Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long‐term outcomes of CMV DNAemia in pediatric SOTR. We performed a single‐center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue‐invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High‐risk (OR 6.86 [95% CI, 3.6–12.9]) and intermediate‐risk (4.36 [2.3–8.2]) CMV status and lung transplantation (4.63 [2.33–9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p < .01). DNAemia was not associated with an increase in graft failure, all‐cause mortality, or other organ‐specific poor outcomes. We report one of the lowest rates of CMV disease after SOTR, showing that universal prophylaxis is effective and should be continued. However, we observed CMV morbidity and mortality in a subset of patients, highlighting the need for research on optimal prevention strategies. This study was IRB approved.
Background EBV infections cause significant morbidity and mortality in pediatric SOTR and can be complicated by post-transplant lymphoproliferative disorder (PTLD). Contemporary data on CHL EBV DNAemia and the development of PTLD are limited. Methods A retrospective cohort study of patients ≤ 21 years of age who received heart, lung, liver, kidney, or multi-organ transplants at TCH between 2011–2018 was conducted. Primary outcome was CHL EBV DNAemia, defined as peripheral blood lymphocyte EBV values ≥ 500 copies/ug or whole blood EBV values ≥ 10,000 IU/mL for ≥ 6 months. Associations with CHL EBV DNAemia were measured using chi-squared or Fisher exact test and multivariate logistic regression. Time to CHL EBV DNAemia was assessed using Kaplan-Meier method. Results Among 687 SOTR (152 heart, 87 lung, 259 liver, 175 kidney, 14 multi-organ), 87 (13%) developed CHL EBV DNAemia; this included 15 (9%) heart, 9 (10%) lung, 59 (22%) liver, 2 (1%) kidney, and 2 (14%) multi-organ recipients. Receiving a heart [OR 2.1, 95% CI (2.1 – 62.4)], lung [7.7, 95% CI (1.5 – 39.3)], liver [OR 31.8, 95% CI (4.9 – 208.7)], or multi-organ [OR 18.3, 95% CI (2.0 – 170)] transplant and being 1–5 years of age [OR 4.0, 95% CI (1.6 – 9.8)] were associated with CHL EBV DNAemia. SOTR transplanted from 2015–2018 were less likely to develop CHL EBV DNAemia than those transplanted from 2011–2014 [OR 0.5, 95% CI (0.3 – 0.8)]. EBV risk status, CMV risk status, gender, and induction therapy were not associated with developing CHL EBV DNAemia. The median maximum peripheral blood lymphocyte and whole blood EBV values for those with CHL EBV DNAemia were 9475 (993 – 258151) copies/ug and 22093 (564 – 550000) IU/mL, respectively. Organ transplanted (p< 0.01), age (p< 0.01), and EBV risk status (p< 0.01) were associated with time to CHL EBV DNAemia (Figure 1). PTLD occurred in 28 (4%) of SOTR; 14 (50%) had preceding CHL EBV DNAemia (p< 0.01). Figure 1 Time to CHL EBV DNAemia. Conclusion This cohort of pediatric SOTR demonstrates a low prevalence of CHL EBV DNAemia and PTLD. Receiving a heart, lung, liver, or multi-organ transplant and being 1–5 years of age were associated with developing CHL EBV DNAemia. SOTR who developed CHL EBV DNAemia were more likely to develop PTLD, suggesting that further interventions targeting this group may be warranted. Disclosures Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support Elizabeth A. Moulton, MD, PhD, Pfizer: Co-investigator for SARS-CoV-2 pediatric vaccine trials.
Our patient is a 3-year-old African-American female renal transplant recipient, with history of a seizure disorder which is well controlled on levetiracetam, who was admitted to the hospital due to elevated aminotransferases discovered on routine labs. She had a history of end-stage renal disease secondary to congenital nephrotic syndrome and received a deceased donor renal transplant 213 days prior to presentation. She received induction immunosuppression with antithymocyte globulin and one dose of methylprednisolone and her maintenance immunosuppression included tacrolimus (goal trough 5-7 nanograms (ng)/milliliter (ml) and 180 mg (290 mg/m 2 / dose) of mycophenolate twice daily. The patient presented with a low grade elevated temperature of 38°C and mild rhinorrhea. The patient was up to date on her immunizations and her mother denied known sick contacts. The initial exam was unremarkable. Laboratory findings included elevated liver enzymes [aspartate transaminase (AST) 281 U/L, alanine aminotransferase (ALT) 239 U/L, and gamma-glutamyl transferase 34 U/L], an elevated creatine kinase (CK) of 11 151 U/L, and a normal white blood cell count of 5130/µl with a normal absolute neutrophil count of 2420/µl but an elevated absolute eosinophil count of 850/µl. Her kidney function was normal and her tacrolimus troughs were in goal range (5-7 ng/ml). The differential diagnosis included hepatitis versus myositis, and viral etiologies versus non-infectious etiologies including an adverse drug reaction were considered. A viral work-up
Perinatal human immunodeficiency virus transmission, while rare in the United States, should be considered in children with a history of recurrent infections, chronic respiratory symptoms and developmental delay. A delayed diagnosis of human immunodeficiency virus in children can lead to significant morbidity and mortality. We present a 6-year-old male who presented for evaluation and management of antibiotic refractory chronic cough and purulent nasal secretions, with a history of recurrent bacterial pneumonias and sinus infections, disseminated varicella zoster, and global developmental delay. He likely had perinatally acquired human immunodeficiency virus. At the time of his human immunodeficiency virus diagnosis, he met the criteria for acquired immunodeficiency syndrome and was ultimately diagnosed with lymphocytic interstitial pneumonia (LIP). Our case illustrates the importance of universal human immunodeficiency virus screening of pregnant women, consideration of human immunodeficiency virus, and the prompt initiation of treatment. We believe this case serves as an important reminder for all medical providers who care for pregnant women and children.
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