Minimising the risk of monkeypox virus transmission during faecal microbiota transplantation: recommendations from a European expert panel

Faecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection, recommended by several guidelines for this indication.1, 2 FMT is not only more effective than antibiotics for recurrent C difficile infection,³ but also able to prevent C difficile infection-related complications.⁴ Several actions have been taken to guarantee and expand FMT availability, and to increase its safety. Stool banks are a model that ensures a high level of product quality and reliability of supply.1, 2 The need for stool banks became evident during the COVID-19 pandemic, when, because of concerns about the potential transmission of SARS-CoV-2 virus via faeces, FMT was temporarily withheld in some countries.⁵ In response to this issue, the FMT community has provided recommendations with the aim of safely continuing the routine provision of FMT by reorganising workflows, mainly of donor screening.⁵ These recommendations have proved to be effective in retaining a similar number of donors and patients as before the pandemic and maintaining safety.

As of Sept 7, 2022, monkeypox virus infection has been reported in over 100 countries or territories since January, 2022, including 97 that have not ever reported an outbreak before.⁷ Consequently, on July 23, 2022, WHO declared the monkeypox virus outbreak to be a public health emergency, advocating common actions aimed at preventing it.⁸

Monkeypox virus is a DNA virus belonging to the Poxviridae family, close to the variola virus (known as smallpox). It typically has a 1–2 week incubation period, a prodromal period with fever and lymphadenopathy, and finally a macular rash progressing through papular, vesicular, and pustular stages. Monkeypox virus is usually a self-limiting disease, with symptoms lasting 2–4 weeks.⁹

Monkeypox virus is believed to be transmitted predominantly through direct contact with lesions or infected body fluids, with possible involvement of fomites and large respiratory droplets. However, the current outbreak differs from previous ones because it seems to spread mainly (90–95%) via sexual contact among men who have sex with men, with a high frequency of anogenital lesions and proctitis.⁹ Moreover, some affected individuals can be asymptomatic or have few symptoms.¹⁰

Some reports have identified the monkeypox virus genome in rectal swabs or faecal samples,10, 11 and viable virus has been isolated from rectal swabs in one of these studies,¹⁰ supporting the theoretical risk of transmission of monkeypox virus via FMT.

In August, 2022, the US Food and Drug Administration (FDA) issued a safety alert concerning this risk, advising the need for increased safety protections to be applied to the FMT workflow related to the monkeypox virus, including additional questions to identify donors who might have recent or active infection or be at high risk of infection.¹²

As a European expert panel, we agree that there is a need for expanding the donor questionnaire to decrease the risks of transmission of monkeypox virus. This outbreak appears to spread mainly through sexual contact. Current guidelines for donor screening already recommend excluding individuals with risky sexual behaviour (including sexual contacts with sex workers, with anonymous individuals, or individuals with sexually transmittable diseases), which is also applicable for identifying potential donors with monkeypox virus.1, 2 Moreover, we recommend screening potential donors, at the first evaluation and at each donation, for both the presence of prodromal non-specific symptoms (including fever, lymphadenopathy, or myalgias) or of newly appeared skin lesions (mainly macular rash progressing to vesicula and pustula) within the previous 30 days; or close contact with individuals with proven or suspected infection within the previous 30 days, or both. If either of these items is positive, the potential donor should be prohibited from donating at least for 30 days.

We also agree with the suggestion from the FDA to retrospectively extend this screening to donors whose stool batches have been collected since March, 2022.¹² Notably, the FDA has not suggested any additional testing. PCR-based tests for detecting viral DNA in biological samples are available for monkeypox virus, but accuracy on stool samples is unknown.

Additionally, the FDA recommends informing patients of the potential risk of monkeypox virus transmission. We agree with the importance of informing patients about the potential risks of transmission of infectious agents but believe that the current incidence of monkeypox virus (which seems to be limited to risks groups who are excluded from donation) does not justify emphasising it as a separate entity.

We agree that, on the basis of current knowledge of the transmission of monkeypox virus and the performance of available tests, the addition of laboratory testing would not increase safety, and is not clinically justified at present.

These recommendations count for both research and clinical practice and should be adapted to local health-care systems and regularly updated on the basis of new insights in the epidemiology of monkeypox virus and potential advantages of specific diagnostics.

EJK and GC are joint senior authors. GI has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics, and Tillotts Pharma, and for acting as consultant or advisor for Ferring Therapeutics, Giuliani, Malesci, and Tillotts Pharma. BHM has received consultancy fees from Finch Therapeutics Group and Ferring Pharmaceuticals. HS reports personal fees from Danone, Enterome, Takeda, AbbVie, Roche, Amgen, Danone, BiomX, Ferring, BMS, Astellas, MSD, Novartis, Tillotts Pharma, and Biose; grants from Biocodex, Danone, and BiomX; and is a co-founder of Exeliom Biosciences. MJGTV has received research grants from 3M, Astellas Pharma, Biontech, DaVolterra, Evonik, Gilead Sciences, Glycom, Immunic, MaaT Pharma, Merck/MSD, Organobalance, Seres Therapeutics, and Takeda Pharmaceutical, and speaker or consultancy fees from Alb Fils Kliniken, Arderypharm, Astellas Pharma, Basilea, Bio-Mérieux, DaVolterra, Farmak International Holding GmbH, Ferring, Gilead Sciences, Immunic, MaaT Pharma, Merck/MSD, Pfizer, Roche, Organobalance, and SocraTec R&D. AG reports personal fees for consultancy from Eisai, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie Srl, Board MRGE, and Sanofi; personal fees for acting as a speaker for Takeda, AbbVie, and Sandoz; and personal fees for acting on advisory boards for VSL3 and Eisai. JJK and EJK have received unrestricted research grants from the Vedanta Biomedical Company, Boston. GC has received personal fees for acting as advisor for Ferring Therapeutics. All other authors declare no competing interests. GI is supported by the Linea D-1 of the Catholic University of Rome and by the Ricerca Finalizzata Giovani Ricercatori 2018 of the Italian Ministry of Health (project GR-2018-12365734) AG, GC, and GI are supported by the BIOMIS grant of the Italian Ministry of Research. BHM is supported by a National Institute of Health Research (NIHR) Academic Clinical Lectureship (CL-2019-21-002). GI, AG, and GC thank the Fondazione Roma for the invaluable support to their scientific research.