Clade I Mpox Surges in the Democratic Republic of the Congo: How the U.S. Prepared, 2024

The global mpox outbreak that began in 2022, caused by clade II monkeypox virus, showed that mpox can spread worldwide. Clade I, endemic in several Central African countries including the Democratic Republic of the Congo (DRC), is generally deadlier: case fatality rates of 1.4% to more than 10%, against 0.1% to 3.6% for clade II. People catch mpox from infected wild animals or through close, prolonged contact with an infected person; the clade II outbreak spread mainly through sex between men. In 2023–2024 the DRC reported an unprecedented number of suspected clade I infections.

The outbreak in the DRC

From January 1, 2023, to April 14, 2024, the DRC reported 19,919 suspected clade I cases and 975 deaths (4.9%), in outbreaks across 25 of its 26 provinces — and, for the first time, in the capital, Kinshasa. In two outbreaks, sexual transmission was reported among men who have sex with men, male and female sex workers, and their contacts.

Suspected clade I mpox cases (bars) and deaths (line) by week, DRC, January 2023–April 2024. CDC.

• Children bear the brunt. Two-thirds (67%) of suspected cases and more than three-quarters (78%) of suspected deaths were in people 15 or younger; children aged 12–59 months were 28% of all cases.
• Provinces differ. In Equateur, 69% of cases were in people 15 or younger; in South Kivu and Kinshasa, people over 15 were the largest group (69%). Equateur reported half of all suspected cases, and a higher case fatality rate (5.7%) than the rest of the country (4.3%).
• Little testing. In remote places many suspected cases are never tested, and testing varies widely. Of 2,016 specimens tested up to March 24, 2024 — 11% of suspected cases — 1,302 (65%) were confirmed; among 480 confirmed cases in early 2024 with a recorded age, half were in people 15 or younger.

Suspected clade I mpox cases by province, January 2023–April 2024. CDC.

Ages of suspected cases and deaths: children under 5 make up a larger share of deaths than of cases. CDC.

How it spreads there

Limited genetic data (from the DRC's national biomedical research institute, unpublished) suggest many separate jumps from animals rather than one introduction spreading nationwide, with household spread adding many cases. Differences between provinces point to different drivers — animal, household or sexual. In South Kivu, where sexual transmission was reported, a distinct lineage carries signs of sustained person-to-person spread and a deletion in the part of the genome that includes the C3 gene — the target of CDC's clade I–specific PCR test.

CDC's support to the DRC

Over the last 15 years CDC has helped the DRC set up mpox laboratory testing and training, sequencing, clinical research on the JYNNEOS vaccine, and training for frontline health workers. For this outbreak the U.S. government formed an interagency team to support the DRC and its neighbours with funding, technical help and deployed staff, and to direct U.S. preparedness.

Preparing the United States

No clade I case had been found in the United States or any country where the virus is not endemic.

• Alerts. A Health Alert Network notice on December 7, 2023, asked clinicians to consider clade I mpox in anyone with mpox symptoms recently in the DRC, with fast clade-specific testing; CDC also issued a Level 2 travel notice for the DRC.
• Who might be at risk. Given sexual transmission in the DRC, men who have sex with men with multiple partners and sex workers might face higher risk if clade I arrived. Widespread spread among U.S. children is much less likely: no animal reservoirs, smaller households, and ready access to cleaning and hygiene supplies.
• Reporting and handling. Case report forms now record clade I results. The Department of Transportation, after consulting CDC, classes diagnostic specimens (other than clade I cultures) and clinical waste with either clade as Category B infectious substances.
• Clinicians. A March 2024 survey of 100 U.S. providers found gaps in knowledge about diagnosing and treating clade I mpox; about two-thirds wanted more guidance. Treatment follows the same U.S. guidelines for both clades, based on the patient's condition rather than the clade. Early diagnosis and reporting allow contact tracing, isolation, vaccination of contacts and strict infection control.
• Vaccination. Only 23% of Americans at risk of clade II mpox have completed the two-dose JYNNEOS series. CDC urges them to get both doses — which should also protect against clade I. JYNNEOS is on the routine adult schedule and went on commercial sale in April 2024.

Testing and surveillance

CDC's FDA-cleared non-variola orthopoxvirus (NVO) PCR test diagnoses mpox but cannot tell the clades apart. Some laboratories offer tests that detect clade II (ruling out clade I), and a few detect clade I directly. Because genome deletions can defeat some tests, CDC advises running the NVO test alongside clade-specific tests and sequencing any sample that is NVO-positive but clade II–negative.

• From December 1, 2023, to April 14, 2024, CDC found no clade I among 343 NVO-positive specimens, and other U.S. laboratories none among about 900.
• By April 22, 2024, 186 wastewater sites in 32 jurisdictions were using tests that detect both clades; every positive matched a known clade II location.
• From December 22, 2023, to April 11, 2024, 282 samples from four U.S. airports were tested; none was positive.

Why urgency matters

The 2014 West African Ebola outbreak showed the cost of a slow global response. In 2022 the United States mounted a strong response built on two decades of smallpox preparedness, but the world missed earlier chances to contain clade II, which had been spreading person to person in Nigeria since at least 2016. Rising mpox in neighbouring countries — including 19 confirmed cases in the Republic of the Congo — adds to the concern. Vaccines and treatments were not yet authorized in the DRC, though its national immunization advisory group had recommended them; partners now need to help the DRC obtain and deliver vaccine where it is needed most.

Sources

• Jennifer H. McQuiston, Richard Luce, Dieudonne Mwamba Kazadi and colleagues, with the CDC 2024 Clade I Mpox Response Team, "U.S. Preparedness and Response to Increasing Clade I Mpox Cases in the Democratic Republic of the Congo — United States, 2024," MMWR, May 2024. https://www.cdc.gov/mmwr/volumes/73/wr/mm7319a3.htm
• CDC Health Alert Network notice, December 7, 2023: https://emergency.cdc.gov/han/2023/han00501.asp