With Pride events scheduled worldwide over the coming weeks, U.S. officials are bracing for a return of mpox, the infectious disease formerly called monkeypox that struck tens of thousands of gay and bisexual men worldwide in 2022. A combination of behavioral changes and vaccination quelled that outbreak, but a majority of those at risk have not yet been immunized.
On Thursday, the Centers for Disease Control and Prevention warned of a deadlier version of mpox that is ravaging the Democratic Republic of Congo and urged people at risk to be vaccinated as soon as possible. No cases of that subtype have been identified outside Africa so far. But the escalating epidemic in Congo nevertheless poses a global threat, just as infections in Nigeria set off the 2022 outbreak, experts said.
“This is a very important example of how an infection anywhere is potentially an infection everywhere, and why we need to continue to improve disease surveillance globally,” said Anne Rimoin, an epidemiologist at the University of California, Los Angeles.
Dr. Rimoin has studied mpox in Congo for more than 20 years, and first warned of its potential for global spread in 2010.
The C.D.C. is focusing on encouraging Americans at highest risk to become vaccinated before the virus resurges. The agency’s outreach efforts include engaging with advocacy groups and social media influencers who have broad appeal among the L.G.B.T.Q. community. In December, the agency urged clinicians to remain alert for possible cases in travelers from Congo.
There are two main types of mpox: Clade I, the type that is dominant in Congo, and Clade II, a version of which caused the 2022 global outbreak. (A clade is a genetically and clinically distinct group of viruses.) Both clades have circulated in Africa for decades, sporadically erupting into outbreaks.
People with mpox may have fever, intense headache and back pain, followed by a rash. Many patients also develop painful sores, often at the site of infection. People who have weakened immune systems, including those living with H.I.V., are most likely to become severely ill and die.
The version of mpox that caused the 2022 outbreak, called Clade IIb, led to more than 30,000 cases in the United States that year. The epidemic quieted in 2023 with only about 1,700 cases but is now showing signs of a resurgence: The number of cases in the United States this year is nearly double the tally at this time last year.
In Congo, as of April 14, the Clade I virus has led to about 20,000 cases and nearly 1,000 deaths since January 2023. Infection with Clade I has a mortality of roughly 5 percent, compared with less than 0.2 percent for Clade IIb.
Most cases among children in Congo are thought to result from direct contact with infected animals such as monkeys, prairie dogs, squirrels and shrews, or from eating contaminated bush meat. The children may live in crowded households and be in poor health generally.
The country is troubled by armed conflicts, floods, poverty, malnutrition and multiple infectious diseases, including cholera, measles and polio.
“There’s just a difference in living in D.R.C. that probably promotes higher spread among kids,” said Dr. Jennifer McQuiston, the deputy director of the Division of High Consequence Pathogens at the C.D.C.
Adult cases in Congo have likewise been attributed to interactions with infected animals or close, sustained contact with infected people. But last year, for the first time, scientists discovered sexual transmission of Clade I mpox among male and female sex workers and their contacts.
In one outbreak in Kamituga, a mining town in Congo, heterosexual prostitution in bars appeared to be the main form of transmission. Genetic analysis showed that, sometime around September, the virus gained mutations, enabling it to spread more readily among people.
This chain of transmission appears to be a second, distinct outbreak in the country, caused by a new version of the virus called Clade Ib, with cases split about equally among young men and women, said Marion Koopmans, a virologist at Erasmus Medical Center in Rotterdam, the Netherlands.
“I do think there is more than one outbreak ongoing, and it is important to continue to evaluate what that means,” Dr. Koopmans said. “We cannot assume” all forms of mpox behave in the same way, she said.
The development has also alarmed scientists because miners and sex workers in the region are transient and may ferry the virus to the neighboring nations of Rwanda, Burundi, Uganda and Tanzania.
In many of these countries, limited access to tests, vaccines and treatments gives the virus ample opportunity to thrive and evolve. A vast majority of mpox cases are diagnosed based on symptoms alone.
Some countries rely on tests that detect only Clade I or only Clade IIb. Those tests may not pick up Clade Ib, the new version that emerged in September, according to a recent study.
That finding prompted the World Health Organization to alert nations to revisit their testing procedures “and make sure they don’t miss a diagnosis,” said Dr. Rosamund Lewis, who leads the W.H.O.’s mpox response.
In the United States, a test approved by the Food and Drug Administration detects all versions of mpox but cannot distinguish between them. A positive result on that test should be followed by more specific tests that can identify the clade, Dr. McQuiston said.
So far at least, the available vaccines and antiviral drugs are expected to be effective against all forms of the virus. The 2022 outbreak began in Europe in May and picked up steam in the United States during Pride Month in June and afterward.
Early in the outbreak, there was a shortage of the two-dose mpox vaccine, called Jynneos. But many gay and bisexual men, accustomed to heeding public health messaging on H.I.V., curbed their sexual activity, precipitating a decline in cases even before vaccines were broadly available.
The drop in numbers may have produced a false sense of security, however.
“A sense of complacency set in that this wasn’t really something that people needed to have an ongoing worry about, and we saw those vaccination rates rapidly decline,” said Dr. Boghuma Titanji, a virologist and infectious disease physician at Emory University.
Behavioral changes are difficult to sustain, so vaccination is important for long-term control of the virus, Dr. Titanji said.
Two doses of the vaccine are more powerful than one, with an effectiveness of up to 90 percent, according to an analysis last month of 16 studies. Even when the vaccine did not prevent infections, it tempered the severity and duration of illness.
Still, fewer than one in four Americans at risk received two doses.
“We’ve continued to saturate the space with the messaging, and uptake is not really shifting a lot,” Dr. McQuiston said, suggesting a need for more creative approaches.
In 2022, the vaccine was available only in the United States through federal agencies and plagued by problems with delivery, limiting its availability; it is now commercially available. The W.H.O., which recommends vaccines for African countries, has been slow to approve it, and has not even initiated the approval process.
Still, the W.H.O.’s advisory group on immunizations has recommended that, where available, the vaccine can be used to protect adults and children at risk of mpox, Dr. Lewis said.
In addition to preparing for mpox’s return to the United States, the C.D.C. is supporting Congo’s efforts to obtain vaccines and drugs and contain the epidemic.
“It’s much better to help them get this outbreak under control before it spills over into other areas and becomes more of a global risk,” Dr. McQuiston said. “And, ethically, it’s the right thing to do.”