Monkeypox DNA in semen supports advice to use condoms for eight weeks after infection has cleared

Although recent outbreaks of monkeypox (MPX) were largely reported in sexual networks, it was not referred to as a sexually transmitted infection. This was largely due to lack of data about whether the virus (MPXV) was present in genital fluids.

However,  an open-access study published in Eurosurveillance on 2 June 2022, reports that MPX DNA has been found in the semen of four men diagnosed in Italy between 17 and 22 May 2022.

All were in gay men in their 30s who had travelled in the first two weeks of May (including three to an event in Gran Canaria linked to other MPX cases. Two were HIV positive and on ART and two were HIV negative and on PrEP.

Only 3/4 had systemic symptoms (fever or fatigue). All had mostly genital and/or anal MPX ulcers, occurring 2-3 days after other symptoms, with 3/4 also having ulcers in other body areas (including thorax, arms, legs, hands and feet). Unlike the historical MPX pathogenesis indicating that ulcers usually develope at the same time, presentation was asynchronous in these four people.

Three different PCR tests were used to test semen samples.  Initially for orthopoxviruses generically, then confirmed for MPXV DNA, and finally to determine MPXV clade.

MPXV DNA was positive in semen samples for all 3/4 men with results (5-7 days since first symptoms). However, although quantitative levels of viral load were not available, these are estimated as being very low, based on having a quantification cycle (Cq) range of 27 to 30.

Cq is a marker for viral load and for most PCR tests a Cq of 36 to 40 would be the equivalent to a negative result. This supports the researchers comment that at these levels it is unlikely that virus could be isolated from these samples.

Seminal fluid was only one of a panel of nine samples tested, which included serum, plasma, MPX ulcers (skin and genital), throat swab, scab, faeces and saliva. Although many of these results were not yet available for all cases, especially at multiple timepoints, most of these other samples were also positive for MPXV DNA, but at a higher likely viral load.

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The investigators are to be congratulated on producing this first early data, even with significant gaps where analyses are still ongoing, including PCR and viral culture in other compartments. It should therefore be a priority to promptly update this report as soon at the additional data become available.

It is also possible that the DNA detected might be spillover of virus (or fragments) into semen from urethritis/urethral or penile lesions, rather than being a true measure in semen.

The current study doesn’t mean that MPX is a sexually transmitted infection. Or that it was sexually transmitted in these cases, even though all men had sex without condoms.

The results do support the caution to use condoms for eight weeks after MPX and its symptoms have resolved. The eight weeks is not evidence based, but a stop-gap measure while data are being collected at timepoints after recovery. Finding MPXV DNA during this eight-week period is likely to be more clinically important as genital fluids in very early stages are unlikely to contribute to further increasing the risk of transmission. [2]

This is in case genital fluids prove to be a reservoir site, as has been reported for other viral infections, including Zika and Ebola. [3]

This will require larger studies with longitudinal samples over three months.

The researchers also note the importance of further research as other viruses that can be detected in seminal fluid are not necessarily transmitted sexually. [3, 4]

The same issue of Eurosurveillance also includes case reports from the MPX outbreaks in Australia, Portugal and the UK. [5]

References

1. Andrea A et al for the INMI Monkeypox Group.. Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022. Euro Surveill. 2022;27(22):pii=2200421. (2 Jun 2022).
   https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.22.2200421
   https://doi.org/10.2807/1560-7917.ES.2022.27.22.2200421. 
2. UK Health Security Agency (UK-HSA). Principles for monkeypox control in the UK: 4 nations consensus statement. (30 May 2022).
   https://www.gov.uk/government/publications/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement
3. Le Tortorec A et al. From ancient to emerging infections: the odyssey of viruses in the male genital tract. Physiol Rev. 2020;100(3):1349-414. doi:10.1152/physrev.00021.2019. (20 May 2020).
   https://journals.physiology.org/doi/full/10.1152/physrev.00021.2019
4. Matusali G et al. Infectious Toscana virus in seminal fluid of young man returning from Elba island, Italy. Emerg Infect Dis. 2022;28(4):865-9. (April 2022).
   https://doi.org/10.3201/eid2804.211920.
5. Eurosurveillance, 27(22), (2 June 2022).
   https://www.eurosurveillance.org/content/eurosurveillance/browse