Measuring Immunoglobulin Titers Among Healthcare Workers After Hepatitis B Vaccination: A Cross-Sectional Study in Kuwait

Introduction Hepatitis B virus (HBV) is a highly infectious disease affecting the liver, causing life-threatening acute and chronic hepatitis. It poses a significant global public health burden and is a major occupational risk for healthcare workers (HCWs) due to transmission through blood and blood products. Given their increased risk compared to the general population, vaccination is crucial in limiting the spread of HBV and protecting HCWs. This study aims to measure the anti-HBs titers of HCWs in the Farwaniyah Health District in Kuwait after completing three doses of the HBV vaccine. Methods This cross-sectional study was conducted in the Farwaniyah Health District of Kuwait between May and July 2023. We collected data from 556 participants from various departments, including physicians, nurses, and laboratory technicians, chosen through simple random sampling. Inclusion criteria included the completion of three doses of the HBV vaccine (Engerix-B recombinant vaccine, GlaxoSmithKline Biologicals, Brentford, UK). Demographic data were collected, and blood samples were tested for hepatitis B surface antigen antibody titers using fourth-generation enzyme-linked immunosorbent assay. Participants were categorized based on sex, age, specialty, and time since the last vaccine dose. The chi-square test and Fisher’s exact test assessed differences in categorical variables, with a p-value of <0.05 considered statistically significant. Results The study included 556 participants, with 304 (54.7%) women and 252 (45.3%) men. Participants were assigned into two age groups: 294 (52.9%) were 18 to 40 years old and the remainder (262) were over 40. Most participants were nursing staff (n=392; 70.5%), followed by physicians (n=110; 19.7%) and technicians (n=54; 9.7%). A high proportion (n=340; 61.2%) received their last vaccine dose within the last five years. Overall, 375 (67.4%) HCWs developed sufficient anti-HBs titers of ≥100 mIU/mL while 181 (32.6%) had levels below 100 mIU/mL. Age between 18 and 40 years and receiving the vaccine within the last five years were significantly associated with protective titer levels, while sex was not. Nurses had significantly higher immunity levels compared to doctors and technicians. Conclusions HCWs in the Farwaniyah area of Kuwait generally responded positively to the HBV vaccine. Younger HCWs and those who received the vaccine more recently were more likely to have a protective immune response. Nurses demonstrated higher rates of seroconversion compared to doctors and technicians. These results suggest that HBV vaccination programs should prioritize timely booster doses, especially for older HCWs and those vaccinated long ago. Monitoring antibody levels is crucial to ensure ongoing protection, particularly in high-risk groups such as nurses. Implementing these measures can enhance the effectiveness of HBV vaccination programs, reduce HBV incidence among HCWs, and contribute to a safer healthcare environment. Post-vaccination testing is essential to ensure the safety of all HCWs against HBV.


Introduction
Hepatitis B virus (HBV) is a highly infectious disease that affects the liver, causing life-threatening acute and chronic hepatitis.This viral infection poses a significant global public health burden.According to the World Health Organization, 296 million people worldwide are chronically infected with HBV, with 60 million of them in the Eastern Mediterranean region [1].In 2019, HBV was estimated to be responsible for 820,000 deaths worldwide [1].
HBV is transmitted parenterally through blood and blood products, making it a significant occupational risk for healthcare workers (HCWs).Studies have shown that HCWs injured by needles contaminated with both hepatitis B surface antigen (HBsAg) and hepatitis B e (HBeAg) antigen have a 37% to 62% risk of developing serologic evidence of HBV infection [2].Another study reveals that approximately 66,000 HCWs acquire HBV infections annually due to occupation-associated sharps injuries, with an incidence rate of 5.9% [3].
Given the increased risk of HBV transmission among HCWs compared to the general population [4], vaccination plays a crucial role in limiting the spread of the disease and protecting HCWs.Completing three doses of the HBV vaccine has been shown to provide immunity against HBV infection [5].The efficacy of the vaccine is measured by the levels of anti-HBs antibodies.The Centers for Disease Control and Prevention (CDC) reports that seroprotection against HBV is achieved with anti-HBs levels of ≥10 mIU/mL [6].Additionally, the Hepatitis B Vaccination Greenbook states that an individual with a titer above 10 mIU/mL is considered protected; however, for healthcare and laboratory workers, levels above 100 mIU/mL are preferable [7].This level ensures that further doses of the vaccine and additional titer testing are not required.Consequently, it is recommended that the HBV vaccine be enforced among HCWs and that antibody levels be measured to ensure adequate protection [8].Our study aims to measure the anti-HBs titers of HCWs in the Farwaniyah Health District in Kuwait after three doses of the HBV vaccine, providing insight into the vaccine's effectiveness in conferring immunity to HCWs.Overall, 375 HCWs (67.4%) developed sufficient anti-HBs titers of ≥100 mIU/mL while 181 (32.6%) had levels below 100 mIU/mL.After assessing four different categorical variables in relation to having protective anti-HBs titer levels, sex was the only category not significantly associated with the outcome (p = 0.103).Ages 18 to 40 years and receiving the vaccine within the last five years were both significant factors, with p = 0.007 and p = 0.00001, respectively.Additionally, immunity against HBV was significantly higher in nurses compared to doctors and technicians (p = 0.007;

Discussion
HBV is a recognized serious occupational risk among HCWs worldwide.Although Kuwait has a comprehensive HBV vaccination program for all citizens, including HCWs, assessing the vaccine's immunogenicity is crucial to ensure an adequate protective response for those at increased risk of exposure.
Our study assessed 556 HCWs in the Farwaniyah Health District, aged 18 to 70 years, and measured anti-HBs antibody levels.We considered levels above 100 mIU/mL to be protective.
The overall seroprotection rate was 67.4%, comparable to findings from studies in Bulgaria, Sri Lanka, and India, which showed 62.7%, 66.2%, and 76.5%, respectively [9][10][11].According to our study, 32.2% of participants had antibody titers below 100 mIU/mL even after receiving three vaccine doses.This necessitates providing an additional dose of the vaccine for those with antibody levels from 10 to 100 mIU/mL or repeating the vaccine course for non-responders (levels below 10 mIU/mL), according to UK guidelines [7].
Our study found a statistically significant difference between age groups below and over 40 years, with the older group showing lower titer levels.This finding is consistent with a systematic review by Yang et al. in 2016, which found lower vaccine response rates in adults aged 40 years and older [12].This difference may be due to older participants receiving their vaccine earlier, affecting titer levels over time, as shown in other studies [10,13].Our study also demonstrated that titer levels decline over time since receiving the last vaccine dose.Sex did not appear to affect vaccine immunogenicity, consistent with other published studies [10,14].Notably, nurses had significantly higher titer levels than doctors and technicians, which might be due to their more stringent adherence to vaccination schedules and boosters, given their higher exposure to needle-stick injuries [15].
Our study faced several limitations.We did not obtain certain factors, such as vaccination schedules and receipt of booster doses, which should be explored concerning the outcome.Participants with anti-HBs titers below 100 mIU/mL should be further tested to determine if they are hypo-responders (i.e., they have antibody levels between 10-100 mIU/mL) or non-responders (i.e., they have antibody levels below 10 mIU/mL) and managed accordingly.Furthermore, the study does not take into account whether the participants have been vaccinated within one to two months before obtaining the titer levels.This information is crucial to determine the next step of action.
We recommend implementing a public health program in Kuwait to screen HCWs for immunity postimmunization.Once HCWs are documented to be hyper-responsive, further primary doses and retesting are unnecessary [8], which could reduce the economic burden on the Ministry of Health.

TABLE 2 : Association of different categorical variables with HBsAg antibody titer concentrations
*Statistically significant difference at p ≤ 0.05.**Fisher exact test is significant at p ≤ 0.05.HBsAg, hepatitis B surface antigen; NA, not applicable