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The increasing number of suspected clade I mpox virus cases in the Democratic Republic of the Congo (DRC) poses a global threat for potential spread, the CDC said.

From Jan. 1, 2023 to April 14, 2024, multiple outbreaks of clade I mpox occurred across 25 of the DRC's 26 provinces, with nearly 20,000 suspected cases and 975 deaths, reported Jennifer McQuiston, DVM, of the CDC's National Center for Emerging and Zoonotic Infectious Diseases, and colleagues in the .

Half of those cases occurred in the Equateur province, with a case fatality rate of 5.7% compared with 4.3% for the rest of the country.

"In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus," McQuiston and team wrote.

Of the two distinct mpox subtypes, clade I causes more severe illness than the clade II subtype and may be more transmissible. To date, no clade I cases have been reported in the U.S. or outside of the countries of Central Africa where the virus is endemic.

Notably, 67% of suspected cases and 78% of deaths from mpox in the DRC during 2023 and 2024 have occurred in children and adolescents ages 15 years and younger, while children ages 12 to 59 months have accounted for 28% of all suspected cases. In some provinces, including Equateur, most of the cases (69%) have occurred in children and adolescents, but in other provinces, people over the age of 15 have accounted for most cases (69%).

Genetic analysis has indicated that the outbreaks in the DRC have involved multiple introductions from animal hosts, rather than a single introduction followed by nationwide spread. Nonetheless, spread among close household contacts has likely contributed to the high number of cases.

The differences in demographic characteristics and genetic diversity suggest that zoonotic, household, and sexual transmission are driving transmission in the DRC, but these factors vary by province, "resulting in a complex epidemiologic picture," the authors wrote.

If clade I mpox is introduced in the U.S. at some point, it is more likely to be sexually transmitted, affecting populations such as men who have sex with men and sex workers, and less likely to affect children, McQuiston and colleagues noted. This is because there are no zoonotic reservoirs in the U.S., household contacts are fewer, and cleaning and hygiene resources are widely available.

In response to the increase in clade I cases in the DRC, the CDC is taking steps to increase surveillance and expand its diagnostic testing capacity for this subtype. The authors emphasized that clinicians in the U.S. should be alert for possible cases in travelers from the DRC and should request clade-specific testing in suspected cases.

The CDC previously issued a Health Alert Network advisory in December 2023 to alert physicians to the rise in clade I cases in the DRC, and also issued a for the DRC.

"Appropriate medical treatment is critical given the potential for severe illness, and contact tracing and containment strategies, including isolation, behavior modification and vaccination, will be important to prevent spread if any U.S. clade I mpox cases occur," the authors wrote.

From Dec. 1, 2023 to April 14, 2024, CDC testing of 343 mpox-positive specimens detected no clade I mpox. Also, among laboratories with clade I testing capability, this subtype was not detected among approximately 900 specimens, the report detailed.

U.S. wastewater surveillance for both clade I and II has also been underway at 186 sites in 32 jurisdictions. All positive detections have occurred at locations with known clade II occurrences. In addition, from late December 2023 to mid-April 2024, 282 samples were collected at four U.S. airports, all of which were negative for mpox.

Current guidelines for the clinical management of mpox are applicable to clade I cases, McQuiston and team said, but they emphasized that diagnosis and reporting of clade I mpox is important so that early containment measures can be implemented. Isolation, contact tracing, use of the mpox vaccine for contacts, and other infection control practices should be used.

The FDA-approved mpox vaccine (Jynneos) became commercially available in . Previously, the vaccine had been available only through public health channels. However, of those in the U.S. at risk for mpox infection have completed the two-dose vaccine series, the authors pointed out.

The CDC strongly recommends that those at risk for clade II infection should complete the vaccination series. An additional benefit of vaccination is protection against clade I mpox infection, they added.

For diagnosing mpox, the CDC recommends use of the nonvariola orthopoxvirus (NVO) polymerase chain reaction test. However, the test does not distinguish between clade I and clade II subtypes. Some laboratories offer laboratory-developed tests that can distinguish between the clades, but they may lead to , so the CDC recommends that the NVO test be used, in addition to any clade-specific testing. Positive NVO or negative clade II test results should be followed up with sequence analysis.

The CDC and U.S. government have been providing ongoing support to the DRC to help in its response to the outbreaks.

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