Fatal Primary Infection Due to Human Herpesvirus 6 Variant a in a Renal Transplant Recipient

Abstract

We describe a fatal primary human herpesvirus 6 (HHV-6) variant A infection in a kidney transplanted adult woman. On day 20 post transplantation (TX), after rejection therapy, the patient presented an acute hemophagocytic syndrome with hepatitis and central nervous system involvement. HHV-6 IgG and IgM antibodies seroconversion was demonstrated. HHV-6 variant A was the sole pathogen detected by nested PCR and/or culture in blood, bone marrow aspiration, liver biopsy, cerebrospinal fluid and bronchoalveolar lavage. The graft was HHV-6 seropositive and the patient was not transfused before day 28 post TX, suggesting that the virus was transmitted by the graft. Despite immunoglobulins, ganciclovir and foscarnet therapy, the HHV-6 infection progressed and led to severe aplasia. The patient developed Aspergillus fumigatus pneumonia and died from fulminant candidemia. This case demonstrated for the first time that HHV-6 variant A primary infection can cause life-threatening disseminated infection in immunosuppressed patients.

Human herpesvirus 6 infections after liver transplantation

“…Acyclovir [73,81] No No Ganciclovir [66][67][68][70][71][72] Yes Yes Mutation in U38 DNA polymerase Mutation in U69 phosphotransferase Foscarnet [65,[82][83][84][85] Yes Yes 2 Mutation in U38 DNA polymerase Cidofovir [76,86,95] Yes Yes Mutation in U38 DNA polymerase Maribavir [87,88] No Not available Cyclopropavir [89] Yes…”

“…In vitro studies demonstrated the activity of ganciclovir against HHV-6 [64,65] . Clinically, ganciclovir has been shown to be effective in HHV-6 infected bone marrow transplant recipients [66][67][68][69][70] . Likewise, case reports suggest that ganciclovir is effective for the treatment of HHV-6 infections after liver transplantation [66][67][68][70][71][72] .…”

“…Clinically, ganciclovir has been shown to be effective in HHV-6 infected bone marrow transplant recipients [66][67][68][69][70] . Likewise, case reports suggest that ganciclovir is effective for the treatment of HHV-6 infections after liver transplantation [66][67][68][70][71][72] . Ganciclovir prophylaxis has been shown to be effective in preventing HHV-6 reactivation in stem cell transplant recipients [73][74][75] .…”

Human herpesvirus type 6 reactivation after haematopoietic stem cell transplantation

“…In most reports, some antiviral activity is reported for ganciclovir although in certain cases of fulminant HHV6 infection showed no response. [44][45][46][47][48] Use of ganciclovir is complicated by severe bone marrow suppression which is an unwanted side-effect early after HSCT. 49 As in almost all patients suffering from HHV6 reactivation, prophylactic acyclovir was prescribed to prevent VZV/HSV reactivation, acyclovir appears to be ineffective against HHV6.…”

Viral Infection in the Renal Transplant Recipient

“…The role of HHV-6 and HHV-7 in solid-organ transplant recipients is incompletely defined. HHV-6 has been associated with fever, rash, encephalitis, hepatitis, myelosuppression, and interstitial pneumonitis (115)(116)(117)(118)(119). HHV-6 and CMV are significantly and independently associated with biopsy-proven graft rejection after liver transplantation (119,120).…”