Condition

An orthopox virus infection related to smallpox, cowpox and vaccinia. Previously endemic in some regions of Central and West Africa as a zoonotic infection of mammals. In 2022, an outbreak occurred Europe and spread globally, in which the disease was transmitted between humans, mainly through sexual contact among men who have sex with men. Over 99,000 total cases were confirmed.

Since November 2023, the Democratic Republic of the Congo (DRC) has seen a significant increase in mpox cases and the emergence of a new mpox clade Ib variant. This has subsequently spread to several other African countries including Burundi, Rwanda, Uganda and Kenya Person-to-person transmission has occurred during this outbreak, including through sexual contact, household contact, and within the healthcare setting. In August 2024, the Africa Centres for Disease Control and Prevention (Africa CDC) and the World Health Organization (WHO) declared public health emergencies over a large epidemic of MPXV clade I in the Democratic Republic of the Congo (DRC) and several other African countries. Up to August 2024, the Africa CDC announced that at least 13 African countries have reported 2 863 confirmed mpox cases (all clades combined) and 517 deaths so far in 2024 (until August). On 15 August 2024, one case of MPXV clade Ib was reported in the EU/EEA and more imported MPXV clade I cases will likely occur.

Infection can be asymptomatic (1.3-6.5%), but typical symptoms include an influenza-like prodrome, a rash that becomes vesicular and then pustular, and lymphadenopathy. The majority of human mpox cases experience mild to moderate symptoms, typically lasting from 2-4 weeks. Many cases during the 2022 outbreak presented with genital and peri-anal lesions, fever, lymphadenopathy, mouth lesions and sore throat. Information on clinical features in the clade I outbreak is still emerging at the time of writing, but reports suggest that among cases exposed through sexual contact in DRC, some individuals only present with genital lesions, rather than the more typical extensive rash.

The incubation period for mpox is usually 7 to 14 days, but can range from 5 to 21 days, with some shorter incubation periods of 2-4 days also reported in the 2022 epidemic.

Individual at Risk

Recipient

Donor

Donor with (history of) Mpox infection

Guidance at RECRUITMENT

ACCEPT

Guidance at CT

14 DAYS OR MORE AFTER FULL RECOVERY - accept.

Full recovery can be defined as the complete resolution of all symptoms, including resolution of skin lesions (i.e. vesicles have crusted, the scabs have fallen off and a fresh layer of skin has formed underneath).

LESS THAN 14 DAYS AFTER FULL RECOVERY – disclose history of recent infection to transplant centre, including source of infection. Any known risk activities that have implications for other transmissible infections should be noted.
IF NOT YET FULLY RECOVERED – defer sample collection until full recovery. Disclose current infection to transplant centre, including source of infection, any associated risk activities, illness severity and date of onset. Where possible, estimate the likely timeframe for sample collection.

Guidance at WORK-UP

IF FULLY RECOVERED – proceed with work-up assessment. If the donor is assessed as fit, donation should be scheduled no less than 14 days after full recovery.
IF NOT YET FULLY RECOVERED – defer physical examination, sample collection and other testing until full recovery. Disclose current infection to transplant centre, including source of infection, any associated risk activities, illness severity and date of onset. Estimate the likely timeframe for work-up, clearance and collection, noting that collection will be permitted no less than 14 days after full recovery.

Donor has been in contact with Mpox

Contact with mpox can be defined as close contact, including any sexual contact, with a person who has active mpox infection (i.e. after exposure but before full recovery).

Guidance at RECRUITMENT

Accept

Guidance at CT

Disclose to the transplant centre any associated risk factors for STIs.

Guidance at WORK-UP

Disclose to the transplant centre any associated risk factors for STIs.

Vaccination against Mpox

Background

Smallpox vaccine is believed to be effective against other orthopox viruses including mpox. While vaccine availability has been limited, many countries are targeting high-risk groups for smallpox vaccination during the 2022 mpox outbreak.

From a HPC safety perspective, there are existing guidelines for smallpox vaccine in its usual role for protecting at-risk individuals such as military personnel from smallpox. These guidelines are based on the ability of live/attenuated vaccinia virus to cause severe, life-threatening infection in immunocompromised recipients.

Many international safety regulations and guidelines define a post-vaccination risk period of up to 8 weeks – or longer, if the donor suffers vaccination complications or a persistent localised reaction. More pragmatically, the US FDA only requires deferral for 21 days or until the vaccination scab falls off spontaneously – whichever is longer – for uncomplicated vaccinations, while severe complications require deferral for at least 14 days after full recovery.

There is also a vaccinia-based smallpox vaccine that is not replication-capable (Modified Vaccinia Ankara, Bavarian Nordic – also known as MVA-BN, Imvanex, Imvamune and JYNNEOS) and would therefore require no deferral period for recipient safety.

Guidance at RECRUITMENT

ACCEPT.

Guidance at CT

8 WEEKS OR MORE AFTER VACCINATION – accept if there are no ongoing complications of vaccination and the scab has fallen off spontaneously.
WITHIN 8 WEEKS OF VACCINATION – report date and type of vaccine to transplant centre, as well as the indication for vaccination. Any known risk activities that have implications for other transmissible infections should be noted.

Guidance at WORK-UP

8 WEEKS OR MORE AFTER VACCINATION – accept if there are no ongoing complications of vaccination and the scab has fallen off spontaneously.
WITHIN 8 WEEKS OF VACCINATION – report date and type of vaccine to transplant centre. as well as any known STI risk factors. Any known risk activities that have implications for other transmissible infections should be noted.If there are ongoing complications of vaccination, advise the transplant centre that clearance may be delayed. Otherwise:
- For a replication-competent smallpox vaccine (i.e. one that forms a scab):
  - Collection may be scheduled at least 21 days after vaccination, or after the vaccination scab falls off spontaneously.
  - If serious complications occur, delay collection until at least 14 days after full recovery.
- For a smallpox vaccine that is not capable of replication (e.g. MVA-BN):
  - Commencement of G-CSF mobilisation or harvest of HPC(M) can proceed as long as the donor is free of any vaccination complications.

Justification for guidance

While mpox is usually a self-limiting disease with symptoms lasting for 2 to 4 weeks, immunocompromised patients are believed to be at higher risk of severe disease.

The potential for transmitting mpox virus via haemopoietic stem cell transplantation is not known and may be considered theoretical. However, the existence of a viraemic phase, reports of vertical transmission and the infection’s association with white blood cells indicate that HPC donation should be avoided during mpox infection – particularly during the prodromal and symptomatic phases.

The potential for transmitting vaccinia virus via smallpox vaccination is already assumed in existing regulations and guidelines, which are designed to mitigate the risk of severe vaccinia infection in immunocompromised patients.

The 2022 global mpox outbreak was primarily sexually-transmitted, and most affected individuals report male-to-male sexual contact, multiple sex partners, and other high-risk sexual practices that increase the risk of other STIs such as HIV. Therefore HPC donors who report a recent history of mpox, close contact with mpox or targeted vaccination against mpox should be assessed for any known risk activities that have implications for other transmissible infections.

References