Monkeypox: Causes, Symptoms, Diagnosis and Treatment

The worldwide outbreak of monkeypox has found the population with little information about this virus. Here we compile all the evidence on its origin, the symptoms it generates, the available treatment and the possibility of a vaccine.

Written and verified by the doctor Leonardo Biolatto.

Last update: 21 November, 2022

Monkeypox is the focus of current health news around the world. However, it isn’t a new disease. In fact, human cases have been reported since the 1970s.

The name may seem confusing and the information circulating about it also generates controversy. How is it transmitted between humans? Why did it go from being a pathology endemic to the Congo to generating outbreaks in Europe, America, and Australia?

Since the 1980s, cases of monkeypox have been multiplying. Slowly, but steadily. Scientific studies have been filling in some gaps about the causal virus, but there are still many questions.

In this article, we’ll explain what we know about the disease and the very latest evidence, in the context of an outbreak which the World Health Organization (WHO) is paying close attention to.

What is monkeypox and how did it originate?

Monkeypox in humans was first discovered in 1970. Patient zero was a child in the Democratic Republic of Congo who had smallpox-like vesicles, but who didn’t meet all the conditions to be declared a case of that already known disease.

However, the virus’ journey didn’t start there. In fact, the first scientific record of this Orthopoxvirus is in primates, through an outbreak in laboratory animals, recorded in 1958.

Antibodies against the viral agent were later isolated in rodents and in apes of various species with habitats in Africa. However, isolation of the virus as such, in vivo, was only obtained twice in the African forest. Therefore, we don’t know what or who the real reservoir is, i.e. where it finds a niche to survive and then causes outbreaks.

Therefore, it’s correct to say that we’re dealing with a zoonosis. These are diseases that are usually transmitted between certain animals, but are occasionally transmitted to humans and may (or may not) follow a subsequent inter-human transmission pathway.

This group of Orthopoxviruses is part of the Poxviridae family. So far, there are 4 species in this category that can infect humans:

• Smallpox virus: This is the classic agent known worldwide that had a period of intense spread and was then eradicated from several countries.
• Vaccinia virus: This is the virus that was used for the smallpox vaccine. It was precisely this huge worldwide vaccination campaign that led to the declaration of eradication in various geographical areas.
• Bovine smallpox virus: This is transmitted from rural animals, but its behavior is associated with captivity,  and human cases have also been reported from zoos and circuses.
• Monkeypox virus: The one we are currently dealing with.

Monkeypox virus transmission

Zoonotic transmission, i.e. from animals to humans, is the best documented transmission about this disease. And the reports we have come from Africa, where the viral agent was almost restricted for decades.

Although the name monkeypox suggests that non-human primates are mainly responsible for the transmission to our species, the truth is that research points to rodents. The consumption of rodents in rural homes, hunting to eradicate them as pests, and the handling of rats and squirrels seem to be the first point of contact for infection.

Thus, in rural areas of Africa, they have identified situations that make animal-to-human transmission more likely. For example, when people sleep on the ground. This is also the case if people eat wild animals (specifically, rodents).

Other evidence has ruled out factors that could be considered risk factors, but which, so far, are not, such as the following:

• Owning pets
• Coming into contact with the excrement of wild animals

Interhuman transmission

The current outbreak of monkeypox is due to interhuman transmission, since the distant geographical areas and the simultaneity of the cases practically rule out that they are all due to zoonotic reasons. This isn’t anything new, as, since its discovery, there have been reports of inter-human infections.

Perhaps the most striking thing now is the number of patients that make up the chain of transmission. Even with people in whom the chain itself can’t be defined; we don’t know how they could have become infected and all their close contacts have no symptoms.

In previous reports of outbreaks in the 1980s and 1990s, the chain of transmission reached, at most, 8 people. This means that no more than that number of close contacts since patient zero could be confirmed with a diagnosis.

This represents a very low attack rate when compared to other similar pathologies. Attack rate is a measure of epidemiology to determine what percentage of a patient’s closest contacts become infected by living or spending time together.

Seismic smallpox had attack rates of a maximum of 11%. Compared to classic smallpox, this is insignificant, as the latter has an attack rate of 80%.

Although close contact is assumed to be the route of transmission, the most specific known route is that inter-human transmission would come from the airborne and cutaneous routes, through respiratory droplets and skin-to-skin.

As with common smallpox, skin lesions and the fluids that are shed from them are contagious. The virus can travel through secretions to reach other objects and other humans.

The low attack rate and lack of information on the chain of transmission of the current outbreak don’t allow us to define more clearly the circumstances that make contagion effective. If it’s a common airborne route (like influenza), why aren’t more close contacts of confirmed patients becoming infected?

A particular issue being discussed in the current outbreak is sexual transmission. It seems to be a common factor among patients in whom the chain of infection has been established. But there’s no confirmation and some specialists don’t even consider it a possible route.

What are the symptoms of the disease?

The incubation period of monkeypox, i.e. the time from contact with the virus to the appearance of the first symptoms, ranges from 6 to 16 days. It’s not totally clear, but 2 weeks seems to be the average.

The classic cases begin with fever that may last from 1 to 4 days. It’s accompanied by the classic febrile symptoms, with headache, fatigue, myalgia, and somnolence.

Then the characteristic dermal outbreak begins. What has been described so far is a centrifugal presentation (starting on the trunk of the body and proceeding to the extremities) of macules (spots) and papules (skin elevations), together with vesicles (with fluid content) and pustules (with pus content) that evolve into crusts.

Inflammation of the lymph nodes is notorious in monkeypox. This distinguishes it from classic smallpox, which has almost no lymphadenopathy.

The severity is mild most of the time, but it can be fatal in a few cases (1% is the mortality rate in Africa). Severe cases are often complicated by vomiting and diarrhea, encephalitis, and pneumonia. Some of them reach sepsis and die from multi-organ failure.

There’s a reduction the patient’s immune response, which may favor superinfection with bacteria. This is one of the explanations for the fatal cases that reach sepsis.

There’s a particular situation in pregnant women, because they present a higher mortality and complication rate when infected with monkeypox. Likewise, some reports have confirmed that there’s vertical transmission, that is, from the mother to the fetus.

Identifying cases

Throughout history, from 1970 until now, there have been different definitions of suspected cases of monkeypox. This is done to identify patients and isolate them.

Each country establishes the warning signs that we should be aware of, and what characteristics the health systems should respond to. But, broadly speaking, it’s agreed that a person is suspected of having the disease when they have a fever and a vesicular rash, along with at least one of the following three symptoms:

1. A rash on the palms of the hands or soles of the feet.
2. Inflammation of the lymph nodes.
3. Episodes of elevated body temperature before the rash appears.

This is, of course, in addition to the investigation of who was with the suspected patient. If the person with these signs has been in close contact with someone who already has a confirmed diagnosis, then the chance of being positive increases.

How is the diagnosis confirmed?

The first step in the monkeypox diagnostic pathway begins with suspicion. These would be those suspected cases according to the definition we gave earlier.

These patients would have to be isolated and testing would have to begin to determine whether or not the pathology can be confirmed. This isn’t a quick fix, as it isn’t yet a viral agent that can be widely tested worldwide.

Several places have opted to request IgG and IgM immunoglobulin testing against Orthopoxvirus. It isn’t specific, but if the result is positive it allows confirmation to proceed, while awaiting more specific results that could take some time.

These specific tests depend on the availability at each health center:

1. Polymerase chain reaction (PCR)
2. Immunohistochemistry
3. Electron microscopy

These methods are only available in some centers that receive samples from other geographical areas. Therefore, delay is almost unavoidable and isolation of suspects should be applied while waiting.

Immunglobulins, PCR, and immunohistochemistry require a blood sample from the patient. Electron microscopy is used to make a visual analysis of secretions if secretions are collected to be sent to the laboratory.

What’s the treatment of monkeypox?

Monkeypox has no concrete and specific treatment. Like many viral pathologies, there’s no particular drug that can block or nullify the replication of the pathogen.

Therefore, what experts advocate is isolation with supportive measures. Some patients with mild cases don’t require any pharmacological approach. Others are severe enough to warrant testing with antivirals.

There’s insufficient evidence on the effectiveness of antivirals to reduce complications. They’re reserved for use at the discretion of the treating team in those who worsen or are at risk of death, that is, in 1% of those diagnosed.

Brincidofovir and tecovirimat are the names of two drugs that have been studied for the treatment of Orthopoxviruses. They have worked more in the field of classic smallpox, so today they represent the best option for the outbreak.

On the other hand, complications merit their own therapeutic scheme. Bacterial superinfections, which are common in severe cases, are treated with antibiotics specific to the microorganism that has been identified.

In pneumonias or encephalitis that appear as a complication during hospitalization, the medical team may decide to provide life support. This is achieved with assisted ventilation, if the patient’s condition warrants it. It isn’t much different from what’s done with similar conditions caused by other etiologies.

Discharging patients

There’s still discussion about when to discharge patients. Most recover satisfactorily and have no sequelae. But it’s the issue of inter-human transmission that determines the question of when to allow isolation to end.

In previous outbreaks, both in Africa and in some in the United States and the United Kingdom, discharge was proposed when the patients’ scabs disappeared. It’s assumed that, at that point, the person is no longer contagious. This is the case with classic smallpox.

However, some patients have been found to have positive PCR results in the respiratory tract up to 3 weeks after the scabs have disappeared. It isn’t confirmed whether this is synonymous with infectiousness.

Also from previous reports, we know that there are patients who have lymphadenopathy and skin rash again after sexual intercourse after they’ve been discharged. This raises suspicion of an entrenchment of the virus in the genital area, which could prolong transmission by that route long afterward.

Is there a vaccine?

The U.S. Food and Drug Administration (FDA) approved a vaccine called JYNNEOS in 2019. This immunization would be effective against both smallpox and monkeypox.

It hasn’t been decided that it should be available for mass marketing, although the indication for at-risk populations is being studied. People living in endemic areas, close contacts of confirmed cases, and workers with exposure to animals known to be reservoirs could be recipients.

The vaccination schedule here is two doses that should be one month apart. But we emphasize that there’s still no approval for its inclusion in official vaccination schedules or for application under the circumstances of this current outbreak.

However, the European Union countries are working on the legal issues to acquire doses and give them to close contacts, assuming that it could generate protection to stop the spread in exposed groups.

It’s known that those vaccinated with the classic smallpox vaccine have an advantage. The protection afforded by such immunization against monkeypox is estimated to be 85%, which is considered more than acceptable.

Indeed, part of the uniqueness of this current outbreak is due to the fact that there are fewer people vaccinated with smallpox due to the geographic areas that have been declared eradicated. This would have increased the sensitivity of populations to viruses of the same family.

The current outbreak: what we know

The current monkeypox outbreak is considered to have started on May 7, 2022, when the United Kingdom reported a case out of Africa. Despite this, some epidemiologists propose extending the period from 2021, when the United States reported a small number of cases on its territory.

From the beginning of May to the present, there are more than 250 confirmed cases outside Africa. This involves 16 countries.

It’s an unprecedented situation, especially with more than 100 suspects in isolation, awaiting confirmation. The World Health Organization has declared the outbreak, but specifies that it’s possible to control it. In addition to the fact that the risk for the general population is low.

In Spain there are 84 confirmed cases, Northern Ireland had its first positive patient on May 26, as did Wales. Australia registered the first case in Melbourne, in a person returning from the United Kingdom.

The Massachusetts case from Montreal triggered an intensive search for suspects in Canada, where 13 people were isolated. At the same time, the United States raised the alert recommendation for international travel, so that extreme precautions are taken to prevent inter-human transmission.

What can we do?

The prevention measures to avoid contracting monkeypox have to do with some general guidelines and with restrictions to be applied in specific circumstances. Among the former, we can mention the following:

• Frequent hand washing.
• Handle food of animal origin with maximum sanitation measures.
• Only purchase food products of animal origin in authorized places and establishments.
• When traveling, stay in places that are certified by health authorities and where the pest controls carried out in the rooms are clear.
• When visiting nature reserves, such as theme parks or zoos, don’t come into contact with animals and keep a safe distance from them.

Regarding particular restrictions, it should be emphasized that a contact in the last 14-21 days with sick people or the fact of having traveled to a geographical area with an outbreak, means that you should consult the health authorities. Isolation and screening with complementary methods should be carried out.

Self-isolation until consultation should be the rule for persons with these characteristics. Similarly, family members and cohabitants should follow the same procedure until there’s positive or negative confirmation.

It’s important not to panic. As the WHO has made clear, we aren’t in a pandemic situation yet and there’s no increased risk for the general population, so general hygiene measures, early identification of symptoms, and consultation in case of doubt are sufficient.