Demystifying Smallpox: A 5 Comprehensive Guide

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In light of recent global health crises, including the COVID-19 pandemic and outbreaks of diseases like smallpox, an ad hoc committee convened under the National Academies of Sciences, Engineering, and Medicine to conduct a thorough investigation. This committee sought to glean valuable insights from these events, particularly focusing on the recent pandemic and the multi-country spread of mpox. The resulting report, titled “The Future State of Smallpox Medical Countermeasures,” serves as a clarion call for the United States and the global community to brace themselves for the potential resurgence of smallpox.


The report underscores the sobering reality that smallpox could reemerge through various means, ranging from accidental leaks to deliberate acts of bioterrorism. Consequently, it emphasizes the critical importance of assessing the current landscape of research, development, and stockpiling of smallpox medical countermeasures (MCMs). Furthermore, the report highlights the pivotal role of preparedness in mitigating the spread of other diseases caused by viruses within the Orthopoxvirus genus.

A devastating disease responsible for an estimated 500 million deaths in the 20th century alone, remains humanity’s only eradicated disease. However, despite this monumental achievement, the threat of its resurgence looms large. The emergence of mpox virus-associated outbreaks, particularly in Central and West Africa, serves as a stark reminder of the persistent risk posed by related pathogens.

Since May 2022, an outbreak of the mpox Clade 2b virus has ravaged numerous countries, while Clade 1 has notably impacted central Africa in 2024. Remarkably, Cameroon presents a unique scenario, with both clades concurrently circulating within its borders.

Dr. Zhilong Yang, an esteemed associate professor at the Texas A&M School of Veterinary Medicine & Biomedical Sciences Department of Veterinary Pathobiology, lent expertise to the committee responsible for the report. In a press release dated April 12, 2024, Dr. Yang emphasized the transformative potential of smallpox vaccines and drugs, not only in combating smallpox but also in addressing related viruses within the same viral family. This underscores the urgent imperative for sustained research into poxviruses and the continued development of smallpox medical countermeasures, encompassing diagnostics, vaccines, and therapeutics.

Despite the limited availability of virus collections, confined to just two laboratories worldwide, including the U.S. Centers for Disease Control and Prevention (CDC), the proliferation of publicly accessible genetic sequences raises significant concerns. Advances in synthetic biology and artificial intelligence have heightened the feasibility of recreating the virus, amplifying the urgency for preparedness efforts.

Dr. Yang emphasized that even a single smallpox outbreak would precipitate a global health crisis, necessitating unwavering vigilance. It is imperative for scientists and medical professionals to possess the expertise to promptly identify smallpox symptoms and distinguish them from those of diseases like mpox, which have garnered prominence in recent years. Swift recognition and response are paramount to containing the potential impact of a smallpox outbreak.

In November 2021, the U.S. CDC vaccine committee unanimously endorsed Bavarian Nordic’s JYNNEOS® vaccine as a viable alternative to the second-generation ACAM2000® vaccine for both primary and booster doses against smallpox. As of April 2024, healthcare providers in the U.S. have the option to procure JYNNEOS through distributors, facilitating its commercial availability for at-risk individuals at local pharmacies, physician offices, and public health clinics.

The report serves as a clarion call for the maintenance of rigorous standards in medical advisory and preparedness. It underscores the imperative for stakeholders at all levels to prioritize ongoing research, development, and deployment of smallpox medical countermeasures. With concerted effort and strategic interventions, the global community can bolster its readiness to confront the potential resurgence of smallpox, thereby safeguarding public health and security.

What is smallpox

Smallpox is a serious disease caused by the variola virus. It spreads from person to person through the air or by touching objects contaminated with the virus. Smallpox used to be a widespread and deadly disease, but thankfully, it was eradicated in 1980 thanks to vaccination efforts.

What is Smallpox?

  1. It is a highly contagious and sometimes fatal disease caused by the variola virus. It’s characterized by a distinctive rash and flu-like symptoms. The disease has plagued humanity for centuries, causing widespread outbreaks and claiming millions of lives.
  2. How Does Smallpox Spread?
    It spreads from person to person through respiratory droplets expelled when an infected person coughs or sneezes. It can also be transmitted by touching objects contaminated with the virus, such as clothing or bedding.
  3. Symptoms of Smallpox
    The symptoms of it typically appear about 12 to 14 days after infection. They start with flu-like symptoms such as high fever, fatigue, and body aches. After a few days, a rash develops, starting on the face and spreading to the rest of the body. The rash progresses from red spots to fluid-filled blisters, which eventually scab over and fall off, leaving scars.
  4. Variola Virus and its Types
    The variola virus is the causative agent of it. There are two main types of smallpox: variola major and variola minor. Variola major is the more severe form, causing higher mortality rates, while variola minor is less deadly.
  5. History of SmallpoX
  6. It has been documented throughout history, with outbreaks occurring across the globe. It had a devastating impact on indigenous populations during European colonization and played a significant role in warfare and conquest.
  7. Eradication Efforts
    In the 20th century, efforts to eradicate smallpox intensified. Mass vaccination campaigns, along with surveillance and containment measures, led to the successful eradication of the disease in 1980. This monumental achievement marked the first and only time a human disease has been eradicated.
  8. Smallpox Vaccination
    Vaccination played a crucial role in the eradication of it. The vaccine, made from a live virus called vaccinia, was highly effective in preventing the disease. It was administered through a technique called scarification, where the vaccine was scratched into the skin using a bifurcated needle.
  9. Global Impact of Smallpox Eradication
    The eradication of it had far-reaching implications for global health. It demonstrated the power of vaccination and public health measures in controlling infectious diseases. It also paved the way for future disease eradication efforts, inspiring confidence in the feasibility of eliminating other diseases.
  10. Post-Eradication Risks
    Despite the eradication of it, the virus still poses a potential threat. Samples of the virus are kept in secure laboratories for research purposes, raising concerns about accidental release or deliberate misuse. Additionally, advances in biotechnology have raised the possibility of synthesizing the virus, highlighting the need for continued vigilance and preparedness.
  11. Prevention and Preparedness
    While it is no longer a widespread threat, vaccination remains an important tool for preventing its resurgence. Healthcare workers and laboratory personnel who handle the virus are vaccinated to protect against accidental exposure. Additionally, surveillance systems are in place to detect any potential cases and respond promptly to prevent further transmission.



Smallpox, caused by the variola virus, is a highly contagious and potentially fatal disease. Recognizing its symptoms is crucial for early diagnosis and treatment. Here’s a detailed overview of the signs and symptoms of smallpox:

Incubation Period: After exposure to the virus, there’s an incubation period of about 12 to 14 days before symptoms appear.

Early Symptoms: The initial symptoms of smallpox are similar to those of many viral infections and may include:

  • High fever
  • Severe headache
  • Muscle aches
  • Fatigue
  • Malaise (feeling unwell)

Prodromal Phase: Following the early symptoms, individuals may experience a prodromal phase characterized by:

  • Persistent high fever
  • Severe headache
  • Severe back pain
  • Abdominal pain
  • Vomiting

Rash: One of the hallmark features of smallpox is the appearance of a characteristic rash, which progresses through several stages:

  • Maculopapular Stage: Flat, red spots appear on the face and then spread to the trunk and limbs.
  • Pustular Stage: The spots become filled with fluid, forming pus-filled lesions.
  • Vesicular Stage: The lesions become raised and fluid-filled, resembling blisters.
  • Pustular Crust Stage: The fluid-filled lesions become pustules, which eventually crust over and scab.

Distribution of Rash: The rash tends to start on the face and then spread to other parts of the body, including the trunk, arms, and legs. It can also appear on the palms of the hands and soles of the feet.

Systemic Symptoms: In addition to the rash, individuals with smallpox may experience systemic symptoms such as:

  • Severe itching
  • Swollen lymph nodes
  • Photophobia (sensitivity to light)
  • Delirium

Complications: Smallpox can lead to severe complications, including:

  • Secondary bacterial infections of the skin
  • Encephalitis (inflammation of the brain)
  • Blindness
  • Pneumonia
  • Death

Variola Major vs. Variola Minor: There are two main forms of smallpox:

  • Variola Major: This is the more severe form of the disease, with a higher mortality rate and more extensive rash.
  • Variola Minor: This form is less severe, with a lower mortality rate and milder symptoms.

Diagnosis: Diagnosis of smallpox is primarily based on clinical symptoms, particularly the characteristic rash. Laboratory tests, including viral culture and polymerase chain reaction (PCR), can confirm the presence of the variola virus.

Treatment: There is no specific treatment for smallpox, but supportive care can help manage symptoms and reduce complications. This may include bed rest, hydration, pain relief, and antipyretic medications to reduce fever.

Prevention: Vaccination remains the most effective method for preventing smallpox. Additionally, isolation of infected individuals and quarantine measures can help prevent the spread of the disease.

Recognizing the symptoms of smallpox is essential for prompt diagnosis and appropriate management. Vaccination and public health measures play a critical role in controlling the spread of this potentially deadly disease.

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