A Primer on Mpox

One of Shakespeare’s most memorable (and lasting) lines from “Romeo and Juliet” is “A plague o’ both your houses.” While his cleverly dismissive insult is still remembered more than 420 years after the play’s premiere, these days that line is more likely to be misquoted as “a pox on both your houses” ­— speaking to the fact that while the word “plague” has lost much of its power to convey fear, “pox” has not.

That etymological development may be due to the fact that bubonic plague is curable and we haven’t had a major outbreak in more than a century (the United States has an average of only seven cases per year), whereas the equally deadly smallpox wasn’t eradicated until 1977.¹ And chickenpox, while unrelated to smallpox and generally a much milder and less dangerous disease, remained a common childhood ailment until introduction of a vaccine just 35 years ago. The idea of a “pox” became more alarming than a “plague.”

Thus, when outbreaks of monkeypox were reported in various places around the world beginning a couple of years ago, yet another generation of English speakers was reminded that a “pox” is nothing you want wished upon your house.

What Is Monkeypox (Mpox)?

Mpox is an infectious disease caused by the monkeypox virus.² However, the term “monkeypox” is being phased out and replaced with the term “mpox” upon a recommendation by the World Health Organization (WHO).³

The current outbreak in the United States has infected just more than 30,000 people in this country as of this writing.⁴ Another 57,000 cases have been reported around the world during the past year, ranging from Brazil (more than 10,000) to Spain (7,500), Great Britain (3,700) to Germany (3,700). Other nations that have reported lower case numbers range from Australia to Japan, Iceland to South Africa. Overall, cases have been reported in more than 110 nations — with close to 100 of them reporting mpox for the first time.

Still, in the past few years, with more than 87,000 cases worldwide, there have been fewer than 120 deaths — and many of those who died had other underlying health conditions such as a weakened immune system, so mpox is clearly a far less virulent disease than smallpox.

The mpox virus is a member of the Orthopoxvirus genus, which also includes the viruses that cause cowpox and smallpox in humans. It was first described and isolated in 1958 by Preben von Magnus, MD, who noticed an outbreak of a skin infection among cynomolgus macaques (a type of long-tailed monkey) in a research laboratory in Copenhagen.⁶

The first time a human case was documented was in 1970 in a 9-year-old patient who lived in what is now the Democratic Republic of Congo. Since the patient lived in an area where there had not been any cases of smallpox for more than nine months, researchers conducted additional tests and eventually discovered the patient had mpox, not smallpox.⁷

There are two known strains, or variants, of mpox: Clade I and Clade II. Clade I is found primarily in the Congo Basin in Central Africa. Clade II was originally found in West Africa. Clade II has two subvariants, Clade IIa and Clade IIb. Clade IIb is the variant that has mostly been found outside of Africa.⁸

Symptoms, Diagnosis and Treatment

As with cowpox and smallpox, mpox symptoms include a distinctive rash (pox) that progresses from small, flat spots to pus-filled lesions that eventually dry out and fall off. The lesions appear in a pattern that generally includes the face, arms and legs.

After an incubation period of one to two weeks,⁹ initial symptoms will appear prior to the appearance of skin lesions and will generally include fever, severe headache, muscle pain and heavy fatigue, along with swollen lymph nodes.²

Patients are contagious throughout the time they have symptoms and should isolate as much as possible during that time. Recent research suggests patients may begin shedding viruses even before symptoms occur.¹⁰

In rare cases, the virus will travel through the body to the genitals, eyes (causing vision issues or even blindness) or lungs (which can lead to pneumonia). If it spreads to the brain, it can cause encephalitis.

Diagnosis is generally made by polymerase chain reaction from a sample taken from an active skin lesion. The sample is sent to a qualified laboratory in a cold, dry tube.¹⁰ It is important to note that WHO notes that antigen and antibody tests cannot differentiate between mpox and other orthopoxviruses.

While the disease can, in rare cases, prove deadly (about a 1 percent mortality rate for the mpox variant, Clade II, found most often in the United States⁴), most patients will recover on their own in two to four weeks. Antiviral medications can be used in severe cases. Otherwise, treatment is generally targeted to control the symptoms of fever and pain.¹¹

Although fatalities have been rare in the United States, the mortality rate has run as high as 10 percent for those who contract the variant Clade I found most often in Central Africa, where mpox is thought to have originated and where it is now endemic.¹²

Other serious side effects can include severe facial or other scarring (from heavy lesions or scratching of lesions) and secondary bacterial infections from scratching of lesions.¹¹

How Is Mpox Transmitted?

Much is still not known about mpox, including its natural reservoir and the most common modes of transmission. It is thought that mpox rates have been increasing in the past few years due to the cessation of the smallpox vaccines after the successful extermination of smallpox. It is known that at least some of the types of smallpox vaccine also conferred mpox immunity, since the two viruses are so closely related.⁷

Zoonotic transmission (transmission between species) likely occurs from exposure to infected animals (including scratches and bites, or airborne droplets from their breath), cuddling with infected pets or from eating infected meat that is not properly cooked.² While the original host of mpox is not yet known, numerous species of rodents have been found with the mpox virus, leading researchers to identify them as the likely natural reservoir. (One of the earliest human outbreaks in the United States involved pet prairie dogs that were temporarily housed next to a shipment of Gambian pouched rats being imported from West Africa in 2003.¹³)

Human-to-human transmission is thought to be rare, but it is been increasingly documented. Researchers are unsure whether this represents a mutation in the virus’ gene, or if it is simply the result of more opportunity due to greater numbers of infected patients contracting mpox from animals. Human-to-human transmission is most likely accomplished in some of the same ways people get it from animals: touching an infected lesion or breathing in microscopic droplets from someone who has mpox in the lungs. Mpox can also spread through exposure to contaminated bedding or clothing and, increasingly, via unprotected sex.¹¹ Pregnant women can transmit mpox to their unborn child, as well as after birth by cuddling with the baby.

Prevention

As noted above, several existing smallpox vaccines can help prevent mpox as well, including the ACAM2000 and Jynneos vaccines. Healthcare workers treating mpox patients or lab workers handling suspected mpox samples may consider receiving one of these vaccines. In addition, the Centers for Disease Control and Prevention recommends a vaccine for immunocompromised patients, as well as those who engage in certain types of risky sexual activity.¹⁴

For those who lack access to a vaccine, prevention comes down to basic precautions:

• Avoiding physical contact with anyone who displays symptoms of mpox
• Avoiding handling bedding or clothing of anyone who has had mpox (or bedding or toys of an infected animal)
• If contact is accidentally made, or unavoidable, washing hands with hot water and soap immediately after
• Self-isolating from an infected family member or roommate until symptoms have cleared

Research

Because existing smallpox vaccines already confer protection against mpox, and because most cases of Clade II mpox are fairly mild, there is relatively little research going on into mpox at this time. A search for both “monkeypox” and “mpox” on the U.S. Food and Drug Administration’s Clinical Trials website (clinicaltrials.gov) revealed fewer than three dozen current or recent trials.

One study being jointly conducted by the University of California, San Diego, George Washington University and Emory University is looking at whether the dose of one of the existing vaccines (MVA-BN) can be reduced and still confer protection.

Other studies are looking at whether administering a smallpox vaccine after exposure to mpox can still help the body fight off infection, or perhaps reduce the severity of symptoms. And, still other studies are looking at the efficacy of existing antiviral drugs in lowering the severity of an mpox infection.

Looking Ahead

Because homo sapiens were the one and only reservoir for smallpox, eradicating smallpox was scientifically straightforward — if financially expensive and politically challenging. But once the last human being with smallpox was inoculated, there was nowhere else for the smallpox virus to live. But mpox is zoonotic, living in the tissue of unknown numbers of species of wild animals, so eradicating it is impossible with current technology.

Widespread inoculation — particularly against the more lethal Clade I variant — may be the best hope of reducing deaths due to mpox. Treatment of symptoms, including reducing pain and itching of the lesions, can help reduce scarring, as well as decrease the chances of a secondary infection. Those diagnosed with the Clade I variant might be candidates for antivirals to reduce the severity of the infection.

It is likely that mpox remained a largely local disease in Africa due to the lack of modern transportation infrastructure in that part of the world. Now that modern road, air, rail and sea travel are bringing those once-remote areas more fully into the global community, we are seeing mpox showing up in more than 100 nations. With mpox having been diagnosed everywhere from Iowa to Los Angeles in the United States, physicians in every community will need to be familiar with the symptoms and be ready to diagnose and treat mpox for the foreseeable future.