Smallpox

Smallpox: Symptoms, Causes, Types, Diagnosis, and Treatments

Smallpox is one of the deadliest diseases in human history, responsible for hundreds of millions of deaths before its eradication. Caused by the variola virus, smallpox was a highly contagious and deadly infection that affected people of all ages across the globe. Thanks to an intensive global vaccination campaign, smallpox was officially declared eradicated by the World Health Organization (WHO) in 1980. However, the threat of its use in bioterrorism still makes it a relevant topic in medicine and public health today.

In this article, we’ll explore smallpox in depth — including its symptoms, causes, types, diagnostic methods, and treatment approaches — to provide a comprehensive understanding of this historic but still-relevant disease.

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What is Smallpox?

Smallpox is an acute, infectious disease caused by the variola virus, a member of the Orthopoxvirus genus. It was once a leading cause of death and disfigurement, with an estimated mortality rate of 30% in its most severe forms. The virus primarily spread from person to person through respiratory droplets, direct contact, or contaminated objects like bedding or clothing.

There is currently no known natural reservoir for smallpox; it exists only in secure laboratory environments in the United States and Russia.

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History and Eradication of Smallpox

Smallpox has plagued humanity for at least 3,000 years, with evidence of the disease found in Egyptian mummies. It has influenced the outcome of wars, wiped out populations, and significantly shaped the course of global history.

The landmark Global Smallpox Eradication Campaign, launched by WHO in 1967, resulted in the successful eradication of smallpox by 1980. The last naturally occurring case was reported in Somalia in 1977. Routine vaccination was discontinued in most countries after eradication.

Despite this, smallpox remains a topic of concern due to the potential for bioterrorism using stored virus samples.

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Symptoms of Smallpox

Incubation Period

The incubation period of smallpox is typically 7 to 17 days (average 12 days). During this time, the infected person is not contagious and usually experiences no symptoms.

Early Symptoms (Prodrome)

The initial symptoms resemble those of flu and usually appear 2 to 4 days before the rash:

• High fever (101–104°F or 38–40°C)
• Chills
• Severe headache
• Back pain
• Fatigue and malaise
• Vomiting
• Abdominal pain
• Delirium (in severe cases)

Rash Stage

The smallpox rash progresses through several distinct stages over a period of about 2 to 4 weeks:

1. Macules (flat red spots): Appear first on the face, then spread to the arms, legs, hands, and feet.
2. Papules (raised bumps): Form within 1–2 days.
3. Vesicles (fluid-filled blisters): Develop around day 3–4.
4. Pustules (filled with thick, opaque fluid): Form by day 5–7 and are often deep and firm.
5. Scabs: Around day 10–14, pustules begin to crust and scab over.
6. Scarring: The scabs fall off after about 3 weeks, often leaving pitted scars.

Contagious Period

A person becomes contagious as soon as the rash appears and remains so until the last scab falls off.

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Causes of Smallpox

Variola Virus

Smallpox is caused by the variola virus, which exists in two major forms:

• Variola major – the more severe and deadly form
• Variola minor – a milder form with a much lower death rate

The virus is transmitted via:

• Respiratory droplets (most common)
• Direct contact with infected lesions
• Contaminated clothing or bedding

Unlike some other viruses, smallpox does not have an animal reservoir, meaning it is not transmitted by animals.

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Types of Smallpox

There are several clinical forms of smallpox, each with differing severity and mortality rates.

1. Variola Major

The classic and most severe form, responsible for the majority of smallpox deaths.

• Mortality rate: 30%
• Severe symptoms, extensive rash, and significant scarring

Subtypes:

• Ordinary Smallpox: Most common form (90% of cases)
• Modified Smallpox: Occurs in vaccinated individuals; milder symptoms
• Flat-Type Smallpox: Rare, with lesions that remain flat; often fatal
• Hemorrhagic Smallpox: Extremely rare and deadly, with internal bleeding

2. Variola Minor (Alastrim)

A milder form of the disease:

• Mortality rate: <1%
• Less severe rash and systemic symptoms

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Diagnosis of Smallpox

Diagnosing smallpox today would require extreme caution, as the disease no longer circulates naturally. A confirmed case would constitute a global public health emergency.

Clinical Diagnosis

Healthcare providers would consider:

• Characteristic rash (especially the simultaneous development of lesions)
• Fever preceding rash
• Distribution of lesions (more on face/extremities than trunk)

Laboratory Diagnosis

Definitive diagnosis requires laboratory confirmation:

1. PCR (Polymerase Chain Reaction) – Detects variola DNA in samples
2. Electron Microscopy – Visual identification of the virus
3. Culture of the Virus – Requires high-security biosafety level-4 (BSL-4) laboratories
4. Serologic Testing – To detect antibodies (less useful for early detection)

Samples are typically taken from skin lesions or throat swabs.

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Treatment of Smallpox

There is no specific antiviral cure for smallpox, but several approaches can help manage and mitigate the disease.

Supportive Care

Treatment primarily involves symptom management:

• Fluids and electrolytes to prevent dehydration
• Pain relief (e.g., acetaminophen)
• Antibiotics to treat secondary bacterial infections
• Isolation to prevent spread

Antiviral Drugs

Although smallpox is eradicated, several antiviral agents have shown potential:

1. Tecovirimat (TPOXX)
   • FDA-approved for smallpox treatment in the event of a bioterror attack
   • Inhibits virus spread within the body
2. Cidofovir
   • Broad-spectrum antiviral with some activity against poxviruses
   • Can cause kidney toxicity
3. Brincidofovir
   • An oral version of cidofovir with fewer side effects

Vaccination (Post-Exposure)

Smallpox vaccination is effective within 3 to 4 days of exposure and may prevent or lessen the severity of the disease. After 5–7 days, it may still offer some protection.

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Smallpox Vaccine

The smallpox vaccine uses a live virus called vaccinia, which is related to but less harmful than variola. It does not contain the actual smallpox virus.

Key Points:

• Provides immunity for about 3–5 years, with declining protection afterward
• Given using a bifurcated needle via multiple skin pricks
• Produces a “vaccine take” (a small blister that forms a scab and heals with a scar)

Side Effects

Most side effects are mild, but some rare and serious complications can include:

• Eczema vaccinatum (in individuals with eczema)
• Progressive vaccinia (in immunocompromised individuals)
• Encephalitis
• Myocarditis

Because of these risks, routine vaccination is not recommended for the general population today.

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Bioterrorism and Smallpox

Despite eradication, smallpox remains a bioterrorism threat. Concerns exist that the variola virus could be weaponized or escape from research labs.

Preparedness Measures:

• Stockpiles of smallpox vaccines in many countries
• Development of newer, safer vaccines (e.g., ACAM2000, JYNNEOS)
• Antiviral drugs for emergency use
• Global surveillance systems to detect any outbreaks quickly

The Centers for Disease Control and Prevention (CDC) and WHO have detailed response protocols in the event of a smallpox outbreak.

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Smallpox vs Chickenpox

While both diseases cause a rash, they are very different viruses:

Feature	Smallpox	Chickenpox
Causative Virus	Variola virus	Varicella-zoster virus
Rash Distribution	Starts on face and extremities	Starts on trunk
Lesion Progression	Uniform stage	Lesions in various stages
Severity	Often severe, deadly	Usually mild
Scarring	Common	Rare
Vaccine	Discontinued (routine)	Still administered (MMRV)

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Can Smallpox Come Back?

Naturally, no — smallpox does not exist in the environment anymore. However, concerns remain:

• Accidental release from labs
• Deliberate use in biowarfare
• Synthetic biology potentially recreating the virus

Thus, continued vigilance, research, and preparedness are essential.

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Conclusion

Smallpox may be a disease of the past, but its impact on humanity and relevance in the context of global security make it a critical subject even today. Understanding its symptoms, causes, types, and treatment options is vital, especially for healthcare professionals and public health authorities. Thanks to coordinated global vaccination efforts, smallpox is the only human disease ever eradicated — a testament to what global cooperation can achieve.

Frequently Asked Questions (FAQs) About Smallpox

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