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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2018  |  Volume : 29  |  Issue : 2  |  Page : 376-380
Comparison of intradermal route and dose of Hepatitis B vaccine administration in chronic dialysis patients: A pilot study


1 Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
2 Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, Rajasthan, India

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Date of Web Publication10-Apr-2018
 

   Abstract 

We aimed to study the seroconversion rate in two arms of intradermal (ID) route: low dose with high-frequency and high dose with low-frequency hepatitis B (HB) vaccination in dialysis patients. A total of 56 patients, on either hemodialysis or peritoneal dialysis, were included. Patients were enrolled and randomized into two groups. The first group was immunized through the ID route and received weekly 10 μg of vaccine at 0, 1, 2, 3, 4, 5, 6, and 7 weeks (low-dose with high frequency). The second group was immunized through the ID route and received two doses of 40 μg at one-month interval (high dose with low frequency). Anti-HBs antibody titers were measured at one month and one month after completion of the vaccination, i.e., at three months in each group. At one month, each group had received 40 μg of vaccine. The seroconversion rate was 28.57% in each group. At one month after completion of vaccination, seroconversion rate in low-dose ID and high-dose ID was 60% and 58.33%, respectively (P = 0.911) at 80 μgm of total vaccine dose. The overall “good” responders in low-dose versus high-dose ID route were 30% and 50%, respectively (P = 0.179). However, among responders, anti-HBs antibody titers ≥100 mIU/mL in low-dose and high-dose ID route were 50% and 85.7%, respectively (P = 0.049). The rate of seroconversion is comparable in both low dose with high-frequency and high dose with low-frequency ID route.

How to cite this article:
Jhorawat R, Shah P, Beniwal P, Agarwal D, Nijhawan S, Malhotra V. Comparison of intradermal route and dose of Hepatitis B vaccine administration in chronic dialysis patients: A pilot study. Saudi J Kidney Dis Transpl 2018;29:376-80

How to cite this URL:
Jhorawat R, Shah P, Beniwal P, Agarwal D, Nijhawan S, Malhotra V. Comparison of intradermal route and dose of Hepatitis B vaccine administration in chronic dialysis patients: A pilot study. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Dec 3];29:376-80. Available from: https://www.sjkdt.org/text.asp?2018/29/2/376/229283

   Introduction Top


Hepatitis B virus (HBV) infection is a serious problem in dialysis units. The most cost-effective strategy against it is “vaccination.” In 1999, it was reported that the risk for HBV infection was 70% lower in vaccinated hemodialysis (HD) patients compared to those who did not receive the vaccine.[1] It has been repeatedly noted that immune responses to HB vaccination are impaired among chronic kidney disease (CKD) populations proportionally to the degree of kidney failure. Patients with CKD experience lower seroconversion rates (40–70%), lower peak antibody titers and shorter duration of seroprotection.[2]

Various approaches have been adopted to improve the response rate to HB vaccine in patients with end-stage renal disease (ESRD). One strategy to improve response rates in CKD patients is vaccination through the intradermal (ID) route. Many investigators, including one meta-analysis, have shown that the ID route achieves higher seroconversion than the intramuscular route. The authors believed that this might be related to larger number of vaccine shots by the ID route.[3] However, the dose and frequency of HB vaccine used in ID route were different in different studies. No study is available that compares the effect of dose and frequency of HB vaccination by the ID route. We designed this study to compare the high dose with low-frequency and low dose with high-frequency ID HB vaccination in dialysis patients.


   Materials and Methods Top


A total of 56 patients on maintenance dialysis who were negative for anti-HBsAg antibody and HBsAg were included. The patients were enrolled and randomized into two groups after obtaining written consent. The first, low dose with high-frequency ID group included 28 patients and received vaccine at 0, 1, 2, 3, 4, 5, 6, and 7 weeks with 10 μg dose each time. The second, high dose with low-frequency ID group included 28 patients and received vaccine at 0 and one month with 40 μgm dose at each time. The inoculated ID vaccine dose was 10 μg (5 μg in each shoulder) and 40 μg (20 μg in each shoulder) in low-dose and high-dose ID route, respectively. All were immunized with the recombinant HB vaccine.

The syringe used for ID injection was 1 mL tuberculin syringe with permanently attached needle with 27G ×1/2 inch with regular bevel. The technique used was according to ID guidelines that the skin was spread taut, and the needle tip was inserted at a 10°–15° angle. The vaccine was injected slowly and the “wheal” was formed. All patients were immunized with the recombinant HB vaccine (GeneVac-B) which is a non-infectious recombinant DNA HB vaccine. It contains purified surface antigen of the virus obtained by culturing genetically engineered Hansenula polymorpha yeast cells.

Anti-HBs antibody titers were measured at one month and one month after completion of the vaccination, i.e., at three months. Anti-HBs antibody titers were estimated by chemilumine-scence method using the instrument of Architect/Advia Centaur and Abbott/Siemens reagent kit. Anti-HBs antibody titer ≥10 mlU/mL was considered as “positive” or “responder.” The patients who achieved titers ≥100 mIU/mL were labeled as “good” responder and titer <100 mIU/mL but ≥10 mIU/mL were “weak” responders. The side effects at the injection site were noted at one month after completion of vaccination, i.e., pigmentation, skin nodules, and itching any time during vaccination were all recorded. Written consent was obtained from all the included patients, and ethical clearance was obtained from Institutional Ethics Committee (1051/MC/EC/2014).

The results were summarized as mean ± standard deviation. The association between the two groups was estimated using Chi-square test and student's t-test for the unpaired variable. P <0.05 was considered as statistically significant.


   Results Top


A total of 56 patients with ESRD on dialysis were included in this study. At one month, each group had 28 patients. At three months (1 month after completion of vaccination), low-dose ID group had 20 patients, and high-dose ID group had 24 patients (6 patients changed the dialysis center, 3 patients underwent renal transplant, 1 patient withdrew the consent, 3 patients were lost to follow-up, and one patient died).

The demographic and characteristic parameters in each group are shown in [Table 1]. All parameters were comparable in the two groups except for age and body mass index. HD was the predominant mode of dialysis. The demographic profile, causes of CKD, and dose and frequency of HB vaccination in each group are shown in [Table 1]. The dose and duration were equal in the two groups; however, the number of injections was four times more in the low-dose group compared to the high-dose group.
Table 1: Demographic profile of the patients and hepatitis B vaccination with dose and duration in each group.

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The laboratory parameters were comparable in each group as shown in [Table 2].
Table 2: Laboratory parameters of patients in the low dose with high-frequency and high dose with lowfrequency intradermal administration of vaccine against hepatitis B.

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The seroconversion rate in each group, both at one month and three months, is shown in [Table 3]. The overall “good” responders in the low-dose ID group were 30% and 50% at one and three months, respectively, while it was 50% and 85.70% in the high-dose ID group. The dermatologic side effects at inoculation site were not different as shown in [Table 3].
Table 3: Outcome and side effects of vaccination against hepatitis B.

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   Discussion Top


This study is the first, to the best of our knowledge, which compared the ID route at low dose with high frequency and high dose with low frequency in dialysis patients. The seroconversion rate at one month of vaccination was 28.57% in each group after receiving 40 μg of vaccine. At one month after completion of the schedule, the seroconversion rate was 60% and 58.33%, respectively in the low dose with high-frequency and high dose with low-frequency ID route at equal dose of vaccine (i.e., 80 μg) (P = 0.911). However, the overall sero-conversion rate was not high in either group, which highlights the significance of immunization in the early course of CKD.[4]

Overall, the number of “good” responders was not different in the two groups. However, among the responders, high-dose ID had higher “good” responders than the low-dose ID route group (P = 0.049). This indicates that increase in the dose is helpful in inducing response among patients with ESRD. However, patients in the high-dose group were younger and had better nutrition compared to the low-dose group. In addition, evidence has suggested that human skin has many immunologically active cells such as epidermal Langerhans cells (CD207/langeripos) and dermal langerinneg Langerhans cell, which are very capable antigen-presenting cells and are thought to participate in enhancing the immune response with antigen dose.[5] However, whether it would really help in maintaining the antibody titer is another question that needs to be answered.

The ID route is not free from local dermatologic side effects which can range from pain and change in skin color at injection site to nodule formation. However, the side effects were not statistically different in the two groups [Table 3].

In CKD patients, many other factors contribute to poor response. Uremia impairs antigen presentation, T-cell activation, and subsequent antibody production, which may explain that advanced renal failure has an impaired immune response to conventional recombinant HBV vaccines when compared with healthy individuals.[6] Increase in the dose of vaccine did not increase seroconversion rate in our study, although it increased the antibody titer in those who responded to vaccination.

There are many limiting factors of our study. First, the adequacy of dialysis (i.e., kt/v) was not measured. Second, the mode of dialysis was not uniform in our study population. However, a meta-analysis by Fabrizi et al does not support the role played by mode of dialysis in patients immunized by the intramuscular route.[7] Third, the high-dose group had more younger and well-nourished patients than the low-dose group, which might have skewed the result toward the high-dose group. Fourth, the number of patients who were lost to follow-up was quite large since many patients either underwent renal transplantation or were shifted to the local dialysis center. Fifth, the sample size of our study was small. Hence, studies with adequate number of patients are required to confirm these results.

In conclusion, early vaccination of patients against HB should be undertaken before starting dialysis, to improve the response rate. The sero-conversion rate did not differ in patients of either group.


   Acknowledgment Top


I would like to thank our dialysis staff in helping in the recruitment of patients for the study.

Conflict of interest: None declared.

 
   References Top

1.
Miller ER, Alter MJ, Tokars JI. Protective effect of hepatitis B vaccine in chronic hemodialysis patients. Am J Kidney Dis 1999;33:356-60.  Back to cited text no. 1
[PUBMED]    
2.
Rangel MC, Coronado VG, Euler GL, Strikas RA. Vaccine recommendations for patients on chronic dialysis. The Advisory Committee on Immunization Practices and the American Academy of Pediatrics. Semin Dial 2000;13: 101-7.  Back to cited text no. 2
[PUBMED]    
3.
Fabrizi F, Dixit V, Magnini M, Elli A, Martin P. Meta-analysis: Intradermal vs. intramuscular vaccination against hepatitis B virus in patients with chronic kidney disease. Aliment Pharmacol Ther 2006;24:497-506.  Back to cited text no. 3
[PUBMED]    
4.
Dukes CS, Street AC, Starling JF, Hamilton JD. Hepatitis B vaccination and booster in predialysis patients: A 4-year analysis. Vaccine 1993;11:1229-32.  Back to cited text no. 4
[PUBMED]    
5.
Angel CE, Lala A, Chen CJ, et al. CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts. Int Immunol 2007;19:1271-9.  Back to cited text no. 5
[PUBMED]    
6.
Pesanti EL. Immunologic defects and vaccination in patients with chronic renal failure. Infect Dis Clin North Am 2001;15:813-32.  Back to cited text no. 6
[PUBMED]    
7.
Fabrizi F, Dixit V, Bunnapradist S, Martin P. Meta-analysis: The dialysis mode and immunological response to hepatitis B virus vaccine in dialysis population. Aliment Pharmacol Ther 2006;23:1105-12.  Back to cited text no. 7
[PUBMED]    

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Correspondence Address:
Dr. Rajesh Jhorawat
Department of Nephrology, SMS Medical College and Hospital, Jaipur - 302 004, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.229283

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    Tables

  [Table 1], [Table 2], [Table 3]

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    Abstract
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