Status:
Ready to upload
Record number:
2372
Adverse Occurrence type:
MPHO Type:
Estimated frequency:
Only a limited number of case reports have been published in the literature.
Time to detection:
At some point between 23 to 34 days after transplantation
Alerting signals, symptoms, evidence of occurrence:
Disorientation and diarrhea were the initial symptoms. Neither magnetic resonance imaging (MRI) nor cerebrospinal fluid (CSF) analysis revealed signs of encephalitis. However, commercial PCR tests were positive for HHV-6 in blood, CSF, and various tissues, definitively confirming disseminated HHV-6 disease.
Demonstration of imputability or root cause:
The authors sequenced HHV-6 U39 gene that has a 6% nucleotide divergence in donor's spleen and liver and the recipient's colon, CSF and saliva. The same viral sequence was detected in all samples, suggesting that transmission from donor to recipient is plausible.
Imputability grade:
2 Probable
Groups audience:
Keywords:
References:
Suggest new keywords:
HHV-6; Human herpesvirus 6; iciHHV-6; inherited chromosomally integrated HHV-6; HSCT; hematopoietic stem cells transplantation; donor-derived; reactivation
Reference attachment:
Suggest references:
Fatal outcome after reactivation of inherited chromosomally integrated HHV-6A (iciHHV-6A) transmitted through liver transplantation. Bonnafous P, et al. Am J Transplant. 2018 Jan 9
Pellett Madan R, Hand J; AST Infectious Diseases Community of Practice. Human herpesvirus 6, 7, and 8 in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13518. doi: 10.1111/ctr.13518. Epub 2019 Apr 4. PMID: 30844089
Petit V, Bonnafous P, Fages V, Gautheret-Dejean A, Engelmann I, Baras A, Hober D, Gérard R, Gibier JB, Leteurtre E, Glowacki F, Moulonguet F, Decaestecker A, Provôt F, Chamley P, Faure E, Prusty BK, Maanaoui M, Hazzan M. Donor-to-recipient transmission and reactivation in a kidney transplant recipient of an inherited chromosomally integrated HHV-6A: Evidence and outcomes. Am J Transplant. 2020 Dec;20(12):3667-3672. doi: 10.1111/ajt.16067. Epub 2020 Jun 28. PMID: 32428994.
Bonnafous P, Phan TL, Himes R, Eldin K, Gautheret-Dejean A, Prusty BK, Agut H, Munoz FM. Evaluation of liver failure in a pediatric transplant recipient of a liver allograft with inherited chromosomally integrated HHV-6B. J Med Virol.2020 Feb;92(2):241-250. doi: 10.1002/jmv.25600. Epub 2019 Oct 20. PMID:31579937.
Kondo K, Yamanishi K. HHV-6A, 6B, and 7: molecular basis of latency and reactivation. In: Arvin A, Campadelli-Fiume G, Mocarski E, et al., editors. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007. Chapter 47. Available from: https://www.ncbi.nlm.nih.gov/books/NBK47366/
Note:
Oscar: I have added two more references from the same group on investigators addressing the same issue.
Melissa: Agut H, Bonnafous P, Gautheret-Dejean A. Update on infections with human herpesviruses 6A, 6B, and 7. Med Mal Infect. 2017 Mar;47(2):83-91. doi: 10.1016/j.medmal.2016.09.004. Epub 2016 Oct 20. PMID: 27773488.
Melissa: The editorial group decided that for this record, for HHV-6A, we will create one description summarizing the known cases (done, this record) to include liver and kidney, and then clone the record to ensure the library includes a separate listing for each of the organs with transmission cases (done EP)
Expert comments for publication:
HHV-6 has the ability to integrate covalently into human chromosomes. When this occurs, HHV-6 DNA is transmitted through Mendelian inheritance via germ cell lineages. Individuals with chromosomal integrated HHV-6 (ciHHV-6) have at least one copy of the DNA in every cell and, therefore, exhibit persistently elevated levels of DNA in blood and tissue samples. This phenomenon is observed in approximately 1% of the population. Conversely, about 90% of the population demonstrates seropositivity for HHV-6, as the virus is commonly transmitted from adults to children via saliva during early childhood.
In the reported case, the donor's spleen and liver exhibited high levels of HHV-6 DNA, consistent with ciHHV-6. In contrast, the recipient’s native liver was HHV-6 DNA-negative. Although the recipient was seropositive, immunosuppression likely rendered their antibodies ineffective at preventing viral reactivation from the integrated HHV-6 present in the donor's liver.
Interestingly, some case reports in the literature have been published by the same authors from a center in France who have developed their own real-time PCR method for HHV-6 detection.
Practice guidelines for HHV 6, 7, and 8 in solid organ transplantation were published by the American Society of Transplantation Infectious Diseases Community of Practice in 2019 (Pellet).