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Smallpox

Humza Khizer

Overview

Smallpox is a contagious and fatal illness caused by the smallpox virus. 
Smallpox has been a threat to humanity for thousands of years. It was eradicated globally by 1980 owing to smallpox vaccines. However, smallpox has lately gained attention because of the possibilities of its use as a weapon of warfare or bioterrorism.

&nbsp;

Based on the discovery of smallpox-like lesions on Egyptian mummies, the disease can be dated back 3,000 years. The first documented case of a smallpox-like illness was made in China, in the 4th century CE (Common Era<a href="#accordion">[11]</a>.

Since its eradication, there have been no verified cases of smallpox. The last smallpox case occurred in 1977. Before its eradication, however, smallpox was a highly fatal illness, with a case fatality rate of 30%<a href="#accordion">[9]</a>. The disease infected and killed millions of people worldwide for over two centuries. People who survived the disease frequently suffered long-term complications, such as blindness and severe scarring.

Currently, the smallpox virus exists only in two locations - the Centers for Disease Control and Prevention (CDC) in Atlanta and Russian government laboratories in Moscow.&nbsp; 
&nbsp;

There are two types of smallpox virus: variola minor and variola major.

<ul>
	<li>Variola Minor: It is the less virulent strain, with a mortality rate of 1%[5]. It was endemic in some European countries, North America, South America, and many parts of Africa. 
	&nbsp;</li>
	<li>Variola Major (Classic Smallpox): It is the more virulent strain, with a case fatality rate of 30%[5]. Variola major was the world&#39;s most common endemic strain. By the end of the 18th century, it was responsible for nearly 400,000 deaths each year in Europe<a href="#accordion">[8]</a>. 
	&nbsp;</li>
</ul>

Variola major smallpox has four subcategories, which are as follows<a href="#accordion">[8]</a>:

<ul>
	<li>Ordinary Smallpox - This was the most prevalent type, accounting for 90% or more of all instances of smallpox. 
	&nbsp;</li>
	<li>Modified Smallpox - A mild variant that occurred in previously immunized people. 
	&nbsp;</li>
	<li>Flat Smallpox (Malignant Smallpox) - This is a severe form of smallpox in which lesions do not protrude beyond the skin&#39;s surface. 
	&nbsp;</li>
	<li>Hemorrhagic Smallpox (Fulminant Smallpox) - A rare, extremely severe, and lethal form of smallpox in which hemorrhages form in the skin and mucous membranes. 
	&nbsp;</li>
</ul>

Other types of smallpox include the following:

<ul>
	<li>Variola Sine Eruptione (Variola Sine Exanthemata) - This is a rare kind of smallpox. 
	&nbsp;</li>
	<li>Pulmonary Form Of Smallpox - Severe symptoms, cyanosis, and bilateral infiltrates in individuals with little or no immunity to the disease characterize this form of smallpox. It has an undetermined mortality rate. 
	&nbsp;</li>
	<li>The Pharyngeal Variant Of Smallpox - This form appears in inoculated people and is distinguished by a patchy enanthem over the soft palate, uvula, and throat. 
	&nbsp;</li>
	<li>Influenza-Like Form Of Smallpox - This type rarely results in a rash. 
	&nbsp;</li>
</ul>

Signs and Symptoms

According to historical reports, those who were infected with the smallpox virus exhibited no symptoms for seven to nineteen days. This is called the incubation stage. However, when the incubation period (or viral development phase) ends, flu-like symptoms appear, such as:

<ul>
	<li>High fever</li>
	<li>Chills</li>
	<li>Headache</li>
	<li>Severe back pain</li>
	<li>Abdominal pain</li>
	<li>Vomiting 
	&nbsp;</li>
</ul>

Initial Stage: This stage lasts around three days. It is characterized by fever, headaches, muscular pains, backaches, and vomiting.&nbsp; A body-wide rash emerges after the initial symptoms. The person is most infectious during this period. Coughing, sneezing, and even talking can spread the virus to others. 
&nbsp;

During the first rash stage:

<ul>
	<li>A rash appears on the tongue, as well as inside the throat and mouth. The red patches can transform into sores and rupture.</li>
	<li>The rash typically spreads to the face, back, arms, legs, and body. In approximately a day, the rash spreads across the body, including to the soles of the feet and palms of the hand.</li>
	<li>Pus-filled bumps form on the skin. These lesions typically fill with fluid in around 2 days. 
	&nbsp;</li>
</ul>

These bumps then develop into pustules. During the next 10 days, the pustules become covered with crusty scabs. These scabs come off after about three weeks. A smallpox patient is infectious until the final scab falls off. Scars result from the scabs falling off. 
&nbsp;

Causes

Smallpox results from the smallpox virus. The virus can spread as follows: 
&nbsp;

<ul>
	<li>Directly From One Person To Another: Being around someone who has smallpox can expose one to the virus. When an infected individual coughs, sneezes, or speaks, they can transmit the virus. Smallpox can also be contracted by coming into touch with skin lesions. 
	&nbsp;</li>
	<li>Indirectly From An Infected Individual: Smallpox can occasionally spread through the air within buildings, infecting people in different rooms or levels. 
	&nbsp;</li>
	<li>Using Infected Products: Contact with infected clothing and bedding can potentially transmit smallpox. However, catching smallpox this way is less likely. 
	&nbsp;</li>
	<li>As A&nbsp;Terrorist Weapon: Smallpox as a weapon is a remote possibility. However, because unleashing the virus might swiftly spread the disease, governments are reluctant to do so. 
	&nbsp;</li>
</ul>

Diagnosis

There are currently no screening tests for smallpox. People at high risk of smallpox may be required to undergo laboratory testing with PCR tests.

The diagnosis of smallpox is typically based on the appearance of the rash and the patient&rsquo;s symptoms. 
&nbsp;

<h5>History And Physical Examination:</h5>

The doctor will inquire about:

<ul>
	<li>Any symptoms preceding the onset of rash, including prodromal symptoms and clinical features in the 1 to 4 days before rash onset.</li>
	<li>Contact with any sick people (especially those with a rash illness).</li>
	<li>Recent travel history.</li>
	<li>Interaction with sick or exotic animals.</li>
	<li>Medication and medical history.</li>
	<li>Previous varicella or herpes zoster infection.</li>
	<li>Varicella vaccination history (vaccine available since 1995) 
	&nbsp;</li>
</ul>

<h5>Laboratory Evaluations:</h5>

Because a positive smallpox test result has a limited predictive value in the absence of established smallpox sickness, only patients that fulfill the clinical criteria of the disease should be examined. 
&nbsp;

The laboratory criteria for diagnosis are as follows:

<ul>
	<li>Polymerase chain reaction (PCR) detection of variola DNA in a clinical specimen, or</li>
	<li>Electron microscopy or viral culture of material scraped from skin lesions and subsequently confirmed by PCR. 
	&nbsp;</li>
</ul>

Treatment

There is no cure for smallpox. Treatment is mostly supportive, and antibiotics are administered for secondary bacterial infections. As per the FDA, two antiviral drugs - tecovirimat and brincidofovir -&nbsp; are approved for use in the treatment of smallpox. While these drugs have demonstrated effectiveness in animal and laboratory experiments, they have not been tested on people. However, they can both be used in case of an outbreak. 
&nbsp;

Isolation is a key aspect of smallpox treatment. Infected people are isolated in an air-borne infection isolation room, while their contacts are placed under surveillance. Home isolation may be required in case of mass outbreaks.

The widespread use of the smallpox vaccine helped completely eradicate the disease. However, the vaccine cannot prevent illness or attenuate the disease if given too late following exposure. Currently, the vaccines are only recommended for people at high risk of exposure to the virus, for example, laboratory workers. 
&nbsp;

Hemorrhagic and malignant smallpox most commonly led to death. The most lethal types of the disease are more likely to harm pregnant women and individuals with compromised immune systems.

Smallpox survivors may have scars on their faces and bodies. Rarely, they can develop blindness. Smallpox can also lead to infertility in males and miscarriage or stillbirth in women. 
&nbsp;

Serious complications occur in around one out of every 10,000 individuals following their initial (primary) immunization. Includes the following:

<ul>
	<li>Postvaccinal <a href="https://merisehat.pk/disease/encephalitis">encephalitis</a></li>
	<li>Progressive vaccinia&nbsp;</li>
	<li>Eczema vaccinatum</li>
	<li>Generalized vaccinia</li>
	<li>Pericarditis and/or Myocarditis</li>
	<li>Vaccinia virus keratitis</li>
	<li>Noninfectious rashes 
	&nbsp;</li>
</ul>

The following factors increase the risk of smallpox:

<ul>
	<li>Physical contact with someone with smallpox</li>
	<li>Expose to infected bodily fluids</li>
	<li>Exposure to contaminated surfaces</li>
	<li>Contact to aerosolized particles from someone with smallpox</li>
	<li>Mishandling while working in a laboratory with a virus. 
	&nbsp;</li>
</ul>

In case of a smallpox outbreak, those carrying the virus should be isolated to prevent the virus from spreading. Anyone who comes in contact with a person who has smallpox will require a smallpox vaccine.&nbsp; The vaccine should be administered either before or one week after being exposed to the virus. There are two vaccinations available:

The ACAM2000 Vaccination Employs a live virus that is similar to smallpox but less dangerous. It can occasionally produce significant adverse effects, including heart or brain infections. For this reason, not everyone receives the immunization. Unless there is a smallpox outbreak, the hazards exceed the benefits for the vast majority of individuals. 
&nbsp;

A Second Vaccination, Jynneos Employs a much weaker strain of the virus and is safer than ACAM2000. It can be utilized in persons who are unable to take ACAM2000 because of compromised immune systems or skin issues. 
&nbsp;

Smallpox immunizations also protect against other viral illnesses that are comparable to smallpox, such as monkeypox and cowpox. 
&nbsp;
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Key points

<ul>
	<li>Smallpox is a potentially contagious and fatal illness caused by a brick-shaped, double-strand DNA virus from the genus Orthopoxvirus.</li>
	<li>The origin of smallpox is unknown. Smallpox has been a threat to humanity for thousands of years, but it was eradicated globally by 1980 owing to smallpox vaccines. It can no longer be found in nature.</li>
	<li>The last case of smallpox was recorded in 1977.</li>
	<li>Before its eradication, smallpox was a deadly infectious disease caused by the variola virus.</li>
	<li>Smallpox develops in stages. Some common symptoms include fever, headaches, backache, fatigue, vomiting, and a characteristic rash.</li>
	<li>The rash typically begins in the mouth and spreads to the rest of the body. It can develop into a sore and then pustules. These pustules then scab and as the scab falls off, it leaves behind disfiguring scars.</li>
	<li>Smallpox virus is commonly divided into variola major and variola minor. Variola major was responsible for 90% of cases.&nbsp;</li>
	<li>Smallpox can manifest in four clinical forms. The most prevalent kind, known as ordinary smallpox, accounted for 90% of occurrences. Flat smallpox, hemorrhagic smallpox, and vaccine-modified smallpox are the other forms.</li>
	<li>People who contracted hemorrhagic or malignant smallpox were more likely to die.</li>
	<li>If there is a smallpox outbreak, those carrying the virus would be isolated to try to stop the virus from spreading. Anyone who comes into contact with a person who has smallpox will require a smallpox vaccine.&nbsp; The vaccine should be administered either before or one week after being exposed to the virus.</li>
	<li>Smallpox immunizations also protect against other viral illnesses that are comparable to smallpox, such as monkeypox and cowpox. 
	&nbsp;</li>
</ul>