fbpx

 

 

Smallpox Infection

Updated : January 29, 2024





Background

Smallpox is an infectious disease caused by the variola virus and is primarily spread through the air by inhaling droplets released when an infected person speaks, coughs, or sneezes. Once the droplets are inhaled, the virus enters the body through the respiratory tract, usually through the nose or mouth.

The exact origins of smallpox are unknown, but the disease has likely been present in human populations for thousands of years. The disease was responsible for numerous epidemics and pandemics throughout history, and it is cause of mortality in millions of people before it was officially eradicated in 1980.

The World Health Organization (WHO) led a successful global smallpox eradication campaign, using a combination of vaccination and surveillance to eliminate the disease.

 

 

Epidemiology

Smallpox is a highly contagious disease that exclusively infects humans and has no animal reservoirs, with an infection rate of up to 80% in unvaccinated populations. In the late 1700s, Edward Jenner discovered that the cowpox virus could protect people from smallpox, and later on vaccinia virus was used as a vaccine.

Throughout the 20th century, smallpox caused significant mortality and morbidity, with an estimated death of over 300 million worldwide and a case fatality rate of around 30%. The last naturally occurring case of smallpox was recorded in Somalia in 1977.

During the smallpox eradication program, two main forms of the disease were identified: Variola major and Variola minor. Variola major, had a fatality rate of 30%, was primarily found in the Indian subcontinent, Africa, and Asia. In contrast, Variola minor, which had a much lower fatality rate of less than 5%, was mainly found in East Africa and Latin America and characterized by fewer skin lesions.

 

 

Anatomy

 

 

Pathophysiology

The pathophysiology of smallpox involves a complex process between viral replication and host immune response. The variola virus enters the body through the respiratory tract and replicates in the lymphoid tissues, particularly in the tonsils and spleen. The virus then spreads through the bloodstream and infects various organs and tissues, including the skin, mucous membranes, and lymph nodes.

During the incubation period, which lasts 7-17 days, the virus replicates and spreads within the body without causing symptoms. Once symptoms appear, the virus causes a characteristic rash and fever. The rash starts as small red spots, which then develop into raised bumps that resemble pimples. The bumps eventually fill with pus and form scabs, which then fall off, leaving behind scars.

The virus can also infect the eyes, causing conjunctivitis, which can lead to blindness. The host’s immune response also plays an important role in the pathogenesis of smallpox. The body’s immune response to the virus is initially non-specific, with the release of inflammatory mediators, such as interferons, that can help to limit viral replication.

However, this response is not sufficient to clear the virus, and the host eventually develops a specific immune response, which is mediated by T cells and antibodies. This response is responsible for controlling the virus and ultimately leading to recovery. The severity of smallpox depends on the virulence of the virus strain, the genetic susceptibility of the host, and the timing and quality of the host’s immune response.

 

 

Etiology

The etiological cause of smallpox is the variola virus, a member of the genus Orthopoxvirus in the Poxviridae family. Poxviruses are the most prominent human viral pathogens and have a brick-shaped appearance on electron microscopy, measuring approximately 300 nm to 350 nm long. The poxviruses possess a linear, double-stranded DNA genome.

They are unique in their genetic makeup, encoding all the proteins necessary for replication, allowing them to replicate in the host cell cytoplasm. The virus is highly contagious and primarily spreads through respiratory droplets when an infected person speaks, coughs, or sneezes.

It can also be spread through contact with infected bodily fluids or contaminated objects. Smallpox can cause severe symptoms such as fever, muscle aches, and a distinctive rash, leading to death in up to 30% of cases.

 

 

Genetics

 

 

Prognostic Factors

The prognosis of smallpox varies depending on the severity of the infection and the person’s overall health. In general, the death rate for smallpox is around 30%. However, the death rate can be as high as 80% in people with compromised immune systems. People who recover from smallpox can have long-term effects, such as scarring and blindness.

 

 

Clinical History

Clinical History

Smallpox is a highly contagious and potentially fatal disease caused by the variola virus. The clinical history of smallpox typically begins with a non-specific febrile prodrome, which includes symptoms such as high-grade fever, chills, abdominal pain, vomiting, headache, and backache. These symptoms occur 1 to 3 days before the appearance of the characteristic skin lesions.

The rash appears first on the face or arms and spreads to the rest of the body, often including the palms and soles. The rash starts as small red spots that quickly progress to raised bumps, filled with pus, and eventually forming scabs.

The scabs eventually fall off, leaving behind pitted scars. Other manifestations of smallpox include swollen lymph nodes, chest pain, and a distinctive backache. Smallpox can lead to serious complications such as pneumonia and brain inflammation in severe cases.

 

 

Physical Examination

Physical Examination

Specific symptoms and characteristics, such as fever and flu-like symptoms before the rash appears, the characteristic appearance of the skin lesions, and the consistent progression of the lesions are present. Other indicators used to establish the diagnosis by the CDC include the distribution of the rash, primarily on the face and extremities, the presence of a rash on the palms and soles, the slow development of the rash, and the overall appearance of the patient.

These factors classify patients as having a low, moderate, or high risk of having smallpox. During smallpox infection, the skin lesions are most concentrated on the face and extremities, with fewer on the torso. The lesions on one part of the body will appear and progress simultaneously throughout the illness.

The skin lesions will change from flat spots to raised bumps, to fluid-filled blisters, to pus-filled blisters, and then to scabs, with about 48 hours between each stage. The scabbing of all the lesions are typically completed 2-3 weeks after the onset of the rash. The skin lesions are deep, circular, firm, distinct, and about 7-10 mm in diameter.

 

 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential Diagnoses

Atypical measles

Erythema multiforme (Stevens-Johnson syndrome)

Insect bites

Kawasaki disease

Monkeypox

Parvovirus B19

Rat-bite fever

Rocky Mountain spotted fever

Scarlet fever

Syphilis

 

 

Laboratory Studies

 

 

Imaging Studies

 

 

Procedures

 

 

Histologic Findings

 

 

Staging

 

 

Treatment Paradigm

Before smallpox eradication, treatment primarily involved supportive care to help the patient manage symptoms and complications. This included measures to reduce fever, such as cold compresses and pain management for skin lesions. Patients were also isolated to prevent the spread of the disease to others.

In 2018, the United States Food and Drug Administration (FDA) approved tecovirimat as the first antiviral drug specifically indicated for the treatment of smallpox.

Although the drug has not undergone extensive testing in humans, it has been studied in animal models and administered to human volunteers in a safety trial. It has also been used as an emergency investigational drug in patients who experienced complications following smallpox vaccination.

 

 

by Stage

 

 

by Modality

 

 

Chemotherapy

 

 

Radiation Therapy

 

 

Surgical Interventions

 

 

Hormone Therapy

 

 

Immunotherapy

 

 

Hyperthermia

 

 

Photodynamic Therapy

 

 

Stem Cell Transplant

 

 

Targeted Therapy

 

 

Palliative Care

 

 

Medication

 

 

 

tecovirimat 

Oral-
For 40 kg to less than 120 kg: 600 mg orally twice daily for 14 days
For >120 kg: 600 mg orally thrice daily for 14 days
Take the dose within half an hour after eating full meal (containing moderate/high fat)
Intravenous-
Use this route if the patient is unable to go through oral medication
In the patients receiving an intravenous infusion, administer 1st oral dose at the time of upcoming IV dosing
For 35kg to less than 120 kg: 200 mg intravenously over 6 hours, every 12 hours for 14 days
For more than 120 kg: 300 mg intravenously over 6 hours every 12 hours for 14 days



brincidofovir 

For patients (oral suspension or tablet) ≥48 kg: 2 doses of 200 mg orally every week (on 1st and 8th day)
For patients <48 kg (oral suspension) 2 doses of 4 mg/kg orally every week (on 1st and 8th day)



 

tecovirimat 

Oral-
For 40 kg to less than 120 kg: 600 mg orally twice daily for 14 days
For >120 kg: 600 mg orally thrice daily for 14 days
Take the dose within half an hour after eating full meal (containing moderate/high fat)
Intravenous-
Use this route if the patient is unable to go through oral medication
In the patients receiving an intravenous infusion, administer 1st oral dose at the time of upcoming IV dosing
For 3 kg to <35 kg: 6 mg/kg intravenously over 6 hours, twice daily for 14 days
For ≥13 kg: patients should turn to capsules, to complete 14-day treatment (sooner the oral is tolerated)
For 35 kg to less than 120 kg: 200 mg intravenously over 6 hours, every 12 hours for 14 days
For more than 120 kg: 300 mg intravenously over 6 hours every 12 hours for 14 days



brincidofovir 

For ≥48 kg: 2 doses of 200 mg orally each week (on 1st and 8th day)
For patients 10-48 kg: 2 doses of 4 mg/kg orally every week (on 1st and 8th day)
For patients <10 kg: 2 doses of 6 mg/kg orally every week (on 1st and 8th day)



 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK470418/

 

Smallpox Infection

Updated : January 29, 2024




Smallpox is an infectious disease caused by the variola virus and is primarily spread through the air by inhaling droplets released when an infected person speaks, coughs, or sneezes. Once the droplets are inhaled, the virus enters the body through the respiratory tract, usually through the nose or mouth.

The exact origins of smallpox are unknown, but the disease has likely been present in human populations for thousands of years. The disease was responsible for numerous epidemics and pandemics throughout history, and it is cause of mortality in millions of people before it was officially eradicated in 1980.

The World Health Organization (WHO) led a successful global smallpox eradication campaign, using a combination of vaccination and surveillance to eliminate the disease.

 

 

Smallpox is a highly contagious disease that exclusively infects humans and has no animal reservoirs, with an infection rate of up to 80% in unvaccinated populations. In the late 1700s, Edward Jenner discovered that the cowpox virus could protect people from smallpox, and later on vaccinia virus was used as a vaccine.

Throughout the 20th century, smallpox caused significant mortality and morbidity, with an estimated death of over 300 million worldwide and a case fatality rate of around 30%. The last naturally occurring case of smallpox was recorded in Somalia in 1977.

During the smallpox eradication program, two main forms of the disease were identified: Variola major and Variola minor. Variola major, had a fatality rate of 30%, was primarily found in the Indian subcontinent, Africa, and Asia. In contrast, Variola minor, which had a much lower fatality rate of less than 5%, was mainly found in East Africa and Latin America and characterized by fewer skin lesions.

 

 

 

 

The pathophysiology of smallpox involves a complex process between viral replication and host immune response. The variola virus enters the body through the respiratory tract and replicates in the lymphoid tissues, particularly in the tonsils and spleen. The virus then spreads through the bloodstream and infects various organs and tissues, including the skin, mucous membranes, and lymph nodes.

During the incubation period, which lasts 7-17 days, the virus replicates and spreads within the body without causing symptoms. Once symptoms appear, the virus causes a characteristic rash and fever. The rash starts as small red spots, which then develop into raised bumps that resemble pimples. The bumps eventually fill with pus and form scabs, which then fall off, leaving behind scars.

The virus can also infect the eyes, causing conjunctivitis, which can lead to blindness. The host’s immune response also plays an important role in the pathogenesis of smallpox. The body’s immune response to the virus is initially non-specific, with the release of inflammatory mediators, such as interferons, that can help to limit viral replication.

However, this response is not sufficient to clear the virus, and the host eventually develops a specific immune response, which is mediated by T cells and antibodies. This response is responsible for controlling the virus and ultimately leading to recovery. The severity of smallpox depends on the virulence of the virus strain, the genetic susceptibility of the host, and the timing and quality of the host’s immune response.

 

 

The etiological cause of smallpox is the variola virus, a member of the genus Orthopoxvirus in the Poxviridae family. Poxviruses are the most prominent human viral pathogens and have a brick-shaped appearance on electron microscopy, measuring approximately 300 nm to 350 nm long. The poxviruses possess a linear, double-stranded DNA genome.

They are unique in their genetic makeup, encoding all the proteins necessary for replication, allowing them to replicate in the host cell cytoplasm. The virus is highly contagious and primarily spreads through respiratory droplets when an infected person speaks, coughs, or sneezes.

It can also be spread through contact with infected bodily fluids or contaminated objects. Smallpox can cause severe symptoms such as fever, muscle aches, and a distinctive rash, leading to death in up to 30% of cases.

 

 

 

 

The prognosis of smallpox varies depending on the severity of the infection and the person’s overall health. In general, the death rate for smallpox is around 30%. However, the death rate can be as high as 80% in people with compromised immune systems. People who recover from smallpox can have long-term effects, such as scarring and blindness.

 

 

Clinical History

Smallpox is a highly contagious and potentially fatal disease caused by the variola virus. The clinical history of smallpox typically begins with a non-specific febrile prodrome, which includes symptoms such as high-grade fever, chills, abdominal pain, vomiting, headache, and backache. These symptoms occur 1 to 3 days before the appearance of the characteristic skin lesions.

The rash appears first on the face or arms and spreads to the rest of the body, often including the palms and soles. The rash starts as small red spots that quickly progress to raised bumps, filled with pus, and eventually forming scabs.

The scabs eventually fall off, leaving behind pitted scars. Other manifestations of smallpox include swollen lymph nodes, chest pain, and a distinctive backache. Smallpox can lead to serious complications such as pneumonia and brain inflammation in severe cases.

 

 

Physical Examination

Specific symptoms and characteristics, such as fever and flu-like symptoms before the rash appears, the characteristic appearance of the skin lesions, and the consistent progression of the lesions are present. Other indicators used to establish the diagnosis by the CDC include the distribution of the rash, primarily on the face and extremities, the presence of a rash on the palms and soles, the slow development of the rash, and the overall appearance of the patient.

These factors classify patients as having a low, moderate, or high risk of having smallpox. During smallpox infection, the skin lesions are most concentrated on the face and extremities, with fewer on the torso. The lesions on one part of the body will appear and progress simultaneously throughout the illness.

The skin lesions will change from flat spots to raised bumps, to fluid-filled blisters, to pus-filled blisters, and then to scabs, with about 48 hours between each stage. The scabbing of all the lesions are typically completed 2-3 weeks after the onset of the rash. The skin lesions are deep, circular, firm, distinct, and about 7-10 mm in diameter.

 

 

Differential Diagnoses

Atypical measles

Erythema multiforme (Stevens-Johnson syndrome)

Insect bites

Kawasaki disease

Monkeypox

Parvovirus B19

Rat-bite fever

Rocky Mountain spotted fever

Scarlet fever

Syphilis

 

 

 

 

 

 

 

 

 

 

 

 

Before smallpox eradication, treatment primarily involved supportive care to help the patient manage symptoms and complications. This included measures to reduce fever, such as cold compresses and pain management for skin lesions. Patients were also isolated to prevent the spread of the disease to others.

In 2018, the United States Food and Drug Administration (FDA) approved tecovirimat as the first antiviral drug specifically indicated for the treatment of smallpox.

Although the drug has not undergone extensive testing in humans, it has been studied in animal models and administered to human volunteers in a safety trial. It has also been used as an emergency investigational drug in patients who experienced complications following smallpox vaccination.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

tecovirimat 

Oral-
For 40 kg to less than 120 kg: 600 mg orally twice daily for 14 days
For >120 kg: 600 mg orally thrice daily for 14 days
Take the dose within half an hour after eating full meal (containing moderate/high fat)
Intravenous-
Use this route if the patient is unable to go through oral medication
In the patients receiving an intravenous infusion, administer 1st oral dose at the time of upcoming IV dosing
For 35kg to less than 120 kg: 200 mg intravenously over 6 hours, every 12 hours for 14 days
For more than 120 kg: 300 mg intravenously over 6 hours every 12 hours for 14 days



brincidofovir 

For patients (oral suspension or tablet) ≥48 kg: 2 doses of 200 mg orally every week (on 1st and 8th day)
For patients <48 kg (oral suspension) 2 doses of 4 mg/kg orally every week (on 1st and 8th day)



tecovirimat 

Oral-
For 40 kg to less than 120 kg: 600 mg orally twice daily for 14 days
For >120 kg: 600 mg orally thrice daily for 14 days
Take the dose within half an hour after eating full meal (containing moderate/high fat)
Intravenous-
Use this route if the patient is unable to go through oral medication
In the patients receiving an intravenous infusion, administer 1st oral dose at the time of upcoming IV dosing
For 3 kg to <35 kg: 6 mg/kg intravenously over 6 hours, twice daily for 14 days
For ≥13 kg: patients should turn to capsules, to complete 14-day treatment (sooner the oral is tolerated)
For 35 kg to less than 120 kg: 200 mg intravenously over 6 hours, every 12 hours for 14 days
For more than 120 kg: 300 mg intravenously over 6 hours every 12 hours for 14 days



brincidofovir 

For ≥48 kg: 2 doses of 200 mg orally each week (on 1st and 8th day)
For patients 10-48 kg: 2 doses of 4 mg/kg orally every week (on 1st and 8th day)
For patients <10 kg: 2 doses of 6 mg/kg orally every week (on 1st and 8th day)



 

 

https://www.ncbi.nlm.nih.gov/books/NBK470418/