A recent review published in The Pediatric Infectious Disease Journal highlighted the diagnosis and management of transplant-associated viral infections in children, while underscoring the challenges encountered during treatment.
“Viral infections in pediatric transplant patients frequently complicate care and contribute to mortality,” Benjamin Hanisch, MD, at Children’s National Medical Center in Washington, D.C., and colleagues wrote. “These infections can present in a wide variety of manifestations and often need to be evaluated and treated much different than they would in a previously healthy child.”
According to the review, clinicians can determine the risk of cytomegalovirus (CMV) by using pre-transplantation CMV serology. A CMV seronegative recipient receiving a transplant from a CMV seropositive donor is at the highest risk for infection. In addition, a CMV seropositive recipient receiving a transplant from a CMV seronegative donor is at risk for overwhelming viremia.
Clinicians should initiate management of the disease upon detection of greater than 1,000 copies or a 0.5 log or greater increase on serial viral load, using PCR, while recipients of unrelated cord blood or haploidentical transplant should receive therapy earlier. Clinicians can manage CMV by using preemptive therapy based on detection of quantitative PCR, which is preferred, or based on detection of CMV antigens, pp65 antigenemia, in the blood.
In addition, clinicians can begin empiric antiviral prophylaxis for a predetermined period after transplant, or they can use a hybrid approach to manage the disease. Ganciclovir is the first-line treatment for CMV, with foscarnet and cidofovir reserved for resistant cases. In most cases of neutropenia, foscarnet should be used first. Treatment can be discontinued after two negative studies. For CMV pneumonitis, CMV hyperimmune globulin should be used.
Clinicians can identify post-transplant lymphoproliferative disorder (PTLD), caused by Epstein-Barr virus (EBV), by increasing levels of EBV PCR in the blood or by observing a mononucleosis-like syndrome or lymphoma symptoms.
For a definitive diagnosis, clinicians need to perform a tissue biopsy utilizing EBV-specific assays, such as EBV encoded RNA staining. As a first line therapy, clinicians should manage EBV by reducing immunotherapy. To treat PTLD, they can use anti-CD20 antibodies, such as rituximab (Rituxan; Genentech, Biogen Idec).
Varicella zoster virus
Clinicians can detect varicella zoster virus (VZV) with PCR for CSF, which is preferred, or with direct fluorescent antibody testing of skin or mucosal lesions. It is recommended that clinicians treat VZV with antiviral prophylaxis before and after transplant.
Clinicians should administer varicella-zoster immunoglobulin (VZIG) or standard immunoglobulin (IG) to seronegative immunocompromised patients within 10 days of exposure to varicella. In immunocompromised patients, clinicians should administer intravenous acyclovir, with foscarnet (Foscavir, Clinigen) and cidofovir (Vistide, Gilead Sciences) as options in case of resistant strains.
Herpes simplex virus
Clinicians can distinguish herpes simplex virus (HSV) by testing skin, usually vesicular, or mucosal lesions using PCR, which is preferred, or performing a direct fluorescent antibody testing of cells scraped from the base of a lesion. Cerebrospinal fluid specimens should be tested by PCR.
For seropositive patients, clinicians should use antiviral prophylaxis with oral or intravenous acyclovir. If antiviral resistance is confirmed, clinicians should use agents that do not utilize the viral thymidine kinase, such as foscarnet and cidofovir.
Clinicians can identify human herpes viruses 6A and 6B (HHV-6) in patients with limbic encephalitis, based on symptoms such as altered mental status, seizures, and temporal lobe changes on MRI. They can treat the infection with ganciclovir (Cytovene, Hoffmann-La Roche) as well as foscarnet.
Clinicians can detect adenoviruses in the blood or stool before symptoms develop, and should be treated with cidofivir or by reducing immunosuppression. The addition of probenecid to cidofovir significantly reduces the associated nephrotoxicity.
Clinicians should treat influenza with neuraminidase inhibitors, such as oseltamivir and zanamivir (Relenza, GlaxoSmithKline). For critically ill patients, clinicians should treat with intravenous neuramidase inhibitors, such as IV zanamivir or peramivir (Rapivab, Biocryst).
Clinicians can diagnose patients with parainfluenza virus by using PCR, which is preferred, or by using antigen detection as well as viral culture from nasopharyngeal swab specimens.
Clinicians can treat respiratory syncytial virus with early oral and intravenous ribavirin to prevent the progression of the disease.
“Viral infections are a common complication of pediatric transplantation populations with high morbidity and mortality,” Hanisch and colleagues wrote. “Molecular diagnostics for surveillance and diagnosis, as well as a high degree of clinical suspicion can help identify infection earlier, and allow prompt institution of therapy to ameliorate disease.”– by Will Offit
Disclosures: Infectious Diseases in Children could not confirm relevant financial disclosures at the time of publication.