Diarrhea

Diagnosis

Indications for Testing

• Symptoms
  • Persistent or chronic diarrhea
  • Bloody diarrhea
  • Diarrhea in association with systemic illness
• Patient history
  • Immunocompromised status
  • Returned traveler
  • Hospitalized patient
• Outbreak identification

Laboratory Testing

For most cases, no testing is necessary at initial presentation – most etiologies of acute diarrhea are viral and do not require treatment

• Exceptions (Steffen, 2015)
  • Immunocompromised or hospitalized patients
  • Returned travelers with any of the following
    • Fever >101.3F degrees
    • Bloody stools
    • Dysentery

• Parasites often cause prolonged diarrhea; if no previous testing has been performed, consider also testing for Salmonella sp, Shigella sp, and Campylobacter spp (Steffen, 2015)
• Parasitic testing leads to highest yields at this stage

Differential Diagnosis

• Gastrointestinal disorders
  • Postdiarrheal malabsorption
  • Inflammatory bowel disease
  • Irritable bowel syndrome
  • Celiac disease
  • Pancreatic insufficiency
  • Diverticulitis
• Immunodeficiency syndromes
• Cystic fibrosis
• Lactose intolerance
• Malignancy
  • Primary or metastatic cancer
    • Colorectal cancer
    • VIPoma syndrome
• Laxative abuse

Background

Epidemiology

• Incidence – the CDC estimates >350 million acute diarrheal incidences annually (Mead, 1999)
  • The CDC's Foodborne Diseases Active Surveillance Network (FoodNet) reports ~48 million cases of foodborne illness annually

Risk Factors

• Immunocompromised status
  • HIV, primary immunodeficiency
    • Most common organisms include viruses, C. difficile, Campylobacter jejuni, Salmonella spp, E. coli, Giardia, Cryptosporidium spp, and microsporidia
  • Transplantation (solid organ and stem cell)
    • Usually noninfectious
    • Infectious diarrhea most commonly caused by viruses (norovirus predominates), C. difficile, and microsporidia
• Advanced age (>65 years)
  • Salmonella spp and Shigella spp may require treatment, so identification is important
• Comorbid illnesses (eg, chronic heart, liver, or kidney disease; diabetes mellitus)
  • Increased risk of complications (eg, sepsis)
• Institutional residency
  • Norovirus
• Daycare setting
  • Norovirus
  • Giardia
  • Cryptosporidium spp
  • Salmonella spp

Clinical Presentation

• Community acquired
  • Acute diarrhea (acute gastroenteritis)
    • Duration – 1-14 days
    • Transmission – foodborne, waterborne, or outbreak associated
    • Most commonly caused by viruses and occasionally bacteria
  • Persistent diarrhea
    • Duration – >14 days, often longer
    • Often noninfectious
    • Testing for parasites may be considered
    • Persistent diarrhea may lead to malabsorption following an infectious diarrhea
• Hospital acquired
  • Presentation may be similar to community-acquired disease
  • Most commonly caused by viruses
  • Rule out bacterial agent C. difficile if patient history is correct

Organisms Associated with Diarrhea

• The following organisms are associated with diarrhea (CDC, 2014).
  • Norovirus
    • Epidemiology
      • Incidence
        • Leading cause of nonbacterial gastroenteritis worldwide
        • Norovirus causes millions of infections annually, with outbreaks commonly occurring in all age groups and in varied environments
          • Cruise ships
          • Restaurants (salad bar contamination most common)
          • Schools
          • Daycares
          • Healthcare facilities
      • Transmission
        • Fecal-oral route by ingestion of contaminated food (eg, shellfish) or water
        • Can be airborne (in vomitus)
        • Low infectious dose; can survive relatively high levels of disinfectants and varying temperatures
    • Clinical presentation
      • Usually mild or self-limiting disease with high transmission rates
      • Onset of symptoms occurs 24-48 hours after infection
      • Symptoms – generally last 12-60 hours
        • Acute onset diarrhea
        • Vomiting with abdominal cramps
        • Nausea
        • Fever
        • Headache
      • Transplant patients often have chronic diarrhea
        • Symptoms in small bowel transplant patients resemble allograft rejection
  • Rotavirus
    • Epidemiology
      • Incidence
        • Most important cause of severe dehydrating diarrhea worldwide in children <5 years
          • Declined 67% in U.S. since introduction of vaccine
          • Universal infection – nearly all children have circulating antibodies by 2-3 years
      • Transmission
        • Fecal-oral route
    • Clinical presentation
      • Varies from asymptomatic to severe dehydration leading to death
      • Mild fever and emesis for 2-3 days
      • Watery diarrhea for 3-5 days following fever
        • Bloody diarrhea rare
      • Severe and prolonged disease may occur in patients with the following
        • Significant malnutrition
        • Immune deficiencies (eg, HIV)
        • Other chronic disease such as diabetes mellitus, congenital heart disease, or pulmonary disease
      • May involve extra intestinal sites – central nervous system, liver, spleen, or kidney, especially in immunocompromised children
  • Campylobacter
    • Epidemiology
      • Incidence
        • Leading cause of bacterial gastroenteritis worldwide
        • Peak incidence in children <5 years
      • Occurrence
        • Sporadic, but most cases occur in spring and fall
      • Transmission
        • Associated with incorrect food handling practices, consumption of poorly cooked poultry or raw milk, contact with pets, travel
        • Outbreaks most often associated with raw milk and contaminated water
    • Clinical presentation
      • Varies from asymptomatic infection to severe inflammatory diarrhea
      • Onset of symptoms occurs 2-5 days after ingestion of contaminated food or water
      • Symptoms – generally last 7-10 days
        • Abdominal pain
        • Watery stools containing blood and mucous
        • Fever
        • Nausea or vomiting
      • Complications
        • Reactive arthritis (increased risk if individual is positive for HLA-B27 phenotype)
        • Guillain-Barré syndrome
        • Hemolytic uremic syndrome (HUS)
        • Complications in patients with HIV or hypogammaglobulinemia – relapse osteomyelitis (especially with HLA-B27 phenotype)
        • Local complications – hemorrhage, megacolon
        • Bacteremic complications – cellulitis, meningitis
  • Salmonella
    • Epidemiology
      • Incidence
        • Most U.S. cases are related to international travel or immigrant status
        • Remaining cases are from large, sporadic outbreaks
          • Incidence nearly equal to Campylobacter
      • Transmission
        • Undercooked or uncooked foods (eg, raw meat and vegetables, poultry, eggs, milk, salad dressing, shrimp, peanut butter)
        • Contact with infected animals
        • Contact with nonsymptomatic patients
    • Clinical presentation
      • Typhoid fever
        • Incubation period is 3-21 days
        • Prodrome of chills, headache, sore throat, fever, anorexia, cough
        • Progresses to rash (rose spots), epistaxis, diarrhea, relative bradycardia
        • Blood cultures are of higher yield than stool cultures for typhoid fever
          • 90% have positive blood cultures in week 1; drops to 50% by week 3
        • Complications
          • Late complications found in untreated adults – intestinal perforation, gastrointestinal hemorrhage
          • Rare complications – pancreatitis, hepatic and splenic abscesses, endocarditis, pericarditis, orchitis, meningitis, parotitis, osteomyelitis
          • Up to 5% of infected patients develop chronic carrier state
            • Usually occurs in patients with gall bladder disease or gastric carcinomas
      • Enteritis
        • Onset of symptoms occur 6-48 hours after exposure
        • Symptoms – gererally last 1-2 days
          • Fever, headache
          • Intestinal symptoms – diarrhea (watery), abdominal pain
  • Shiga-toxigenic E. coli
    • Epidemiology
      • Incidence
        • Under-recognized illness
        • Not uncommon
      • Transmission
        • Person-to-person contact in daycare facilities and nursing homes
        • Consumption of undercooked meats and produce (washing produce has been shown to be ineffective)
    • Clinical presentation
      • Watery diarrhea progressing to bloody diarrhea
      • Abdominal pain
      • Symptoms usually resolve within 8 days
      • Hemolytic uremia syndrome (HUS) – fever, renal dysfunction and hemolytic anemia, thrombocytopenia
        • Virulence is attributable to production of Shiga-like toxin 1 and/or 2
        • Most frequent in children <15 years and adults >65 years
  • Shigella spp
    • Epidemiology
      • Incidence
        • Common in countries with poor sanitation
        • Accounts for small percentage of reported outbreaks of foodborne illness in U.S.
      • Transmission
        • Fecal-oral route; no nonhuman hosts
        • Higher-risk groups – daycare personnel and clients, nursing home residents, and men who have sex with men
    • Clinical presentation
      • Onset of symptoms occurs 12-50 hours after exposure
      • Symptoms
        • Diarrhea
          • Frequently bloody
          • May contain mucous or pus
        • Fever
        • Abdominal pain, cramps
        • Dysentery (10-30 stools/day)
      • Associated with Reiter syndrome (arthritis, uveitis, urethritis)
      • Complications
        • Reactive arthritis (increased risk of development if patient is positive for HLA-B27 allele)
        • Hemolytic uremic syndrome (HUS) (usually S. dysenteriae type 1)
  • Yersinia spp
    • Epidemiology
      • Incidence
        • Most often in young children
        • Y. pseudotuberculosis and Y. pestis are uncommon causes of gastrointestinal disease
      • Transmission
        • Soil, water, animals, food
        • Y. enterocolitica found in meats (eg, beef, pork), oysters, fish, and unpasteurized milk
    • Clinical presentation
      • Onset of symptoms occurs 24-48 hours after ingestion of contaminated food or drink
      • Symptoms
        • Diarrhea (loose, watery, or bloody stools)
        • Abdominal pain
        • Fever
        • Infections with Y. enterocolitica and Y. pseudotuberculosis can be asymptomatic, mild, or severe, with infection resolving within a few weeks (with or without use of antibiotics)
        • Yersinia infections are known for mimicking appendicitis
      • Complications include reactive arthritis which can manifest 1-4 weeks post infection (increased risk of development if patient is positive for HLA-B27 allele)
        • The most commonly affected joints are knees and ankles, but other joints such as toes, fingers, and wrists can be involved
        • In most cases, 2-4 joints become involved sequentially and asymmetrically over a period of a few days to 2 weeks
          • Joint fluid is sterile
        • Chronic joint disease or ankylosing spondylitis occurs rarely
        • Acute arthritis persists for 1-4 months
        • Reiter syndrome (arthritis, uveitis, and urethritis) may occur
        • Less common nonsuppurative sequelae of Y. enterocolitica infections include reactive uveitis, iritis, conjunctivitis, glomerulonephritis, urethritis, hemolytic uremic syndrome (HUS)
  • Vibrio spp
    • Epidemiology
      • Incidence
        • Vibrio cholerae
          • Several pandemics have occurred
          • No major outbreaks in U.S. since 1911
        • V. vulnificus
          • Outbreak reported in New Orleans after hurricane Katrina
          • Usually several lethal cases annually in Florida, typically in summer months
      • Transmission
        • Ingestion of contaminated seafood (eg, crab, shrimp, lobster)
          • V. parahaemolyticus is the leading cause of bacterial diarrhea associated with seafood
        • Through open wounds in sea water
    • Clinical presentation
      • Onset of symptoms occurs within 16 hours of ingestion of contaminated seafood for healthy individuals
      • Symptoms
        • Watery diarrhea
        • Abdominal pain
        • Cramps
        • Vomiting
      • Immunocompromised individuals and patients with cirrhosis may present with primary septicemia
        • Associated with >50% mortality
      • No associated long-term complications
  • Giardia duodenalis (synonyms Giardia lamblia, Giardia intestinalis)
    • Epidemiology
      • Incidence
        • Most common cause of parasite-associated diarrhea in the U.S.
        • Increased frequency in children, men who have sex with men, and residents of institutional care facilities
      • Transmission
        • Waterborne, foodborne, or fecal-oral
    • Clinical presentation
      • Most infections are asymptomatic
      • Symptoms may last from weeks to months
        • Acute or chronic nonbloody diarrhea, nausea, vomiting, dehydration, abdominal discomfort, malabsorptive symptoms (eg, flatulence, greasy malodorous stools)
      • Intermittent or recurrent symptoms are common
  • Cryptosporidium spp
    • Epidemiology
      • Incidence
        • Increased risk in patients with HIV, residents of households with infected patients, daycare personnel and clients, and returned travelers
      • Transmission
        • Waterborne, sporadic, or outbreak associated
          • Found in large outbreaks associated with contaminated water sources
          • Can occur year round when artificial water storage systems are involved
    • Clinical presentation
      • Immunocompetent patients
        • Usually asymptomatic or mild, self-limiting gastroenteritis
        • Nonbloody, watery diarrhea, dehydration, nausea, vomiting, abdominal pain, low-grade fever, and malaise lasting from a few days to >30 days
      • Immunocompromised patients
        • General immunodeficiencies (particularly T-cell deficiencies) – chronic diarrhea (often more severe than expected for pathogen), dehydration, weight loss
        • HIV – chronic diarrhea; others include cholecystitis, hepatitis, pancreatitis
  • Entamoeba histolytica
    • Epidemiology
      • Incidence
        • Increased risk in men who have sex with men, recent immigrants, residents of institutional care facilities, returned travelers, and HIV patients
        • Typically limited to individual cases with possible spread to sex partners or close contacts
      • Transmission
        • Waterborne, foodborne, or fecal-oral
    • Clinical presentation
      • Most individuals are asymptomatically colonized (~90%)
        • Subacute onset
      • Disease may be intestinal or extraintestinal
        • Intestinal disease
          • Fulminant or chronic, with abdominal pain, tenderness, tenesmus, and bloody diarrhea
        • Extraintestinal disease
          • May include liver, brain, and lung abscesses
  • Cystoisospora belli
    • Epidemiology
      • Incidence
        • Increased risk in HIV patients, recent immigrants, and travelers from endemic regions
      • Transmission
        • Waterborne
    • Clinical presentation
      • Immunocompetent patients
        • Acute, self-limiting watery or malodorous diarrhea (similar to Giardia or Cryptosporidium infection)
      • Immunocompromised patients
        • General immunodeficiencies – chronic diarrhea (occasionally severe), dehydration, weight loss
        • HIV – diarrhea, cholecystitis, reactive arthritis
  • Microsporidia
    • Epidemiology
      • Incidence
        • Undetermined in non-HIV populations
        • Increased risk in HIV patients presenting with chronic diarrhea
          • Predominately affects immunocompromised hosts
          • Includes Enterocytozoon bieneusi, Encephalitozoon intestinalis, Pleistophora, Septata, Vittaforma spp
          • ~15% prior to combination antiretroviral therapy (cART)
          • Rates are lower for patients on cART
      • Transmission
        • Waterborne
    • Clinical presentation
      • Immunocompetent patients
        • Rare cause of acute, self-limiting diarrhea
      • Immunocompromised patients (most often with HIV)
        • Chronic diarrhea, dehydration, anorexia, weight loss, abdominal pain, nausea, vomiting
  • Cyclospora cayetanensis
    • Epidemiology
      • Incidence
        • Unknown in U.S.; usually tropical/subtropical regions
      • Transmission
        • Foodborne or waterborne
        • Clustered outbreaks associated with contaminated food products
        • Recent outbreaks occurring at higher frequency
          • Not associated with foreign travel, but rather, foreign food products sold domestically
      • Clinical presentation
        • Immunocompetent patients
          • Anorexia, nausea, emesis, flatulence, watery diarrhea, low grade fever, fatigue, cramping
          • Typically does not resolve without treatment
        • Immunocompromised patients
          • May cause chronic diarrhea
        • Endemic – frequent mild or asymptomatic cases