1. Campylobacter jejuni “Bad Bug” Presentation by Kim Mihalek

2. What Is Campylobacter jejuni? Bacteria Bacteria Slender, Rod Shaped* Slender, Rod Shaped* Flagellate Flagellate Motile Motile Gram negative Gram negative Microaerophilic Microaerophilic Thermophilic Thermophilic

3. What is known about the Genome of C. jejuni? First published 2/10/2000 in Nature by Parkhill, et al. First published 2/10/2000 in Nature by Parkhill, et al. Unusual points Unusual points –Almost complete lack of repetitive DNA sequences. –No functional inserted sequences or phage- related sequences. –Little organization of genes into operons or clusters. –Broad set of regulatory systems to adapt to varying environmental conditions

4. What is Campylobacteriosis? Infectious disease caused by bacteria of genus Campylobacter. Infectious disease caused by bacteria of genus Campylobacter. 99% C. jejuni, 1% other. 99% C. jejuni, 1% other. Affects the small intestine. Affects the small intestine. Not recognized as cause of human food borne illness prior to 1975. Not recognized as cause of human food borne illness prior to 1975. Most common bacterial cause of diarrheal illness in the United States -More cases than Shigella and Salmonella combined. Most common bacterial cause of diarrheal illness in the United States -More cases than Shigella and Salmonella combined.

5. How Prevalent Is This Disease In the United States? Most common cause of food borne illness in the United States. Most common cause of food borne illness in the United States. 15 cases diagnosed/100,000 people annually. 15 cases diagnosed/100,000 people annually. Approximately 100 people die each year.. Approximately 100 people die each year.. Most cases go unreported or undiagnosed Most cases go unreported or undiagnosed –Estimated 1-4 million cases in U.S. yearly.

6. How Prevalent Is This Disease Worldwide? Leading cause of food borne illness worldwide. Leading cause of food borne illness worldwide. Many countries do not have national survey programs for Campylobacteriosis; worldwide incidence numbers do not exist. Many countries do not have national survey programs for Campylobacteriosis; worldwide incidence numbers do not exist. Prevalent in developing countries. Prevalent in developing countries. Study by University of Lagos, Nigeria showed that in developing countries, 40-60% of children under 5 with diarrhea were positive for Campylobacter spp. Study by University of Lagos, Nigeria showed that in developing countries, 40-60% of children under 5 with diarrhea were positive for Campylobacter spp. Worldwide, gastroenteritis is second only to respiratory infections in causing deaths. Worldwide, gastroenteritis is second only to respiratory infections in causing deaths.

7. Who is affected? All warm-blooded animals can become affected. Some animals carry the disease without exhibiting symptoms. All warm-blooded animals can become affected. Some animals carry the disease without exhibiting symptoms. Any person can become infected. Any person can become infected. Children under 5 and young adults ages 15-29 are most often affected. Children under 5 and young adults ages 15-29 are most often affected. Most deaths occur among the elderly and the immune-suppressed. Most deaths occur among the elderly and the immune-suppressed.

8. What Are the Symptoms? Diarrhea Diarrhea –Usually watery and sticky –Can contain blood and fecal leucocytes Fever Fever Abdominal pain Abdominal pain Nausea and vomiting Nausea and vomiting Headache Headache Muscle pain Muscle pain

9. Are There Long-Term Effects? Guillain-Barre Syndrome Guillain-Barre Syndrome –Immune system attacks own nerves –40% caused by C. jejuni infection Arthritis, Reiter’s Syndrome Arthritis, Reiter’s Syndrome Hemolytic Uremic Syndrome Hemolytic Uremic Syndrome Septicemia Septicemia –Leading to infection of nearly any organ, including appendix, abdominal cavity, heart, nervous system, etc.

10. How Does Campylobacter affect individual cells in the intestines? Produces a toxin called Cytolethal Distending Toxin (CDT). Produces a toxin called Cytolethal Distending Toxin (CDT). CDT activity requires activation of three genes: cdtA, cdtB, and cdtC. CDT activity requires activation of three genes: cdtA, cdtB, and cdtC. CdtB is nuclease that damages DNA and causes cell cycle arrest. CdtB is nuclease that damages DNA and causes cell cycle arrest. Causes cell death. Causes cell death.

11. How Does Campylobacter Affect Individual Cells In the Intestines?

12. What Is the Incubation Period and How Long Does the Illness Last? Onset of symptoms 2-10 days after ingestion. Onset of symptoms 2-10 days after ingestion. Duration of illness 2-21 days, typically 5-7 days. Duration of illness 2-21 days, typically 5-7 days. Relapses occur in 25% of cases. Relapses occur in 25% of cases.

13. What are the Diagnostic Tests? Present in feces of infected individuals Present in feces of infected individuals Cultured sample of stool from ill person Cultured sample of stool from ill person Isolation requirements: Isolation requirements: –Special antibiotic containing media –Microaerophilic atmosphere 5% oxygen 5% oxygen 2-10 % carbon dioxide 2-10 % carbon dioxide

14. How is the Illness Treated? – Most cases Most infections are usually self-limited. Most infections are usually self-limited. –> 95% of infections clear up on their own. –Affected persons should drink plenty of fluids to avoid dehydration. –Antidiarrheal medications such as loperamide may help symptoms.

15. How is the Illness Treated? – Severe cases Antibiotics used in severe cases of gastroenteritis. Antibiotics used in severe cases of gastroenteritis. –Macrolide antibiotics including Erythromycin are effective and may shorten course of illness. –Resistance developing to Fluoroquinolone antibiotics due to use in poultry feed.

16. How do people get infected? Single, sporadic cases Single, sporadic cases –Eating raw or undercooked poultry meat Fact: Even one single drop of juice from raw chicken meat can infect a person. Fact: Even one single drop of juice from raw chicken meat can infect a person. –Handling raw poultry –Contact with infected fecal matter

17. How do people get infected? Outbreaks Outbreaks –Unpasteurized or under-pasteurized milk Children on class trip drinking unpasteurized milk Children on class trip drinking unpasteurized milk Dairy under-processed surplus raw milk for schools. Dairy under-processed surplus raw milk for schools. Cow-leasing program in Wisconsin. Cow-leasing program in Wisconsin. –Contaminated water source Bennington, VT using non-chlorinated water. Bennington, VT using non-chlorinated water.

18. How does food or water become contaminated? Poultry Poultry –63-88% of all chickens carry latent infection. –Spread through flock through drinking water and feces. –Spread to meat from intestines during slaughter. –Present in giblets, especially liver. Milk Milk –Infected udder. –Contact with manure. Surface water Surface water –Infected manure from cows or wild birds. –Enters streams through runoff.

19. What can be done to prevent Campylobacter infections? Food Industry Food Industry –Provide chickens with chlorinated water. –Avoid fecal contamination of udders or milk. –Strictly adhere to pasteurization time and temperature requirements. –Avoid fecal and/or intestinal contamination in meat processing.

20. What can be done to prevent Campylobacter infections? Individuals Individuals –Avoid drinking unpasteurized milk or untreated surface water. –WASH HANDS!!! after having contact with pet feces. after having contact with pet feces. after using the restroom or changing a diaper. after using the restroom or changing a diaper.

21. What can be done to prevent Campylobacter infections? Individuals Individuals –Use safe food handling practices Cook all poultry products thoroughly Cook all poultry products thoroughly Wash hands before handling foods. Wash hands before handling foods. Wash hands after handling raw foods of animal origin. Wash hands after handling raw foods of animal origin. Prevent cross-contamination in the kitchen. Prevent cross-contamination in the kitchen.

22. What are the latest morbidity and mortality reports? CDC Morbidity and Mortality Weekly CDC Morbidity and Mortality Weekly –Published April 30, 2004 “Preliminary FoodNet Data on the Incidence of Infection with Pathogens Transmitted Commonly Through Food --- Selected Sites, United States, 2003 “ “Preliminary FoodNet Data on the Incidence of Infection with Pathogens Transmitted Commonly Through Food --- Selected Sites, United States, 2003 “ –Published June 28, 2002 “Outbreak of Campylobacter jejuni infections associated with drinking unpasteurized milk procured through a cow-leasing program.” Wisconsin, Nov 10 - Dec 18, 2001. “Outbreak of Campylobacter jejuni infections associated with drinking unpasteurized milk procured through a cow-leasing program.” Wisconsin, Nov 10 - Dec 18, 2001.

23. What is the latest research? CDC Emerging Infectious Diseases CDC Emerging Infectious Diseases –Published March 2002 –“Human Campylobacteriosis in Developing Countries.” Akitoye O. Coker, et al. University of Lagos. Infection and Immunity Infection and Immunity –Published July 2001 “CdtA, cdtb, and cdtC form a tripartite complex that is required for Cytolethal Distending Toxin activity.” Maria Lara-Tejero and Jorge Galan. Yale School of Medicine. “CdtA, cdtb, and cdtC form a tripartite complex that is required for Cytolethal Distending Toxin activity.” Maria Lara-Tejero and Jorge Galan. Yale School of Medicine.

24. What were my sources? Bad Bug Book: U.S. Food & Drug Administration Center for Food Safety & Applied Nutrition Food borne Pathogenic Microorganisms and Natural Toxins Handbook; vm.cfsan.fda.gov/~mow/chap4.html. Bad Bug Book: U.S. Food & Drug Administration Center for Food Safety & Applied Nutrition Food borne Pathogenic Microorganisms and Natural Toxins Handbook; vm.cfsan.fda.gov/~mow/chap4.html. vm.cfsan.fda.gov/~mow/chap4.html CDC Division of Bacterial and Mycotic Diseases, Disease Information; Campylobacter infections; www.cdc.gov/ncidod/dbmd/diseaseinfo/campylobacter_g.htm. CDC Division of Bacterial and Mycotic Diseases, Disease Information; Campylobacter infections; www.cdc.gov/ncidod/dbmd/diseaseinfo/campylobacter_g.htm. www.cdc.gov/ncidod/dbmd/diseaseinfo/campylobacter_g.htm Campylobacter Facts and Information; www.foodborneillness.com/ecoli1/campylobacter- overview.htm. Campylobacter Facts and Information; www.foodborneillness.com/ecoli1/campylobacter- overview.htm.www.foodborneillness.com/ecoli1/campylobacter- overview.htmwww.foodborneillness.com/ecoli1/campylobacter- overview.htm Preliminary FoodNet Data on the Incidence of Infection with Pathogens Transmitted Commonly Through Food --- Selected Sites, United States, 2003; www.cdc.gov/mmwr/preview/mmwrhtml/mm5316a2.htm. Preliminary FoodNet Data on the Incidence of Infection with Pathogens Transmitted Commonly Through Food --- Selected Sites, United States, 2003; www.cdc.gov/mmwr/preview/mmwrhtml/mm5316a2.htm. www.cdc.gov/mmwr/preview/mmwrhtml/mm5316a2.htm Outbreak of Campylobacter jejuni Infections Associated with Drinking Unpasteurized Milk Procured through a Cow-Leasing Program, Wisconsin, 2001; www.cdc.gov/mmwr/preview/mmwrhtml/mm5125a2.htm. Outbreak of Campylobacter jejuni Infections Associated with Drinking Unpasteurized Milk Procured through a Cow-Leasing Program, Wisconsin, 2001; www.cdc.gov/mmwr/preview/mmwrhtml/mm5125a2.htm. www.cdc.gov/mmwr/preview/mmwrhtml/mm5125a2.htm Nature 403, 665 - 668 (10 February 2000); The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences; J. PARKHILL, et al.; www.nature.com/cgitaf/DynaPage.taf?file=/nature/journal/v403/n6770/full/403665a0_fs.html; Nature 403, 665 - 668 (10 February 2000); The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences; J. PARKHILL, et al.; www.nature.com/cgitaf/DynaPage.taf?file=/nature/journal/v403/n6770/full/403665a0_fs.html; www.nature.com/cgitaf/DynaPage.taf?file=/nature/journal/v403/n6770/full/403665a0_fs.html