Poxviruses and Mpox
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Direct answer
Poxviruses are large, enveloped, double-stranded DNA viruses that replicate entirely in the cytoplasm, using many of their own enzymes. Mpox is a zoonotic orthopoxvirus infection that now also spreads between people, and it is the most important human orthopox infection since smallpox was eradicated. Molluscum contagiosum, a benign skin infection, is caused by a poxvirus from a different genus.
What you must remember
- Virion: Brick-shaped or ovoid, enveloped, with a dumbbell-shaped core, and it replicates in the cytoplasm rather than the nucleus.
- Smallpox eradication: The World Health Assembly declared smallpox eradicated in 1980, and variola stocks are held only in two WHO-approved repositories.
- Molluscum contagiosum: A molluscipoxvirus causing pearly, umbilicated papules, mainly in children and in HIV-infected adults.
- Molluscum bodies: Large intracytoplasmic inclusions, also called Henderson-Patterson bodies, seen in infected keratinocytes.
- Mpox virus: An orthopoxvirus with clade I in Central Africa and clade II in West Africa, and clade IIb caused the 2022 global outbreak.
- Clinical course: A prodrome of fever and lymphadenopathy, followed by vesicles that become umbilicated pustules, often on the face, palms and soles.
- Diagnosis: Orthopoxvirus PCR on lesion material is the preferred test, since antibodies appear too late to guide early management.
- Vaccination: Older smallpox vaccination gives cross-protection against mpox, and MVA-BN is a non-replicating vaccine used for mpox prevention.
Comparing three pox infections
The three diseases share a rash but differ in agent, transmission and status. The table below sets out the features most often tested.
| Feature | Smallpox | Mpox | Molluscum contagiosum |
|---|---|---|---|
| Causative agent | Variola virus, an orthopoxvirus | Monkeypox virus, an orthopoxvirus | Molluscum contagiosum virus, a molluscipoxvirus |
| Current status | Eradicated, with stocks held only in two approved repositories | Ongoing zoonotic spread with human-to-human transmission | Common, self-limiting benign skin infection |
| Lymphadenopathy | Not a typical feature | Prominent and a key distinguishing feature | Absent |
| Lesion appearance | Deep-seated lesions with centrifugal distribution | Umbilicated vesicles progressing to pustules | Pearly, umbilicated papules |
| Key laboratory marker | Historical electron microscopy and variola PCR in approved labs | Orthopoxvirus PCR on lesion swab | Clinical diagnosis, with molluscum bodies on histology |
Three features separate these diseases in an exam: the eradicated status of smallpox, the lymphadenopathy that marks mpox, and the benign papule of molluscum. Cross-protection between orthopoxviruses explains why smallpox vaccination protected against mpox, whereas smallpox vaccination gives no protection against molluscum because it belongs to a different genus.
Where the exam tries to catch you
Pox questions usually hinge on the genus, the lymphadenopathy and the status of each disease.
- Trap: Treating mpox as eradicated because smallpox was eradicated. Correct: Eradication applied only to variola, while mpox is zoonotic and still circulates in animal reservoirs and humans.
- Trap: Counting lymphadenopathy as a feature of smallpox. Correct: Lymphadenopathy is a prominent feature of mpox, so its presence favours mpox over smallpox.
- Trap: Expecting serology to confirm acute mpox. Correct: PCR on lesion material is the preferred acute test, because antibody responses develop too late to guide early care.
Frequently asked questions
Why was smallpox eradicated but mpox has not been?
Smallpox was eradicated through global vaccination and surveillance because humans were its only natural host, so it had no animal reservoir. Mpox has zoonotic reservoirs in rodents and other animals, so it continues to circulate even after human transmission is controlled.
Which poxvirus genus causes molluscum contagiosum?
Molluscum contagiosum is caused by a molluscipoxvirus, a different genus from the orthopoxviruses that cause smallpox and mpox. It produces pearly, umbilicated papules, mainly in children, and is usually self-limiting in immunocompetent hosts.
What are molluscum bodies and why do they matter?
Molluscum bodies are large intracytoplasmic inclusions, also called Henderson-Patterson bodies, found in the infected keratinocytes of molluscum lesions. Their presence on histology or a curettage smear establishes the diagnosis of molluscum contagiosum.
Why does lymphadenopathy matter when distinguishing mpox from smallpox?
Lymphadenopathy is a prominent feature of mpox and is one of its key clinical differences from smallpox. Its presence in a patient with a vesicular rash favours mpox, although confirmation still depends on orthopoxvirus PCR.
Which vaccine is used for mpox prevention?
MVA-BN is a non-replicating modified vaccinia Ankara vaccine used for mpox prevention in high-risk groups. Older smallpox vaccination also gives cross-protection against mpox, which is why populations vaccinated before smallpox vaccination stopped are considered less susceptible.