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As concerns mount about a large outbreak of an especially virulent form of mpox in central Africa and an uptick in U.S. cases since early last year, the mpox vaccine appears to give long-term protection, the Centers for Disease Control and Prevention reported Thursday.

In a separate report, the CDC indicated that overall new mpox infections across the U.S. have remained at a steady, low level — about 60 cases weekly, compared with 3,000 cases a week at the outbreak’s summer 2022 peak — in recent months. However, cases so far this year are elevated nationally compared with the same period in 2023 and have seen a sharp increase in New York City. 

People who have gotten two doses of the Jynneos mpox vaccine are protected against infection and don’t need a booster at this time, according to the CDC. 

Public health experts are concerned that the launch of the summer travel season and the upcoming LGBTQ Pride festivals in cities across the country will drive greater sexual connectivity among gay and bi men and potentially hasten mpox transmission.

Christina Hutson, chief of the CDC’s Poxvirus and Rabies Branch, and other public health experts told NBC News that this is no time for complacency about mpox (formerly called monkeypox). The various factors that likely have kept the U.S. outbreak relatively in check since late 2022 — including vaccination, infection-driven immunity, and sexual behavioral change — may be tenuous.

The mpox outbreak is “poised to return under the right conditions,” said Dr. Jeffrey Klausner, an infectious disease expert at the University of Southern California. Infections rapidly tore around the globe beginning in May 2022 and made that summer a misery for many gay and bisexual men before collapsing worldwide.

Critically, the proportion of at-risk American gay and bi men who are fully vaccinated against mpox is considered inadequate to assure long-term protection for this vulnerable population.

“Vaccination is a critical way to help protect yourself and others,” Hutson said. “It’s important that people at risk for mpox exposure who have not previously recovered from mpox — including certain gay, bisexual, and other men who have sex with men — complete the two-dose Jynneos vaccination series.” 

On May 16, the CDC published an ominous report about nearly 20,000 recent cases of what is known as clade 1 of mpox that have been documented in the Democratic Republic of Congo, or DRC, since January 2023. 

Concerningly, this viral clade appears to be more transmissible and to cause higher rates of severe disease and death compared with clade 2 of mpox, which drove the recent global outbreak. Five percent of those diagnosed with clade 1 in the DRC have died, compared with just 0.2% of the 96,000 people in the global clade 2 outbreak.

To date, there have been no reports of clade 1 cases outside of the handful of African nations where mpox has been endemic for decades. In December, the CDC first alerted health care providers of the possibility that this more harmful viral clade could hit the United States.

“We’re facing a big, potentially dangerous situation,” Ira Longini, a biostatistician at the University of Florida, said of the potential for global spread of clade 1. “But we really don’t know.”

Dr. Boghuma Titanji, an assistant professor at the Emory University School of Medicine, suggested that the Jynneos vaccine will likely provide protection against clade 1. The Jynneos vaccine is approved in the U.S. for mpox regardless of clade. 

“It’s reasonable to anticipate that there would be some immune cross-protection,” she said of immunity stemming both from the vaccine and previous infection with clade 2.

A clinical trial of the Jynneos vaccine is ongoing among health care workers in the DRC. It is not expected to be completed until the end of next year.

But the vaccine has not otherwise been rolled out in the DRC, a lost opportunity to help control the nation’s outbreak and prevent clade 1 from spreading globally, Titanji said.

Dr. Placide Mbala, the head of epidemiology and the global health department at the University of Kinshasa in the DRC, said the nation has seen “a lot of interest” from global public health leaders in providing such assistance. 

“But we are still waiting for concrete action,” Mbala said.

During the clade 2 outbreak, mpox has overwhelmingly transmitted via intercourse, both oral and anal, between men. Transgender people have also been disproportionately affected. The virus has not transmitted readily through the air or surfaces, in health care settings, or through casual,nonsexual contact.

In an interview earlier this year, CDC epidemiologist Dr. Jennifer McQuiston said mpox “needs to be thought about as an STD. The good news is it’s a preventable STD.”

Multiple studies of real-world uptake of the Jynneos vaccine have suggested that receiving both doses is associated with a 66% to 89% lower infection rate and one dose is 36% to 75% effective.

In one of the new CDC reports, agency investigators analyzed demographic data and clinical characteristics concerning 271 mpox cases from the U.S. outbreak’s outset in May 2022 to May 2024 among fully vaccinated people in 27 U.S. jurisdictions that provided sufficient related data. 

According to a CDC official, the agency estimates that only 0.1% of the fully vaccinated population developed a breakthrough infection. Reported such cases amounted to 0.8% of all 32,819 mpox diagnoses nationally. Thirteen percent of mpox cases were in partially vaccinated people.

The CDC estimates that 2 million men in the U.S. are at significant risk of mpox because they engage in sex with multiple male partners or otherwise are HIV positive; people with HIV have had a high mpox diagnosis rate. Of the overall group of at-risk gay and bi men, only approximately 25% have been fully vaccinated and an additional 14% have received one Jynneos shot.

In keeping with previous studies, the CDC’s new report found that full vaccination was associated with less severe disease and a lower hospitalization rate.

All 56 mpox deaths were among unvaccinated people.

Recent research has raised concerns that the antibodies Jynneos prompts wane over time. But the CDC investigators found evidence that, at least so far, the vaccine’s actual protection against infection hasn’t waned, possibly due to what’s known as innate or cell-based immunity.

Shortly after the vaccine was first rolled out in midsummer 2022, U.S. health authorities began stretching the temporarily short supply by changing its administration from a traditional subcutaneous (under the skin) shot to an intradermal (within the skin) shot that allowed for a much lower dose.

The new CDC report found no evidence that this vaccine-application shift compromised vaccine effectiveness.

A separate new CDC analysis of recent U.S. mpox diagnoses found the virus is still overwhelmingly seen among gay and bi men. Just 0.4% of recent cases were in people younger than 18.

Between October and April, 1,802 probable and confirmed mpox cases were reported to the CDC by 42 jurisdictions — for an average weekly rate, which remained essentially steady, of 59 cases. By stark contrast, the nation saw 2,000 to 3,300 weekly cases at the outbreak’s peak between mid-July and late August 2022.

And yet, CDC records show that the nearly 750 mpox cases seen this year through mid-April is more than twice the figure reported during the comparable period in 2023. New York City has seen a nearly five-fold case-rate increase between these two periods, with 191 cases thus far in 2024.

As for concerns about how a U.S. outbreak of clade 1 might transpire, infectious disease experts said they could only speculate whether higher quality health care, for one, might yield a lower death rate than in the DRC. Global clade 2 deaths have largely occurred among people with compromised immune systems, mostly due to untreated HIV.

Other unknowns include how and among which groups clade 1 might tend to transmit in Western nations. The DRC outbreak has occurred both in men with multiple male sex partners and in female sex workers and their contacts. And two- thirds of the DRC’s clade 1 outbreak has been in people under age 16; only a bit over 1% of the global clade 2 outbreak was in minors.

Epidemiologists see evidence of sustained person-to-person transmission in one DRC province, where cases are primarily in adults. 

While this transmission apparently has largely been through sex, compared with clade 2 of mpox clade 1 shows signs that it can nevertheless transmit more readily absent sexual contact. However, clade 1 still seems to require close personal contact, and nonsexual transmission appears largely limited to household settings. Also, the substantial transmission in children could be driven in part, the recent CDC report suggested, by multiple spillovers from wild animals encountered by young people in rural settings.

CDC officers believe that widespread transmission of clade 1 among children in the U.S. is much less likely, owing to a lack of an animal reservoir, less- crowded living quarters, and better cleaning and hygiene.

Emory’s Titanji reported worries that the gay and bi men she cares for quickly lost interest in mpox vaccination after the outbreak stopped being a primary concern for them. During the fall of 2022, the nation’s weekly distribution rate of Jynneos shots plummeted in tandem with the mpox case rate. 

Since then, no substantial progress has been made in raising the proportion of at-risk gay and bi men who have received both Jynneos doses.

“If you’re not yet vaccinated and you meet criteria, go and get vaccinated,” Titanji said. “We can’t be complacent about the response now moving forward.”

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