A public health scientist from CDC’s Enteric Diseases Laboratory Branch, preparing a portable sequencing instrument for whole genome sequencing (WGS). WGS provides detailed genetic information about pathogens that make people sick. Source: Lauren Bishop, CDC/Courtney Wheeler.
Periodically, reports of mysterious outbreaks bubble up. The latest concerns an outbreak of unidentified illness in the southwestern region of the Democratic Republic of Congo. According to Reuters, the outbreak killed over a hundred people in mid-November. Symptoms include high fever and headache, and women and children are said to be more heavily affected.
Outbreaks that initially have no clear cause happen pretty regularly. Other examples include events in Sudan and Nigeria in November, India in September, and so on. These reports can be alarming, especially when they involve high mortality rates or affect vulnerable populations, like children. When reports like these appear in your news feed, how should you think about it?
As an epidemiologist, I tend to group “unidentified” outbreaks into three main possibilities. While just a rough sketch, this loose approach provides a useful starting point for assessing mysterious events, while waiting for more information to come in.
The most likely possibility is that the pathogen is an “unknown known,” to borrow a common framework. These are (generally speaking) flare-ups of endemic or common diseases. Examples include cholera, malaria and influenza. Such outbreaks can still be dangerous and difficult to control, but they are also reasonably common, and the steps needed to combat them are well understood. In low-resource settings, the outbreaks are “unidentified” in that they begin in places without readily accessible diagnostic infrastructure. The odds of these being the culprit in any given “mystery” outbreak are relatively high.
Next up is “known unknowns”, which are diseases we are aware of but that are rare and poorly understood. These are pathogens like Marburg virus, Middle East Respiratory Syndrome coronavirus, or Nipah virus. These outbreaks demand swift and decisive action because they are especially deadly or dangerous. Often, there are no vaccines or specific treatments for pathogens in this category. They must instead be brought under control through non-pharmaceutical measures like contact tracing, which becomes more difficult as the outbreak grows larger, lending extra urgency to the situation. These outbreaks often take longer to diagnose, because samples must be transported to and analyzed at specialty labs. (This is becoming less true as diagnostic technology and access matures.) The probability of an outbreak falling into this category is lower, but the potential impact is high.
Finally, “Unknown unknowns” are the true wildcards. These are outbreaks of pathogens that are novel, unexpected, or highly consequential. The “novel coronavirus” that emerged five years ago certainly fit in this category, because the pathogen was new. In my mind, the 2014 Ebola outbreak in West Africa also fit the bill, because the virus had not been recognized in that region before and there were no vaccines at the time. I would have also put both clades of mpox in this category when they first began to circulate widely, though now they may be well understood enough to no longer qualify. These unknown unknown outbreaks often take the longest to diagnose, because they require extensive testing and investigation. The chances of a mystery illness falling into this category are slim, but not zero.
Public health officials may have initial suspicions of which category is in play based on early reports of symptoms and demographic patterns, but confirming the pathogen requires laboratory testing and epidemiological investigation. This process can take days, weeks, or even months depending on the location of the outbreak, the availability of diagnostic resources, and the complexity of the disease itself. In any case, the key is not to jump to conclusions based on limited data.
If you enjoyed this newsletter, you will likely enjoy my new book Crisis Averted: The Hidden Science of Fighting Outbreaks.
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