Vaccine Recommendations for Solid-Organ Transplant Recipients and Donors

Vaccine-preventable infections represent a significant burden of disease in solid-organ transplant (SOT) recipients. Respiratory infections caused by Streptococcus pneumoniae and influenza viruses are more prevalent and associated with worse outcomes compared with the general population1,2 Chickenpox and herpes zoster are associated with significant morbidity in these patients. Meningococcal disease, although rare in SOT recipients, is at greater risk in patients receiving the terminal complement inhibitor eculizumab.3 In addition, SOT recipients live longer and have better quality of life; and therefore, they are more likely to travel to tropical regions.4 Together with increasing activity of transplant centers located in tropical regions, SOT recipients have a greater potential to be exposed to vaccine-preventable infections. General Principles of Immunization Immunosuppressive drugs administered after transplant impair vaccine immune responses. Also, live-attenuated vaccines may have safety concerns in immunocompromised patients. Therefore, it is highly recommended to vaccinate patients before transplantation; particularly, at early stages of the underlying disease to avoid any effect of end-organ disease on vaccine immunogenicity.5 Because there is a risk of no response to the vaccine, it is also recommended to perform vaccine serology after vaccination when available. Vaccination of healthcare workers and households is also of importance to decrease exposure to the pathogen. This review will discuss routine vaccination for candidates and recipients in Latin American (LA) and specific consideration for candidates and recipients traveling to/from LA. Routine Vaccination Some routine vaccines are recommended to candidates and recipients of SOT who live in endemic regions or who will return to live in endemic regions. Recommendations are based on the routine schedule for immunocompetent individuals, according to a persons age, vaccination, and exposure history.6 The routine recommendation for vaccination in adults transplant candidates or recipients is summarized in Table 1.TABLE 1: Recommendation for vaccination in adults transplant candidates or recipientsTetanus, Diphtheria, and Pertussis Vaccine The complete vaccination schedule against tetanus/diphtheria/pertussis in LA countries consists of 3 primary doses for all candidates with a booster dose of tetanus/diphtheria-containing vaccine every 10 to 20 years. Bordetella pertussis is the main causative agent of pertussis, also known as whooping cough, which remains a serious public health problem worldwide. In LA, the annual number of suspected pertussis cases over the last 10 years has ranged from 1500 to 43000 with significant increases in the number of cases in Argentina, Brazil, Mexico, Chile, Colombia, Paraguay, Peru, and Uruguay, among others. Possible reasons for the increasing number of pertussis cases are the suboptimal coverage rates of vaccination, the waning of immunity conferred by vaccination and/or natural infection, the reduction in the number of natural boosters, and the adaptability of the bacteria to the immunity conferred by the vaccines. Other more noticeable causes are the higher awareness of the disease, and the improvements in epidemiological surveillance and diagnostic tests.8 Also, divergence between vaccine strains and local isolates could contribute to the described pertussis epidemiology.9 In many countries including some from LA, pertussis is now increasing in adolescents and adults, probably due to the fast waning immunity postimmunization.8 The assessment in the burden of pertussis in LA is complex, especially in regard of comparisons between countries. This may be mainly due to the differences in vaccination (type of vaccine and/or producer of vaccines) and the quality of the surveillance systems adopted. Data from other countries of LA (Argentina, Brazil, Chile, Colombia, and Mexico) have evidence of an increase in pertussis-related morbidity in recent years, as compared to previous periods.8 Immunization against pertussis (combined with tetanus and diphtheria-containing vaccine) has been included in the World Health Organization's (WHO) Expanded Programme on Immunization in 1974 for children. In recent years, an increasing number of cases have been registered in older children, adolescents, and adults. Based on this, the current Centers for Disease Control and Prevention (CDC) recommendation is that adolescents and adults receive a 1-time booster dose of tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis (Tdap) vaccine. After receiving Tdap, individuals should continue to receive Td for routine booster vaccination against tetanus and diphtheria, in accordance with previously published guidelines.10 Influenza Vaccine Influenza disease affects up to 10% of the world's population every year. Transplant recipients belong to the high-risk group of complications and death compared to general population, and should receive an annual influenza vaccine.11 The WHO Global Influenza Surveillance and Response System define the vaccine composite for the following influenza season in the northern and southern hemisphere in February and September, based on the influenza viruses circulating in the last influenza season. Influenza occurs year-round in the tropics; although, recent data suggests that there are also specific epidemic peaks in tropical countries.12 The updated annual influenza vaccine distribution usually starts from April to May. There are 2 types of influenza vaccine, the trivalent (or quadrivalent) inactivated influenza vaccine (TIV) and the live-attenuated influenza vaccine (LAIV). Because of safety concerns, LAIV is contraindicated in immunocompromised patients. A significant amount of data has confirmed that TIV in SOT recipients is safe and immunogenic.13 Although antibody responses are expected to be lower in SOT recipients, studies found that vaccinated patients have lower rates of complications and improved allograft and patient survival14,15 Although some studies correlated influenza vaccination with production of anti-HLA antibodies, this has not confirmed in subsequent larger studies.16 The exact timing of administration of influenza vaccine after transplant has not been completely defined; whereas, immunogenicity may be reduced during the first weeks posttransplant, which is the period when influenza is associated with impaired outcomes. Recommendations suggest that 1 to 3 months is the minimal period for vaccination.13 However, the influenza vaccine can be administered 1 month after transplantation during a community influenza outbreak,6 and revaccination 3 to 6 months after transplantation could be considered if influenza activity persists after this period. Recent clinical trials have studied alternative immunization scheme for SOT recipients, such as administration of a booster doses, a double dose of antigen, intradermal preparations and adjuvanted vaccine, in an attempt to improve the efficacy of the vaccine.17-19 Although these strategies have yet to be validated in large clinical trials, adjuvanted and high-dose vaccines have been well tolerated and may have increased immunogenicity compared with the standard dose.18-20 Households and close contacts of transplant recipients should receive influenza vaccine yearly, preferably the inactivated vaccine. However, if only LAIV is available, they must be aware of handwashing frequently for a 2-week period after vaccination.5 Although antiviral prophylaxis with neuraminidase inhibitors is not recommended in high-risk or unvaccinated patients, patients can be given empiric antiviral therapy if symptoms compatible with influenza appear while waiting for a confirmatory diagnosis.21 Measles-Mumps-Rubella Vaccine Severe cases of measles, including the development of subacute measles encephalopathy, have been described in SOT recipients.22 Seronegative pediatric transplant candidates should receive 2 doses of the vaccine 1 month apart and seronegative adult transplant candidates should receive 1 dose of the vaccine, with seroconversion confirmation after 1 month (and a booster dose in case of undetectable antibody levels).5 These patients should be put on temporary hold for transplant for a minimum interval of 28 days. Experience with the use of MMR vaccine in the posttransplant period is limited to selected cases of pediatric liver transplant recipients on low doses of immunosuppression.23 Otherwise, MMR vaccine should not be used in SOT recipients. Households and close contacts of transplant recipients should also receive MMR vaccine.5 Pneumococcal Vaccines S. pneumoniae causes a wide range of diseases such as pharyngitis, acute otitis media, meningitis, septic arthritis, and bacteremia beyond pneumonia. Invasive pneumococcal disease (IPD) is a vaccine-preventable disease that causes around a million deaths each year worldwide; approximately 90% of these deaths occur in developing countries.24 In LA and the Caribbean, WHO reports that 1.6 million children younger than 5 years suffer an episode of IPD each year and among 12 000 to 28 000 deaths occur annually.24S. pneumoniae is the most prevalent agent associated with pneumonia cases in LA, accounting for at least 11% of all disease causes. Pneumococcal meningitis is also a relevant issue in LA with an incidence of 8.34 per 100 000 in children aged 0 to 23 months, and 4.62 per 100 000 in the age group of up to 5 years. The mortality rate is high among the elderly reaching 80%.25 Two types of pneumococcal vaccines are available: polysaccharide (PPV) and conjugate vaccines (PCV). Pneumococcal vaccines in different age groups can reduce the burden of disease, morbidity, mortality, and hence the high costs in healthcare attention of the affected patients, providing protection against the most common serotypes. In LA and the Caribbean regions, PCV has been incorporated as part of the universal immunization programs for children under 2 years. It has also been approved for use in adult patients with underlined risk factors for IPD.24 The immunization of high-risk population against IPD aged between 2 and 65 years has been conducted in several countries with the administration of PPV23. However, immunocompromised patients do not present a good response to polysaccharide vaccines, conjugate vaccines are the best option for this group.26 PCV7 was licensed in 2000 to provide protection against 7 of the most common pneumococcal serotypes. In early 2010, new formulations with protection against 10 and 13 serotypes have become available for use. Serotypes 1, 3, 5, 6A/B, 7F, 9V, 14, 18C, 19A/F, and 23F are the most frequently found in LA. These serotypes are covered by both conjugate vaccines (PCV7 contains 4, 6B, 9V, 14, 18C, 19F, and 23F serotypes; PCV10 also covers serotypes 1, 5 and 7F in addition to PCV7; and PCV13 contains serotypes 1, 3, 5, 6A, 7F and 19A in addition to PCV7) and the polysaccharide vaccine PPV23 (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F).25 Thus, despite the high incidence of IPD, available vaccines show potential efficacy in this scenario, setting up a preventable health problem in these countries. Studies comparing PCV7 and PPV23 in the adult organ transplant population show that there is a trend to greater vaccine immunogenicity with PCV7; however, a longer-term follow-up of this cohort showed that titers declined to baseline by 3 years regardless of vaccine type.27 In addition, no boosting effect was seen with PPV23 after PCV7 was administered.28 One dose of PCV13 is recommended for adult transplant candidates or recipients, followed by a dose of PPV23 after a minimum interval of 8 weeks to expand serotype coverage.29 In some countries, where there is little additional coverage of the invasive serotypes with the PPV23, a second dose of the PCV13 is recommended. Immunocompromised adults aged 19 years or older who previously have received at least 1 PPV23 vaccine dose should be given a PCV13 vaccine dose at least 1 year interval after last PPV23 vaccine.29 For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23.29 Meningococcal Vaccine Neisseria meningitidis remains a major cause of invasive bacterial disease worldwide and is associated with substantial morbidity and overall case fatality rates of around 10%. In LA, incidence rates and serogroup distribution of meningococcal disease are highly variable (from <0.1 to almost 2 cases per 100 000 inhabitants), with the highest burden of disease reported in Brazil and the Southern Cone countries (Argentina, Chile, and Uruguay)30; very limited data are available from the Andean region, Mexico, and Central America. Overall, in LA, there is a need to improve the surveillance system (including case definition, laboratory procedures and surveillance). According to the SIREVA surveillance (Sistema de Redes de Vigilancia de los Agentes Responsables de Neumonías y Meningitis Bacterianas), since 2000 in LA and the Caribbean, the most prevalent meningococcal serogroups circulating are B and C, with 69% and 26% of the total group, and there is a progressive increase in circulation of serogroups W and Y.31 Meningococcal outbreaks occur periodically in some parts of LA. The recent emergence and spread of serogroup W disease in Argentina and Chile have determined the changes in routine meningococcal vaccination programs.30 Meningococcal polysaccharide vaccines (MPV against N. meningitidis serotypes A, C, Y and W) are important to control outbreaks and epidemics. They are not used, however, in the routine immunization because they stimulate immune response T cell-independent and do not induce immunological memory and protection is short-lived. The conjungation of polysaccharide to a protein carrier (meningococcal conjugate vaccines, MCV) provides a T cell dependent immune response, immune memory and long-term protection. A recent N. meningitidis serotype B vaccine obtained by reverse vaccinology was recently licensed in some countries, but there is still no data on its use in immunocompromised patients.32 Both MCV4 and MPV4 (against serotypes A, C, W, and Y) are recommended for use in control of meningococcal outbreaks caused by vaccine-preventable serogroups. Specific recommendations should be reinforced for vaccination of high-risk groups.33 The Brazilian current recommendation is to vaccinate with MCV-C all SOT candidates and recipients.34 The recommended schedule in SOT recipients or candidates for meningococcal vaccine is 2 doses 2 months apart. Meningococcal disease does not seem to occur at higher rates after transplantation, with only a few case reports published.35 Therefore, meningococcal vaccination has not routinely been recommended in SOT recipients, except in patients with risk factors (eg, splenectomy, military recruits), or those who travel to high-risk areas (Hajj) (see below). Cases of meningococcal disease have been recently reported; however, in patients receiving eculizumab, a terminal complement pathway inhibitor, which is authorized for the treatment of atypical hemolytic-uremic syndrome, and is increasingly used for the treatment of antibody-mediated rejection posttransplant.3 Few studies have evaluated the immunogenicity of meningococcal vaccine in SOT recipients. Humoral responses to the polysaccharide vaccine appear to be worse compared to the conjugated vaccine, so that this latter vaccine is preferred.36 Because of the potential impaired responses to meningococcal vaccine in the early posttransplant period (usually when eculizumab is administered), vaccination in transplant candidates with a higher immunological risk before transplant (ie, highly sensitized, high panel of reactive antibody) may be a more effective strategy to protect against meningococcal disease, although there are no data to support this recommendation.37 Varicella and Zoster Vaccines Both varicella and zoster vaccines are live-attenuated vaccines and should be given before transplant. Varicella vaccine is indicated for those that are VZV IgG negative and do not have documented proof of receipt of 2 doses of varicella vaccine. Zoster vaccine contains approximately 14 times the amount of attenuated virus than varicella vaccine and is indicated for before transplant in those candidates aged 50 years or older who are VZV IgG positive and not on immunosuppressive drugs.38 However, the effect of pretransplant zoster vaccination on posttransplant protection from shingles is largely unknown. Although the varicella vaccine is live-attenuated, it has been administered safely posttransplant in selected long-term transplant (primarily pediatric) recipients on low-dose immunosuppression.39,40 Because there are no large studies, the risk and benefits of this approach need to be carefully weighed on a case-by-case basis. A recent study suggested that zoster vaccine was generally well tolerated in patients receiving chronic/maintenance corticosteroids, as is the case of SOT Households and close contacts of transplant recipients should also receive varicella vaccine.5 A inactivated vaccine VZV is under study in transplant recipients. In older adults years of a 3 study was recently conducted in countries, the safety and efficacy of the vaccine to reduce the risk of herpes B Vaccine In LA, the countries are considered low regions for B virus For more epidemiological to the review on in this B vaccine should be given as a before transplantation when and titers should be to 8 weeks to In previously vaccinated patients during titers should be also to booster doses are to B vaccine can occur in disease and patients on high dose B vaccine should be administered to patients on and all posttransplant patients. Although the standard schedule for vaccination is 1, and 6 months, at and 28 and 1, 2 months a booster dose at 6 have been studied and are The Brazilian current recommendation for immunocompromised patients is a schedule with according to the age group standard Although B antibody titers should be routinely after transplantation and booster doses given if titers a recent review that clinical trials are to the benefits of booster dose vaccination for A Vaccine factors for A virus who have with travel to high-risk and or LA is a to high-risk for For more epidemiological to the review on in this Vaccine against A is an inactivated virus vaccine, which has safety and high immunogenicity in the general A vaccine is in routine vaccination schedule 1 in some countries of LA, such as Brazil and The vaccine schedule 2 doses, 6 months but the first dose is usually to protection in immunocompetent patients. Studies the immunogenicity of vaccine in SOT recipients have generally showed a lower antibody response after vaccination as compared with Vaccination against in seronegative patients before transplant or with the vaccine) is Vaccine The region, which LA, Caribbean, and and the the of in by vaccine and was as of in most LA and Caribbean countries on the to the inactivated vaccine by can be administered to SOT recipients as a The live-attenuated virus vaccine is contraindicated in transplant recipients and contacts due to the risk of of Vaccine Disease caused by including and occurs with greater in SOT Because vaccine is recommended before routine immunization with a at 2, 6 months should be followed according to the current or for routine vaccination of aged to 14 years to years who have not been vaccinated previously or who have not the and or for routine vaccination of aged to 12 years to years who have not been vaccinated previously or who have not the or vaccination is recommended for who have with and for immunocompromised age years if not vaccinated Although routine immunization with has been used as an alternative to the standard it has not been studied yet in immunocompromised patients. vaccine is an inactivated vaccine based on the protein of and can be to or Although immunogenicity or efficacy has not been studied in the pretransplant studies in the posttransplant setting showed good immunogenicity in but lower immunogenicity in the adjuvanted the vaccines have been studied in transplant recipients, although could be used if recommended in Vaccination for Vaccination for SOT recipients should be several months before travel to/from LA. The vaccination schedule to the risk of exposure to vaccine-preventable disease in the of as well as the travel Vaccines attenuated viruses measles, are contraindicated for SOT recipients if there is a potential risk of exposure in a It is recommended that live-attenuated vaccines be administered during pretransplant period. is a good for healthcare to review the immunization of patients. should be up to with routine before the Thus, vaccines previously described must be the protection or should be updated diphtheria, pertussis, However, some vaccines are not routinely indicated and should be administered in case of exposure during Although it is for to have an of immunization during an of specific immunization is only for for those traveling to and vaccine for those traveling to countries that require proof of The recommendation for vaccination in adults transplant candidates or recipients traveling to LA is summarized in Table For more specific or the specific review of routine can be found in the Health for Recommendation for vaccination in adults transplant candidates or recipients traveling to Latin Vaccine previously are in the with peaks and year-round Therefore, influenza immunization should be given to all SOT recipients who not vaccinated the before traveling to LA and from LA to the northern hemisphere during the Meningococcal Vaccine Vaccination with meningococcal vaccines is by all to including to the and is recommended for those traveling to the meningitis in WHO provides with of countries A Vaccine individuals that have in potential travel to endemic areas should receive the vaccine. For in case of from vaccination to travel patients should receive in addition to 1 vaccine dose at a who are exposed to should be administered 1 dose of A vaccine or as as 2 weeks of Vaccine For traveling to countries where the is still it does not LA countries. For SOT recipients traveling from LA to parts of and which may be at risk for 1-time inactivated vaccine booster is Vaccine is not present in all parts of LA, and in most of the countries the virus is to For more epidemiological to the review on in this Vaccination is the most important against The vaccine is recommended to all individuals if traveling to endemic it is for and in some countries from all or of of The vaccine are by is available from the vaccine is a live-attenuated virus vaccine contraindicated in the posttransplant Some SOT recipients have received the vaccine with no major complications However, the immunogenicity of vaccine on these patients is and because of the potential development of the disease by the vaccine it is not recommended in SOT recipients. A dose of vaccine is to immunity in immunocompetent and booster doses every 10 years are no longer that have been vaccinated before transplant are probably still years after to risk areas are generally not recommended for SOT recipients, in case of SOT recipients who have to travel to risk areas should be to use to including and to countries a vaccine in those with a to vaccination a the of Vaccination or Vaccine is a by and is endemic in several countries, especially in if to Therefore, vaccination must be considered only for those travel from LA to endemic The inactivated virus vaccine can be administered to SOT recipients and is given as a 28 A booster dose be recommended for who was vaccinated more than a year and remains at risk for There is a vaccine live-attenuated viruses available in that is contraindicated for SOT recipients. Vaccine incidence in LA and the Caribbean has and several countries Chile, Mexico, and and there are areas to which this disease is still The areas for by are and parts of Brazil and in these areas In LA and the Caribbean, around of cases of are by and by Although control in LA and the Caribbean has been should be for avoid Transplant recipients who exposure to during travel should receive available, vaccine should be after vaccination has not been given and the transplant is exposed to the they should be for and the vaccine schedule should be of the of the and the with vaccination who are exposed to virus should complete the vaccination schedule after Vaccine and important public health and major causes of morbidity in the developing The of in LA from 10 to 100 000 cases but there is the incidence due to the of surveillance is a problem in to endemic especially those and the 2 main vaccines recommended for are the inactivated vaccine bacterial polysaccharide and the live-attenuated bacteria vaccine. These licensed vaccines are safe and effective against However, there is no available vaccine against which is increasingly reported as a cause of remains a common cause of in for those who been vaccination is indicated for traveling to endemic The live-attenuated bacteria vaccine is contraindicated for SOT recipients. The inactivated polysaccharide vaccine is indicated for SOT recipients traveling to endemic regions and is administered as a A booster dose is recommended for vaccinated more than 2 years and still at risk of vaccination does not the use of other protection to Vaccine The epidemic still high morbidity and mortality due to and The of in LA the need for development and of and control In LA, the most affected countries have been between and with a annual incidence of cases per 100 000 population but a low case fatality rate and between and with a annual incidence of per 100 000 population and a case fatality rate of vaccination is indicated for traveling to endemic areas during but it is not routinely recommended administered vaccines are available. The vaccine contains the of the which is to the and protection by The vaccine contains from 2 strains of Both vaccines can be administered to SOT recipients as a least 1 A booster dose is recommended for who was vaccinated more than 2 years and is still at risk of because the vaccine efficacy may be additional for of diseases should be is a live vaccine against disease caused by serogroup that it is indicated for adults to years of age traveling to but it is contraindicated in SOT Vaccine to control based on protection against and million cases of occur worldwide. of in LA, where the disease is largely in the areas and where the serotype of the virus and For more epidemiological to the review on in this Therefore, vaccine is a public health and an vaccine is a vaccine that immunity against the serotypes. The first licensed vaccine is the a live attenuated vaccine by that the virus as a and protein from Vaccine efficacy was the serotype specific efficacy for was not is approved by Mexico, and Brazil, for aged to years. The vaccine is not recommended under age data from clinical trials showed that among children younger than years, the risk of vaccinated children for a increased Other vaccine candidates are in clinical stages of including a study of in Brazil, a live-attenuated vaccine by the between the in Brazil and the of Health of the well as all other attenuated vaccines, vaccine is contraindicated for SOT recipients.

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