Objectives: Vaccine-preventable diseases remain a major cause of morbidity and mortality in solid-organ transplant candidates and recipients. Newer recom-mendations include vaccination of all household members to create a herd immunity around the transplant recipient. This study evaluated the vaccination status of pediatric solid-organ transplant recipients and their household members.
Materials and Methods: We evaluated 30 pediatric solid-organ transplant recipients (14 kidney, 13 liver, 3 heart) and their household members (26 siblings, 30 parents) at time of transplant.
Results: Fourteen recipients (47%) received scheduled vaccinations before solid-organ transplant and were up to date for their age with their diphtheria, tetanus, pertussis; hepatitis B virus; poliomyelitis; Haemophilus influenzae type B; Streptococcus pneumoniae conjugate vaccine; and measles, mumps, and rubella vaccinations. Another 7 recipients (23%) had partially completed their schedules, only missing the second dose of the measles, mumps, and rubella vaccine. Fifteen siblings (58%) had either completed (n = 13, 50%) or partially completed (n = 2, 8%) their vaccinations. All 30 parents were either unaware of their vaccination status (n = 10, 33%) or had only incomplete vaccination records (n = 20, 67%).
Conclusions: We found that most pediatric solid-organ transplant recipients to be appropriately vaccinated. However, vaccination status in household members, especially in parents, was disappointing.
Key words : Herd immunity, Infection, Vaccine-preventable diseases
Vaccine-preventable diseases remain a major cause of morbidity and mortality in solid-organ transplant (SOT) recipients. Immunosuppression has greatly improved transplant outcomes by preventing rejection; on the other hand, it can also lead to severe and life-threatening infections.1 Because immune responses to vaccines are diminished during organ failure and after SOT, SOT candidates should be vaccinated as early as possible. Recommendations for vaccination of pediatric SOT candidates and recipients have been previously presented.1-4 These recommendations include accelerated schedules to improve vaccination rates without compromising immunogenicity.3,4 However, most children who receive SOT have not completed their primary vaccinations. In one study, as many as 70% of SOT recipients were not up to date with their vaccination schedule at time of transplant.5 The reasons for this ranged from medical issues, such as young age and chronic ill health, to nonmedical issues, including parental aversion against vaccinations.6 Paradoxically, as a consequence, children who receive the most advanced medical treatment do not benefit from simple and inexpensive prevention strategies like vaccinations.
Household transmission of vaccine-preventable diseases represents a potentially important source of infection for children after SOT. Therefore, newer recommendations include the appropriate vaccination of all household members, thus providing a household herd immunity for vulnerable SOT recipients. Although some studies have evaluated the vaccination status of pediatric SOT recipients,5-8 none has additionally assessed vaccination rates in household members. Here, we conducted an observational study to determine vaccination rates in our SOT recipients and their household members at time of transplant, with the goal of identifying patients at risk for household transmission of vaccine-preventable diseases.
Materials and Methods
This study was conducted at the Department of Pediatrics of the Medical University of Innsbruck, a major transplant center in Austria. All pediatric SOT candidates who received regular follow-up between April 2007 and December 2014 were invited to participate in this study, which was approved by the local ethics committee. Parents willing to participate in the study were instructed to present vaccination records for the SOT recipient and for all household members, including siblings and parents. After giving written informed consent, parents were interviewed and vaccination records were evaluated. Only charts filled out by a physician and only proper records of administered vaccines, including date of vaccination, were assessed. Hearsay information about vaccines not recorded was disregarded.
Siblings and parents participating in this study were healthy; none had an underlying condition thought to contraindicate vaccination. Vaccination status was compared to the 2014 national immu-nization schedule recommended by the Austrian Immunization Committee (Table 1). We considered vaccination status complete if a child had received all recommended doses for their age of the 6-fold vaccine (containing diphtheria/tetanus/pertussis [DTaP], hepatitis B virus [HBV], poliomyelitis, and Haemophilus influenzae type B [HiB]), the Streptococcus pneumonia conjugate vaccine, and the measles, mumps, and rubella (MMR) vaccine. A vaccination status was considered partially complete if the child had received each vaccine but insufficient doses and incomplete if the child was not vaccinated at all against one or more of these antigens.
We also recorded status regarding additional vaccines recommended for patients at higher risk for infection, such as Neisseria Meningitis Type C conjugate vaccine, varicella-zoster virus, and seasonal influenza vaccinations. We recorded the total number of doses and the mean number of doses against all antigens. Demographic data of the SOT recipients, siblings, and parents (age, sex, body weight) and the type of SOT performed were noted. Additionally, we compared vaccination status among the different SOT recipients (liver, kidney, heart) and between SOT recipients and their siblings.
To evaluate vaccination status at SOT, vaccination records of 30 SOT recipients were reviewed. Median patient age at SOT was 9.7 years (range, 5 mo to 15.3 y); 20 recipients were boys. Fourteen patients received a kidney SOT (median age of 9.8 y), 13 received a liver SOT (median age of 1.5 y), and 3 received a heart SOT (median age of 10.1 y). Twenty-six siblings (median age of 12.1 y; range, 1.5-20 y) and 30 parents (median age of 37.2 y; range, 24-60 y) were also included in our analyses.
At time of SOT, vaccination status was complete in 14 recipients (47%); these recipients were up to date for their age for DTaP, HBV, poliomyelitis, HiB, Streptococcus pneumoniae, and MMR vaccinations (Figure 1). Another nine recipients (30%) had only partially completed their schedules, missing the second dose of MMR vaccination. Seven SOT recipients (23%) had an incomplete vaccination status, mainly missing Streptococcus pneumoniae vaccinations (Figure 1).
In detail, all 30 SOT recipients (100%) had been vaccinated against diphtheria/tetanus (mean number of doses = 3.8), poliomyelitis (mean number of doses = 3.2), pertussis (mean number of doses = 3.3), HiB (mean number of doses = 3.1), and HBV (mean number of doses = 2.8).
Eighteen recipients (60%) had been vaccinated against MMR (mean number of doses = 1.6). Twenty-two recipients (73%) had been vaccinated against Streptococcus pneumoniae (mean number of doses = 1.7). Ten recipients (33%) had also been vaccinated against Neisseria meningitidis, 7 (23%) against seasonal influenza, and 6 (20%) against varicella-zoster virus.
The main differences among SOT recipient groups were in regard to live-virus vaccination rates. Whereas 3/3 heart SOT recipients (100%) and 10/14 kidney SOT recipients (71%) had been vaccinated against MMR, only 5/13 liver SOT recipients (38%) had received this vaccination (Figure 2).
Vaccination status was complete in 13 siblings (50%), partially complete in 2 siblings (8%), who were missing the second dose of MMR vaccine, and incomplete in 11 siblings (42%), who did not receive any Streptococcus pneumoniae vaccination. All 26 siblings (100%) had been vaccinated against diphtheria (mean number of doses = 4.3), tetanus (mean number of doses = 4.5), pertussis (mean number of doses = 3.8), and poliomyelitis (mean number of doses = 3.7).
In the sibling group, 22 (85%) had been vaccinated against HiB (mean number of doses = 3.5) and 23 (88%) against HBV (mean number of doses = 3.1). Twenty-four children among siblings (92%) had been vac-cinated against MMR (mean number of doses = 1.7). Fifteen siblings (58%) had undergone Streptococcus pneumoniae vaccination (mean number of doses = 2.1). Two each (8%) had additionally been vaccinated against Neisseria meningitidis and varicella-zoster virus, and 4 siblings (15%) had been vaccinated against seasonal influenza.
When we compared vaccination rates of SOT recipients and their siblings, no major differences were found in vaccinations against diphtheria, tetanus, pertussis, HBV, poliomyelitis, and HiB. However, SOT recipients had higher rates of vaccinations against Streptococcus pneumoniae, Neisseria meningitides, varicella-zoster virus, and seasonal influenza. On the other hand, siblings of SOT recipients had higher rates of MMR vaccinations (Figure 3).
Among 30 parent participants, 10 (33%) could not find their vaccination records and were unaware of their vaccination status. Most stated that they had received the “usual” vaccinations as a child, but could give no further details. Vaccinations against diphtheria (mean number of doses = 2.8), tetanus (mean number of doses = 3.8), and poliomyelitis (mean number of doses = 4) were documented in 16 parents’ charts (53%). There was documentation of vaccinations against pertussis (mean number of doses = 2.8) in 8 parents (26%) and vaccinations against HBV (mean number of doses = 3) in 3 parents (10%).
Records of 5 parents (17%) revealed vaccinations against measles and mumps (mean number of doses = 1.4). Vaccinations were documented in 7 parents (23%) against rubella (mean number of doses = 1.2) and in another 7 parents (23%) against seasonal influenza. None of the evaluated records showed vaccinations against Streptococcus pneumoniae, Neisseria meningitidis, HiB, or varicella-zoster virus (Figure 4).
Solid-organ transplant candidates and recipients are at high risk for infections from vaccine-preventable diseases.1-4 Recent outbreaks of measles show that this disease still poses a threat to immunocom-promised individuals.9 This and other vaccine-preventable diseases, if acquired after transplant, carry increased risks of hospitalization, complications, graft rejection, and mortality.10,11 During the 2009 to 2010 pandemic, influenza A H1N1 infection caused substantial morbidity and mortality among SOT recipients. A multicenter study from the United States12 revealed that 57% to 70% of infected SOT recipients required hospitalization, 16% required admission to an intensive care unit, and mortality occurred in 4%. A recent study found that SOT recipients are at increased risk of invasive pneumococcal disease, as the incidence rate was found to be higher than in the general population.13 Therefore, the vaccination status of potential SOT candidates should be evaluated at the initial visit and a plan should be made to complete primary vaccinations as soon as possible as the immune response to vaccines may be reduced in end-stage liver or renal disease.4
Transplantation continues to contraindicate live-virus vaccination, despite several reports of safe administration of live-virus vaccines after transplant.14-16 For this reason, every effort should be made to administer pretransplant vaccinations as early as possible, according to current recommendations,1-4 which include accelerated schedules for SOT candidates. The live-virus vaccines against MMR and varicella-zoster virus can be administered as early as 6 months old in children who may require transplant, with a minimum interval of 4 weeks between the 2 doses and at least 1 month before transplant.3,4 Moreover, it has been shown that pretransplant immunization results in higher antibody titers compared with posttransplant vaccinations.17
Overall, we found appropriate vaccination status in our SOT recipients, most of whom had received the recommended doses for their age of DTaP, poliomyelitis, HiB, HBV, Streptococcus pneumoniae, and MMR vaccine. Vaccination rates for Neisseria meningitidis, seasonal influenza, and varicella-zoster virus have room for improvement. The main differences among SOT recipient groups can be explained by younger ages and often shorter time from organ failure to transplant in liver SOT recipients; this sometimes precluded completion of primary immunizations before SOT, especially for live-virus vaccinations.
Household transmission of vaccine-preventable diseases constitutes an important source of infection in all children, including SOT recipients. Wendelboe and associates showed that parents accounted for 55% and siblings for 16% of identified sources of Bordetella pertussis infections in young infants,18 and de Greef and associates reported similar findings, with the most likely source of infection in the infant being a sibling (41%), the mother (38%), or the father (17%).19 Thus, the vaccination status of not only the SOT candidate but also of all household contacts should be reviewed and updated before SOT. One must remember that the vaccination of household contacts with live-virus vaccines against MMR and varicella-zoster virus is not contraindicated even after SOT, as transmission of vaccine-strain virus to the immunocompromised patient has not been documented.1-4 In fact, vaccination of household members against MMR and varicella-zoster virus is preferable because herd immunity within the family protects the SOT recipient against wild-type viruses. However, oral poliomyelitis vaccine should not be used, as prolonged shedding may permit transmission.14,15 In siblings of our patients, we found good vaccination rates for the primary vaccinations against DTaP, poliomyelitis, HiB, HBV, and MMR but poorer rates for Streptococcus pneumoniae, seasonal influenza, Neisseria meningitis, and varicella-zoster virus. It might be of interest to report that, during this study period, one of our young liver SOT recipients (18 months) acquired a varicella-zoster virus infection from his twin and required hospitalization and intravenous acyclovir therapy. Both children had not been vaccinated against varicella-zoster virus.
Immunization status of parents was alarming. One-third of the participating parents could not find their vaccination records (ie, they had no documented vaccinations). Records for the other two-thirds were incomplete. Most parents claimed they had received most of the “usual” vaccinations, and some degree of immunity can be assumed. However, a high degree of uncertainty remains. Most parents seemed unaware of the risk of infection that they can pose to their immunocompromised child.
This study has several limitations, including the retrospective nature of the study and the low number of patients, limiting the informative value. The goal of the study was only to describe the number of vaccinations that the patients received. However, this does not necessarily reflect good protection against a given antigen as we did not measure seroprotective titers.
One study that evaluated serologic response to vaccines in SOT candidates that had received all recommended doses for their age found protective antibodies in 65% to 84% and another study found that only 26% of SOT candidates had protective antibodies against all tested pathogens.20,21 Even if protective antibodies are demonstrated, antibody avidity to the specific antigen may be diminished in SOT recipients.22 Together, serologic testing should document seroefficacy after vaccination in SOT candidates and recipients. However, this was beyond the scope of our study.
In summary, the consistent use of vaccines in SOT candidates and their household members according to existing guidelines is key to minimizing vaccine-preventable diseases and associated complications in SOT recipients. The vaccination records of both SOT recipients and household members should be constantly reviewed, and vaccination status should be complete before transplant. Our study highlights the need for additional strategies to protect immuno-compromised children. Offering vaccinations to parents and other family contacts in the pediatric outpatient setting could be an option to increase vaccination coverage and diminish infections in this high-risk population.23
DOI : 10.6002/ect.2018.0184
From the 1Department of Pediatrics, Medical University of Innsbruck, Innsbruck,
Austria; and the 2Department of Pediatrics, Klinikum Ostallgäu Kaufbeuren,
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Gerard Cortina, Department of Pediatrics, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
Phone: +43 512 504 23600
Figure 1. Immunization Rates in Solid-Organ Transplant Recipients at Time of Transplant
Figure 2. Comparison of Immunization Rates Among Kidney, Liver, and Heart Transplant Recipients at Time of Transplant
Figure 3. Comparison of Immunization Rates in Solid-Organ Transplant Recipients Versus Siblings at Time of Transplant
Figure 4. Immunization Rates in Parents of Solid-Organ Transplant Recipients at Time of Transplant
Table 1. Routine Immunization Schedule in Austria for 2014