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The coronavirus disease 2019 (COVID-19) pandemic has created many challenges for pediatric solid organ transplant (SOT) recipients and their families. As the pandemic persists, patients and their families struggle to identify the best and safest practices for resuming activities as areas reopen. Notably, decisions about returning to school remain difficult. We assembled a team of pediatric infectious diseases (ID), transplant ID, public health, transplant psychology, and infection prevention and control specialists to address the primary concerns about school reentry for pediatric SOT recipients in the United States. Based on available literature and guidance from national organizations, we generated consensus statements pertaining to school reentry specific to pediatric SOT recipients. Although data are limited and the COVID-19 pandemic is highly dynamic, our goal was to create a framework from which providers and caregivers can identify the most important considerations for each pediatric SOT recipient to promote a safe return to school.

Background: Better access to direct‐acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. Aim: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. Methods: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. Results: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV‐) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV‐ livers as well as non‐liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41–1117) days post‐transplant in the setting of missing, inadequate, or truncated prophylaxis. Conclusion: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non‐transplant population, possibly due to the common use of HBV prophylaxis in the at‐risk transplant population. [ABSTRACT FROM AUTHOR]

BackgroundInvasive mold infections (IMIs) are a leading cause of mortality in immunocompromised children, yet there has never been an international epidemiologic investigation of pediatric IMIs.MethodsThis international, prospective cohort study was performed to characterize the epidemiology, antifungal therapy, and outcomes of pediatric IMIs. Children (≤18 years) with proven or probable IMIs were enrolled between August 2007 and May 2011 at 22 sites. Risk factors, underlying diagnoses, and treatments were recorded. Outcomes were assessed at 12 weeks after diagnosis using European Organization for Research and Treatment of Cancer/Mycoses Study Group response criteria.ResultsOne hundred thirty-one pediatric patients with IMIs were enrolled; the most common IMI was invasive aspergillosis ([IA] 75%). Children with IA and those with other types of IMIs had similar underlying risk factors, except that children with IMIs caused by non-Aspergillus species were more likely to have received mold-active antifungal agents preceding diagnosis. The most commonly used antifungal classes after diagnosis were triazoles (82%) and polyenes (63%). Combination therapy was used in 53% of patients. Use of combination therapy was associated with an increased risk of adverse events (risk ratio, 1.98; 95% confidence interval, 1.06-3.68; P = .031), although there was no detectable difference in outcome.ConclusionsAlthough risk factors for IMIs are similar across specific subtypes, preceding antifungal therapy may be an important modifier. Combination antifungal therapy requires further study to determine its true risks and benefits.

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. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) remains a common cause of mortality in pediatric immunocompromised populations. Much of our knowledge of IA stems from adult literature. We conducted a retrospective evaluation of cases of proven or probable IA, defined according to the 2019 EORTC/MSG criteria, in patients with underlying immunocompromising conditions at Boston Children's Hospital from January 1, 2007 to January 1, 2019. We estimated survival curves over 12 weeks using the Kaplan-Meier method for all-cause mortality, and we used univariate Cox proportional hazards modeling to evaluate for mortality risk factors. We identified 59 cases, 29% with proven and 71% with probable IA. Pulmonary IA was the most common presentation (78%). The median age at diagnosis was 11 years (range, 0.5–28). Hematopoietic cell transplantation (HCT) was the most frequent predisposing underlying condition (41%). Among affected patients, 44.8% were neutropenic and 59.3% were lymphopenic at diagnosis. The 12-week all-cause mortality rate was 25.4%; HCT recipients comprised the majority of deaths (9/15) with a hazard ratio of 2.47 [95% CI, 0.87–6.95]. No patients with congenital immunodeficiencies (n = 8) died within 12 weeks of IA diagnosis. Other risk factors that were significantly associated with mortality included mechanical ventilation at diagnosis, intensive care unit stay, and lymphopenia; treatment with an Aspergillus -active azole was associated with decreased mortality. In conclusion, our study found that in pediatric immunocompromised hosts, IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the HCT population. Lay abstract This study explores the epidemiology, outcomes and predictors of mortality of invasive aspergillosis (IA) at a high-volume pediatric center for immunocompromised hosts. Much of our understanding of pediatric IA is extrapolated from the adult literature. Our study found that IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the hematopoietic cell transplantation study cohort. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic continues to generate challenges for pediatric solid organ transplant (SOT) recipients and their families. As rates of COVID-19 fluctuate, new SARS-CoV-2 variants emerge, and adherence to and implementation of mitigation strategies vary from community to community, questions remain about the best and safest practices to prevent COVID-19 in vulnerable patients. Notably, decisions about returning to school remain difficult. We assembled a team of specialists in pediatric infectious diseases, transplant infectious diseases, public health, transplant psychology, and infection prevention and control to re-address concerns about school re-entry, as well as COVID-19 vaccines, for pediatric SOT recipients in the United States in 2021. Based on available literature and guidance from national organizations, we generated expert statements specific to pediatric SOT recipients focused on school attendance in 2021. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction (MD) is linked to cardiometabolic complications, such as obesity and insulin resistance (IR), the frequencies of which are higher in adults living with HIV infection and receiving combination antiretroviral therapies (ARV). ARV-treated youth living with perinatally acquired HIV infection (YLPHIV) may be especially susceptible to IR due to long-term exposure to both factors. Medical histories, fasting blood chemistry panels, and mitochondrial function in banked peripheral blood mononuclear cells (PBMCs) were assessed in eligible YLPHIV from the Pediatric HIV/AIDS Cohort Study (PHACS)/Adolescent Master Protocol (AMP) Mitochondrial Determinants Component cohort, stratified by Homeostatic Model Assessment of IR (HOMA-IR) score: case (score ≥4, n = 39) or control (score <4, n = 105). PBMCs were sources for mitochondrial (mt) DNA copies/cell; mtRNA transcript levels of oxidative phosphorylation (OXPHOS) subunits NADH dehydrogenases 1 and 6, and cytochrome B; and enzymatic activities of OXPHOS Complexes I (CI) and IV (CIV). Logistic regression models were fit to estimate the odds of IR case diagnosis, adjusted for sex, race/ethnicity, body mass index (BMI) z-score, and Tanner stage. IR cases were similar to controls by age, sex, and race/ethnicity. Cases had higher median levels of peak HIV viral load, lactate, pyruvate, triglycerides, and BMI z-scores. OXPHOS CI enzymatic activity was lower in cases (log10 1.62 vs. 1.70) and inversely correlated with HOMA-IR score (r = −0.157, p = .061), but did not associate with IR in adjusted models. Fully adjusted models indicated associations of nadir CD4% [odds ratio (OR) = 0.95, 95% confidence intervals (CIs) = 0.90–1.00] or peak HIV load (OR = 3.48, 95% CIs = 1.70–10.79) with IR. IR in YLPHIV was strongly associated with morphometrics, but early virologic and immunologic factors may also influence MD. [ABSTRACT FROM AUTHOR]

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Human T‐cell lymphotrophic virus 1 (HTLV)‐1 in the pre‐ and post‐transplant period. HTLV‐1 is an oncogenic human retrovirus rare in North America but endemic in the Caribbean and parts of Africa, South America, Asia, and Oceania. While most infected persons do not develop disease, <5% will develop adult T‐cell leukemia/lymphoma or neurological disease. No proven antiviral treatment for established HTLV‐1 infection is available. The effect of immunosuppression on the development of HTLV‐1‐associated disease in asymptomatically infected recipients is not well characterized, and HTLV‐1‐infected individuals should be counseled that immunosuppression may increase the risk of developing HTLV‐1‐associated disease and they should be monitored post‐transplant for HTLV‐1‐associated disease. Currently approved screening assays do not distinguish between HTLV‐1 and HTLV‐2, and routine screening of deceased donors without risk factors in low seroprevalence areas is likely to result in significant organ wastage and is not recommended. Targeted screening of donors with risk factors for HTLV‐1 infection and of living donors (as time is available to perform confirmatory tests) is reasonable. [ABSTRACT FROM AUTHOR]