Sandbox:GE

Overview

Acute gastroenteritis and diarrhea are among the leading causes of seeking medical care. Approximately, 48 million cases occur annually that cost about $150 million for the U.S. health care system.(1,2) Gastroenteritis is defined as inflammation of the stomach or intestinal mucosa. It typically presents with acute diarrhea, fever, nausea and vomiting, anorexia and crampy abdominal pain and is defined as passage of loose stool for at least 3 times per day for less than 14 days. It may be cause by viruses, bacteria or parasites. Most cases of acute gastroenteritis are caused by viruses and among them, Norovirus is the most common etiology for adults. Other common viral causes include, Rotavirus, Adenovirus and Astrovirus. Common bacterial causes of gastroenteritis include, Escherichia coli sp, Salmonella sp, Yersinia enterocolitica and Vibrio sp that can cause watery diarrhea and Shigella sp and Campylobacter sp that can cause dysenteric diarrhea. Parasites are other causes of gastroenteritis especially in developing countries which Giardia lamblia and Entamoeba histolytica are the most frequent causes. First step in management of this patients is to evaluate the hydration status and vital signs. Once the patient is stabilized proceed to diagnostic evaluation. There are some principles to decrease the risk of acquiring infection which include, using safe water and foods, avoid unsafe foods during traveling and hand washing.

Classification

Abbreviations: ETEC: Enterotoxigenic Escherichia coli, EPEC: Enteropathogenic Escherichia coli, EHEC: Enterohemorrhagic Escherichia coli, EAEC: Enteroaggregative Escherichia coli, EIEC: Enteroinvasive Escherichia coli, SARS: severe acute respiratory syndrome

Gastroenteritis

Viral

Bacterial

Parasites

Common

Less Common

Common

Less Common

Helminthic

Protozoal

❑Rotavirus ❑Norovirus ❑Enteric Adenovirus ❑Astroviruses

❑Kobuviruses ❑Enterovirus ❑Orthoreovirus ❑Torovirus ❑Coronavirus (including SARS) ❑Parvovirus

Gram Positive

Gram Negative

Gram Positive

Gram Negative

❑Trichinella spiralis ❑Trichuris trichiura ❑Strongyloides stercoralis ❑Taenia solium ❑Taenia saginata ❑Diphyllobothrium latum ❑Schistosoma mansoni

❑Giardia lamblia ❑Entamoeba histolytica‡ ❑Cryptosporidium parvum ❑Cyclospora cayetanensis

❑Clostridium perfringens ❑Clostridium difficile

Dysenteric diarreha

Watery diarrhea

❑ Bacillus cereus ❑Listeria monocytogenes

❑Bacteroides fragilis ❑Aeromonas hydrophila

❑Shigella sp., ❑Campylobacter sp.

❑Escherichia coli (ETEC, EPEC, EHEC, EAEC, EIEC)§ ❑Salmonella sp.† ❑Yersinia enterocolitica† ❑Vibrio cholerae ❑Vibrio parahemolyticus

§ EHEC, EIEC, EPEC and EAEC may cause bloody diarrhea, but they are classically associated with watery diarrhea.
† Either Salmonella and Yersinia can cause dysentery.
‡ Entamoeba histolytica may cause dysentery

Patient Evaluation

Initial Management

Shown below is an algorithm depicting the initial management of acute diarrhea is based on the 2001 IDSA practice guidelines for the management of infectious diarrhea.

Characterize the symptoms: ❑ Onset ❑ Duration ❑ Pattern (continuous or intermittent) ❑ Stool characteristic (watery, bloody, mucous or greasy) ❑ Frequency of bowel movements ❑ Dysenteric symptoms (fever, tenesmus, blood and/or pus in stool) Associated symptoms: ❑ Abdominal pain ❑ Nausea and vomiting ❑ Weight loss Epidemiological factors: ❑ Travel ❑ Food (raw meat, eggs, shellfish, unpasteurized cheese or milk) ❑ Outbreaks ❑ Sexual history ❑ Day care attendance ❑ Previous evaluations ❑ Medications, radiation therapy or surgery ❑ Underlying medical condition (cancer, diabetes, hyperthyroidism or AIDS)

Examine the patient: ❑ Temperature ❑ Pulse ❑ Blood pressure ❑ Respiratory rate ❑ Signs of volume depletion (decreased skin turgor, dry mucosa) ❑ Abdominal tenderness ❑ Level of consciousness

Assessment of volume status General condition Normal Irritable/less active* Lethargic/comatose§ Eyes Normal Sunken - Mucosa Normal Dry - Thirst Normal Thirsty Unable to drink§ Radial pulse Normal Low volume* Absent/ uncountable§ Skin turgor Normal Reduced - † Some dehydration = At least two signs, including at least one key sign (*) are present. ‡ Severe dehydration = Signs of “some dehydration” plus at least one key sign (§) are present.

No dehydration

Some dehydration

Severe dehydration

Start altered diet ❑ Stop lactose products ❑ Avoid alcohol and high osmolar supplements ❑ Drink 8-10 large glasses of clear fluids (Fruit juices, soft drinks etc) ❑ Eat frequent small meals (Rice, potato, banana, pastas etc) Can start oral rehydration therapy (ORT) for replacement of stool losses

❑ Start ORT at a volume of 50-100 mL/kg ❑ Start altered diet ❑ Reassess status every 4 hr

❑ Start IV fluids: Ringer lactate at 30ml/kg in the first 1/2hr and 70ml/kg for the next 2 1/2 hr, if unavailable use normal saline ❑ CBC ❑ Electrolytes ❑ Assess status every 15 mins until strong pulse felt and then every 1 hr

Patient stable and able to drink ❑ Start ORT at a volume of 100 mL/kg over 4 hour ❑ Calculate the continuing stool and emesis losses every hour for additional maintenance ORT therapy ❑ Reassess status every 4 hr

Hemodynamic stabilized Proceed to Diagnosis and Management

Diagnostic and Management approach

Passage of ≥3 unformed stools in 24 h + An enteric symptom (nausea, vomiting, abdominal pain/cramps, tenesmus, fecal urgency, moderate to severe flatulence)                                                                                                               Watery diarrhea ± Vomiting                                   Dysenteric diarrhea (passage of grossly bloody stools)                                                                                                               Mild Illness†             Moderate to Severe†               No or low-grade fever(≤100°F)       Severe illness† with fever≥(101°F) in a single case (not outbreak)                                                                                                           Hydration only May use loperamide 4 mg initially to control stooling   Travel associated         Non travel associated                   Non travel associated     Travel associated                                                                                                   Antibiotic therapy   No or low-grade fever (≤100°F)       Fever (≥101°F)                         Empiric treatment Azithromycin 1 g in single dose OR 500 mg once daily for 3 days                                                                                                     <72 h duration   ≥72 h duration                                                                                                         Loperamide therapy for 48 h                                                                                   Microbiologic assessment and appropriate treatment                                                                                                                                                                                                                                                                                                                                                                                                                                           Persistent diarrhea (14–30 days) should be worked up by culture and/or culture independent microbiologic assessment, then treatment with anti microbial agent directed to cause

†Illness severity:

• Severe: Total disability due to diarrhea;
• Moderate: Able to function but with forced change in activities due to illness;
• Mild: No change in activities

Synopsis

Organism			Age predilection	Travel History	Incubation Size (cell)	Incubation Time	History and Symptoms			Diarrhea type∞				Food source	Specific consideration
							Fever	N/V	Cramping Abd Pain	Small Bowel	Large Bowel	Inflammatory	Non-inflammatory
Viral	Rotavirus		<2 y	-	<102	<48 h	✔	✔	-	✔			✔	-	Mostly in day cares, most common in winter.
	Norovirus		Any age	-	10 -103	24-48 h	✔	✔	✔	✔			✔	-	Most common cause of gastroenteritis, abdominal tenderness,
	Adenovirus		<2 y	-	105 -106	8-10 d	✔	✔	✔	✔			✔	-	No seasonality
	Astrovirus		<5 y	-		72-96 h	✔	✔	✔	✔			✔	Seafood	Mostly during winter
Bacterial	Escherichia coli	ETEC	Any age	✔	108 -1010	24 h	-	✔	✔	✔			✔	-	Causes travelers diarrhea, contains heat-labile toxins (LT) and heat-stable toxins (ST)
		EPEC	<1 y	-	10†	6-12 h	-	✔	✔	✔			✔	Raw beef and chicken	-
		EIEC	Any ages	-	10†	24 h	✔	✔	✔		✔		✔	Hamburger meat and unpasteurized milk	Similar to shigellosis, can cause bloody diarrhea
		EHEC	Any ages	-	10	3-4 d	-	✔	✔		✔	✔		Undercooked or raw hamburger (ground beef)	Known as E. coli O157:H7, can cause HUS/TTP.
		EAEC	Any ages	✔	1010	8-18 h	-	-	✔		✔		✔	-	May cause prolonged or persistent diarrhea in children
	Salmonella sp.		Any ages	✔	1	6 to 72 h	✔	✔	✔		✔	✔		Meats, poultry, eggs, milk and dairy products, fish, shrimp, spices, yeast, coconut, sauces, freshly prepared salad.	Can cause salmonellosis or typhoid fever.
	Shigella sp.		Any ages	-	10 - 200	8-48 h	✔	✔	✔		✔	✔		Raw foods, for example, lettuce, salads (potato, tuna, shrimp, macaroni, and chicken)	Some strains produce enterotoxin and Shiga toxin similar to those produced by E. coli O157:H7
	Campylobacter sp.		<5 y, 15-29 y	-	104	2-5 d	✔	✔	✔		✔	✔		Undercooked poultry products, unpasteurized milk and cheeses made from unpasteurized milk, vegetables, seafood and contaminated water.	May cause bacteremia, Guillain-Barré syndrome (GBS), hemolytic uremic syndrome (HUS) and recurrent colitis
	Yersinia enterocolitica		<10 y	-	104 -106	1-11 d	✔	✔	✔		✔	✔		Meats (pork, beef, lamb, etc.), oysters, fish, crabs, and raw milk.	May cause reactive arthritis; glomerulonephritis; endocarditis; erythema nodosum. can mimic appendicitis and mesenteric lymphadenitis.
	Clostridium perfringens		Any ages		> 106	16 h	-	-	✔		✔		✔	Meats (especially beef and poultry), meat-containing products (e.g., gravies and stews), and Mexican foods.	Can survive high heat,
	Vibrio cholerae		Any ages	-	106-1010	24-48 h	-	✔	✔	✔			✔	Seafoods, including molluscan shellfish (oysters, mussels, and clams), crab, lobster, shrimp, squid, and finfish.	Hypotension, tachycardia, decreased skin turgor. Rice-water stools
Parasites	Protozoa	Giardia lamblia	2-5 y	✔	1 cyst	1-2 we	-	-	✔	✔			✔	Contaminated water	May cause malabsorption syndrome and severe weight loss
		Entamoeba histolytica	4-11 y	✔	<10 cysts	2-4 we	-	✔	✔		✔	✔		Contaminated water and raw foods	May cause intestinal amebiasis and amebic liver abscess
		Cryptosporidium parvum	Any ages	-	10-100 oocysts	7-10 d	✔	✔	✔	✔			✔	Juices and milk	May cause copious diarrhea and dehydration in patients with AIDS especially with 180 > CD4
		Cyclospora cayetanensis	Any ages	✔	10-100 oocysts	7-10 d	-	✔	✔	✔			✔	Fresh produce, such as raspberries, basil, and several varieties of lettuce.	More common in rainy areas
	Helminths	Trichinella spp	Any ages	-	Two viable larvae (male and female)	1-4 we	-	✔	✔		✔		✔	Undercooked meats	More common in hunters or people who eat traditionally uncooked meats
		Taenia spp	Any ages	-	1 larva or egg	2-4 m	-	✔	✔	✔			✔	Undercooked beef and pork	Neurocysticercosis: Cysts located in the brain may be asymptomatic or seizures, increased intracranial pressure, headache.
		Diphyllobothrium latum	Any ages	-	1 larva	15 d	-	-	-	✔			✔	Raw or undercooked fish.	May cause vitamin B12 deficiency

∞Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient's immunity system.

General principles for treatment

• Rehydration with a balanced sodium-glucose solution is The first step for treatment. Oral rehydration solution (ORS) has reduced infant mortality in developing countries by at least 50%. ORS has no effect on disease course however, it's valuable to treat dehydration.
• For infants and the elderly with severe travelers diarrhea (TD) and in anyone who develops profuse cholera-like watery diarrhea, balanced ORS and medical evaluation are advised.
• For most otherwise healthy adults with TD, formal ORS is not needed as they can keep up with fluid losses by taking in salty soups, fruit juices and carbohydrates to provide enough compensation.
• In severe diarrhea, a balanced ORS can usually be found at a local pharmacy with sodium of 60–75 mEq/l and glucose of 75–90 mmol/l for replacing salt and water.
• Bismuth subsalicylates (BSSs) can be administered to control rates of passage of stool and may help travelers function better during bouts of mild to moderate illness. The recommended dose of BSS for therapy of acute diarrhea is 30 ml (525 mg) of liquid formulation or two tablets (263 mg per tablet) chewed well each 30–60 min not to exceed eight doses in 24 h. The drug will cause black stools and black tongues.
• In patients receiving antibiotics for TD, adjunctive loperamide therapy can be administered to decrease duration of diarrhea and increase chance for a cure. The recommended dose of loperamide for therapy for adults with diarrhea is 4 mg initially followed by 2 mg after subsequently passed watery stools not to exceed 8 mg per day. Loperamide is not given for more than 48 h. The most valuable use of loperamide in the self-treatment of TD is as a combination drug with antibacterial drugs where the antimotility drug quickly reduces the number of diarrhea stools passed while the antibiotic cures the enteric infection.
• empiric anti-microbial therapy for routine acute diarrheal infection, except in cases of TD where the likelihood of bacterial pathogens is high enough to justify the potential side effects of antibiotics.
• Use of antibiotics for community-acquired diarrhea should be discouraged as epidemiological studies suggest that most community-acquired diarrhea is viral in origin (norovirus, rotavirus, and adenovirus) and is not shortened by the use of antibiotics.
• Antibiotics shorten the overall duration of moderate-to-severe TD to a little over 24 h and are recommended in TD. The following table summarizes the recommended antibiotics for TD.

Antibiotic treatment recommendations Antibiotic Dose Duration† Levofloxacin 500 mg PO Single dose or 3 days Ciprofloxacin 750 mg PO Single dose 500 mg PO 3 days Ofloxacin 400 mg PO Single dose b or 3 days Azithromycin‡ 1000 mg PO Single dose 500 mg PO 3 days Rifaximin¶ 200 mg PO, TID 3 days

†: If symptoms are not resolved after 24 h, complete a 3-day course of antibiotics. ‡: Preferred regimen for dysentery or febrile diarrhea. ¶: Do not use if clinical suspicion for Campylobacter , Salmonella , Shigella , or other causes of invasive diarrhea.

Prevention

Non travel setting

• Contaminated foods are major causes of foodborne illness in the United states.
• To prevent food preparation chain from contamination, every steps of this process including, products in the farms, packaging industries, stores, restaurants and individuals in the home who are buying and preparing food must be take in to consideration.
• Proper maintaining the filtration systems at water plants is also essential.
• Avoid consuming unpasteurized milk or soft cheeses.
• Frequent and effective hand washing and alcohol-based hand sanitizers.
• Rotavirus vaccination is recommended for all infants unless there is a contraindication for it.

Travel setting

• A simple rule is, boil it, cook it, peel it, or forget it!
• Use bottled water or boil all drinking water while on outdoor adventures.
• Frequent and effective hand washing and alcohol-based hand sanitizers especially for cruise travelers.
• Chemoprophylaxis with Bismuth subsalicylate (BSS) has been shown to reduce the frequency of TD when used during period of risk for 3 weeks. The recommended dose of BSS for TD prevention is two tablets four daily doses at mealtimes and at bedtime. BSS could be used for trips up to 2 weeks.
• Offer the typhoid vaccine to travelers going to countries with high prevalence of typhoid fever.