Monkeypox in the United States, 2024–2025: Low-Level Spread, a Fall Surge, and the Case for Two Doses

Monkeypox is a blistering-rash illness caused by monkeypox virus (MPXV), an orthopoxvirus, and it's nationally notifiable in the United States. There are two clades, I and II, each with subclades a and b.

U.S. clade II cases peaked at about 3,000 a week in 2022, then fell and stayed under 150 a week through 2023. The infection hits people with HIV and gay, bisexual and other men who have sex with men (MSM) hardest, and people with unsuppressed HIV or low CD4 counts are at higher risk of severe illness and death.

The numbers

Confirmed and probable cases by week, 2024–2025. CDC

The fall 2025 surge

Cases roughly doubled from 423 in September–October 2024 to 873 in the same months of 2025, then dropped to 448 in November–December 2025 — back to background levels by year's end.

Confirmed and probable cases by state, 2024 and 2025. CDC

Who got it

The patient profile barely changed from earlier years:

• Male: 96.5% in 2024, 97.8% in 2025.
• Of men, 79% identified as gay or bisexual.
• Hispanic or Latino (36.3%) and Black (22.8%) patients were affected out of proportion to their share of MSM and of the U.S. population.
• Ages 30–39 made up 42.2% of cases.

Vaccination

Vaccination status was known for only 2,049 patients (38.5%). Of them:

Across both years, 76.1% of those with a known status were unvaccinated.

Hospitalizations and deaths

Of the 4,635 patients whose hospital status was known, 9.5% were hospitalized, with no difference between years; among vaccinated patients with known status, 2.0% were. In 2024, two of the five who died were unvaccinated and three had an unknown status; the one death in 2025 was in an unvaccinated patient. Three of the 11 clade Ib patients were hospitalized, and all recovered without antiviral treatment.

Among 860 patients with complete data, controlling for age and HIV status:

What the genomes show

About 97.5% of U.S. sequences in 2024–2025 descended from lineage B of the 2022 outbreak. Case and genetic data pointed to 21 importations.

• Clade Ib: six sequences from the 11 cases were tied to travel from affected countries; two came from a small domestic cluster in late 2025 — three cases in October 2025 linked to one travel-related introduction, which didn't spread further. No sustained clade Ib transmission was found.
• Clade IIb lineage A.2.2: 12 cases in eight states. Ten patients had traveled to a country with an A.2.2 outbreak; the other two lacked travel histories but their virus had more mutations than local spread would explain. In several West African countries, A.2.2 outbreaks have affected men and women about equally, with evidence of heterosexual spread — in the U.S., that pattern has been seen only in travelers.

What it means

Steady spread of clade IIb, over wide areas for three years, suggests monkeypox is becoming endemic in the United States. Infection among vaccinated people was stable and consistent with the vaccine's known effectiveness, with no sign of waning immunity.

Clade Ib keeps spreading worldwide among both MSM and heterosexual people — about 89% of cases in several European countries with sustained spread are among MSM — and more U.S. importations were seen in 2026 and are expected. CDC's recommendations on treatment, infection control, vaccination and case investigation are the same whatever the clade.

CDC recommends that anyone at risk — including travelers to countries with clade I or II spread — complete both JYNNEOS doses, along with continued surveillance of cases and virus genetics, and education for people at risk.

Limits

• Mild cases where no one sought care may be missed.
• The reason for hospitalization isn't always recorded, though only monkeypox-related stays were requested.
• Viral suppression and CD4 counts aren't collected, so HIV status was used as a rough stand-in.
• Data collection varies by jurisdiction.
• Much data was missing — 62% for vaccination, 68% for HIV status, 70% for sexual orientation — and leaving it out may bias results.

Sources

Based on Sandford R, Tuttle A, Aeschleman L, et al., "Monkeypox Virus Surveillance — United States, 2024–2025," MMWR volume 75, number 32, Centers for Disease Control and Prevention; a work of the United States government in the public domain. The report gives median patient ages in its text that differ from those in its table, so neither is used; it says Hispanic patients made up a smaller share than White patients while its table shows the reverse, so that comparison is left out; and it describes the 860 patients in the hospitalization model as 39% of cases, which that count is not, so only the count is given.