While most people with monkeypox in the current outbreak have been gay men, some women are susceptible as well. A new study published today in The Lancet describes 136 cases among cisgender and transgender women and non-binary individuals in 15 countries.
The epidemiology, clinical presentation and outcomes of cases among men, cis women and trans women are similar in many respects, but the study reveals some notable differences. While monkeypox spread rapidly this summer among highly sexually active gay men, the cisgender women in the case series have far fewer sex partners and their cases are less likely to result in onward transmission. So far, there has been no sustained spread outside networks of men who have sex with men.
Nonetheless, cases among women warrant attention, in part because monkeypox can lead to complications during pregnancy. This research highlights the potential for under-diagnosis of cis women and the socially precarious position of at-risk trans women.
“During the global outbreak, case definitions have rightly focused on the most affected group, sexually active men who have sex with men. The public health response has been tailored to reach this group,” said Professor Chloe Orkin of Queen Mary University of London, who spearheads an international collaboration of clinicians studying monkeypox. “However, as the outbreak progresses, it’s important to also focus attention on under-represented groups such as women and non-binary individuals to better understand their risk…These learnings will help inform and tailor effective public health measures to be inclusive of these groups.”
As aidsmap previously reported, the UK Health Security Agency (UKHSA) reported the first monkeypox cases in the current outbreak in early May. As of 14 November, UKHSA has identified more than 3700 confirmed or probable cases in the UK. As of 16 November, the World Health Organisation (WHO) has tallied more than 80,000 cases worldwide, mostly in countries that have not historically reported monkeypox, resulting in 51 deaths.
Among cases with available data, about 97% are men, 86% identify as men who have sex with men and around half with a known status are living with HIV. This differs from the historical pattern in central and western Africa, where a third to a half of people with monkeypox are women and cases among children are not unusual.
Monkeypox incidence has declined dramatically from its July peak, with new cases in the UK falling to single digits in recent weeks. However, many experts think the virus will not be eliminated but rather could continue to circulate at low levels, especially among disadvantaged communities.
Orkin and a large team of collaborators in the SHARE-net international clinical network previously described more than 500 monkeypox cases diagnosed during the first months of the outbreak, primarily among gay men.
Now, the collaborators have published a new case series that describes 69 cisgender women, 62 transgender women and five non-binary individuals assigned female at birth who were diagnosed with monkeypox between 11 May and 4 October 2022. The median age was 34 years, slightly younger that the median of 39 in the earlier analysis of gay men. Most were Latina (45%), White (29%) or Black (21%). About half lived in Europe and half in the Americas; only three were in Africa.
Monkeypox transmission
While sexual contact was the suspected route of transmission for nearly all of the men in the earlier case series, this fell to 74% in the new analysis. But rates diverged for cis and trans women. While 61% of the cisgender women and non-binary people are thought to have acquired monkeypox via sex, this rose to 89% for the trans women; 15% and 11%, respectively, had an unknown transmission route.
All trans women and 14% of cis women and non-binary people reported anal sex, while 69% of cis women and no trans women reported vaginal sex (few of the trans women had undergone vaginoplasty, or gender-affirming ‘bottom’ surgery). Trans women had a median of 10 sex partners in the past three months, and 73% reported multiple male partners. Meanwhile, cis women had a median of one partner and were much more likely than trans women to say they had a single regular partner (61% vs 13%, respectively).
More than half (55%) of the trans women reported sex work, compared with just 3% of the cis women and non-binary people. Among those tested, 21% of trans women and 7% of cis women had concurrent sexually transmitted infections (STIs). One in 10 reported injection drug use (11% of trans women and 9% of cis women). Eight individuals (6%) were experiencing homelessness and four (3%) were migrants.
Only cisgender women had suspected non-sexual routes of transmission, including household contact (10%), non-sexual close contact (10%) and occupational exposure of healthcare workers (5%). The case series includes two nurses who presumably contracted the virus while caring for patients with monkeypox. One sustained an accidental scalpel wound while taking a lesion sample and the other did not have access to personal protective equipment while handling monkeypox virus samples. Reassuringly, although about a quarter of the cis women had children living in the same household, only two children acquired monkeypox, suggesting “very limited chains of transmission,” the study authors wrote.
Just over a quarter (27%) of the women with a known status were living with HIV, somewhat lower than the 41% rate seen in the earlier analysis of mostly gay men. But again, the overall rate hides the wide disparity between trans women (50% HIV positive) and cis women and non-binary people (8% positive). Almost everyone with HIV was on antiretroviral therapy, 81% had an undetectable viral load and the median CD4 count was 600. Among HIV-negative individuals, 58% of the trans women, but only 2% of the cis women, were using pre-exposure prophylaxis (PrEP).
“The inclusion of transgender women and non-binary individuals in this series illustrates the importance of demographic and outcome data being disaggregated by both sex and gender,” said co-author Dr Asa Radix of the Callen-Lorde Community Health Center in New York City.
However, this type of analysis has not yet been done for transgender men, some of whom are part of gay men’s sexual networks and therefore at risk for monkeypox. The US Centers for Disease Control and Prevention reports some 70 cases among trans men.
Symptoms and care
Like the gay men in the earlier case series, a majority of trans women with suspected monkeypox visited sexual health or HIV clinics. Cisgender women, in contrast, presented at emergency departments, sexual health or HIV clinics, hospital dermatology or obstetrics/gynaecology departments or primary care providers. “This reinforces the need for education for health professionals beyond sexual health clinics to ensure that monkeypox symptoms are not misdiagnosed and to limit onward transmission,” say the study authors.
In general, women in this case series reported symptoms similar to those of men in the earlier analysis. Almost everyone (93%) developed a skin rash or lesions, with a median of 10 sores. Cis and trans women, and people with sexual and non-sexual routes of transmission, had similar numbers of lesions. Just over 60% had systemic symptoms such as fever and fatigue. Compared with cis women, trans women more often had localised infections unaccompanied by systemic symptoms, as was seen in the earlier men’s analysis.
Nearly three quarters (74%) had at least one anal or genital lesion while about a quarter had oral lesions. A majority of cisgender women and non-binary people had lesions on the vulva (outer genitalia) or in the vagina. Most trans women and about a quarter of cis women had external or internal anal or rectal lesions or proctitis (rectal inflammation). These symptoms often resembled other sexually transmitted infections, and 34% of cis women and 10% of trans women were initially misdiagnosed.
"As the outbreak progresses, it’s important to also focus attention on under-represented groups such as women and non-binary individuals."
“[T]he site of the lesions largely corresponded to the type of sexual activity reported,” the study authors noted. “Clinicians must be made aware of the differing clinical presentations according to gender identity and sexual practices.” People with suspected non-sexual transmission were much less likely to develop anal or genital lesions, but some did.
Monkeypox DNA was detected in all 14 women who had vaginal swabs collected, as was the case for 29 of the 32 men with semen samples in the earlier analysis. What’s more, about three quarters of anal/rectal swabs, oral swabs and blood samples tested positive. “This strengthens the likelihood of sexual transmission through bodily fluids as well as skin-to-skin contact,” according to the authors. Other studies suggest that monkeypox could potentially be transmitted in the absence of symptoms.
Most people with monkeypox recovered without incident, and no deaths were reported. However, 13% required hospitalisation, mostly for pain management, difficulty swallowing and bacterial superinfections. Hospitalisation rates were similar for HIV-positive and HIV-negative people. Two women were pregnant at the time of the report with no complications reported so far.
Trans women were about twice as likely as cis women to be treated with tecovirimat (TPOXX), 34% vs 16%, respectively. Only six people received monkeypox vaccination for post-exposure prophylaxis. Eight trans women and two cis women who acquired monkeypox reported that they had received pre-exposure vaccines during this outbreak.
This international case series “provides valuable insights into the clinical features of monkeypox in women,” said co-author Dr Boghuma Titanji of Emory University in Atlanta. “Importantly, it also highlights emerging areas of inequity which require our urgent and targeted attention…As the monkeypox outbreaks evolve, we must draw from these emerging lessons and have a more holistic approach to monkeypox in women. This will ensure that women are not left behind as they often are when addressing other diseases.”
Thornhill JP et al. Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series. The Lancet 2022.