A review of cases of monkeypox from Canada and other countries

An outbreak of monkeypox continues to affect North America, Europe and other regions
Researchers analysed data from 528 patients and found that monkeypox caused a variety of symptoms
Painful anal, genital and oral lesions were a relatively common symptom

In late July, the Director General of the World Health Organization declared the escalating global monkeypox outbreak a Public Health Emergency of International Concern (PHEIC). A striking feature of this outbreak is that the vast majority of affected people in North America and Europe are gay, bisexual and other men who have sex with men (MSM).

Some men who develop monkeypox in the current outbreak have reported very painful ulcers on the genitals, on or in the anus/rectum, and in the mouth and/or throat. Fatalities so far have been very rare.

In this CATIE News bulletin, we review data collected from cases mainly in Canada, the U.S. and Europe.

Study details

Researchers analysed data on 528 cases of monkeypox from 43 clinics; all of the cases were in men. The men were diagnosed with monkeypox between April 27 and June 24, 2022. All of them were confirmed to have monkeypox through PCR (polymerase chain reaction) tests, which seek the genetic material of monkeypox virus in fluid samples and, if it’s found, confirm this viral infection. None of the men had been vaccinated against smallpox/monkeypox in the current era. About 9% of the men had been vaccinated against smallpox during childhood.

A brief average profile of the men is as follows:

98% were gay or bisexual
age – 38 years
HIV status – 41% were HIV positive
57% had used HIV pre-exposure prophylaxis (PrEP) in the month before they developed monkeypox

Lesions and other symptoms

At the time they sought care, nearly all the men (95%) had skin lesions. Commonly affected body parts were:

anus and genitals – 73%
arms, legs or torso – 55%
face – 25%
palms of hands and soles of feet – 10%

We will return to the issue of monkeypox lesions later in this bulletin.

Other symptoms noted by doctors included the following:

fever – 62%
persistently swollen lymph nodes – 56%
lethargy or exhaustion – 41%
muscle pain or soreness – 31%
“low mood” – 10%

HIV

A total of 218 people (41%) with monkeypox also had HIV. About 96% of them were on HIV treatment (ART). As a result, their CD4+ counts were relatively high (700 cells/mm³) and most of them had a suppressed viral load (less than 50 copies/mL). Symptoms of monkeypox did not appear to be worse in people with HIV compared to people without HIV. Three people became aware of their HIV infection status as a result of testing during evaluation for monkeypox.

Sexually transmitted infections (STIs)

Among 377 people with monkeypox who were screened for STIs, nearly 30% were found to have the following STIs (in decreasing frequency):

gonorrhoea
chlamydia
syphilis
herpes
lymphogranuloma venereum (LGV)
a combination of chlamydia and gonorrhoea

Monkeypox skin lesions

Prior to the current outbreak, the rash typically associated with monkeypox first appeared as small flat red areas on the skin, usually affecting the face, hands and legs—rarely the anus and genitals. Subsequently, these areas with rash would simultaneously become raised and a few days later lesions would form. Eventually the lesions would become softer and ooze fluid. After this stage, they would harden and form scabs. Several days later the scabs would fall off, leaving a scar, and the person would be considered recovered from monkeypox. Overall, the lesions would evolve at the same rate in the same person.

However, in the current outbreak, reports have suggested that skin lesions do not evolve at the same rate. In the present study, at the time people sought care, 95% of them had skin lesions. Researchers found that many patients had skin lesions at different stages of evolution. They also found that at the time patients sought care, blisters from monkeypox had formed on their skin.

The researchers stated that “the number of lesions varied widely with most people having less than 10 lesions.” They also stated that “a total of 54 persons presented with only a single genital ulcer, which highlights the potential for misdiagnosis as a different STI.”

Anal and rectal issues

In 61 people, anal/rectal issues, such as the following, were the reason they sought medical care:

pain in the anus or rectum
inflammation of the rectum
painful defecation
diarrhea

Some people had a combination of these symptoms.

Mouth and throat issues

A total of 26 people sought care because of initial symptoms that affected their mouth and/or throat, such as the following:

sore throat
pain while swallowing
lesions in the mouth or throat
difficulty breathing

Serious complications

There were two types of complications arising from monkeypox that researchers graded as “serious”:

Epiglottis

One person with HIV and a CD4+ count below the 200 cell/mm³ mark (indicating severe immunodeficiency) developed inflammation of the flap of tissue that covers the opening of the windpipe (epiglottis). This tissue prevents liquid and food from entering the lungs. When the tissue becomes inflamed, people can encounter pain upon swallowing or develop difficulty breathing. This can lead to life-threatening complications. The affected patient was treated with the antiviral drug tecovirimat and subsequently fully recovered from monkeypox (and complications).

Myocarditis

The heart is a muscular pump, and when it becomes inflamed it has a harder time pumping blood. Two people in the study developed heart inflammation (myocarditis), which can cause symptoms such as the following:

chest pain
shortness of breath
abnormal heart rhythms

In severe cases of myocarditis, excessive clotting of the blood can occur, leading to a stroke or heart attack.

One of the people with myocarditis had HIV and a CD4+ count of 800 cells/mm³. The other person with myocarditis did not have HIV. Fortunately, in these two people, myocarditis resolved within a week of onset.

Hospitalization

Seventy people (13%) required hospitalization. The main reasons for hospitalization (in decreasing frequency) were as follows:

severe pain (mostly affecting the anus and/or rectum)
treatment of bacterial infections of the skin
severe throat inflammation that caused people to stop drinking fluids and/or eating
treatment of eye lesions
kidney injury
heart inflammation

Another reason for hospitalization was that some people were not able to isolate at home.

All of the patients in this report, whether hospitalized or not, eventually recovered from monkeypox.

Transmission

Doctors involved in caring for patients whose data were used in this study suspected that monkeypox virus was sexually transmitted in 95% of cases. This is a significant departure from previous outbreaks of monkeypox, in which non-sexual contact was the presumed mode of transmission.

The study researchers stated: “The strong likelihood of sexual transmission was supported by the findings of primary genital, anal and oral mucosal lesions, which may represent the inoculation site.” This means that the first monkeypox lesion that many people developed was inside the body, likely around the place where monkeypox virus first entered the body. This would explain the cases of lesions in or on the genitals, anus/rectum and mouth/throat.

In 32 men, semen samples were analysed with PCR and were found to contain the genetic material of monkeypox virus. By itself, this finding does not indicate whether the virus could cause infection via exposure to semen. Additional studies are needed with people at different stages of monkeypox to better understand their potential for transmission.

Bear in mind

Historically, in reports from countries where monkeypox outbreaks occurred (the Democratic Republic of Congo and Nigeria) as well as from isolated cases (travellers from those countries), monkeypox was not commonly associated with anal, genital or oral lesions. The present report underscores the new presentation of monkeypox in the current outbreak among MSM. Among MSM, monkeypox virus appears to be sexually transmitted. Anyone can get monkeypox regardless of sexual orientation and it can also be spread through skin-to-skin contact. However, the location of the first monkeypox lesion in many men in this study suggests that the virus was sexually transmitted.

Not all participants had anal, genital or oral lesions, at least initially. The researchers made the following statement: “Solitary genital skin lesions and lesions involving the palms and soles may easily lead to misdiagnosis as syphilis and other STIs, which may in turn delay detection. Concomitant laboratory-confirmed STIs were also reported in 29% of the persons tested. Consequently, we recommend consideration of monkeypox in at-risk persons presenting with traditional STI symptoms.”

Although monkeypox can cause painful and debilitating symptoms in some people, the researchers stated: “Most cases were mild and self-limited, and there were no deaths. Although 13% of the persons were admitted to a hospital, no serious complications were reported in the majority of those admitted.”

Monkeypox is a new illness for the vast majority of healthcare providers in Canada and other high-income countries. There is much about the virus that is unknown and it may take additional months or years to understand. This lack of knowledge has occurred because monkeypox was a neglected disease.

For the future

The researchers stated the following important points:

“Healthcare professionals need to be educated to recognize and manage cases of monkeypox.”
“Targeted health promotion that sensitively supports enhanced testing and education in populations at risk is needed. Involving communities from the outset in shaping the implementation of public health interventions is essential to ensure that they are appropriate and non-stigmatizing and to avoid messaging that will drive the outbreak underground.”
“The duration of potential infectious viral shedding after lesions have cleared remains unclear. [Public Health authorities in the UK] have advised condom use for eight weeks after infection, but the potential duration and infectiousness of viral shedding in semen requires study.”
“The potential role of vaccines in pre-exposure prophylaxis requires study.”
“Although the current outbreak is disproportionately affecting gay, bisexual and other MSM, monkeypox is no more a ‘gay disease’ than it is an ‘African disease.’ It can affect anyone. We identified nine heterosexual men with monkeypox. We urge vigilance when examining unusual acute rashes in any person, especially when rashes are combined with systemic symptoms, to avoid missing diagnoses in heterosexual persons.”

—Sean R. Hosein

Resources

Monkeypox: How it spreads, prevention and risks – Government of Canada

What you need to know about monkeypox in Montreal – Santé Montreal

Monkeypox – B.C. Centre for Disease Control (BCCDC)

Monkeypox – U.S. Centers for Disease Control and Prevention (CDC)

REFERENCES:

Thornhill JP, Barkati S, Walmsley S, et al. Monkeypox virus infection in humans across 16 countries – April-June 2022. New England Journal of Medicine. 2022; in press.
Sukhdeo SS, Aldhaheri K, Lam PW, et al. A case of human monkeypox in Canada. CMAJ. 2022 Aug 2;194(29):E1031-E1035.