Mpox outbreak in 2022: implications for blood component and donor human milk safety in Australia.

Ongoing surveillance for emerging and re-emerging infectious diseases is essential to assess their impact on blood and breastmilk safety Before 2022, human mpox (formerly monkeypox) was rarely reported outside Africa,1 but in May 2022, an outbreak of human mpox was reported in historically non-endemic countries. As the outbreak increased, the World Health Organization declared it a Public Health Emergency of International Concern on 23 July 2022.2 Between 1 January 2022 and 12 February 2023, 85 765 laboratory-confirmed mpox cases and 93 deaths had been reported to WHO from 110 member states, making it the largest recorded mpox outbreak.3 The six countries with the highest cumulative number of cases globally to 7 February 2023 were the United States (29 948 cases), Brazil (10 758), Spain (7533), France (4128), Colombia (4074) and the United Kingdom (3735), all countries where mpox was historically not endemic.3 Coinciding with this multicountry mpox outbreak, the first ever cases in Australia were reported in May 2022.4 On 26 July, the outbreak was declared a Communicable Disease Incident of National Significance, and as of 31 January 2023, 144 mpox cases had been reported in Australia, predominantly in Victoria (70 cases) and New South Wales (56 cases).4 Compared with previous mpox outbreaks, the 2022 outbreak is characterised by differences in epidemiology and transmission modes, and patients usually show atypical clinical manifestations. In this article, we critically evaluate the available evidence to determine the likely risks of monkeypox virus (MPXV) transmission via blood component and pasteurised donor human milk (PDHM) in Australia. Mpox is caused by MPXV, a member of the Orthopoxvirus genus. MPXV has been divided into two clades that historically circulated in different regions of Africa: clade I (formerly known as the Congo Basin/central African clade), which is the more virulent clade, and clade II (formerly known as the West African clade). Clade II consists of two subclades: IIa and IIb; clade IIb is associated with the ongoing 2022 outbreak.5 As of 13 February 2023, the European Centre for Disease Prevention and Control reported that among cases with known sexual orientation, 96.0% (10 636/11 089) identified as men who have sex with men (MSM).6 Mean incubation period estimates of between seven and nine days have been reported.7, 8 Patients often present with atypical anogenital and mucosal lesions, and rash may not be widely disseminated to other parts of the body. Non-specific systemic symptoms include fever, headaches, lethargy, lymphadenopathy and myalgia.9, 10 Before the 2022 mpox outbreak, most reported human MPXV infections were in rural areas in Central and West Africa. Historically, mpox in Africa is typically a sylvatic zoonosis, acquired through contact with an infected animal's bodily fluids or through a bite.11 MPXV can be transmitted human to human via direct contact with infectious lesions or body fluids. Indirect transmission via contact with contaminated material or fomites, although rare, may also occur. MPXV is thought to be transmitted between humans by respiratory droplets, but this appears to require prolonged face-to-face contact. Transmission via the placenta from mother to fetus has been reported.11, 12 The epidemiology of the 2022 mpox outbreak in historically non-endemic countries suggests that MPXV is being transmitted by sexual contact, potentially facilitated by skin-to-skin contact that occurs during sexual encounters.13 Viruses may represent a threat to blood safety if infection includes an asymptomatic viable blood phase, results in disease symptoms in at least a proportion of recipients, if transmissible by the intravenous route and survives blood processing. Since the 2022 outbreak, the Australian Red Cross Lifeblood (www.lifeblood.com.au) has put in place specific MPXV deferrals whereby donors with diagnosed MPXV infection are deferred for four weeks from the date of recovery, and donors who are close contacts are deferred for four weeks from the date of last contact with the infectious person. Donors who have been unwell or seen a doctor in the past 12 months are assessed for eligibility on an individual basis, which would cover those who have had an undiagnosed symptomatic MPXV infection. Furthermore, donors with pre-symptomatic or asymptomatic infection are likely to be deferred due to other risk factors, including male to male sex within the past three months or recent mpox vaccination. To date, Lifeblood has not had to use the specific MPXV deferrals, demonstrating the negligible blood safety risk. Although data are limited, MPXV DNA has been detected in human blood samples, including samples taken during the 2022 outbreak.9 Although infectious virus has not been found in human samples, it has been detected in experimentally infected prairie dogs.14 One study of cases reported in the Democratic Republic of the Congo between 2007 and 2011 indicated that DNAaemia (detection of DNA in blood samples) was detectable one to two days before, and peaked one to two days after, rash onset.15 Blood MPXV DNA levels up to 105 to 106 genomes per millilitre were reported. Transmission of MPXV by intravenous inoculation has been found in non-human primates, with DNAaemia detectable within two to four days of inoculation.16 A small number of cases of MPXV transmission via needlestick have recently been reported.17 The implications for transfusion transmission have not been evaluated formally and, therefore, there is some uncertainty. However, these cases had skin lesions predominantly in the area of inoculation, suggesting the possibility of direct skin inoculation and local infection, rather than intravenous inoculation caused by viraemia. In Australia, red blood cell and platelet components are leukodepleted. As poxviruses are known to be associated with leukocytes,18 leukodepletion may further reduce MPXV blood component risk. In addition, for donations used to manufacture plasma-derived products, the virus inactivation and removal steps would likely inactivate infectious MPXV if present.19 Despite MPXV being theoretically transfusion-transmissible, no cases have been reported. Even though the detection of MPXV in, or transmission by, human breastmilk has not been reported, this may in part be due to the absence of studies.20 Similar to blood donors, milk donors are assessed if unwell at presentation, have had an illness outside of routine pregnancy care, or have had sores or rashes in the past week. As milk donors are women, any potential risk to PDHM associated with the 2022 mpox outbreak would be further reduced by the epidemiology of the outbreak, which is primarily associated with MSM. In addition, MPXV is inactivated at 60°C for a minimum of 15 minutes in viral transport media or fetal calf serum, and the vaccinia virus (a related poxvirus) is deactivated by pasteurisation at 60°C, albeit for ten hours.21 As PDHM is subject to Holder pasteurisation (62.5°C for 30 minutes), this would likely inactivate MPXV if present. Although MPXV is theoretically transfusion-transmissible, our review has indicated that transfusion transmission of MPXV has not been reported historically or during the ongoing 2022 outbreak, the largest ever recorded. In addition, MPXV appears to be only briefly detectable in peripheral blood, and the 2022 outbreak is primarily among MSM who would typically be excluded from donating. This indicates that transfusion transmission of MPXV is probably rare at present, if it is occurring at all. However, transfusion transmission remains a risk, particularly if the mpox outbreak spreads to the wider community.22 The number of new mpox cases globally was declining by August 2022 and has continued to decline since then.3 In Australia, only a relatively small number of mpox cases have been reported during this outbreak and, in line with international trends, the number of reported new cases is declining.23 Mpox is a notifiable disease in Australia and national guidelines have been developed for reporting and case and contact management.24 In addition, given Lifeblood's deferral policies for blood and milk donors, and that the 2022 outbreak is primarily associated with MSM, we can be confident that MPXV represents a low risk to blood component or PDHM safety in Australia. Further studies are required to address current knowledge gaps, including testing asymptomatic at-risk population groups to determine the asymptomatic rate of MPXV infection and testing serial blood samples from patients with mpox to clarify the duration and level of detectable plasma viral DNA and whether this represents infectious virus. A few months before the 2022 mpox outbreak, for the first time, the Australian mainland experienced an outbreak of autochthonous human Japanese encephalitis virus infection.25 These two events in the first half of 2022 are a reminder that viruses can, under optimal conditions, quickly give rise to large regional or multicountry outbreaks and potentially represent a threat to blood and PDHM safety. Cognisant of this risk, Lifeblood continues to maintain ongoing surveillance for emerging and re-emerging infectious diseases and their potential blood and PDHM safety impact. For infectious disease pathogens that are theoretically transmissible by transfusion or donor breastmilk, if the infectious period is brief (ie, days to weeks), low case numbers are reported in the Australian population, and given Lifeblood's deferral of unwell and/or at-risk donors, the risk to blood component and PDHM safety will typically be negligible. Australian governments fund Australian Red Cross Lifeblood to provide blood, blood products, and services to the Australian community. No relevant disclosures. Not commissioned; externally peer reviewed.