Recent outbreaks of mpox, an infection caused by the monkeypox virus (MPXV), have captured scientists’ and the public’s attention. In 2021, two mpox cases were reported in patients traveling directly from African countries to the United States, and cases increased at an alarming rate in multiple countries throughout the following year.1 Although the source of the virus is unknown, scientists detected strains in monkeys and humans decades ago, and its spread was mainly limited to direct human-to-animal contact.1 However, the strain causing the recent mpox outbreak has been closely associated with sexual contact between human patients harboring laboratory confirmed infections. Patients with mpox exhibit rashes on their hands, feet, chest, face, mouth, or near the genitals, which can progress through several painful and itchy stages.2 It remains unclear whether the spread is due to skin-to-skin contact with lesions and bodily fluids or transmission through seminal fluids. Answering this question has substantial implications for public health and is a topic currently pursued by many research groups.1
In a recent study published in Nature Microbiology, Kevin Zeng and his group at the United States Army Medical Research Institute of Infectious Diseases conducted a retrospective study on archival testicular tissue samples from MPXV-infected crab-eating macaques, a non-human primate model commonly used to study mpox and evaluate treatments.3 "In our institute, we have been working on the monkeypox infection animal model for the last two decades. So, we have old animal tissue archives. At the beginning stage of the outbreak, I said why don’t we just go back to look at those tissues," said Zeng.
This is a very important piece of information for public health because we don't want to stigmatize the patient. But at the same time…we want to closely monitor and pay extra attention to the semen or body fluids just in case of some persistent infection.
-Kevin Zeng, United States Army Medical Research Institute of Infectious Diseases.
The researchers probed samples from acute and convalescent phases of infection and detected MPXV RNA and proteins in several testicular tissues, including sites of sperm production and maturation. Zeng and his team did not see viral infection in any other organs during convalescence. “That means the virus had been cleared in other organ systems but somehow the virus can infect the testes longer, and the longest one was at day 37 post exposure. That was very striking at the time,” said Zeng. “So, a patient, even though they recovered and the skin lesion is healed, may still be able to transmit the virus." This was one of the first studies to provide the scientific support that MPXV could be transmitted via infected semen.
“The paper puts up some ideas on where we can go and what we can do in the future. But I think we need pretty good animal models, and more studies are required,” said Siddappa Byrareddy, a professor at the University of Nebraska Medical Center, who not involved in the study. “I think it's a timely, important message to convey so people can be aware of it.” Additional studies have begun to confirm these findings in humans, although with relatively small sample sizes.4,5 As a result of these data, the World Health Organization (WHO) has recently officially advised condom use for those at risk.6
While the researchers were performing these studies, time was of the essence. "We were very cautious; at the same time, we want to move as fast as we can. You want people to know—it’s important to publish—because it's guidance and it's going to impact public health," said Zeng. "This is a very important piece of information for public health because we don't want to stigmatize the patient. But at the same time…we want to closely monitor and pay extra attention to the semen or body fluids just in case of some persistent infection." In the future, Zeng and his group plan to conduct additional animal studies to validate the archival samples.
- N. Kumar et al., “The 2022 outbreak and the pathobiology of the monkeypox virus,” J Autoimmun, 131:102855, 2022.
- “Mpox signs and symptoms,” CDC Centers for Disease Control and Prevention, https://www.cdc.gov/poxvirus/monkeypox/symptoms/index.html, accessed December 16, 2022.
- J. Liu et al., “Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors,” Nat Microbiol, 7:1980-86, 2022.
- A. Peiro-Mestres et al., “Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022,” Euro Surveill, 27, 2022.
- D. Lapa et al., “Monkeypox virus isolation from a semen sample collected in the early phase of infection in a patient with prolonged seminal viral shedding,” Lancet Infect Dis, 22:1267-69, 2022.
- “Public advice for men who have sex with men on preventing mpox (monkeypox),” WHO World Health Organization, https://www.who.int/news-room/public-advice/men-who-have-sex-with-men-preventing-monkeypox, accessed December 16, 2022.