MMR and the EMR: Hunting for National-level Vaccine Data in Transplant Recipients

The growing threat posed by vaccine-preventable infections such as measles, mumps, and rubella has been highlighted by the resurgence of measles in the United States in 2025, in conjunction with declining vaccination rates.1,2 Although these outbreaks portend broad societal risk, the alarming consequence for immunocompromised people is the weakening of the circle of protection around them. Vaccines remain key, but there are safety constraints; except for carefully selected pediatric solid organ transplant recipients (SOTRs),3 live measles-mumps-rubella (MMR) vaccine historically cannot be given posttransplant or within 30 d before transplant.4 Transplant recipients are at risk for severe disease if they become infected, and the duration of posttransplant immunity is uncertain. An understanding of pretransplant seroprevalence for measles, mumps, and rubella, and incidence and outcomes of these infections posttransplant, would be important for designing strategies to mitigate risk. We lack national-level data in these domains, which interferes with our ability to keep SOTRs safe from these vaccine-preventable illnesses. In this issue of Transplantation, Chiu et al present an analysis of the retrospective electronic medical record (EMR)-based TriNetX database, to evaluate on a national level the IgG seroprevalence to measles, mumps, and rubella in adult solid organ transplant (SOT) candidates who were tested pretransplant.5 The authors also sought to describe the incidence and outcomes of infections with these 3 pathogens post SOT, particularly in a subgroup who received MMR vaccination within 30 d before transplant (typically in the setting of negative IgG or undervaccinated status). The authors identified 313,548 SOTRs between 2009 and 2024, spanning many regions of the United States and demonstrating a key strength of this national federated database. In keeping with the general SOT population, 62% were kidney recipients, 39% were born before 1957, and median age was 60 y (interquartile range 41–63 y). Only about 8%, however, had record of an IgG serologic test result for ≥1 of measles, mumps, or rubella pre-SOT (~4%–5% for each pathogen), using a variety of identified tests. Thoracic recipients, particularly lung recipients, were more likely to have had 1 of these tests performed than other SOTRs, as were people born after 1957. For those who were tested, there were reasonable overall seroprevalence rates of 72%–80%, albeit lower versus measles, especially in younger persons (69% versus 84%). Chiu et al identified a total of 269 measles, mumps, and rubella infections using ICD codes (<0.1% of identified SOTRs, with an average of ~15–20 infections per year of study). The authors ascertained 20 cases of rubella in SOTRs in 2021, alone, which far outnumbered the typical confirmed number of sporadic cases in all-comer US adults (<10/y) and did not concord with a reported epidemic. Although highest peaks in the claims-based ascertainment of mumps and measles cases in SOTRs corresponded with known US outbreaks in 2016 and 2019, respectively, these case numbers also likely far overestimated true diagnoses in SOTRs. These discrepancies highlight a major concern with infection ascertainment when using TriNetX or other claims-based datasets. The authors appropriately provide some of many examples of potential miscoding pitfalls such as clinician use of diagnosis codes when an infection is being ruled out, rather than the stricter sense of when it has been ruled in. Additionally, the authors confirm that the vast majority of reported cases in this study did not have ascertainable supporting laboratory testing, although they comment that PCR tests were likely sent to external laboratories as a rationale for lack of availability in the primary database. However, the tight-knit transplant infectious disease community would likely have recorded and communicated upticks in any of these uncommon and morbid diseases in our patient population during the study period. Of additional interest, 114 persons in this database had a record of receiving MMR vaccine within 30 d before SOT, none of whom was identified as having developed clinical infection with measles, mumps, or rubella posttransplant (although vaccination data were not ascertained for most people). A few of these SOTRs also received therapies that could have plausibly been for postexposure prophylaxis. This provides intriguing potential insight regarding the safety of this debated practice, as demonstrating acceptable outcomes could avoid delaying transplants in candidates who inadvertently receive MMR vaccine in that time period. Yet, it remains difficult to confidently extrapolate this finding to the bedside given sparse clinical information owing to the nature of the database. Additional limitations of this study related to generalizability, given only 4%–5% of SOTRs had available IgG serology data per pathogen. TriNetX data are also mainly from large, academic health systems, which is less helpful for medical events farther out from the time of transplant when SOTRs may have returned to community providers for follow-up. As discussed earlier, there are issues with claims-based data regarding operating characteristics of ascertainment procedures: lack of a gold standard or method of independent verification, the fact that not all reporting will be in the EMR, and the possibility of “over-calling” infections based on diagnosis codes. Moreover, the database does not provide granular clinical information for people identified as having had MMR infections. Despite these limitations, the study is a helpful addition to the literature, first by demonstrating the use of national federated data to extract infectious disease-related elements for SOTRs that are not well represented in other datasets. Second, the study identifies vulnerabilities (eg, low seroprevalence in lung candidates) and hence, opportunities for developing systems of care to optimize pretransplant vaccinations. Third, these data do suggest a need to evaluate the safety of administering MMR vaccine closer to the time of transplant in adult SOT candidates, namely through prospective studies to complement studies in pediatric transplantation.3 With the likelihood of further outbreaks of vaccine-preventable diseases in the community, this study ultimately highlights the need for accurate data to devise optimal measures for protecting SOTRs from these infections in an increasingly complex environment. If clinical transplant infectious diseases care policies such as use of live viral vaccination are to be based on large EMR database outputs, it will be critical to include supporting confirmatory data for infection ascertainment and clinical outcomes.