(Science) Analysis of hundreds of mpox patients suggests it is “a different disease” in those with compromised immune systems
In June 2022, a young man in his 30s severely sick with mpox, the viral disease formerly known as monkeypox, was admitted to the Salvador Zubirán National Institute of Health Sciences and Nutrition hospital in Mexico City. Tests showed the patient was also HIV-positive, which he had not known, and that his blood had few CD4 cells, critical immune cells that HIV attacks. The man’s immune system was so weak it could not keep mpox in check and painful lesions kept spreading across his body, eating away at, or necrotizing, the flesh, according to HIV researcher Brenda Crabtree Ramirez, who was on his care team. Then the virus spread to his lungs, too. “He just kept getting worse and worse and worse,” she says.
With no treatments available, his doctors got the hospital’s ethics board to approve a desperate plan: They would transfer blood plasma from a colleague who had been vaccinated in the United States against mpox to the patient, in the hope that the antibodies from the donation might help fight his infection with the poxvirus. The experimental therapy failed—the man died 2 weeks later, one of the first deaths from the disease in Mexico.
Although mpox cases have plummeted globally since then, the outbreak still simmers in Latin America and other locations. The World Health Organization (WHO) last week reaffirmed that the disease remains a global emergency. And a grim report today in The Lancet and being presented at a conference in Seattle, which analyzes the death last summer in Mexico and the cases of 381 other mpox patients who also had advanced HIV infections, makes clear the disease poses an enormous risk to those living with uncontrolled HIV. Of the 179 patients with less than 200 CD4 cells per microliter—more than 500 is considered normal—27 died.
Mpox isn’t just more severe in these immunocompromised patients, says Oriol Mitjà, an infectious disease researcher at the Germans Trias i Pujol University Hospital in Barcelona and one of the study authors. “It’s like a different disease.” In the cases where people had few CD4 cells, mpox’s normally small skin lesions grew into large necrotizing patches and their infection sometimes spread to the lungs or caused severe secondary infections with bacteria.
Mitjà, Crabtree Ramirez, and their colleagues argue this disseminated form of mpox should be added to the list of AIDS-defining conditions, opportunistic secondary infections that are a typical sign of advanced HIV infection. That might alert physicians to test mpox patients for HIV to be able to prioritize them for any possible treatments. Health authorities should also prioritize people living with HIV for mpox vaccination, Mitjà says. But the Lancet report also contained a warning for physicians: Starting coinfected patients on antiretrovirals for their HIV infection could worsen their mpox. The data presented in the Lancet report are compelling and WHO plans to assemble a group to consider the research team’s recommendation to make mpox an AIDS-defining condition, says Meg Doherty, who heads the program for HIV and other sexually transmitted infections at the agency.
In some ways the world may have been lucky with the strain of mpox virus that has been spreading globally. The two types previously known from cases in Africa were thought to kill 10% and 1% of patients, respectively. The current outbreak strain has infected more than 85,000 people globally, predominantly affecting gay men and their sexual networks, and caused fewer than 100 deaths, or a mortality rate of about 0.1%. A paper published last week in the Proceedings of the National Academy of Sciences found that in a particular strain of laboratory mice, this virus, known as clade IIb, is far less deadly than its relatives. “We were unable to cause the mice to be sick even at 100 times the lethal dose [for the current strain],” says Bernard Moss, a poxvirus researcher at the U.S. National Institute of Allergy and Infectious Diseases and one of that study’s authors.
But the Lancet paper, which covers more than one-quarter of all known mpox deaths for the clade IIb strain, shows the virus can still cause devastating disease in a particularly vulnerable group of people. Men who have sex with men are much more likely to acquire an HIV infection, but are also less likely in most parts of the world to have access to HIV testing and treatment, notes Gregg Gonsalves, a Yale School of Public Health epidemiologist and former HIV activist. “This creates a dangerous situation, in which our failures to address the AIDS epidemic among this population now may create new risks” for this group, he says.
The Lancet report also revealed an important dilemma for physicians caring for these coinfected people. When those with untreated HIV were given antiretrovirals, one-quarter of them seemed to develop a condition in which the recovering immune system responds to the opportunistic infection—mpox in this case—with an overzealous inflammatory response. More than half the patients suspected to have this overreaction, known as immune reconstitution inflammatory syndrome, died. “We are grappling with these scenarios and clinicians do not know what the best approach is at this time,” says Boghuma Titanji, a virologist at Emory University who was not involved with the study.
For now, there are far fewer severely sick patients to care for globally than in the summer and Europe is working on a plan to eliminate the virus entirely. Still, cases continue to be reported from dozens of countries, especially in Latin America. The disease might not cause another large outbreak, Mitjà says. “But I think that it will continue to circulate as an STI [sexually transmitted infection] … with the potential to cause death in a few people.”
When WHO extended the Public Health Emergency of International Concern (PHEIC) for mpox for another 3 months on 15 February, it noted the risk of a resurgence in some regions and “a potential shift in some countries towards the most marginalized populations who have the least access to prevention measures and treatments.”
The extension is an opportunity for the world to address the inequities in how it has responded to mpox, Titanji says. The PHEIC keeps the disease “on the radar globally and hopefully this will also translate into better access to vaccines and therapeutics as well as diagnostics for low- and middle-income countries in Africa and South America,” she says.
So far, the countries in Central and West Africa that have borne the burden of mpox longer than anywhere else have gained little from the global attention on the disease, says Dimie Ogoina, an infectious disease specialist at Niger Delta University in Nigeria and a co-author on the Lancet paper. “The ‘package for Africa’ is largely still in the realm of promises.”
Continued attention on the disease is important for Mexico, too, Crabtree Ramirez says. She worries conditions there could let the disease linger. On the one hand, there is little incentive for those with milder infections to be diagnosed because neither treatment nor a preventive vaccine is available in the country. The main consequence of a diagnosis is mandatory isolation, Crabtree Ramirez says. “And for many people in Mexico, if they don’t work, they don’t eat,” she adds. On the other hand, there are many people at a high risk for deadly disease—almost half the people diagnosed with HIV in Mexico are at an advanced stage of the infection with a CD4 count of 200 or less—which makes it clear that vaccines and drugs are needed, Crabtree Ramirez says. “For me, it’s unacceptable that people do not have access to what is needed to survive.”