FDA Grand Rounds: Cyclospora cayetanensis

Though much has been done in an effort to close them, there are still significant gaps in knowledge and research advancement on outbreaks of infection with Cyclospora cayetanensis.
There are still significant gaps in knowledge and research advancement on outbreaks of infection with Cyclospora cayetanensis.

Though much has been done in an effort to close them, there are still significant gaps in knowledge and research advancement on outbreaks of infection with Cyclospora cayetanensis. In an effort to increase awareness of these gaps, the United States Food and Drug Administration (FDA) held a Grand Rounds presentation on June 13, 2019, presented by Alexandre J. da Silva, MSc, PhD, Senior Biomedical Research Service, Research Microbiologist and Lead Parasitologist at the FDA’s Center for Food Safety and Applied Nutrition Office of Applied Research and Safety Assessment.

In 2015, the World Health Organization published an article which reported that between 2010 and 2015, approximately 5 million people worldwide were affected by a food-borne parasite-related disease. However, this research was limited by the knowledge and ability to identify specific parasitic infections, and therefore Cyclospora was not significantly addressed. The article referenced the severe burden of Taenia solium and Toxoplasma spp given the tools and serologic techniques available to identify these two infections, but there are no such tests to identify Cyclospora.

The burden of food-borne parasites, such as Cyclospora, is shared across all nations, including the US, though it does disproportionately affect individuals of developing nations. This may be a result of the route of transmission: humans are infected by the consumption of food or water sources that are contaminated by parasites at the infective stages of their life cycles (eggs, larvae, oocytes).

Parasites have complex life cycles that are dependent on a series of different categories of hosts. The definitive host is that host in which the parasite undergoes sexual reproduction; once this occurs an intermediate host may be found for the larval stage, wherein the parasite may mature unimpeded. The paratenic host can act as an amplifier, as it allows the parasite to grow actively and remain unchanged. Should the paratenic host be consumed by a definite host, the parasite may complete its life cycle. Paratenic hosts also allows for an increase in possible definitive hosts, as it may be consumed by atypical definitive hosts. The reservoir host is one which is unaffected, and allows for transmission to typical definitive hosts at a mature stage in the parasite’s life cycle. The accidental host is most commonly the category that humans enter this cycle. In this host, the most harmful response to the parasite occurs as the process of maturation triggers illness; with regard to the parasite, the accidental host is a ‘dead end’ because despite allowing it to reach maturity, the accidental host allows no route of transmission for the parasite.

In the US, there are many known parasites that can be acquired domestically. These include the nematodes Trichinella spp and Ascaris spp as well as the cestode Diphyloborthrium, which can grow to large sizes in the host. The protozoan parasites in the US include Toxoplasma, Cryptospora, Giardia, Entamoeba histolytica, and Cyclospora spp.

Protozoan parasites present a unique limitation in food-borne parasitology because of their ultramicroscopic size. Until recently, microscopy has been the cornerstone for identification and classification of food-borne parasites; however, the many species of protozoan parasites are morphologically identical. In addition, microscopy techniques do not have a high enough sensitivity to detect parasitic eggs, oocysts, and larvae. This created the impetus to develop DNA-based detection for identifying parasites. Polymerase chain reaction testing and DNA sequencing can now differentiate over a dozen distinct parasite species from many different sources, including stool, water, food, and common intermediate hosts such as slugs and snails.

Specifics on C cayetanensis

How do humans get infected with C cayetanensis?

This parasite is commonly found in fresh produce but can be acquired by consumption of any foods or water contaminated with sporulated oocysts, which then undergo the process of excystation within the human host. The cysts infect the epithelial cells of the gastrointestinal tract in order to sexually reproduce and mature. As unsporulated oocysts are produced, they are eliminated in the stools, where the parasite will continue its maturation process before it can continue the life cycle when ingested again. During the process of creating these progeny, the human host experiences the symptoms related to this infection.

Of note, C cayetanensis is the only known species of Cyclospora to infect humans, however there are no available in vivo or in vitro methods to grow C cayetanensis from clinical or food samples, which is imperative to understand what environments the parasite thrives in and what antiparasitic medications are most efficacious in killing it.

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.

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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.

This article originally appeared on Infectious Disease Advisor