Infectious Diarrheas and Foodborne Illnesses

Sandro Cinti, MD 13 year old WM presents with severe diarrhea, N/V, to 103 F two days after eating at a fast food restaurant. He initially has some tenderness on abdominal exam. He is admitted for hydration and observation. His stool cultures eventually grow Salmonella typhimurium. His abdominal exam improves over 48 hours but he continues to have fevers up to 103 F. An abdominal CT shows diffusely thickened large bowel with ? fluid around the cecum.

Treatment?

Salmonella (non-typhoidal)

◼ S enteritidis, S typhimurium (50%) ◼ Transmission – Food- meat, poultry, eggs, dairy » Contaminated fruits and vegetables – Water – Animals-lizards, snakes, turtle, cats, dogs, turkeys, pigs, cows – Human to human-highest risk among children (low gastric acidity) • Salmonella is an intracellular pathogen • Neutrophilic infiltrate of large and small bowel causes pathology and symptoms

Salmonella- Presentation

◼ Diarrhea, N/V, fevers 6-48 hours after ingestion – Diarrhea rarely bloody – + fecal leukocytes – + stool culture ◼ Bacteremia in 5% – Higher in HIV(recurrent), SSD, txp pts, immunocompromised – S choleraesuis, S dublin – High grade bacteremia=endovascular source » Endovascular involvement more in age>50 Salmonella- Treatment

◼ None for uncomplicated disease – Fevers resolves after 48-72 hrs and other symptoms resolve over 3-7d – Treatment increases carrier state and recurrence ◼ Treat neonates, Pts>50 yrs and immunocompromised until afebrile ◼ Treat bacteremia and endovascular disease – Β-lactams, floroquinolones, TMP/SMX Salmonella Outbreaks

◼ Salmonella serotype Saintpaul- raw tomatoes, jalapeno, serrano peppers- 2008

◼ Salmonella in peanut butter – 2006-2007 Salmonella serotype Tennessee – 2008-2009 Salmonella typhimurium

◼ 715 people; 48 states – 37% of isolates from urine – Late UTI cases (59 days) suggest weeks of shedding of Salmonella ◼ Peter Pan and Great Value peanut butter (ConagraFoods) ◼ ?Pre-heating contamination- water, animals, humans ◼ ?Post-heating contamination - Salmonella can survive up to 6 months ◼ High fat, low water in peanut butter sustains Salmonella even at high temps – roasting temp is 350 ° F but heterogeneous temps may allow survival •529 people US; 47 states; 26 Michigan •Peanut Corp of America (PCA), GA •King Nut peanut butter •Austin and Keebler pb crackers •431 pb containing products from 54 companies recalled

A previously healthy 28 y.o. woman who is 6 months pregnant goes into premature labor and delivers a stillborn infant. Two weeks prior she developed a diarrheal illness after going to a wedding. The illness lasted 2 days and she recovered fully. She was not ill in the week prior to delivery. Autopsy studies on the infant demonstrated widespread microabscesses and in the liver and .

What is the diagnosis? Listeria monocytogenes Gastroenteritis

◼ Intracellular organism- , enterocytes, hepatocytes ◼ Foodborn- coleslaw, milk, cheeses, pate, ready-to-eat-meats (delicatessen) ◼ Sxs-, chills, diarrhea, abd cramps – Incubation 9-20 hours ◼ Self-limited in healthy populations Listeria monocytogenes Gastroenteritis- Complications

◼ Infection in pregnancy – Can be asymptomatic in mother – 22% end in stillbirth or neonatal death » Granulomatosis infantiseptica ◼ CNS Infection – Meningitis- elderly, immunocomp and neonates – Rhomboencephalitis- occurs in healthy adults – Brain abscess ◼ Endocarditis 35 WM yo presents with an ascending paralysis 2 weeks after an illness characterized by fever, abdominal cramps and non-bloody diarrhea. The illness lasted several days and resolved without treatment. The patient thought it was something he ate.

What is the diagnosis? Campylobacter

◼ C jejuni ◼ Transmission – Poultry, water, unpasteurized milk, goats, beef, clams, household pets » Many animals are chronically infected – Human to human is rare ◼ Pathogenesis- neutrophilic infiltrate in small and large bowel

Campylobacter-Presentation

◼ Incubation 1-7 days ◼ Prodrome fever, myalgias 12-24 hrs prior to GI symptoms ◼ Diarrhea, fevers up to 104 F, – Diarrhea watery (>10 BM/d) or bloody – Tenesmus is common ◼ Dx- +stool culture, + fecal leucocytes ◼ Bacteremia uncommon (<1%) with C jejuni Campylobacter-Complications

◼ Toxic megacolon ◼ Surgery for pseudoappendicitis in patients with no diarrhea ◼ Reiter’s-HLA-B27 ◼ GBS- (1/2000 cases) occurs 2-3 weeks after infection – Autoimmune disease (molecular mimicry)- Campylobacter contains ganglioside-like epitopes elicit autoantibodies reacting with peripheral nerve targets Campylobacter- Treatment

◼ Fluid replacement ◼ Antibiotics – Treat children, pts with bloody diarrhea, pts with> 8 stools/d – Erythro, clarithro, azithro, cipro » Cephalosporins and Pcns are not active – Treat for 5-7 days ◼ Bacteremia- Use IV antibiotics 12 y.o. WM presents with 2 d history of RLQ pain, fevers, and a . On exam he has a tender RLQ. He denies diarrhea, tenesmus, bloody or mucoid stools. He goes to surgery for presumed . The appendix is normal and he only has a mild ileitis.

What is the diagnosis? Yersinia enterocolitica

◼ Uncommon in US ◼ Risk – Children>adults – Food (milk, bean sprouts, raw pork), water – Contact with infected animal (dogs), human ◼ Pathology- terminal ileum and mesenteric lymph nodes are most commonly involved Yersinia enterocolitica- Clinical Presentation ◼ Enterocolitis- – Fever, diarrhea abdominal pain for 1-3 weeks – Most common in <5 yr old – Bloody diarrhea with fecal leukocytes is less common ◼ Mesenteric adenitis/terminal ileitis – Fever, RLQ pain, leukocytosis – >5 yr old – Mimics appendicitis- also Y pseudotuberculosis Keratoderma

Balanitis Yersinia enterocolitica- Complications ◼ Reactive polyarthritis (formerly Reiter’s) – 10-30% of Y enterocolitica in Scandinavia – Also caused by Chlamydia species, Salmonella, Shigella and Campylobacter, and ?Clostridium difficile – Triad- urethritis, arthritis, conjuntivitis/uveitis ◼ Septicemia- DM, cirrohsis, malignancy, iron overload (desferrioxamine) – Mortality is 50% Yersinia enterocolitica- Treatment

◼ Y enterocolitica is sensitive to AGs, tetracycline, Bactrim, chloramphenicol, 3rd gen cephlosporins ◼ Resistant to PCN, amp, 1st gen cephlosporins ◼ Enterocolitis and mesenteric adenitis are self-limited Escherichia coli

◼ ETEC (enterotoxigenic)- Traveler’s Diarrhea – Nonbloody diarrhea – Heat-labile toxin (LT)-similar to cholera toxin – Incubation 1-2 days and diarrhea for 3-4 days – Self-limited Aeromonas

◼ Waterborn gram negative rod ◼ Causes travelers diarrhea and outbreaks in daycare centers ◼ Self-limited Bacterial Gastroenteritis

◼ Campylobacter ◼ Food/water associated ◼ Salmonella ◼ Incubation 1 to 7 days ◼ E coli (ETEC) ◼ Watery diarrhea ◼ Listeria ◼ Non-bloody ◼ Yersinia ◼ Self-limited ◼ Aeromonas 45 y.o WF presents to the ER with severe nausea and vomiting. She is previously healthy. She is nauseated but is afebrile and has stable vital signs. She had eaten chinese food earlier that evening and began to feel ill 4 hours after the meal.

What did she eat? What is the diagnosis?

Bacillus cereus

◼ Emetic form-toxin mediated – Associated with fried rice » Boiled rice “dried off” at ambient temp then quick fried with eggs. » Spores germinate at ambient temps. » Quick fry does not kill bacteria Toxin Mediated GI Disease

Source Incubation Symptoms Complications Staphylococcus Dairy, produce, 6-12 hrs Mostly Self-limited aureus meats, salad N/V, (food worker is diarrhea the main also occurs source) Bacillus cereus Fried rice 1-6 hrs N/V Self-limited Clostridium Meats, poultry, 6-24 hrs diarrhea Enteritis perfringens gravy necroticans (pig- bel)-protein deficiency (New Guinea) 6 y.o. WF presents with bloody diarrhea and tenesmus. Her illness started 3 d ago with fever abdominal pain and voluminous diarrhea. Her fevers began to resolve 1 d ago but she developed increasing frequency of stools with small volumes of bloody mucoid stools. Her 13 y.o.brother had been ill the week before with a less severe diarrhea.

What is the diagnosis? Shigellosis- Bacillary Dysentary

◼ Most communicable of diarrheas-<200 organisms can cause disease. ◼ Person to person transmission is most common – Children are most susceptible-day care outbreaks – High transmission rates in NH ◼ Food and water outbreaks occur Shigella-Pathogenesis

◼ Shigella invades the mucosa to cause a superficial infection – Bacteremia is rare ◼ Shiga toxin production plays a secondary role in mucosal destruction – ??Neurotoxin ◼ S dysenteriae more severe (20% mort) Shigellosis-Presentation

◼ Small bowel phase-12-48 hrs after ingestion – Fever, cramping, voluminous diarrhea ◼ Colonic (dysentary)phase-1-3 days after symptoms – Decrease in fever – Increase in # of stools but decreased volume – Tenesmus with bloody mucoid stools Shigellosis ◼ Diagnosis – Clinical picture – Fecal leukocytes and stool cultures ◼ Treatment – Rehydration – Ceftriaxone IV-toxemia, bacteremia – TMP-SMX-resistance in SE Asia, SA, Africa – Amp and tetracycline decrease carrier state – Flouroquinolones – Azithromycin ◼ Complications- Reiters, HUS (S. dysenteriae) 24 y.o HIV + male with a CD4-40 from S.F. presents with 3 days of mucoid bloody diarrhea, abdominal pain and tenesmus. He has no fevers. Stool is negative for fecal leukocytes. He is on HAART, Bactrim, and Azithromycin.

Dysentary

Source Complications Treatment Shigella species Human-human, Toxic megacolon, •Mild dz-fluids 20% food Reiter Syndrome, •Moderate dz-oral Bacteremia (rare), bactrim, azithro, hemolytic uremic FQ syndrome •Severe-IV ceftriaxone Entamoeba Food, water, fecal Liver abscess, •Diarrhea- histolytica oral (homosexual toxic megacolon, metronidazole males) amoeboma, brain followed by anti- abscess, cyst (paromomycin) •Liver abscess- metronidazole E coli Meats, lettuce, Toxic megacolon Supportive, severe (enteroinvasive) water dz-FQ Amoebiasis Amoebic Liver Abscess Ameboma Other Organisms Causing Dysentery

◼ Vibrios- non-cholera – V parahaemolyticus ◼ Balantidium coli (Ciliary dysentery)- parasite with swine as a reservoir ◼ Schistosomiasis (Bilharzial dysentery) Escherichia coli

◼ EHEC (enterohemorrhagic)- E coli 0157:H7 – Undercooked beef, lettuce, water – Afebrile with bloody diarrhea – Shiga-like toxin (Vero cytotoxin) » EHEC attaches to gut epithelium and toxin is released causing epithelial destruction, vascular necrosis and . – HUS- Hemolytic Uremic Syndrome German Outbreak (E coli 0104:H4)

◼ 3910 cases of HUS or EHEC (May-July 2011) – 728 HUS cases; 48 fatalities – Sprouts have been implicated by epidemiologic studies (?fenugreek seeds from Egypt) » Initially attributed to cucumbers from Spain ◼ Looks like a hybrid strain-human tropic – enteroaggregative strain (traveler’s diarrhea) – produces Shiga/Verotoxins – Multi-drug resistant – EaggEC VTEC O104:H4 Twenty-four hours after having a box lunch in its home town, a North Carolina college football team traveled to Florida for a 7 p.m. game. During the game 11 NC players became ill with N/V and profuse diarrhea. They continued to play despite illness and despite the fact that “the nature of the game made it difficult for players to avoid contact with feces and vomitus.” After 48 hrs 11 Florida players came down with a similar illness Epidemic Curve Norovirus Virus

◼ Transmission – Food (shellfish), water – Swimming pools, lakes – Person-person » Fecal-oral, vomitus » Very high secondary attack rates ◼ Pathogenesis – Blunted villi and CDC, 348 outbreaks transient malabsorption Norovirus Virus

◼ Clinical Presentation – Incubation 24-48 hrs – Abdominal cramps, low grade fever followed by N/V and watery non-bloody diarrhea. – Lasts 48-72 hrs ◼ Diagnosis – Clinical picture in epidemic setting – Cannot be cultivated – Serology and ELISA ◼ Treatment- symptomatic Rotavirus

◼ Highest incidence among 6-24 months old – Onset of susceptibility correlates with decline of maternal acquired immunity – Most adult disease associated with sick child ◼ Transmission is fecal oral (?respiratory) – Not associated with common-source outbreaks but is a seasonal pandemic illness » “rotovirus season” begins mid-January – No animal reservoir Rotavirus

◼ Pathogenesis- – Rotavirus invades epithelial cells in sm bowel and induces malabsorption – Rotavirus-induced lactose intolerance can last weeks after illness ◼ Presentation- – Fever, N/V, watery diarrhea for 2-4 days » Cough and coryza may precede GI symptoms – Chronic illness can occur in children with HIV Rotavirus

◼ Diagnosis – Rotavirus in stool – ELISA – Latex agglutination for rapid identification ◼ Treatment- hydration ◼ Vaccine – Licensed by FDA 8/31/98 – ACIP pulled its recommendation after 102 cases of post-vaccine intussusception Rotavirus Vaccine

◼ Licensed by FDA 8/31/98 ◼ ACIP pulled its recommendation after 102 cases of post-vaccine intussusception ◼ 2006 ACIP recommended approved licensed vaccine- 3 doses ◼ 2009 ACIP recommended either RV5-3 doses (2,4,6 mos) or RV1-2 doses (2, 4 mos) ◼ 1st dose should be given between ages 6 wks-15 wks 34 y.o. WM with HIV CD4-10, presents with 1 week of profuse watery diarrhea with >10 BMs/d. He has no fevers, sweats and no cramping, no HA. Labs are unremarkable. Stool specimen shows:

What is the diagnosis? Protozoal Diarrheas (except E histolytica)

Source Symptoms Treatment Complications Cryptospoidium Food/water Diarrhea, N/V Nitazoxanide Hepatitis, parvum cholecystitis Giardia lamblia Water Diarrhea, gas metronidazole malabsorption Cyclospora Water, Diarrhea, gas Bactrim Cholangitis lettuce, raspberries Microsporida Fecal-oral Watery Albendazole HIV-Biliary (major), diarrhea disease, liver person- disease, ocular person, pet- disease, CNS person invasion Isospora belli Fecal-oral N/V, diarrhea, Bactrim None (subtropics) steatorrhea, abdominal pain Protozoal Diarrhea-Diagnosis

◼ Stool ova and parasite – Acid fast +-Isospora, Cryptosporidium, Cyclospora ◼ Biopsy ◼ ELISA – Cryptosporidium, Microsporidium, Giardia (antigen assay) ◼ PCR – Cryptosporidium O&P

Cryptosporidium- (acid-fast stain)

Giardia Biopsy

Cryptosporidium Microsporidium

Giardia Incidence of lab-confirmed cases per 100,000 persons (2006)

◼ Salmonella 14.8 ◼ Campylobacter 12.7 ◼ Shigella 6.1 ◼ Cryptosporidium 1.9 ◼ E coli 0157 (EHEC) 1.8 ◼ Yersinia 0.4 ◼ Vibrio 0.3 ◼ Listeria 0.3 ◼ Cyclospora 0.1 34 yo HIV+ patient from Kentucky with a CD4- 50 presents with abdominal pain diarrhea, diffuse pulmonary infiltrates. He looks septic and his blood cultures are positive for Klebsiella. His WBC is 15.0 with 67% segs, 30% eosinophils.

What is the diagnosis? Strongyloides stercoralis

◼ Nematode that invade through the skin and go to the GI tract – Pass through blood to the lungs ◼ Autoinfection- larva transforms to an infective organism – Infection may recur years later ◼ Hyperinfection syndrome- HIV, steroids – Eosinophilia, pulm infiltrates, larvae carry GNRs into the bloodstream

25 yo presents with sudden onset of RUQ abdominal pain after eating. Patient has otherwise been healthy. RUQ ultrasound is done. Labs are normal except for an eosinophilia of 35%.

Ascariasis lumbricoides

◼ Hand-mouth transmission- seen mostly in children – Eggs live for up to 2 years and can survive 3 months without oxygen ◼ Pts present with abd pain, cholangitis, pancreatitis, intestinal obstruction, pulmonary symptoms and eosinophilia ◼ Treat with albendazole, mebendazole

Two men dined at a restaurant where each had onion soup, salad, grilled tuna, steamed vegetables, cheese and coffee. They shared a bootle of wine. As they completed the meal, both men began to have severe HA, , urticaria, palpatations, nausea and abdominal cramping. One also had bronchospasm and tightness of the throat. -Scromboid fish poisoning -Ciguatera fish poisoning -B cereus food poisoning -Clostridial food poisoning -Reaction to tyramine Fish Poisoning (Scromboid)

◼ Tuna Sashimi ◼ Histamine in fish flesh ◼ Flushing, HA, dizziness, abd pain, N/V, diarrhea, urticaria, bronchospasm ◼ Symptoms within 5 min-1 hr and resolve in a few hrs to days Ciguatera Fish Poisoning

◼ Dinoflagellate acquired by fish (barracuda, snapper, grouper) produces Ciguatoxin – Ciguatoxin changes electrical potential in cells ◼ 1-6 hrs after eating- paresthesias lips, tongue and throat followed by diarrhea, abd cramps, N/V – Shooting leg pain, sensation of loose teeth – Hypotension and resp paralysis ◼ Duration of illness is days to months

Amnesic Shellfish Poisoning

◼ Domoic acid produced by a dinoflagellate (Nitzchia pungens) ◼ Vomiting, abd cramping, diarrhea, confusion, antegrade amnesia in 25 % ◼ Amnesia may be permanent due to damage to the hippocampi Paralytic Shellfish Poisoning

◼ Saxitoxin producing dinoflagellates ◼ Obtained from eating bivalved mollusks ◼ Parasthesias of mouth, lips, face, extremities ◼ Dysphagia, muscle weakness, ataxia, respiratory insufficiency in severe cases ◼ 1-10 hrs after eating and lasts hours to days