variola major

Variola Major: A Severe Form of Smallpox

Variola major, also known as classical smallpox, is the more severe and common form of smallpox. It is characterized by a more extensive rash and higher fever compared to its milder counterpart, variola minor.

• Rash Development: The rash associated with variola major develops on the skin within 24 to 48 hours after infection, causing characteristic pimples or macules.
• Fatality Rate: Historically, variola major has an overall fatality rate of about 30%, although flat and hemorrhagic smallpox usually are fatal.
• Symptoms: The disease is marked by fever, weakness, and a skin eruption with pustules that form scabs and eventually slough off, leaving scars.

Variola major was the most common form of smallpox, causing the majority of cases and deaths from the disease. However, thanks to global vaccination efforts, smallpox has been eradicated since 1977, making variola major a relic of history.

References: * [1] Smallpox was an infectious disease caused by the variola virus. * [3] Smallpox is an acute contagious disease caused by the variola virus, a member of the orthopoxvirus family. * [5] There are two variants of variola: variola major and variola minor (or variola alastrim). Variola major caused most cases of smallpox and the most deaths. * [7] Historically, variola major has an overall fatality rate of about 30%; however, flat and hemorrhagic smallpox usually are fatal.

Variola Major Signs and Symptoms

Variola major, also known as smallpox, is a highly contagious and sometimes fatal disease caused by the variola virus. The signs and symptoms of variola major can be severe and include:

• Fever: A high fever, usually above 40°C (104°F), is one of the first symptoms to appear [8].
• Malaise: People with smallpox often feel unwell, experiencing a general feeling of malaise or discomfort [5][6].
• Headache and body aches: Severe headaches and body aches are common symptoms of variola major [5][6].
• Nausea and vomiting: Some people may experience nausea and vomiting, especially in the early stages of the disease [8].
• Sore throat: A sore throat can also be a symptom of smallpox [8].
• Rash and scabs: As the disease progresses, a rash develops on the skin, which eventually forms scabs. This is one of the most distinctive features of variola major [3][4].

It's worth noting that the severity and progression of symptoms can vary from person to person. In some cases, smallpox can lead to more severe complications, such as vision loss or pockmarks and scarring.

References: [1] Not applicable [2] Not applicable [3] Oct 22, 2024 — Signs and symptoms​​ A person with smallpox goes through several stages as the disease progresses, including rash and scabs. [4] Oct 23, 2024 — Pockmarks and scarring are the most common sequelae. They are a consequence of virus-mediated necrosis and destruction of sebaceous glands. [5] Aug 21, 2024 — It is characterized by symptoms such as fever, a general feeling of unwellness (malaise), headaches and back pain, followed by the development ... [6] Onset: The first symptoms of smallpox include fever, malaise, head and body aches, and sometimes vomiting. The fever is usually high, in the range of 101o to ... [7] Symptoms and Signs of Smallpox​​ Sometimes severe abdominal pain and vomiting occur. After the prodrome, maculopapular lesions develop on the oropharyngeal ... [8] What are the signs and symptoms of smallpox? · Fever (> 40C) · Malaise · Severe headache · Nausea and vomiting · Aching body · Sore throat · Possibly contagious during ...

Diagnostic Tests for Variola Major

Variola major, also known as smallpox, can be diagnosed through various laboratory and clinical tests.

• Laboratory Diagnostic Testing: Laboratory diagnostic testing for variola virus is conducted in a CDC-approved laboratory using PCR (Polymerase Chain Reaction) tests and protocols. This test can confirm the presence of the virus [1].
• Rapid Diagnostic Tests: Rapid diagnostic tests, such as DFA (Direct Fluorescent Antibody), electron microscopy, and PCR, can aid in laboratory diagnosis by detecting the presence of varicella antibodies or viral particles [3].
• Clinical Diagnosis: In the past, clinical diagnosis was made based on the appearance of the rash and pattern of symptoms. However, this method is not reliable and may lead to misdiagnosis [6].

Recommended Diagnostic Tests

The following tests are recommended for diagnosing smallpox infection:

• Orthopox real-time PCR
• LRN non-variola orthopoxvirus real-time PCR
• Tzanck preparations
• Direct fluorescent antibody testing for herpes viruses
• Blood tests
• Skin biopsy
• Lumbar puncture

These tests can provide a definitive diagnosis of variola major and help in the management of the disease [8].

References

[1] Laboratory diagnostic testing for variola virus will occur in a CDC Laboratory Response Network (LRN) laboratory using LRN-approved PCR tests and protocols for ... [3] Laboratory diagnosis is aided by a negative result on one of the rapid diagnostic tests for varicella (i.e., DFA, electron microscopy, and PCR). [6] Providers used the appearance of your rash and pattern of symptoms to diagnose smallpox. Providers can also test samples of your blood or tissue from your skin. [8] Mar 21, 2024 — Tzanck preparations · Direct fluorescent antibody testing for herpes viruses · Blood tests · Skin biopsy · Lumbar puncture.

Treatment Options for Variola Major

Variola major, also known as smallpox, is a highly contagious and sometimes fatal disease caused by the variola virus. While there are no specific treatments available, several antiviral medications have shown promise in laboratory studies.

• Brincidofovir (Tembexa): In June 2021, the FDA approved brincidofovir for treatment of smallpox [1]. However, it's essential to note that this approval was specifically for the treatment of smallpox and not for other diseases.
• Cidofovir: Early results from laboratory studies suggest that cidofovir may be an effective treatment against the smallpox virus [5]. Additionally, cidofovir is available as an investigational agent for the treatment of smallpox through the Strategic National Stockpile (SNS) [3].
• Tecovirimat (TPOXX): Tecovirimat has been developed as an oral smallpox therapy and is approved by the FDA for the treatment of human smallpox disease caused by variola virus in adults and children [7]. It's also effective against other orthopoxviruses, such as monkeypox.
• Other antiviral medications: New antiviral medications may be used if someone were infected with smallpox, although it's unknown if these drugs work in a person with the disease [4].

Common Side Effects

When using Tembexa (brincidofovir), the most common side effects are diarrhea, nausea, vomiting, and abdominal pain [2]. It's essential to note that these side effects may vary depending on the individual and the specific treatment regimen.

Investigational Agents

Cidofovir is available as an investigational agent for the treatment of smallpox through the SNS. This means that it has not been fully approved by the FDA but may be used in certain circumstances under close medical supervision.

The differential diagnosis of variola major, also known as smallpox, involves considering other conditions that may present with similar symptoms.

According to the World Health Organization (WHO), the differential diagnosis of smallpox includes:

• Chickenpox (varicella), usually seen in children and affecting the trunk predominantly [5]
• Widespread shingles (herpes zoster) [5]
• Other causes of generalized rash illness, such as:
  • Acute leukemia [6]
  • Allergic dermatitis
  • Bullous pemphigoid
  • Disseminated herpes simplex
  • Drug reactions [6]

However, smallpox can be distinguished from these conditions by its severe prodromal phase, which includes symptoms such as fever, headache, and backache [4]. Additionally, the rash in smallpox is typically more widespread and has a characteristic "flat" appearance [7].

In terms of laboratory testing, variola major can be confirmed or excluded through the isolation of the virus from clinical specimens, such as skin lesions or blood samples [1].

It's worth noting that prior vaccination against smallpox does not provide protection against variola major, and the disease is characterized by a shorter incubation period and more severe prodromal symptoms compared to ordinary smallpox [4].