FDA Warns of Potential Monkeypox Transmission via FMT, Implements Additional Protections

The Food and Drug Administration (FDA) is advising that the clinical use of fecal microbiota for transplantation (FMT) has the potential to transmit monkeypox virus and for serious adverse events to occur, according to a safety alert.

Any investigational use of FMT must follow additional protections, the FDA said, if the stool was donated on or after March 15, 2022. This includes stool used as part of a study under an Investigational New Drug Application (IND) on file with the FDA or otherwise, the FDA said.

The FDA said it is not yet known whether the monkeypox virus can be transmitted through feces or from asymptomatic individuals. Typically, monkeypox is spread through close contact with an infected and symptomatic individual.

With that said, the FDA noted evidence pointing to monkeypox’s presence in DNA from rectal swabs and/or stool samples from those who were infected, with one study even finding virus DNA in rectal swabs from three individuals who reported no monkeypox symptoms. The risk for transmission of monkeypox via FMT is unknown, but these findings suggest the possibility, the FDA said.

There are additional protections outlined by the FDA:

• Donor screening with questions that aim to identify donors at high risk for monkeypox, that may be currently infected with monkeypox, or may have recently been infected with monkeypox.
• Development of exclusion criteria for donors and donor stool based on the screenings
• Informed consent that includes information about the potential transmission of monkeypox via FMT, including from asymptomatic donors

The FDA has notified IND holders about potential risks and notified them that they need to develop and implement additional safety precautions, they said. They are also communicating with other stakeholders and plan to communicate any further information to these parties as it becomes available.

Currently, monkeypox tests look for virus DNA from swab samples from lesions, the FDA explained, but there is little information around direct testing of stool for monkeypox.

In a related commentary published in The Lancet: Gastroenterology & Hepatology, an expert panel from Europe wrote in response to the FDA that they “agree that there is a need for expanding the donor questionnaire to decrease the risks of transmission of monkeypox virus.”

The authors said that while the current guidelines screen for risky sexual behavior, but expanding the screening questionnaire could include questions about the presence of non-specific symptoms like fever, lymphadenopathy, or myalgias or about newly appearing skin lesions within the previous 30 days, or close contact with confirmed or suspected infection within the previous 30 days, or both. The panel said that if either of these items is positive, the potential donor should be prohibited from donating for at least 30 days.

The panel also supported the FDA’s recommendations to extend this screening to March 2022 and to inform FMT patients of the potential risks of monkeypox transmission. The European panel also agreed that additional laboratory testing would not increase safety and would not be clinically justified.

“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,” the authors concluded.