Our results show the heterogeneity in the practicing clinicians for the administration of live vaccines in patients with cellular immune deficiency disorders. This is likely a reflection of insufficient data available and most recommendations are based on expert opinions. In recent years, there has been evidence of waning herd immunity due to decreased rates of immunization by the general population . Children with a history of combined immunodeficiency are especially susceptible to these vaccine preventable disease, likely contributed in part by the inherent shortcomings of their immune system, but also due to the fact that there may hesitancy in administering live vaccines in many of these patients, especially the ones with severe T -cell immunodeficiencies . Guidelines regarding the administration of live vaccines in patients with more mild immunodeficiency, however, are ill-defined leaving clinicians with the difficult choice of deciding which immune deficient patients are able or not able to receive them.
Given that there is insufficient data regarding the administration of live vaccines in specific combined immunodeficiencies, clinicians draw information from several resources when deciding to give live vaccines to patients with milder defects. One source is to extrapolate data from studies in mild HIV and partial DiGeorge syndrome cohorts [4-6]. Al-Sukaiti and Grunebaum reported no moderate or severe reactions in a cohort of 80 DiGeorge patients after administration of MMR in patients with a CD4 count of >500 T cells / mm3. Mild reactions occurred in only 6 patients . There have also been some reports of safely administering varicella vaccine in children with a CD4 T cell count > 200cells/mm3 in addition to giving MMR in HIV patients with >15% CD4 T cells and a CD4 count of >200cells/mm3 [10-14]. Furthermore, common guidelines that clinicians might reference include those from the IDSA and ACIP. Unfortunately, these guidelines differ slightly when it comes to recommendations for patients with milder combined disease , creating additional uncertainties for the practicing clinician.
The IDSA guidelines support the administration of MMR and varicella vaccine but not combined MMRV in patients with partial DiGeorge syndrome who demonstrate ≥500 CD3+ T lymphocytes/mm3, ≥200 CD8+ T lymphocytes/mm3, and normal mitogen response. Patients with SCID, DiGeorge syndrome, and other combined immunodeficiencies with T-cell lymphocyte count <500cells/mm3 are recommended to avoid all live vaccines. However, in other non-DiGeorge syndrome T-cell defects, the IDSA indicates that extrapolation of data from HIV-infected persons suggests that a CD4 count ≥ 200cells/mm3 in adults or percentage ≥ 15 may be reasonable but has uncertain validity . In contrast, the Advisory Committee on Immunization Practices (ACIP) does not recommend administering live vaccines in patients with partial combined immunodeficiencies . Additionally, severe cell-mediated immunodeficiency are considered a contraindication for receipt of live vaccines, however the definition of severe cell-mediated immunodeficiency is lacking . Furthermore, the IDSA recommends against combined MMRV administration and administering MMR and varicella as separate vaccines given that MMRV has a higher antigenic load and as such, is more likely to be associated with adverse effects such as fever and febrile seizure .
In our study, most clinicians reported comfort with live vaccine administration to mild immunodeficient patients. The majority (80%) of respondents did administer live vaccines to patients with humoral defects but this decreased to 61% in those with cell mediated defects and 55% to those with combined defects. These findings are not unexpected given that most live and inactivated vaccines can be tolerated in patients with non-severe humoral immunodeficiencies while the benefit/safety of administration of these vaccines in patients with T-cell deficits is more questionable . Clinicians also reported that the most frequently used parameters when making the decision to administer live vaccines include the CD4 count and functional T-cell studies, which was used amongst 88% and 86% of clinicians respectively. In contrast, the CD8 count was used amongst only 54% of clinicians – a surprising finding given that the CD8 count is indicated as an important parameter for the administration of live vaccines in patients with partial T cell defects and partial DiGeorge syndrome in the Red Book and IDSA guidelines respectively [7,18].
Our aim through this survey was to create a threshold parameter, that the practicing clinician may use as a guideline when they encounter the clinical conundrum of whether or not to administer live vaccines in cellular immune defects. Our results indicate that most clinicians who do administer live vaccines to patients with cellular immune deficiencies would confidently consider administration at a CD4 count of ≥ 400 cells/mm3 (MMR 48/60 [80%], Varicella 42/53 [79%], Rotavirus 40/45 [88.89%]), a CD8 count of ≥ 250 cells/mm3 (MMR 30/39 [76.92%], 29/37 [78.34%], Rotavirus 27/34 [79.41%]), and normal mitogen function( MMR 44/53 [83.02%], Varicella 40/48 [83.33%], 37/40 [92.5%]) (Table 4). Based on these responses, clinicians who are considering the administration of live vaccines to patients with cellular immune deficiency may wish to consider these threshold parameters.
Although the administration of live vaccines in patients with partial DiGeorge syndrome and low-level immunosuppression HIV has been well tolerated , complications of live viral vaccines have also been reported including chronic rotavirus infection , disseminated measles , and varicella [21,22] in T-cell deficient patients. One last observation from our findings includes nine respondents reporting having a patient who experienced a vaccine related adverse event. Seven of these reactions were identified as being consistent with infections resulting from the vaccine virus. Five of these were from varicella, two of which required hospitalization. One patient was described having granulomatous skin lesions which were positive for vaccine strain rubella. The rest were described as rashes (ie. rubella rash, varicella rash). Lymphocyte counts and function studies in patients who had a reaction were not reported individually.
This study does have several limitations. Although there are a number of other live vaccines, our focus was on MMR, varicella, and rotavirus given that these are the first vaccinations to be administered in childhood and are more frequently given in the general population. With that said, our study is naturally focused more toward pediatric patients. We cannot exclude that those caring primarily for adults may practice differently and have different threshold parameters. Additionally, our study cannot comment on the safety of these threshold parameters. While there were 9 respondents who reported a previous vaccine related reaction, the goal of our study was not to evaluate the safety of administering vaccines but rather to identify a threshold for administering them based on the experiences of clinician experts in immunodeficiency. Lastly, the majority of our respondents practice primarily in the United States, limiting the generalizability of our findings.