CHAPTER 2: LITERATURE REVIEW
2.11 Prevention of HBV infection
2.11.2 Monitoring the impact of hepatitis B vaccination
Monitoring the impact of introducing universal hepatitis B immunization programmes may involve evaluating the prevalence of HBV exposure within a population by conducting serosurveys of current (HBsAg) and past infections (anti-HBc), and population infectivity (HBeAg/anti-HBe) as well as monitoring the incidence (IgM anti-HBc) of new infections, acute diseases (jaundice and acute hepatitis) and chronic sequelae (cirrhosis and HCC) (WHO, 2011). Such impact assessments may focus on either the short-term or long-term achievements of introducing the hepatitis B immunization programme.
2.11.2.1 Monitoring the short-term impact of hepatitis B vaccination
Monitoring the short-term impact of hepatitis B vaccination involves conducting serosurveys in targeted vaccinated cohorts after at least 5 years of implementing the immunization programme (Rani et al., 2009; WHO, 2011). The goal of monitoring the short-term impact of hepatitis B vaccination is to measure the prevalence of new or acute HBV infections particularly in children under the age of 5 years. This population represents the age group at which contracting HBV infection is highest, either through vertical or horizontal transmission routes, especially in hyperendemic regions (Shepard et al., 2006; Rani et al., 2009; WHO, 2011). The prevalence of HBsAg within this age group serves as an indication of future chronic carriage and related sequelae and as such can be used to monitor the immunization programme at least over the short term. Thus the short-term indicator of the success of the hepatitis B immunization programme will be a reduction in the prevalence of new HBV infections measured within the targeted cohort (Shepard et al., 2006; Rani et al., 2009).
Studies monitoring the short-term impact of implementing universal hepatitis B immunization have revealed a significant influence on the disease burden due to a reduction in the prevalence of new HBV infections on a global scale. This success is a collective of individual achievements by the various countries that heeded the WHO recommendation. Taiwan for example, was the first country to introduce the hepatitis B vaccine into their national EPI in July 1984. As a result, chronic carriage in vaccinated cohorts in Taiwan was found to have declined from 10% in 1984 to 0.6% in 2004 (Ni et al., 2007; Ni and Chen, 2010). Similar reductions have also been noted in vaccinated cohorts from other regions including Spain (0.8% to 0.3%), Columbia (8% to 1.1%), South Korea (8% to 3.7%), Alaska, USA (>6% to 0%) and Italy (2.5% to 0%) (Sanmarti et al., 2000; de la Hoz et al., 2008; Zanetti et al., 2008;
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Park et al., 2010; McMahon et al., 2011; Coppola et al., 2012). The short-term impact of universal hepatitis B immunization has also been noted within the African region with countries such as The Gambia, the first in the sub-continent to include the hepatitis B vaccine into their EPI in 1986, observing a reduction in chronic carriage rate from 10% to 0.6% (Viviani et al., 1999). Similarly, Egypt recorded a 5% reduction (from <6% to ~1.5% in 2002) in chronic carriage rates after almost a decade of nationwide hepatitis B immunization (Sherbini et al., 2006).
Figure 2.9: Graphical representation of the prevalence of HBsAg before and after the introduction of the hepatitis B vaccine in various regions
In view of the high prevalence (>10%) of childhood HBV infections in the country, the hepatitis B vaccine was introduced also into the South African EPI (EPI-SA) in as early as April 1995 (South African National Department of Health, 1995; Vardas et al., 1999). The first hepatitis B vaccine that was licensed for use within EPI-SA was a plasma-derived vaccine (Hepaccine B; Chiel Foods and Chemicals, South Korea) which was later replaced, as in most countries, by a recombinant DNA vaccine (Engerix B vaccine; GlaxoSmithKline, Belgium) in 1999 (Burnett et al., 2012). Within the EPI-SA schedule, the hepatitis B vaccine is administered to infants as a monovalent vaccine in 3 doses at 6, 10 and 14 weeks of age, along with the Diphtheria-Tetanus-acellular Pertussis, inactivated Polio and Heamophilus influenzae type b combined vaccine (DTaP-IPV/Hib) as well as the oral Polio (at 6 weeks)
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and the Rotavirus and Pneumococcal vaccines (both at 6 and 14 weeks) (South African National Department of Health, 2012). Coverage of the hepatitis B vaccine 3rd dose (HepB3) in South Africa is continuously at an increase; currently reported at 97% by the WHO (2012b). Although this figure may be a slight overestimation as vaccine coverage estimates are not necessarily based on scientific surveys, the increase in vaccine coverage is evident in that there has been an observed decline in the incidence of early childhood HBV infections in the country as well as a significant reduction in hepatitis B chronic carriage rates from a previously reported >10% (Vardas et al., 1999), to under 1% in vaccinated cohorts (Table 2.2) (Tsebe et al., 2001; Schoub et al., 2002).
Table 2.2: Pre- and post- hepatitis B immunization data on immunity and chronic carriage of HBV in South African children
Pre-immunization Post-immunization
Study Vardas et al., 1999 Tsebe et al., 2001 Schoub et al., 2002
Age (years) 0-6 0.7-6 1.5
Immunity - 86.8%
(N = 519)
87.0%
(N = 769)
Chronic carriage 10.4%
(N=2 288)
0.0%
(N = 578)
0.4%
(N = 756)
2.11.2.2 Monitoring the long-term impact of hepatitis B vaccination
Hepatitis B serosurveys conducted within targeted vaccinated cohorts may not always report the holistic impact of the immunization programme especially in missed populations who did not receive the hepatitis B vaccine and remain susceptible to HBV infection (Advanced Immunization Management, 2009). Measuring population immunity and chronic carriage of HBV infection within a national representative population, regardless of vaccination status, allows for monitoring the long-term impact of the hepatitis B immunization programme (Advanced Immunization Management, 2009; WHO, 2011). The timing for monitoring the
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long-term impact requires that the immunization programme should have been in effect long enough to measure the prevalence of chronic HBV infection and its related sequelae. The long-term indicator of the success of the hepatitis B immunization programme would therefore be an increase in immunity and a reduction in fatal chronic liver disease (including cirrhosis and HCC) as compared to when the programme was not in effect (Rani et al., 2009).
Quite a number of countries including Australia (Gidding et al., 2007), China (Liang et al., 2009), Cambodia (Soeung et al., 2009), Korea (Park et al., 2010), Mongolia (Davaalkham et al., 2007) and Italy (Coppola et al., 2012) have implemented such nationwide serosurveys in order to monitor the long-term impact of introducing the hepatitis B vaccine into their national EPIs, the output of which has advocated for the continuation of the hepatitis B immunization programme in the relevant countries. The nationwide serosurveys in China for example, revealed a reduction in the prevalence of HBsAg from 9.8% in 1995 to 7.2% in 2006 with the most significant impact noted in children <5 years of age; a 90% reduction (9.7% to 0.96%) in HBsAg prevalence in just over a decade of the hepatitis B immunization programme (Figure 2.10).
Figure 2.10: Comparison of the prevalence of HBsAg from two serosurveys conducted in China in 1992 and 2006 (Liang et al., 2009).
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This reduction also meant that an estimated 16-20 million HBV carriers and 2.8-3.5 million future HBV-related deaths would be prevented in the future, backing the continuation of the programme and recommending an increase in hepatitis B vaccination coverage in the country (Liang et al., 2009).