Herpes simplex virus 2 (HSV-2)

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Record number: 
Adverse Occurrence type: 
MPHO Type: 
Estimated frequency: 
2 in 4 to 2 in 2 depending on recipient serostatus and antiviral prophylaxis
Time to detection: 
9 days
Alerting signals, symptoms, evidence of occurrence: 
Donor A died of hypoxic ischaemic brain inlury with no evidence or history of recurrent HSV 2 infection. Retrospective testing revealed positive IgG, negative IgM and negative PCR for HSV 2. The liver recipient of donor A was investigated in the light of the fidings. Recipient had serological evidence of HSV 1and HSV 2 infection prior to transplant (positive IgG) and was also receiving Valganciclovir (VGCV) prophylaxis for CMV. Despite of these, there was viraemia, disseminated skin rash and hepatitis (ALT 236 U/L, AST 72 U/L, GGT 130 U/L). Interruption of prednisolone and IV aciclovir (ACV) were successful in controlling infection. The heart and lung recipient from donor A had no serological evidence of HSV infection prior to the transplant. Having received IV ganciclovir and human hyperimunoglobulin for prophylaxis of CMV mismatch, this recipient did not develop HSV 2 vireamia nor symptoms. It is not described whether serology was performed to check for seroconversion. The recipeint of the other kidney from donor A had a pre-transplant HSV 1 IgG positive but HSV 2 IgG negative result. He was receiving oral VGCV as CMV prophylaxis and did not develop any HSV symptoms. His post transplant HSV 2 serology is not mentioned. The kidney-pancreas recipient from donor A had an acute myocardial infarction with cardiac arrest on day 2 post transplant. Extended antimicrobial cover was introduced due to fever and negative bacterial cultures. Patient showed minimal neurological resposne despite weaning of sedation, progressive deterioration with increased inotrope requirements and died on day 9. Retrospective testing showed that this patient was seronegative for HSV before transpant and had high HSV 2 viral load in blood at time of death, consistent with primary HSV 2 infection. This patient went on to donate the transplanted kidney and lungs (donor B) before the herpetic infection was diagnosed. At retrieval, macroscopic fatty changes were noted in the liver and subsequent histology (coagulative parenchimal necrosis and nuclear inclusion) and PCR revealed HSV 2 infection. The biopsy of the kidney graft also revealed HSV 2 infection by immunohistochemical staining. The recipient of the re-transplanted kidney from donor B had been previoulsy infected with HSV 1and HSV 2 according to his serology results. Due to the suspicion of HSV 2 infection in the donor, he was started on VGCV; due to detectable viraemia, he was switched to IV ACV, with control. The bilateral lung recipient form donor B was seropositve for both HSV 1 and HSV 2 IgG pre-transplant. Because HSV 2 viraemia was detected on day +2 whilst on IV ganciclovir, VGCV 1gr tds was commenced, with resolution of viraemia.
Demonstration of imputability or root cause: 
Donor-derived HSV infection affected two clusters of recipients because of transplantation of organs from a prior organ recipient. The association of cases in the 2 clusters and demonstrable primary infection in recipients of organs from a common donor is sufficient to demonstarte imputability. The 100 % homology over the portion of the genome analysed also supports that. However, due to high sequence conservation over the regions analysed, the sequences from the cases also had high homology to unrelated, Genebank sequences.
Imputability grade: 
3 Definite/Certain/Proven
Reference attachment: 
Suggest references: 
Macesic N, Abbott IJ, Kaye M, Druce J, et al. Herpes simplex virus-2 transmission following solid organ transplantation: Donor-derived infection and transplantation from prior organ recipients. Transpl Infect Dis. 2017 Jun 15
Expert comments for publication: 
The role of HSV re-infection in the context of SOT and immunosuppressions has been demonstrated in this paper. Different outcomes were likely to be related to recipient previous HSV 1 and HSV 2 serostatus, the anti-CMV prophylaxis regimen they were receiving and the level of immunosupprssion. Viral transmission and detectable viraemia were demonstrated even in the presence of pre-exisitng antibodies and prophylatic antiviral for herpes viruses. This report also highlights the infectious issues that need to be considered when a transplant recipient becomes an organd donor. Infectious complications causing or contributing to the death must be considered and fully characterised in order to minimise the risk of onwards transmission.