Risk of Clade 1 Mpox Outbreaks Among Gay, Bisexual, and Other Men Who Have Sex With Men in the United States

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At a glance
Background
Key findings

Public health considerations
Methods

July 4, 2024

This report is one of two modeling studies exploring the potential spread of clade I mpox in the United States. This study explores the impacts of population-level immunity and transmissibility on sexual transmission of mpox among gay, bisexual, and other men who have sex with men. A separate study explores the impact of household and other non-sexual spread on number of cases and number of households infected in an outbreak.

At a glance

Clade I mpox is causing an ongoing outbreak in the Democratic Republic of the Congo (DRC). During the ongoing clade II mpox outbreak that began in 2022, the main transmission route was associated with sexual activity among certain gay, bisexual, and other men who have sex with men (MSM). As such, CDC modeled varying levels of transmissibility of clade I mpox and county-specific population-level immunity—from either previous infection or one or two doses of the JYNNEOS vaccine— among MSM in the United States to explore potential impacts of clade I mpox introduction to these sexual networks in the United States. Our modeling results indicate that:

Despite a higher presumed transmissibility of clade I mpox compared to clade II, in 13 U.S. counties, simulated clade I outbreaks among MSM were smaller than ongoing clade II outbreaks. The clade I outbreaks were likely smaller because of prior immunity from vaccination and previous infection, as well as the population’s related behavior change.
The size and duration of potential mpox outbreaks varied across individual counties due to differences in vaccination coverage and previous clade II mpox case rates, together referred to as population-level immunity.
As population-level immunity increased, the chances of a prolonged or large outbreak decreased. Therefore, CDC recommends all eligible people get vaccinated.

Background

In previous outbreaks in endemic African countries, clade I virus has caused a higher proportion of severe disease and been more transmissible than clade II within close-contact settings. To date, no cases of clade I mpox have been detected in the United States, despite wastewater monitoring for community detection and testing a high proportion of presumed mpox specimens with tests that can identify mpox by clade.

The current DRC outbreak of clade I mpox has likely resulted from transmission through several modes in different settings, including household, zoonotic, and sexual exposures. A 2024 outbreak in the Kamituga mining region in DRC has been associated with transactional sex, as 88% of hospitalized cases reported recent transactional sex. Additionally, health authorities reported six cases among MSM in a rural town in DRC in 2023. In a rapid risk assessment updated as of May 10, 2024, CDC assessed the risk posed by the clade I mpox outbreak in the DRC to the U.S. MSM population as low to moderate, higher than the risk posed to the general population.

Here, we use a dynamic, agent-based transmission model to explore in more detail the risk of prolonged sexual transmission among MSM in 13 counties in the United States if clade I monkeypox virus were to be introduced to this population. The 13 counties in this analysis were selected from 50 jurisdictions in the Ending the HIV Epidemic (EHE) Initiative to represent a range of population size and immunity profiles (see Methods for additional information). However, many of the EHE counties not included in our analysis likely are similar to the considered counties and would be expected to have similar probabilities of prolonged transmission.

Key findings

The county-level modeling results showing the size and duration of potential mpox outbreaks varied across individual counties due to differences in population-level immunity. For example, results indicated that outbreaks averaging more than 100 cases did not occur when population-level immunity from vaccination or previous infection was greater than 50% among MSM (Figure 1). Additionally, our simulation results showed that counties with higher population-level immunity had smaller outbreaks—defined as cumulative infections one year after introduction—and lower chance of prolonged transmission—defined as continued incident infections one year after introduction (Figure 2).

Our results suggest that high population-level immunity in a county, coupled with related behavior change, would lead to a much smaller mpox clade I outbreak among MSM compared to the ongoing mpox clade IIb outbreak. When comparing modeling results to number of confirmed diagnoses in the 2022 outbreak, only three of the 13 counties had more mpox diagnoses across all transmissibility scenarios modeled, and only two additional counties had more mpox diagnoses in the 20% more transmissible scenario modeled (data not shown to maintain anonymity). All five of these counties had estimated levels of population-level immunity below 25%.

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Boxplot of mpox transmission among MSM in 13 US counties with a range of immunity profiles across 3 transmission scenarios.

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Figure 1. Transmission of mpox among MSM in U.S. counties with a range of immunity profiles across three transmission scenarios: box plots of distribution of the cumulative number of infections expected within a year, following introduction of five individuals with mpox and with high levels of sexual activity. Transmission scenarios represent clade II (74.5% per-contact transmissibility), clade I (with 10% relative increased transmission over clade II), and clade I (with 20% relative increased transmission over clade II).

Line graph of probability of prolonged mpox transmission among MSM in 13 US counties across 3 transmission scenarios.

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Figure 2. Transmission of mpox among MSM in U.S. counties with a range of immunity profiles across three transmission scenarios: probability of prolonged transmission after one year following introduction of five individuals with mpox with high levels of sexual activity. Transmission scenarios represent clade II, clade I (with 10% relative increased transmission over clade II), and clade I (with 20% relative increased transmission over clade II).

Among counties with population-level immunity lower than 50%, increases in immunity were correlated with lower probabilities of prolonged transmission among MSM for all three levels of transmissibility we analyzed (Figure 2). These results suggest that as the population-level immunity of a county increases, the probability of prolonged transmission decreases linearly, for all three levels of transmissibility we analyzed (Figure 2). In particular, counties with >50% population-level immunity had a <12% probability of prolonged transmission.

Public health considerations

Increasing population-level immunity through vaccination in counties can reduce both the number of infections as well as the chance of prolonged transmission of mpox. Vaccination is an important—yet underutilized—tool in preventing the spread of mpox. The Advisory Committee on Immunization Practices recommends people with potential risk of exposure to mpox receive two doses of the JYNNEOS vaccine. Despite this, only one in four of the approximately two million people recommended to receive the vaccine in the United States based on risk of exposure to clade II mpox have received both doses. JYNNEOS is also expected to protect against clade I mpox. CDC will continue to evaluate available data and assess the risk posed to MSM in the United States by the clade I mpox outbreak in DRC.

If you are a public health partner interested in learning more about your county-specific population-level immunity, please contact us.

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We developed an agent-based model to simulate sexual mpox transmission among MSM. We adapted a previous model that assessed clade II transmission in MSM networks, adding new data on U.S. sexual network structures and exploring transmission parameters to represent clade I mpox.

We produced simulations for 13 counties among 50 jurisdictions in the Ending the HIV Epidemic (EHE) Initiative. The 50 EHE jurisdictions account for more than half of all new HIV diagnoses, and many represent urban areas across the United States with large MSM populations. We chose 13 counties that represent a range of mpox population immunity levels (11%-88%) across the 50 non-state EHE jurisdictions, prioritizing counties that are hubs for international travel and large events. For each of the 13 counties, we established baseline population-level immunity based on vaccination and case reporting to DCIPHER as of February 2024. We assumed that prior infection with clade II mpox provides full protection against both mpox clades, and that vaccination with the JYNNEOS vaccine provides partial but strong immunity (75.2% and 85.9% for one dose and two doses, respectively).

We then generated sexual networks with sizes equivalent to the estimated MSM population for each county. The sexual behavior within the networks was estimated from an online survey of cisgender MSM from across the United States. We assumed that the distribution of type and frequency of sexual behavior is the same across all counties as data does not exist to estimate these parameters at a local level. Finally, we also modeled short-term behavioral adaptations as a reduction in the frequency of spontaneous or one-time sexual encounters, assuming a level of behavioral adaptation in our analyses similar to what occurred in the District of Columbia in 2022 based on previous modeling work and documented across the United States.

The cumulative number of infections and proportion of simulation runs with infections remaining one year after introduction of the virus were compared across three transmission scenarios. Transmission scenarios included the following: 1) baseline, parameterized for clade II (74.5%); 2) clade I, assumed 10% more transmissible than clade II (81.9%); and 3) clade I, assumed 20% more transmissible than clade II (89.4%). For each simulation, we assumed that five MSM with the highest levels of sexual activity (defined as having one or more spontaneous/one-time sexual partners per week in addition to any main or casual partners) were exposed to mpox and ran the simulation for one year. We summarized results across 1,000 simulation runs for each county and scenario combination.

How did this model differ from previous modeling during the clade II outbreak?

The updated model was fit to sexual network data that was collected more recently (2017-2019), representing MSM across the United States rather than a single geographic region. Furthermore, we added data on oral sex partnerships in addition to anal sex partnerships and recalibrated sexual activity group strata to better characterize the range of sexual activity reported in the data. We also calibrated the clade II transmissibility parameter using clade II mpox case data from early in the 2022 outbreak. This parameter has a calibrated distribution of β(4.24, 1.45), with mean equal to 74.5% probability of transmission per contact.

We also added additional transmission parameters to explore possible clade I scenarios. While there are no studies that estimate the exact difference in per-contact transmissibility between the globally circulating clade II virus and clade I in humans, there is evidence that rash intensity and detectable viral loads are greater for clade I relative to clade II in traditional zoonotic and household transmission settings, and a small mammal model demonstrated that virulence of clade I is greater than clade II. We generalized these lines of evidence, assuming a 10% increase relative to clade II (81.9% per-contact transmissibility) and a 20% increase (89.4% per-contact transmissibility).

Lastly, previous work modeled a range of immunity to mpox using a single population size, where in this work we modeled county-specific MSM population size and composition of population-level immunity. This generates more variance in our results, but both approaches come to similar conclusions about the overall level of population-level immunity that is protective against prolonged transmission of mpox.

What data did you use to estimate county-level immunity coverage?

Population-level immunity was calculated as the total number of immune people in each county divided by the estimated size of the MSM population with increased risk of mpox exposure in that county. Total number of immune people included everyone reported to have received one or two doses of the JYNNEOS vaccine through January 2024, all people with diagnosed mpox through March 2024, and an estimate of the number of undiagnosed mpox infections based on previous modeling work. We estimated the size of the MSM population with increased risk of mpox exposure in each county using county-level estimates from survey data reduced by 40% to reflect the smaller proportion of MSM considered higher activity based on national survey data.

Limitations

Our analysis is subject to several limitations, including some that could lead to underestimation of outbreak size and probability of prolonged transmission. We assumed that prior infection with clade II mpox provides full protection against both mpox clades, that vaccination with the JYNNEOS vaccine provides partial immunity, but did not account for waning immunity from either previous infection or vaccination in this model. We also assumed that the JYNNEOS vaccine and prior infection with clade II will provide similar protection against clade I as for clade II, all of which could reduce our estimates of outbreak size. In addition, variations in vaccination reporting requirements between counties—including some that have stopped reporting to CDC since immunity estimates were previously published and/or have individual opt-in reporting—may mean that true population immunity could be higher than is estimated here. Lastly, the number of infections reported in these counties and included in our analysis may be lower than the actual number of infections, given under-detection and reporting of cases.

We also made several assumptions that could have led to overestimates of outbreak size and probability of prolonged transmission. We seeded simulations with a high number of infections in highly connected individuals. In addition, we assumed substantial behavioral adaptation in the face of an outbreak. Our sensitivity analysis for clade II indicated that substantially larger outbreaks could occur if this assumption is violated, though outbreak sizes did not exceed 100 cases on average for counties with >50% immunity among MSM with increased risk of mpox exposure (defined in our model as MSM who are likely to form spontaneous or one-time partnerships in addition to having main and/or casual partners). We also assumed that no vaccination occurred during the simulated year. In counties where analysis indicates that large outbreak sizes are possible, we expect—but did not model—that additional health interventions would be implemented that could potentially reduce outbreak sizes.

This analysis only explicitly modeled 13 counties; therefore, it is not representative of the entire U.S. However, many of the counties not included in our analysis likely are similar to the considered counties and would be expected to have similar probabilities of prolonged transmission.

Finally, we acknowledge substantial uncertainty in the size of the MSM population with increased risk of mpox exposure (which affects coverage estimates) and note that sexual networks may not be accurately reflected for all counties, as the survey data could not be disaggregated to the county level. While unaccounted-for geographic variation in sexual behavior could influence the absolute outbreak size in a given county, because previous modeling work used networks with lower levels of sexual activity and had similar outcomes, we expect that the general conclusions presented here would hold.

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