Smallpox

Dr. Ajay Mohan (AIIMS)MBBS

September 28, 2020

September 28, 2020

Smallpox
Smallpox

Smallpox is a highly contagious disease caused due to variola virus infection. The viral infection spreads through respiratory droplets or fomites (contaminated objects) and causes fever and rashes on the body.

Due to widespread immunization, smallpox was declared eradicated about 40 years back and no vaccination is now needed against the disease. However, the virus has been kept at at least two different labs in the world to keep the research going since some government organisations have suggested that it can be used as a bio-weapon.

There is no cure for smallpox. Vaccination is suggested to those who are at risk of coming in contact with the virus.

What is smallpox?

Smallpox is a disease caused by the variola virus. The virus spreads through respiratory droplets and causes a flu-like illness followed by the development of skin lesions that slowly scab and scar.

According to the Federation of American Scientists, smallpox killed around 500 million people in the 20th century. The disease itself, however, is quite old and is believed to have been present in Egypt in the 3rd century BCE.

Smallpox eradication

In 1948, the World Health Organization (WHO) decided to form a small study group to find out which strain of the variola virus would be most effective for making a vaccine against the disease. By 1959, a programme had begun to provide smallpox vaccine to various countries. However, it wasn’t successful because of shortages of supplies and funds. 

In 1967, a mass vaccination programme was again launched by the World Health Assembly, the governing body of the WHO. The programme aimed at vaccinating 80% of the global population, and maintaining continuous surveillance and containment to keep the disease from spreading. Weekly reports were given to the WHO about any cases in an area so appropriate measures could be taken to avoid an outbreak. 

The last naturally acquired case of variola major was seen in 1975 in Bangladesh and that of variola minor in Somalia in 1977.

On 8 May 1980, the World Health Assembly declared that smallpox had been eradicated from the world.

In 2017, a study from China stated that five processing workers had acquired smallpox while handling skins from rabbits that were being used to study the virus in a lab. None of the workers had been wearing protective clothing. Three other employees who were there but were wearing masks and did not touch the rabbit skins did not get the disease. One person was hospitalised while three of the infected workers were previously vaccinated for smallpox and hence did not develop severe disease.

Though the disease was declared eradicated in 1980, four labs in different parts of the world had kept samples of variola major—these labs were in the US, England, Russia and South Africa. However, as of now, only two of these stocks remain—one in Russia and one in the US. 

As per the WHO, the stocks have been kept because some governments thought the variola virus may be present outside the designated labs and is so contagious that it can be used as a bio-weapon. The WHO is working with various countries to avoid such a situation.

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Smallpox stages and symptoms

Smallpox infection goes through the following stages and each stage has its own set of symptoms:

Incubation period: Smallpox has an incubation time (time between exposure to the virus and development of symptoms) of about 12 days (between seven and 17 days). 

Prodrome stage: The prodrome stage lasts from two to four days. During this stage, the patient experiences flu-like symptoms including high fever (101º F to 104º F), headache, malaise and fatigue

Early rash: This stage lasts for about four days. It is characterised by the presence of an enanthem—a rash on the mucous membrane inside the mouth, nose or throat.  Within the next 24 hours, rashes appear all over the body with higher concentrations on the face and limbs (arms and legs). Smallpox lesions look firm with an indentation (dent) in the centre. The patient will again get fever which will stay until the lesions scab off. 

Pustules and scabbing: This stage lasts for about five days. The lesions turn into pustules (filled with pus). The pustules feel like there is something embedded in them. In the next 10 days, the pustules slowly start to scab and then fall off. The scabs leave pitted scars on the skin.   

A patient with smallpox is contagious starting from the flu-like stage until the lesions are scabbing.

Smallpox causes

Smallpox occurs due to variola virus infection. There are two types of variola viruses that can cause smallpox in humans—variola major and variola minor. 

The virus enters the body when a person inhales respiratory droplets from an infected person (spread by sneezing or coughing) or through direct contact with contaminated objects like the clothes of a patient.

Once inside the body, the virus replicates in the throat lining. From here, the variola virus is transferred to lymph nodes by the white blood cells.

The virus can evade the immune system, and after replicating for three to four days, spreads to the bone marrow and spleen and then back to blood vessels, which ultimately results in the appearance of fever and the other symptoms of the disease.

Smallpox types

Smallpox caused due to variola minor virus usually shows the clinical features of ordinary smallpox but has less severe lesions and toxaemia and a shorter healing period. Variola minor infection has a fatality rate of less than 1%.

According to the Centers for Disease Control and Prevention, USA, smallpox has four major clinical forms. These include:

  • Ordinary smallpox: Ordinary smallpox is caused by the variola major virus and was responsible for about 85% of all cases of smallpox until 1980. 
  • Malignant or flat-type smallpox: This type of smallpox is characterized by intense toxaemia, a condition that is equated with present-day definitions of sepsis and septic shock. Malignant smallpox is rare but occurs more commonly in children. Flat type smallpox usually leads to death. However, the lesions that form in this type of smallpox do not form papules or leave scars—they merge together and give a velvety appearance.
  • Modified type smallpox: This type of smallpox occurs in those who have already been vaccinated against the disease. Patients show the initial flu-like symptoms, however, the lesions quickly clear away and are not as deep.
  • Hemorrhagic smallpox: In this type of smallpox, the patient gets bleeding in the lesions on the skin and mucous membranes. Hemorrhagic smallpox also has more severe initial symptoms and a comparatively shorter incubation period. Most (about 95%) people die within a week of symptom showing up due to multiorgan failure and toxaemia.
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Prevention of smallpox

Vaccination is the best way to prevent smallpox. However, since the disease has been eradicated, a smallpox vaccine is not mandatory in any country. Mostly due to the possible side effects associated with the vaccine.

Smallpox vaccine was the first-ever vaccine made. Edward Jenner, an English physician had developed the earliest form of smallpox vaccine through scabs obtained from cowpox lesions. Then, the term variolation (named after the variola virus) was used for this procedure instead of vaccination. Unlike the modern vaccines, variolation involved inoculation of material taken from cowpox vesicles into the scraped skin of a healthy person.

The modern smallpox vaccine is made from the vaccina virus, which is similar to the smallpox virus but less deadly. The vaccine is given through a two-pronged needle into the skin, Usually, a smallpox lesion develops at the vaccine site. This lesion should not be touched to avoid spreading the virus to other parts of the body. The lesion eventually scabs and falls off. Some rare but severe side effects of smallpox vaccine include generalised lesions on the body, eczema vaccinatum (a condition that occurs in eczema patients) or encephalitis.

Diagnosis of smallpox

Smallpox is diagnosed based on the clinical presentation of the disease, patient history and the patient's risk of exposure to the virus. The typical lesions on the face, limbs and trunk are the main diagnostic feature of the disease. 

Chickenpox was often confused with smallpox. However, the former has more superficial lesions, which are more prominent on the trunk rather than the hands, legs and face and reoccur in the same areas. 

The Centers for Disease Control and Prevention, USA, lists the following emergency measures in case a smallpox case shows up:

  • Isolate the patient, preferably in a room where the airborne infection can't spread to others.
  • Cover the patient with a sheet and give them N95 masks to cover their nose and mouth.
  • All people close to the patient to wear protective gloves, gowns and N95 masks.
  • If the case is in a hospital, the infection control department should be notified immediately.

Smallpox treatment

There is no cure for smallpox. Patients are given supportive treatment to manage their symptoms. An antiviral drug called cidofovir had shown positive results in early studies done by the US National Institute of Allergy and Infectious Diseases (NIAID). The NIAID got the drug approved by the US Food & Drug Administration (FDA) for experimental use in case of a bioterrorist attack. However, the drug can damage the kidneys and can only be given through the intravenous (IV) route. 

A derivative of cidofovir called brincidofovir was later developed by the NIAID. This drug is less toxic and can be taken orally. Brincidofovir was shown to be effective in phase 1 clinical trials and has moved on to further trials.

In 2018, the US FDA approved an antiviral called tecovirimat for smallpox treatment. As per the CDC (US Centers for Disease Control and Prevention), vaccinating people within the first two or three days of exposure can reduce symptom severity.

Vaccinia immune globulin (antibodies against the virus) are given for the management of complications that may occur due to the smallpox vaccine.

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Smallpox risks and complications

Three out of 10 (30%) people who got variola major infection and one in 10 people (10%) who got infected with variola minor virus died from smallpox. The rest suffered scarring and some of the other conditions mentioned above.

The scabbing and scarring in smallpox occur due to necrosis (cell death) of sebaceous glands (oil glands) and is more prevalent on the face—because the face has more sebaceous glands. 

The condition may also lead to:



References

  1. Centers for Disease Control and Prevention [internet], Atlanta (GA): US Department of Health and Human Services; History of Smallpox
  2. World Health Organisation [Internet]. Geneva. Switzerland; Statue commemorates smallpox eradication
  3. Bray Mike, Buller Mark. Looking Back at Smallpox. Clinical Infectious Diseases. 2004 March; 38(6): 882–889.
  4. Stanford University [Internet]. California. US; Variola minor
  5. National institute of Allergy and Infectious Diseases [Internet]. National Institute of Health. US Department of Health and Human Services; Smallpox Treatment
  6. Yuhong Xiao, Stuart N. Isaacs. Therapeutic Vaccines and Antibodies for Treatment of Orthopoxvirus Infections. Viruses. 2010 Oct; 2(10): 2381–2403. PMID: 21197387.

Medicines for Smallpox

Medicines listed below are available for Smallpox. Please note that you should not take any medicines without doctor consultation. Taking any medicine without doctor's consultation can cause serious problems.