Is Mpox the Same as Smallpox?
No — mpox and smallpox are not the same disease, but they are caused by related viruses from the same family. Both Monkeypox virus (which causes mpox) and Variola virus (which causes smallpox) belong to the Orthopoxvirus genus. They share significant genetic similarity, which is why vaccines developed against smallpox also provide approximately 85% protection against mpox. However, mpox is far less transmissible, far less lethal, and causes a less severe illness than smallpox. Smallpox was declared eradicated in 1980 and no longer circulates in nature.
| Feature | Mpox | Smallpox |
|---|---|---|
| Virus | Monkeypox virus (MPXV) | Variola virus (VARV) |
| Current status | Endemic + ongoing outbreaks | Eradicated 1980; only in WHO-designated repository labs |
| Case fatality rate | 0.1–10% (varies by clade) | ~30% (Variola major); ~1% (Variola minor) |
| Transmission | Close skin contact; less efficiently respiratory | Respiratory droplets; more efficiently person-to-person |
| R0 | ~1.5–2 (2022 outbreak) | ~5–7 (historical) |
| Swollen lymph nodes | Yes (characteristic) | Less common |
| Rash distribution | Often concentrated; may be genital | Centrifugal (face and extremities first) |
| Vaccine (current) | JYNNEOS (2-dose) | ACAM2000 (stockpile only); not in routine use |
Orthopoxviruses share substantial genetic sequences — approximately 95–97% genetic similarity in key protective antigen regions between Monkeypox and Variola viruses. The immune response triggered by smallpox vaccination (whether using Vaccinia virus in ACAM2000 or the modified vaccinia Ankara in JYNNEOS) cross-reacts with Monkeypox virus antigens. Historical data from African studies showed people vaccinated against smallpox had approximately 85% protection against mpox — explaining why mpox incidence rose after routine smallpox vaccination ended in the 1980s and the post-1980 birth cohort (with no smallpox immunity) grew.
Smallpox is the only human infectious disease to have been deliberately eradicated. The global eradication campaign, led by WHO and completed in 1980, involved universal vaccination with the live Vaccinia virus vaccine. The last known natural case was in Somalia in 1977. Today, Variola virus is kept in only two WHO-authorized repositories — CDC in Atlanta, USA, and VECTOR Institute in Kolkata (previously Novosibirsk), Russia. All other samples were destroyed. Debate continues about whether these final stocks should also be destroyed.
- Could mpox evolve to become as deadly as smallpox?
- This is theoretically possible through mutations or recombination events, but there is no evidence it is occurring. Mpox and smallpox viruses differ in many genetic regions that affect transmissibility and lethality. Scientists actively monitor Mpox genomes for concerning changes. The 2024 Clade I outbreak shows that mpox can evolve toward greater human-to-human spread, but lethality and transmissibility comparable to smallpox would require extensive genetic changes.
- If smallpox is eradicated, why do we need mpox vaccines?
- Mpox is a distinct circulating disease. The 2022 outbreak demonstrated it can spread globally without the smallpox-immune population that previously kept it in check. JYNNEOS was specifically designed as a safer, modern mpox/smallpox vaccine — unlike the old live Vaccinia vaccines which caused significant side effects and were contraindicated in immunocompromised people. Mpox vaccination is recommended for high-risk individuals regardless of smallpox eradication.
- Are there other orthopoxviruses I should know about?
- Yes — Cowpox (found in Europe; transmitted from cats and rodents; causes localized skin lesions), Vaccinia (used in vaccines; can rarely spread from vaccinated individuals), and Horsepox (possibly ancestral to Vaccinia). None cause pandemics. Monkeypox is currently the orthopoxvirus of greatest public health concern after Variola's eradication.