The potential impact of monkeypox infection and vaccination on blood donor deferrals and the blood supply

Human monkeypox, a viral zoonotic disease similar to, but clinically less severe than smallpox, was first identified in humans in 1970 in the Democratic Republic of the Congo (DRC).1 Monkeypox presents as a febrile illness with rash, and transmission occurs via direct contact with infected individuals, infected bodily fluids, or indirect contact via fomites. Although no transfusion-transmitted cases have been described,2 viraemia is consistently detected during symptomatic infection and can persist for 2–3 weeks after resolution of a rash in some patients,3 creating a theoretical risk to the blood supply. The kinetics of viraemia during the presymptomatic phase and during asymptomatic infection are not well characterized. Since its discovery, most cases of human monkeypox have occurred in rural regions of Africa, particularly in the DRC and across Central and West Africa. There are two known clades of monkeypox virus — West African and Congo Basin (Central African), which vary by their endemic geography and pathogenicity.4 The Congo Basin clade, currently listed as a Health and Human Services Select Agent in the United States, is associated with higher mortality (up to ~11%), whereas the West African clade has a lower mortality rate (up to ~4%) and is not a Select agent.4 The first outbreak outside of Africa occurred in 2003 in the United States, resulting in over 70 cases.1 In 2022, the largest recorded outbreak of human monkeypox continues to evolve, with 6027 laboratory-confirmed cases as of 4 July 2022 according to the WHO,5 though Our World in Data has reported 11 595 cases as of 14 July 2022.6 Both the 2003 and 2022 outbreaks are attributed to the West African clade, though there is evidence that the strain responsible for the current outbreak continues to evolve into a novel phylogenetic branch.7 Currently, no in vitro screening assay for monkeypox virus in blood donors exists, and regarding monkeypox, the Association for the Advancement of Blood and Biotherapies (AABB) has stated that “evidence does not support the implementation of a donor question or provision of written donor education materials.”2 The AABB did offer prescriptive recommendations for centres choosing to defer, with donation allowed after resolution of symptoms with complete separation of scabs or a minimum of 21 days deferral after asymptomatic exposure.2 While many cases of monkeypox infection have been identified in individuals who would likely be deferred from blood donation based on social practices [e.g. men who have sex with men (MSM)], the US Centers for Disease Control (CDC) states that any individual having close contact with a person infected with monkeypox is at risk of acquiring the disease.8 Furthermore, multiple studies have demonstrated that members of the MSM community donate blood despite the self-exclusion questions.9 Therefore, blood donation deferral policies based on self-exclusion questions for social practices cannot be expected to completely eliminate the threat of monkeypox infection to the blood supply. While viraemia does not necessarily equate to transfusion transmissibility, given that current knowledge of viraemia, infectivity, and transmissibility via blood transfusion is limited, there is significant need to investigate the potential for transfusion transmission via focused studies on detection of monkeypox DNA and infectivity in relevant patient and blood donor populations (e.g., donors with multiple sexual partners of recent syphilis seroreactivity). Furthermore, evaluation of the potential for transfusion transmission during presymptomatic or asymptomatic infection, and the development of appropriate animal models to answer these questions are needed, as mounting evidence suggests that asymptomatic monkeypox infection may be theoretically possible.10 As of June 23, 2022, the US CDC's Advisory Committee on Immunization Practices (ACIP) recommends that persons needing pre- or postexposure prophylaxis for monkeypox receive one of two vaccines (ACAM2000 and JYNNEOS) which have previously been licensed for use in the US against smallpox.11 While the ACAM2000 vaccine is administered as a live, replicating Vaccinia virus, the JYNNEOS vaccine is a live, non-replicating Vaccinia virus and is administered through two injections, separated by approximately four weeks.11 As this vaccine strain is non-replicative, it is considered a potentially safer option, and is currently the only US FDA-licensed vaccine for use against monkeypox.12 In contrast, there is currently no vaccine licensed in the United Kingdom or Europe for immunization against monkeypox, though Imvanex, the same vaccine as JYNNEOS, is currently being used off-label to prevent monkeypox in Europe.13 As countries begin to vaccinate high-risk individuals and contacts of possible or confirmed cases, the use of these vaccines is expected to increase, as evidenced by the recent announcement regarding vaccinations in New York City, US and Ottawa, Canada.14, 15 While studies are currently underway to evaluate the efficacy and side effects of the JYNNEOS, and potentially other, monkeypox vaccines, one unknown consequence of this abrupt implementation is the potential impact on the international blood supply. Like the issues that have been encountered with severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infections and vaccination,16 the effects on the blood donation community, particularly regarding blood donation deferrals for monkeypox vaccine recipients, contacts of infected individuals, and infected patients themselves, remain uncertain. Furthermore, the US Food and Drug Administration (FDA) has no deferral period for otherwise healthy blood donors following receipt of the JYNNEOS vaccine.17 Conversely, donors that receive replicating Vaccinia virus vaccines, such as ACAM2000, should be deferred based on 2002 deferral guidance.18 These guidelines are dictated by the nature of the vaccination scab separation and the development of vaccinia symptoms, with additional deferral policies for individuals exposed to vaccine recipients (Table 1). As few donors were receiving smallpox vaccines when this schema was proposed, this algorithm may have been more appropriate, but if replicating Vaccinia virus vaccines see widespread use, the complexity of these guidelines represents a significant barrier to donation. If vaccine date known: If vaccine date unknown but within past three months: The distinct, and potentially confusing, differences between policies for vaccination against, and infection with, a disease that remains obscure to much of the public may cause complications and frustration for blood centre staff and donors, with the potential to further disrupt an already shrinking donor pool. Given the paucity of data, official guidelines are currently unavailable from various organizations across the world regarding deferrals for vaccine recipients. Similarly, deferrals vary for individuals diagnosed with monkeypox. However, deferral policies tend to be available and are generally consistent among various organizations for individuals who come into close contact with a monkeypox case (Table 2). 14 days from the end of symptoms and the disappearance of the vesicular lesion scabs If hospitalization is required — three months We must achieve a fine balance between ensuring both the safety and availability of blood, with primary risk factors to the safety of blood products including: (1) lack of or too lenient donor deferral criteria; (2) confusing donor deferral criteria leading to misinterpretation and/or inaccurate implementation; and (3) preventing disease transmission during the donation process. We must ensure that overly conservative deferral policies that unnecessarily deny otherwise eligible and willing donors are not implemented to prevent exacerbating the persistent blood shortages, while maintaining the safety of blood donors, blood centre staff, and transfusion recipients. While the monkeypox outbreak continues to unfold worldwide and public health officials and researchers attempt to understand the transmission dynamics of the virus, countries have begun to implement vaccination campaigns to bring the outbreak under control. Though live non-replicating vaccines are currently preferred and should not result in deferrals, utilization of replicating Vaccinia immunizations represents an area of concern if their use is necessitated. As policies are being developed and modified in real time, the international blood donation community must actively engage with experts and stakeholders to ensure deferral policies are clear and readily available to maintain an adequate and safe blood supply. Jeremy W. Jacobs performed the research, wrote the first draft of the manuscript, and approved the final version; Laura Filkins revised the manuscript and approved the final version; Garrett S. Booth supervised the research, revised the manuscript, and approved the final version; Brian D. Adkins supervised the research, revised the manuscript, and approved the final version. No funding was received for this research. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Institutional review board approval was not required as all data are publicly available and no human or animal research was performed. No patients were involved in this research, therefore informed consent is not applicable.

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