Is Monkey Pox a Sexually Transmitted Infection?

By Lao-Tzu Allan-Blitz, MD Chief Resident Physician, Global Health  Brigham and Women’s Hospital and Boston Children’s Hospital

Jeffrey D. Klausner, MD, MPH  Clinical Professor of Medicine, Infectious Disease, Population and Public Health Sciences, Keck School of Medicine, University of Southern California  Former US CDC Medical Officer  Former San Francisco City and County Deputy Health Officer

The rapidly developing global outbreak of human monkeypox, declared a Public Health Emergency of International Concern by the World Health Organization [1], has demonstrated transmission dynamics uncharacteristic of prior outbreaks.

Historically, outbreaks of human monkeypox have been short-lived, mostly limited to already endemic tropical rainforest regions, with infections transmitted through predominantly animal-to-human contact, as well as human-to-human transmission via close contact with an infected individual [2.]

Over the past several months, however, the current outbreak of human monkeypox has spread more rapidly and pervasively than any previous outbreak [1], and with mounting evidence that sexual transmission is the most common mode of transmission [3–6].

But whether human monkeypox constitutes a sexually transmitted infection, and why that would be important, are subject to ongoing debate.

Sexually transmitted infections are typically defined as being caused by an infectious microorganism transmitted from one person to another though bodily fluids (blood, semen, vaginal fluids, rectal fluid, saliva) during oral, anal, or genital sex with an infected partner [7].

Thus, to classify as a sexually transmitted infection, human monkeypox virus must be predominantly transmitted via sexual contact though sexual fluids. Viral DNA of human monkeypox has been identified in seminal fluid [4,8,9], rectal swab specimens [8], tests of respiratory secretions [2,8,10], as well as from the blood [10].

A growing body of published reports suggest that transmission can and does occur via exposure to those sexual fluids, noting a temporal and anatomic association between sexual practices like anal and oral sex and the development of human monkeypox lesions.

Furthermore, there is a high prevalence of sexual risk behaviors among patients with human monkeypox, and frequent localization of the rash to the genitalia and rectum [3–6,8,11–13].

Recent reports have highlighted the temporal association of sexual practices conferring elevated risk for other sexually transmitted infections with the acquisition of human monkeypox; such practices have included attending sex-on-site venues, multiple recent sex partners, and condomless receptive anal intercourse [4,6,8].

One series, for example, reported that the risk of proctitis due to human monkeypox was 5.5 times higher among those who recently engaged in receptive anal intercourse, and that 95% of patients that presented with tonsillitis reported receptive oral intercourse in the preceding days [6].

Second, case series of patients with human monkeypox infection have documented high rates of sexual risk behaviors, from condomless anal intercourse, sex with multiple partners, use of drugs during sex, to attendance of sex-on-site venues [3,4,8,11].

Additionally, numerous reports have documented index lesions occurring at the genitalia, rectum, and oropharynx [4–6,12,13], suggesting direct inoculation of infection during sexual intercourse.

Such transmission dynamics would further explain the vastly disproportionate burden of disease among gay and bisexual men with men, who constitute 92%-100% of cases of the reported cases [3,4,6,13], as well as the high prevalence of concurrent sexually transmitted infections (17–29%) among the patients with human monkeypox [4,6,8].

Finally, a recent study identified protracted shedding over 19 days of human monkeypox DNA in the semen of an infected individual [9]. Investigators isolated human monkeypox virus and subsequently demonstrate infectivity in cell culture [9].

Taken in context, the temporal and anatomic association with various sex practices, the high prevalence of sexual risk behavior among patients with human monkeypox, and the in vitro infectivity of human monkeypox DNA isolated from semen strongly suggest that human monkeypox is transmitted through sexual activity.

Indeed, one report concluded that all secondary cases of human monkeypox were likely due to sexual transmission — that conclusion based on anogenital and perineal localization of the rash in 72% of cases, associated inguinal lymphadenopathy in 72% of cases, and frequent report of sexual risk behaviors including condomless anal intercourse and sex with multiple partners within the preceding three weeks among 84% of cases [11].

Another report similarly noted that the clinicians seeing more than 500 patients with human monkeypox globally suspected sexual transmission in 95% of cases [4], although the specifics on how that determination was made were unavailable.

Finally, further supporting the nearly exclusive sexual spread of infection in the current outbreaks is the absence of any substantial number of cases of human monkeypox associated with household or casual, non-sexual transmission.

Worth highlighting are the fact that recent findings are derived from the current outbreaks in the United States and Europe. The role of sexual transmission among endemic cases in Africa is less clear.

An unpublished report of cases of human monkeypox presenting to a hospital in the Democratic Republic of the Congo between 2007–2011 identified exposure to wild animals and handling of uncooked meat as the primary source of exposure for most cases [14]. Data from cases of human monkeypox in Nigeria from 2017–2018, however, noted that the rash localized to the genitalia in 47% — 68% of cases [15–17]. Sexual risk factors were not explored in those studies, but the authors speculated on the possibility of sexual transmission. There are limited data on the transmission dynamics of human monkeypox within Africa during the current global outbreak. Thus, the actual proportion of cases being transmitted globally outside of the current outbreaks via sexual contact is unknown.

The ramifications of classifying human monkeypox as a sexually transmitted infection are double-edged.

The stigma surrounding sexually transmitted infections in gay men and other sex with men limits healthcare seeking and partner-notification behaviors [18,19], directly subverting our primary means of outbreak control — namely, early identification and behavior change in infected individuals.

Furthermore, such stigma can fuel further homophobia, particularly in areas without human rights protections for individuals who engage in same-sex relationships [20]. Conversely, failure to appropriately identify and disseminate to the public the predominant mode of transmission will likely perpetuate behaviors that are driving transmission.

Identifying high-risk sub-populations, in this case gay, bisexual or other men who have sex with men, who have multiple partners, will facilitate targeted awareness and education efforts, exposure reduction and other disease intervention activities such as testing, treatment and vaccination, which in turn may augment control efforts and prove to be cost effective.

Such efforts are analogous to what was eventually implemented in partnership with community-based organizations to combat the human immunodeficiency virus pandemic with notable success [21].

Further, the current guidelines recommend isolation of individuals infected with human monkeypox until complete resolution of symptoms and healing of the rash, which can last for up to four weeks [22].

We have already observed the numerous socioeconomic consequences of 10-14 days of isolation recommended during the SARS-CoV-2 pandemic in the form of productivity, supply chain disruptions, and agriculture production [23].

If human monkeypox is in fact predominantly transmitted through sexual contact, which the evidence above suggests that it is, that duration of isolation, and thus the consequent adverse socioeconomic impact, may be unnecessary.

Human monkeypox is not exclusively transmitted through sexual contact [2]. A related poxvirus, molluscum contagiosum, has similar transmission characteristics, which can be transmitted via both skin-to-skin contact and/or sexual contact [24]. Human herpes simplex viruses similarly can be transmitted via close skin-to-skin contact as well as through contact with bodily fluids during sex [25].

Similarly, Treponema pallidum pallidum, the cause of syphilis, is predominantly transmitted through sexual contact [26], yet historical reports prior to the routine use of protective gloves among medical professionals frequently noted syphilitic lesions on the fingers of physicians acquired via non-sexual skin-to-skin contact [27,28], as well as via human bites [29]. In contrast, Neisseria gonorrhoeae is thought to be nearly exclusively transmissible among adults via sexual contact [30].

Thus, human monkeypox appears to occupy a space that overlaps with many sexually transmitted infections, one shared by diseases such as molluscum contagiosum, genital herpes and syphilis, one in which sexual transmission is a key component of but not an exclusive means of transmission.

The transmission dynamics of human monkeypox, at least across the United States and Europe, appears to be highly consistent with a sexually transmitted infection.

Our public health response, therefore, should incorporate sexual health into its response to the current outbreak, including frank discussion of specific sexual behaviors like condomless anal sex that increase the risk for transmission.

At the same time, we must destigmatize both the disease and its route of transmission. Targeted screening among populations with high risk for other sexually transmitted infections may be important strategies for case identification.

Finally, further work should evaluate formally the transmissibility of human monkeypox from different bodily fluids through experimental studies and careful epidemiologic analyses with particular attention to the possibility of differing transmission dynamics in different regions of the globe.

1. World Health Organization. Second Meeting of the International Health Regulations (2005) (IHR) Emergency Committee Regarding the Multi-Country Outbreak of Monkeypox — 23 July 2022. Available at: https://www.who.int/news/item/23-07-2022-second-meeting-of-the- international-health-regulations-(2005)-(ihr)-emergency-committee-regarding-the-multi- country-outbreak-of-monkeypox.

2. Titanji B, Tegomoh B, Nematollahi S, Konomos M, Kulkarni PA. Monkeypox — A Contemporary Review for Healthcare Professionals. Open Forum Infectious Diseases. 2022;doi:10.1093/ofid/ofac310

3. Philpott D, Hughes, CM, Alroy, KA, et al. Epidemiologic and Clinical Characteristics of Monkeypox Cases — United States, May 17–July 22, 2022. MMWR Morb Mortal Wkly Rep ePub: 5 August 2022.

4. Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox Virus Infection in Humans across 16 Countries — April-June 2022. N Engl J Med. Jul 21 2022;doi:10.1056/NEJMoa2207323

5. Antinori A, Mazzotta V, Vita S, et al. Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022. Euro Surveill. Jun 2022;27(22)doi:10.2807/1560–7917.ES.2022.27.22.2200421

6. Tarín-Vicente E, Alemany, A, Agud-Dios, M, et al. Clinical Presentation and Virological Assessment of Confirmed Human Monkeypox Virus Cases in Spain: A Prospective Observational Cohort Study. The Lancet. 2022;

7. National Institutes of Health: National Cancer Institute. Sexually Transmitted Infection. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/sexually- transmitted-infection Accessed August 10, 2022.

8. Peiro-Mestres A, Fuertes I, Camprubi-Ferrer D, 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. Jul 2022;27(28)doi:10.2807/1560–7917.ES.2022.27.28.2200503

9. Lapa D, Carletti F, Mazzotta V, 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. Aug 2 2022;doi:10.1016/S1473–3099(22)00513–8

10. Adler H, Gould S, Hine P, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. May 24 2022;doi:10.1016/S1473–3099(22)00228–6

11. Inigo Martinez J, Gil Montalban E, Jimenez Bueno S, et al. Monkeypox outbreak predominantly affecting men who have sex with men, Madrid, Spain, 26 April to 16 June 2022. Euro Surveill. Jul 2022;27(27)doi:10.2807/1560–7917.ES.2022.27.27.2200471

12. Patrocinio-Jesus R, Peruzzu F. Monkeypox Genital Lesions. N Engl J Med. Jul 7 2022;387(1):66. doi:10.1056/NEJMicm2206893

13. Girometti N, Byrne R, Bracchi M, et al. Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. Lancet Infect Dis. Jul 1 2022;doi:10.1016/S1473- 3099(22)00411-X

14. Pittman PR, Martin JW, Kingebeni PM, et al. Clinical characterization of human monkeypox infections in the Democratic Republic of the Congo. medRxiv. 2022:2022.05.26.22273379. doi:10.1101/2022.05.26.22273379

15. Yinka-Ogunleye A, Aruna O, Dalhat M, et al. Outbreak of human monkeypox in Nigeria in 2017–18: a clinical and epidemiological report. Lancet Infect Dis. Aug 2019;19(8):872–879. doi:10.1016/S1473–3099(19)30294–4

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17. Ogoina D, Izibewule JH, Ogunleye A, et al. The 2017 human monkeypox outbreak in Nigeria-Report of outbreak experience and response in the Niger Delta University Teaching Hospital, Bayelsa State, Nigeria. PLoS One. 2019;14(4):e0214229. doi:10.1371/journal.pone.0214229

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19. Fortenberry JD, McFarlane M, Bleakley A, et al. Relationships of stigma and shame to gonorrhea and HIV screening. Am J Public Health. Mar 2002;92(3):378–81. doi:10.2105/ajph.92.3.378

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But whether human monkeypox constitutes a sexually transmitted infection, and why that would be important, are subject to ongoing debate.

What Constitutes a Sexually Transmitted Infection?

Furthermore, there is a high prevalence of sexual risk behaviors among patients with human monkeypox, and frequent localization of the rash to the genitalia and rectum [3–6,8,11–13].

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