Smallpox

Smallpox: Causes, Symptoms, Treatment and Prevention|

What is smallpox?

Smallpox is a highly contagious and serious infectious disease caused by the variola virus. It is characterized by fever, fatigue, and a distinctive skin rash that progresses to pus-filled blisters. The rash typically begins on the face and spreads to the rest of the body. The disease can be fatal, with a high mortality rate, especially in severe cases.

Smallpox has been responsible for millions of deaths throughout history, but thanks to global vaccination efforts, it was declared eradicated by the World Health Organization (WHO) in 1980. The last known natural case occurred in 1977. Since eradication, smallpox is no longer a public health concern, and the smallpox vaccine is no longer administered except in certain research settings.

Does smallpox still exist?

Smallpox no longer exists as a naturally occurring disease. It was officially declared eradicated by the World Health Organization (WHO) in 1980 after a successful global vaccination campaign. The virus has not been found in the natural environment since the last known case in 1977.

However, samples of the variola virus (which causes smallpox) are still kept in two secure laboratories: one in the United States and the other in Russia. These samples are used for scientific research, mainly to study the virus and develop treatments or vaccines in case of a bioterrorism threat or accidental release. The possibility of smallpox re-emerging is extremely low due to these controlled environments and global surveillance.

How did we eradicate smallpox?

The eradication of smallpox was a monumental achievement in public health, accomplished through a coordinated global effort led by the World Health Organization (WHO). Several key strategies were employed in this effort:

1. Global Vaccination Campaign:

 A major component of smallpox eradication was widespread vaccination. The smallpox vaccine, developed by Edward Jenner in the 18th century, became more effective and widely distributed over time. During the eradication campaign, health workers vaccinated millions of people in affected regions, often going door-to-door in rural areas to ensure coverage. Mass vaccination campaigns were particularly crucial in regions with high transmission rates.

2. Surveillance and Containment: 

A key strategy that set the smallpox eradication effort apart from other disease control programs was the focus on surveillance. Once a case of smallpox was identified, health authorities quickly isolated the infected individual and their contacts to prevent further spread. This "surveillance-containment" approach was critical, especially after the disease was reduced to only a few countries.

3. Ring Vaccination:

 In regions where smallpox was still active, health authorities used ring vaccination, where anyone who had come into contact with an infected person was vaccinated. This approach helped contain outbreaks by creating a "ring" of immune individuals around each case, preventing the virus from spreading.

4. International Coordination and Commitment: 

The WHO played a vital role by coordinating efforts between countries, providing technical assistance, and ensuring that vaccines and resources were available. There was a strong global commitment to eradicating the disease, which involved governments, health organizations, and local health workers.

5. Public Education and Awareness:

 The success of the campaign also depended on educating people about the importance of vaccination and recognizing the symptoms of smallpox, which helped increase participation and early detection.

The last known natural case of smallpox occurred in Somalia in 1977. After the successful vaccination and containment efforts, smallpox was declared eradicated in 1980. This remains one of the most successful public health interventions in history.

What are the symptoms of smallpox?

The symptoms of smallpox generally appear about 7 to 17 days after exposure to the virus. The disease progresses in stages, and its symptoms are quite distinctive. Here's how they typically unfold:

1. Initial Symptoms (Prodromal Phase):

● Fever: 

Often high, typically around 101°F (38.3°C) to 104°F (40°C).

● Fatigue: 

A feeling of extreme tiredness and weakness.

● Headache: 

Often severe and accompanied by back pain.

● Muscle aches: 

General body aches.

● Chills: 

Accompanied by sweating.

● Vomiting: 

Sometimes present in severe cases.

● Rash: 

The first sign of the skin rash appears 2 to 3 days after the fever starts.

2. Rash Development:

● The rash usually starts on the face and mouth, then spreads to the arms, legs, and torso. It progresses in several stages:

     • Macules (flat red spots) appear first.

     • These evolve into papules (raised bumps) after 1-2 days.

     • The papules turn into vesicles (fluid-filled blisters), which then become pustules (pus-filled blisters) by the fourth day.

● The pustules form scabs by the end of the second week.

● The rash is characteristic of smallpox and can help doctors differentiate it from other diseases like chickenpox.

3. Late Stage (Pustular and Scabbing):

● The pustules crust over and scab, leaving deep scars once they heal.

● The individual typically remains contagious until the scabs fall off.

4. Complications:

● In severe cases, smallpox can cause secondary bacterial infections (such as pneumonia or sepsis), blindness, or severe scarring.

● Some individuals may experience encephalitis (inflammation of the brain), which can lead to seizures or permanent neurological damage.

● The disease has a high mortality rate, especially in the more severe forms.

Smallpox is most contagious during the early stages of the disease, especially when the fever and rash appear. The rash is a key diagnostic feature that helps distinguish smallpox from other similar illnesses like chickenpox.

What does a smallpox rash look like?

The smallpox rash is one of the most distinctive features of the disease, and it follows a specific pattern as it progresses. Here's a description of what it looks like:

1. Initial Appearance:

■ The rash typically begins 2 to 3 days after the onset of fever, usually starting on the face and mouth, then spreading to the arms, legs, and torso.

■ The first rash appears as red, flat spots (called macules). These spots look similar to mild sunburn and are often small and round.

2. Progression of Rash:

■ Papules: 

After about 1-2 days, the red spots develop into raised bumps (papules). These bumps feel firm and are typically the same size.

■ Vesicles: 

The papules then become fluid-filled blisters (vesicles), which appear within 2-3 days. These vesicles are often round and clear at first.

■ Pustules:

 The vesicles later turn into pus-filled blisters (pustules), which are dense, round, and raised, with a central depression. The pustules may look yellow or cloudy.

3. Scabbing:

■ After about a week, the pustules begin to dry out and form scabs. The scabs often become thick and dark, and the skin beneath them may begin to show signs of deep scarring.

■ The scabs eventually fall off after 2-3 weeks, leaving behind scars that can be pitted or disfiguring.

4. Uniformity:

■ A key feature of the smallpox rash is that the spots or blisters are often in similar stages of development across the body. For example, you may see macules, papules, vesicles, and pustules all at the same time, which is different from other rashes like chickenpox, where the spots are in different stages.

The rash is typically more concentrated on the face and upper body, and it can be quite severe, often resulting in deep scarring once the scabs fall off. The rash is highly contagious, especially in the earlier stages when the vesicles and pustules are present.

What causes smallpox?

Smallpox is caused by the variola virus, a member of the poxvirus family. There are two main types of the variola virus:

1. Variola major: 

The more severe form, with a higher mortality rate.

2. Variola minor: 

A less severe form, with a lower mortality rate.

The virus is transmitted from person to person, primarily through respiratory droplets when an infected person coughs, sneezes, or talks. The virus can also spread through direct contact with bodily fluids (such as saliva or pus from pustules) or contaminated objects (such as bedding or clothing).

Once the virus enters the body, it primarily infects the respiratory system and then spreads through the bloodstream to other organs, including the skin. The virus causes the characteristic rash and other symptoms of smallpox.

Key factors that contribute to the spread of smallpox include:

● Close contact:

 People in close quarters or households with an infected person are at higher risk.

● Contaminated surfaces: 

Smallpox can also be transmitted through objects contaminated with the virus, such as clothes, towels, or bedding used by an infected person.

The virus is highly contagious during the early stages of infection, particularly when fever and the rash are first developing. However, it is less contagious in the later stages, after the rash has scabbed over.

How did smallpox spread?

Smallpox spread primarily through direct person-to-person contact and respiratory droplets. Here’s a breakdown of how the disease spread:

1. Respiratory Droplets:

 The most common way smallpox was transmitted was through the air when an infected person coughed, sneezed, or talked. The virus is contained in respiratory droplets that can travel through the air and be inhaled by someone nearby. This is why smallpox spread easily in crowded places and close living conditions.

2. Direct Contact with Infected Fluids or Lesions:

 Smallpox can also be spread through direct contact with the bodily fluids of an infected person, including saliva, pus from pustules, or blood. The fluid-filled lesions (pustules) that appear on the skin are highly contagious.

3. Contaminated Objects:

 The virus can survive on contaminated objects, such as clothing, bedding, or towels that were used by an infected person. If someone else touches these items, they could become infected, especially if the contaminated objects come into contact with broken skin or mucous membranes.

4. Mother to Child: 

Though rare, smallpox could also spread from an infected mother to her baby during birth if the mother had the active disease.

Smallpox is contagious from the onset of the fever and rash until all scabs have fallen off, which usually takes about 3-4 weeks. This long contagious period contributed to its spread in communities before the advent of vaccination and public health measures.

What were the complications of smallpox?

Smallpox could lead to serious complications, many of which were life-threatening. Some of the major complications included:

1. Secondary Bacterial Infections:

 The pustules and open sores created by smallpox were susceptible to bacterial infections. Common infections included:

■ Pneumonia (lung infection)

■ Sepsis (a severe, widespread infection in the body)

■ Bacterial skin infections (such as cellulitis)

2. Scarring: 

As the pustules dried and formed scabs, they often left deep scars or pockmarks on the skin. These scars could be disfiguring, especially when the disease affected the face.

3. Blindness: 

Smallpox could cause keratitis (inflammation of the cornea) and conjunctivitis (inflammation of the eye), leading to permanent vision loss or blindness in some cases.

4. Encephalitis: 

This is the inflammation of the brain, which could lead to seizures, neurological damage, or even death. Encephalitis was a rare but severe complication of smallpox.

5. Hemorrhagic Smallpox: 

A rare and very severe form of the disease, hemorrhagic smallpox caused bleeding in the skin, mouth, and other organs, leading to a high mortality rate.

6. Pregnancy Complications: 

Pregnant women who contracted smallpox had an increased risk of miscarriage, premature delivery, or death. The virus could also be passed to the baby, leading to neonatal smallpox.

7. Death: 

Smallpox had a high mortality rate, especially in its more severe forms. Variola major, the more common form of smallpox, had a death rate of about 30%, though this could vary based on factors like age, health, and access to care.

The severity of complications varied depending on factors like the individual's overall health, age, and the type of smallpox (variola major or minor). Some people survived but were left with lasting scars or other long-term health issues.

Why was smallpox so fatal?

Smallpox was particularly fatal due to several factors related to the nature of the virus and the way it affected the body:

● Immune System Overload: 

The variola virus attacked multiple organs, including the skin, lungs, and sometimes the brain, overwhelming the immune system. It caused a systemic infection, meaning it affected the entire body rather than just one part, making it harder for the body to fight off the infection.

● Complications and Secondary Infections: 

As smallpox caused severe damage to the skin, it created open sores that were susceptible to bacterial infections like pneumonia, sepsis, and cellulitis. These secondary infections often worsened the condition and could be fatal, particularly in the absence of antibiotics (which were not available until the 20th century).

● Hemorrhagic Form:

 In rare cases, smallpox could develop into hemorrhagic smallpox, which caused bleeding in the skin, mouth, and internal organs. This form of the disease often led to rapid death due to blood loss and organ failure.

● Damage to Vital Organs: 

The virus could directly damage vital organs, such as the lungs (causing pneumonia) and the brain (causing encephalitis). Pneumonia and brain inflammation significantly increased the risk of death.

● Lack of Effective Treatment: 

Before the development of vaccines and antibiotics, there were few treatments available to address the virus's complications. Most cases were managed with supportive care, but this was often not enough to save patients, especially those with severe symptoms or secondary infections.

● High Transmission Rate: 

Smallpox was highly contagious, especially in the early stages of infection when people were most infectious. This rapid spread meant that people were often infected before the disease was recognized, which contributed to widespread outbreaks and a higher overall death toll.

● Vulnerable Populations:

 Certain populations, including the very young, the elderly, and those with compromised immune systems, were especially susceptible to the severe effects of smallpox. These groups had a higher risk of complications, which increased the fatality rate.

Together, these factors made smallpox one of the most deadly infectious diseases in history, with a high fatality rate, particularly in its severe forms.

Do we still vaccinate for smallpox?

No, smallpox vaccination is no longer routinely given to the general public. Smallpox was eradicated in 1980 following a successful global vaccination campaign led by the World Health Organization (WHO), and because the disease no longer exists in nature, there is no longer a need for widespread vaccination.

However, there are still some cases where smallpox vaccination may be administered:

1. Bioterrorism Preparedness: 

While smallpox has been eradicated, there are concerns about the potential use of the variola virus as a biological weapon. As a result, smallpox vaccination is still recommended for certain individuals who may be at risk of exposure, such as military personnel, emergency responders, and laboratory workers who handle the virus in secure settings.

2. Research and Laboratory Settings: 

Smallpox vaccine may be administered to those working with the virus in specialized laboratories, as there are still small samples of the virus stored in high-security labs in the U.S. and Russia for research purposes.

3. Emergency Situations:

 In the event of a smallpox outbreak (which would likely result from a deliberate release of the virus), emergency vaccination campaigns could be launched to control and contain the spread of the disease.

For the general public, however, smallpox vaccination is no longer necessary, as the disease has been eradicated.

What year did the U.S. stop giving the smallpox vaccine?

The United States stopped giving the routine smallpox vaccine in 1972. By this time, smallpox had been largely controlled in the U.S. and around the world, thanks to extensive vaccination campaigns. The decision to stop routine vaccination was made after smallpox was declared eradicated in the Western Hemisphere.

The U.S. government continued to stockpile smallpox vaccines as a precaution in case of an outbreak or emergency, but routine vaccination ceased because the risk of the disease was considered very low. The global eradication of smallpox was officially declared by the World Health Organization in 1980, further confirming that widespread vaccination was no longer necessary.

Does the smallpox vaccine last a lifetime?

No, the smallpox vaccine does not provide lifetime immunity. Over time, immunity from the vaccine diminishes, meaning that people who were vaccinated many years ago may no longer have complete protection against the virus.

The smallpox vaccine typically provides strong protection for 3 to 5 years, with some level of immunity possibly lasting up to 10 years or more, but it is not indefinite. If someone is vaccinated later in life, their immunity may still wane after several years.

For this reason, the U.S. and other countries discontinued routine smallpox vaccination after the disease was eradicated, as the risk of exposure to the virus became extremely low. However, in the event of an outbreak or bioterrorism threat, people who are at risk could be re-vaccinated or given booster shots to ensure immunity.

Was smallpox the first disease to have a vaccine?

Yes, smallpox was the first disease to have a vaccine. The vaccine was developed by Edward Jenner, an English physician, in 1796. Jenner observed that milkmaids who had contracted cowpox, a milder disease related to smallpox, seemed to be immune to smallpox. He hypothesized that exposure to cowpox could protect against smallpox.

To test this, Jenner inoculated a young boy with material from a cowpox sore, and later exposed him to smallpox. The boy did not develop the disease, demonstrating that cowpox provided immunity to smallpox. This was the first recorded use of a vaccine, and Jenner's work laid the foundation for modern immunology.

Jenner's smallpox vaccine became widely adopted, and vaccination programs helped reduce and eventually eradicate smallpox globally, making it the first disease to be eradicated through vaccination.

What is variolation?

Variolation is an early method of preventing smallpox by deliberately introducing material from a smallpox lesion (usually from an infected person) into a healthy person’s body, typically through a scratch or small incision in the skin. This was done to induce a mild form of the disease, with the goal of providing immunity to smallpox without causing the full, severe illness.

The practice of variolation dates back to ancient China, India, and Africa, where it was used to protect individuals from smallpox. It was introduced to Europe in the early 18th century, primarily by the work of Lady Mary Wortley Montagu, who observed the practice while in Turkey and advocated for its use in England.

Variolation was not as safe or effective as modern vaccination. While it did provide some level of immunity to smallpox, it also carried a significant risk of severe disease, disability, or death, as the person could still develop a full-blown case of smallpox. The practice was eventually replaced by vaccination after Edward Jenner developed the smallpox vaccine in 1796, which used cowpox virus and was far safer and more effective.

Why does the smallpox vaccine leave a scar?

The smallpox vaccine leaves a scar because of the way the vaccine was administered and the immune response it triggered. Here’s why:

1. Vaccination Method: 

The smallpox vaccine was typically given using a method called scarification, in which a bifurcated needle (a two-pronged needle) was used to introduce the vaccine into the skin. The needle would be dipped in the vaccine and then pricked into the skin, usually on the upper arm. This method caused small cuts or punctures in the skin.

2. Immune Response: 

The vaccine contains a virus called the vaccinia virus, which is related to the smallpox virus but much less harmful. When the vaccine was administered, the body’s immune system responded by producing antibodies to fight off the vaccinia virus. This immune response caused inflammation at the site of the vaccination.

3. Formation of a Scab: 

As the immune system fought off the vaccinia virus, a blister or pustule would form at the vaccination site, much like a mild case of smallpox. Over time, the blister would turn into a scab, which would eventually fall off, leaving a scar. The scarring was a natural part of the body’s healing process.

The scar from the smallpox vaccine is usually round and may appear as a depression in the skin, often referred to as a "vaccination scar." It became a common and recognizable sign that someone had been vaccinated, and it was often seen as a mark of protection against smallpox.

Are there treatments for smallpox?

There is no specific cure for smallpox once a person has contracted the disease, and treatment mainly focused on relieving symptoms and managing complications. Historically, smallpox treatment involved:

1. Supportive Care: 

This was the primary approach. Patients were often isolated to prevent spreading the disease and given supportive care to manage symptoms such as fever, pain, and dehydration. This included:

■ Fluids to prevent dehydration.

■ Pain relievers (such as acetaminophen or ibuprofen) to alleviate fever and body aches.

■ Antibiotics to treat secondary bacterial infections (like pneumonia or skin infections), though these would not treat the virus itself.

2. Antiviral Research: 

Although no specific antiviral treatment for smallpox was available before the disease was eradicated, researchers began exploring antiviral drugs in the later stages of the disease’s existence. For example:

■ Tecovirimat (TPOXX): 

This antiviral drug, approved by the FDA in 2018, is effective against poxviruses, including smallpox. It works by inhibiting the virus's ability to spread within the body. It has been stockpiled for emergency use in the event of a smallpox outbreak.

■ Brincidofovir and Cidofovir: 

Other antiviral drugs that have shown activity against poxviruses in research settings.

3. Post-Exposure Vaccination:

 In the event of exposure to smallpox, vaccination within 3 to 4 days could significantly reduce the severity of the disease or prevent it altogether. This was one of the key strategies used during the final phases of the smallpox eradication campaign.

Despite these efforts, smallpox was ultimately eradicated through vaccination, which remains the most effective preventive measure against the disease. Today, because smallpox no longer exists naturally, there are no widespread treatments for it. The remaining focus is on preparedness in case of a bioterrorism threat.

How was smallpox diagnosed?

Smallpox was diagnosed primarily based on its clinical symptoms and distinctive rash. Healthcare providers used several key signs to identify the disease:

1. Fever and General Symptoms:

● Smallpox usually started with a high fever, fatigue, headache, back pain, and sometimes vomiting. These initial symptoms could help differentiate smallpox from other diseases, though at this stage, it could still be confused with other febrile illnesses like influenza or measles.

2. Distinctive Rash:

● The most definitive diagnostic feature of smallpox was the appearance of the rash. The rash typically began 2 to 3 days after the onset of fever, starting on the face and arms before spreading to the torso and legs.

● The rash progressed through several stages: macules (flat red spots), papules (raised bumps), vesicles (fluid-filled blisters), and finally pustules (pus-filled blisters). The uniformity of the rash — with lesions appearing in similar stages across the body — was a key indicator of smallpox.

3. Lesions in the Mouth and Throat:

● Smallpox also caused lesions in the mouth and throat, which could help confirm the diagnosis in the early stages, before the rash spread to the skin.

4. Laboratory Tests (if necessary):

● In cases where the diagnosis was unclear or there was a need for confirmation, laboratory tests could be used:

     • PCR (Polymerase Chain Reaction) testing:

 This test could detect the genetic material of the variola virus, confirming the presence of smallpox.

     • Virus isolation: 

A sample from the patient's lesions or blood could be cultured to grow the virus for identification.

     • Serological tests:

 Blood tests could identify antibodies specific to the variola virus, though this was less common for diagnosis in the early stages of disease.

Because of the distinct and recognizable nature of smallpox's symptoms, it was relatively easy for experienced healthcare workers to diagnose in the pre-eradication era, especially once the rash appeared. However, with the eradication of the disease and no cases in the general population, diagnoses today are extremely rare.

What’s the difference between smallpox, mpox and chickenpox?

Smallpox, mpox (formerly known as monkeypox), and chickenpox are all viral infections that cause skin rashes, but they are caused by different viruses and have distinct characteristics. Here are the main differences:

1. Causative Virus:

Smallpox:

Caused by the variola virus, which is a member of the poxvirus family.

Mpox:

Caused by the mpox virus (formerly called monkeypox virus), which is also part of the poxvirus family.

Chickenpox: 

Caused by the varicella-zoster virus (VZV), which is a member of the herpesvirus family.

2. Transmission:

Smallpox: 

Spread mainly through respiratory droplets (coughing, sneezing), as well as direct contact with bodily fluids or contaminated objects.

Mpox: 

Spread through close contact with infected animals (especially rodents), infected humans, or contaminated materials. It can also spread through respiratory droplets, though this is less common than smallpox.

Chickenpox: 

Spread primarily through respiratory droplets when an infected person coughs or sneezes. It is also highly contagious through direct contact with fluid from the blisters.

3. Rash Appearance:

Smallpox:

The rash starts as flat red spots (macules) that develop into raised bumps (papules), followed by fluid-filled blisters (vesicles), and finally, pus-filled pustules. The rash is typically more uniform and appears in similar stages across the body, beginning on the face and spreading downwards.

Mpox:

The rash starts as small, raised bumps that eventually turn into larger, fluid-filled lesions. The rash can appear in different stages (like chickenpox) and tends to be more concentrated on the face, hands, and feet. Mpox lesions may be deeper and more painful compared to chickenpox.

Chickenpox: 

The rash begins as small red spots that develop into fluid-filled blisters and then scab over. It usually starts on the torso, face, or scalp and spreads to other parts of the body. Chickenpox lesions appear in various stages, with new blisters constantly forming.

4. Symptoms:

Smallpox: 

Starts with fever, fatigue, headache, and back pain, followed by the development of the characteristic rash. The fever is typically high, and the disease has a high mortality rate (about 30% for variola major).

Mpox: 

Symptoms include fever, swollen lymph nodes, headache, muscle aches, and fatigue, followed by the rash. The disease is generally less severe than smallpox and has a lower fatality rate, although it can be more severe in certain individuals.

Chickenpox: 

Early symptoms include fever, tiredness, and loss of appetite, followed by thecharacteristic itchy rash. Chickenpox is typically mild, especially in children, but can be more severe in adults.

5. Complications:

Smallpox: 

Can lead to severe complications like pneumonia, encephalitis, and severe scarring. It has a high mortality rate.

Mpox: 

Complications can include bacterial infections of the skin, pneumonia, or sepsis, though it is less deadly than smallpox. In some cases, it can be fatal.

Chickenpox: 

Complications may include bacterial skin infections, pneumonia, and encephalitis, particularly in adults or immunocompromised individuals. It can also cause shingles later in life.

6. Vaccine:

Smallpox:

A vaccine was developed in the 18th century and led to the eradication of the disease by 1980. The smallpox vaccine is no longer given, as smallpox no longer exists.

Mpox: 

There is a smallpox vaccine (which also protects against mpox), but it is not routinely administered. Vaccines and antivirals are used for prevention and treatment in cases of exposure.

Chickenpox: 

A vaccine is available to prevent chickenpox, and it is now part of routine childhood immunizations in many countries.

7. Severity:

Smallpox: 

Highly fatal with a death rate of about 30% for variola major and much higher in immunocompromised individuals.

Mpox: 

Generally less severe than smallpox, with a much lower fatality rate, but can still cause significant illness and complications.

Chickenpox: 

Typically mild in children but can cause serious complications in adults, such as pneumonia or encephalitis.

Summary Table:

Feature	Smallpox	Mpox	Chickenpox
Causative Virus	Variola virus	Mpox virus (formerly monkeypox virus)	Varicella-zoster virus (VZV)
Transmission	Respiratory droplets, direct contact	Close contact, respiratory droplets	Respiratory droplets, direct contact
Rash Appearance	Pustules, uniform across body	Raised bumps, different stages	Fluid-filled blisters, various stages
Symptoms	High fever, severe fatigue, headache	Fever, swollen lymph nodes, fatigue	Mild fever, itchy rash
Complications	Pneumonia, encephalitis, scarring	Bacterial infections, pneumonia	Skin infections, pneumonia, shingles
Vaccine	Yes (no longer in use)	Smallpox vaccine (not routine)	Yes (routine childhood vaccine)
Severity	Very high mortality (30%)	Less severe, but can cause illness	Typically mild, severe in adults

While all three diseases involve rashes, their causative viruses, severity, and management strategies are very different. Smallpox has been eradicated, chickenpox is preventable with vaccination, and mpox is generally mild but still requires attention in certain cases.