The clinical features, pathology, microbiology and ER management of acute diarrheal diseases, including HIV-related gastrointestinal infections

Dr. Peter Andre Soltau

Background / Incidence• The W.H.O reports > 3 million episodes of diarrhea annually and

estimates > 2.2 million diarrheal deaths occur mainly in children, especially in low- and middle-income countries

• Diarrheal diseases represent one of the five leading causes of death worldwide

• Commonly called the "nuisance disease"

Definitions

• Acute primary diarrhea defined as 3 or more loose/ watery/ diarrheal stools in a 24-hour period

• Duration:• Acute < 14 days• Persistent > 14 days• Chronic > 30 days

• Dysentery - frequent passage of small volume stools assoc. blood, mucus, abdominal cramping and tenesmus

Severe Diarrhea - 4 or more stools per day for 3 or more days associated with [abdominal symptoms(cramps, nausea, vomiting, tenesmus) or systemic symptom (fever, malaise, dehydration)].

Classifying Diarrhea• Secretory vs Osmotic

• Infectious vs Non-Infectious

• Inflammatory vs Non Inflammatory

Secretory diarrhea• Due to abnormal electrolyte transport across the intestinal

epithelial cells • Increased secretion and/or decreased absorption result • The diarrhea is not related to the intestinal contents and

therefore typically does not stop with fasting.• Infection (e.g., cholera) is the most common cause of

secretory diarrhea• The fluid losses can be enormous.

Osmotic diarrhea• The presence of nonabsorbable solute exerts an osmotic

pressure effect across the intestinal mucosa, resulting in excessive water output

• Stops during fasting• The offending molecule is usually a carbohydrate or divalent

ion. • Common examples include mannitol or sorbitol, epson salt

(MgSO4) and some antacids (MgOH2).

Malabsorption• Inability to absorb certain carbohydrates is the most common

deficit, but it can result virtually from any type of malabsorption.

• E.g. lactose intolerance: a deficiency in the brush border enzyme lactase.

Etiology

• Infectious:• Viruses • Norovirus, rotavirus, adenoviruses, astrovirus, and others

• Bacteria • Salmonella, campylobacter, shigella, enterotoxigenic E. coli, C. difficile,

vibrio species and others

• Protozoa• Cryptosporidium, giardia l., cyclospora, entamoeba h., and others

Etiology • Dietary Disturbances:• Overfeeding, food allergy, starvation stools

• Anatomic Abnormalities• Intussusception, hirschsprung, partial obstruction, appendicitis,

blind loop syndrome, short bowel syndrome• Inflammatory Bowel disease• Malabsorption or secretory diseases• Cystic fibrosis, celiac disease, disaccharidase deficiency

• Systemic Diseases• Immunodificiency, endocrinopathy (CAH, thyroid disorders)

• Miscellaneous • Antibiotic associated, secondary lactase deficiency, irritable colon

syndrome, toxins, HUS

Pathology - Infectious

• Pathogenic organisms must be swallowed, they must survive the acid in the stomach, intestinal immunity, motility, mucus, and the resident micro flora, then colonize the small bowel and stick to the enterocytes. They then produce their harmful effects by one of several mechanisms

Viral Pathogens• Invade & destroy the small intestinal mucosa villous epithelium

• Loss of mature absorptive cells

• Regeneration of poorly differentiated intestinal epithelial cells

• Impaired salt and water absorption

• Carbohydrate malabsorption leading to osmotic diarrhea

Bacterial Pathogens• Invasive:• Adhere to mucosal cells followed by invasion and multiplication,

initiating an acute mucosal inflammatory reaction, leading to ulceration and synthesis of a variety of secretagogues. esp. in large intestine

• E.g. Shigella, Salmonella, Yersinia enterocolitica, campylobacter jejuni, vibrio parahemolyticus

• Cytotoxic:• Elaboration of cytotoxins which can either inhibit protein synthesis

or induce secretion of inflammatory mediators causing cell death and hence decrease the intestinal absorptive surface area

• E.g. Shigella, E.coli, clostridium difficile

Bacterial Pathogens• Toxigenic• Colonize the small intestines and secrete enterotoxins which bind

mucosal receptors and increase an intracellular mediator altering salt and water transport (mucosal integrity is unchanged)

• E.g. Shigella, E.coli, Yersinia E., Vibrio cholerae

• Adherent:• Colonize and adhere to intestinal surface of small and large

intestine, indenting the surface and flattening the microvilli, thereby decreasing the surface area

• E.g. E. coli

Microbiology• Laboratory testing: • Routine testing for specific pathogens is not recommended• Reserve laboratory testing and stool cultures for select

circumstances.

• Criteria vary but often include bloody diarrhea, weight loss, diarrhea leading to dehydration, fever, neurologic involvement, sudden onset of severe abdominal pain, persistent (> 7 days) diarrhea, or possible community-acquired diarrhea, traveler’s diarrhea, or nosocomial diarrhea

ED management

ED ManagementHistory Of Present Illness

• Type and volume of stools: • Associated symptoms: nausea, vomiting, abdominal pain, fever, and tenesmus• Character and location of any abdominal pain • Duration of symptoms• Weight loss• Indicators of dehydration• Epidemiological risk factors • Recent diet, ingestion of seafood, raw or undercooked meat, eggs, or milk

products • Recent foreign travel• Lake or stream swimming• Visits to a farm• Ill contacts,• Group living arrangements (e.g., nursing home, college dormitory) or day

care attendance

• Past Medical History• Comorbidities• Immunosuppression• Crohn’s disease or ulcerative colitis

• Medications• prescription, over-the-counter, and herbal preparations

• laxatives, antibiotics, magnesium- or calcium-containing antacids.• alpha-glucosidase inhibitors (e.g., acarbose, miglitol)

• Artificial sweeteners containing sorbitol or mannitol • Enteral tube feedings

• Social History• Occupational history (veterinarian, food handler, or

day care center or nursing home employee) • Sexual preference• Inquire about alcohol and drug use

Indications for diagnostic evaluation

• Profuse watery diarrhea with signs of hypovolemia• Passage of many small volume stools containing blood and

mucus• Bloody diarrhea• Temperature ≥38.5ºC (101.3ºF)• Passage of ≥6 unformed stools per 24 hours or a duration of

illness >48 hours• Severe abdominal pain• Recent use of antibiotics or hospitalized patients• Diarrhea in the elderly (≥70 years of age) or the

immunocompromised

Tests• Blood Tests• CBC: unnecessary in most• Chem Path: unnecessary in most

• Fecal Leukocyte/Lactoferrin Testing:• Community-acquired or traveler’s diarrhea, nosocomial

diarrhea, and diarrhea persisting more than seven days have been suggested

• Stool Culture• the yield on routinely obtained stool cultures is low (1 -5%)• Indicated :• history of bloody stools (grossly bloody or heme-positive stools)• stools containing leukocytes or lactoferrin;• immunocompromised patients; fever higher than 38.5°C (101.3°F);• systemic illness or an illness that is clinically severe or persistent; • patients with severe abdominal pain.

• Stool testing for Parasites• diarrhea lasting more than 14 days• immunocompromised• not responded to antimicrobial therapy

ED Management

HIV/ AIDS• Prone to diarrheal Illnesses, in developing world up to 100%• Increased risk due to:• Develop enteric infections from a variety of unusual viral,

parasitic, protozoal, and bacterial organisms• Malignancies (lymphoma/Kaposi's sarcoma)• Multiple course of antibiotics – antibiotic associated diarrhea

• Stool culture should be done, along with C. difficile toxin and ova and parasite

• If negative consider endscopic investigation

Treatment• Rapidly assess hydration status, risk factors for likely bacterial

pathogen, and need for symptomatic relief

• Rehydration - IV VS ORT

• Diarrhea relief include loperamide, diphenoxylate, and bismuth subsalicylate

Oral rehydration Therapy• Directed at preventing or treating dehydration, replacing

ongoing fluid loss, and meeting nutritional needs• Correct fluid deficit over 4 hours• 50 – 100mls of ORS/ kg• Aim for 30mls of ORS/kg per hour• Pedialyte, Lytren, and Rehydrolyte

IV Fluids• Indicated for severe dehydration, hemodynamic instability,

altered mental status• 20 ml/kg bolus in children

Controversial Treatments

• Probiotics – microorganisms used to colonize the intestine and treat or prevent diarrhea, found to reduce duration on average 0.7 days, and frequency by 1.6 per day

• Zinc – RCT suggests a reduction in duration and severity of acute and persistent diarrhea, however more likely to vomit

• Ramoplanin – a new antibiotic in Phase II development for C. difficile associated diarrhea

Role of Antibiotics• Empiric antibiotics should be considered for patients:• with acute dysentery• moderate-to-severe traveler’s diarrhea• Diarrhea lasting longer than two and a half days• fever greater than 38.5°C (101.3°F) plus either leukocyte-,

lactoferrin-, or hem occult-positive stools

• Fluoroquinolones for adults and trimethoprimsulfamethoxazole (TMP-SMX) for children are reasonable

Disposition / Follow Up• Decision relies heavily on physician judgment

• Most commonly – clinically stable, benign exam and low risk for complications – safely discharged with follow up

• Moderate or severe dehydration, intractable or bilious vomiting, surgical cause of vomiting, neurological abnormalities, large ongoing losses, poor social support are candidates for admission

• Special consideration for patients with diagnostic dilemma, extremes of age, immunocompromised, or multiple or severe comorbidities

• Discharge instructions are mandatory both verbal and written

Transmission Prevention• Good hand washing hygiene

• Travel Precautions

• Immunization - Rotavirus vaccines

• Patient & family education

Summary• The role of the emergency physician is to exclude serious

illness, ensure patient stability, begin an investigation to exclude infectious causes of diarrhea, and provide timely referral for further evaluation

• This diagnostic evaluation usually exceeds the scope of most ED capabilities

• If there is a doubt about the diagnosis, ED observation and repeated examinations can be helpful.

• Patients warranting a greater level of concern are the very young, the elderly, immunocompromised individuals, those with major comorbidities, and those with unusual or atypical presentations