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Vacunas

www.elsevier.es/vac

Original article

Evaluation of hepatitis B vaccination status


and immune response among health care workers
in a tertiary care hospital in western India

K. Mehta Tanmay ∗ , D. Shah Parul


Department of Microbiology, Smt. N.H.L. Municipal Medical College, Ahmedabad, India

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: Hepatitis B virus infection is still an important health problem worldwide. The
Received 11 July 2020 risk of contracting HBV by health-care workers (HCWs) is higher than that of the general
Accepted 6 September 2020 adult population. Seroprotection is defined as anti-HBs level 10 mIU/ml or more following a
Available online xxx successful three-dose vaccination course.
Objective: To find out the hepatitis B vaccination status and test immune response using
Keywords: anti-HBs titer among HCWs.
Hepatitis B vaccination coverage Methods: We carried out a retrospective observational study of 218 serum samples from vac-
Hepatitis B vaccine cinated HCWs tested for anti-HBs ELISA from January 2016 to December 2017. We collected
Antiviral immune response demographic, health, and HBV vaccination details from test requisition forms.
Seroprotection Results: We found that 195 (89.44%) HCWs had received a complete course of HBV vaccina-
Anti-HBs tion. 74.87% HCWs showed a protective level (10 mIU/ml or more) of antibodies. We noted a
statistically significant association between the protective antibody level and the complete
course of vaccination (P < 0.001). HCWs had protective levels of antibodies even after 25 years
post-vaccination. We found a statistically significant decrease in mean antibody titer with
duration (in years) of post-primary vaccination (P < 0.001). We noted higher seroprotection
in females, age group of 21–30 years, and weight range of 51–70 kg.
Conclusion: Hepatitis B vaccination coverage is still inadequate even among HCWs. Even with
recommended three dose full vaccination, some HCWs have not achieved protective anti-
HBs titer, so we have to make testing of anti-HBs compulsory irrespective of the vaccination
status. We noted a decrease in mean antibody titer with duration (in years) of post-primary
vaccination.
© 2020 Elsevier España, S.L.U. All rights reserved.


Corresponding author.
E-mail address: tanmay.smit@gmail.com (K. Mehta Tanmay).
https://doi.org/10.1016/j.vacun.2020.09.004
1576-9887/© 2020 Elsevier España, S.L.U. All rights reserved.

Please cite this article in press as: Mehta Tanmay K, Shah Parul D. Evaluation of hepatitis B vaccination status and immune response among
health care workers in a tertiary care hospital in western India. Vacunas. 2020. https://doi.org/10.1016/j.vacun.2020.09.004
VACUN-166; No. of Pages 6
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Evaluación del estatus de la vacunación frente a la hepatitis B y de la


respuesta inmune entre los trabajadores sanitarios de un hospital de
atención terciaria del Oeste de India

r e s u m e n

Palabras clave: Introducción: La infección por virus de la hepatitis B (VHB) sigue siendo un problema de salud
Cobertura de la vacuna frente a importante a nivel mundial. El riesgo de que los trabajadores sanitarios (TS) contraigan
la hepatitis B el VHB es más elevado que el riesgo de la población general adulta. La seroprotección se
Vacuna frente a la hepatitis B define como el nivel de anticuerpos anti-HB de 10 mIU/ml o más, tras una serie de 3 dosis
Respuesta inmune antiviral de vacunación exitosa.
Seroprotección Objetivo: Estudiar el estatus de la vacunación frente a la hepatitis B, y probar la respuesta
Anti-HB inmune utilizando el título anti-HB entre los TS.
Métodos: Realizamos un estudio observacional retrospectivo de 218 muestras séricas de TS
vacunados utilizando ELISA anti-HB, desde enero de 2016 a diciembre de 2017. Recopilamos
los datos demográficos, de salud y de vacunación frente al VHB a partir de formularios de
solicitud.
Resultados: Encontramos que 195 TS (89,44%) habían recibido una serie completa de vacunas
frente al VHB. El 74,87% de los TS reflejaron un nivel protector de anticuerpos (10 mIU/ml
o más). Encontramos una asociación estadísticamente significativa entre el nivel de antic-
uerpos protectores y la serie completa de la vacunación (P < 0,001). Los TS tenían niveles
protectores de anticuerpos transcurridos incluso 25 años de la vacunación. Encontramos
una reducción estadísticamente significativa del título de anticuerpos medio en función del
tiempo transcurrido (en años) desde la primera vacunación (P < 0,001). Encontramos una
mayor seroprotección en mujeres, del grupo de edad de 21 a 30 años, y rango de peso de 51
a 70 kg.
Conclusión: La cobertura de la vacunación frente a la hepatitis B sigue siendo inadecuada,
incluso entre los TS. Aun con la vacunación completa de 3 dosis, algunos TS no han logrado
el título anti-HB protector, por lo que debemos realizar pruebas obligatorias anti-HB, inde-
pendientemente del estatus de vacunación. Advertimos una reducción del título medio de
anticuerpos en función del tiempo transcurrido (en años) desde la primera vacunación.
© 2020 Elsevier España, S.L.U. Todos los derechos reservados.

assay within one to three months of the last dose of primary


Introduction vaccination.3–5 Anti-HBs titer more than 10 mIU/ml should
be considered protective and the individual immune to hep-
Hepatitis B virus (HBV) infection is still an important health
atitis B. If the anti-HBs titer is less than 10 mIU/ml, further
problem with about 2 billion people worldwide infected with
three doses of HBV vaccine should be given and anti-HBs titer
HBV. In India, hepatitis B surface antigen prevalence among
reassessed 1–2 months thereafter. Vaccinated HCWs whose
the general population ranges from 2% to 8% which places
anti-HBs titer is less than 10 mIU/ml after revaccination, i.e.,
India in an intermediate endemicity zone, and India with
after receiving 6 doses in total, should be tested for HBsAg
50 million cases is the second-largest global pool of chronic
and anti-HBc to determine the infection status. If not found
HBV infection. The risk of contracting HBV by health-care
to be infected, they should be considered susceptible to HBV
workers (HCWs) is four times greater than that of the general
infection.6
adult population.1
There are only a few studies are available from India regard-
Fortunately, there are effective vaccines against the virus,
ing the hepatitis B vaccination status and immune response
which are about 95% effective.2 The protective efficacy of
among HCWs. We carried out this study to find out hepatitis B
hepatitis B vaccination relates to the development of anti-
vaccination status and test immune response using anti-HBs
bodies to hepatitis B surface antigen (anti-HBs). In India,
titer among HCWs in a tertiary care hospital to identify those
pre-vaccination serologic testing is indicated using the hep-
who are at risk and to advise them regarding revaccination
atitis B surface antigen [HBsAg]. All HCWs with or without
and further testing.
prior serologic testing should receive at least three doses of
the hepatitis B vaccine. A 4-week gap between the first two
doses is recommended along with an 8- and 16-week gap
between second and third and first and third doses, respec- Methods
tively. As per Occupational Safety and Health Administration
We conducted a retrospective observational study at a tertiary
(OSHA) recommendation, HBV vaccination is followed by con-
care hospital in western India from January 2016 to December
firmation of vaccine response in all HCW by ‘initial’ anti-HBs
2017 after the permission of the Institutional Review Board.

Please cite this article in press as: Mehta Tanmay K, Shah Parul D. Evaluation of hepatitis B vaccination status and immune response among
health care workers in a tertiary care hospital in western India. Vacunas. 2020. https://doi.org/10.1016/j.vacun.2020.09.004
VACUN-166; No. of Pages 6
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We included HBs Ag negative health care workers who had health care workers. However, we found no statistically sig-
received one or more of the three doses of hepatitis B vaccine nificant difference in mean antibody titer between male and
intramuscularly with a dose of 20 ␮g of HBsAg (Hepatitis B sur- female HCWs (P = 0.8764). The age range of the study subjects
face Antigen) vaccine in the study. We analyzed the data of 218 was 21–65 years. The age group of 21–30 years has shown
serum samples from such health care workers (63 consultant protective antibody titer values in 120 (61.53%) of completely
doctors, 84 resident doctors, 27 lab technicians, 16 nurses, and vaccinated health care workers (Table 3).
28 servants) tested for anti-HBs ELISA. On observing the relationship between the weight of com-
Commercially available anti-HBs ELISA tested the serum pletely vaccinated health care workers and anti-HBS titer
samples for the quantitative assay of IgG anti-HBs, as per the value, we noticed that protective titer in 86 (44.10%) health
manufacturer’s instruction. We noted their anti-HBs titer level care workers with a weight range of 51–70 kg. Lower weight
in the data collection form. We grouped the levels of anti-HBs range of 30–50 kg and higher weight range of 71 kg or more
titer: less than 10 mIU/ml, 10–100 mIU/ml, 100–1000 mIU/ml, had shown protective titer only in 23 (11.79%) and 37 (18.97%)
and 1000–10 000 mIU/ml. We considered anti-HBs levels of respectively (Table 4).
10 mIU/ml or more seroprotective. We considered HCWs with
the anti-HBs titer of less than 10 mIU/ml, 10–100 mIU/ml,
over 100 mIU/ml, and 1000 mIU/ml were as hypo respon- Discussion
ders, responders, high responders, and very high responders
respectively. In our study, only 89.44% had received three doses of hepati-
We collected demographic, health, and HBV vaccination tis B vaccine (complete vaccination), while 6.42% and 4.12%
details and other data of health care workers from test req- had received one and two doses vaccine respectively (incom-
uisition forms. We presented data as an absolute number and plete vaccination). This is low compared to a study done in
percentage. We used SPSS 21 Package program (Chicago, IL, New Delhi, where 96% of doctors got vaccinated.1 It shows
USA) for statistical analysis. We used unpaired t-test to com- that hepatitis B vaccination coverage is still inadequate, even
pare the means of two independent groups to determine if among high-risk groups such as HCWs. The primary reason
there is a significant difference between them. A P value of behind this could be a failure in implementing vaccination
less than 0.05 is considered statistically significant. policies established by hospital management, and a lack of
awareness among healthcare workers. We advised the HCWs
with incomplete vaccination to take complete the course of
Results hepatitis B immunization and anti-HBs assay within one to
three months of primary vaccination.
Among 218 healthcare workers, 195 healthcare workers However, 16 (8.2%) HCWs with incomplete vaccination sta-
(89.44%) had received a complete course (three doses) of HBV tus attained protective antibody levels, probably because of
vaccination. The rest of the 14 (6.42%) and 9 (4.12%) HCWs the acquisition of natural infection in the past which conferred
had received one and two doses of vaccine, respectively. None natural immunity to these individuals.
of the HCWs had received hepatitis B vaccine four times or In the present study, 74.87% HCWs showed a protective
more. None of them had got themselves tested for anti-HBs level (10 mIU/ml or more) of antibodies after three doses of
titer value. vaccine. The seroprotection rate of the hepatitis B vaccine
The difference in the seroprotection rates among those globally ranges from 85 to 90%.7 Other studies in the past
who received three doses of vaccination (74.87%) and those observed higher such as Tripathy et al. (100%), Jain et al.
who received less than three doses (7.33%) was statistically (98.45%), and Kruman et al. (99%).8–10 We advised HCWs with
significant (P < 0.001). We found that 146 (74.87%) healthcare ant-HBs levels less than 10 mIU/ml, revaccination with a
workers developed protective anti-HBs titer (10 mIU/ml or complete course (0, 1, 6 months) and to return after 1 month
more) with three doses of vaccine. We observed high anti-HBs for a repeat test.
titer levels (100 mIU/ml or more) in 132 (60.55%) healthcare Among seroprotected individuals 17.43% were high respon-
workers who have received three doses of vaccine. However, ders (anti-HBs titer 100–1000 mIU/ml), 67.12% very high
we noted that 49 (22.47%) healthcare workers were non- responders (anti-HBs titer 1000 mIU/ml or more) and 9.58%
responders (anti-HBs level less than 10 mIU/ml) even after hypo-responders (anti-HBs titer 10–mIU/ml–100 mIU/ml) and
receiving all the three doses of vaccination (Table 1). 22.47% were non-responders (anti-HBs titer less than
In the present study, there was a statistically significant 10 mIU/ml). In a study by Tripathy et al., 80% had a high
decrease in mean antibody titer with duration (in years) of response, 20% were hypo-responders and nobody was non-
post-primary vaccination (P < 0.001). We noted protective anti- responder.8 In another Indian study conducted by Das showed
body titer in 77 (39.48%) and 38 (19.48%) health care workers that among seroprotected individuals there were 32.4% hypo-
even up to 5 years and 6–10 years after the last dose of vaccine. responders (and 52.9% were responders).11 We know that
We found out that the protective antibody titer lasted even up hepatitis B vaccination induces a protective level of antibod-
to 30 years after the last dose of complete vaccination in 5 ies after a complete course of vaccination, but there are a few
(2.56%) health care workers (Table 2). genuine non-responders.8
In our study 81 (41.53%) female and 65 (33.33%) male health The assessment of anti-HBs titer in vaccinated HCWs
care workers were having protective antibody titer value after showed a statistically significant association between anti-
complete vaccination. We observed higher mean antibody body titration and complete vaccination series. This is
titer values in female health care workers compared to male comparable to a study by Sugunan et al. in India.12 We observe

Please cite this article in press as: Mehta Tanmay K, Shah Parul D. Evaluation of hepatitis B vaccination status and immune response among
health care workers in a tertiary care hospital in western India. Vacunas. 2020. https://doi.org/10.1016/j.vacun.2020.09.004
VACUN-166; No. of Pages 6
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Table 1 – Anti-HBs titer as per dose(s) of hepatitis B vaccine received.


Anti-HBs titer (mIU/ml) Incomplete vaccination Complete vaccination Total
n (%)

After 1 dose After 2 doses After 3 doses


n (%) n (%) n (%)

Mean ± SD 573.23 ± 765.91 168.22 ± 244.02 460.14 ± 702.22


Less than 10 5 (2.29%) 2 (0.91%) 49 (22.47%) 56 (25.68%)
10–100 2 (0.91%) 4 (1.83%) 14 (6.42%) 20 (9.17%)
100–1000 2 (0.91%) 3 (1.37%) 34 (15.59%) 39 (17.88%)
1000–10 000 5 (2.29%) 0 (0%) 98 (44.95%) 103 (47.24%)

Total 14 (6.42%) 9 (4.12%) 195 (89.44%) 218 (100%)

Table 2 – Anti-HBs titer as per duration after last dose of vaccine in completely vaccinated healthcare workers.
Anti-HBs titer Duration after receiving last dose of hepatitis B vaccine Total
(mIU/ml) n (%)

0–5 years 6–10 years 11–15 years 16–20 years 21–25 years 26–30 years
n (%) n (%) n (%) n (%) n (%) n (%)

Mean ± SD 757.56 ± 725.85 475.53 ± 688.67 921.61 ± 725.69 430.06 ± 512.58 1130.17 ± 208.47 1034.29 ± 0 706.52 ± 702.22
Non- 29 (14.87%) 10 (5.12%) 6 (3.07%) 2 (1.02%) 2 (1.02%) 0 (0%) 49 (25.12%)
responders
(less than 10)
10–100 6 (3.07%) 5 (2.56%) 1 (0.51%) 2 (1.02%) 0 (0%) 0 (0%) 14 (7.17%)
100–1000 16 (8.2%) 7 (3.58%) 7 (3.58%) 3 (1.53%) 0 (0%) 1 (0.51%) 34 (17.43%)
1000–10 000 55 (28.2%) 26 (13.33%) 7 (3.58%) 6 (3.07%) 0 (0%) 4 (2.05%) 98 (50.25%)
Total 77 (39.48%) 38 (19.48%) 15 (7.69%) 11 (5.64%) 0 (0%) 5 (2.56%) 146 (74.87%)
responders
(10 or more)

Total 106 (54.35%) 48 (24.61%) 21 (10.76%) 13 (6.66%) 2 (1.02%) 5 (2.56%) 195 (100%)

Table 3 – Relationship of gender and age with anti-HBs titer in completely vaccinated healthcare workers.
Anti-HBs titer Gender Age group
(mIU/ml)

Male Female 21–30 years 31–40 years 41–50 years 51 years or more
n (%) n (%) n (%) n (%) n (%) n (%)

Mean ± SD 698.94 ± 700.59 714.72 ± 709.70 703.16 565.62 802.99 776.23


± 723.32 ± 653.73 ± 624.24 ± 753.61
Non-responders 25 (12.82%) 24 (12.30%) 35 (17.94%) 8 (4.10%) 5 (2.56%) 1 (0.51%)
(less than 10)
10–100 5 (2.56%) 9 (4.61%) 5 (2.56%) 3 (1.53%) 5 (2.56%) 1 (0.51%)
100–1000 17 (8.71%) 17 (8.71%) 18 (9.23%) 8 (4.10%) 6 (3.07%) 2 (1.02%)
1000–10 000 43 (22.05%) 55 (28.20%) 62 (31.79%) 20 (10.25%) 14 2 (1.02%)
Total responders 65 (33.33%) 81 (41.53%) 85 (43.58%) 31 (15.89%) 25 (12.82%) 5 (2.56%)
(10 or more)

Total 90 (46.15%) 105 (53.85%) 120 (61.53%) 39 (20%) 30 (15.38%) 6 (3.07%)

Table 4 – Relationship of weight and anti-HBs titer in completely vaccinated healthcare workers.
Anti-HBs titer (mIU/ml) 30–50 kg 51–70 kg 71 kg or more
n (%) n (%) n (%)

Mean ± SD 963.10 ± 723.79 678.49 ± 705.24 585.34 ± 651.74

Anti-HBs negative
Non-responders (less than 10) 6 (3.07%) 32 (16.41%) 11 (5.64%)

Anti-HBs positive
10–100 2 (1.02%) 7 (3.58%) 5 (2.56%)
100–1000 4 (2.05%) 19 (9.74%) 11 (5.64%)
1000–10 000 17 (8.71%) 60 (30.76%) 21 (10.76%)
Total responders (10 or more) 23 (11.79%) 86 (44.10%) 37 (18.97%)

Total 29 (14.87%) 118 (60.51%) 48 (24.61%)

Please cite this article in press as: Mehta Tanmay K, Shah Parul D. Evaluation of hepatitis B vaccination status and immune response among
health care workers in a tertiary care hospital in western India. Vacunas. 2020. https://doi.org/10.1016/j.vacun.2020.09.004
VACUN-166; No. of Pages 6
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anti-HBs titer levels of 100 mIU/ml or more in approximately shows statistically significant mean antibody titer value.8 Liu
60% of the healthcare workers who have received three doses F noted that individuals above 40 years could not respond.26
of vaccine. So as per the recommendation of the CDC, HCWs The protective antibody titer was maximum in the weight
should receive at least 3 doses of hepatitis B vaccine to ensure range of 51–70 kg. 50 kg or less and 71 kg or more both groups
an adequate immune response.6 have shown protective antibody titer values in less frequency.
We noted that 22.47% of healthcare workers did not develop In a study by Liu F, they noted that obese could not respond.26
protective HBs antibody titer (less than 10 mIU/ml) even after In the obese individuals the vaccine may get deposited in
3 doses of vaccines. This suggests that we have to implement fat tissue rather than muscle and this causes diminished
testing of anti-HBs for all health care workers as a manda- immunity response. Some believed that hormonal effects in
tory investigation irrespective of their vaccination status. We overweight persons can decrease antibody titers.27 Unfortu-
also found that 7.33% of healthcare workers who developed nately, ours was a retrospective study, so we could not get the
protective HBs antibody levels even with incomplete vaccina- height of participants and as a result, we could not use a more
tion (after one or two doses). We should not consider HCW sensitive parameter of obesity like body mass index here.
immune who tested before receiving 3 documented doses of
the hepatitis B vaccine achieved protective antibody titer (anti-
HBs 10 mIU/ml or more) because anti-HBs 10 mIU/ml or more Conclusion
is a known correlate of protection only when testing follows a
documented 3-dose vaccination series.6 Hepatitis B vaccination coverage is still inadequate even
We found that participants had protective levels of antibod- among HCWs and needs better implementation of vaccina-
ies, even after 25 years of post-vaccination. Studies by Tripathy tion policies and awareness campaigns. We recommend three
et al. and Jafar Zadeh et al. also noted protective antibody lev- doses (complete) hepatitis B vaccine to achieve protective
els even after 10 years of post-primary vaccination.8,13 Some anti-HBs levels. Even with full vaccination, some HCWs have
long-term studies suggest that the hepatitis B vaccine protects not achieved protective anti-HBs titer even with a complete
an individual for over 15 years.14,15 Protection against acute vaccination course, so we have to make testing of anti-HBs
symptomatic and chronic HBV infection persists for 30 years compulsory irrespective of the vaccination status. We noted
or more among immunocompetent persons who originally a decrease in mean antibody titer with duration (in years) of
responded to the hepatitis B vaccine.6,16–19 In the present study post-primary vaccination. Future long-term follow-up studies
there was a statistically significant decrease in mean anti- can monitor immunized individuals to determine hepatitis
body titer with duration (in years) of post-primary vaccination. B or carrier state development to help decisions on booster
Studies by Tripathy et al., Sugnan et al., and Murhekar et al. policies. We could not establish any significant association of
also concluded that antibody decay occurs with time.8,12,20 gender, age, and body weight with anti-HBs status.
In a long time follow-up study, some observed that approx-
imately 20% geometric mean titer decay occurs per year.21
Conflict of interests
The responders can be considered as protected even if the
anti-HBs level falls to less than 10 mIU/ml with no booster
The authors declare no conflict of interests.
requirement or any periodic antibody concentration testing.
However, it is advisable to administer a booster dose when
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Please cite this article in press as: Mehta Tanmay K, Shah Parul D. Evaluation of hepatitis B vaccination status and immune response among
health care workers in a tertiary care hospital in western India. Vacunas. 2020. https://doi.org/10.1016/j.vacun.2020.09.004
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Please cite this article in press as: Mehta Tanmay K, Shah Parul D. Evaluation of hepatitis B vaccination status and immune response among
health care workers in a tertiary care hospital in western India. Vacunas. 2020. https://doi.org/10.1016/j.vacun.2020.09.004

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