Foodborne Toxoplasmosis

CDC’s Center for Global Health

Anne Straily, DVM, MPH, DACVPM Veterinary Medical Officer Rocky Mountain Food Safety Conference

June 13, 2019 Today’s Agenda: . A brief update on 2018 cyclosporiasis season . Foodborne toxoplasmosis – Background – Transmission – Prevention Cyclosporiasis . Gastrointestinal illness caused by the parasite Cyclospora cayetanensis . Humans are only known reservoir host – Fecal‐oral transmission . Endemic in the tropics and subtropics . U.S. infections typically associated with – International travel to areas of endemicity – Consumption of imported fresh produce from areas of endemicity – Seasonal onset, primarily during spring/summer months Update on cyclosporiasis – 2018 . 3,614 cases (3,280 confirmed, 334 probable) were reported by 47 jurisdictions (45 states, DC, and NYC) – 2,657 (74%) cases reported in persons with onset during May – August and no history of international travel – 221 hospitalizations reported, no deaths – Approximately 1/3 were linked to one of two large multistate outbreaks . More than 50 clusters/outbreaks were identified and investigated in U.S.

Slide courtesy of S. Casillas; Data are current as of 4/25/19. Number of reported cyclosporiasis cases, by year of report and international travel history – United States, 2010‐2018

Slide courtesy of S. Casillas; Data are current as of 4/25/19. Multistate cyclosporiasis outbreaks – 2018 . Vegetable trays from Kwik Trip/Del Monte – 267 reported cases (250 confirmed, 17 probable) – Cases reported by 4 states: IA, MI, MN, WI – Pre‐packaged vegetable trays with broccoli, cauliflower, & carrots . Salads from McDonald’s/Fresh Express – 559 reported cases (516 confirmed, 43 probable) – Cases reported by 16 jurisdictions, exposures occurred in 11 states: CT, NY, VA, FL, TN, KY, OH, MI, IN, IL, WI, MN, IA, MO, SD, NE – Multiple types of McDonald’s salads (all share common base ingredients)

Slide courtesy of S. Casillas; Data are current as of 4/25/19. Additional cyclosporiasis outbreaks – 2018 . Mexican‐style restaurant outbreaks – Three separate clusters in 3 different states in the Midwest – Total of 53 laboratory confirmed cases – Cilantro identified as likely food source in all 3 clusters . Basil‐associated clusters – Two clusters, 8 cases each in 2 different states . Many cases could not be directly linked to an outbreak – Lack of validated molecular typing tools – CDC working to develop genotyping technique for C. cayetanensis

Slide courtesy of S. Casillas; Data are current as of 4/25/19. Foodborne Toxoplasmosis Toxoplasmosis . Toxoplasma gondii . Obligate intracellular protozoal parasite . Named for its arc‐like shape – Greek tóxicon (poisoned arrow, from tóxon [bow]) – Greek plasma (something molded) . Discovered in 1909 in the blood, spleen, & liver of North African rodent Ctenodactylus gondii T. gondii tachyzoites, Giemsa stain

Image: DPDx https://www.cdc.gov/dpdx/toxoplasmosis/index.html Toxoplasmosis . Cats (Felidae) only known definitive host – Definitive host = the host in which the parasite undergoes sexual reproduction

. All warm‐blooded animals may be intermediate hosts – Intermediate host = a host normally used by a parasite in the course of its lifecycle where it may multiply asexually but not sexually

Photo courtesy of Dr. Cara Cherry Geographic distribution . One of the most common human infections globally . Everywhere cats are found . In the U.S. – 41.7 million households owned a pet cat – 94.2 million pet cats (~2.2 cats/household) – ~80 million feral cats – ?? Felid wildlife

Photo courtesy of Dr. Cara Cherry Toxoplasma gondii Lifecycle

Image: DPDx https://www.cdc.gov/parasites/toxoplasmosis/biology.html Vocabulary review . Bradyzoite – slowly dividing, forms cysts in tissues, more chronic phase . Encysted . Tachyzoite . Oocyst

Images: DPDx https://www.cdc.gov/dpdx/toxoplasmosis/index.html Vocabulary review . Bradyzoite . Encysted – the bradyzoite stage in tissues in a host . Tachyzoite . Oocyst Vocabulary review . Bradyzoite . Encysted . Tachyzoite – rapidly dividing, intracellular, found primarily in the acute phase of illness . Oocyst

Images: DPDx https://www.cdc.gov/dpdx/toxoplasmosis/index.html Vocabulary review . Bradyzoite . Tachyzoite . Encysted . Oocyst – the egg stage resulting from sexual reproduction in the definitive host

Images: DPDx https://www.cdc.gov/dpdx/toxoplasmosis/index.html Other important terms . Seropositive = detectable antibody titers above a pre‐determined cut‐off . Seroprevalence = the proportion of a population with detectable antibodies to T. gondii . Presence of antibodies is an indication of exposure Toxoplasma “in the wild” . Spread naturally among Felidae by predation . Almost all cats infected by eating tissue cysts will shed oocysts . <25% of cats infected by eating oocysts or tachyzoites will shed oocysts . Parasite damages brains of infected rodents – Less neophobic – Less fearful of odor of cats – Get eaten  parasite completes its lifecycle

Image: DPDx https://www.cdc.gov/parasites/toxoplasmosis/biology.html Human toxoplasmosis . Among healthy adults, majority of infections are mild (swollen lymph nodes, flu‐like illness) or asymptomatic – Chorioretinis (ocular infection) – blurred vision, pain, vision loss . Disease in immunocompromised persons can be fatal (toxoplasmic encephalopathy) . An infection occurring during pregnancy or shortly before pregnancy can result in congenital transmission – Risk and outcome vary by stage of gestation when infection occurred – Stillbirth, premature birth, developmental and ocular abnormalities Transmission to humans . Ingestion . Transplacentally . Organ transplantation & blood transfusion Transmission to humans . Ingestion . Transplacentally . Organ transplantation & blood transfusion Foodborne toxoplasmosis . Estimated >86,000 infections acquired annually in the U.S. . Most common parasitic foodborne illness . 2nd leading cause of foodborne illness deaths . 4th leading cause of foodborne illness hospitalizations . 32,700 disability‐adjusted life years (DALYs) – DALY = aggregated loss of life/health due to illness compared to ‘perfect health’ over time – Second only to non‐typhoidal Salmonella – More than Campylobacter (22,500), norovirus (9900), Listeria (8800), C. perfringens (4000) and E. coli (1200) Foodborne Transmission Transmission by ingestion . Tissue cysts from infected raw/undercooked meat . Sporulated oocysts – Unwashed, contaminated produce – Untreated, contaminated water – Oocysts on your hands • Contact with contaminated soil • Cleaning litter box of a cat actively shedding oocysts . Tachyzoites in unpasteurized milk (particularly goat milk)

Images: DPDx https://www.cdc.gov/dpdx/toxoplasmosis/index.html Transmission by ingestion . Tissue cysts from infected raw/undercooked meat . Sporulated oocysts – Unwashed, contaminated produce – Untreated, contaminated water – Oocysts on your hands • Contact with contaminated soil • Cleaning litter box of a cat actively shedding oocysts . Tachyzoites in unpasteurized milk (particularly goat milk)

Images: DPDx https://www.cdc.gov/dpdx/toxoplasmosis/index.html Transmission by ingestion of tissue cysts

Image: DPDx https://www.cdc.gov/parasites/toxoplasmosis/biology.html Meat . Pork . Poultry . Sheep/goat . Venison and other wild game . Shellfish (oysters, clams, and mussels) T. gondii and pork . Prevalence of T. gondii in U.S. pork is declining . Risk varies by production system – Seroprevalence among confinement‐raised hogs: ~0‐2.7% – Seroprevalence among pasture‐raised hogs: as high as 93% – Seroprevalence studies from the Netherlands: • 18% of hogs from organic farms • 59% of hogs from free‐range farms • 0% of hogs from conventional farms . No certification programs exist to address risk of T. gondii in pork in U.S. A word about cured pork products… . Studies have identified cured, dried, and smoked meats as a potential risk factor . Ability of curing process to destroy T. gondii depends on salt concentrations and curing time and method – Parma hams cured according to standards did not have viable T. gondii – Serrano hams cured for <14 months still had viable T. gondii – Pepperoni sausage fermented >6 hours did not have viable T. gondii T. gondii in poultry . Risk from commercial chicken is likely small – Retail meat surveys ~0%, no viable T. gondii cysts isolated . Risk varies by production system – Free‐range/backyard chickens up to 100% seropositive, viable cysts isolated from meat . Uncooked eggs not a proven risk

Photo: www.pinterest.com Why are pasture‐raised animals more likely to be infected? . Exposed to environmental contamination with cat feces – Oocysts in soil, grass, feed, or water . Exposed to infected rodents or wildlife

Photo: https://phil.cdc.gov/default.aspx Sheep and goats . Not frequently consumed in the U.S. . Seroprevalence can be high – 77.9% in slaughter lambs – 25.8% in retail goat meat . These animals tend to be raised on pasture Venison Other wild game . White‐tailed deer . Feral swine . Mule deer . Black bear . Elk . Caribou . Moose White‐tailed deer . U.S. population ~30 million animals . Nearly 6 million animals harvested each year – The most commonly/frequently hunted big game animal in the U.S.

Map: https://nhpbs.org/natureworks/whitetaileddeer.htm Map: Seropositive MN: 23‐56% white‐tailed deer and reported 42% seroprevalence 60% levels 54‐64% 56‐74% NJ: 29% 43% 60%

40% 45% 47% 44% White‐tailed deer . Older deer are more likely to be seropositive . Atypical genotypes common – May be associated with severe disease and unusual presentations in immunocompetent human patients

Photo: https://phil.cdc.gov/default.aspx Recent venison‐related toxoplasmosis outbreaks . Wisconsin, 2017 . Quebec, Canada, 2019 Wisconsin, October, 2017 . Acute illness in a group of men following a church retreat Wisconsin, October, 2017 . Acute illness in a group of men following a church retreat . Fever, fatigue, muscle aches, sweats Wisconsin, October, 2017 . Acute illness in a group of men following a church retreat . Fever, fatigue, muscle aches, sweats . Serologic testing consistent with recently acquired Toxoplasma infection Wisconsin, October, 2017 . Acute illness in a group of men following a church retreat . Fever, fatigue, muscle aches, sweats . Serologic testing consistent with recently acquired Toxoplasma infection . Venison from a locally, recently harvested deer was served at the retreat Wisconsin, October, 2017 . Acute illness in a group of men following a church retreat . Fever, fatigue, muscle aches, sweats . Serologic testing consistent with recently acquired Toxoplasma infection . Venison from a locally, recently harvested deer was served at the retreat – 9/10 ate the venison – reported it was definitely/possibly undercooked – 1 attendee who did not eat venison was not ill – Venison tested positive for T. gondii, atypical genotype identified – Venison had not been frozen between harvest and the retreat Quebec, Canada, 2019

https://montrealgazette.com/news/local-news/quebec-outbreak-of-toxoplasmosis-linked-to-undercooked-venison Quebec, Canada, 2019

https://montrealgazette.com/news/local-news/quebec-outbreak-of-toxoplasmosis-linked-to-undercooked-venison Seroprevalence levels in other deer species

CA (15%) KY (56%) and PA (70%) NE (35%) AK (23%) and MN (10%) MT (100%, n=2)

Photos: Mule deer ‐ https://phil.cdc.gov/default.aspx; Moose ‐ https://www.nps.gov/lacl/learn/nature/moose.htm; Elk ‐ https://en.wikipedia.org/wiki/Elk Feral swine . Escaped domestic swine, Eurasian wild boar, or hybrids . U.S. population estimated ~6 million animals in at least 35 states . Are destructive – cause estimated $1.5 billion each year in damage . Hunting allowed in most states with viable populations

Image: https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/operational‐activities/feral‐swine/sa‐fs‐history https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/operational‐activities/feral‐swine/sa‐fs‐history =Seropositive swine identified (Hill et al., 2014)

https://www.aphis.usda.gov/aphis/ourfocus/wildlifedamage/operational‐activities/feral‐swine/sa‐fs‐history Black bears . Seroprevalence ranges from 14% (AK) to 85% (MD) . Older animals more likely to be seropositive . Atypical genotypes identified

Map: https://bear.org/black‐bear‐range/ Oysters, clams, and mussels

Images: https://www.cdc.gov/vibrio/vibrio‐oysters.html; https://www.cdc.gov/vibrio/prevention.html Oysters, clams, and mussels . Sea otters in CA infected with toxoplasmosis

Photo credit: Oregon Coast Aquarium, http://aquarium.org/tag/sea‐otter/ Oysters, clams, and mussels . Sea otters in CA infected with toxoplasmosis . T. gondii identified by PCR and DNA sequencing in CA mussels . Oocysts are environmentally resistant – not killed by sewage treatment, water, or salt water

Photo credit: Oregon Coast Aquarium, http://aquarium.org/tag/sea‐otter/ What about beef? . Role of beef in human toxoplasmosis is unclear . Human studies: eating raw/undercooked beef identified as risk factor . Cattle studies: discrepancies between seropositivity, positive PCR, and recovery of viable tissue cysts . Unknown if cattle remain infected for life or somehow overcome infection and eliminate parasite . More formal risk assessments needed Transmission by ingestion . Tissue cysts from infected raw/undercooked meat . Sporulated oocysts – Unwashed, contaminated produce – Untreated, contaminated water – Oocysts on your hands • Contact with contaminated soil • Cleaning litter box of a cat actively shedding oocysts . Tachyzoites in unpasteurized milk (particularly goat milk)

Images: DPDx https://www.cdc.gov/dpdx/toxoplasmosis/index.html Transmission by ingestion of sporulated oocysts

Image: DPDx https://www.cdc.gov/parasites/toxoplasmosis/biology.html Produce . Limited information available in published literature . Eating unwashed raw fruits and veg associated with increased risk of acquiring toxoplasmosis . Sporulated oocysts can attach to and remain infectious on raspberries and blueberries for at least 8 weeks under refrigerator conditions . Oocysts detected on both organic and conventionally grown spinach

Images: CDC Public Health Image Library https://phil.cdc.gov/Default.aspx/ Which one (oocysts or tissue cysts) causes more illness? . Difficult to attribute source of infection to oocyst vs. tissue cysts – Laboratory test to detect oocyst‐specific antibody is research only – Antibody degrades ~6 mo after exposure . Boyer, et al (2011): 78% of U.S. mothers of congenitally infected infants had primary infection from ingesting oocysts – Only 49% had recognized risk factors for oocyst exposure – Oocyst exposure did not correlate with hometown location or size, socioeconomic status, or ethnicity Transmission by ingestion . Tissue cysts from infected raw/undercooked meat . Sporulated oocysts – Unwashed, contaminated produce – Untreated, contaminated water – Oocysts on your hands • Contact with contaminated soil • Cleaning litter box of a cat actively shedding oocysts . Tachyzoites in unpasteurized milk (particularly goat milk)

Images: DPDx https://www.cdc.gov/dpdx/toxoplasmosis/index.html Unpasteurized milk . Limited evidence available in published literature . Drinking unpasteurized goat’s milk increased odds of toxoplasmosis in case‐control study . Case report of a CA infant developing toxoplasmosis after being fed raw goat’s milk Unpasteurized milk . Simultaneous toxoplasmosis infection in a goat herd and herd owner’s family – 4/6 goats from small British goat herd gave birth to weak or stillborn kids, all of which were seropositive for T. gondii – T. gondii isolated from one kid and a milk sample – Goat owner’s sons were seropositive, one acutely ill at time of investigation – Family had a habit of drinking raw goat milk Cheese made from unpasteurized milk . Limited information available in published literature . Study indicated that tachyzoites may be able to survive cheese‐making process (cold‐enzyme treatment) – No mice fed cheese made from infected goat milk developed illness – Only 1 of 4 cats fed cheese produced oocysts . No reported human toxoplasmosis cases linked to unpasteurized cheese products Prevention Dietary habits . Avoid consuming raw or undercooked: – Meat (any kind) – Oysters – Clams – Mussels – Milk (any kind) or cheese made from raw milk

. Cured/dried/smoked meats also a risk factor

Images: http://www.nationalgeographic.com/people‐and‐culture/food/the‐plate/2016/06/sustainable‐oyster‐harvest‐chesapeake‐bay/ Practice good food hygiene . Freezing meat to destroy tissue cysts – ‐12°C (10°F) or below for at least 2‐3 days . Cook meat thoroughly to destroy cysts (USDA Guidelines) – Whole cuts of meat – 145°F with 3 minute rest – Ground meat and wild game – 160°F – Poultry – 165°F . Wash all surfaces and utensils that came into contact with raw meat . Wash and/or peel fruits and vegetables (or cook them) WASH YOUR HANDS . Always before eating or preparing food . After handling raw meat, unwashed produce . After cleaning cat litter boxes . After working in the soil

Photo: https://www.cdc.gov/handwashing/buttons.html Other preventive measures . Clean cat litter boxes every day . Keep cats indoors to prevent them from hunting and becoming infected . Feed cats only commercially prepared canned or dried food . Cover children’s sandboxes when not in use . Wear gloves when gardening or working in the soil

Photo credit: CDC PHIL In summary… . Toxoplasmosis is caused by T. gondii . Felines are the definitive host . Transmission from food: meat, milk, shellfish, fresh produce . Prevention: – Avoidance – Good food hygiene practices – Hand washing Questions?

For more information, contact CDC 1‐800‐CDC‐INFO (232‐4636) TTY: 1‐888‐232‐6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.