Mpox Guide 2025: Clade Ib, Vaccines, Symptoms & What You Need to Know
From the 2022 global outbreak to the 2024 WHO PHEIC for Clade Ib — a comprehensive, up-to-date guide to mpox.
What Is Mpox?
Mpox (formerly known as monkeypox) is a viral zoonotic disease caused by Monkeypox virus (MPXV), an Orthopoxvirus in the Poxviridae family — the same family as smallpox. First identified in humans in 1970 in the DRC, it was historically considered a mild, self-limiting disease endemic to Central and West Africa. That changed dramatically in 2022.
The virus was renamed "mpox" by WHO in November 2022 to reduce stigma associated with the "monkeypox" name (rodents, not monkeys, are the likely reservoir).
Two Clades, Very Different Severity
| Feature | Clade I (Central African) | Clade II (West African) |
|---|---|---|
| CFR | 1–10% | <0.1% |
| Severity | More severe, higher viral load | Milder; severe mainly in immunocompromised |
| 2022 Global Outbreak | No | Yes — Clade IIb |
| 2024 PHEIC | Yes — Clade Ib | Ongoing but lower-level |
| Geographic range | DRC, Central Africa → East Africa | West Africa; globally 2022+ |
The 2022 Global Outbreak (Clade IIb)
In May 2022, mpox cases began appearing in countries with no epidemiological link to Africa — starting in the UK, then rapidly spreading to Europe, the Americas, and beyond. By December 2022, over 87,000 cases had been reported in 110 countries. The 2022 outbreak was declared a PHEIC in July 2022 (WHO's highest alert level) — then de-escalated in May 2023 as cases fell sharply following vaccination campaigns and behavior change.
Key features of the 2022 outbreak: Transmission primarily through sexual contact networks (especially among men who have sex with men); genital, perianal, and oral lesions were common; the rash was often fewer and more localized than classic mpox; many patients had no prodromal phase before rash appeared.
The 2024 Clade Ib Emergency
In August 2024, WHO declared a second PHEIC for mpox — this time driven by Clade Ib, a new sublineage of the more severe Clade I virus emerging in eastern DRC and spreading to neighboring countries (Burundi, Uganda, Rwanda, Kenya). Clade Ib shows evidence of efficient sexual transmission — a new behavior for Clade I — as well as child-to-child transmission in household and school settings.
The 2024 emergency is fundamentally different from 2022: higher severity, a different geographic epicenter, and spread in contexts of conflict and displacement where health systems are fragile. As of early 2025, cases have been reported in over 10 African countries and a handful of imported cases elsewhere.
Symptoms: What to Expect
Fever (38–40°C), intense headache, fatigue, myalgia (muscle pain), backache. Crucially, lymphadenopathy (swollen lymph nodes) — especially cervical, inguinal, or axillary — distinguishes mpox from smallpox and chickenpox, which don't cause lymph node swelling. The 2022 outbreak sometimes skipped the prodromal phase entirely.
Rash typically begins on the face and spreads centrifugally (outward to extremities including palms and soles). Progresses through five synchronized stages: macule → papule → vesicle → pustule → crust. All lesions are at the same stage simultaneously (unlike chickenpox where lesions appear in waves at different stages). Rash may affect 5 to 5,000 lesions depending on severity. In 2022, genital and perianal lesions were common.
Crusts fall off naturally over 2–4 weeks. Person is infectious until ALL lesions have crusted, dried, and fallen off completely — not just until they feel better. Scarring is possible, especially with secondary bacterial infections or severe disease. Corneal involvement can cause vision loss.
Transmission
Mpox spreads through:
- Direct skin/mucosa contact: Touching rashes, scabs, or lesions on an infected person
- Bodily fluids: Saliva, respiratory secretions during prolonged face-to-face contact
- Contaminated objects (fomites): Bedding, clothing, towels used by infected person
- Sexual transmission: A key route for both Clade IIb (2022) and Clade Ib (2024)
- Zoonotic spillover: Contact with infected animals (rodents, primates) — still important in endemic areas
Mpox is not as contagious as COVID-19 or measles. R0 in the 2022 outbreak was estimated at 1.7–2.1, falling sharply with behavioral interventions and vaccination.
Vaccines
JYNNEOS (Imvamune/Imvanex): FDA-approved two-dose live attenuated vaccine. Based on Modified Vaccinia Ankara (MVA), a non-replicating strain. Efficacy approximately 85% against mpox. Safe in immunocompromised individuals (unlike ACAM2000). The 2022 outbreak drove a massive scale-up; demand vastly exceeded supply. Subcutaneous or intradermal dosing.
ACAM2000: Replication-competent smallpox vaccine. Available under expanded access. Provides cross-protection against mpox due to shared Orthopoxvirus antigens. Contraindicated in immunocompromised patients, those with eczema, pregnant women. One-dose; takes 4 weeks for full protection.
Both vaccines provide some protection even post-exposure if given within 4 days of exposure (up to 14 days to reduce severity).
Treatment
Tecovirimat (TPOXX/ST-246): Antiviral specifically targeting the orthopoxvirus VP37 protein. FDA-approved for smallpox; used under IND/EAP for mpox. Most prescribed mpox antiviral in 2022. Recent PALM-007 trial results showed mixed efficacy data — ongoing research. Generally used in severe disease, immunocompromised patients, and children.
Brincidofovir (Tembexa): FDA-approved for smallpox; used for severe mpox off-label. Nucleotide analog.
Cidofovir: Older antiviral; nephrotoxic but available in settings where other agents are not.
For most patients with Clade IIb, mpox is self-limiting: supportive care (pain management, wound care, hydration) is sufficient. Secondary bacterial infections are the most common complication and require antibiotics.
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Frequently Asked Questions
No. Both are Orthopoxviruses and the diseases are clinically similar, but mpox is distinct and less severe than smallpox. Smallpox was eradicated in 1980. Mpox remains endemic in Central and West Africa with ongoing global spread. Smallpox vaccines (including JYNNEOS and ACAM2000) provide cross-protection against mpox.
The 2022 outbreak was Clade IIb (West African clade), which is milder with CFR <0.1%. Clade Ib is a sublineage of the more severe Clade I (Central African clade) with CFR 1–10%. Clade Ib is spreading through DRC and East Africa (2024 PHEIC) with evidence of efficient sexual transmission new to Clade I viruses.
WHO and CDC recommend JYNNEOS for: people with known or suspected exposure to mpox; gay, bisexual, and other men who have sex with men with multiple partners; people with HIV; laboratory workers handling Orthopoxviruses. Post-exposure vaccination within 4 days of exposure can prevent disease; within 4–14 days may reduce severity.
Mpox is not exclusively an STI — it can spread through any close physical contact. However, sexual contact was the predominant transmission route in the 2022 Clade IIb global outbreak, and sexual transmission is also driving the Clade Ib outbreak. Condom use reduces but does not eliminate transmission risk (skin contact beyond genital areas can transmit).
Sources: WHO mpox situation reports; CDC mpox guidance; NEJM 2022 outbreak characterization; Lancet Infectious Diseases Clade Ib analyses; PALM-007 trial data.
See also: Mpox disease overview
Related: Mpox disease page · Ebola history · Is mpox the same as smallpox?