Hepatitis A virus genotype distribution during a decade of universal vaccination of preadolescents

Abstract

A universal vaccination program among preadolescents was implemented in Catalonia, Spain, during the period of 1999-2013 and its effectiveness has been clearly demonstrated by an overall significant attack rate reduction. However, reductions were not constant over time, and increases were again observed in 2002-2009 due to the occurrence of huge outbreaks. In the following years, in the absence of large outbreaks, the attack rate decreased again to very low levels. However, an increase of symptomatic cases in the <5 age group has recently been observed. This is an unexpected observation since children younger than 6 are mostly asymptomatic. Such a long vaccination campaign offers the opportunity to analyze not only the effectiveness of vaccination, but also the influence of the circulating genotypes on the incidence of hepatitis A among the different age groups. This study has revealed the emergence of genotype IC during a foodborne outbreak, the short-lived circulation of vaccine-escape variants isolated during an outbreak among the men-having-sex-with-men group, and the association of genotype IIIA with the increase of symptomatic cases among the very young. From a public health perspective, two conclusions may be drawn: vaccination is better at an early age, and the vaccination schedule must be complete and include all recommended vaccine doses.

Figure 1

Hepatitis A attack rates in the decade 2004–2013 in Catalonia, Spain, in the context of a universal vaccination campaign for preadolescents at the age of 12 years. Data is distributed in natural years. Attack rates are defined as the number of cases per 100,000 inhabitants.

Figure 2

Hepatitis A attack rates for different age groups during the 2009–2013 period in Catalonia, Spain, in the context of a universal vaccination campaign for preadolescents at the age of 12 years. Data is distributed in natural years. Attack rates are defined as the number of cases per 100,000 inhabitants of each age group.

Figure 3

Hepatitis A attack rate of the 15–19 age group during the 2009–2013 period in Catalonia, Spain, in the context of a universal vaccination campaign for preadolescents at the age of 12 years. The 15–19 age group mostly includes young adults who have been vaccinated. Attack rates are defined as the number of cases per 100,000 inhabitants of the 15–19 age group.

Figure 4

Hepatitis A attack rates of different age groups during September 2011–August 2013 in Catalonia, Spain, in the context of a universal vaccination campaign of preadolescents at the age of 12 years. Data is distributed in two sets: September 2011–August 2012 and September 2012–August 2013. Attack rates are defined as the number of cases per 100,000 inhabitants of each age group.

Figure 5

Distribution of HAV genotypes in Catalonia, Spain, in the decade 2004–2013. A universal vaccination campaign of preadolescents at the age of 12 years started in 1999 and finished in 2013. Data is distributed in natural years. Genotypes are molecularly defined using the VP1X2A genomic region. Attack rates are defined as the number of cases per 100,000 inhabitants.

Figure 6

Phylogenetic trees based on the VP1/2A junction region, from strains belonging to subgenotype IA and IB. Neighbor-Joining, Kimura 2-parameter, bootstrap 1000 replicates.

Figure 7

Origin of the HAV strains isolated in the decade 2004–2013. Data is distributed in natural years. Attack rates are defined as the number of cases per 100,000 inhabitants.