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Table of Contents
REVIEW ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 5  |  Page : 106-111

Pre and posttransplant vaccination for solid organ transplant recipient and in South Asia - Expert group opinion


1 Department of Nephrology and Renal Transplant Medicine, Medanta Kidney and Urology Institute, Medanta Medicity, Sector 38, Gurgaon, Haryana, India
2 Consultant Infectious Diseases and Tropical Medicine, Apollo Hospitals; Adjunct Prof Infectious Diseases - Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
3 Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, India
4 Department of Transplant and Immunocompromised Host Infectious Diseases Infectious Diseases Division, Massachusetts General Hospital Harvard Medical School, Massachusetts, USA

Date of Submission04-Oct-2021
Date of Acceptance19-Jan-2022
Date of Web Publication18-Oct-2022

Correspondence Address:
Dr. Shyam Bihari Bansal
Department of Nephrology and Renal Transplant Medicine, Medanta Kidney and Urology Institute, Medanta Medicity, Sector 38, Gurugram - 122 001, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_100_21

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  Abstract 


Infections are common after solid organ transplantation (SOT) and are an important cause of significant morbidity and mortality. Many of these infections can be prevented or their severity reduced by vaccination in pre and posttransplantation period. It is better to complete the vaccination before transplantation as protection and seroconversion is better, and live vaccines are mostly contraindicated after SOT. Live vaccines should be given at least 4 weeks before transplantation but killed vaccines can be given up to 2 weeks before the planned transplantation. Vaccination for some diseases which are endemic in South Asia should be given, along with usual vaccinations. Serological monitoring is required for some vaccines to check their efficacy. Similarly, some vaccines are recommended for SOT recipients traveling to various endemic regions.

Keywords: Solid organ transplant, south Asia, travel vaccines, vaccination


How to cite this article:
Bansal SB, Ramasubramanian V, Sethi S, Prasad N, Kotton CN. Pre and posttransplant vaccination for solid organ transplant recipient and in South Asia - Expert group opinion. Indian J Transplant 2022;16, Suppl S1:106-11

How to cite this URL:
Bansal SB, Ramasubramanian V, Sethi S, Prasad N, Kotton CN. Pre and posttransplant vaccination for solid organ transplant recipient and in South Asia - Expert group opinion. Indian J Transplant [serial online] 2022 [cited 2022 Dec 9];16, Suppl S1:106-11. Available from: https://www.ijtonline.in/text.asp?2022/16/5/106/358655




  Introduction Top


Solid-organ transplant (SOT) candidates are at an increased risk for infections, some of which are preventable by vaccines. Not only are certain infections more common in posttransplant immunosuppressed individuals, increased complications and poorer outcomes are also seen after transplantation. Patients should be screened for vaccination history and should ideally be immunized early in the course of their disease, when vaccines are most likely to be effective, or during pretransplant evaluation. Posttransplant immunosuppressive drugs impair vaccine immune responses resulting in decreased efficacy and duration of vaccine-induced protection.[1] Routine transplant serologies for certain vaccine-preventable diseases should also be done to help guide vaccine planning.[1],[2] Certain infections are more common in the South Asian region, so the vaccination for prospective transplant recipients and for those traveling to these regions should be advised accordingly.


  General Guidelines of Immunization with Respect to Vaccines for Transplant Candidates Top


  • There is no consensus on the stage of prior illness including chronic kidney disease (CKD) that is ideal for vaccination, although earlier in the disease state usually results in better immunologic response[1],[2]
  • Vaccination schedules should be completed at least 2 weeks for killed vaccines and at least 4 weeks for live vaccines before transplantation
  • Live vaccines are generally not advised after transplantation in view of immunosuppression and risk of disseminated disease from vaccine strain (i.e., varicella, measles, mumps, rubella, yellow fever, dengue, live zoster, and polio vaccines)
  • Posttransplant vaccines are initiated no sooner than 3–6 months after transplant, once baseline immunosuppression levels are attained. It is important to realize that they often have lower rates of serological conversion, lower mean antibody titers, and waning immunity over time, which may imply a need for repeat vaccination. In general, vaccines should be given starting a year after transplant, except for influenza and severe acute respiratory syndrome-coronavirus-2 vaccines
  • Multiple vaccines can be given at a single setting. Live vaccines (pretransplant only) should be given on the same day or at a minimum of 4 weeks apart; inactive vaccines can be given at any time interval
  • Serological conversion can be documented by serologic assays a minimum of 4 weeks after vaccination for specific vaccines where assays are available and protective titers established; while not recommended as a universal practice, this is sometimes helpful
  • The risk to family members or close household contacts from live vaccines is limited to oral polio vaccine only, so they should be preferably given injectable polio vaccine. Frequent hand washing for a 2-week period is recommended for household contacts of candidates receiving the live influenza vaccine
  • Blood products like intravenous immune globulin can interfere with the response to live vaccines; live vaccines such as measles, mumps, and rubella (MMR) should be deferred for 3 months after the receipt of blood products
  • Live vaccines can interfere with the tuberculin test (TST). TST should be done on the same day of the live vaccine or 4–6 weeks later
  • Travel should preferably be restricted until after the first 12 months' posttransplantation, once their health and the graft function are stable.[3]



  Routine Vaccinations Top


Influenza vaccine

Posttransplant influenza is common and is associated with higher morbidity and mortality. It is also associated with an increased risk of rejection in kidney transplant recipients. Vaccinated patients have significantly lower complications and better graft and patient survival.[4] Even in the tropics, there is a significant burden of influenza. Unlike the West, in tropical countries of the Indian sub-continent, flu is not seasonal and can occur throughout the year. Both the killed and the live attenuated vaccines are equally effective, though the live vaccine is not recommended posttransplant. Live vaccine can be given to patient in pretransplant period, at least 4 weeks prior to the surgery.[2] The vaccine is recommended whenever the new batch arrives. Both the trivalent and quadrivalent vaccines are effective. Concerns for increased risk of rejection were only limited to the 2009 influenza pandemic due to the use of ASO3 adjuvant in the vaccine.[5] The flu vaccine is recommended annually, although the immunogenicity may be reduced in the first 3–6 months after transplant, suggesting revaccination again halfway through the year may be useful, especially if the disease is prevalent. KDIGO guidelines recommend giving the vaccine starting 1–3 months after transplant, since missing a dose might put the patient vulnerable for the entire influenza season;[6] however, the Infectious Disease Society of America recommends the vaccine starting 2–6 months after transplantation.[1] If there is a community influenza outbreak, the vaccine can be given as soon as 1 month after transplantation, but re-vaccination should be done 3–6 months later if influenza activity persists.[2] Household and close contacts of transplant recipients should also receive the flu vaccine annually, particularly the inactivated vaccine.

Diphtheria, tetanus, pertussis vaccine

Recent outbreaks of pertussis are believed to be due to waning immunity in adulthood after childhood vaccination. Diphtheria, tetanus, pertussis (DPT) vaccination is universal in children in South Asian region.[7] A single dose of DPT vaccine is recommended for all adults over the age of 18 years to boost pertussis immunity.[8] All adults who have had their childhood immunization schedule are otherwise advised tetanus and diphtheria boosters every 10 years [Table 1].
Table 1: Vaccination in solid organ transplantation candidates and recipients in South Asia

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Measles, mumps, rubella vaccine

MMR vaccination is given universally to all children in the region of South Asia,[7] however due to a poor uptake of childhood MMR vaccination, all transplant candidates should have either proper documentation of two doses of vaccine or have their serologies checked for measles, MMR before transplant and immunized if indicated.[2] Two doses of MMR vaccine 4 weeks apart are indicated for susceptible persons. Transplant should be deferred for 4 weeks after the vaccine. Since it is a live vaccine, it is contraindicated after transplant. Household and close contacts of transplant recipients should also receive the vaccine.[2]

Meningococcal vaccine

Meningococcal infections are seen in certain parts of the Indian sub-continent. Although transplant recipients are not at an increased risk of meningococcal infections, specific recommendations are made for high-risk groups including splenectomized patients, military recruits and those traveling to Hajj or Sub-Saharan Africa.[1] Patients receiving the terminal complement inhibitor eculizumab are also at high risk for meningococcal infection.[9] The vaccine is recommended at least 2 weeks before the first dose of eculizumab. Two doses of the quadrivalent conjugate vaccine, 2 months apart are recommended. A booster may be advised after 5 years. The immunologic response of the polysaccharide vaccine is only 40% in SOT recipients.

Pneumococcal vaccine

Transplant recipients are at increased risk of invasive pneumococcal disease. There are two formulations of the pneumococcal vaccine: A 23-valent polysaccharide vaccine and a 13-valent conjugate vaccine. Though the conjugate vaccine is recommended as part of the childhood vaccination, only a limited population of the Indian sub-continent has been vaccinated in the past decade.[7] There is a trend for greater vaccine immunogenicity with the conjugate vaccine.[10] All candidates need the conjugate vaccine, followed 2 months later by the polysaccharide vaccine.[2] If the candidate has received the polysaccharide vaccine initially, the conjugate vaccine is recommended after 1 year. A repeat of the polysaccharide vaccine is recommended after 5 years in both situations.[10]

Hepatitis B vaccine

The Indian sub-continent comes under the intermediate prevalence (2%–5%) area for Hepatitis B, with similar rates in South Asia. Hepatitis B vaccine should be given to all candidates as a standard 3-dose series at 0, 1, and 6 months. An accelerated schedule can also be given at 0, 7, 21, and 28 days or 0, 1, 2 months, and 6 months (with a double-dose for patients with CKD patients on dialysis).[1] Hepatitis B antibody titers should be routinely monitored 4–8 weeks after the last dose.[1] Revaccination is recommended if HBs antibody titers fall <10 IU/ml.[11]

Hepatitis A vaccine

South and south-east Asia come under the high-risk areas for hepatitis A. Other risk factors include intravenous drug use, men who have sex with men, and certain ethnic or religious groups. Hepatitis A is not part of the routine childhood vaccination in India.[7] The inactivated vaccine schedule includes 2 doses, 6 months apart. This provides lifelong immunity, though the antibody response is poorer in SOT recipients.[12] This vaccine is also recommended to SOT recipients traveling to South Asia.[3] The live attenuated hepatitis A vaccine (Biovac-A) is not recommended in transplant recipients but could be given at least a month before transplant. Routine serological testing is not indicated post vaccination.

Human papilloma virus vaccine

Both cervical and anogenital warts and cancer caused by the human papillomavirus are seen more commonly in SOT recipients.[13] Two formulations of the vaccine are available in India: A quadrivalent vaccine and a bivalent vaccine that are recommended between 9 and 26 years of age.[8] A 3 dose prophylactic vaccine schedule is recommended prior to transplant at 0, 2, and 6 months. If the doses are not completed pretransplant, they can be resumed posttransplant. Immunogenicity may be sub-optimal in adult transplant recipients.[14]

Polio vaccine

Although the last case of polio reported in India was in 2011, it remains endemic in Afghanistan and Pakistan. A booster dose of inactivated polio vaccine as an intramuscular dose can be given for all SOT candidates and recipients. The oral live-attenuated virus vaccine is contraindicated for all transplant recipients and their household contacts, as fecal-oral transmission could occur, with risk for prolonged shedding and reversion to pathogenic virus.

Varicella vaccine

Varicella-zoster infection after SOT is associated with increased morbidity and mortality. Varicella-zoster vaccine is a live attenuated virus vaccine that is indicated pretransplant in those who are not immune and not yet immunocompromised.[2] The vaccine is given as 2 doses 4 weeks apart. Postvaccination serology can be performed in certain situations, although is likely not necessary most of the time, as seroconversion occurs up to 95% before transplantation.[15] Although there is evidence for the safety of varicella vaccine posttransplant in a small number of pediatric patients on low dose immunosuppression, the vaccine is best avoided posttransplant.[16] For nonimmune transplant recipients exposed to a patient with VZ virus infection, immune-prophylaxis with either acyclovir or varicella-zoster immune globulin is recommended as early as possible but may be given up to 10 days following the exposure.

Herpes zoster vaccine

Reactivation of VZ (Herpes Zoster) is common after SOT. Herpes Zoster vaccine is a live-attenuated virus vaccine indicated in those older than 50 years to prevent shingles and postherpetic neuralgia. Zostavax is a live-attenuated HZ virus vaccine given as a single dose. It is contraindicated posttransplant but can be used at least 4 weeks before in the pretransplant setting, assuming they are not otherwise on immunosuppression.[2] Shigrix is a recombinant protein zoster vaccine with a potent adjuvant (RZV) given as a 2 dose vaccination 2–6 months apart and is recommended after 50 years of age. It is not available in India.

Typhoid vaccine

Typhoid is endemic in several parts of South and Southeast Asia. Two formulations of typhoid vaccine are available: a polysaccharide and a conjugate vaccine. Both vaccines are safe and reasonably effective. A third formulation of oral live attenuated vaccine is currently unavailable in India. The polysaccharide vaccine is recommended every 3 years whereas one dose of the conjugate vaccine is believed to offer a more robust and prolonged immunogenicity.[17] The typhoid vaccine does not protect against paratyphoid and hence other protection measures such as discretion in food and water consumption are necessary after transplantation.

COVID vaccine

Organ transplant recipients are at heightened risk for severe COVID-19 infection, hence there is a paramount need for vaccination in this vulnerable population.[18]

Prospective transplant recipients and their household members should receive any COVID-19 vaccine that is authorized or approved by designated advisory authority. Countries in the Southeast Asian Region are administering Astra Zeneca, Covaxin, Janssen, Moderna, Sinopharm, Sinovac, Sputnik V, and Pfizer following emergency use authorization being granted by their national regulatory authorities.[19] Efficacy and safety of COVID-19 vaccine in SOTs have been scientifically documented only for few m RNA vaccines and many are still under clinical trial.[20] Efficacy of the two widely available recombinant viral vector/inactivated vaccines in India: ChAdO × 1 nCoV-19 Corona Virus Vaccine (Recombinant) and COVAXIN® (India's indigenous COVID-19 vaccine by Bharat Biotech) for SOT recipients is still sparingly reported.[21]

The current data suggest there may be a diminished antibody response in this population. Maintenance immunosuppression should be maintained throughout the vaccination period and not reduced.[22] Some countries are recommending a third dose of mRNA vaccine for transplant recipients. Consensus on giving additional doses of other vaccines is yet not clear pending trial results.

Travel vaccines

Yellow fever vaccine

Yellow fever (YF) is not endemic in south Asia. The vaccine is recommended to all nonimmunocompromised susceptible individuals traveling to endemic areas. The YF vaccine requirements are regulated by international law. It is a live-attenuated virus vaccine that is contra-indicated in the posttransplant setting. A single dose of YF is sufficient to provide life-long immunity in immune-competent hosts and booster doses every 10 years are no longer required.[23] SOT recipients who travel to YF risk areas should be counseled on mosquito bite prevention measures and given a signed contraindication to vaccination in an International Certificate of Vaccination or Prophylaxis (also called a Yellow Card) so that they can cross international borders without mandatory vaccination.

Japanese B encephalitis vaccine

Japanese Encephalitis (JE) is a mosquito-borne flaviviral infection. Risk areas include rural areas where the breeding of pigs and rice farming is carried out. Vaccine is indicated for persons exposed to such conditions or persons traveling for prolonged periods (>1 month) in endemic areas [Table 2].[24] The inactivated JE virus vaccine is given as a 2 dose series 28 days apart. We do not have data on vaccine efficacy in transplant recipients. The live vaccine is contraindicated in SOT recipients but could be given at least a month before transplant in those who are not yet immunocompromised.
Table 2: Travel vaccines for solid organ transplantation recipients in South Asia

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Rabies vaccine

South and South-east Asia are endemic for rabies and worldwide, have the most rabies-related deaths. Transplant recipients should be advised to avoid exposure to these animals during their travel. However, transplant recipients expecting intense exposure to rabies are advised preexposure rabies vaccination (0 and 7 days). Post vaccination titers should be checked.[24] In the event of a suspected rabid animal bite, 4 doses on day 0, 3, 7, and 14/28 is recommended. For those who have not had a preexposure vaccine, immunoglobulin, and the complete vaccine course should be given, regardless of the severity of the bite or animal status.[25]

Dengue vaccine

Another endemic mosquito-borne flaviviral infection, dengue is endemic to South Asia. Currently, a live-attenuated virus tetravalent chimeric vaccine (Dengvaxia®, Sanofi Pasteur) is available with an estimated efficacy of 56.6%.[26] Dengue vaccine is contraindicated posttransplant as it is a live vaccine. The vaccine is indicated in countries where dengue seroprevalence is >70% and is usually reserved for higher risk, prolonged exposures, not routine travel. Although it is available in several countries, it is not available in India.

Cholera vaccine

Cholera vaccine is currently indicated for travelers to endemic areas during cholera outbreaks. Three orally administered vaccines are available (Dukoral, which offers cross-protection to Enterotoxigenic Escherichia coli), Shancol, a 2 dose series 1 week apart (comprised of killed bacteria), and Vaxchora, a live vaccine that is contraindicated in SOT recipients.[2]


  Conclusions Top


Vaccination can provide protection against numerous illnesses, which is especially important in more vulnerable immunocompromised transplant patients. Pretransplant evaluation of vaccine status provides an opportunity to update vaccines, including with protection from live vaccines that should not be given after transplant. Nonlive vaccines can be given after transplant, although generally with attenuated immunologic response and decreased protection. Transplant providers are encouraged to include this in their optimal transplant management strategies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58:e44-100.  Back to cited text no. 1
    
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Danziger-Isakov L, Kumar D; AST ID Community of Practice. Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant 2019;33:e13563.  Back to cited text no. 2
    
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Hurst FP, Lee JJ, Jindal RM, Agodoa LY, Abbott KC. Outcomes associated with influenza vaccination in the first year after kidney transplantation. Clin J Am Soc Nephrol 2011;6:1192-7.  Back to cited text no. 4
    
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Brakemeier S, Schweiger B, Lachmann N, Glander P, Schönemann C, Diekmann F, et al. Immune response to an adjuvanted influenza A H1N1 vaccine (Pandemrix(®)) in renal transplant recipients. Nephrol Dial Transplant 2012;27:423-8.  Back to cited text no. 5
    
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Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009;9 Suppl 3:S1-155.  Back to cited text no. 6
    
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Available from: https://iapindia.org/pdf/124587-IAP-GUIDE-BOOK-ON-IMMUNIZATION-18-19.pdf. [Last accessed on 2021 Sep 15].  Back to cited text no. 7
    
8.
Guidelines for vaccination in normal adults in India. Indian J Nephrol 2016;26 Suppl 1:S7-14.  Back to cited text no. 8
    
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Struijk GH, Bouts AH, Rijkers GT, Kuin EA, ten Berge IJ, Bemelman FJ. Meningococcal sepsis complicating eculizumab treatment despite prior vaccination. Am J Transplant 2013;13:819-20.  Back to cited text no. 9
    
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Blanchard-Rohner G, Enriquez N, Lemaître B, Cadau G, Giostra E, Hadaya K, et al. Pneumococcal immunity and PCV13 vaccine response in SOT-candidates and recipients. Vaccine 2021;39:3459-66.  Back to cited text no. 10
    
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Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008;57:1-20.  Back to cited text no. 11
    
12.
Jeon HJ, Ro H, Jeong JC, Koo TY, Han M, Min SI, et al. Efficacy and safety of hepatitis A vaccination in kidney transplant recipients. Transpl Infect Dis 2014;16:511-5.  Back to cited text no. 12
    
13.
Wieland U, Kreuter A, Pfister H. Human papillomavirus and immunosuppression. Curr Probl Dermatol 2014;45:154-65.  Back to cited text no. 13
    
14.
Kumar D, Unger ER, Panicker G, Medvedev P, Wilson L, Humar A. Immunogenicity of quadrivalent human papillomavirus vaccine in organ transplant recipients. Am J Transplant 2013;13:2411-7.  Back to cited text no. 14
    
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Broyer M, Tete MJ, Guest G, Gagnadoux MF, Rouzioux C. Varicella and zoster in children after kidney transplantation: Long-term results of vaccination. Pediatrics 1997;99:35-9.  Back to cited text no. 15
    
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Posfay-Barbe KM, Pittet LF, Sottas C, Grillet S, Wildhaber BE, Rodriguez M, et al. Varicella-zoster immunization in pediatric liver transplant recipients: Safe and immunogenic. Am J Transplant 2012;12:2974-85.  Back to cited text no. 16
    
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Sahastrabuddhe S, Saluja T. Overview of the typhoid conjugate vaccine pipeline: Current status and future plans. Clin Infect Dis 2019;68:S22-6.  Back to cited text no. 17
    
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Akalin E, Azzi Y, Bartash R, Seethamraju H, Parides M, Hemmige V, et al. COVID-19 and kidney transplantation. N Engl J Med 2020;382:2475-7.  Back to cited text no. 18
    
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Meshram HS, Kute VB, Shah N, Chauhan S, Navadiya VV, Patel AH, et al. Letter to editor: COVID-19 in kidney transplant recipients vaccinated with oxford – AstraZeneca COVID-19 vaccine (Covishield): A single center experience from India. Transplantation 2021;105:e100-3.  Back to cited text no. 21
    
22.
Stock PG, Henrich TJ, Segev DL, Werbel WA. Interpreting and addressing suboptimal immune responses after COVID-19 vaccination in solid-organ transplant recipients. J Clin Invest 2021;131:151178.  Back to cited text no. 22
    
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24.
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