With Pride events scheduled around the world in the coming weeks, U.S. officials are preparing for a return of monkeypox, the infectious disease formerly called monkeypox that has affected tens of thousands of gay and bisexual men around the world in 2022. A combination of behavioral changes and vaccination quelled the epidemic, but the majority of people at risk have not yet been vaccinated.
The Centers for Disease Control and Prevention warned Thursday of a deadlier version of the disease ravaging the Democratic Republic of Congo and urged people at risk to get vaccinated as soon as possible. So far, no cases of this subtype have been identified outside Africa. But the escalating outbreak in Congo still poses a global threat, just as infections in Nigeria sparked 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, a Los Angeles.
Dr. Rimoin has studied the disease in Congo for more than 20 years and first warned of its potential for global spread in 2010.
The CDC is focusing on encouraging Americans at highest risk to get vaccinated before the virus returns. The agency's outreach efforts include engaging advocacy groups and social media influencers who have broad appeal in the LGBTQ community. In December, the agency urged doctors to remain vigilant for possible cases in travelers from Congo.
There are two main types of mpox: Clade I, the dominant type in Congo, and Clade II, a version of which caused the 2022 global epidemic. (A clade is a genetically and clinically distinct group of viruses.) Both clades they have been circulating in Africa for decades, sporadically breaking out in epidemics.
People with smallpox may have fever, severe headache, and back pain, followed by a rash. Many patients also develop painful sores, often at the site of the infection. People who have weakened immune systems, including those living with HIV, are at the highest risk of becoming seriously ill and dying.
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 calmed down in 2023 with only about 1,700 cases, but now shows signs of resurgence: The number of cases in the United States this year is nearly double compared to the same period last year.
In Congo, as of April 14, the Clade I virus has caused approximately 20,000 cases and nearly 1,000 deaths since January 2023. Clade I infection has a mortality of approximately 5%, compared to less than 0.2% for Clade IIb .
More than three-quarters of deaths in Congo linked to Clade Impox have occurred among children under 15.
Even if the deadliest strain were to emerge in the United States, American children would be less likely to be exposed to smallpox, and less vulnerable to it, than those in Congo, experts say.
Most cases among children in Congo are believed to result from direct contact with infected animals such as monkeys, prairie dogs, squirrels and shrews, or from eating contaminated bushmeat. Children may live in crowded households and be generally in poor health.
The country is plagued by armed conflicts, floods, poverty, malnutrition and multiple infectious diseases, including cholera, measles and polio.
“There is simply a difference in living in the DRC that likely promotes greater spread among children,” said Dr. Jennifer McQuiston, deputy director of the Division of High Consequence Pathogens at the CDC.
Adult cases in Congo have also been attributed to interactions with infected animals or close and prolonged contact with infected people. But last year, for the first time, scientists discovered sexual transmission of the Impox Clade between male and female sex workers and their contacts.
In an outbreak in Kamituga, a mining town in Congo, heterosexual prostitution in bars appeared to be the main form of transmission. Genetic analysis showed that around September, the virus acquired mutations, allowing it to spread more easily between people.
This chain of transmission appears to be a second, distinct epidemic in the country, caused by a new version of the virus called Clade Ib, with cases split evenly among young men and women, said Marion Koopmans, a virologist at Erasmus Medical Center in New York. Rotterdam, Netherlands.
“I think there is more than one outbreak going on, and it's important to continue to evaluate what that means,” Dr. Koopmans said. “We cannot assume” that all forms of smallpox behave the same way, he said.
The development has also alarmed scientists because miners and sex workers in the region are temporary and could carry the virus to neighboring nations such as 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. The 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. According to a recent study, such tests may not detect Clade Ib, the new version that emerged in September.
This finding prompted the World Health Organization to alert nations to review their testing procedures “and make sure they don't miss a diagnosis,” said Dr. Rosamund Lewis, who is leading the WHO's mpox response.
In the United States, a test approved by the Food and Drug Administration detects all versions of MPOX but cannot distinguish them. A positive result from that test should be followed by more specific tests that can identify the clade, Dr. McQuiston said.
At least so far, 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 took hold in the United States during Pride Month in June and thereafter.
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 messages about HIV, have curbed their sexual activity, resulting in a decline in cases even before vaccines were widely available.
The decline in numbers may, however, have produced a false sense of security.
“There was a sense of complacency that this wasn't really something that people needed to worry about constantly, and we saw those vaccination rates decline rapidly,” 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.
According to an analysis last month of 16 studies, two doses of the vaccine are more potent than one, with up to 90% effectiveness. Even when the vaccine did not prevent infections, it mitigated the severity and duration of the disease.
However, fewer than one in four at-risk Americans have received two doses.
“We've continued to saturate the space with messages, and the uptake isn't changing much,” Dr. McQuiston said, suggesting the need for more creative approaches.
In 2022, the vaccine was only available in the United States through federal agencies and was beset by delivery issues, limiting its availability; it is now commercially available. The WHO, which recommends the vaccines for African countries, has been slow to approve them and has not even started the approval process.
However, the WHO Advisory Group on Immunization has recommended that, where available, the vaccine can be used to protect adults and children at risk of smallpox, Dr. Lewis said.
In addition to preparing for Mpox's return to the United States, the CDC is supporting Congo's efforts to obtain vaccines and drugs and contain the outbreak.
“It is much better to help them get this epidemic under control before it spreads to other areas and becomes a global risk,” Dr. McQuiston said. “And, ethically, it's the right thing to do.”