FDA Grand Rounds: Cyclospora cayetanensis

What are the symptoms and how to treat?

The symptoms of C cayetanensis infection include explosive watery diarrhea, loss of appetite, abdominal cramping, bloating, nausea, and fatigue, and may also include vomiting and low-grade fever. The only treatment presently available is trimethoprim-sulfamethoxazole. As this is the only known efficacious treatment, patients with sulfa allergy may have infection for >45 days.

A case of misidentification and interesting relatives

Cyclospora was identified as a separate parasite in 1993 to 1994. From its first observation in the early 1970s, it was believed to be part of the Cyanobacteria phylum. However, later investigations noted certain morphologic traits that researchers noted were better aligned with Cyclospora.

The FDA has also demonstrated in previous research that Cyclospora has a close phylogenetic relation to a zoonotic parasite. Therefore, researchers endeavored to find Cyclospora in stool samples of animals in an effort to identify hosts and reservoirs of the parasite. However, none of the research thus far in this area has presented any evidence that Cyclospora may have a zoonotic component. In the FDA Grand Rounds, Dr da Silva noted that during his research at the United States Centers for Disease Control and Prevention (CDC) investigating this possible zoonotic component of Cyclospora, he initially believed that they found evidence of Cyclospora in the semen of monkeys that were morphologically identical to C cayetanensis. However, phylogenetic analysis using the 18S ribosomal subunit demonstrated that these strains were not C cayetanensis, but altogether new and previously unidentified strains of the parasites C cercopitheci, C colossi, and C paplonis.

How does food get contaminated?

After accepting that there may not be a zoonotic reservoir, researchers focused on identifying better sequencing of C cayetanensis. In fact, there has been no evidence of a human infection with Cyclospora that does not match C cayetanensis.

C cayetanensis may contaminate fresh produce in 2 ways:

1. Agricultural water sources may be contaminated from oocytes in the soil.

2. Human hosts may contaminate water with unsporulated oocysts.

Why Should There Be Concern Regarding C cayetanensis?

C cayetanensis is a major public health concern because it can cause outbreaks. This is pivotal as there is a lack of surveillance programs. Recent events have spurred a change in this gap.

In 1999, there was an outbreak of C cayetanensis as a result of contaminated raspberries from Guatemala, causing 1465 cases of parasitic infection in 20 states. In 2000, oocysts in the raspberry filling of a wedding cake in Pennsylvania infected 54 of 79 people, and DNA polymerase testing confirmed infection was due to Cyclospora. The raspberries in this case were also sourced from Guatemala, making these 2 cases the first in the US to implicate raspberries as a source food for potential C cayetanensis infection. Another outbreak in 1999 in Missouri implicated fresh basil that was used to create sauces, which were then used as samples and found positive for C cayetanensis via polymerase chain reaction testing.

An outbreak in 2013 was the largest until 2018 and provided much of the epidemiologic data regarding this parasite. It was the first time data demonstrated that outbreaks of C cayetanensis could occur from multiple sources in multiple areas in the same time period (ie, 631 cases in 23 states). This was the catalyst to propel the development of a methodology in cases of C cayetanensis infection. In a joint investigation, the CDC and FDA published an article in 2015 that highlighted the absence of practical tools to detect C cayetanensis in food and other potentially contaminated environmental sources (eg, soil). This article also noted the need for molecular subtyping to augment evidence from epidemiologic studies.