The First Clade Ib Mpox Case in the Americas: California, November 2024

In short

• An outbreak of clade I monkeypox virus (MPXV) has been under way in the Democratic Republic of the Congo, and travel-related clade I infections have been reported outside Africa.
• The first reported clade Ib infection in the Americas was found in California, through electronic laboratory reporting, in a U.S. traveller back from East Africa. Because it was identified fast, contacts could be traced thoroughly; no one else was infected.
• Public health authorities should be told at once of suspected clade I infections — matching symptoms and travel, or matching lab results (a non-variola orthopoxvirus detected, with no clade II MPXV) — so that further testing and precautions can start quickly.

Background

The clade I outbreak in the Democratic Republic of the Congo has run since 2023, alongside a worldwide clade II outbreak that began in 2022. A newly emerged subclade, clade Ib, has been spreading through close person-to-person contact in sub-Saharan African countries where mpox is not normally found. Clade I infections have historically been deadlier (case fatality 1.4%–11%) than clade II (0.1%–3.6%), but recent estimates are lower: 1.4%–1.7% for clade Ia with optimal supportive care, and under 1% for clade Ib in the Congo and East African countries where only Ib has been found. Isolated travel-related clade Ib cases outside Africa had caused no serious illness or deaths.

A week before the question was asked

Before leaving the United States, the man — otherwise healthy — noticed what he took for a small "ingrown hair" in his pubic area, which grew more tender and swollen during a one-week trip to East Africa. He felt feverish on the flight home (day 0).

• Day 2. With fever, shortness of breath, fatigue, nausea and new swollen lymph nodes on one side of the groin, he visited two urgent care clinics. They found a 1 cm draining ulcer at the base of the penis and tender left groin nodes, but no other rash. Nobody asked about travel. Tests for other infections were negative, and he was given two oral antibiotics for presumed folliculitis.
• Day 4. Still feverish, with chills and a headache, he went to an emergency department. The ulcer was healing, but the lymph nodes were still swollen and a small pustule had appeared on his forearm. Blood tests showed inflammation and a sudden rise in creatinine, and he was admitted for presumed groin cellulitis that had not responded to antibiotics, and acute kidney injury. An infusion of vancomycin caused flushing and a rash, which settled when the drip was slowed, and he was given other broad-spectrum antibiotics. Over the next days an itchy rash of "tiny bumps" appeared on his arms, chest and belly; thought to be a drug reaction, it improved with hydrocortisone cream.
• Day 6. Better, with no fever and normal kidney function, he went home on oral antibiotics.
• Day 7. The groin pain worsened and distinct raised, blistered and pus-filled spots appeared on his face, back, arms and legs. At this emergency visit his trip to East Africa finally came up. A scan showed the swollen nodes but no abscess, and pustules on his arm and back were swabbed for varicella zoster virus and MPXV.
• Day 11. The commercial lab reported a non-variola orthopoxvirus with no clade II MPXV — pointing to clade I. San Mateo County Health, having conferred with the California Department of Public Health, visited him at home the same day and took new swabs.
• Day 12. The state's Viral and Rickettsial Disease Laboratory confirmed clade I MPXV.
• Day 14. Whole-genome sequencing at the state laboratory and CDC confirmed clade Ib.

The course of illness, by days after the patient's return from East Africa. CDC.

He had been to social gatherings and had a full-body massage in East Africa, and reported no sexual contact on the trip. He isolated at home until a county health department physician confirmed at a home visit on day 23 that every lesion had healed. He recovered without lasting effects.

Lesions on the forearm on day 7, when the trip was disclosed; day 11, when samples were taken for clade I testing; and day 23, when they had fully resolved. CDC, published with the patient's written permission.

Tracing contacts

Eighty-three contacts were identified: one household member (high risk), four travel companions and 10 passengers seated within 6 feet on the flight (both uncertain or minimal risk), and 68 health care workers (three intermediate risk, 56 uncertain or minimal, nine none). Seventy-seven were enrolled in automated twice-daily symptom checks for 21 days; six passengers could not be reached. Six health workers reported spots on their necks, backs or legs, but these did not look like mpox and tested negative for orthopoxvirus. The household member and the four companions received the JYNNEOS vaccine after exposure. No one else was infected.

How it was caught

Before this case, CDC and its partners had begun adapting clade II surveillance to prepare for clade I: using commercial and public health lab results (orthopoxvirus positive, clade II negative) as a signal, adding tests at public health labs and CDC, and sending guidance to clinicians and laboratories. When the African clade I outbreak was first reported, the California Department of Public Health set up a statewide system that scans electronic lab reports daily for results suggesting clade I. That is how San Mateo County Health learned of this one. Once it was confirmed, monitoring continued during contact tracing, alongside clear guidance and ongoing contact with local health departments and clinicians.

What followed

As with other travel-related clade Ib cases outside Africa, the illness was not severe. In late November 2024 Canada confirmed its first clade I case, in Manitoba. In January 2025 another travel-related clade I case was reported in Georgia, also mild, with no further cases among contacts, and in February 2025 two more travel-related clade Ib cases were reported, in New Hampshire and New York State.

The infection was presumed to have been caught in East Africa. The "ingrown hair" that came before the trip was not typical of mpox and was never tested; the rest of the illness fitted infection during travel, and no other mpox cases in or near San Mateo County in the 21 days after the ulcer appeared were unaccounted for by clade IIb. The broken skin may have made infection easier during the trip, but infection before it is unlikely.

What to do

• Public health agencies should consider automated alerts like California's, scanning lab reports for orthopoxvirus-positive, clade II-negative results.
• Health care workers should take a thorough travel history from every patient with an acute infection, and consider mpox in anyone with matching lesions or symptoms.
• Those who see a patient with signs of mpox who meets at least one of the exposure criteria for clade I should notify public health authorities immediately.

Words on this page from people and organisations outside the federal government are paraphrased; rewritten in hubnx's own words.

Sources

• Vivian Levy, Anna Branzuela, Kristina Hsieh, Shiffen Getabecha, Ricardo Berumen III, Kayla Saadeh, and others, with the Clade I Mpox Response Team, "First Clade Ib Monkeypox Virus Infection Reported in the Americas — California, November 2024," Morbidity and Mortality Weekly Report. https://www.cdc.gov/mmwr/volumes/74/wr/mm7404a1.htm
• Authors from San Mateo County Health, Stanford University, the California Department of Public Health and CDC.