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Smallpox, Chickenpox, Mpox: Understanding the Differences

The recent emergence of mpox has brought about confusion about the differences between the three viral infections.

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- Mpox has recently been declared a public health emergency by multiple different organizations. This spread of the disease has brought about much confusion about if and how the disorders are related, how to treat them, and how to prevent their further spread. Understanding the differences between the disease can help determine the best course of action and improve overall public health.

Smallpox

The WHO defines smallpox as “an acute contagious disease caused by the variola virus, a member of the orthopoxvirus family.” Although smallpox was first documented in ancient Egyptian mummies, it is suspected that the disease has been around for a minimum of 3,000 years.

History of Smallpox

The CDC provides a brief overview of the historical spread of smallpox: In the sixth century, it is thought that trade led to the introduction of smallpox in Japan, and it wasn’t until the seventeenth century that European settlers brought smallpox to North America.

According to the CDC, in the United States, the last smallpox outbreak occurred in 1949. However, the last global outbreak of the disease was not until nearly 20 years later, in 1977.

The WHO states that eradication of smallpox occurred when “widespread immunization and surveillance were conducted around the world for several years. The last known natural case was in Somalia in 1977. In 1980, the WHO declared smallpox eradicated — the only infectious disease to achieve this distinction. This remains among the most notable and profound public health successes in history.”

Symptoms

The symptoms of smallpox include fever, fatigue, back pain, abdominal pain, and vomiting in the early stages. Within three days of infection, the patients will develop a rash with liquid-filled bumps, typically beginning on the face and hands but can spread all over the body.

Smallpox transmission occurs from close person-to-person contact and has an incubation period between 1 week and 17 days.

Historically, approximately 30% of cases were fatal.

Phases

The CDC suggests that the average incubation period for this disease is 10 days to 2 weeks. During the incubation period, people typically have no symptoms.

The first stage of smallpox can last between two and four days. At this stage, patients can be contagious and typically experience symptoms such as fever, headaches, body aches, and vomiting. This stage of illness is when patients cannot proceed as usual.

The next stage, also known as the most contagious stage, is when rashes begin to appear. At first, the small red spots start on the tongue and mouth. These spots become sores and can spread to the face, arms, legs, hands, and feet.

The CDC states, “by the fourth day, the skin sores fill with a thick, opaque fluid and often have a dent in the center. Once the skin sores fill with fluid, the fever may rise again and remain high until scabs form over the bumps.”

The next phase is the pustular rash and scab stage. At this point, “The sores become pustules (sharply raised, usually round and firm to the touch, like peas under the skin). After about five days, the pustules begin to form a crust and then scab. By the end of the second week, after the rash appears, most of the sores have scabbed over.”

The scabs will then begin to fall off until there are no more, at which point the patient will no longer be contagious.

Transmission

While the disease is thought not to become contagious until the first sores appear, the virus is spread by respiratory droplets from coughing or sneezing. The patients do not stop being contagious until the last scab falls off.

In addition to direct contact spreading the disease, indirect contact with materials contaminated by patients can also spread the virus.

This disease is contained to the human species and has yet to be discovered in insects or animals.

Prevention and Treatment 

The smallpox vaccine was first developed in 1796 by Edward Jenner. At one point, the smallpox vaccine was widely administered; however, since the eradication of the disease, the vaccines are not widely recommended.

According to the CDC, the virus uses vaccinia, a pox virus like smallpox. The vaccine can provide varying forms of protection depending on when it is administered.

The FDA approved Tecovirimat and Brincidofovir as antivirals for the treatment of smallpox.

Chickenpox (Varicella)

According to the CDC, chickenpox, also known as varicella, is caused by the varicella-zoster virus. Unlike smallpox, the rash from this virus typically begins on the chest, back, and face before spreading all over the body.

Prevalence

Chickenpox is less common in the United States today than it was in the early 1990s. Then, approximately 4 million people in the US got chicken pox, and 100–150 died yearly.

The chickenpox vaccine was first distributed in the US in 1995. The CDC estimates that each year, approximately 3.5 million chickenpox cases are prevented by vaccination.

Symptoms and Risk

While smallpox is a much more prolonged illness, chickenpox typically will last between 4 and 7 days. The chickenpox rash turns into fluid-filled blisters, which eventually scab up. The rash can also spread to the mouth, eyelids, and genitalia. Additional symptoms may include fever, fatigue, lack of appetite, and headaches.

This disease is highly contagious. The CDC states, “if one person has it, up to 90% of the people close to that person who are not immune will also become infected. The virus spreads mainly through close contact with someone who has chickenpox.”

Chickenpox can be fatal for high-risk populations such as infants, adolescents, pregnant, or immunocompromised people. Deadly side effects include bacterial infection, pneumonia, encephalitis, excessive bleeding, sepsis, and dehydration.

Prevention

The varicella vaccine is the best way to prevent the disease and is the only widely recommended prevention method aside from avoiding infected people.

The CDC recommends the varicella vaccine be administered as a two-dose series, with the first dose being given between 12 and 15 months and the second dose given between ages 4 and 6.

While chickenpox vaccination helps prevent infection, it does not provide complete protection. However, vaccinated individuals who are infected may experience mild or no symptoms.

Contrary to what unreliable sources may state, chickenpox parties are ineffective in preventing the disease's spread.

The CDC says, “in the past, some parents participated in “chickenpox parties” to intentionally expose their unvaccinated children to a child with chickenpox in hopes that they would get the disease. CDC strongly recommends against hosting or participating in these events. Chickenpox can be serious and can lead to severe complications and death, even in healthy children. There is no way to tell in advance how severe your child’s symptoms will be. So, it is not worth taking the chance of exposing your child to someone with the disease.”

Mpox

According to the CDC, “mpox virus is part of the same family of viruses as variola virus, the virus that causes smallpox. Mpox symptoms are similar to smallpox symptoms but milder, and monkeypox is rarely fatal. mpox is not related to chickenpox.”

Transmission

Transmission can occur between animals and humans and humans to humans. Transmission can happen through contact with respiratory secretions, skin lesions, or recently contaminated objects.

Symptoms

While most people’s symptoms appear between 6 and 13 days after infection, it can take up to 21 days for them to appear.

Within the first five days, symptoms may include fever, headaches, swelling of the lymph nodes, muscle ache, and lack of energy. Up to three days after fever onset is when skin eruptions begin to appear. They can impact the face, hands, feet, genitalia, corneas, and beyond.

Prevention

The JYNNEOS vaccine is currently being used to protect against mpox. Other prevention strategies may include avoiding contact with infected people or animals.

What is the difference?

While all three illnesses may sound similar and involve skin eruptions, they are different diseases. Each illness's transmission, severity, treatment, and prevention are different. Understanding the differences between each disease can help inform treatment regimens and protect individuals and their loved ones.

Anyone experiencing skin lesions or symptoms similar to any of these viruses should seek the help of a licensed healthcare professional to diagnose their conditions properly, determine the best course of action, and mitigate public health risks.

Editor's Note: This article has been edited to change monkeypox to mpox, following industry guidance.