What was ‘Disease X’ and what can we learn from it?

In early December, international alarm bells went off because of a mysterious disease circulating in a remote part of the Democratic Republic of Congo. The Africa Centers for Disease Control and Prevention dubbed it “Disease X.”

National and international health experts raced to the scene. But because the rainy season made dirt roads hard to pass, it took days to get from the capital Kinshasa to villages in the Panzi district in Kwango Province, located in the south of the vast country. It was in these far-flung villages that about 900 people had fallen ill between late October and mid-December with symptoms ranging from fever to body weakness to difficulty breathing. Forty-eight of them died. And many of the ill are young children. At the very end of November, local medical providers alerted national authorities that they weren’t sure what was causing all these people to fall sick.

Once the medical experts arrived, they quickly gathered samples from the sick to take back to the provincial capital of Kenge and the national capital of Kinshasa so diagnostic tests could be run. But because of the arduous journey, when the first samples arrived “the blood and serum were poorly preserved,” said Dr. Jean Kaseya, the director general of Africa CDC. “There was no way for them to conduct the testing.”

WHO issues a finding

Finally, four weeks after learning about the situation, the World Health Organization says it now has pieced together a picture of this puzzling outbreak.

On December 27, WHO announced the results from 430 samples: The outbreak was caused by a familiar enemy — or, more accurately, multiple familiar enemies. Patients had acute respiratory infections — think COVID, flu or rhinoviruses — complicated by malaria as well as widespread malnutrition.

“If there’s a main message here it’s strengthening primary health-care systems. That’s the key,” says Dr. William Moss, a deputy director of the Johns Hopkins Malaria Research Institute and a professor in the departments of Epidemiology, Molecular Microbiology and Immunology, and International Health at the Johns Hopkins Bloomberg School of Public Health. “If we can strengthen the primary health-care system in settings like this, then you’re much better positioned to not only provide preventive care or treatment care but also to respond to outbreaks.”

The DRC government estimates that almost 40% of the population in this region is malnourished and the WHO says, in recent months, the level of acute malnutrition has increased. “Children who are undernourished have weakened immune systems and are really more susceptible to severe disease from any pathogen,” Moss says. Ideally, a stronger health system could support those with malnutrition both by helping them quickly when they fall ill and by addressing the underlying issue with therapeutic feeding centers and other interventions.

The unusual is … unusual

There’s another lesson to draw from this outbreak, he says: “Unusual manifestations of common diseases may be more likely than unusual diseases themselves.” Indeed, during this outbreak, global health experts debated the best way to refer to the situation, wondering whether the disease should be described as “unknown” or simply “undiagnosed” — and whether the name “Disease X” was too alarmist.

When the news first broke in the DRC, Michael Osterholm — director of the Center for Infectious Disease Research and Policy at the University of Minnesota — told NPR that this type of mysterious outbreak happens several times a year worldwide. The vast majority of the time the unknown disease turns out to be something familiar. It’s the rare case where it’s a novel pathogen that goes on to spread globally, as happened with COVID.

But, Moss says, it’s worth being vigilant because, if it is something new or particularly worrisome, a timely response is critical.

“A degree of heightened awareness is of value,” he says. And the long delay in this case identifying the underlying causes was because “it was just a very difficult place to investigate.”