A quick algorithmic review on management of viral infectious diseases in pediatric solid organ transplant recipients

Abstract

Pediatric solid organ transplant is a life-saving procedure for children with end-stage organ failure. Viral infections are a common complication following pediatric solid organ transplantation (SOT), which can lead to increased morbidity and mortality. Pediatric solid organ transplant recipients are at an increased risk of viral infections due to their immunosuppressed state. The most commonly encountered viruses include cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), adenoviruses, and BK polyomavirus. Prevention strategies include vaccination prior to transplantation, post-transplant prophylaxis with antiviral agents, and preemptive therapy. Treatment options vary depending on the virus and may include antiviral therapy and sometimes immunosuppression modification. This review provides a Quick Algorithmic overview of prevention and treatment strategies for viral infectious diseases in pediatric solid organ transplant recipient.

Keywords: antiviral; pediatrics; solid organ; transplantation; viral infections.

Figure 1

Prevention of CMV infection after pediatric SOT. CMV, cytomegalovirus; D, donor; IV, intravenous; PCR, polymerase chain reaction; R, recipient; rATG, rabbit antithymocyte globulin; SOT, solid organ transplantation. ¹5 mg/kg/dose once daily in normal kidney function. ²Dose (mg): 7 × BSA × CrCl once daily.

Figure 2

Treatment of CMV infection or disease after pediatric SOT. CBC, complete blood count; CMV, cytomegalovirus; IgG, immunoglobulin G; IV, intravenous; IVIG, intravenous immunoglobulin; PCR, polymerase chain reaction; SOT, solid organ transplantation; Sr Cr, serum creatinine. ¹Dose (mg): 7 × BSA × CrCl twice daily. ²5 mg/kg/dose twice daily in normal kidney function. ³60 mg/kg/dose every 8 h OR 90 mg/kg/dose twice daily in normal kidney function. ⁴10 mg/kg/dose twice daily in normal kidney function.

Figure 3

Prevention of EBV infection after pediatric SOT and preemptive intervention. CNI, calcineurin inhibitor; D, donor; DNA, deoxyribonucleic acid; EBV, Epstein–Barr virus; mTORi, mammalian target of rapamycin inhibitors; PCR, polymerase chain reaction; R, recipient.

Figure 4

Prevention and treatment of HSV infection after pediatric SOT. CMV, cytomegalovirus; CNS, central nervous system; HSV, herpes simplex virus; intravenous; IgG, immunoglobulin G; rATG, rabbit antithymocyte globulin. ¹Acyclovir: 200 mg/dose, 3–5 times/day in normal kidney function. ²Valacyclovir: <40 kg: 250 mg every 12 h, ≥40 kg: 500 mg every 12–24 h in normal kidney function. ³20 mg/kg/dose every 6 h in normal kidney function. ⁴10–15 mg/kg/dose every 8 h in normal kidney function.

Figure 5

Prevention and treatment of VZV infection after pediatric SOT. CMV, cytomegalovirus; HSV, herpes simplex virus; intravenous; IV, intravenous; IVIG, intravenous immunoglobulin; VZIG, varicella zoster immune globulin; VZV, varicella zoster virus. ¹Acyclovir: 200 mg/dose, 3–5 times/day in normal kidney function. ²Valacyclovir: <40 kg: 250 mg every 12 h, ≥40 kg: 500 mg every 12–24 h in normal kidney function. ³Acyclovir: 20 mg/kg/dose every 6 h and valacyclovir: 20 mg/kg/dose every 8 h in normal kidney function. ⁴10 mg/kg/dose every 8 h in normal kidney function.

Figure 6

Prevention and treatment of influenza infection after pediatric SOT. yo, years old. ¹Children who are 36 months of age or older should receive a 0.5-ml dose of IIV, while children aged between 6 and 35 months may receive either a 0.25-ml or 0.5-ml dose based on the manufacturer's recommendations.

Figure 7

Approach to management of HBV in liver transplant candidates or recipients according to recipient HBV serology. Ab, antibody; Ag, antigen; DNA, deoxyribonucleic acid; HBe, hepatitis B e; HBc, hepatitis B core; HBs, hepatitis B surface; HBV, hepatitis B virus; HDV, hepatitis D virus; HBIG, hepatitis B immune globulin; HCV, hepatitis C virus; HIV, human immunodeficiency virus; LT, liver transplantation; RNA, ribonucleic acid. ¹This recommendation is based on ESPGHAN guideline, while the AST guideline does not recommend for the using of antiviral prophylaxis in this context unless for patients with intense immunosuppression such as patients who received lymphocyte depleting agents.

Figure 8

Approach to management of HBV in liver transplant candidates or recipients according to doner HBV serology. Ag, antigen; DNA, deoxyribonucleic acid; HBc, hepatitis B core; HBs, hepatitis B surface; HBV, hepatitis B virus; HDV, hepatitis D virus; HBIG, hepatitis B immune globulin.

Figure 9

Approach to management of HBV in non-liver SOT transplant candidates or recipients according to recipient and doner HBV serology. Ab, antibody; Ag, antigen; DNA, deoxyribonucleic acid; HBe, hepatitis B e; HBc, hepatitis B core; HBs, hepatitis B surface; HBV, hepatitis B virus; HDV, hepatitis D virus; HBIG, hepatitis B immune globulin. *Vaccination should be considered for HBV-uninfected, non-immune SOT candidates or recipients. ¹This recommendation is based on ESPGHAN guideline, while the AST guideline recommends antiviral prophylaxis is not necessary for in HBV immune recipients and it should be considered only in non-immune (anti-HBs -) recipients up to 1-year after transplantation.

Figure 10

Approach to management of COVI-19 infection in pediatric SOT recipients. ECMO, extracorporeal membrane oxygenation; JAK, Janus kinase; IVIG, intravenous immunoglobulin; MIS-C, multisystem inflammatory syndrome in children; MV, mechanical ventilation; NIV, non-invasive ventilation; SOT, solid organ transplantation.

Figure 11

Approach to screening and treating BKPyV in pediatric kidney transplant recipients. PyVAN, polyomavirus-associated nephropathy; IVIG, intravenous immunoglobulin. ¹To confirm BKPyV viremia, it is essential to have either sustained viral load above 1,000 copies/ml in two consecutive measurements within a 3-week period or an increase to over 10,000 copies/ml in one of two measurements. ²If the serum creatinine level rises by 25% or more from its initial level during immunosuppression reduction, acute rejection should be evaluated. ³Two consecutive undetectable plasma viral load tests, performed at least one week apart.