The clade I mpox situation has entered a new and more concerning phase as of June 2026. The Centers for Disease Control and Prevention confirmed that more than 20 clade I cases have been detected in the United States, all diagnosed in individuals with recent travel to regions with active clade I outbreaks or exposure to people with such travel histories. But the more significant development — the one that changes the risk calculus — is a statement buried in the same CDC update: beginning in Fall 2025, several European countries began reporting locally acquired clade Ib cases among men who have sex with men who had no documented travel to Central or Eastern Africa. The CDC states explicitly: "We expect additional cases in Europe and the United States."
This is not a theoretical escalation. It is a documented epidemiological shift, confirmed by the European Centre for Disease Prevention and Control, which noted in its May 2026 surveillance report that from April 2025 to March 2026, 336 clade I mpox cases were confirmed across 15 European countries. Some of those cases reflect local community transmission that has taken root independent of African source countries — exactly the scenario that global health officials feared when the WHO declared clade I mpox a Public Health Emergency of International Concern in August 2024.
Understanding Why Clade I Is Different from the 2022 Outbreak Strain
The global 2022 mpox outbreak that infected more than 90,000 people in over 100 countries was driven by clade IIb — a strain that spreads primarily through close physical contact, particularly sexual contact, and causes significantly less severe disease than its Central African cousin. Case fatality rates for clade IIb in high-income countries were under 0.1 percent. That outbreak was eventually controlled, largely through targeted vaccination of high-risk networks and behavioral change.
Clade I — and particularly its subclade Ib, which is driving the current international concern — has historically caused more severe disease. In endemic settings in Central Africa, case fatality rates have reached 1 to 10 percent in unvaccinated populations, though researchers caution that these figures come from settings with limited healthcare access and that case fatality rates outside endemic zones may be lower. What makes clade Ib distinctly alarming, however, is that it has demonstrated the capacity to sustain transmission in the same close-contact sexual networks that drove the 2022 clade IIb outbreak — which means it has found an efficient transmission pathway in populations outside Africa that could allow it to spread in ways not seen with classic clade I outbreaks.
The rash associated with clade I tends to be more painful, more widely distributed, and more likely to involve lesions in multiple anatomical sites simultaneously. Complications, including secondary infections, encephalitis, and scarring, are more common with clade I. The illness typically lasts longer, and the convalescence period is more difficult.
The Vaccine Gap in the United States
Two vaccines offer meaningful protection against both clade I and clade II mpox: JYNNEOS (Bavarian Nordic), the preferred option, and ACAM2000, which is more reactive and generally reserved for settings where JYNNEOS is unavailable. JYNNEOS was central to the 2022 response, and significant quantities were procured and distributed across the U.S. However, vaccination campaigns have been inconsistent, booster timing guidance has been updated multiple times, and awareness has dropped sharply as clade IIb receded from public attention.
The CDC recommends JYNNEOS for adults at increased risk, including gay, bisexual, and other men who have sex with men with multiple partners; transgender individuals; people with recent sexually transmitted infections; and healthcare workers likely to encounter mpox patients. A two-dose regimen given 28 days apart is required for full protection for those who have not previously been vaccinated. For people who received two doses during the 2022 response, the CDC recommends assessment of current risk and consideration of a booster, particularly given the emerging evidence that immunity may wane.
The most important step clinicians can take right now is maintaining a high index of suspicion for mpox in any patient presenting with a new, unexplained vesicular or pustular rash — regardless of whether they have a history of international travel. The emergence of local clade I transmission in Europe means that travel exposure history is no longer a reliable rule-out for clade I mpox in sexually active patients seen at urban clinics in the United States.
What High-Risk Individuals Should Do
If you are in a group at elevated risk for mpox and have not been vaccinated, contact your local sexual health clinic, primary care provider, or city health department to access JYNNEOS. If you were vaccinated during the 2022 outbreak response and continue to have new or multiple partners, discuss your booster status with a healthcare provider. Use the CDC's mpox vaccine locator to find providers in your area.
Anyone who develops an unexplained rash involving lesions on the genitals, rectum, face, or hands — particularly after close physical contact with a new partner — should seek evaluation promptly and specifically ask that mpox be considered in the diagnosis.
Frequently Asked Questions
Q: How many clade I mpox cases have been confirmed in the U.S. in 2026?
A: More than 20 confirmed cases as of June 2026, all in individuals with travel links to affected regions or exposure to people with such travel histories.
Q: Why is clade I more concerning than clade II?
A: Clade I historically causes more severe disease with higher mortality. Subclade Ib has demonstrated the ability to spread through the same sexual networks that drove the 2022 clade IIb global outbreak, meaning it could find an efficient transmission pathway in high-risk populations outside Africa.
Q: Is clade I now spreading locally in the United States?
A: Not yet confirmed in the U.S. All current U.S. cases are travel-linked. However, local clade Ib transmission has been confirmed in multiple European countries among men who have sex with men with no travel to Africa, and the CDC explicitly warns that additional U.S. cases are expected.
Q: Who should get vaccinated against mpox?
A: Men who have sex with men with multiple partners, transgender individuals, people with recent STIs, and healthcare workers who may encounter mpox patients are the primary target groups. Two-dose JYNNEOS is the recommended vaccine.
Q: How is clade I mpox diagnosed?
A: By PCR testing of lesion swabs. Clinicians should test any patient with an unexplained vesicular or pustular rash and relevant exposure history, even without travel to Africa, given the evidence of local European transmission.
