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Differential diagnosis of microbial foodborne disease Close to one in five episodes of diarrhea is likely to be due to a foodborne disease. More than 200 known microbes are capable of transmission through food. Foodborne pathogens ranked according to their frequency Campylobacter spp Escherichia coli O157:H7 Listeria monocytogenes Bacteria Salmonella spp Shigella spp Vibrios Yersina Protozoa Cryptosporidium Cyclospora APPROACH TO THE PATIENT A probable diagnosis of foodborne disease is based upon the combination of: o Clinical manifestations. o Food history. o Relevant pathogenic mechanism. Clinical manifestations Gastrointestinal symptoms including nausea, vomiting, abdominal pain, diarrhea and fever. Neurologic symptoms (eg, headaches, paralysis or tingling), Hepatitis. Renal failure. Food history Should include: o Consumption of a particular type of food o Time interval between exposure to the suspect food and the onset of symptoms. Pathogenic mechanisms Pathogenetic mechanisms by which microbes cause foodborne disease can generally be categorized in three ways: Organisms that make a toxin in the food before the food is consumed (ready-made toxin) o o Examples o o o Rapid onset of symptoms (6 to 12 hours. Predominantly upper intestinal. Staphylococcus aureus. Bacillus cereus. Botulism. Pathogens that make toxin once they have been ingested o Takes longer (approximately 24 hours or longer). o Causes diarrhea that may be: o Watery. 1 Vibrio cholerae. Enterotoxigenic Escherichia coli Shiga toxin-producing E. coli. o Bloody. Microbes that cause pathology by either: Damaging the epithelial cell surface. or by Invading across the intestinal epithelial cell barrier. A wide spectrum of clinical presentations: o Watery diarrhea (eg, Cryptosporidium parvum, enteric viruses). o Inflammatory diarrhea (eg, Salmonella, Campylobacter, Shigella). o Systemic disease (eg, L. monocytogenes). Most common microbial causes of foodborne disease Norwalk-like viruses Cryptosporidium parvum Yersinia enterocolitica Campylobacter spp Clostridium spp Bacillus cereus Giardia lamblia Toxoplasma gondii Cyclospora cayetanensis Salmonella Staphylococcal food poisoning Listeria monocytogenes Shigella Shiga toxin producing E. coli VOMITING AS THE MAJOR PRESENTING SYMPTOM A sudden onset of nausea and vomiting is likely due to: o Ingestion of a preformed toxin: S. aureus toxins. B. cereus toxins. Chemical irritant. Identification of the contaminated food is important to prevent exposure of others. Staphylococcus aureus S. aureus enterotoxin o Heat-stable. o Dairy products, meats, eggs, and salads. o Food handlers are usually the source of contamination. o Foods left at room temperature organisms multiply produce a substantial quantity of toxin. Symptoms o Begin within one to six hours of ingestion. o Nausea, vomiting and abdominal cramps. o Fever and/or diarrhea may occur in a minority of patients. o Self limited. Diagnosis o Clinical + enterotoxin in vomitus and/or food. Bacillus cereus B. cereus enterotoxin Heat-stable enterotoxin. 2 o Typically in starchy foods such as rice. Symptoms o Onset within one to six hours. o Nausea and profuse vomiting. o Usually self-limited. o Very rarely associated with acute hepatic necrosis. Diagnosis o Clinical + enterotoxin in vomitus and/or food. Noroviruses (Norwalk-like viruses) Most common foodborne diseases and the most frequent cause of acute gastroenteritis. Transmission (low infectious dose around 10 particles) o Contaminated food. Shellfish are known to harbor noroviruses. Prepared food (eg, salads, sandwiches, fruit). o Vomitus of an infected person. o Food handler via food. o Aerosol. o Person-to-person. Symptoms o Nausea, vomiting and watery diarrhea. o Usually lasts for 48 to 72 hours with a rapid and full recovery. o No long-lasting immunity. Diagnosis o Electron microscopy. o Enzyme immunoassay. o RT-PCR WATERY DIARRHEA AS THE MAJOR PRESENTING SYMPTOM Differential diagnosis Bacterial V. cholerae massive watery diarrhea Clostridium perfringens. Enterotoxigenic E. coli (ETEC). B. cereus. Viral Rotavirus Astroviruses Enteric adenoviruses Noroviruses Clostridium perfringens Toxin-mediated illness produced in the gut. Requires ingestion of large numbers of organisms. Spores can germinate in foods such as meats, poultry. Symptoms watery diarrhea. Diagnosis Testing of stool or food for the toxin. 3 Parasitic Cryptosporidium parvum I.P. 7 days Cyclospora cayetanensis. Enteritis necroticans (pigbel) o o o o C. perfringens type C produces a beta toxin. Hemorrhagic necrosis of the jejunum. Consumption of pig intestines. Sweet potatoes contain trypsin inhibitors preventing the intestinal degradation of the toxin, can be a potentiating factor. Enterotoxigenic Escherichia coli (discus) Cryptosporidium parvum Persistent chronic diarrhea in immunocompromised patients. The organism is endemic in cattle. Acquired in humans from contaminated water, unpasteurized milk or person-toperson spread. The incubation period is one week, but can be as long as 28 days. Cause large outbreaks. Diagnosed by acid-fast staining of stools, immunofluorescence microscopy, or enzyme immunoassay. There is no current reliable therapy for cryptosporidiosis, although nitozoxanide elixir has been approved for use in children aged one to 11 years. Cyclospora cayetanensis Consumption of imported berries; the fruit was probably infected via fecally contaminated water. Diagnosed by direct acid-fast microscopy of stool. Readily treatable with trimethoprim-sulfamethoxazole (TMP-SMX). INFLAMMATORY DIARRHEA AS THE MAJOR PRESENTING SYMPTOM Inflammatory cells in stool or lactoferrin o Defines an inflammatory diarrhea. o Not good negative. Symptoms and signs include: o Diarrhea with blood or mucus. o Severe abdominal pain. o Fever. Salmonella The incubation period for non-typhoidal Salmonella is usually one to three days. The diagnosis is undertaken with routine stool cultures. Campylobacter The incubation period ranges from two to five days. Poultry is a frequent source of the organism. Diagnosed by culture on selective plates. 4 Shiga toxin producing E. coli (enterohemorrhagic E. coli EHEC) E. coli O157:H7 is the serotype most frequently causing human disease Over 50 other STEC serotypes are associated with diarrheal disease as well as the hemolytic uremic syndrome (HUS). STEC typically found in ground beef, unpasteurized juice, raw fruits and vegetables. The incubation period ranges from one day up to a week. The presentation usually begins with watery diarrhea that usually becomes bloody. Diagnosed using Shiga toxin based assays, which have advantages over the more conventional sorbitol MacConkey test. O157:H7 STEC using sorbitol MacConkey plates (O157:H7 ferments sorbitol slowly compared with other E. coli. Antibiotic treatment of STEC-infected patients may increase the risk of developing HUS. Shigella Other pathogens V. parahaemolyticus. Inflammatory diarrhea due to Yersinia enterocolitica consumption of undercooked pork, unpasteurized milk and fecally contaminated water. NON-GASTROINTESTINAL MANIFESTATIONS Neurologic manifestations as the presenting symptom Botulism Due to Clostridium botulinum toxin. A detailed food history should be obtained in any patient with visual disturbance and/or descending paralysis. Consumption of foods in which C. botulinum spores have germinated and the resulting vegetative cells have produced toxin. Canned fermented fish, herb-infused oils, and foods held warm for extended periods of time. Stool and serum can be tested for toxin by reference laboratories. Ciguatera toxin Nausea, vomiting, diarrhea and abdominal pain in the first two to six hours. Paresthesia, weakness and/or reversal of hot or cold. Cardiovascular abnormalities can develop in two to five days. Ciguatera toxin disease is associated with consumption of large reef fish. Scombroid Scombroid occurs within minutes to hours of consumption of certain fish (blue fish, tuna, mackerel, marlin, or mahi mahi), or occasionally cheese. Patients complain of flushing, burning sensation, urticaria, dizziness, and paresthesia. 5 Other shellfish and mushroom toxins Shellfish may also contain toxins that fall into three groups (diarrheic, neurotoxic, and amnesic) causing the various symptoms that their names imply. Symptoms usually occur within 30 minutes to several hours following exposure. Listeria monocytogenes Rare foodborne disease with a mortality of approximately 20 percent. Immunocompromised, elderly, or pregnant women. Meat, raw hot dogs and unpasteurized soft cheese are risk factors. The incubation period may be as long as six weeks but can be as short as 6 to 10 hours during outbreaks in normal adults. Culturing L. monocytogenes from the blood or cerebrospinal fluid (CSF). Stool cultures are unhelpful since 5 to 10 percent of the general population have L. monocytogenes in their stool. Vibrio vulnificus Unusual, affects the immunocompromised, especially with chronic liver disease. It is associated with exposure to raw shellfish. Incubation period of one to seven days. Gastrointestinal symptoms or skin infections that rapidly develop into bacteremia and systemic disease. Culture for Vibrios requires special media. Toxoplasma gondii Hepatitis A virus PREVENTION Notification of local health authorities. Newer techniques, such as pulsed field gel electrophoresis (PFGE), allow determine outbreaks much earlier than in the past. The infected patient must be instructed to avoid spreading the infection to others, either at home or at work. Careful handwashing, particularly after using bathroom facilities. Aware of the dangers of certain foods, which carry a greater risk of contamination with foodborne microbes. Differential diagnosis of foodborne disease by item consumed Item Commonly associated microbes Raw seafood Norwalk-like virus, Vibrio spp, hepatitis A Raw eggs Salmonella spp Undercooked meat or poultry Salmonella spp, Campylobacter spp, STEC, C. perfringens Unpasteurized milk or juice Salmonella spp, Campylobacter spp, STEC, Y. enterocolitica Unpasteurized soft-cheeses Salmonella spp, Campylobacter spp, STEC, Y. enterocolitica, L. monocytogenes Home made canned goods C. botulinum Raw hot dogs, deli meat L. monocytogenes STEC: shiga toxin producing Escherichia coli. 6 Major foodborne microbes by the principal presenting gastrointestinal symptom Major presenting Likely microbes Incubation period Likely food sources symptom S. aureus 1 to 6 hours Prepared food, eg, salads, dairy, meat Vomiting B. cereus 1 to 6 hours Rice, meat Norwalk-like viruses 24 to 48 hours Shellfish, prepared foods, salads, sandwiches, fruit C. perfringens 8 to 16 hours Meat, poultry, gravy Enterotoxigenic E. 1 to 3 days Fecally contaminated food coli or water Enteric viruses 10 to 72 hours Fecally contaminated food Watery diarrhea or water C. parvum 2 to 28 days Vegetables, fruit, unpasteurized milk, water C. cayetanensis 1 to 11 days Imported berries, basil Campylobacter spp 2 to 5 days Poultry, unpasteurized milk, water Non-typhoidal 1 to 3 days Eggs, poultry, meat, salmonella unpasteurized milk or Inflammatory juice, fresh produce diarrhea Shiga toxin1 to 8 days Ground beef, producing E. coli unpasteurized milk and juice, raw vegetables, water Shigella spp 1 to 3 days Fecal contamination of food and water V. parahemolyticus 2 to 48 hours Raw shellfish Major foodborne microbes that usually have non-gastrointestinal manifestations Manifestations Agent of illness IP Likely food sources C. botulinum (botulism) 12 -72 h Home canned foods, fermented fish, herb-infused oils, bottled garlic, foods held warm for long periods Neurologic Ciguatara toxin 2 -6 h Large reef fish: grouper, red snapper, amberjack, barracuda Scromboid 1 min - 3 h Fish: bluefin, tuna, skipjack, mackerel, marlin, mahi mahi L. monocytogenes (listeriosis) 2 - 6 wks Ready to eat deli meats, hot dogs, Systemic unpasteurized soft cheese and milk V. vulnificus 1 - 7 ds Shellfish Hepatitis Hepatitis A 15 - 50 ds Shellfish, prepared foods infected by a food handler 7