Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

A large ongoing outbreak of hepatitis A predominantly affecting young males in Lazio, Italy; August 2016 - March 2017

<div><p>The hepatitis A virus (HAV) is mainly transmitted through the faecal-oral route. In industrialized countries HAV infection generally occurs as either sporadic cases in travelers from endemic areas, local outbreak within closed/semi-closed population and as foodborne community outbreak. Recently, an increasing number of HAV infection clusters have been reported among young men-who-have-sex-with-men (MSM).</p><p>The Lazio Regional Service for the epidemiology and control for infectious diseases (SeRESMI) has noticed an increase of acute hepatitis A (AHA) since September 2016. Temporal analysis carried out with a discrete Poisson model using surveillance data between January 2016 and March 2017 evidenced an ongoing outbreak of AHA that started at the end of August. Molecular investigation carried out on 130 out of 513 cases AHA reported until March 2017 suggests that this outbreak is mainly supported by an HAV variant which is currently spreading within MSM communities across Europe (VRD_521_2016).</p><p>The report confirms that AHA is an emerging issue among MSM. In addition through the integration of standard (case based) surveillance with molecular investigation we could discriminate, temporally concomitant but epidemiologically unrelated, clusters due to different HAV variants. As suggested by the WHO, in countries with low HAV circulation, vaccination programmes should be tailored on the local epidemiological patterns to prevent outbreaks among high risk groups and eventual spillover of the infection in the general population.</p></div

Phylogenetic analysis.

<p>Phylogenetic tree, built with a total of 174 460nt-long sequences encompassing the VP1/2A junction region of HAV genome, based on the maximum-likelihood method with the Hasegawa-Kishino-Yano model + G. All the sequences obtained in 2016–2017 from Lazio region (N = 130, patient number, in red) are included. In addition, HAV sequences from Lazio cases referred to the Laboratory from 2013–2015 (N = 24, patient number, in black) are included. The tree also includes 16 reference sequences from GenBank (genotype IA: X75215; EU131373; AB020565; X83302; genotype IB: M14707; DQ646426; NC001489; AF314208; genotype IIA: AJ644676; genotype IIB: AY644670; genotype IIIA: AJ299464; DQ991030; AB279733; genotype IIIB: AB279735; AB425339; AB258387, in blue), and the 4 sequences (VRD_521_2016 and RIVM-HAV16-90, RIVM-HAV16-69 and V16_25801, in green) recently reported to be associated with epidemic clusters among MSM in other European countries (in blue). One genotype IIA sequence (AY644676) was used as the outgroup. The bar represents the genetic distance (substitution per nucleotide position). Bootstrap analysis with 1000 replicates was performed to assess the significance of the nodes; values greater than 80.</p

Temporal cluster analysis.

<p>Temporal cluster analysis.</p

Incidence of AHA cases.

<p>A) Incidence of the AHA cases occurred among people resident in Lazio, according to area of residence (i.e. Frosione (FR) 17 cases; Latina (LT) 13 cases; Rieti (RI) 6 cases; Metropolitan area of Rome (RM) 61 cases; City of Rome (ROMA) 377 cases; Viterbo (VT) 12 cases; total cases: 486). Cases occurred in non-resident people (N = 27) were not included. B B) Temporal distribution of the 513 cases of AHA occurred in Lazio between 1 January 2016 and 31 March 2017, according to risk class, i.e. men (N = 449); women (N = 32); children (N = 32).</p

Geographical distribution of HAV isolates.

<p>The figure describes the distribution in Lazio of the 125 HAV isolates according to the 5 clusters (i.e.: Cluster A N = 112 -red, cluster B N = 6 -green, cluster C N = 3 -blue, cluster D N = 3 -orange, cluster E N = 1 -yellow). The figure did not include the 5 sporadic HAV isolates.</p