for the containment of the disease in settings at an intermediate level of endemicity.

Section snippets

Background

Hepatitis A is an acute usually self-limiting and rarely fatal disease of the liver caused by the hepatitis A virus (HAV). Hepatitis A infection is mainly transmitted by the oro-faecal route, either through direct person-to-person contact or through contaminated food and water [1].

Hepatitis A has a worldwide distribution: in 2000, WHO estimated about 1.5 million cases of clinical hepatitis each year all over the world. The risk of developing symptomatic illness following HAV infection is

Source of data

To describe the trend of hepatitis A in Puglia, data from the regional database of routine notification of infectious diseases (from 1996 it was replaced by SIMI, Computerized System of Infectious Diseases) were used. This database was linked with a database of the Italian surveillance system of acute viral hepatitis (SEIEVA). Starting from January 2008, an active surveillance system was implemented at the Regional Observatory for Epidemiology: every week an operator calls the Infectious

Temporal trends

Between 1989 and 2008, the highest number of cases/year (5395) was reported in 1996, and the lowest in 2006 (29 cases, incidence rate: 0.7 × 100,000). The most important incidence rate (130 × 100,000) was reported during the biennium 1996–1997. Since 1999, the epidemic curve has decreased and changed its usual yearly structure that typically presented two peaks, one after the Christmas holidays and the second in summer. This incidence rates was observed in all age groups, without any differences

Discussion and conclusions

The role of the basic reproductive number R₀ and the effective reproductive number R_e in the evaluation of vaccination coverage is well known to epidemiologists in modelling the spread of directed transmitted disease. Their use in analysis of the spread of diseases simultaneously transmitted by direct and indirect contacts results more complex [19], [23].

The value of R₀ = 2.01 estimated for hepatitis A in Puglia in 1996, according to the formula proposed by Ajelli et al., describes the large

Acknowledgments

The authors very much thank Giovanni Caputi and Vanessa Cozza for their important support in data collection.

References (31)

L. Romanò et al.
The changing face of the epidemiology of type A, B, and D viral hepatitis in Italy, following the implementation of vaccination
Vaccine
(2009)
M. Ajelli et al.
Basic mathematical models for the temporal dynamics of HAV in medium-endemicity Italian areas
Vaccine
(2008)
M. Ajelli et al.
An individual-based model of hepatitis A transmission
J Theor Biol
(2009)
M. Chironna et al.
Detection of hepatitis A virus in mussels from different sources marketed in Puglia region (South Italy)
Int J Food Microbiol
(2002)
M. Quarto et al.
Sources in food and risk for health
World Health Organization. Hepatitis A vaccines. World Health Organizzation position paper. Wkly Epidemiol Rec...
N.J. Gay
A model of long-term decline in the transmissibility of an infectious disease: implications for the incidence of Hepatitis A
Int J Epidemiol
(1996)
K.J. Jacobsen et al.
The effects of socioeconomic development on worldwide hepatitis A virus seroprevalence patterns
Int J Epidemiol
(2005)
A. Gupta et al.
Changing epidemiology of hepatitis A infection
Indian J Med Res
(2008)
C.I. Kang et al.
Incidence and seroprevalence of hepatitis A virus infections among young Korean soldiers
J Korean Med Sci
(2007)

D. Lavanchy

Viral hepatitis: global goals for vaccination

J Clin Virol

(2009)

J. Luyten et al.

Costing infectious disease outbreaks for economic evaluation: a review for hepatitis a

Pharmacoeconomics

(2009)

R. D’Amelio et al.

Hepatitis A, Italy

Emerg Infect Dis

(2005)

F. Ansaldi et al.

Hepatitis A incidence and hospital-based seroprevalence in Italy: a nation-wide study

Eur J Epidemiol

(2008)

A. Mele et al.

Epidemiology of hepatitis B

Rapporti ISTISAN

(2006)

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Impact of the national targeted Hepatitis A immunisation program in Australia: 2000–2014
2017, Vaccine
Citation Excerpt :
In most Western European countries hepatitis A incidence has also declined to below 1.0 per 100,000, in the context of immunisation programs targeting only individuals at high risk [43]. Universal routine vaccination of children has been associated with increased age of infection, and hence risk of more severe disease [44,45]. In the context of the targeted Australian immunisation program we found no change in the median age of notified and hospitalised cases between pre- and post-vaccine periods.
In November 2005, hepatitis A vaccine was funded under the Australian National Immunisation Program for Aboriginal and Torres Strait Islander (Indigenous) children aged 12–24 months in the targeted jurisdictions of Queensland, South Australia, Western Australia and the Northern Territory.
We reviewed the epidemiology of hepatitis A from 2000 to 2014 using data from the Australian National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and Australian Bureau of Statistics causes-of-death data. The impact of the national hepatitis A immunisation program was assessed by comparison of pre-vaccine (2000–2005) and post-vaccine time periods (2006–2014), by age group, Indigenous status and jurisdiction using incidence rate ratios (IRR) per 100,000 population and 95% confidence intervals (CI).
The national pre-vaccine notification rate in Indigenous people was four times higher than the non-Indigenous rate, and declined from 8.41 per 100,000 (95% CI 5.03–11.79) pre-vaccine to 0.85 per 100,000 (95% CI 0.00–1.99) post-vaccine, becoming similar to the non-Indigenous rate. Notification and hospitalisation rates in Indigenous children aged <5 years from targeted jurisdictions declined in the post-vaccine period when compared to the pre-vaccine period (notifications: IRR = 0.07; 95% CI 0.04–0.13; hospitalisations: IRR = 0.04; 95% CI 0.01–0.16). As did notification rates in Indigenous people aged 5–19 (IRR = 0.08; 95% CI 0.05–0.13) and 20–49 years (IRR = 0.06; 95% CI 0.02–0.15) in targeted jurisdictions. For non-Indigenous people from targeted jurisdictions, notification rates decreased significantly in children aged <5 years (IRR 0.47; 95% CI 0.31–0.71), and significantly more overall (IRR = 0.43; 95% CI 0.39–0.47) compared to non-Indigenous people from non-targeted jurisdictions (IRR = 0.60; 95% CI 0.56–0.64).
The national hepatitis A immunisation program has had a significant impact in the targeted population with relatively modest vaccine coverage, with evidence suggestive of substantial herd protection effects.
Vaccination against hepatitis A
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Safety of shellfish and epidemiological pattern of enterically transmitted diseases in Italy
2013, International Journal of Food Microbiology
Citation Excerpt :
It would be useful to evaluate the drastic reduction in the incidence of hepatitis A related to the safety of shellfish farming in Puglia in the last 20 years. Martinelli et al. (2010) showed that the universal routine vaccination against hepatitis A, introduced in Puglia for the first time in Italy in 1998 and aimed to all children 15–18 months of age and to 12-year-olds, represents a milestone in the containment of the direct transmission of the disease. A model proposed by Ajelli et al. (2008) suggested that vaccination is effective since the reduction of circulation among individuals also reduces circulation in seafood.
In recent decades in South-Italy, drastic epidemiological changes in the pattern of the enterically transmitted diseases were recorded. This work aims to support the hypothesis that universal routine vaccination against hepatitis A started in Puglia in 1998 could be also effective in reducing contamination in seafood.
Three studies on different samples of Mitylus edulis lamellibranch were conducted over 20 years. Microbiological analysis measured both the standard bacteriological indexes (faecal coliforms, Escherichia coli, Salmonella spp.) and the presence of hepatitis A, enterovirus, norovirus and rotavirus.
Between 1989 and 2009, the highest number of hepatitis A cases was reported in 1996 and in 1997 (mean incidence rate of 130 per 100,000). Since 1999, the number of cases progressively decreased, reaching 29 cases in 2006 (incidence rate of 0.7 per 100,000). A progressive improvement in vaccination coverage of newborns was recorded ranging from 1997 (38.3%) to 2005 birth-cohorts (63.4%). Vaccination coverage of 12-year-old adolescents was 67.6% (95% CI: 58.4–76.8%).
Hepatitis A was detected in 3.7% of samples in the 1987 study, in 18.3% of samples in the 1999–2000 study and it was absent in the 2007 study.
The decreasing of HAV circulation in humans and in shellfish provides support for the link between vaccination efforts and the safety of molluscs.
Universal hepatitis A vaccination programmes in the world
2012, Vacunas
La hepatitis A es una enfermedad de distribución mundial que causa gran morbilidad. Se estima que se producen decenas de millones de infecciones cada año, aunque se declaran muchas menos porque en un alto porcentaje son asintomáticas. La presencia de clínica se relaciona con la edad: la mayoría de los casos de niños menores de 6 años son asintomáticos, por lo que representan una importante fuente de infección, mientras que los adultos suelen mostrar síntomas. La enfermedad se transmite por vía fecal-oral y su incidencia depende de las condiciones higiénicas y el acceso a agua potable. En las áreas de muy baja endemia (países de renta alta), prácticamente no hay circulación del virus y la enfermedad ocurre principalmente en los grupos de alto riesgo, motivo por el cual la Organización Mundial de la Salud (OMS) recomienda su vacunación. En las zonas de alta endemia (países de renta baja), la mayor parte de la población se infecta durante la infancia y se producen muy pocos casos de infección clínica, por lo que la OMS no recomienda la vacunación. En los países con endemia intermedia o baja (países con una economía de transición al desarrollo) es donde con mayor frecuencia se observa hepatitis clínica, y la OMS recomienda los programas de vacunación universal contra esta enfermedad. Recientemente, en julio de 2012, la OMS ha publicado un documento de actualización de las vacunas contra la hepatitis A. En los últimos 15 años se han implantado programas de vacunación universal contra la hepatitis A en diversos países, como Estados Unidos e Israel, y en algunas zonas de España e Italia. En este artículo se revisan las diferentes estrategias seguidas y los resultados obtenidos con cada programa.
Hepatitis A occurs worldwide and has high morbidity. Tens of millions of infections are estimated to occur every year, but many are not reported due to the high percentage of asymptomatic cases. The presence of clinical manifestations is related to age: most cases in children aged < 6 years are asymptomatic and thus represent an important source of infection, while adults usually present symptoms. Hepatitis A is transmitted by the faecal-oral route and its incidence is related to hygiene and access to safe water.
In areas of very low endemicity (high income countries), the virus hardly circulates, and the disease mainly occurs in high risk groups, in whom the World Health Organization (WHO) recommends vaccination. In areas of high endemicity (low income countries) most people are infected during childhood, so very few cases of clinical infection occur. In these countries, the WHO does not recommend vaccination. Clinical hepatitis occurs more frequently in areas of low or intermediate endemicity (developing countries) and the WHO recommends universal vaccination programs against hepatitis A in these countries. Recently, in July 2012, the WHO published an update document on hepatitis A vaccines.
In the last 15 years, some countries, such as the USA, Israel and some parts of Spain and Italy, have implemented universal vaccination programs against hepatitis A. In this article, we review the different strategies used and the results obtained with each program.
Spatiotemporal dynamics of viral hepatitis A in Italy
2011, Theoretical Population Biology
Viral hepatitis A is still common in Italy, especially in Southern regions. In this study, a metapopulation model for hepatitis A virus (HAV) transmission is proposed and analyzed. Analytical results on the asymptotic and transient behaviors of the system are carried out. Based on the available Italian movement data, a national spatial contact matrix at the regional level, which could be used for new studies on the transmission dynamics of other infectious diseases, is derived for modeling fluxes of individuals. Despite the small number of fitted parameters, model simulations are in good agreement with the observed average HAV incidence in all regions. Our results suggest that the mass vaccination program introduced in one Italian region only (Puglia, the one with the highest endemicity level) could have played a role in the decline of HAV incidence in the country as a whole. The only notable exception is represented by Campania, a Southern region showing a high endemicity level, which is not substantially affected by HAV dynamics in Puglia. Finally, our results highlight that the continuation of the vaccination campaign in Puglia would have a relevant impact in decreasing long-term HAV prevalence, especially in Southern Italy.
Estimating the critical immunity threshold for preventing hepatitis A outbreaks in men who have sex with men
2016, Epidemiology and Infection

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¹: These authors contributed equally to this study.

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Control of hepatitis A by universal vaccination of children and adolescents: An achieved goal or a deferred appointment?

Abstract

Section snippets

Background

Source of data

Temporal trends

Discussion and conclusions

Acknowledgments

Vaccine

Vaccine

J Theor Biol

Int J Food Microbiol

Sources in food and risk for health

A model of long-term decline in the transmissibility of an infectious disease: implications for the incidence of Hepatitis A

Int J Epidemiol

The effects of socioeconomic development on worldwide hepatitis A virus seroprevalence patterns

Int J Epidemiol

Changing epidemiology of hepatitis A infection

Indian J Med Res

Incidence and seroprevalence of hepatitis A virus infections among young Korean soldiers

J Korean Med Sci

Viral hepatitis: global goals for vaccination

J Clin Virol

Costing infectious disease outbreaks for economic evaluation: a review for hepatitis a

Pharmacoeconomics

Hepatitis A, Italy

Emerg Infect Dis

Hepatitis A incidence and hospital-based seroprevalence in Italy: a nation-wide study

Eur J Epidemiol

Epidemiology of hepatitis B

Rapporti ISTISAN