The Disease Detective

Meningitis itself isn’t a disease, just a description meaning that the tissues around the brain and spinal cord have become inflamed. In the United States, bacterial infections can cause meningitis, as can enteroviruses, mumps and herpes simplex. But a high proportion of cases have, as doctors say, no known etiology: No one knows why the patient’s brain and spinal tissues are swelling.

This was the case with the Dhaka outbreak. C.H.R.F. is one of the premier microbiology labs in Southeast Asia and is in charge of tracking meningitis in the country for the World Health Organization. “Every meningitis case that comes in, we culture,” Saha told me. “We do antigen tests for pneumococcus, Neisseria meningitidis, Hemophilus influenzae and G.B.S.,” or Group B streptococcus — the four infections most likely to cause meningitis. “Then we do a much more sensitive and specific test for Streptococcus pneumoniae bacteria, since that causes the highest proportion of cases. And then we also do real-time P.C.R. looking for fragments of DNA from any of these pathogens.”

When the outbreak began, it was assumed that the cause would again be bacterial, but none of the tests could pinpoint a pathogen. Over the next year, Saha worked to solve the mystery, at times in collaboration with other labs. One partnership, with an organization in China, fell apart when the group wasn’t willing to share its techniques. Another set of researchers, in Canada, ran their own tests on the meningitis samples, but couldn’t figure out the cause either. Not long after, Saha attended a conference at the British Museum, where she gave a presentation titled “The Dark Side of Meningitis.” “It was a negative talk,” Saha recalls. “Like: Why does everybody talk only about the successful cases? We need to talk about the thousands of cases every year where we have no idea what’s causing the disease.”

Before meeting DeRisi, Saha was skeptical about yet another collaboration. But the two instantly hit it off. Though DeRisi could be impatient, Saha liked that he was direct, and appreciated that his “ethics are very strong. In his head, he’s like: This is right; this is wrong; this is what I’m going to do.” Still, she proceeded carefully. “Because IDseq was new, and because I am very meticulous, I included a lot of controls,” she told me. Of the 97 samples of cerebrospinal fluid, only 25 were from actual mystery-meningitis cases. The rest were either from cases for which Saha’s lab had already identified the cause, or weren’t meningitis at all. Several were simply water. “The idea was that all of these would be tested, and the process would be blinded,” Saha says. “Because I had to see whether the platform worked or not.”

When Saha and her team ran the mystery meningitis samples through IDseq, though, the result was surprising. Rather than revealing a bacterial cause, as expected, a third of the samples showed signs of the chikungunya virus — specifically, a neuroinvasive strain that was thought to be extremely rare. “At first we thought, It cannot be true!” Saha recalls. “But the moment Joe and I realized it was chikungunya, I went back and looked at the other 200 samples that we had collected around the same time. And we found the virus in some of those samples as well.”

Until recently, chikungunya was a comparatively rare disease, present mostly in parts of Central and East Africa. “Then it just exploded through the Caribbean and Africa and across Southeast Asia into India and Bangladesh,” DeRisi told me. In 2011, there were zero cases of chikungunya reported in Latin America. By 2014, there were a million.

Ordinary chikungunya can cause lasting neurological damage and lifelong joint pain. DeRisi called the disease “hugely devastating” and noted that chikungunya, in the Kimakonde language, spoken in Tanzania, means “to become contorted.” But a neuroinvasive version that caused brain damage and primarily affected children and infants was especially alarming.