PATTERN OF RESPONSES TO HEPATITIS B VIRUS VACCINE IN BASRAH , IRAQ

A serological study was carried out in Basrah governorate, southern Iraq, from October 2004 to the end of September2006 aimed at estimating the prevalence of HBs-antibody among four groups of individuals: Children under 15 years of age, medical personnel, barbers and unvaccinated adults, to determine HBV vaccination coverage in our area, also to evaluate the duration of vaccine induced immunity and the rate of waning immunity as well as the determination of the proportion of hepatitis type B among the other causes of hepatitis occurring in the community. A total of 762 individuals were included in the study from whom blood samples were collected. The overall vaccination coverage among the study population was 62.9% leaving 37.1% unvaccinated. An enzymelinked Immunosorbent assay (ELISA) was used for the determination of anti-HBs-IgG antibody, showed a prevalence of 71.2%, 66.7%, 51.4%, and 8.7% for barbers, medical personnel (occupational exposure), children under 15years of age and unvaccinated adults respectively. There was a clear effect for the number of vaccine doses administered on the levels of seroconversion, with no significant differences in antibody associated with sex or geographical distribution of vaccinees, but there was a difference in relation to occupation. There was a significant decline in the levels of antibody overtime post vaccination and the losses of protective levels of antibodies were quite evident by 3-4 years post the primary vaccine doses which stress the need for booster doses. In the primary vaccination schedule the time interval of 5-6 months between the 2nd and 3rd vaccine doses is suitable for better responses to HBV vaccine. The proportion of icteric HB was 14.7% while 85.3% was due to other hepatitis causes, and the rate of hepatitis B among individuals with no history of hepatitis was 2.6% referring to the subclinical cases.


INTRODUCTION
epatitis B virus (HBV) is one of the most widespread infectious agent and causes millions of hepatitis cases and deaths each year. [1]It is estimated that approximately 2 billions persons world wide have been exposed to the virus and approximately 350 million persons are chronically infected carriers to HBV; [2,3] the total population of the world is approximately 6 billions, therefore about 5% of the world population are persistently infected with HBV. [4]All of these chronic carriers of the virus are at 100-200 times the risk of non carriers of developing hepatocellular carcinoma, [4,5] a disease that kills about one million person each year. [6]Chronically it occurs in 90% of patients with perinatal transmission and in 5-10% when HBV is acquired during adulthood. [7]accination is the most important tool for hepatitis B prevention.It provides 90% protection to neonates whose mothers are HBV carriers when given as soon as possible. [8]Since 1991, WHO has called for all countries to include hepatitis B vaccine into their national immunization programs. [6]By March 2002, 16 countries have included HBV vaccine in their national programes including most countries in Eastern and south east Asia, the Pacific Island, Australia, north and south America, western Europe and middle east. [6]However, because of hepatitis B vaccine prices, many low income countries in sub-Saharan Africa, the Indian subcontinents and in newly independent states do not use the vaccine.The present study aimed on estimating HBsantibody prevalence among 4 groups of individuals (children under 15 years of age, medical personnel, barbers and unvaccinated adults), estimation of HBV vaccination coverage in our area, evaluation of the duration of vaccine induced immunity and the rate of waning immunity as well as the estimation of the proportion of type B viral hepatitis among the other causes of hepatitis occurring in the community of Basrah.The first, randomly selected with no history of clinical hepatitis or exposure to any risk factor(s) and the second were selected on the basis of occurrence of hepatitis infections and exposure to risk factor(s) such as blood transfusion, surgical procedure, needle stick injuries.These informations were collected on special questionnaire form to cover the relevant data.The study was carried out from October 2004 to the end of September 2006.Hepatitis Bs-IgG antibody was measured by Enzymelinked immunosorbent assay (ELISA) test using Bioelisa anti-HBs in a direct immunoenzymatic method (bioelisa kit, Spain) and the procedure was carried out as described by the manufacturers instructions.The results were expressed as Elisa titers which was converted into mIU/ml through the standard method provided by the kit instructions (bioelisa, Spain).RESULTS Among 432 children of 1-15 years of age from various areas in Basrah city, 22% were covered with a single dose only of HBV vaccine (Table-1).Vaccination coverage with 2 and 3 doses (primary doses) of vaccine was 23.5% and 35.5% respectively.Only 7.2% had boosted with a 4 th dose and the unvaccinated proportion of children at this age range accounted for 12%.

DISCUSSION
High vaccination coverage is the most important factor needed to interrupt HBV transmission; lack of hepatitis B vaccine was the factor most strongly associated with HB susceptibility.The overall vaccination coverage was 42.8% and the seropositivity of all vaccinated children (at least one dose) was 57.9% [9] which is low that may be attributed to the inadequate vaccination schedule and the late introduction of HBV vaccine in the immunization program in Iraq beside the in availability of the vaccine to health authorities to do their jobs.Also there is no school based immunization schedule similar to that found in other countries. [10,11]The results showed a clear effect for the vaccination to rise the immunity levels, but the overall immunity is inadequate to prevent HBV infections especially among those at risk.Experience from the USA suggested that the incidence of HB would decline rapidly if vaccination coverage kept high in order of 90%. [12]Knowledge about the distribution of an infectious agent immunity in relation to age in a country is useful to determine the target population for an effective mass vaccination program.Among the occupational group (medical personnels and barbers) the distribution of antibody in different age groups is not significant, because the vaccination and natural infections is not limited to specific age which is in consistent with other studies. [13]owever, children group showed quite significant differences in the presence of anti-HBV antibodies in relation to age, a trend which was correlated to the vaccination time.The value of antibodies indicates high protective levels among the recently vaccinated children a finding that in consistent with other studies. [14,15,16]The rate of susceptibility to HBV infections is greater than 50% among children over 7 years of age since the levels of antibody drops to a lower levels by 3-6 years postvaccination due to waning immunity overtime and most of our children are not boosted with the relevant booster doses required after a period to keep antibodies at their protective levels. [15,16]These observation imply the urgent need for more than one booster dose to maintain the protective levels of anti-HBV antibodies over age.HBV antibody loses overtime significantly correlated with the number of vaccine doses given to the vaccinees and the time interval between the primary doses.Reported data from other studies are conflicting; some results showed a variable periods for vaccine induced antibody to persist, where in some other studies the immunologic memory against vaccination remain for 9 years and confer protection against HBV infection [16] while other studies indicates a postimmunization antibody decline by 5 years. [13]However, many authors agreed with our observed range of 3-6 years in a declined levels of HBs-antibody at various degree may reach the non-protective levels. [14,16,18]On the other hand, the first two doses of HBV vaccine should be at least one month a part, but increasing the interval beyond one month add no immunologic advantage [14,19] and the second and the third doses should be separated by 2 months, and interval of 4 months or more is optimal. [18,19,20]on-responder or poor responders (with postvaccination antibody levels never exceed 10 mIU/ml or less than 100 mIU/ml respectively) to HBV vaccine was obtained in our study which is indicated by the presence of a fair number of vaccinees with low antibody levels after the primary vaccine doses.The administration of booster dose(s) to those with low antibody levels increased significantly the titer which stress the need for booster doses to maintain the protective levels of immunity and to cover the overtime loses of immunity.
However, HBV antibody level among poor responders and non-responders can be increased up to 1000 mIU/ ml after a 4 th booster dose. [21,22]These results are in agreement with other studies. [23]The presence of HBs-antibody without immunization refer to natural exposure by different mode of HBV transmission as perinatal or occupational hazard of health workers and other risk groups. [6]However, the present study showed that HBs-antibody prevalence among unvaccinated medical personnels is higher than that among the unvaccinated individuals in other groups, which indicates the impact of the occupational exposure on this group, considering that medical personnel as high risk group since the prevalence of HBV antibodies among unvaccinated was 23.1% which is relatively high.These results are in consistent with another study. [24]Similarly, the unvaccinated barbers presented with high percentage of HBsantibody (18.2%) which suggest that HBV infections constitute an occupational hazard for them.It was found that most of the studied barbers had been exposed to scissor cuts and accidental injuries by razors and become in contact with blood sheds.However, in a study in Turkey higher prevalence of anti-HBsantibody among unvaccinated barbers that reach 39.8%. [25]Once an immune response has been induced by vaccination, it can be stimulated by natural exposure to the virus, with an active increase in anti-HBs-antibody during the early phase of incubation period of the disease hence protection against clinical illness or development of the carrier status can be achieved.In endemic setting repeated exposure to HBV carriers could sustain or even boost HBV-antibody responses without any serological evidence of infections. [26]The proportion of HBV infections among those with previous history of icteric hepatitis was 14.7% leaving the major proportion to the other causes of hepatitis, possibly viral hepatitis type A which is more endemic in our area. [27]The prevalence of anti-HBs-antibody among individuals reported no history of the occurrence of icteric hepatitis was 2.6% which represent the ordinary exposure to HBV and most of these infections were subclinical.However, exposure rate to HBV was reported to be up to 11.7% in some regions of Saudi Arabia [28] which is almost in consistent with our figure.
In conclusion, despite the introduction of HBV vaccine and the presence of reasonable vaccination coverage in our community, still there were a fair number of susceptible to HBV infections and the occupational exposure can be considered as risk factor for medicals and barbers professions, where there was an indication for the overtime waning immunity post vaccination.Hence, the implementation of good follow-up and stressing on vaccination program to be achieved and monitored through serological surveys are highly recommended to maintain the protective levels of anti-HBV antibody.

Table 1 . Hepatitis B vaccination coverage among children in relation to vaccine doses.
The overall serologic profile to HBV in the study population is shown in table-2.The overall sereopositivity among unvaccinated individuals (natural exposure) was 8.4% compared to 3.8% among unvaccinated children which differ from that observed among risk groups (occupational); Barbers: 18.2% (30 had razor cut, 47 razor cut and exposed to customer's blood sheds, 6 none; these figures may overlaped); medical personnels: 23.1%.

Table 2b . Occupational exposure to a risk factor(s).
* These figures may overlapped.