An outbreak of monkeypox in Canada and other countries

• Until now, high-income countries have not observed outbreaks of monkeypox unrelated to travel
• There are recent confirmed cases of monkeypox in people in Canada and other high-income countries; most cases appear to be relatively mild
• People who develop a rash and other related symptoms should contact a healthcare provider

Monkeypox is a virus that is related to another virus called smallpox. From time to time, documented outbreaks of monkeypox have occurred in Nigeria and the Democratic Republic of the Congo since 1970. Cases of monkeypox in North America and Western Europe have traditionally been rare, mostly affecting people who have travelled to regions where monkeypox occurs. About 20 years ago in the U.S., some cases of monkeypox also occurred in people who came into contact with prairie dogs sold as pets, which had previously been warehoused with small mammals from endemic regions, where community transmission of monkeypox occurs on an ongoing basis. None of the people in that outbreak died as a result of monkeypox.

In mid-May 2022, an outbreak of monkeypox in people with no history of travel to endemic regions was first reported in the U.K., then in Europe. Subsequent cases were also reported in Canada, the U.S. and other countries. Many of these cases are in gay, bisexual and other men who have sex with men (MSM). In the current outbreak, most of the cases are mild. After affected people are seen by medical personnel, public health authorities in these countries have encouraged many monkeypox patients to stay at home until they have recovered. In some cases, people have been hospitalized. The outbreak is ongoing and public health authorities are assessing the situation and providing advice in affected cities and regions.

In this CATIE News bulletin, we summarize key information on monkeypox. This information is not comprehensive. Furthermore, note that the current outbreak is evolving and information can change. We encourage readers to stay abreast of developments by consulting public health websites in their city or region for further information.

What is monkeypox?

Monkeypox is the name of a disease caused by a germ called monkeypox virus. This virus is related to smallpox. Monkeypox virus was first isolated in 1958 in a colony of monkeys shipped to Denmark from East Asia.

Monkeypox was first documented in humans with a child in the Democratic Republic of the Congo in 1970. From time to time, monkeypox has also been reported in some people in parts of West Africa, mostly in Nigeria.

Scientists are not certain which animals are natural hosts for monkeypox virus, but the virus is likely to be in rodents and monkeys.

There are two main strains of monkeypox virus—one from Central Africa and another from West Africa. In the current outbreak that is affecting North America, Europe and other high-income regions, the strain of monkeypox virus in circulation appears to be one that is closely related to the strain in West Africa. This strain tends to cause relatively mild illness.

Why has monkeypox become an emerging issue in the 21st century?

As monkeypox virus is related to smallpox virus, vaccination against smallpox very likely provided a high degree of protection from monkeypox. The smallpox vaccination campaign carried out by the World Health Organization (WHO) in the 1960s and 1970s was so successful that by 1980, the WHO considered smallpox to be eradicated. Small samples of smallpox virus are now kept in a limited number of research facilities.

Several teams of scientists have suggested that once smallpox vaccination campaigns ended in the late 1970s, people living in regions where animals harboured monkeypox virus gradually became more susceptible to monkeypox. Research suggests that, at first, children in these regions were more likely to get monkeypox than adults. However, over the past 40 years, the average age of people who have developed monkeypox has increased in endemic regions, and now adults are also susceptible.

Factors such as hunting wild animals, deforestation (which can put people into closer proximity with wild animals) and climate change may also have contributed to the expansion of cases of monkeypox in endemic regions over the past 40 years.

Transmission of monkeypox virus and related issues

Here is some key information from the U.S. Centers for Disease Control and Prevention (CDC) on the spread of monkeypox virus: “Human-to-human transmission is thought to occur primarily through large respiratory droplets. Respiratory droplets generally cannot travel more than a few feet, so prolonged face-to-face contact is required. Other human-to-human methods of transmission include direct contact with body fluids or lesion material, and indirect contact with lesion material, such as through contaminated clothing or linens.”

The scenarios above are the most common ways that monkeypox virus has traditionally been transmitted.

The current outbreak has disproportionally affected men who have sex with men. As a result, it is possible that in addition to the ways described above, monkeypox virus is transmitted during sex among some of these men. That monkeypox virus may also be transmitted sexually is not a new idea. In an outbreak that occurred several years ago in Nigeria, researchers suspected that monkeypox virus was, in some cases, sexually transmitted due to oral and genital lesions in affected patients (both men and women were affected by monkeypox in that outbreak). This does not make monkeypox virus a sexually transmitted infection. Note that it is common for some viruses to have multiple ways of being spread.

What’s more, although many of the people with monkeypox in the current outbreak are MSM, anyone can acquire monkeypox virus from close contact with an infected person.

Since monkeypox is an understudied illness, public health researchers and scientists have much work ahead to find out the precise ways in which monkeypox virus can be transmitted among people in high-income countries. As with any emerging disease, this may take time, and patience is required as people with monkeypox are interviewed and their samples analysed. As more information becomes available, public health authorities in affected regions will provide advice about reducing the risk of acquiring monkeypox virus. As we wait for this information and advice, it is important to remain calm and focus on prevention and control efforts that are rational, effective and appropriate. Outbreaks of viral diseases occur all of the time around the world. In the recent past there have been much larger outbreaks of monkeypox in parts of West Africa. However, this has not garnered much media attention in high-income countries.

Symptoms of monkeypox

Typically, the course of monkeypox virus–related illness can last up to a month. According to the Public Health Agency of Canada (PHAC), monkeypox “symptoms occur in two stages and typically last from two to four weeks.”

The symptoms of monkeypox virus infection usually begin within a week or two following infection. However, in some people, initial symptoms can take up to three weeks after exposure to occur, such as:

• fever
• chills
• headache
• muscle pain/soreness
• tiredness or lack of energy
• backache
• swollen lymph nodes

Some people also develop a sore throat and cough.

Once these symptoms occur, a rash appears (usually within several days). However, there are reports from some people who developed monkeypox in past outbreaks that they developed a rash before other symptoms.

Rash and lesions

The rash tends to first appear on the face, then spreads to other areas of the body, including the arms and legs, and then eventually to the soles of the feet and palms of the hands. Lesions develop on the skin where the rash is located, and they can also sometimes occur in the mouth. The lesions are initially flat but over the course of days become rounded and raised. A few more days later the lesions become filled with a clear fluid, which subsequently turns cloudy. The lesions then develop a depression in their centre, and in this phase of development they are called pustules. Over the course of a week, the pustules begin to form a crust and then scabs. The scabs are present for a week and then fall off.

In areas where the scabs have fallen off, the affected skin may be lighter or darker than the surrounding skin.

Once all the scabs have fallen off, a person is no longer contagious.

The initial symptoms of monkeypox can be similar to other infections, such as chickenpox, herpes or even syphilis. This is why if a rash develops, affected people, particularly MSM, should call their doctor to ask for help diagnosing their condition. If they do not have a doctor, they should contact their regional telehealth service or public health clinic for advice and assessment.

So far, the majority of people who have developed monkeypox in the current outbreak have mild illness. 

Supportive care

Many people who have developed monkeypox in the present outbreak can recover at home under medical supervision. They are given advice about keeping lesions clean, use of over-the-counter pain relief medicine and other measures. Public health authorities also advise them how to minimize the risk of passing on monkeypox virus.

Some people with monkeypox can develop lesions in their mouth, tongue or throat or experience a sore throat. These issues can make eating and drinking painful. It is important to remember to eat sufficient food and drink enough water.

People with monkeypox should wash their hands frequently and should avoid touching their eyes, as monkeypox virus can be transferred from a lesion to the eyes, causing inflammation. The consequences of such inflammation in people with monkeypox are not clear. Serious eye complications occurred in about 5% to 9% of people with the related condition smallpox.

Monkeypox and vulnerable populations

The impact of monkeypox virus on the health of the following vulnerable populations has not been well studied:

• children
• pregnant people
• people with chronic liver disease
• people with chronic kidney disease
• people with HIV
• people taking medicines that weaken their immune system (such as people with rheumatoid arthritis, Crohn’s disease, colitis, severe eczema or psoriasis, or people who have a transplanted organ)

Monkeypox virus and HIV

Limited information exists about monkeypox and HIV. Researchers in Nigeria conducted a study whereby they reviewed information from an outbreak of monkeypox virus that occurred in that country in 2017 and 2018. The researchers focused on 40 people who were hospitalized with monkeypox, nine of whom had HIV. Data were unavailable about many aspects of HIV treatment (ART), lab test results and medical history for these people. However, the very limited information provided suggests that most people with HIV had some degree of immune deficiency, with CD4+ cell counts (when available) generally being below 360 cells/mm3 (in some people cell counts were very low—between 20 and 100 cells/mm3). Four people were newly diagnosed with HIV and unlikely to be on ART in this study.

The researchers found that compared to people without HIV, people with HIV were more likely to have the following:

• a longer duration of illness – 28 days or more
• larger rash
• genital ulcers
• bacterial infection, which can arise from infected lesions on the skin and perhaps other complications

Five people died, two of whom were HIV positive. The causes of death among the people with HIV were as follows:

• A 42-year-old man developed an extreme inflammatory reaction to possible bacterial infection and died 37 days after he was hospitalized. His CD4+ count and other medical history was not disclosed.
• A 43-year-old man with less than 20 CD4+ cells/mm3 (indicating extreme immune deficiency) developed seizures; doctors think that this likely occurred because a germ infected his brain (the nature of the germ was not mentioned).

Among HIV-negative people, the causes of death were as follows:

• A 28-day-old baby died from complications of pneumonia and a brain infection (the nature of the germ that caused brain infection was not mentioned).
• A 27-year-old man who died from complications of pneumonia and an extreme inflammatory reaction.
• A 34-year-old man died from self-harm.

The report from Nigeria relied on data captured in the past for one reason and then subsequently reanalysed several years later for another reason. Such study designs are prone to cause researchers to arrive at inadvertently biased conclusions when interpreting the data. At this time, it appears to be the largest publicly available dataset on people with HIV and monkeypox, although it is important to note that this very small sample is not representative of most people living with HIV.

In Canada and other high-income countries, the majority of people with HIV are taking ART, have a suppressed viral load in their blood and are in relatively good health. Therefore, the results that were reported with nine people with HIV in the Nigerian outbreak (most of whom were not on ART) may not be relevant to many people with HIV in Canada. Still, people with HIV (like everyone else) should call their doctor should a rash and other symptoms associated with monkeypox occur so that their condition can be investigated.

Mental health and monkeypox

The same researchers in Nigeria stated that patients (regardless of HIV status) reported that they were most distressed by the following:

• disfigurement arising from many lesions on the body
• itchy skin
• pain from some lesions
• genital lesions

The doctors also stated that almost 30% of patients “developed symptoms of anxiety and depression during [hospital] admission, requiring psychological counselling.”

Mental health is another understudied aspect of monkeypox virus outbreaks. Hopefully, doctors and nurses caring for patients in the current outbreak will be alert for any issues affecting mental and emotional health, and will intervene if necessary.

Monkeypox virus vs. COVID-19

Learning about the sudden spread of a new virus that can cause illness is always scary, particularly in light of the past two years of the COVID-19 pandemic. Some people understandably are concerned that the arrival of monkeypox virus in countries that had never had outbreaks may lead to a potential epidemic. However, the spread of monkeypox virus is unlikely to turn into an epidemic or global pandemic for at least the following reasons:

Scientists have developed a generally safe and effective vaccine (mentioned later).

At least one antiviral drug with the potential to treat monkeypox has been created and approved by regulatory authorities in some countries (mentioned later).

Monkeypox does not spread as easily as SARS-CoV-2, the virus that causes COVID-19.

When SARS-CoV-2 first appeared in the city of Wuhan in late 2019, it was a new virus with unknown potential for causing disease. There were no antiviral drugs available that worked against it and no vaccine. In contrast, monkeypox virus has been studied for decades, and because of the vaccine and drugs mentioned below, the world has a head start against this virus. Furthermore, so far monkeypox virus generally causes mild illness.

All of these are reasons to not panic about the arrival of monkeypox. However, it is important to remain vigilant. Contact a healthcare provider should a rash occur in association with the symptoms previously mentioned.

Biomedical prevention and possible treatment

Thanks to widespread vaccination in the past, smallpox was declared eradicated by the WHO in 1980. After that time, routine vaccination against smallpox virus was discontinued. As smallpox virus is closely related to monkeypox virus, vaccines and antiviral drugs developed for the prevention and treatment of smallpox are likely to be effective against monkeypox.

Note that in the current outbreak most cases of illness caused by monkeypox virus have been relatively mild and people recover without the need for serious intervention.

Vaccination

A third-generation vaccine against smallpox was developed in the 21st century. This vaccine is approved in Canada, the U.S., the U.K. and Europe. It is known by the following names in different places:

• Canada – Imvamune
• Europe – Imvanex
• U.S. – Jynneos

The vaccine has been tested in more than 4,000 healthy adults; it was generally safe and boosted immunity to smallpox (and by extension, monkeypox). It was also found to be safe in elderly people. It is approved for the prevention of smallpox (and in some countries, such as Canada, also monkeypox) in adults. Research suggests that this vaccine will provide about 85% protection against monkeypox.

Imvamune has also been tested in nearly 700 people with HIV who had CD4+ cell counts of 100 or more and has been found safe. The levels of antibodies produced by vaccination were similar in people with and without HIV.

The vaccine is injected just under the skin in the upper arm, and is given in two doses, four weeks apart. It does not contain smallpox or monkeypox viruses and cannot cause these infections.

Imvamune is not readily available in pharmacies. However, some governments are securing supplies of this vaccine for use by healthcare workers and contacts of people with monkeypox. Public health authorities in your city or region will decide if deployment of the vaccine becomes necessary and which populations will get access.

Selected antiviral drugs and their potential against monkeypox virus

As routine vaccination against smallpox virus ceased more than 40 years ago when smallpox virus was eradicated, most people born since that time have no immunity to smallpox virus. Stocks of smallpox virus are kept in a couple of laboratories.

In the past, researchers estimated that smallpox killed about 30% of people who became infected. If this germ were reintroduced as a bioweapon, there would be potential for much for loss of life and catastrophic disruption to society. As a precaution against such an occurrence, governments encouraged the development of new vaccines and potential antiviral drugs against smallpox virus. As it would be unethical to infect people with smallpox or monkeypox viruses to test the effectiveness of antiviral drugs, these drugs were only tested in animals infected with monkeypox virus.

It is upon this basis — animal experiments — that regulatory authorities have approved brincidofovir in the U.S. and tecovirimat in Canada, the U.S. and other countries (details about these drugs appear later).

As these drugs have not been tested in large human clinical trials, it is not known if one antiviral drug by itself is adequate or whether combinations of antiviral drugs might be needed to treat monkeypox in people. The potential advantage of combination therapy is that it will likely be harder for monkeypox virus to become resistant than if one drug alone were used. The disadvantage is that there may be increased potential for side effects. Should cases of monkeypox continue to increase over the long term, or should the current strain of monkeypox virus mutate, clinical trials of antiviral drugs may become necessary to explore their effectiveness. However, since most cases of monkeypox associated with the present outbreak are mild, the need for antiviral therapy does not appear to be urgent.

Here is some background information about antiviral drugs mentioned in the media as having potential to be used against monkeypox virus in people:

• Tecovirimat (Tpoxx) – This antiviral drug was developed for the treatment of smallpox. In a clinical trial in healthy people, it was generally safe. In studies with animals, if given within a few days after infection with monkeypox virus, the drug can prevent serious disease from developing. The capsule formulation of tecovirimat is approved in Canada and the European Union, the U.S. and some other countries but not available in pharmacies. A liquid formulation of tecovirimat for intravenous use is approved in the U.S.
• Brincidofovir – A capsule formulation of this antiviral drug is approved in the U.S. and E.U. for the treatment of smallpox, but not in Canada. Once inside the body, brincidofovir is converted into cidofovir and allows for a higher concentration of cidofovir inside cells than in the blood. This distribution inside cells reduces the potential for brincidofovir to cause kidney injury. In the most recent published experiments, brincidofovir by itself had modest antiviral activity against severe monkeypox virus infection in prairie dogs. When brincidofovir was given to animals one day after exposure to the virus, 29% survived compared to 14% given placebo. Experiments with animals could be done to find out if the combination of brincidofovir + tecovirimat is safe and has better antiviral effect than either drug alone. Brincidofovir has been tested in a randomized, placebo-controlled clinical trial with 452 people undergoing a bone marrow transplant (none of whom had monkeypox virus). This study aimed to reduce the impact of CMV (cytomegalovirus) reactivation, a common side-effect of immunosuppressant transplant drugs. In this study, a greater proportion of people who received brincidofovir died (16%) than did people on placebo (5%). The use of brincidofovir was associated with an increased risk for diarrhea, nausea and vomiting.
• Cidofovir – This drug is approved in Canada and many other high-income countries for the prevention and treatment of a sight-threatening complication caused by cytomegalovirus (CMV). Today other drugs, such as letermovir or valganciclovir, are routinely used for CMV treatment or suppression. Cidofovir also has antiviral activity in experiments with animals infected with monkeypox and related viruses. Before the widespread availability of ART, cidofovir was used to successfully treat molluscum contagiosum virus infection in some people with HIV. Molluscum contagiosum virus is a member of the pox virus family and can cause small nodules in the skin of immune-suppressed people. Cidofovir is administered via intravenous infusion and has the potential to cause kidney injury.

—Sean R. Hosein

Resources

Public Health Agency of Canada information on monkeypox:

• Outbreak updates
• Symptoms and Management
• Risks
• Interim guidance on infection prevention and control for suspect, probable or confirmed monkeypox within healthcare settings

Monkeypox – Centers for Disease Control and Prevention

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