Epidemiology and Characteristics of MPXV Clade I cases in the WHO European Region, 2024-2025

This study characterizes 82 MPXV clade I cases in the WHO European Region from August 2024 to November 2025, revealing a shift from imported infections to emerging autochthonous transmission among men who have sex with men, which underscores the need for intensified surveillance to prevent sustained spread.

The Gist

The Big Picture: A New "Strain" Arrives

Imagine the Monkeypox virus (MPXV) as a family of viruses. For a long time, the world was worried about Clade II (the "West African" cousin), which caused a huge global party in 2022 that eventually died down.

However, in August 2024, a different, older, and generally more dangerous cousin called Clade I (the "Central African" cousin) started causing a massive outbreak back home in the Democratic Republic of the Congo. This new version, specifically a sub-type called Clade Ib, decided to travel.

This paper is like a travel log and security report from the WHO European Region. It tracks what happened between August 2024 and November 2025 when this "Clade I" virus showed up in Europe.

The Story So Far: Two Acts

The report divides the story into two distinct chapters:

Act 1: The Tourists (August 2024 – October 2025)

The Analogy: Imagine a group of travelers returning from a vacation in a place where a contagious flu is going around. They bring the virus home, but they mostly stay in their own houses.

• What happened: Most of the 82 cases reported were imported. People traveled to countries like Uganda, the DRC, or Thailand, got infected there, and came back to Europe.
• How it spread: Once they got home, the virus mostly stayed inside their households. It spread to spouses or children through close hugging, sharing beds, or skin-to-skin contact.
• The "Household" Effect: Think of the virus as a quiet guest that only talks to the people sitting right next to it on the couch. It didn't jump to the whole neighborhood.
• The Result: 45 cases were travelers. They caused 13 secondary cases (mostly family members). The virus didn't seem to be spreading wildly in the community yet.

Act 2: The Local Party (October 2025 – Present)

The Analogy: Now, imagine the virus stops needing a "tour guide" (travelers) to get in. It starts finding its own way into local social circles, specifically at a nightclub.

• What changed: Starting in October 2025, the report noticed a shift. New cases appeared in Europe that had no travel history.
• The New Pattern: These new cases were mostly men who had sex with other men (MSM).
• The "Nightclub" Clue: Researchers found a cluster of cases in the Netherlands. It turned out several of these men had visited the same sex venue in Amsterdam around the same time.
• The Meaning: This suggests the virus has found a foothold in specific social networks in Europe. It's no longer just "imported luggage"; it's now "local inventory."

Key Takeaways (The "So What?")

1. It's not as scary as the news might say (yet).
The "Central African" cousin (Clade I) is known to be more deadly than the "West African" cousin (Clade II). However, in Europe, the virus acted more like a mild flu.

• No deaths were recorded in this group.
• Very few people needed to go to the hospital.
• Why? The people getting sick in Europe were generally healthier, got medical care faster, and didn't have the same underlying health issues as the children and vulnerable populations affected in Africa.

2. The "Silent" Travelers.
Some people flew into Europe while they were already sick (or just about to get sick), sometimes with visible rashes.

• The Airplane Risk: The report checked if the virus spread on planes. The answer? Almost zero. The virus didn't jump to other passengers on the flight. It's like a sneeze in a crowded room that doesn't actually hit anyone else.

3. The "Household" vs. "Club" Dynamic.

• Early on: The virus spread like a family secret—quietly, within homes, often involving children and partners.
• Later on: The virus started spreading like a rumor in a club—fast, within specific social networks (MSM), and without a clear link to a traveler.

What Are the Doctors and Officials Doing?

The paper suggests three main strategies to stop the virus from making a permanent home in Europe:

1. Catch it Early: Doctors need to look for Monkeypox rashes immediately, even if the patient hasn't traveled recently. Don't wait for the "travel history" to check the box.
2. Know the "Who": Since the virus is now spreading in specific social networks, health officials need to talk directly to those communities to offer vaccines and advice, rather than just waiting for people to get sick.
3. Watch the Genes: Scientists are sequencing the virus to make sure it doesn't mutate into something worse. They found a "recombinant" virus (a mix of two strains) in the UK, proving that if we stop watching, we might miss a surprise.

The Bottom Line

The virus arrived in Europe as a traveler, mostly stayed in homes, and caused mild illness. But recently, it has started to find its own way into local social circles.

The goal now is to stop the "local party" from becoming a "permanent resident." By catching cases early, vaccinating the right groups, and keeping a close eye on how the virus moves, Europe hopes to prevent this new strain from becoming a long-term problem.

Technical Summary

1. Problem Statement

Following a sharp increase in mpox cases linked to the emergence of Monkeypox Virus (MPXV) Clade Ib in the Democratic Republic of the Congo (DRC), the World Health Organization (WHO) declared a Public Health Emergency of International Concern (PHEIC) in August 2024. Unlike the 2022 global outbreak driven by Clade IIb (which primarily affected men who have sex with men [MSM] networks), Clade I has historically been associated with higher case-fatality rates and transmission via heterosexual contact and household settings in Africa.

The primary concern for the WHO European Region was the potential for imported Clade I cases to seed sustained local transmission, particularly given the virus's ability to spread through both sexual and non-sexual (household/fomite) routes. There was an urgent need to characterize the epidemiology of these imported cases, assess the risk of secondary transmission within Europe, and determine if transmission patterns were shifting toward local, sustained spread.

2. Methodology

• Study Design: Descriptive epidemiological study based on case-based surveillance data.
• Data Collection Period: 14 August 2024 to 23 November 2025.
• Data Source: WHO Regional Office for Europe collected data from Member States (MS) via International Health Regulations (IHR) channels. Reporting countries were contacted via email or teleconference to gather standardized data.
• Case Definitions:
  • Confirmed: Laboratory confirmation of MPXV Clade I via molecular detection (PCR).
  • Probable: Symptomatic persons epidemiologically linked to a confirmed case without lab confirmation.
  • Classification: Cases were categorized as Imported (infection acquired outside the reporting MS within 21 days of symptom onset) or Autochthonous (locally acquired).
• Variables Analyzed: Age, sex, travel history, transmission route, clinical course, hospitalization, HIV/immunosuppression status, vaccination history, contact tracing outcomes, and time delays in diagnosis.
• Statistical Analysis: Continuous variables were compared using the Kruskal-Wallis test (Stata v19.5).

3. Key Contributions

• First Comprehensive Regional Analysis: This is the first detailed report characterizing MPXV Clade I (specifically Ib and Ia) cases in the WHO European Region during the 2024–2025 period.
• Epidemiological Shift Detection: The study documents a critical transition from isolated importation events to sustained local transmission within specific sexual networks (MSM) in Europe.
• Transmission Dynamics: It distinguishes between the transmission patterns of imported cases (often heterosexual/household) and autochthonous cases (increasingly MSM-driven), providing early warning signals for potential endemicity.
• Clinical Severity Assessment: It provides early data suggesting that Clade I cases in Europe, while requiring attention, presented with lower severity (fewer hospitalizations, no deaths) compared to historical African outbreaks, likely due to earlier healthcare seeking and supportive care.

4. Key Results

• Case Volume and Classification:
  • Total Cases: 82 cases reported across 13 Member States.
  • Breakdown: 45 (54.9%) were Imported; 37 (45.1%) were Autochthonous.
  • Subclades: 79 cases were Clade Ib; 2 were Clade Ia; 1 was a recombinant virus (Ib/IIb).
• Transmission Routes:
  • Imported Cases: The most likely route was sexual contact (26/45), often heterosexual. Other routes included close physical contact (e.g., saunas) and unknown.
  • Autochthonous Cases:
    • Household Transmission: 13 cases were secondary household contacts of imported cases (7 were children <15 years).
    • MSM Networks: Since October 2025, 17 autochthonous cases in men were linked to sexual contact with other men. A cluster of 6 cases in the Netherlands was linked to a specific sex venue in Amsterdam.
  • Healthcare: One healthcare worker was infected after caring for a patient before mpox was suspected (standard precautions were used initially).
• Clinical Outcomes:
  • Hospitalization: 18 of 79 cases (22.8%) were hospitalized, but only 4 were admitted for clinical mpox reasons (the rest for isolation).
  • Mortality: Zero deaths were reported.
  • Comorbidities: 6 cases were HIV-positive; no other immunocompromising conditions were reported.
  • Vaccination: Only 4 cases had prior mpox vaccination.
• Diagnostic Delays:
  • Median time from symptom onset to seeking care was 5.0 days for imported cases vs. 3.0 days for autochthonous cases with known contacts.
  • Median time from seeking care to subclade assignment was 6.0 days, with a total median delay of 9.5 days from symptom onset to subclade assignment.
• Secondary Attack Rates:
  • Household transmission occurred in 6 of 25 households with imported cases (39.4% attack rate).
  • No secondary cases were identified among travel or school contacts.

5. Significance and Implications

• Shift in Transmission Dynamics: The emergence of autochthonous cases among MSM, particularly those with no travel history, suggests that MPXV Clade Ib is establishing circulation within European sexual networks, mirroring the pattern seen with Clade IIb in 2022. This raises the risk of sustained endemic transmission.
• Public Health Response:
  • Surveillance: Enhanced genomic surveillance and subclade-specific testing are critical to detect silent transmission and emerging variants (e.g., recombinants).
  • Targeted Interventions: Vaccination campaigns and risk communication must be urgently directed at MSM networks, where vaccine coverage remains heterogeneous and incomplete.
  • Clinical Awareness: Clinicians must maintain a high index of suspicion for mpox in patients with compatible symptoms regardless of travel history, especially given the shift to local transmission.
• Severity Context: While Clade I is historically more severe, the European data suggests that with early detection and supportive care, severe outcomes and mortality can be minimized.
• Limitations: The study relies on self-reported data and variable reporting completeness across countries. Under-ascertainment of mild/asymptomatic cases is likely.

Conclusion: The paper concludes that while early Clade I cases in Europe were primarily imported with limited household spread, the recent rise in autochthonous cases among MSM indicates a shift toward sustained local transmission. Continued surveillance, rapid diagnosis, and targeted engagement with high-risk groups are essential to prevent the establishment of MPXV Clade I in Europe.