GI Parasites

Question 1

Intestinal Protozoan Infections

Overview

Answer 1

• Diversity of organisms
• Ameba, flagellates, apicomplexans, and ciliates
• Unusual biochemistry and cell biology
• Extensive replication in host
• Fecal-oral mode of transmission
• Chronic infections often seen
• Impact on socio-economic development

Question 2

Food-borne and Water-borne

Protozoa

Answer 2

Sarcodina: Entamoeba histolytica, E. dispar, Acanthamoeba, Naegleria

Mastigophora: Giardia spp.

Apicomplexa: Cryptosporidium, Cyclospora, Isospora, Sarcocystis, Toxoplasma

Ciliophora: Balantidium coli

Microspora: Enterocytozoon

Question 3

Entamoeba histolytica

Epidemiology and Transmission

Answer 3

• Causes amebiasis
• Worldwide distribution
  
  • 480 mil infected, 36 mil develop disabling disease, 50-100k deaths per year
• Confused w/ morphologically to similar but non-pathogenic species, E. dispar
• 1-10% carriers
• Transmission: fecal-oral, venereal
• ↑ Incidence in US w/ AIDS epidemic
• Also seen in migrant farm workers, pts in mental institutions

Question 4

Entamoeba histolytica

Life Cycle

Answer 4

Sarcodina protozoa

• Trophozoites
  
  • Replicative and pathogenic stage
  • Heat labile
  • ~20-30 micron motile form
  • No mitochondrial DNA ⇒ a remnant “mitoplast”
  • Phagocytosis of bacteria and red cells
  • Secretion of various cytocidal agents
  • Hydrolytic enzymes ⇒ “Amebapore”
• Cysts
  
  • Trophozoites → cysts (encystation) during gut transit
  • Infectious stage
  • Can tolerate 55°C, chloride, gastric acid

Question 5

Entamoeba histolytica

Pathogenesis

Answer 5

• Transmission by cysts
  
  • Humans are the main reservoir
  • Up to 45 million cysts/day passed in stools of infected person
• Cyst wall disintegrate (excystation) in distal small intestine
• 8 trophozoites released per cyst
• Trophozoites colonize the large intestine
• Adherence to host cell via galactose and N-acetylgalactoseamine specific lectins
• Secretion of pore forming peptides ⇒ cell lysis
• Secretion of various histolytic enzymes (proteinases, hyaluronidase, collagenase) ⇒ mucosal ulcers
• Acute inflammatory response (lots of PMNs)
• Diarrhea, flatulence and cramps
• Chronic amebiasis can last for months or years

Question 6

Extraintestinal Amebiasis

Answer 6

• Hepatic abscess (5%)
  
  • Hepatic abscesses do not have the acute inflammatory response seen in the gut
• Can extend into surrounding ⇒ pneumonia, empyema, peritonitis, chronic pericardial infection
• Death of hepatocytes through apoptosis?
• Misdiagnosis as liver cancer?

Question 7

Amebiasis

Diagnosis and Treatment

Answer 7

• Stool examination of wet mounts to observe cysts and trophozoites
• Enzyme-linked immunoassays available
• Treatment w/ metronidazole and iodoquinol

Question 8

Giardia lamblia

Overview

Answer 8

• Phylum Mastigophora
• Binucleated flagellate w/ four pairs of flagella
• Sophisticated cytoskeletal structure forms a sucker used for attachment
• No mitochondrial DNA ⇒ a remnant “mitoplast”
• Grow anaerobically
• Deep branch in eukaryotic evolution (“primitive” eukaryotes)

Question 9

Giardia lamblia

Lifecycle

Answer 9

• Trophozoites
  
  • Present in small intestine
  • Secretion of proteases to degrade mucosal layer
  • Replicative form
• In lower intestine: trophozoites → cysts
  
  • Cholesterol deprivation likely signal for differentiation
  • Cyst wall proteins are synthesized
  • Flagella are retracted
  • One round of cell division occurs
  • Cyst wall contains GalNAc polymer
  • Infective form

Question 10

Giardiasis

Epidemiology

Answer 10

• Associated w/ poor hygiene
  
  • Day care centers, developing countries, crowded conditions
• ~4% of US pop. chronic carriers, 60-70% of carriers in endemic areas asymptomatic
• Water-borne epidemics seen in many communities
• Wild animals can be carriers (raccoons, beavers etc. living close to water reservoirs)
• Hikers may get exposed by drinking spring water

Question 11

Giardia lamblia

Clinical Disease

Answer 11

• Acute Giardiasis
  
  • Sudden-onset explosive diarrhea, non-bloody, no mucus
  • Greasy, foul-smelling stools that float on water
  • Large amount of gas
  • Lasts ≥ 4 weeks if untreated
• Subacute and Chronic Giardiasis
  
  • Carrier state is established
  • Malabsorption of fats, carbohydrates, and vitamin B12
  • Intermittent bouts of loose stools, flatulence, weight loss, intestinal discomfort

Question 12

Giardiasis

Diagnosis and Treatment

Answer 12

• Stool examination
  
  • Presence of characteristic cysts
  • May be seen in asymptomatic individuals
• Treatment w/ metronidazole and quinacrine

Question 13

Cryptosporidium parvum

Overview

Answer 13

• Member of phylum Apicomplexa
• Belongs to subclass coccidia
• Obligatory intracellular parasites
• Elaborate life cycle
• Extremely streamlined metabolic pathways
  
  • Reliance on host for nutrients
• Lacks apicoplast ⇒ has degenerate mitochondrion that has lost its genome
• Several novel classes of cell-surface and secreted proteins

Question 14

Cryptosporidium

Lifecycle & Epidemiology

Answer 14

• Oocysts (4-5 micron) ⇒ infectious form
  
  • Resistant to chlorine
  • Can pass through standard water filtration methods
  • Boiling for 1 min kills oocysts
• Farm animals can be major reservoir
  
  • Run-off from farms during spring thaw could contaminate water supply
• Organisms are widespread
  
  • Endemic areas: up to 50% of hospitalized pts w/ diarrhea have Cryptosporidium
  • Pts suffering from Cryptosporidum diarrhea are contagious
    
    • Should not swim in recreational water up to 2 wks after diarrhea stops
  • Large outbreak affecting 400k people occurred in Milwaukee in 1993
  • Most surface water has oocysts: viability?

Question 15

Cryptosporidium

Clinical Disease

Answer 15

• Causes self-limiting diarrhea in immunocompetent
  
  • Nitazoxanide approved for pts w/ healthy immune system
• Immunocompromised ⇒ severe form
  
  • Explosive, perfuse, watery diarrhea
  • Severe fluid loss (up to 25 L/day)
  • Severe weight loss, wasting and eventual death
  • No specific tx available
  • HART In AIDs pts helps by restoring immune system

Question 16

Cyclospora cayetanensis

Answer 16

• ↑ Incidence of human infections since 1970’s
• Unknown if parasite found in animals other than humans
• Similar biology to Cryptosporidium (apicomplexan parasites)
• Need to distinguish infections b/c Cyclospora treatable
• Larger oocysts in stools

Question 17

Cryptosporidium vs Cyclospora

Answer 17

Question 18

Microsporidiosis

Overview

Answer 18

• Caused by obligate intracellular “protozoan” parasites belonging to phylum Microsporidia
• Produce resistant spores that vary in size, depending on species
• Polar tubule or polar filament (unique organelle) ⇒ coiled inside spore
• Opportunistic infectious agents worldwide (developed & developing countries)

Question 19

Intestinal Microsporidiosis

Answer 19

• Enterocytozoon bieneusi
  
  • Diarrhea, acalculous cholecystitis
• Encephalitozoon intestinalis
  
  • Gastroenteritis w/ diarrhea
  • Disseminated microsporidiosis to ocular, GU, and respiratory tracts
• Treatment: Albendazole is the drug of choice

Question 20

Balantidium coli

Answer 20

• Phylum Ciliophora
• Large parasitic ciliate
  
  • Sometimes confused w/ Entamoeba histolytica
• Pigs are the major reservoir
• Cysts are infectious
• Most cases are asymptomatic
• Persistent diarrhea, sometimes dysentery
  
  • More severe in disabled individuals
• Treatment:
  
  • Tetracycline
  • Also iodoquinol and metronidazole

Question 21

Protozoan Parasites

GI Invasion Strategies

Answer 21

Parasitic protozoa and their interactions w/ human intestinal mucosa:

• Giardia sp.
  
  • Trophozoites release proteases to degrade mucosal layer
  • Adhere to epithelial cells via a specialized adhesive disc (AD) on anterior ventral surface
• Cryptosporidium sp.
  
  • Sporozoites secrete chemicals from apical organelles (AO) including proteases and gp30 lectin
  • Provide traction for gliding motility across mucosa before invasion of extracytoplasmic niche
• T. gondii
  
  • Tachyzoites traverse mucosal layer via unknown mech
  • Host cell invasion via moving junction (MJ)
  • Organism remains sequestered in a parasitophorous vacuole (PV)
• E. histolytica
  
  • Trophozoites secrete multiple proteases
  • Strip off the mucosa
  • Induce an inflammatory response (IR)
  • Facilitate penetration of lamina propria (LP)
• T. cruzi
  
  • Metacyclic trypomastigotes express gp82 and pepsin-susceptible gp90 (sheared off in stomach) ⇒ binds to gastric mucin
  • Traverse mucus layer to reach underlying gastric epithelial cells
  • Invade in a gp82-dependent manner