Rapid Risk Assessment: Risk Posed to the United States by Clade I Mpox Outbreak in Democratic Republic of Congo

Overall risk

We assess the overall risk to the general U.S. population as very low, with moderate confidence. Overall risk is assessed by considering the likelihood and impact of infection across the population (see Methods section). This assessment may change as new evidence becomes available.

Likelihood

We assess the likelihood of infection for the general population as extremely low. Factors that informed our assessment of likelihood included the following:

• There are no known cases of clade I mpox in the U.S. or any other country outside of endemic areas, although the virus could potentially spread from DRC to the United States or other countries through infected travelers from the DRC.
• There is currently no evidence of widespread community transmission of clade I mpox in DRC, as most cases have stemmed from clusters of cases or small outbreaks.
  • Despite the outbreak in South Kivu province, DRC, involving heterosexual transmission among commercial sex workers, there is no current confirmed evidence of widespread heterosexual transmission. However, epidemiologic data are limited, and we do not know the true number of cases nor how each case acquired infection.
  • Limited genomic data thus far suggest that there have been multiple zoonotic introductions of clade I mpox.
  • The Republic of Congo, which borders DRC to the west, reported 43 cases of mpox on March 13, according to press reporting. As of November 2023, WHO indicated it is unknown whether there are links between the Republic of Congo outbreak and DRC’s outbreak. Clade I is endemic in Republic of Congo, and we assess these cases may have resulted from zoonotic introductions or spread across the border in a relatively localized area and do not yet suggest wider regional spread.
• The potential for sustained heterosexual transmission of clade I mpox is likely to be low based on lack of widespread transmission in heterosexual networks during the 2022 global clade IIb mpox outbreak and insights from modeling studies.
  • Modeling work from the United Kingdom related to the 2022 outbreak indicated that lower partnership formation rates among heterosexuals prevented sustained transmission within these networks. CDC modeling has shown similar results for heterosexual networks in the U.S.¹

Impact

We assess the impact of infection for the general population as low to moderate. Factors that informed our assessment of impact included the following:

• Most of the United States population has no immunity to mpox.
  • Acquired immunity from previous infection with the mpox virus is extremely low for the general population (see separate analysis for MSM, who were disproportionately affected by mpox during the 2022 outbreak).
  • Vaccine-induced immunity from mpox vaccination during the 2022 outbreak is also very low across the general population. During the 2022 outbreak, vaccination was targeted to those at highest risk of infection, including MSM and their partners.
  • Prior smallpox vaccination, which can offer some protection against mpox, has declined substantially in the United States since the 1970s, when population-wide smallpox vaccination ceased.
• Morbidity and mortality from clade I mpox are likely reduced in the United States because of the availability of high-quality supportive care and access to medical countermeasures.
  • DRC health authorities reported the case fatality rate (CFR) from suspected clade I mpox in 2023 was 4.6% and rose to 6.7% throughout early 2024; however, this may be an overestimation because of challenges in completeness of case reporting. In a study of 216 mpox patients from one DRC hospital from 2007-2011, investigators found a CFR of 1.4% among 216 patients who received limited supportive care and no mpox therapeutics.
  • In the United States, the CFR would likely be lower, given better access to high-quality supportive medical care and therapeutics.

Confidence

We have moderate confidence in this assessment.

We note uncertainties around epidemiologic and genomic data in DRC, including transmission dynamics in children and non-MSM sexual networks.

[1] Pollock E, Nakazawa Y, Asher J, Gift T, Spicknall I. Potential mpox transmission among college-attending 18-25-year-olds with opposite-sex contacts in the United States. (2023, July 24-27).  The International Society for Sexually Transmitted Diseases Research.

Overall risk for this population

We assess the overall risk for gay, bisexual, and other men who have sex with men (MSM) in the United States, who have more than one sexual partner, and their sexual partners, regardless of gender as low to moderate, with moderate confidence. Overall risk is assessed by considering the likelihood and impact of infection across the population (see Methods section). This assessment may change as new evidence becomes available.

Likelihood

We assess the likelihood of infection for MSM as low to moderate. Factors that informed our assessment of likelihood included the following:

• There are no known cases of clade I mpox in the United States or any other country outside of endemic areas, although the virus could potentially spread from DRC to the United States or other countries through infected travelers who expose others at their destinations.
• Health authorities have documented sexually transmitted clade I mpox in DRC in MSM among six cases during 2023, indicating the virus could spread among these sexual networks in the United States if cases were imported. During the ongoing 2022 global mpox outbreak, most U.S. cases were among MSM and their sexual partners, suggesting this population could be at increased risk for clade I mpox infection if the clade I mpox virus were to spread to the United States.
• In the United States, there is some level of population immunity among MSM and their sexual partners following the 2022 outbreak of clade IIb mpox, which might reduce the risk of infection if clade I mpox were imported to the United States. In addition, during the 2022 global mpox outbreak in the U.S., MSM reported behavior adaptations that likely contributed to declines in mpox incidence, indicating that similar changes might be expected in response to future outbreaks.
  • However, a minority of MSM who CDC has estimated would benefit from vaccination have been fully vaccinated.
  • A modeling study estimates that depending on population mpox immunity levels, jurisdictions face varying degrees of risk for sustained mpox recurrence and many jurisdictions have a high likelihood of sustained transmission.

Impact

We assess the impact of infection for this population as low to moderate. Factors that informed our assessment of impact included the following:

• Like the general population, we expect that the impacts of clade I mpox among MSM are likely reduced in the United States because of the availability of high-quality supportive care and access to medical countermeasures.
• Population immunity among MSM and their sexual partners is likely to additionally reduce the severity of infection.

Confidence

We have moderate confidence in this assessment.

Given uncertainties around the level of prior immunity and the extent to which behavior adaptations initiated during the 2022 outbreak have continued or could recur, we have moderate confidence in this assessment.

Geographic and population spread

• Detection of clade I mpox cases in the United States, particularly if there is domestic person-to-person transmission in jurisdictions with low estimated population immunity.
• Clade I mpox spreads outside sub-Saharan Africa, including among people attending mass gatherings or among other highly mobile populations.
• The outbreak in DRC intensifies or spreads to countries where mpox is not endemic, in the region or globally.

Transmission dynamics

• Evidence of person-to-person spread among children in DRC, outside of already recognized high-risk activities, such as exposure to animals or close contact with mpox patients.
• Evidence of widespread, prolonged chains of sexual transmission in DRC.

Natural history and medical countermeasures

• Additional data to suggest an increased or decreased illness severity of clade I mpox infection.
• Increased mpox vaccination coverage among high-risk groups in United States.

Descriptive Epidemiology

There is an ongoing outbreak of mpox in DRC caused by the clade I mpox virus, which is distinct from the clade IIb mpox virus that caused the 2022 global outbreak. As of March 29, DRC reported 4,488 confirmed or suspected cases of mpox in 2024. In previous outbreaks, clade I has caused more severe disease and been more transmissible than clade II within close-contact settings, typically in a household. Although clade I mpox is endemic in DRC, in 2023, health authorities reported a higher number of cases and deaths across a wider geographic area that in some provinces affected atypical demographic groups. Approximately 70% of suspected mpox cases in DRC in 2024 were in children under age 15, similar to historical observations. However, adults were disproportionately affected in South Kivu province, where sexual transmission was predominant.

CDC has not detected any cases of clade I mpox in the United States, despite testing a high proportion of presumed mpox specimens—those positive for non-variola orthopoxvirus (NVO)—with tests that can identify mpox by clade. In addition, several commercial and other non-CDC laboratories perform clade II testing in addition to NVO tests, and all specimens tested to date have been clade II. If these laboratories see anything unusual—for example, an NVO positive but clade II negative result—they would alert CDC immediately to ensure additional genotyping is conducted to determine if they are clade I. CDC continues to work, including with other U.S. government agencies, on multiple approaches to expand clade-specific testing domestically. Several public health laboratories (PHLs) have begun or are working to begin clade-specific testing.

Transmission

The DRC outbreak of clade I mpox has likely resulted from transmission through several modes and in different settings. Most cases in 2023 were in children, and in past outbreaks, children have been more likely to acquire infection through contact with infected animals. Transmission caused by close contact within households has occurred in past clade I mpox outbreaks. Household transmission chains have typically been small, although occasionally have involved up to six generations of transmission. Transmission risk is highest among unvaccinated contacts; children and young adults are less likely to have vaccine-induced orthopoxvirus immunity since smallpox vaccination programs ended in 1980 in DRC. Sexual transmission has also been recently reported in 3 localities including the capital city, Kinshasa, and Kamituga, South Kivu province in Eastern DRC, primarily among female sex workers, and in a small outbreak affecting MSM and women in Kenge, Kwango Province in March 2023.

Importation risk

In 2023, outbreaks were reported in urban areas of DRC, including Kinshasa and less-populated regions of DRC, such as Équateur and South Kivu Provinces, where cross-border movement elevates the risk of spread of the disease outside of the country. As of March 13, there are 43 confirmed clade I mpox cases in the neighboring Republic of Congo, where clade I mpox is endemic, likely representing localized transmission in a region with frequent cross-border movement. Only indirect commercial air passenger flights arrive from DRC and its neighboring countries into the United States.

CDC subject-matter experts specializing in risk assessment methods, infectious disease modeling, global health, and mpox and other orthopoxviruses collaborated to develop this rapid assessment. Experts initially convened in February 2024 to discuss the need for an assessment examining the risks posed by the DRC outbreak to the United States, key evidence related to the DRC outbreak, and specific populations to include in the assessment. To conduct this assessment, experts considered evidence including epidemiologic data from DRC, data from the ongoing mpox outbreak in the United States caused by clade IIb, and historical data on clade I mpox outbreaks in DRC. After the initial assessment was finalized in February, experts subsequently re-reviewed evidence and updated this assessment in early March, mid-March, and mid-April.

Overall risk was estimated by combining the likelihood of infection and the impact of the disease. For example, low likelihood of infection combined with high impact of disease would result in moderate risk. The likelihood of infection refers to the probability that members of the general U.S. population or MSM acquire mpox throughout 2024, which in turn depends on the likelihood of exposure, infectiousness of the disease, and susceptibility of the population. The impact of infection considers several factors affecting the consequences of infection, including the severity of disease, level of population immunity, availability of treatments, and necessary public health response resources. A degree of confidence was assigned to each level of the assessment, taking into account evidence quality, extent, and corroboration of information.

For more details on our methods, please see our rapid risk assessment methods webpage.