As cyclosporiasis spreads across the US, what goes into a disease outbreak investigation?

Health officials are continuing to investigate as cases of cyclosporiasis, an intestinal illness caused by a parasite, spread across the United States.

More than 11,500 cases have been detected in 41 states, according to the most recent data from the Centers for Disease Control and Prevention (CDC). Of those cases, about 4,100 have been laboratory confirmed, and about 7,400 have yet to be.

The CDC and Food and Drug Administration (FDA) have linked an outbreak in at least nine states to shredded iceberg lettuce at some Taco Bell locations, supplied by Taylor Farms and sourced from central Mexico.

Federal health officials, along with state and local partners, have been examining the outbreak, looking at other potential sources and investigating unaffiliated clusters across the country.

But what exactly goes into investigating an outbreak of a foodborne illness? Public health specialists told ABC News it is a multi-step process including diagnoses, interviews, traceback and public heath messaging, all of which can take time.

"The U.S. has had, for decades now, very robust infrastructure to investigate, to find and prevent foodborne outbreaks," Dr. Graham Snyder, an infectious diseases expert and medical director of infection prevention and hospital epidemiology for the University of Pittsburgh Medical Center, told ABC News.

Detecting outbreak, finding cases 

Investigating foodborne outbreaks like the ongoing cyclosporiasis outbreak requires multiple steps, which Snyder explained are not sequential and are often occurring simultaneously.

Typically, an investigation begins when clinicians diagnose patients. This can be challenging with cyclosporiasis because the average time between infection and when symptoms appear is one week but can take up to two weeks or longer. This makes it difficult to determine what infected someone.

The most common symptom of cyclosporiasis is watery diarrhea with sometimes "explosive bowel movements," according to the CDC.

However, many people have mild symptoms that can resolve on their own without medical care. Those who have more severe symptoms may choose not to seek care as well.

"Outbreak investigation ... it requires people getting diagnosed," Snyder said. "Cyclospora is a pathogen that doesn't tend to make people seriously ill, ill enough to be hospitalized ... so people may have diarrhea and say, "Ah, just diarrhea, I'll sit this one out' and a lot of people get better without treatment, so they may not get diagnosed."

He noted how "that type of situation is challenging" when it comes to diagnosis.

"In this circumstance, it requires doctors and advanced practice providers to recognize that there is a cyclosporiasis outbreak, that their patient has symptoms that may be compatible with that, and then get the specific test, not one that's routinely occurred," he said.

Testing for Cyclospora -- the parasite that causes cyclosporiasis -- is not typically included in routine U.S. laboratory stool testing and must be specifically requested by a healthcare provider, according to the CDC, which can delay results.

When public health officials investigate a foodborne illness outbreak such as Salmonella or E. coli, a laboratory can grow the bacterium in a culture and use whole-genome sequencing -- a process that figures out the exact order of all the DNA bases in an organism -- to subtype it.

Snyder said officials compare the genetic code of the bacteria to see if different patients are carrying closely related strains, which indicates the bacteria are probably from a common source.

Cyclospora cannot be grown in a laboratory and requires a different type of testing and subtyping.

"Parasites cannot be cultured and we have to rely on more specialized testing like molecular testing," Dr. Peter Chin-Hong, an infectious diseases specialist and associate dean for regional campuses at the University of California, San Francisco, told ABC News.

He noted that whole genome sequencing "can 'fingerprint' bacteria," allowing officials to link cases.

"It is harder to 'fingerprint' Cyclospora and other parasites," he said. "So, investigators in Cyclospora need to rely more heavily on food interviews and epidemiology -- more pattern recognition rather than molecular precision."

The CDC usually identifies a multistate outbreak through the national laboratory network PulseNet, for a bacterial enteric (intestinal) disease outbreaks, or through public health partners, as occurred with the cyclosporiasis outbreak.

Traceback investigation 

After cases are reported to local public health departments -- if officials realize there is a greater than expected frequency of cases -- they begin a traceback investigation. This involves calling those who are infected and asking them to trace back what they've eaten in the past several days.

"The next step is to identify what cases have in common," Snyder said. "So, for example, you may interview people who, in a particular area, went to the doctor and had diarrhea, and some of those people have Cyclospora. Some of those people have something else. So, we'll interview them and ask them, 'Tell us about all the food that you eat.'"

Chin-Hong said this can be difficult to do for lettuce because salad mix at an eating establishment can contain leaves from several different farms.

"It's not like 'Murder She Wrote' or a Netflix crime drama," Chin-Hong said. "The evidence is eaten, the crime scene is cleared, the witnesses don't remember and the traditional forensic tools don't work in the same way."

Snyder said the CDC has an "impressively large tool" that staff uses to conduct "really rigorous interviews" about foods that people have eaten.

"You then compare the frequency of foods that people have eaten among people who are sick and who are not," he said.

Investigators will interview patients to find common exposures -- be it foods, restaurants, grocery stores, or travel.

Snyder added that health officials will then investigate the supply chain, looking at practices, determining if there is anything related to hygiene, food handling, equipment disinfection that is not up to the standard it should have been to prevent contamination or cross-contamination.

Officials may also interview people working in different areas to find out if they've had the illness or not, which may include sampling the food or the equipment being used, Snyder said.

'We know that this lettuce has broad distribution which is likely resulting in broader illness," said John Brownstein, chief innovation officer at Boston Children's Hospital and an ABC News medical contributor. "It's reaching restaurants, retailers, food service distribution and that has a range of different locations from restaurants to Walmarts to U.S. food customers. So, we recognize that there [are] likely many points of intersection with this tainted lettuce."

Voluntary recall, public health messaging 

One of the next steps will be preventing more illnesses, often by making sure the contaminated food is removed from store shelves, restaurant kitchens or homes.

This includes recalling the food, warning people not to eat or sell the food or telling people how to make the food safe to eat, according to the CDC.

Earlier this month, Taylor Farms de Mexico issued a voluntary recall of all iceberg lettuce sourced from central Mexico, with the recall affecting 27 states. The recalled products were distributed from June 29 through July 16 and have best-if-used-by dates up to Aug. 3.

Additionally, Taco Bell said it is no longer using lettuce from Taylor Farms de Mexico at any of its restaurants.

"We then start to give message out to the public about food safety," Snyder said. "We want to prevent harm right off the bat. So, while you're figuring things out, you're doing work to prevent more transmission."

Brownstein said it is important to understand that the investigation will take to time to complete -- as will the outbreak to resolve -- due to delays in symptoms appearing as well as delays in testing and reporting.

The CDC said it can take up to six weeks to determine if a sick person is part of the current cyclosporiasis outbreak.

"This means that we may not know for several weeks when this outbreak is over and in the meantime, we have to practice vigilance," he said. "We have to understand where the sources of potentially tainted lettuce came from, so individuals can make sure that they're not consuming that lettuce. ... Mostly, they just need to follow CDC and FDA guidance to make sure they are practicing safe food consumption habits."