|Year : 2017 | Volume
| Issue : 1 | Page : 1-6
The optimisation of the use of economic resources for hepatitis B vaccination of health care workers
Nivedhana Subburaju, Sulochana Putlibai
Department of Clinical Microbiology and Hospital Infection Control, Kanchi Kamakoti CHILDS Trust Hospital and CHILDS Trust Medical Research Foundation, Chennai, Tamil Nadu, India
|Date of Web Publication||18-Aug-2017|
Kanchi Kamakoti CHILDS Trust Hospital and CHILDS Trust Medical Research Foundation, 12-A, Nageswara Road, Nungambakkam, Chennai - 600 034, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background/Objectives: Hepatitis B virus (HBV) infection and its sequelae is a significant public health problem. Health-care workers (HCWs) are at high risk of occupational exposure to HBV. Centres for Disease Control and Prevention recommends health-care institutions to administer hepatitis B vaccine (0, 1 and 6 months) to HCWs at risk and to check their post-vaccination titre to ensure seroprotectivity. The main aim of this study was to develop a cost-effective protocol for HBV vaccination of HCWs.
Materials and Methods: This descriptive observational study was conducted in the Department of Infection control in a tertiary care hospital from January 2014 to June 2015. Three hundred and ninety-one unvaccinated and 10 remotely vaccinated HCWs were immunised with standard 3 doses (0,1 and 6 months) and a challenge dose of hepatitis B vaccine, respectively, and their anti-hepatitis B surface antibody-titre (HBs titres) were checked 2 months later.
Results: Based on the anti-HBs titres , the HCWs were classified as non-responders (<10 mIU/ml), hyporesponders (10–100 mIU/ml) and those with good immune response (≥100 mIU/ml). 2 (0.5') were non-responders, 8 (2') were hyporesponders and the rest 391 (97.5') showed good immune response. We categorised the HCWs based on age and gender and analysed the co-morbid conditions of hyporesponders.
Conclusions: The seoconversion rate to hepatitis B vaccine was high. The anti-HBs titres of remotely vaccinated HCWs were adequate. Booster doses are not necessary. We emphasise all health-care institutions to follow this cost effective approach rather than pre-vaccination screening for infective hepatitis markers.
Keywords: Anti-HBs titre, health-care workers, Hepatitis b vaccination
|How to cite this article:|
Subburaju N, Putlibai S. The optimisation of the use of economic resources for hepatitis B vaccination of health care workers. J Patient Saf Infect Control 2017;5:1-6
|How to cite this URL:|
Subburaju N, Putlibai S. The optimisation of the use of economic resources for hepatitis B vaccination of health care workers. J Patient Saf Infect Control [serial online] 2017 [cited 2018 Jun 22];5:1-6. Available from: http://www.jpsiconline.com/text.asp?2017/5/1/1/213286
| Introduction|| |
Hepatitis B virus (HBV) infection and its consequences which include chronic liver disease, cirrhosis and hepatocellular carcinoma is a global public health problem. Every year about 600,000 die from HBV-related liver diseases. The Centers for Disease Control and Prevention (CDC) estimates that 5.6 million workers in the health-care sector are at risk of occupational exposure to bloodborne pathogens. Exposure can occur through percutaneous injury or contact with mucous membranes or non-intact skin.
The transmissibility of HBV infection after percutaneous injury is 6%–30% when compared to that of HCV (1.8%) and HIV (0.3%). HBV infectivity after a percutaneous injury ranges from 37% to 62% if the source is both hepatitis B surface antigen (HBsAg)-positive and HBeAg-positive and 23-37% if the source is HBsAg-positive but HBeAg–negative., Although the progression of HBV infection acquired at the adult age to chronicity is <5% its sequelae is still detrimental.,,
HBV endemicity is classified as low (<2%), moderate (2-<8%) and high (≥8%). There are 240 million HBV carriers in the world, with a prevalence of 10%–20% in South East Asia. Considering that India has over 40 million HBV carriers and a point prevalence of 3.7% (moderate endemicity) in general population, health-care workers (HCWs) are at considerable risk of acquiring HBV infection.
Although blood is the most important source of HBV transmission in HCWs, body fluids are also considered potentially infectious. There are also instances of HBV being transmitted by fomites such as finger-stick devices used to obtain blood for glucose measurements, multi-dose medication vials, shared equipment, contaminated instruments and file cards among laboratory technicians. HBV can survive on counter tops for 7 days and remain viable. HBV infections can even be acquired through minor breaks in the skin or mucous membranes., Adding to the problem, there is also under-reporting of needle stick injuries (NSIs) among HCWs in developing countries due to ignorance and negligence.
Despite the high risk of transmission, the HBV infections among HCWs have declined sharply by 98% in developed countries. This is largely due to immunisation of HCWs with highly safe and effective HBV vaccines. The HBV vaccine has been incorporated into national immunisation programmes in over 150 countries. However, vaccine coverage is not uniform globally and is only 50% in South East Asia.
The reason for failure to immunise HCWs is inadequate policies and inconsistent enforcement of policies in developing countries. As per the Occupational Safety and Health (OSHA) Act of 1991 which is also reinforced by CDC and the Advisory Committee on Immunisation Practices , we provided Hepatitis B vaccine (0, 1 and 6 months) free of cost to all unvaccinated HCWs at risk. We also checked the Anti-HBs titre 2 months after completion of vaccine series (HepB3) or after the booster (challenge) dose in remotely immunised HCWs. Based on previous studies and recommendations, we sought to develop a protocol which is cost effective for HBV vaccination of HCWs.
| Materials and Methods|| |
This descriptive observational study was conducted in the Department of Infection control, in a tertiary care paediatric hospital from January 2014 to June 2015.
The Institutional Review Board Ethical clearance was obtained for the same.
Newly inducted and previously unvaccinated 391 HCWs were immunised with 3 doses (0,1 and 6 months) of Hepatitis B vaccine as per the hospital's policy. 10 HCWs who were remotely vaccinated (>10 years back), but did not have their titres checked at that time were given a booster (challenge) dose of vaccine as per CDC's recommendations. We analysed the anti-HBs titres of the 401 HCWs 2 months after the third dose and challenge dose in the former and the latter groups, respectively. The protocol was explained to all HCWs, and informed consent was obtained from them for the same.
The HCWs who were known HBsAg and/or anti-HBc (Antibody to Hepatitis B core antigen) positive were excluded from the study. Furthermore previously immunised HCWs, with a record of their Hepatitis B surface antibody-titre (anti-HBs titre) were excluded from the study.
The recombinant vaccine GeneVac-B, obtained from Serum Institute of India, Pune was used for vaccination. A multidose vial of the vaccine (10 ml) was used which was stored at 2-8°C until use. The vaccine was administered at a dose of 1.0 ml (20 mcg) using 1 inch and 1.5 inch needles in the deltoid for normal and obese HCWs, respectively. We checked the anti-HBs titre 2 months after the 3rd dose and the challenge dose in the former and the latter groups, respectively, to assess the level of protective immunity attained. Their titre was determined in mIU/ml from the serum samples of HCWs with the miniVIDAS (Biomerieux, France) Anti-HBs Total Quick kit using the Enzyme Linked Fluorescent Assay principle. The results were automatically calculated using calibration curve stored in the instrument. The measuring range is 5–500 mIU/ml. The diagnostic sensitivity and specificity of the kit used was 99.65% and 98.2%, respectively.
HCWs with anti-HBs titres of ≥10 mIU/ml were considered responders (seroprotected) while those with levels <10 mIU/ml were labelled as non-responders. The seroprotected group of HCWs were further classified into those with low Immune Response or hyporesponders ( titre of 10–100 mIU/ml) and good immune response (titre >100 mIU/ml) to the HBV vaccine. The study population was divided into four age groups of 20–30 years, 31–40 years, 41–50 years and >50 years.
We developed the following protocol to be followed for the non-responders. Serum samples from non-responders (titre <10 MIU/ml) are to be tested for HBsAg and total anti-HBc Ab. If both HBsAg and anti-HBc Ab are positive the HCW is considered infected with HBV in the past. The following are the possibilities in case of isolated anti-HBc Ab positivity-recovery from acute HBV infection, chronic (occult) infection with undetectable levels of HBsAg in the serum, or may be distantly immune (resolved infection) with a very low level of anti-HBs in the serum. No further doses are to be administered in both the situations.
HCWs who test negative for both HBsAg and anti-HBc Ab are to be given another single dose of Hepatitis B vaccine and tested for anti-HBs antibody in 4-6 weeks. If the HCW is found to be anti-HBs antibody positive, this most likely indicates a booster response in a previous responder, and no further vaccination (or serologic testing) needs to be done. If the titre is still low (<10 MIU/ml) after the 'booster' dose, a second series is to be completed (i.e., two more doses) and titre is to be checked once again.
HCWs whose titres are low even after the second vaccine series are considered vaccine non-responders and susceptible to HBV infection. They should be counselled about precautions to prevent HBV infection and the need to obtain Hepatitis B immune globulin (HBIG) prophylaxis for any known or likely exposure to HBsAg-positive blood.,
Data were entered and statistical analysis performed using SPSS Software (Statistical Package for Social Sciences) version 20. In descriptive analysis, percentages of categorical variables (gender, anti-HBs titre level and age groups) were reported. We analysed the anti-HBs titres of the study population based on age and gender. Univariate analysis was performed using Pearson's Chi-Square Test and Fisher's Exact Test. The value of P < 0.05 was considered statistically significant. We also sought to reason out for vaccine non-responders and hyporesponders by analysing their co-morbid conditions.
| Results|| |
The total strength of HCWs in the hospital is 450. Among them, 2 (1 male and 1 female) known HBs Ag carriers and 47 HCWs who were previously vaccinated and had submitted document evidence of their post-vaccination titres were excluded from the study.
The study population comprised 401 HCWs among which 75 (18.7%) were men and 326 (81.3%) were women. Among them, 391 had received standard 3 dose regimen of Hepatitis B vaccine and 10 HCWs who were remotely immunised (5 men and 5 women) were given the challenge dose [Table 1]. Overall, 2 (0.5%) individuals, both men were non-responders; 8 (2%) were hyporesponders and the rest 391 (97.5%) showed a good immune response.
The anti-HBs response was significantly higher in women than men (P = 0.0006). Among men, 2/75 (2.7%) were non-responders, 6/75 (8%) showed low immune response and 67/75 (89.3%) showed a good immune response. Among women, none were non-responders, 2/326 (0.6%) showed low immune response and 324/326 (99.4%) showed a good immune response.
Interestingly, no significant association was found between age and the immune response (P = 1.00) [Table 2] for both genders. In the 20-30 age group, all 18/18 (100%) men and 179/179 (100%) women showed a good immune response. In the 30–40 age group, 15/21 (71.4%) men and 57/59 (96.6%) women showed a good immune response. In the 40–50 age group, 28/33 (84.8%) men and all women 76/76 (100%) showed a good immune response. All men 6/6 (100%) and women 12/12 (100%) showed a good immune response in the >50 years category [Table 2].
| Discussion|| |
Development of protective titre (≥10 mIU/ml) following first, second and third doses of the recombinant vaccine has been estimated to be 20%–30%, 75%–80% and 90%–95%, respectively. About 5%–10% of healthy immunocompetent responders do not mount seroprotective anti-HBs levels after standard 3 dose regimen. An Anti-HBs titre of ≥ 10 mIU/ml is generally considered protective, whereas some countries like the UK adopt a higher reference level (≥100 mIU/ml).
In this study, the total 99.5% of HCWs had protective levels anti-HBs Ab levels (≥10 mIU/ml) which are greater in comparison with previous studies by Jha et al. (73.5%). The non-responders were 0.5% who were both men which are lesser than the study by Chathuranga et al. (9.9%). The percentage of men who showed good immune response were lower than women (89.3% vs. 99.4%) (P = 0.00006). This is in accordance with the study by Chathuranga et al. (71.7% vs. 62.1%).
The duration of protection afforded by hepatitis B vaccination beyond 10 years and the need for booster dose is still a matter of debate. CDC recommendations are that for HCWs remotely vaccinated and with no record of titre a response ≥10 mIU/mL 2 months following a challenge dose is adequate and that they need not be retested in the future. We followed the CDC approach to eliminate the wasteful use of resources.
Ten HCWs (5 men and 5 women) who were immunised remotely (>10 years) were given a booster dose (challenge dose). Among them, 9 showed good immune response and 1 (male, 30–40 years) showed low immune response (titre = 22 MIU/ml). Various studies suggest that even though the mean anti-HBs becomes lower with longer time lapse after vaccination, the vaccines would still mount an effective immune response when exposed to HBV due to the persistence of an effective immunological memory. This was proved by their response to the challenge dose. This approach was cost-effective, rather than checking their anti-HBs titres first and revaccinating them if their titres are low and checking their titre for the second time.
The probable reasons suggested for poor immune response to HBV immunisation apart from age (seroprotection 92% if age <40 years and 84% if age ≥40 years) and male gender are chronic disease, immunosuppression, obesity, smoking, diabetes mellitus and certain genetic factors.,,,,,,,, However, these factors were not systematically evaluated in the study. We only analysed the co-morbid conditions of the hyporesponders and non-responders.
In total, 6 (8%) of men (3 each in the 30–40 years group and 40–50 years group) and 2 (0.6%) of women (30–40 years) were hyporesponders. One male HCW was a hyporesponder despite having received the challenge dose. 3 among the 6 male HCWs had a history of chronic drinking, smoking and obesity and the 2 women had a medical history of long-term diabetes and hypothyroidism.
Evidence suggest that older adults with diabetes with impaired cellular response may have lesser antibody production after HBV vaccination due to a reduction in the number of circulating helper T cells, the CD4-to-CD8 lymphocyte ratio and defects in antigen presentation. Impaired vaccine response also has been associated with the presence of HLA alleles DR3, DR7 and DQ2 human leukocyte antigen alleles among diabetics. Younger adults with diabetes have similar titres as normal people. Hence, this risk factor was not analysed independently.
In this study, 2 HCWs (both men) were seronegative after standard 3 dose regimen of Hepatitis B vaccine. Both of them were in the age group 40–50 years and had titres of <5 mIU/ml. On testing their serum samples according to our protocol, one of them was found to be positive for HBsAg and anti-HBc Ab and the other was anti-HBc Ab positive. We concluded that the former had chronic HBV infection. He was given appropriate counselling for preventing transmission to others and referred for further medical management. According to CDC, transmission of HBV from infected HCW to patients is rare unless the viral load exceeds 8000 IU/ml. We considered the latter HCW to have developed immunity to past HBV infection and did not do further intervention.
No association between age at vaccination and the rate of seroconversion was found in the current study (P = 1.000) for both genders. This might be because the majority (68.3%) of our study population were <40 years of age. A similar observation was noted by Chathuranga et al. This ensures that major population of HCWs are protected in institutions all over developing countries where under-reporting of NSIs is still a major persisting problem.
The role of pre-vaccination screening of HCWs with anti-HBcAb and HBsAg is to identify previous HBV infected individuals who do not require vaccination. However, various studies and the recommendation by CDC is that pre-vaccination screening is unnecessary since the costs of screening outweigh that of savings on the vaccine. Pre-vaccination screening would be cost effective only if the prevalence of infection exceeds 30%.,, Hence, we contemplated not to screen the HCWs initially for HBV serologic markers as it is usually not cost-effective for groups with a low expected prevalence of HBV serologic markers, such as HCWs. CDC recommends to screen for hepatitis markers suggestive of past infection only after the second vaccine series, but we went ahead and checked the titre after the first series since our responder's rate was very high (99.5%). We were proved right in the sense that both the non-responders were found to infected with HBV in the past.
There are few limitations in this study. First, we did not measure the exact value of anti-HBs titre after dilution of serum samples as it was costly. Second, we did not categorise the HCWs according to the risk factors but only by the demographic details of age and gender. Third, the predominant age group in our study population was between 20-30 years (49%) and the majority were women (81.9%), which could have attributed to the greater percentage of responders (99.5%). Fourth, the study was not of prospective design to see how long the immunological memory would last in case the HCWs were exposed to HBV and to measure the serological evidence of HBV breakthrough infections.
We opted for the standard regimen (0, 1 and 6 months) rather than the accelerated regimen (0, 1 and 2 months) as the immunity lasted longer than the former regimen. We also immunised the HCWs by the intramuscular (i.m) route rather than the intradermal route with low dose of the vaccine due to increased immunogenicity by the i.m route.
In the case of NSIs even if the source is HBsAg-positive, there is no need for vaccination or HBIG administration provided the HCW is fully vaccinated and a known responder. Otherwise, the HCW should be begun on a Hepatitis B vaccine series and given one i.m dose of HBIG (0.06 ml/kg) as per CDC guidelines. Some institutions employ a practice of checking anti-HBs titre during an incident of NSI and vaccinating them if the titre is <10 mIU/ml. This might be misleading since the titre might have declined with time if they had been remotely vaccinated. Hence, vaccinating them once again based on titre value at the time of incurring an NSI is a wasteful expenditure. Furthermore the difference between the cost of 3 doses of Hepatitis B vaccine and the cost of HBIG is huge. The extra cost borne by the health-care institutions in case of NSIs, adds to the economical burden, especially in developing countries.
| Conclusions|| |
From this study, we concluded that seroconversion after standard 3 dose regimen of Hepatitis B vaccine was high as evidenced by good immune response evoked in 97.5% of HCWs. The anti-HBs concentrations of those vaccinated over the past, remain adequate as evidenced by their response to the challenge dose. Since the vaccines available now are highly immunogenic and effective, we recommend to check the infective hepatitis markers for the non-responders alone after a single vaccine series. We also infer that the HCWs remain protected even if their titres decline over time. Booster doses are necessary only if the HCW is immunocompromised. We emphasise all healthcare institutions to vaccinate their HCWs with HBV vaccine, the first 'anti-cancer vaccine' developed as recommended by CDC and OSHA. It is also advisable to check the post-vaccination titre after 6-8 weeks and document it in the employee's health record. Rather than pre-vaccination screening for infective hepatitis markers, we recommend this cost effective rationalistic approach particularly in developing countries to ensure the safety of employees. We also emphasise that 'standard precautions,' including hand hygiene and use of personal protective equipment must be followed by HCWs at all times when caring for all patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]