ABSTRACT.
Cyclosporiasis has been a nationally notifiable disease in the United States since 1999, and cases have increased in recent years. We evaluated characteristics of U.S. cases and outbreaks to identify gaps and potential prevention measures for mitigating cyclosporiasis. We assessed Cyclospora data from the Foodborne Diseases Active Surveillance Network (FoodNet) and from the Foodborne Disease Outbreak Surveillance System (FDOSS) collected between 2015 and 2019. There were 1,376 cyclosporiasis cases in FoodNet between 2015 and 2019. Approximately one-fifth (n = 290, 21.1%) reported recent international travel. Most cases occurred in 2018 (n = 334, 24.3%) and 2019 (n = 758, 55.1%). There was strong seasonality, with 1,160 (90.9%) cases in the summer months. Most travelers reported visiting Mexico (n = 182, 62.8%) and Guatemala (n = 25, 8.6%). Approximately two-thirds of FoodNet cases were outbreak associated (n = 987, 71.7%). Of the 79 outbreaks reported to FDOSS, 31 (39.2%) occurred in 2018 and 40 (50.6%) occurred in 2019. Outbreaks tended to occur in spring and summer months (n = 78, 98.7%), The most common age groups among the 2,335 cases with data available included 20–49 years (n = 1,168, 50.0%), 50–74 years (n = 985, 42.2%), and ≥75 years (n = 120, 5.1%). Although direct comparisons between FoodNet and FDOSS are not possible, both datasets indicate that the majority of Cyclospora transmission is domestic and not travel associated, as previously thought. These findings show the need for continued investment in Cyclospora research, including identifying populations that are underrepresented, or at higher risk for cyclosporiasis, and improved understanding of national sources and pathways of infection.
INTRODUCTION
Cyclospora cayetanensis is a single-celled obligate intracellular parasite that can cause infection in the human gastrointestinal tract. Although cyclosporiasis may be asymptomatic, common symptoms include watery and/or explosive diarrhea, nausea, vomiting, stomach cramps, pain, bloating, gas, headaches, body aches, fever, loss of appetite, weight loss, and fatigue, which occur about a week after infection.1 If untreated, cyclosporiasis can persist with periods of remission and recurrence, and colonization of extraintestinal organs has been noted in immunocompromised individuals.2 Trimethoprim-sulfamethoxazole is a common and effective treatment, but relapses can still occur. For individuals allergic to sulfa drugs, other drug options remain to be identified.3 Treatment and recovery from one infection may not protect against subsequent infection or symptoms.3–6
Infection by Cyclospora generally occurs by consuming food and/or drinking water contaminated with sporulated (infective) oocysts.7–9 Previous work has identified contaminated soil and recreational water as potential transmission vehicles,3 with person-to-person transmission being unlikely. The life cycle of the parasite and specifics of infectivity and survival have not yet been fully characterized.2,7,9 Sporulation outside of the host appears to be necessary and is affected by factors such as temperature and humidity.3,8 Routine chemical disinfection and fresh produce sanitization methods may not remove and/or kill C. cayetanensis.10 Cyclospora oocysts have been found to remain on produce even after washing.11
Cyclosporiasis occurs in many countries and may be seasonably variable. The parasite is endemic mainly in tropical and subtropical countries, including Bangladesh, Brazil, Dominican Republic, Indonesia, Mexico, Thailand, and more. Cyclospora has even be found in nontropical/temperate-continental countries such as Romania.9 The pattern of seasonality in the United States features peaks from May to August, similar to what is seen in Mexico.12 Commonly implicated food sources include basil, berries, cilantro, lettuce, and other produce.1,3,8,10,13–16
After multiple outbreaks, cyclosporiasis was designated a nationally notifiable disease in 1999. Since then, the CDC initiated surveillance of cyclosporiasis, collecting information on cases from 43 states and the District of Columbia.9,10,17,18 Previously, limitations involving available diagnostics and parasitical expertise may have led to Cyclospora cases not being immediately detected, thus requiring health care providers to request specific testing when cyclosporiasis was clinically suspected and potentially hampering surveillance because of original misdiagnosis or underdiagnosis of actual cases.1 Recently, increases in laboratory-confirmed cases have been seen likely because of greater commercial availability of improved diagnostic tools such as the first gastrointestinal polymerase chain reaction (PCR) panel with a target for Cyclospora cleared by the U.S. Food and Drug Administration (FDA) in 2014.1,13,19 Adoption of such PCR panels has been rapid since then. A survey of approximately 700 U.S. diagnostic laboratories found that by 2018–2019, 62% reported the inclusion of tests for Cyclospora as part of routine enteric screening. Among those diagnostic laboratories, 87% relied on PCR panels for Cyclospora.20
Analyses of data from the CDC Foodborne Diseases Active Surveillance Network (FoodNet) revealed a statistically significant 399% increase in cyclosporiasis incidence per 100,000 population in 2018 compared with that in 2015–2017,21 followed by another significant increase of 1,209% in 2019 compared with the incidence in 2016–2018.14 While the COVID-19 pandemic led to widespread decreases in reported incidence of other monitored foodborne pathogens in the United States, Cyclospora incidence did not decrease in 2020.22 Therefore, the observed increases in cyclosporiasis incidence could have been due to improvements in laboratory diagnosis as well as other factors, such as increased exposure to sources of contamination. Here, we use the CDC FoodNet and the Foodborne Disease Outbreak Surveillance System (FDOSS) data to evaluate characteristics of cases and outbreaks toward identifying research gaps and potential prevention measures to complement ongoing efforts to reduce human illness from cyclosporiasis.
MATERIALS AND METHODS
We evaluated cyclosporiasis case data from FoodNet and outbreak data from FDOSS collected from 2015 to 2019.
Foodborne Diseases Active Surveillance Network conducts active surveillance of laboratory-confirmed Cyclospora infections and other illnesses transmitted commonly through food in a collaboration among the CDC, 10 state health departments, the U.S. Department of Agriculture’s Food Safety and Inspection Service (USDA-FSIS), and the FDA, representing 15% of the U.S. population.23 Data collected by FoodNet includes illness onset date, outbreak-related characteristics, symptomology, demographics, diagnostic test type, and history of travel outside the United States within 14 days of illness onset.
The FDOSS collects information from state and local health departments on U.S. foodborne disease outbreaks, including cyclosporiasis. Data from FDOSS included cyclosporiasis outbreak month/year, demographics, case outcome, and food vehicle/source of outbreak.
Descriptive analyses were conducted in SAS 9.4 (SAS Institute, Cary, NC) for Windows using variables coded as reported and provided by the CDC.
RESULTS
FoodNet: Overall.
There were 1,376 Cyclospora cases reported in the FoodNet catchment area between 2015 and 2019. As shown in Table 1, case age range varied widely, between 11 months and 98.3 years, with a mean age of 50 years. Most cases were aged 20–49 (647, 47.0%) or 50–74 (599, 43.5%) years. Table 2 shows the overall characteristics of the FoodNet cyclosporiasis cases. Most cases occurred in 2018 (n = 334, 24.3%) and 2019 (n = 758, 55.1%) and followed the typical seasonal pattern observed in the United States, with 1,160 (90.9%) cases peaking in the summer months of June (n = 283, 20.61%), July (n = 785, 57.0%), and August (n = 185, 13.4%). Minnesota reported the most cases (n = 321, 23.3%), followed by New York (n = 216, 15.7%), Maryland (n = 211, 15.3%), Connecticut (n = 200, 14.5%), and Georgia (n = 182, 13.2%). More than half of FoodNet cases were female (n = 830, 60.3%).
Table 1.
Age characteristics of FoodNet cyclospora cases, 2015–2019
| Characteristics | Min | Max | Mean | Median |
|---|---|---|---|---|
| Age | 11 months | 98.3 years | 50 years | 50.4 years |
| Age group | Category (in years) | Count | Percent | |
| Less than 1 | 1 | 0.1 | ||
| 1–4 | 4 | 0.3 | ||
| 5–9 | 3 | 0.2 | ||
| 10–19 | 25 | 1.8 | ||
| 20–49 | 647 | 47.0 | ||
| 50–74 | 599 | 43.5 | ||
| 75+ | 97 | 7.0 |
Table 2.
Other characteristics of FoodNet Cyclospora cases, 2015–2019
| Characteristics | Response (as reported) | Count | Percent |
|---|---|---|---|
| International travel | Yes | 290 | 21.1 |
| No | 986 | 71.7 | |
| Unknown | 100 | 7.3 | |
| Outbreak | Yes | 389 | 34.6 |
| No | 987 | 65.4 | |
| Sex | Female | 830 | 60.3 |
| Male | 546 | 39.7 | |
| Outcome | Alive | 1,363 | 99.1 |
| Dead | 1 | 0.1 | |
| Unknown | 12 | 0.9 | |
| Hospitalized | Yes | 75 | 5.5 |
| No | 1,276 | 92.7 | |
| Unknown | 25 | 1.8 | |
| Diarrhea | Yes | 1,281 | 94.1 |
| No | 11 | 0.8 | |
| Unknown | 69 | 5.1 | |
| Missing | 6 | ||
| Fever | Yes | 487 | 35.9 |
| No | 694 | 51.1 | |
| Unknown | 177 | 13 | |
| Missing | 18 | ||
| Ethnicity | Hispanic | 119 | 8.6 |
| Non-Hispanic | 1,147 | 83.4 | |
| Unknown | 110 | 8.0 | |
| Race | Asian | 20 | 1.5 |
| Black | 51 | 3.7 | |
| American Indian or Alaskan Native | 3 | 0.2 | |
| Multiracial | 9 | 0.7 | |
| Other | 41 | 3.0 | |
| Pacific Islander or Native Hawaiian | 1 | 0.1 | |
| White | 1,146 | 83.3 | |
| Unknown | 105 | 7.5 | |
| Site* | California | 41 | 3 |
| Colorado | 89 | 6.5 | |
| Connecticut | 200 | 14.5 | |
| Georgia | 182 | 13.2 | |
| Maryland | 211 | 15.3 | |
| Minnesota | 321 | 23.3 | |
| New Mexico | 25 | 1.8 | |
| New York | 216 | 15.7 | |
| Oregon | 10 | 0.7 | |
| Tennessee | 81 | 5.9 | |
| Year | 2015 | 54 | 4.7 |
| 2016 | 55 | 4 | |
| 2017 | 164 | 11.9 | |
| 2018 | 334 | 24.3 | |
| 2019 | 758 | 55.1 | |
| Month | January | 5 | 0.4 |
| February | 4 | 0.3 | |
| March | 9 | 0.7 | |
| April | 8 | 0.6 | |
| May | 37 | 2.7 | |
| June | 283 | 20.6 | |
| July | 785 | 57.0 | |
| August | 185 | 13.4 | |
| September | 23 | 1.7 | |
| October | 13 | 0.9 | |
| November | 13 | 0.9 | |
| December | 11 | 0.8 | |
| Outbreak type | Environmental (not food/water) | 1 | 0.3 |
| Foodborne | 374 | 96.1 | |
| Indeterminate | 6 | 1.5 | |
| Other | 2 | 0.5 | |
| Unknown | 6 | 1.5 | |
| Missing | 987 |
Data were obtained from Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, Tennessee, and selected counties in California, Colorado, and New York.
Ethnicity was reported as Hispanic for 119 (8.6%) individuals, non-Hispanic for 1,147 (83.4%), and unknown for 110 (8.0%) of the cases. Race was reported as Asian for 20 (1.5%), Black for 51 (3.7%), American Indian or Alaskan Native for 3 (0.2%), multiracial for 9 (0.7%), Pacific Islander or Native Hawaiian for 1 (0.1%), White for 1,146 (83.3%), other for 41 (3.0%), and unknown for 105 (7.5%) of the cases. Symptoms included diarrhea for nearly all (n = 1,281, 94.1%), but fever was reported for fewer than half (n = 487, 35.9%) of the cases. Only 75 (5.5%) were hospitalized, and one death was reported. Most cases with data on the outbreak type involved foodborne outbreaks (n = 374, 96.1%); only one case was associated with an outbreak of nonfood/nonwater environmental origin.
FoodNet: Travel status.
Of the 1,376 Cyclospora cases, 290 (21.1%) reported international travel, whereas 986 (71.7%) did not. Travel status was unknown for 100 cases (7.3%). Table 3 shows that the most frequently reported countries of travel were Mexico (n = 182, 62.8%), Guatemala (n = 25, 8.6%), the Dominican Republic (n = 11, 3.8%), Canada (n = 9, 3.1%), and Indonesia (n = 8, 2.8%). Travelers also reported traveling to 37 other countries.
Table 3.
Most common FoodNet travel destinations
| Rank | Country* | Count | Percent |
|---|---|---|---|
| 1 | Mexico | 182 | 62.8 |
| 2 | Guatemala | 25 | 8.6 |
| 3 | Dominican Republic | 11 | 3.8 |
| 4 | Canada | 9 | 3.1 |
| 5 | Indonesia | 8 | 2.8 |
| 6 | China, Cuba | 5 (each) | 1.7 (each) |
| 7 | Bahamas, Colombia, France, Peru, Philippines | 4 (each) | 1.4 (each) |
| 8 | Honduras, Vietnam | 3 (each) | 1.0 (each) |
| 9 | Cayman Islands, Costa Rica | 2 (each) | 0.7 (each) |
| 10 | 26 Other countries traveled by no more than 1 individual | 1 (each) | 0.3 (each) |
Travel countries are not mutually exclusive; i.e., individuals may have visited one or more countries.
Tables 4 and 5 compare the characteristics of travel- and non-travel-associated cases. Overall, the mean age for nontravelers was slightly higher (51.5 years) than for individuals who reported travel (45.4 years), despite nontravelers including the youngest case (11 months). Only 10 (3.5%) individuals who reported travel were part of a recognized outbreak, compared with 341 (34.6%) nontravelers. Travelers and nontravelers were relatively similar regarding some demographic and clinical variables, including sex, hospitalization, diarrhea, and fever. They differed, however, when it came to racial and ethnic identity and year of infection. First, more nontravelers than travelers reported as White (n = 877, 89% versus n = 222, 76.6%, respectively), whereas a larger proportion of travelers than nontravelers reported as Asian (n = 13, 4.5% versus n = 7, 0.7%) or unknown (n = 20, 6.9% versus 38, n = 3.9%). Nearly one-fifth of travelers reported as Hispanic (n = 61, 21.0%), whereas most nontravelers reported as non-Hispanic (n = 890, 90.3%). Finally, a higher proportion of cases occurred earlier during the study period among travelers than nontravelers, with over half of cases among nontravelers occurring in 2019 (n = 576, 58.4%)
Table 4.
Age characteristics, in years, of FoodNet Cyclospora cases, 2015–2019, by travel status
| Travel Status | Age | |||
|---|---|---|---|---|
| Min | Max | Mean | Median | |
| Traveled | 3.2 years | 83.8 years | 45.4 years | 46.3 years |
| Did not travel | 11 months | 98.3 years | 51.5 years | 51.8 years |
| Unknown | 20 years | 83.8 years | 49.1 years | 47.5 years |
Table 5.
Other characteristics of FoodNet Cyclospora cases, 2015–2019, by travel status
| Variables | Response (as reported) | Count: Traveled | % Traveled | Count: Did Not Travel | % Did Not Travel |
|---|---|---|---|---|---|
| Outbreak | Yes | 10 | 3.5 | 341 | 34.6 |
| No | 280 | 96.6 | 645 | 65.4 | |
| Sex | Female | 170 | 58.6 | 598 | 60.7 |
| Male | 120 | 41.4 | 388 | 39.4 | |
| Hospitalized | Yes | 12 | 4.1 | 8 | 5.9 |
| No | 277 | 95.5 | 926 | 93.9 | |
| Unknown | 1 | 0.3 | 2 | 0.2 | |
| Diarrhea | Yes | 277 | 95.8 | 970 | 98.9 |
| No | 3 | 1.0 | 3 | 0.3 | |
| Unknown | 9 | 3.1 | 7 | 0.7 | |
| Missing | 1 | 6 | |||
| Fever | Yes | 105 | 36.3 | 375 | 38.3 |
| No | 155 | 53.6 | 519 | 53 | |
| Unknown | 29 | 10 | 85 | 8.7 | |
| Missing | 1 | 7 | |||
| Immigrated to the United States | Yes | 2 | 0.7 | 0 | 0.0 |
| No | 257 | 88.6 | 593 | 60.1 | |
| Unknown | 31 | 10.7 | 393 | 39.9 | |
| Ethnicity | Hispanic | 61 | 21.0 | 52 | 5.3 |
| Non-Hispanic | 213 | 73.5 | 890 | 90.3 | |
| Unknown | 16 | 5.5 | 44 | 4.5 | |
| Race | Asian | 13 | 4.5 | 7 | 0.7 |
| Black | 17 | 5.9 | 31 | 3.1 | |
| American Indian or Alaskan Native | 1 | 0.3 | 2 | 0.02 | |
| Multiracial | 3 | 1 | 6 | 0.6 | |
| Other | 14 | 4.8 | 24 | 2.4 | |
| Pacific Islander or Native Hawaiian | 0 | 0 | 1 | 0.1 | |
| White | 222 | 76.6 | 877 | 89 | |
| Unknown | 20 | 6.9 | 38 | 3.9 | |
| Site* | California | 11 | 3.8 | 23 | 2.3 |
| Colorado | 63 | 21.7 | 24 | 2.4 | |
| Connecticut | 48 | 16.6 | 149 | 15.1 | |
| Georgia | 42 | 14.5 | 137 | 13.9 | |
| Maryland | 51 | 17.6 | 114 | 11.6 | |
| Minnesota | 36 | 12.4 | 265 | 26.9 | |
| New Mexico | 8 | 2.8 | 17 | 1.7 | |
| New York | 10 | 3.5 | 195 | 19.8 | |
| Oregon | 8 | 2.8 | 2 | 0.2 | |
| Tennessee | 13 | 4.5 | 60 | 6.1 | |
| Year | 2015 | 24 | 8.3 | 39 | 4 |
| 2016 | 22 | 7.6 | 29 | 2.9 | |
| 2017 | 57 | 19.7 | 104 | 10.6 | |
| 2018 | 77 | 26.6 | 238 | 24.1 | |
| 2019 | 110 | 37.9 | 576 | 58.4 | |
| Month | January | 4 | 1.4 | 1 | 0.1 |
| February | 1 | 0.3 | 3 | 0.3 | |
| March | 6 | 2.1 | 2 | 0.2 | |
| April | 7 | 2.4 | 1 | 0.1 | |
| May | 20 | 6.9 | 14 | 1.4 | |
| June | 77 | 26.6 | 192 | 19.5 | |
| July | 111 | 38.3 | 603 | 61.2 | |
| August | 47 | 16.2 | 130 | 13.2 | |
| September | 7 | 2.4 | 15 | 1.5 | |
| October | 2 | 0.7 | 11 | 1.1 | |
| November | 5 | 1.7 | 7 | 0.7 | |
| December | 3 | 1.0 | 7 | 0.7 | |
| Outbreak type | Environmental (not food/water) | 0 | 0 | 1 | 0.3 |
| Foodborne | 10 | 100 | 327 | 95.9 | |
| Indeterminate | 0 | 0 | 6 | 1.8 | |
| Other | 0 | 0 | 1 | 0.3 | |
| Unknown | 0 | 0 | 6 | 1.8 | |
| Missing | 280 | 645 |
Data were obtained from Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, Tennessee, and selected counties in California, Colorado, and New York.
FoodNet: Outbreak association.
More than two-thirds of the FoodNet Cyclospora cases were part of known outbreaks (n = 987, 71.7%), whereas 389 (28.3%) cases were not considered outbreak associated. Table 6 compares the characteristics of outbreak and nonoutbreak Cyclospora cases in FoodNet. The two groups were relatively similar in terms of age distribution and sex. A slightly higher proportion of nonoutbreak cases reported having diarrhea and fevers than outbreak-associated cases (n = 970, 98.9% versus n = 277, 95.8% and n = 105, 36.3% versus n = 375, n = 38.3%, respectively). Similar to the previous travel versus nontravel comparison, differences were seen in terms of race and ethnicity. A higher proportion of nonoutbreak cases reported as White (n = 877, 89.0% versus n = 222, 76.6%), whereas more outbreak cases reported as Asian (n = 13, 4.5% versus n = 7, 0.7%) or Black (n = 17, 5.9% versus n = 31, 3.1%) than nonoutbreak cases. Additionally, more nonoutbreak cases reported as Hispanic (n = 106, 10.7%) than outbreak cases (n = 13, 3.3%). Outbreak cases were more common in Colorado and Maryland, whereas nonoutbreak cases were more common in New York and Minnesota. Outbreak and nonoutbreak cases also differed in terms of temporal distribution. There were no outbreak cases in 2016, whereas there were nonoutbreak cases in all years. There were also more nonoutbreak cases than outbreak cases in 2017 (n = 156, 15.8% versus n = 18, n = 2.1%); however, there were fewer nonoutbreak cases in the two years that followed than outbreak cases (n = 212, 21.5% versus n = 122, 31.4% and n = 519, 52.3% versus n = 239, 61.4%, respectively). Finally, outbreak cases occurred only around the summer months (with the exception of two cases in December), whereas nonoutbreak cases occurred throughout the entire year. It should, however, be noted that the majority of these occurred in the summer months, as with outbreak-related cases.
Table 6.
FoodNet characteristics by outbreak association
| Variables | Category | Min | Max | Mean | Median |
|---|---|---|---|---|---|
| Age (in years) | Outbreak | 17.0 years | 98.3 years | 50.7 years | 50.4 years |
| Non-Outbreak | 11 months | 97.7 years | 49.7 years | 50.4 years | |
| Category | Count: Outbreak | % Outbreak | Count: Non-Outbreak | % Non-Outbreak | |
| Sex | Female | 170 | 58.6 | 598 | 60.7 |
| Male | 120 | 41.4 | 388 | 39.4 | |
| Diarrhea | Yes | 277 | 95.8 | 970 | 98.9 |
| No | 3 | 1.0 | 3 | 0.3 | |
| Unknown | 9 | 3.1 | 7 | 0.7 | |
| Missing | 1 | 6 | |||
| Fever | Yes | 105 | 36.3 | 375 | 38.3 |
| No | 155 | 53.6 | 519 | 53 | |
| Unknown | 29 | 10 | 85 | 8.7 | |
| Missing | 1 | 7 | |||
| Ethnicity | Hispanic | 13 | 3.3 | 106 | 10.7 |
| Non-Hispanic | 342 | 88.0 | 805 | 81.6 | |
| Unknown | 34 | 8.7 | 76 | 7.7 | |
| Race | Asian | 13 | 4.5 | 7 | 0.7 |
| Black | 17 | 5.9 | 31 | 3.1 | |
| American Indian or Alaskan Native | 1 | 0.3 | 2 | 0.02 | |
| Multiracial | 3 | 1 | 6 | 0.6 | |
| Other | 14 | 4.8 | 24 | 2.4 | |
| Pacific Islander or Native Hawaiian | 0 | 0 | 1 | 0.1 | |
| White | 222 | 76.6 | 877 | 89.0 | |
| Unknown | 20 | 6.9 | 38 | 3.9 | |
| Site* | California | 11 | 3.8 | 23 | 2.3 |
| Colorado | 63 | 21.7 | 24 | 2.4 | |
| Connecticut | 48 | 16.6 | 149 | 15.1 | |
| Georgia | 42 | 14.5 | 137 | 13.9 | |
| Maryland | 51 | 17.6 | 114 | 11.6 | |
| Minnesota | 36 | 12.4 | 265 | 26.9 | |
| New Mexico | 8 | 2.8 | 17 | 1.7 | |
| New York | 10 | 3.5 | 195 | 19.8 | |
| Oregon | 8 | 2.8 | 2 | 0.2 | |
| Tennessee | 13 | 4.5 | 60 | 6.1 | |
| Year | 2015 | 20 | 5.1 | 45 | 4.6 |
| 2016 | 0 | 0.0 | 55 | 5.6 | |
| 2017 | 18 | 2.1 | 156 | 15.8 | |
| 2018 | 122 | 31.4 | 212 | 21.5 | |
| 2019 | 239 | 61.4 | 519 | 52.3 | |
| Month | January | 0 | 0.0 | 5 | 0.5 |
| February | 0 | 0.0 | 4 | 0.4 | |
| March | 0 | 0.0 | 9 | 0.9 | |
| April | 0 | 0.0 | 8 | 0.8 | |
| May | 8 | 2.1 | 29 | 2.9 | |
| June | 107 | 27.5 | 176 | 17.8 | |
| July | 258 | 66.3 | 527 | 53.4 | |
| August | 113 | 3.3 | 172 | 17.4 | |
| September | 1 | 0.3 | 22 | 2.2 | |
| October | 0 | 0.0 | 13 | 1.3 | |
| November | 0 | 0.0 | 13 | 1.3 | |
| December | 2 | 0.5 | 9 | 0.9 | |
| Outbreak type | Environmental (not food/water) | 0 | 0 | 1 | 0.3 |
| Foodborne | 10 | 100 | 327 | 95.9 | |
| Indeterminate | 0 | 0 | 6 | 1.8 | |
| Other | 0 | 0 | 1 | 0.3 | |
| Unknown | 0 | 0 | 6 | 1.8 | |
| Missing | 280 | 645 |
Data were obtained from Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, Tennessee, and selected counties in California, Colorado, and New York.
FoodNet: Testing.
Table 7 presents the different testing methodologies used to detect Cyclospora infections in FoodNet. Among 850 infections detected using PCR-based diagnostic tests, the most common test used was the BioFire FilmArray gastrointestinal panel (n = 826, 97.2%). Among 526 infections detected using non-PCR-based diagnostic tests, the most common non-PCR test used was the modified acid-fast stain (n = 252, 47.9%), closely followed by microscopy unspecified (n = 239, 45.4%).
Table 7.
FoodNet testing information
| Diagnostic Tests | Count | Percent |
|---|---|---|
| PCR-based diagnostic tests | ||
| BioFire FilmArray gastrointestinal panel | 826 | 97.2 |
| Laboratory-developed test | 9 | 1.1 |
| Luminex Verigene enteric pathogens test | 1 | 0.1 |
| Luminex xTAG gastrointestinal panel | 2 | 0.2 |
| Unknown | 12 | 1.4 |
| Other diagnostic tests | ||
| Microscopy unspecified | 239 | 45.4 |
| Modified acid-fast stain | 252 | 47.9 |
| Modified safranin stain | 2 | 0.4 |
| Stained wet mount | 10 | 1.9 |
| Unknown | 20 | 3.8 |
| Wet mount | 3 | 0.6 |
FDOSS.
Table 8 shows the date of first illness reported among Cyclospora outbreaks reported through FDOSS. Of the 79 outbreaks reported through FDOSS, only two total (1.3% each) occurred in 2015 and 2016, followed by 6 (7.6%) in 2017, 31 (39.2%) in 2018, and 40 (50.6%) in 2019. Most outbreaks occurred in the spring/summer months in the United States, except for a single outbreak (2.5%) in December 2019. As shown in Table 9, outbreaks were reported in 23 individual states and/or multiple states, with the most in Illinois (n = 21, 26.6%), followed by Florida (n = 9, 11.4%), Massachusetts and Texas (each: n = 6, 7.6%), and Wisconsin (n = 5, 6.3%). Ohio and multistate locations were reported as exposure sites for four outbreaks (5.1%) each. Table 10 shows that of the 650 cases with outcomes available, none died, 68 (10.5%) were hospitalized, 118 (18.2%) visited an emergency room (ER), and 464 (71.4%) visited health care providers other than the ER; it is important to note that these are not mutually exclusive outcomes. The most common age groups among the 2,335 cases with data available included 20–49 years (n = 1,168, 50.0%), 50–74 years (n = 985, 42.2%), and ≥75 years (n = 120, 5.1%).
Table 8.
FDOSS outbreaks by year and month (date of first illness)
| Date of First Illness | Count | Percent |
|---|---|---|
| Year | ||
| 2015 | 1 | 1.3 |
| 2016 | 1 | 1.3 |
| 2017 | 6 | 7.6 |
| 2018 | 31 | 39.2 |
| 2019 | 40 | 50.6 |
| Total | 79 | 100.0 |
| Month | ||
| January | 0 | 0.0 |
| February | 0 | 0.0 |
| March | 0 | 0.0 |
| April | 0 | 0.0 |
| May | 13 | 16.5 |
| June | 39 | 49.4 |
| July | 25 | 31.6 |
| August | 1 | 1.3 |
| September | 0 | 0.0 |
| October | 0 | 0.0 |
| November | 0 | 0.0 |
| December | 1 | 1.3 |
| Total | 79 | 100 |
Table 9.
FDOSS outbreaks by state of exposure
|
Rank |
Exposure State | Count | Percent |
|---|---|---|---|
| 1 | Illinois | 21 | 26.6 |
| 2 | Florida | 9 | 11.4 |
| 3 | Massachusetts, Texas | 12 total; 6 each | 15.2 total; 7.6 each |
| 4 | Wisconsin | 5 | 6.3 |
| 5 | Ohio | 4 | 5.1 |
| 6 | California, Connecticut, Michigan, Minnesota, New York, Tennessee | 12 total; 2 each | 15.2 total; 2.5 each |
| 7 | Colorado, Georgia, Indiana, Kansas, Maryland, Montana, Nebraska, New Mexico, North Carolina, Virginia, Washington, DC | 12 total; 1 each | 15.2 total; 1.3 each |
| 8 | Multistate | 4 | 5.1 |
Table 10.
FDOSS demographic and other characteristics*
| Demographic (n or % of the primary cases with age data) | Count (outbreak- associated cases) | Percent |
|---|---|---|
| Age | ||
| <1 year | 1 | 0.0 |
| 1–4 years | 0 | 0.0 |
| 5–9 years | 3 | 0.1 |
| 10–19 years | 58 | 2.5 |
| 20–49 years | 1,168 | 50.0 |
| 50–74 years | 985 | 42.2 |
| ≥75 years | 120 | 5.1 |
| Total | 2,335 | 100.0 |
| Primary case outcomes | ||
| Died | 0 | 0 |
| Hospitalized | 68 | 10.5 |
| Visited ER | 118 | 18.2 |
| Visited health care provider (excluding ER visits) | 464 | 71.4 |
| Total | 650 | 100.0 |
ER = emergency room.
n presented is for cases with available information, different for each variable.
DISCUSSION
Direct comparisons of findings from FoodNet and FDOSS are not possible because of the different units of analysis found in each dataset: case/patient in FoodNet and outbreak level in FDOSS. This unfortunately limits what can ultimately be assessed. However, the datasets are complementary in terms of providing insights into addressing research gaps and have the potential to enhance prevention activities. For example, the FoodNet data showed that nonoutbreak cases exceeded outbreak cases in all years. Accelerating the development of tools to assay and assess relatedness of Cyclospora isolates could help recognize previously unidentified outbreaks and vehicles. In both datasets, over 90% of reported infections occurred in individuals aged 20–74 years (among those with information), with a slightly higher proportion of cases among the 20- to 49-year range. In areas where cyclosporiasis is endemic, it has been recognized that children are more likely to show symptoms than adults and that infections among adults are frequently asymptomatic.9,24,25 Although the FoodNet data suggest that the majority of Cyclospora cases are occurring among adults and not children and teenagers, it is important to continue to monitor the occurrence of disease in these younger populations, as sustained increases in pediatric cases may indicate a change in the endemicity status of the United States. Additionally, although the FoodNet analysis found that many cases traveled abroad, both datasets show that much of the Cyclospora transmission is likely occurring within the United States itself, highlighting the importance of a better understanding of national sources and pathways of infection.
Most of the cases in FoodNet were reported as White (n = 877, 89.0%), with similar distribution by outbreak (n = 308, 90.3%) versus nonoutbreak (n = 569, 88.2%) status. According to U.S. Census Data, White persons made up an estimated 73.4% on average of the population in the FoodNet catchment area during 2015–2019,26 indicating that White persons are overrepresented among cyclosporiasis cases in the FoodNet dataset. This could reflect issues related to health care-seeking behavior or access to health care that varies by self-reported race27,28 or to underreporting by other populations. Our analysis of FoodNet data also reflected higher percentages of cases that reported as Hispanic among nonoutbreak cases than non-Hispanic among outbreak cases. Previous analyses comparing FoodNet demographics with U.S. population demographics have identified that people of Hispanic ethnicity might be underrepresented in FoodNet datasets,29 so the number of cyclosporiasis cases among Hispanic persons might actually be much higher than what was seen in this analysis. We believe that further research exploring this area is needed to inform new approaches to enhance cyclosporiasis reporting and response.
Although this current analysis does not explore the potential transmission vehicles in depth, FDOSS data include various individual ingredient terms such as “cilantro” or “basil” when describing potential foodborne sources, which may be consumed individually or as part of more complex multi-ingredient foods such as pesto, chimichurri, pico de gallo, or guacamole. Although identifying individual ingredients is helpful in traceback and prevention at the source, additional information on complex, multi-ingredient foods involved could help improve our understanding of specific sources of infection and develop effective public health messages. In particular, it may be of interest to consider tailoring specific outreach and communication materials to the specific communities to increase awareness of the parasite and, consequently, to help reduce the burden of cyclosporiasis in the United States.
The high percentage of nonoutbreak cases also suggests that transmission could be occurring through unrecognized pathways. Accordingly, understanding the prevalence of asymptomatic C. cayetanensis carriage in the United States and further investigating the parasite’s life cycle are important, including addressing the gaps in scientific knowledge regarding parasite infectivity and survival. Although human fecal contamination is the ultimate source of Cyclospora, the process by which produce becomes contaminated has not yet been fully elucidated. For example, it is possible that fecal contamination of produce by food production and/or processing workers may contribute to transmission of the parasite, as many of these workers may come from areas where the parasite is endemic.30 It would be helpful to collect fecal specimens from specific populations who might be at higher risk of cyclosporiasis to better understand the prevalence of asymptomatic carriage as well as the effect this may have on contamination of produce in the United States. This potentially could be accomplished using large-scale, nationally representative studies such as the CDC’s National Health and Nutrition Examination Survey, which would allow for more granular demographic data.31
Finally, as observed by Dubey et al.,7 many unanswered questions persist in terms of oocyst dissemination and survival. Similarly, Ortega and Sanchez noted that despite positive identification of the supposed ideal time (7–15 days) and temperature (23–27°C) required for sporulation,9 attempts to infect animals or cells with sporulated oocysts have failed.32 This, in turn, makes it difficult to understand the activators and mechanisms that take place during the period in which oocysts sporulate and become infective. The availability of C. cayetanensis oocysts for research is limited, as infected humans are the only known source of the parasite. Unfortunately, attempts to develop methods to propagate Cyclospora both in vitro and in vivo to assess viability and infectivity have not yet succeeded; therefore, using other closely related parasite surrogates has been proposed.7,17 Despite such challenges, it is important to continue investing in research to clarify various biological and epidemiologic aspects that could potentially be used to disrupt the parasite’s life cycle.
CONCLUSION
Cyclospora cayetanensis is a major foodborne pathogen of concern, both in the United States and abroad. Although historical outbreak data has provided information on transmission vehicles for the parasite, much remains to be elucidated regarding its epidemiology and biology. This study assessed two CDC epidemiologic datasets (FoodNet and FDOSS), looking at various characteristics potentially associated with cyclosporiasis risk, including demographics and travel. Overall, while limited conclusions can be made from direct comparisons of the two data sources, potentially important research gaps have been identified that could help better understand and lead to ways to prevent future cases of cyclosporiasis and diminish disease burden.
ACKNOWLEDGMENTS
We acknowledge and thank our colleagues at the CDC who helped make this report possible, especially Anne Strailey, Daniel C. Payne, Hazel Shah, and Preethi Sundararaman.
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