Nicholas Scanlon

Bio: Nicholas Scanlon is an academic researcher from Emory University. The author has contributed to research in topics: Medicine & Vaccination. The author has an hindex of 3, co-authored 4 publications receiving 32 citations. Previous affiliations of Nicholas Scanlon include University of Alabama at Birmingham.

Direct oral amoxicillin challenge without preliminary skin testing in adult patients with allergy and at low risk with reported penicillin allergy.

Abstract: Introduction: Ten percent of hospitalized patients report penicillin allergy; however, recent studies indicate that ∼98% of these patients are not acutely hypersensitive. Unconfirmed penicillin allergy poses public health risks, and an evaluation of penicillin allergy labels is recommended to improve antibiotic stewardship. Although the most widely accepted protocol is penicillin skin testing, followed by oral amoxicillin challenge, time constraints and resources may preclude this. Recent literature supports the safety and efficacy of direct oral amoxicillin challenge in individuals at low risk. Methods: We retrospectively evaluated direct oral challenge acceptance and outcomes in eligible adult outpatients with allergy and with a penicillin allergy label over a 6-month period. Direct oral amoxicillin challenge was recommended in patients with a history of benign rash, benign somatic symptoms, or unknown history associated with the last penicillin exposure >12 months ago. Those with severe reactions or reactions within 12 months of evaluation were not challenged. The patients were monitored for 60 minutes after challenge and were discharged with instructions to call in the event of a delayed reaction. Results: There were 50 of 355 adults (14%) with a penicillin allergy label seen by a single allergist; of these patients, 38 (76%) met our criteria for a direct oral challenge. The index penicillin associated reactions were mostly remote, and 44 subjects (88%) reported reactions >10 years earlier. Four patients (8%) were de-labeled based on history alone. Twenty subjects (40%) consented to challenge in the clinic, and none developed immediate, or to our knowledge, delayed hypersensitivity reactions. Three of 20 patients (15%) developed self-limited subjective symptoms that were not deemed to constitute true immunoglobulin E mediated hypersensitivity. A total of 24 patients (48%) had the penicillin allergy label removed from their medical record. Conclusion: This study added to the accumulating body of evidence that supports the safety and efficacy of direct provocative challenge without preliminary skin testing to exclude penicillin allergy in individuals at low risk. Larger prospective studies are necessary to confirm these observations.

Immune Responses to SARS-CoV-2 in Solid Organ Transplant Recipients.

Abstract: Coronavirus disease 2019 (COVID-19) is caused by a complex interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics and host immune responses. Hosts with altered immunity, including solid organ transplant recipients, may be at increased risk of complications and death due to COVID-19. A synthesis of the available data on immune responses to SARS-CoV-2 infection is needed to inform therapeutic and preventative strategies in this special population. Few studies have directly compared immune responses to SARS-CoV-2 between transplant recipients and the general population. Like non-transplant patients, transplant recipients mount an exuberant inflammatory response following initial SARS-CoV2 infection, with IL-6 levels correlating with disease severity in some, but not all studies. Transplant recipients display anti-SARS-CoV-2 antibodies and activated B cells in a time frame and magnitude similar to non-transplant patients—limited data suggest these antibodies can be detected within 15 days of symptom onset and may be durable for several months. CD4+ and CD8+ T lymphopenia, a hallmark of COVID-19, is more profound in transplant recipients, but SARS-CoV-2–reactive T cells can be detected among patients with both mild and severe disease. The limited available data indicate that immune responses to SARS-CoV-2 are similar between transplant recipients and the general population, but no studies have been sufficiently comprehensive to understand nuances between organ types or level of immunosuppression to meaningfully inform individualized therapeutic decisions. The ongoing pandemic provides an opportunity to generate higher-quality data to support rational treatment and vaccination strategies in this population.

The Role of Systems Vaccinology in Understanding the Immune Defects to Vaccination in Solid Organ Transplant Recipients.

Abstract: Solid organ transplant recipients (SOTRs) are at increased risk for many infections, whether viral, bacterial, or fungal, due to immunosuppressive therapy to prevent organ rejection. The same immune defects that render transplanted patients susceptible to infection dampen their immune response to vaccination. Therefore, it is vital to identify immune defects to vaccination in transplant recipients and methods to obviate them. These methods can include alternative vaccine composition, dosage, adjuvants, route of administration, timing, and re-vaccination strategies. Systems biology is a relatively new field of study, which utilizes high throughput means to better understand biological systems and predict outcomes. Systems biology approaches have been used to help obtain a global picture of immune responses to infections and vaccination (i.e. systems vaccinology), but little work has been done to use systems biology to improve vaccine efficacy in immunocompromised patients, particularly SOTRs, thus far. Systems vaccinology approaches may hold key insights to vaccination in this vulnerable population.

Brief Report: Enhanced Allogeneic Cellular Responses to Mismatched HLA-B Antigens Results in More Efficient Killing of HIV Infected Cells.

Abstract: Epidemiologic studies have demonstrated that HIV-1 discordant couples who share HLA-B alleles were more likely to transmit HIV-1. These data lead us to hypothesize that individuals who match at both HLA-B alleles should have a reduced allogeneic response than those who are not matched. We observed diminished killing of CD4 target cells only when HLA-B alleles were matched. We propose that for cell-associated HIV-1 transmission, the ability of the recipient to eliminate infected cells from a donor partner may be enhanced when HLA-B alleles are different between partners. These findings suggest a novel mechanism for protection against HIV infection.

Rare case of homozygous ifnar1 deficiency in a samoan child with disseminated varicella after vaccination

Abstract:

Introduction

Autosomal recessive interferon alpha/beta receptor 1 (IFNAR1) deficiency increases susceptibility to live-attenuated vaccines and wild-type viruses. Currently 16 cases, half with Polynesian ancestry have been reported since the discovery in 2019. Most cases present with severe MMR or yellow fever vaccine-related disease. Some cases report severe SARS-CoV-2, herpes simplex, and enterovirus. Varicella vaccine-related disease has been hypothesized but not previously reported.

Case Description

A pediatric Samoan girl with congenital cardiac anomaly, otherwise healthy until receiving Varicella and MMR vaccines at 12 months. Two weeks later with presumed incomplete Kawasaki Disease with 10-day fever, red lips, and maculopapular rash, given IVIG and infliximab; also, positive SARS-CoV-2 PCR and IgG that admission. Developed diffuse vesicular rash 3 weeks after vaccination requiring re-admission for disseminated varicella. At 14 months, admitted again for acute respiratory failure with viral pericarditis, positive for rhinovirus/enterovirus on respiratory viral panel and varicella serum PCR. Samoan parents are first-degree cousins and her stillborn sister had significant homozygosity on genetic evaluation. Normal lymphocyte subsets, normal mitogen proliferation, absent antigen proliferation in vitro, and normal NK function. Intact humoral immunity. Primary immunodeficiency disease panel identified homozygous pathogenic variant in IFNAR1. Future live viral vaccines contraindicated. Managed with acyclovir with return to baseline.

Discussion

This case demonstrates a novel finding of homozygous IFNAR1 deficiency predisposing to disseminated varicella after vaccination. TNF inhibition may have also contributed. IFNAR1 deficiency should be considered in patients with severe varicella or other severe viral illnesses, especially after live-attenuated viral vaccines in those of Polynesian ancestry.

Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

Abstract: Background Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. Methods We retrospectively analyzed serological response of up to five doses of SARS-CoV-2 vaccine in KTR from December 27, 2020, until December 31, 2021. Particularly, the influence of different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. Results In total, 4.277 vaccinations against SARS-CoV-2 in 1.478 patients were analyzed. Serological response was 19.5% after 1.203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%. In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased serological response rate to 75% in comparison to no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations. Conclusion Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.

Penicillin Allergy Testing Is Cost-Saving: An Economic Evaluation Study

Abstract: Background Having a penicillin allergy label is associated with the use of less appropriate and more expensive antibiotics and increased healthcare utilization. Penicillin allergy testing results in delabeling most allergy claimants and may be cost-saving. This study aimed to project whether penicillin allergy testing in patients reporting a penicillin allergy is cost-saving. Methods In this economic evaluation study, we built decision models to project the economic impact of 2 strategies for a patient with a penicillin allergy label: (1) perform diagnostic testing (drug challenges, with or without skin tests); and (2) do not perform diagnostic testing. The health service perspective was adopted, considering costs with penicillin allergy tests, and with hospital bed-days/outpatient visits, antibiotic use, and diagnostic testing. Twenty-four base case decision models were built, accounting for differences in the diagnostic workup, setting (inpatient vs outpatient) and geographic region. Uncertainty was explored via probabilistic sensitivity analyses. Results Penicillin allergy testing was cost-saving in all decision models built. For models assessing the performance of both skin tests and drug challenges, allergy testing resulted in average savings (in United States [US] dollars) of $657 for inpatients (US: $1444; Europe: $489) and $2746 for outpatients (US: $256; Europe: $6045). 75% of simulations obtained through probabilistic sensitivity analysis identified testing as the less costly option. Conclusions Penicillin allergy testing was projected to be cost-saving across different scenarios. These results are devised to inform guidelines, supporting the adoption of policies promoting widespread testing of patients with a penicillin allergy label.

Safety and efficacy of de-labelling penicillin allergy in adults using direct oral challenge: a systematic review.

Abstract: Background Approximately 10% of people have an unverified penicillin allergy, with multiple personal and public health consequences. Objectives To assess the efficacy and safety of direct oral challenge, without prior skin testing, in this population. Methods MEDLINE, EMBASE, CINAHL, the Cochrane Library and Google Scholar were searched from inception to 28 June 2020 (updated November 2020) to find published and unpublished studies that reported direct oral challenge for the purpose of removal of penicillin allergy labels. Population weighted mean was used to calculate the proportion of patients who developed an immediate or delayed reaction to direct oral challenge across the studies. Results Thirteen studies were included in the review, with a sample size of 1202 (range 7-328). Studies included inpatient and outpatient cohorts assessed as low risk for true allergy. In pooled analysis of all 13 studies there were 41/1202 (3.41%) mild immediate or delayed reactions to direct oral challenge. The population-weighted mean incidence of immediate or delayed reaction to an oral challenge across studies was also 3.41% (95% CI: 2.38%-4.43%). There were no reports of serious adverse reactions, 96.5% of patients could be de-labelled and many were subsequently successfully treated with penicillin. Conclusions Direct oral challenge is safe and effective for de-labelling patients assessed as low risk for true allergy. Non-specialist clinicians competent in using an assessment algorithm can offer evaluation of penicillin allergy labels using direct oral challenge in appropriate patients. These measures will facilitate optimal infection treatment for patients, support antimicrobial stewardship, and minimize antimicrobial resistance.