Management and outcomes of histoplasmosis in youth with inflammatory bowel disease in an endemic area.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) prescribed immunosuppressive therapies including antitumor necrosis factor (aTNF) therapies are at increased risk of histoplasmosis. We aim to evaluate the presentation, management, and outcomes of youth with IBD and concurrent histoplasmosis. METHODS: Single center, retrospective review of youth with IBD diagnosed with histoplasmosis from January 12, 2007 to January 1, 2022. Management and outcomes were followed for up to 2 years after diagnosis. RESULTS: Nineteen patients (10 male, median age 16 years, range 8-22) with IBD were diagnosed with histoplasmosis: disseminated (N = 15/19; 79%), pulmonary (N = 3/19; 16%), lymph node (N = 1/19; 5%). At the time of histoplasmosis diagnosis, patients were predominantly receiving aTNF therapy (N = 17/19; 89%, median duration 21.9 months (interquartile range 8.5-52.0). Thirteen (13/19, 68%) patients required hospitalization and 2/19 (11%) required intensive care. All achieved antigen clearance with no recurrences. At the time of histoplasmosis diagnosis, aTNF was stopped in 15/17 (88%) patients and the following IBD therapies were initiated: 5-aminosalicylates (N = 4/19; 21%), 6-mercaptopurine (N = 3/19; 16%), enteral therapy (N = 2/19; 11%), and vedolizumab (N = 2/19; 11%); 6 of 19 (32%) received no IBD therapy and 2 of 19 (11%) patients continued aTNF. During follow-up, 6 of 19 (32%) patients had an emergency department (ED) visit and/or hospitalization for symptoms attributed to active IBD, all of whom had discontinued aTNF; one patient required colectomy. CONCLUSIONS: Severe histoplasmosis infection in youth with IBD was rare. IBD treatment was modified by reducing immunosuppression. Histoplasmosis outcomes were favorable, but multiple patients required hospitalization or ED visits for IBD symptoms. The optimal approach to managing IBD during histoplasmosis treatment is challenging and requires further study.

Defining the Landscape of Educational Experiences in Transplant Infectious Diseases: A National Survey of Infectious Diseases Fellows in the United States.

Background: Transplant infectious diseases (TID) is a growing area of expertise within infectious diseases (ID), but TID training is not standardized. Previous surveys of fellows identified opportunities to improve TID education resources but did not explore didactic, clinical, and nonclinical experiences comprehensively. Methods: The American Society of Transplantation ID Community of Practice surveyed adult and pediatric fellows in US-based general ID or dedicated TID training programs to explore their didactic exposure, clinical experiences, and non-direct patient care activities in TID. Results: A total of 234 fellows initiated the survey, and 195 (83%) (190 general ID and 19 TID fellows, including 125 adult, 76 pediatric, and 8 combined adult-pediatric fellows) completed the entire survey. More than half of the fellows described receiving no formal curricular content on most foundational topics in transplant medicine. Almost all respondents (>90%) had some inpatient TID experience, but for >60% of fellows this was <12 weeks annually. Clinical exposure varied by fellow and patient type-in an average month rotating on an inpatient TID service, more than half of adult fellows had evaluated ≥10 kidney, liver, or hematopoietic stem cell transplant recipients but <10 heart, lung, pancreas, or intestinal recipients; pediatric fellows saw <10 of all patient types. Nearly half (46%) of general ID fellows had not spent any time in the dedicated TID clinic at their program. Few fellows had participated in protocol development, organ selection meetings, or donor evaluations. Conclusions: This survey highlights important gaps in TID training. Given the increasing need for TID specialists, updated curricula and educational resources are needed.

Immunogenicity and Reactogenicity of High-dose or Standard-dose Influenza Vaccine in a Second Consecutive Influenza Season.

BACKGROUND: Pediatric hematopoietic cell transplant (HCT) recipients are at high-risk for morbidity from influenza virus infection. We demonstrated in a primary phase II randomized controlled trial that two post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given four weeks apart were more immunogenic than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen. METHODS: A subcohort of study participants re-enrolled and had hemagglutinin inhibition (HAI) titers measured at baseline and four weeks after each vaccine dose in year two. We estimated geometric mean fold rise (GMFR) in HAI titer from baseline for each group and used linear mixed effects models to estimate adjusted geometric mean ratios (aGMR, comparing HD-TIV to SD-QIV) for each antigen at each time point. We described systemic and injection-site reactions. RESULTS: A total of 65 subcohort patients participated (33 SD-QIV, 32 HD-TIV). Post-vaccine GMFR and aGMR estimates were higher for both groups following a single influenza vaccine dose in year two compared to two doses of the same formulation in year one. Both groups had similar frequencies of injection-site and systemic reactions. CONCLUSIONS: A single dose of HD-TIV or SD-QIV was more immunogenic in year two than two doses of the same formulation in year one. Reactogenicity was comparable between groups. One dose of influenza vaccine may be sufficient after a two-dose schedule in the prior year post-HCT.

Cytomegalovirus viral load at initiation of pre-emptive antiviral therapy impacts cytomegalovirus dynamics in pediatric allogeneic hematopoietic cell transplantation recipients.

BACKGROUND: Cytomegalovirus (CMV) contributes to morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. Pre-emptive antiviral therapy (PET) reduces the incidence of CMV end-organ disease (EOD), though relevant viral thresholds to initiate PET remain undefined. We evaluated the impact of viral loads (VLs) at PET initiation on virologic and clinical outcomes following pediatric allo-HCT. METHODS: Single-center retrospective cohort analysis of children who underwent their first allo-HCT from January 2014 to December 2020. Weekly quantitative plasma CMV polymerase chain reaction was performed until Day +100 and PET was initiated once VL exceeded a pre-defined threshold per institutional guidelines. Patients were followed for 1-year post-HCT to evaluate virologic and clinical outcomes including end-organ disease (EOD), overall survival (OS), and non-relapse mortality (NRM). RESULTS: Among 146 allo-HCT recipients, CMV DNAemia occurred in 40 patients (27%) at a median of 15 days post-HCT (interquartile range 6-28.5). Ten percent (n = 4) had spontaneous resolution of DNAemia, while 90% (n = 36) required PET. PET initiated when CMV VL was ≥ 1000 IU/mL (n = 21) vs when VL < 1000 IU/mL (n = 15) resulted in higher peak CMV VL (12,670 vs. 1284 IU/mL, p = 0.0001) and longer time to CMV DNAemia resolution (36 vs. 24 days, p = 0.035). There were no differences in EOD, OS, or NRM at 12 months post-HCT based on VL at PET initiation. CONCLUSIONS: Initiating PET when CMV VL was ≥1000 IU/mL resulted in significantly higher peak VL and prolonged DNAemia, with no differences in EOD, OS, or NRM at 12 months post pediatric HCT.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results: Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions: CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.

BACKGROUND: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. METHODS: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. RESULTS: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. CONCLUSIONS: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.

Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies.

The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary Aspergillus prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations. While the figure depicted within this article is static, an internet-based version could provide pop-up highlights of any given flow's origin and destination nodes. A future version could highlight links to publications that support the color-coded incidence rates or other actionable items, such as bundles of applicable pharmacologic or non-pharmacologic interventions. The figure, as part of the upcoming Infectious Diseases Society of America's aspergillosis clinical practice guidelines, can guide decision-making in clinical settings.

Diagnostic limitations and challenges in current clinical guidelines and potential application of metagenomic sequencing to manage pulmonary invasive fungal infections in patients with haematological malignancies.

BACKGROUND: Pulmonary invasive fungal infections (pIFI) disproportionately affect patients with haematological malignancies (HM). Establishing a rapid and accurate diagnosis of pIFI is challenging. Multiple guidelines recommend diagnostic testing of invasive fungal infections but lack consensus and may contribute to inconsistent diagnostic approaches. OBJECTIVE: To identify key diagnostic challenges and review metagenomic sequencing data. SOURCES: PubMed, professional consortium, and scientific society websites search to identify relevant, published, evidence-based clinical guidelines within the past 5 years. PubMed searchs for papers describing clinically relevant novel diagnostic technologies. CONTENT: Current guidelines for patients with HM and suspected pIFI recommend chest computed tomography imaging and specimen testing with microscopic examination (including calcofluor white stain, histopathology, cytopathology, etc.), Aspergillus galactomannan, ß-D-glucan, PCR, and culture, each with certain limitations. Emerging real-world data support the adjunctive use of metagenomic sequencing-based tests for the timely diagnosis of pIFI. IMPLICATIONS: High-quality evidence from robust clinical trials is needed to determine whether guidelines should be updated to include novel diagnostic technologies. Trials should ask whether the combination of powerful novel diagnostics, such as pathogen-agnostic metagenomic sequencing technologies in conjunction with conventional testing can optimize the diagnostic yield for all potential pIFI pathogens that impact the health of patients with HM.

Pre-Transplantation Strategies for Infectious Disease Mitigation and Prevention.

Pediatric Infectious Disease (ID) clinicians play a critical role in helping prevent and mitigate infectious risks in children peri- and post-transplantation. Prevention starts during the pre-transplant evaluation and persists throughout the solid organ transplant and hematopoietic cell transplant continuum. The pre-transplant evaluation is an opportunity to screen for latent infections, plan preventative strategies, optimize immunizations, and discuss risk mitigation practices. An ideal pre-transplant evaluation establishes a relationship with the family that further promotes post-transplant infectious risk reduction. This manuscript builds on shared pediatric ID prevention strategies, introduces updated ID testing recommendations for transplant donors/candidates, highlights emerging data, and identifies ongoing knowledge gaps that are potential areas of research.

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients.

ABSTRACT: Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination inhibition antibody titers (28-42 days, and ∼6 months after 2 doses). For cell subpopulations identified as predictive of a response to all 3 antigens, we conducted a sensitivity analysis including time after transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations; 7 significantly predicted responses to all 3 antigens 28 to 42 days after a 2-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of posttransplant vaccine administration. In conclusion, several B- and T-cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.

Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce.

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.

The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

Emerging Resistance Trends in Viridans Group Streptococci Bloodstream Infections Among Immunocompromised Children Receiving Levofloxacin Prophylaxis.

BACKGROUND: Levofloxacin prophylaxis (LVXp) is often used for patients with underlying leukemia and severe neutropenia to reduce the risk of fever and bacteremia. This study evaluated trends in viridans group streptococci (VGS) antibiotic susceptibilities over time and clinical outcomes of children with VGS bloodstream infections (BSIs) during institutional adoption of LVXp. METHODS: VGS blood culture isolates between 1/1/2010 and 12/31/2021 with susceptibility testing reported were included. Available isolates were re-identified to the species level and additional susceptibility testing was performed. Demographic and clinical data were abstracted from medical records. RESULTS: A total of 264 VGS BSI isolates were identified in immunocompromised (IC, n = 125) and non-immunocompromised subjects, (non-IC, n = 139). IC subjects had lower rates of VGS isolates susceptible (S) to LVX and higher minimum inhibitory concentration (MICs) to LVX (p = 0.004) and ciprofloxacin (p = 0.0005) compared with non-IC subjects. No other evaluated antibiotic had increased MICs in either group. Fifteen of 19 (74%) LVX not susceptible (NS) isolates occurred in IC subjects, 13 represented breakthrough infections. IC subjects had higher rates of VGS-related shock (p = 0.012), need for pressor support (p = 0.039), and longer duration of hospitalization than non-IC subjects (p < 0.001). Clinical outcomes were comparable between subjects with LVX S and NS VGS BSI isolates. CONCLUSIONS: VGS with reduced susceptibility to LVX emerged during institutional adoption of LVXp in high-risk children with immunocompromising conditions, but did not result in significant differences in clinical outcomes. Ongoing surveillance and susceptibility testing are critical in weighing the utility of LVXp against emerging antimicrobial resistance in this high-risk population.

Body surface area compared to body weight dosing of valganciclovir is associated with increased toxicity in pediatric solid organ transplantation recipients.

Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, P <.001), lymphopenia (51% vs 15.0%, P <.001), and acute kidney injury causing treatment modification (8.0% vs 1.8%, P <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.

Barriers to vaccination in immunocompromised children: A needs assessment in children with childhood-onset SLE and inflammatory bowel disease.

Background: Vaccination of immunocompromised children (ICC) remains suboptimal. Methods: Needs assessment surveys were administered to patients and caregivers during routine ambulatory visits to the rheumatology and gastroenterology clinics at Nationwide Children's Hospital (NCH) from January 1 through August 31, 2018, and to community primary care physicians (PCPs) at their monthly meeting and electronically. Results: Completed surveys were received for 57 patients (31 with childhood-onset systemic lupus erythematosus (c-SLE) and 26 with inflammatory bowel disease (IBD)) and 30 PCPs. Of the patient cohort, 93% (n = 53) felt their PCP was well informed about vaccines and 84% (n = 47) received vaccinations from either their PCP or local health department. Two patient surveys noted concerns of vaccine safety. Among the 30 responses completed by PCPs 50% (n = 15) preferred to provide all vaccines themselves, however, only 40% (n = 12) of PCPs felt "very confident" when providing vaccines to ICC. Further, 83% (n = 25) did not stock the 23-valent pneumococcal vaccine and only 27% (n = 8) routinely recommended vaccination of household contacts. Conclusions: Our study found a discordance between parent and PCP comfort in vaccinating ICC, highlighting an important barrier to vaccination in this patient population. In our cohort of patients, vaccine hesitancy was not a barrier to vaccination.

Spotting a potential threat: Measles among pediatric solid organ transplantation recipients.

BACKGROUND: Low-vaccination rates worldwide have led to the re-emergence of vaccine-preventable infections, including measles. Immunocompromised patients, including pediatric solid organ transplant (SOT) recipients, are at risk for measles because of suboptimal vaccination, reduced or waning vaccine immunity, lifelong immunosuppression, and global re-emergence of measles. OBJECTIVES: To review published cases of measles in pediatric SOT recipients to heighten awareness of its clinical manifestations, summarize diagnostic and treatment strategies, and identify opportunities to optimize prevention. METHODS: We conducted a literature review of published natural measles infections in SOT recipients ≤21 years of age, summarizing management and outcomes. We describe measles epidemiology, recommended diagnostics, treatment, and highlight prevention strategies. RESULTS: There are seven published reports of measles infection in 12 pediatric SOT recipients, the majority of whom were unvaccinated or incompletely vaccinated. Subjects had atypical or severe clinical presentations, including lack of rash and complications, most frequently with encephalitis and pneumonitis, resulting in 33% mortality. Updated recommendations on testing and vaccination are provided. Treatment options beyond supportive care and vitamin A are limited, with no approved antivirals. CONCLUSION: While measles is infrequently reported in pediatric SOT recipients, morbidity and mortality remain significant. A high index of suspicion is warranted in susceptible SOT recipients with clinically compatible illness or exposure. Providers must recognize this risk, educate families, and be aware of both classic and atypical presentations of measles to rapidly identify, isolate, and diagnose measles in pediatric SOT recipients. Continued efforts to optimize measles vaccination both pre- and post-SOT are warranted.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.