Picture the scene: It’s May 1991, and a New York gastroenterologist will soon fly home from a medical meeting in Atlanta, all the while pondering a perplexing illness in Nepal.
As Bradley Connor, MD, had just learned, many expats in Kathmandu had been suffering severe diarrhea. But here was the rub: the cause of their flux was still unknown. And unlike people with Delhi belly or Montezuma’s revenge, the patients in Nepal often endured not just days or weeks but months of mushy, watery stool and debilitating fatigue. Most were also losing a surprising amount of weight.
Connor was torn. Yes, his Manhattan practice was busy, but what if he rearranged his schedule and went to Nepal to try to crack the case? Before his plane touched down at La Guardia airport, his mind was made up.
“The more I thought about it,” he recently told me, “the more I thought ‘Wow!’ How amazing to discover something new.” And so, a few weeks later, Connor boarded two more planes with both adult and pediatric endoscopes in his carry-on, performed nearly 20 procedures at Kathmandu’s top English-speaking clinic, and obtained duodenal aspirates and tissue from newly-symptomatic people and healthy controls.
Why did he act so quickly, and why did he want biopsies? For one thing, since the malady invariably struck between April and July, the medical sleuth was determined not to miss this window of opportunity. And Connor needed biopsies to prove his leading explanation for the puzzling blight: severe intestinal damage due to a small bowel pathogen.
Bingo! That’s exactly what pathologists confirmed after Connor returned to New York and shared his blinded specimens. Microscopic exams of the tissue ultimately showed that all nine symptomatic sufferers passing “Coccidia-like” bodies in their stool also had inflamed or destroyed small bowel crypts and villi. This damage, in turn, had caused their profound malabsorption.
Connor’s exploit in Nepal and the subsequent finding by researchers working in Peru that the newly-identified human pathogen was from the genus Cyclospora made the pages of the New York Times 4 years later. Then, in 1996, another article ran in the Times after Cyclospora struck 32 people who all drank from the same water cooler in Westchester County, and further outbreaks linked to various items walloped many New Yorkers that Connor himself cared for.
But there’s far more to the backstory of the small, round protozoan currently suspected of contaminating iceberg lettuce grown in Mexico. So, rather than focusing on water or contaminated edible greens like mesclun, scallions, snow peas, basil, and cilantro, let’s turn to Cyclospora‘s infamous connection to a ruby-red berry.
Consider the Raspberry
Dateline June 2000. At a wedding reception filled with joy, some people are laughing, some talking, and others are eating slices of cake layered with raspberries to put a sweet end to a special day.
One month later, investigators from the Philadelphia Health Department arrive at a not-yet-furnished flat strewn with gifts, where they open the freezer and retrieve the top tier of that cake.
“I think the family was expecting men in white suits,” the lead epidemiologist told me 15 years later. Of course, by then, the family was already reeling because beyond the five wedding guests who had Cyclospora in their stool, roughly 50 additional attendees, including the honeymooning newlyweds, had severe diarrhea. The final evidence linking these illnesses to raspberries came when CDC and FDA researchers detected Cyclospora DNA in the cake’s filling.
Nonetheless, because this ill-fated outbreak occurred during the fifth consecutive year that parasite-laced raspberries entered North America, it was really Guatemalan farmers who suffered the greatest lasting harm. Prior to 2000, certain growers had invested in anything they could — wells, flush toilets, sinks, disposable rubber gloves — to avoid losing the chance to sell raspberries to Norteños with a yen to eat them year-round. But despite their efforts, contamination continued and Guatemala finally lost its overseas raspberries market to Mexico and Chile.
Two more vignettes? Prior to Guatemala’s final concession of defeat, a seasoned pro at CDC’s then-named National Center for Infectious Diseases traveled to the Central American country to personally inspect its groves.
“They were amazing,” my long-time friend Sue Binder, MD, later told me with a tinge of sadness. “Raspberries everywhere, and row upon row of lush green bushes…some so tall I couldn’t see over them.”
However, Binder also noted that outdoor latrines were few and far between (“I’m not sure I would walk that far,” she added), and that a cook at a tortilla shack serving lunch “had a very dirty, half-naked toddler,” uncomfortably close to areas where food was prepared and served.
Binder’s final verdict? Fecal contamination was an ongoing risk. And talk about coincidence. Around the same time, Connor was also part of a team that went to Guatemala to advise government officials. He and his colleagues eventually concluded that untreated groundwater was routinely used to irrigate and dissolve pesticides sprayed on the beautiful bushes.
Recent Progress and What Lies Ahead
Back to the present. If you were to ask Connor or many other parasite mavens, myself included, I doubt you’d find anyone who thinks we won’t see more cyclosporiasis in the future. Most at risk are people never before exposed to the parasite because they grew up in sanitized settings (in short, most readers of this column). Other factors likely to foster additional U.S. outbreaks include our significant consumption of imported fruits and vegetables; our warming climate; and our nation’s now-reduced capacity to quickly track and quash foodborne outbreaks.
Nonetheless, there is good news about diagnosing Cyclospora. Unlike the first two decades following the misery it wreaked in Nepal, no one today needs to order a laborious modified acid-fast stain to find it in a sufferer’s stool. Instead, we have multiplex PCR panels that can identify an array of enteric pathogens — with a couple of caveats.
Frontline clinicians, especially now, need to maintain a high index of suspicion for Cyclospora because it can present atypically or elude diagnosis altogether if no one thinks of it. In addition, as Connor reminded me, not all multiplex panels have it in their list of targets. Which means there’s no time like the present to ask your lab which specific manufacturer and panel version it is using.
Lastly, a few words about treatment and prevention. Although trimethoprim-sulfamethoxazole (Bactrim) is highly effective against Cyclospora (nothing else comes close, according to Connor), in his experience, as many as 15% of patients don’t handle the drug well. So if you or someone you know is already allergic or sensitive to sulfa or possibly intolerant, please exercise special caution over the next few months. And also remember: salad can be great some of the time, but during an active outbreak, cooking produce is another (safer) option. Or, for now, maybe stick with well-washed, locally-sourced greens? That’s what Connor is telling his family to do.
