Smallpox overview

# Overview
Smallpox is a contagious disease unique to humans. Smallpox is caused by either of two virus variants named Variola major and Variola minor. The deadlier form, V. major, has a mortality rate of 3035%, while V. minor causes a milder form of disease called alastrim and kills ~1% of its victims. Long-term side-effects for survivors include the characteristic skin scars.  Occasional side effects include blindness due to corneal ulcerations and infertility in male survivors.

# Historical Perspective
Up until 1977, when it became the only human infectious disease to have been completely eradicated, smallpox had had great impact in human history. The disease is estimated to be at least 16,000 years old and played a major role in the history of Europe, Asia, North America, and Africa. The first clinical evidence of the disease was found in an Egyptian mummy, Ramses V. Smallpox has also been used as a weapon throughout history. The most recent example was the weaponization of smallpox during World War II. After successful vaccination campaigns in the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1980.

## Eradication
Smallpox was declared eradicated in 1980 by the WHO. The eradication of smallpox required a global effort. Since every country was susceptible of the devastating disease, eradicating this infection was expensive and took many years.

## Post-Eradication
After the reported death by smallpox accident in 1978, all known stocks of the virus were destroyed. Today only the United States CDC and Russian State Research Center of Virology and Biotechnology VECTOR have the virus in their laboratories for research purposes.

# Pathophysiology
Smallpox virus may be transmitted from contaminated surfaces or aerosolized particles. It is capable of inducing harm by evading the host's immune system and replicating inside host's cells. The virus may cause 3 forms of the disease: 1) ordinary; 2) flat-type; or 3) hemorrhagic smallpox. It infects different cells of the body, being known by it's characteristic lesions on the skin.

# Causes
Smallpox is caused by the variola virus, a dsDNA virus of the Poxviridae family. There are two forms of this virus with different virulences, evidenced on the discrepancy in respective death rates. The virus survives in the cold and aerosoled environments, what explains its oral transmission among humans, which are it's only host species. Unlike other DNA viruses, it replicates within the cytoplasm, to which it shows tropism.

# Differentiating Smallpox from other Diseases
Prior to its eradication, smallpox would need to be differentiated from other diseases that cause a vesicular rash and a fever including chickenpox (which was often mistaken for smallpox), herpes zoster and erythema multiforme.

# Epidemiology and Demographics
The true incidence of smallpox, before declared eradicated in 1980 by the WHO, wasn't possible to specify due to the lack of new case reports from countries, particularly endemic regions, in which the reported numbers are stipulated to be 1-2% of the reality. Children and young adults were the most affected, especially in regions with low level of immunity. There is no evidence of gender or race difference in the incidence of the disease. Developing countries had a higher incidence of the disease.

# Risk Factors
People who work in laboratories with the virus, or live in areas which have been target of bioterrorism, are at risk of contracting smallpox. Before eradication, risk factors included: physical contact with a patient with the disease, contact with contaminated body fluids, and exposure to contaminated aerosolized particles.

# Natural History, Complications and Prognosis
The natural history and outcome of smallpox depend on the form of disease. The common progress will start with flu-like symptoms followed by a skin rash that generally progresses in a typical fashion, leading to the formation of scabs that will fall off, leaving a scar. The complications may include respiratory conditions, from bronchitis to pneumonia, but may also involve the joints, bones and/or eyes. The overall fatality rate for the variola major form was about 30%.

# Diagnosis

## Diagnostic Criteria
The diagnosis of smallpox is guided by an algorithm, elaborated by the CDC, that follows certain major and minor criteria.

## History and Symptoms
Symptoms of smallpox progress in a typical fashion and some of its common symptoms may include high fever, rash (initially in the oral mucosa, followed by the skin), malaise, fatigue, muscle pain and vomiting.

## Physical Examination
Depending on the stage of the disease, physical findings may include: high fever, tachycardia secondary to the fever, rash of the oral mucosa, skin rash with typical progression, ophthalmological changes, abdominal pain, and altered mental status.

## Laboratory Findings
The polymerase chain reaction test and the growth of the virus in specific cell cultures allow the identification of the smallpox virus.

# Treatment

## Medical Therapy
There is no antiviral treatment for smallpox. In case of disease, it is only possible to manage the wellbeing of the patient, hydrate and administer certain drugs to decrease the fever or pain and to treat concomitant bacterial and/or viral infections.

## Primary Prevention
Primary prevention of smallpox consists in the administration of the vaccinia vaccine, which attenuates or suppresses the manifestations of the disease, if administrated soon after infection has occurred. In the absence of an outbreak, the vaccine is only administered to clinical and/or laboratory workers dealing with the virus in specialized laboratories. It has several adverse effects, particularly in immunosuppressed individuals, those with heart conditions or allergies, for whom its administration must be guided by specific rules.

## Outbreak Prevention
The CDC has elaborated a series of measures to protect the citizens in case of a smallpox outbreak.

## Cost-Effectiveness of Therapy
The efforts made for the eradication of smallpox were cost-effective, since the disease was successfully eradicated in 1980.

## Future or Investigational Therapies
Even though it has been eradicated, there are undergoing studies to find an antiviral drug against smallpox virus due to the potential of an outbreak, and/or use as use in bioterrorism.