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Serological Screening of Deceased Donors for KSHV Infection Recommended

Universal serological screening of deceased donors for Kaposi's sarcoma-associated herpesvirus (KSHV) infection, also known as human herpesvirus 8 (HHV8), should be introduced to reduce deaths, experts said.

Several cases of fatal primary KSHV had been observed in recent years in recipients of solid organ transplants in the UK, highlighted the virology subcommittee of the Advisory Committee on the Safety of Blood, Tissues, and Organs (SaBTO), which advises UK ministers and health departments on the most appropriate ways to ensure the safety of blood, cells, tissues, and organs for transfusion or transplantation.

In their independent report for the Department of Health and Social Care (DHSC), the authors explained that triggered by a diagnosis of KSHV disease in recipients of solid organ transplants, 10 events had been investigated between 2015 and 2019. This had led to the identification of seven clusters involving 23 recipients, with 11 new infections consistent with donor-derived infection. The observed transmission rate in this case series was 48%, with a 64% fatality, the report noted.

Since then and up to July 2021, five more cases had been reported and investigated, with two donor-derived transmissions being identified, with an overall transmission rate of 52%, and a 57% fatality rate.

While the true incidence of donor-derived or newly acquired post-transplant KSHV infection was not known, the severity of disease observed in cases that had been described over the years indicated that "action is necessary", emphasised the authors.

Serological tests were required for the identification of asymptomatic, infected individuals, explained the authors, and a clinical role for serological screening in organ transplantation had been proposed in the past, but "barriers remained, with progress yet to be made", the authors warned.

Moreover, KSHV antibody testing was complex and restricted in availability, they pointed out, and its utility in the context of organ donor screening needed careful investigation.

Unfeasible Costs Not Incurred

The working group explored the current scientific evidence and assessed the size and impact of donor related KSHV infection on recipient outcomes, as well as the feasibility of implementing appropriate interventions. It considered a number of potential initiatives, which included promoting awareness about the infection, and using virological testing strategies to identify risk to recipients.

Potential negative effects on the availability of safe organs for transplantation and on graft function and recipient survival resulting from inadvertent changes in recipients’ immunosuppression regimens were also given consideration. The subcommittee also performed an economic analysis, with the primary aim of examining whether there were evident financial barriers that might mean any specific intervention was too costly to deliver in the setting of deceased organ donation, the authors underlined.

"With a focus on averting deaths due to donor-derived primary KSHV infections occurring within 12 months of transplantation, there was no indication that unfeasible costs would be incurred for the implementation of interventions that have the potential to improve patient outcomes and save lives," the authors stated.

"We strongly recommend the introduction of universal serological screening of deceased donors for KSHV infection," advised the subcommittee. The report added that initially testing should be centralised, and performed as soon as was practical, with the programme monitored and reviewed to inform necessary changes.

Although the work primarily addressed the particular challenges of deceased organ donation and severe post-transplant primary KSHV infection in recipients, it also considered a risk-based assessment option for living donors and recipients. However, the authors stressed that more work was required to guide the KSHV testing of living solid organ donors.

HCP Should 'Familiarise Themselves' With KHSV

The working group also made these additional recommendations:

  • The organ procurement organisation should co-ordinate the collection of information on recipient outcomes in collaboration with transplant centres and review the data on a regular basis, at least on an annual basis
  • Screening activity data shall be reported to SaBTO on an annual basis
  • A full review of screening policy at 3 years, or earlier in the event of significant findings, and reported to SaBTO
  • Unintended negative effects from donor screening on the availability of safe organs for transplantation and recipient management should be mitigated through communication of strategy and rationale across the transplant community
  • Guidance on monitoring and management of recipients identified at risk of KSHV infection and disease should be incorporated into appropriate clinical practice guidelines
  • Guidelines should be developed to inform the need for screening of recipients and for living donors

The group also advised that UK healthcare professionals should familiarise themselves with the epidemiology and post-transplant clinical course of KHSV infection to enable early diagnosis and should report cases of post-transplant KSHV infection and disease to NHS Blood and Transplant (NHSBT) Organ and Tissue Donation and Transplantation (OTDT) to enable appropriate investigations and actions.

Welcome Improvement on Current Situation

The group acknowledged the absence of a gold standard assay but postulated that demand for commercially available assays that were suitable for the proposed use may act as a catalyst to promote more clinically applied developmental work in this field.

In the meantime, they believed that although current testing algorithms may misclassify individuals as infected or uninfected, assay performance was "sufficiently good" to identify those individuals who were likely to have the highest risk of transmitting the virus via a solid organ, the authors reassured.

Despite the limitations, the added information provided through post-donation antibody testing would be welcome and an improvement from the current situation, they stressed.

The group counselled that identification of donor and recipient infection status before disease development was the first step towards enabling the necessary studies into predictors of disease and effective therapeutic modalities for prophylaxis and treatment.

For improved outcomes, early diagnosis with appropriate management was "essential", emphasised the authors, who added that screening had the purpose of offering the opportunity for monitoring and early diagnosis.