Monkeypox a Concern for Donor-derived Infection?

Outbreaks of viruses such as West Nile virus, Zika virus, and severe acute respiratory syndrome coronavirus 2 are a concern for donor-derived infection that may have serious manifestations in a potently immunosuppressed organ recipient. For donation and transplantation, there is a focus on whether the infection has characteristic epidemiological or clinical features to prompt diagnosis; whether there are sensitive, specific, and timely diagnostic tests; the presence and duration of infectivity from donated organs; outcomes of donor-derived infection; the success of risk mitigation strategies; and the efficacy of available treatments. With enough instances of organ utilization from infected donors, knowledge is gained to guide donation and transplantation, as has occurred for coronavirus disease 2019 infection, in which transmission seems to occur only through lung and possibly intestinal donation,1 and for hepatitis C virus infection, which can be effectively cleared after transplantation. Against the risks of donor-derived infection, the transplant community balances the individual and community risks of not proceeding to organ utilization. From January 1 to September 13, 2022, there have been 58 285 laboratory-confirmed monkeypox cases and 22 deaths in 102 Member States of the World Health Organization, with highest case numbers in Europe and the United States.2 Globally, weekly case numbers are reducing2; however, the future of the outbreak is difficult to forecast. The current outbreak has characteristic epidemiology, with 95.0% identifying as men who have sex with men (MSM) and transmission occurring through sexual contact in 90.6% to 93.9% of cases.2,3 The case fatality rate is low, and death may follow the rare development of encephalitis.4 Most HIV-positive cases have had preserved CD4+ lymphocyte count and low viral load on antiretroviral therapy,5 so we are uncertain of clinical outcomes in potently immunosuppressed people. In human studies, virus has been cultured from oropharyngeal, anal, urethral, and skin swabs. Polymerase chain reaction (PCR) is positive in blood and urine, with blood viral load highest during the prodromal and early symptomatic phases of illness.6-8 Animal studies of orthopoxvirus infection following acquisition through the respiratory route show lymphohematogenous spread to the bone marrow, spleen, liver, lungs, kidneys, heart, intestine, and other organs.9,10 Donor assessment should elicit contact with monkeypox in the prior 21 d (the upper range of the incubation period) and involve careful evaluation of donors who are MSM. Focus is on sexual behavior in MSM, increasing the risk of monkeypox infection and examination of MSM for skin lesions at genital, perianal, and oropharyngeal sites. PCR of skin lesion material (fluid, tissue, crust) from several lesions obtained through vigorous swabbing is recommended for diagnosis. It is acknowledged that donor infection in the prodromal and early clinical phase of illness might be missed and present a risk of transmission because the blood viral load is highest at this time.8-10 There is no simple method to detect and diagnose such cases, which should be rare. One hopes that they may have been identified as a close contact, and in these special cases in which there are no skin lesions, PCR of oropharynx swab, anorectal swab, and blood may be considered, although these should not be routine sample sites. With characteristic epidemiology, none of the transplantation bodies currently suggest asymptomatic donor screening, such as through oropharyngeal and/or anorectal PCR (Transplantation Society of Australia and New Zealand [TSANZ], 2022, email memorandum to members),11,12 which would predictably lead to false-positive PCR results and delays because of test turnaround. Based on current limited clinical information and positive viral culture of blood and organs in animal studies, Table 1 shows that transplantation bodies agree that donation should not proceed from actively infected donors (TSANZ),11,12 generally, until skin lesions have scabbed and skin has reepithelialized (TSANZ).12 There are no reports of donor-derived infection, but if this were to occur, treatment is recommended for immunosuppressed people. Tecovirimat has been predominately used and is well tolerated,13 and combination treatment may be considered. TABLE 1. - Management by transplantation societies of United States, United Kingdom, and Australia of solid organ donation from donors infected, recovered, or in contact with monkeypox virus AST 12 NHSBT 11 TSANZ Actively infected cases Proven cases not suitable Proven, probable, and possible cases not suitable Proven, probable, and possible cases not suitable Consideration of donation in recovered cases When all lesions scabbed and skin reepithelialized Eight weeks after recovery When released from isolation (lesions scabbed and skin reepithelialized) Donor contact with monkeypox in the previous 21 d Risk–benefit discussion if high-risk contact Medium- and high-risk contact not suitable. Low-risk contact donation can be considered Consider in exceptional circumstances if high- or medium-risk contact AST, American Society of Transplantation; NHSBT, National Health Service Blood and Transplant; TSANZ, Transplantation Society of Australia and New Zealand. Vaccination used for pre- and postexposure prophylaxis is predominately replication incompetent modified vaccinia Ankara vaccine that poses no risk of transmission from donor to recipient (available as JYNNEOS in the United States and Australia, IMVAMUNE in Canada, IMVANEX in the Europe Union). Uncommonly replication-competent vaccinia virus-based vaccines such as ACAM2000 will be used. As virus may be cultured from the inoculation site to day 42 after vaccination,14 the Food and Drug Administration suggests deferral of blood donation until the vaccine scab has spontaneously separated from the skin (which usually occurs 14–21 d after vaccination).15 The risk of transmission through organ transplantation is probably small because the orthopoxvirus seems localized in this situation, not detected in the blood of 60 vaccines in one study.14 Monkeypox occurs characteristically in MSM presenting with rash, allowing a focus on specific donors at risk for infection and a diagnostic (lesion PCR) rather than screening approach in donors. Screening routine donors without clinical features of monkeypox infection is not recommended. Transmission is unlikely through donor ACAM2000 vaccination. We should follow transplantation society guidance regarding donors infected, recovering, or who have had contact with monkeypox virus. Guidance may evolve if the monkeypox outbreak continues, and we learn from unstable waitlisted patients who receive organs from infected or recovered donors under the cover of antiviral therapy.

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