Time trends in pediatric hospitalizations for hepatitis A in Greece (1999–2013): Assessment of the impact of universal infant immunization in 2008

Abstract

Hepatitis A vaccine was introduced in the Greek National Immunization Program in 2008. To estimate possible impact of the universal vaccination implementation, time trends of hospitalizations for hepatitis A at the Infectious Diseases Unit of a Tertiary Pediatric Hospital in Athens during 1999-2013 were analyzed. Hepatitis A hospitalizations were recorded from the discharge database and were expressed as frequencies and rate of annual departmental hospitalizations. Time series analysis (ARIMA) was used to explore trends and the impact of the vaccination. Moreover, changes in patient age, population group distribution and the duration of hospitalization were also examined. Hepatitis A hospitalizations rate significantly decreased between pre-vaccination (1999-2008) and post-vaccination (2009-2013) era from 50.5 to 20.8/1000 hospitalizations (p D 0.005). A 3-year periodicity and a trend of reduction on hepatitis A hospitalizations rates across years were noted. Roma children had significant higher rates of hepatitis A hospitalization, followed by immigrant children. Importantly, possibly due to preceding vaccine availability with considerable uptake in private market and unvaccinated group/pockets of children (Roma), overall vaccination effect was less apparent when compared to data from other countries that implemented universal vaccination. No significant change in patient age, population group distribution, or duration of hospitalization was observed. High risk groups such as Roma children should be targeted for vaccination to reduce future outbreaks.

Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines – A systematic review

“…The 2011 hepatitis A incidence rate was the lowest ever recorded for the United States, data form the National Inpatient Survey have shown a reduction in the HA hospitalization rates from 0.64 in 2004–2005 vs. 0.29 in 2010–2011, 44 however the relative rates of hospitalized hepatitis A cases among overall acute hepatitis A cases increased. In Greece, the number of HA-related hospital admission per 1000 hospital admissions among children dropped from 77.3 (95% CI 58.7–95.9) in 1999 (year of introduction of vaccine in private market) to 18.5 (95% CI 8.2–28.9) in 2013 45 . Furthermore the outbreaks in 2013 among Roma populations did not spread to the general population 40 …”

“…2012 49 Arizona, US1999 c 2 yrs (1999) 1 yr (2006)VC with 1 dose (by age): −24–59 mo: 36% (2000), 65% (2006) −5–9 yrs: 24% (2000), 77% (2006)Havrix˜ 720EU, Vaqta˜ 25U 69 Arizona Department of Health Services and local public health departments; passive surveillance1994–1995 vs. 2006–200741 (41–42) vs. 2.6 (2.5–2.7)94 e

–Year of denominator data n.r

–COI: n.r.

Ly et al. 2015 45 US1999 f (vaccinating states g ) 2006 (all) 2 yrs (1999) 1 yr (2006)n.r.Havrix˜ 720EU, Vaqta˜ 25U 69 National Notifiable Disease Surveillance System1999 vs. 20116.0 vs. 0.493 e COI: noneSingleton et al. 2010 48 Alaska, US1999 f 2 yrs (1999) 1 yr (2006)VC with ≥1 dose among children aged 24–35 mo:-2003: 72.7% (±95%CI 7.4)-2004: 69.9% (±95%CI 7.9)-2005: 66.8% (±95%CI 9.1)-2006: 65.9% (95%CI 57.1–73.7)Havrix˜ 720EU, Vaqta˜ 25U 69 Alaska Section of Epidemiology; surveillance1994–1995 vs. 2002–200722.2 vs. 0.995.9 e COI: n.r.Wasley et al.…”

“…2014 44 US1999 e (vaccinating states f ) 2006 (nationwide) 2 yrs (1999) 1 yr (2006) 43 n.r.Havrix˜ 720EU, Vaqta˜ 25U 69 National Inpatient Survey discharge data (∼20% of all community hospital discharges)Hospitalizations for HA illness as principal diagnosis per 100,000 persons d 2004–2005 vs. 2010–20110.640.29

Source and year of denominator data n.r.

COI: none

Ly et al. 2014 45 US1999 e (vaccinating states f ) 2006 (nationwide) 2 yrs (1999) 1 yr (2006)n.r.n.rNational Notifiable Disease Surveillance System and Multiple Cause of death% of HA-cases that was hospitalized; and HA-related mortality per 100,000 population g 1999 vs. 20117.3; 0.124.5; 0.02 COI: noneVogt et al. 2008 43 Vaccinating states f , US1999 2 yrsn.r.Havrix˜ 720EU, Vaqta˜ 25U 69 CDC's National Center for Health StatisticsAge-adjusted HA mortality rate per 1 million persons h 1990–1995 vs. 2000–20040.510.28

–Denominator data from 2000–2004, but incidence data from 1990–2004

–Some decline in mortality attributable to temporal trends, as reflected by statistically significant declines in mortality in states in which no large-scale vaccination programs were implemented

–COI: none

Zhou et al.…”

“…2015 50 Panama2000–2006 vs.201012–18 moAge < 1: 100.0%Age 1–4: 95.1Age 5–9: 97.8% Age 10–14: 96.6% Age 15–19:91.7% Age 20–24:90.2% Age 25–49: 88.9%Age ≥50: 61.8%Ly et al. 2015 45 All states, US1999 vs. 20111 yrAge <1: n.r.Age 0–19: 95.9%—Age 20–39: 93.1%Wasley et al. 2005 35 Vaccinating states b , US1990–1997 vs. 20032 yrsAge < 2: 91.4% (95%CI 86.3–94.8)Age 2–9: 95.6% (95%CI 94.8–96.1%) Age 10–18: 90.6% (95%CI 89.4–91.5%)—Age ≥19: 84.5% (95%CI 84.0–85.5)

CI: confidence interval; mo: months; UMV: universal mass vaccination; yr(s): year(s); n.r.

…”

A cross-sectional vaccination coverage study in preschool children attending nurseries-kindergartens: Implications on economic crisis effect

“…35 In addition, hepatitis A hospitalization rate has significantly (p D 0.005) decreased between pre-vaccination (1999-2008) and post-vaccination era (2009)(2010)(2011)(2012)(2013) as shown in a recent study from a tertiary pediatric center in Athens possibly due to the implementation of universal vaccination as well as the improvement of sanitation and living conditions. 36 However, low coverage and significant delay in HepA vaccination of the general population and children of Roma and immigrants might prove to be insufficient in preventing small outbreaks. These data highlight the need for more efficient vaccination of targeted population groups (Roma) in conjunction with improved education and living conditions.…”