Giardia/Giardiasis

Giardiasis is caused by Giardia lamblia (G. lamblia), a flagellated protozoan that can infect the intestinal tract. Giardia transmission occurs most commonly through consumption of cysts in contaminated water or through the fecal-oral route. Excystation occurs in the gastrointestinal (GI) tract, and trophozoites attach to the intestinal wall villi and cause malabsorption. The hallmark symptom of giardiasis is foul-smelling steatorrhea. Patients who develop chronic infections may experience weight loss, failure to thrive, and vitamin deficiencies as a result of malabsorption. The diagnosis is made through detection of Giardia organisms, antigens, or deoxyribonucleic acid (DNA) in the stool. Management includes supportive treatment and antimicrobial therapy with metronidazole, tinidazole, or nitazoxanide. Prevention measures include proper handwashing and water treatment.

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General Characteristics of Giardia

Giardiasis is caused by the flagellated protozoan, Giardia lamblia (G. lamblia, also known as G. duodenalis or G. intestinalis).

Characteristics

  • Unicellular
  • Eukaryotic
  • Oval shaped
  • Anaerobic
  • Reproduces through binary fission
  • Contains a mitosome in place of mitochondria

Forms

  • Trophozoites:
    • Active, feeding, and replicating stage
    • Contain 2 nuclei
    • 4 pairs of flagella
    • Cannot survive outside a host
  • Cysts:
    • Dormant stage
    • Contain 4 nuclei
    • No flagella
    • Resistant to environmental stressors (heat, cold, desiccation)
    • Can survive outside a host and several months in cold water
    • Responsible for transmission
SEM image of Giardia lamblia trophozoites

Scanning electron microscopic (SEM) image of G. lamblia trophozoites

Image: “SEM” by CDC/Dr. Stan Erlandsen. License: Public Domain

Epidemiology and Transmission

Epidemiology

  • Giardiasis occurs worldwide.
    • 3rd most common cause of diarrhea in children < 5 years of age
    • > 300 million cases annually
  • Prevalence: 
    • 2%–5% worldwide
    • 20%–40% in developing countries
  • In the United States:
    • Approximately 5% of adults are asymptomatic carriers.
    • Common regions in the United States:
      • Western mountain regions
      • Northern states
    • Most common July–October

Transmission

  • Fecal-oral transmission
  • Waterborne transmission:
    • Poorly filtered water supplies
    • Mountain streams, lakes, rivers
  • Outbreaks have been associated with:
    • Ski resorts
    • Daycare centers
    • Refugee camps
    • Camping
  • High-risk groups:
    • Young children
    • Immunocompromised (immunoglobulin deficiency states)
    • Cystic fibrosis patients
    • Blood group A
    • Hypochlorhydria
    • Travelers

Pathogenesis

Virulence factors

  • Antigenic variation:
    • Able to express different variant surface-specific proteins (VSPs)
    • Allows escape from a host’s adaptive immunity
  • Adhesive disc: 
    • Composed of microtubules
    • Allows attachment to the intestinal wall

Life cycle and pathophysiology

  • Cysts are ingested → stomach acid, bile, and trypsin trigger conversion into the trophozoite form (excystation)
  • Trophozoites attach to the intestinal wall with the adhesive disc.
    • Results in:
      • Inflammation
      • Villous atrophy
      • ↓ Brush border enzymes (e.g., disaccharidase, lactase)
    • Leads to malabsorption
    • Trophozoites do not invade the intestinal wall.
  • Binary fission occurs → some organisms form into cysts (encystation) → excreted in feces
Cycle of Giardia lamblia

This image shows the life cycle of G. lamblia. Cysts can survive for long periods of time in cold water and then be inadvertently consumed. Once consumed, the cysts transform into trophozoite form, replicate, and infect the intestines. The trophozoites attach to the intestinal villi, resulting in symptoms.

Image: “Giardia life cycle” by LadyofHats. License: Public Domain, edited by Lecturio.

Clinical Presentation

While some patients may be asymptomatic, the hallmark clinical feature of giardiasis is malabsorptive diarrhea.

Acute giardiasis

  • Incubation period: 7–14 days
  • Duration: 2–4 weeks
  • Common symptoms:
    • Diarrhea (often steatorrhea):
      • Foul smelling
      • Watery or greasy
      • Non-bloody
    • Malaise
    • Flatulence
    • Nausea
    • Anorexia
    • Abdominal cramping and bloating
    • Weight loss
    • Low-grade fever (uncommon)

Chronic giardiasis

  • May develop after the acute phase in some patients
  • Symptoms may wax and wane over months.
  • Common signs and symptoms:
    • Loose stools:
      • Often steatorrhea
      • Not diarrhea
    • Malaise and fatigue
    • Abdominal cramping
    • Flatulence and burping
    • Malabsorption:
      • Hypoalbuminemia
      • Vitamin deficiencies (A, B12, folate)
      • Weight loss and failure to thrive

Complications

  • Stunted growth in children
  • Hypersensitivity:
    • Urticaria
    • Aphthous ulcers
  • Reactive arthritis
  • Acquired lactose intolerance
  • Biliary invasion can lead to:
    • Cholecystitis
    • Cholangitis
    • Granulomatous hepatitis

Diagnosis and Management

Diagnosis

  • Enzyme-linked immunosorbent assay (ELISA): detects antigen in the stool
  • Direct immunofluorescence assay (DFA): Utilizes fluorescein-tagged monoclonal antibodies to detect a specific antigen.
  • Nucleic acid amplification assay (NAAT): detects and copies (amplifies) specific Giardia deoxyribonucleic acid (DNA) sequences
  • Stool microscopy:
    • Microscopic evaluation of stool for trophozoites or cysts
    • May require repeated stool examinations
    • Can detect other potential parasites
    • Less sensitive than ELISA, DFA, or NAAT
Fecal sample showing Giardia lamblia cysts

Stool microscopy revealing the presence of 2 G. lamblia cysts

Image: “ 21085” by CDC. License: Public Domain

Management

  • Supportive care:
    • Rehydration
    • Electrolyte replacement
  • Antimicrobial therapy:
    • Options: 
      • Metronidazole
      • Tinidazole
      • Nitazoxanide
    • Consider treating individuals (even asymptomatic) who are:
      • At risk for transmission to others (food handlers, daycare setting)
      • In contact with immunocompromised individuals
      • In contact with pregnant women
  • Recurrent or persistent symptoms:
    • Repeat stool examination.
    • Evaluate for sources of reinfection.
    • Evaluate for immunodeficiency.
    • Repeat antimicrobial therapy.

Prevention

  • Handwashing:
    • Soap and water preferred
    • Alcohol-based disinfection is not effective against cysts.
  • Proper diaper disposal
  • Boiling potentially contaminated water
  • Public water treatment
  • Infected individuals should avoid swimming in recreational water (pools, lakes, rivers).

Comparison of Flagellated Protozoa

Table: Comparison of clinically relevant flagellated protozoa
GiardiaLeishmaniaTrypanosomaTrichomonas
Characteristics
  • 4 pairs of flagella
  • Ovoid shape
  • Adhesive disc
  • Anaerobe
  • Antigenic variation
  • Single, polar flagellum
  • Slender, elongated body
  • Single, polar flagellum
  • Undulating membrane
  • Thin, irregularly shaped
  • Antigenic variation
  • 5 flagella
  • Undulating membrane
  • Ovoid shape
  • Facultative anaerobe
Forms
  • Cyst
  • Trophozoite
  • Promastigote
  • Amastigote
  • Trypomastigote
  • Amastigote
  • Epimastigote
  • Trophozoite
  • No cyst form
Transmission
  • Waterborne
  • Fecal-oral
  • Vector (sandfly)
  • Human to human
  • Zoonotic (rodents, dogs, foxes)
  • Vector (tsetse fly, kissing bug)
  • Blood transfusion
Sexually transmitted
ClinicalGiardiasisLeishmaniasis
  • African sleeping sickness
  • Chagas disease
Trichomoniasis
Diagnosis
  • ELISA
  • DFA
  • NAAT
  • Stool microscopy
  • Blood smear
  • Biopsy
  • PCR
  • Leishmanin skin test
  • Antibody titers
  • Blood smear
  • Antibody titers
  • Xenodiagnosis
  • Microscopy of vaginal secretions
  • NAAT
  • Urine or urethral swab culture
Treatment
  • Metronidazole
  • Tinidazole
  • Nitazoxanide
Depends on the clinical syndrome:
  • Amphotericin B
  • Pentavalent antimonials
  • Miltefosine
Depends on the clinical disease:
  • Suramin
  • Pentamidine
  • Melarsoprol
  • Eflornithine
  • Nifurtimox
  • Benznidazole
  • Metronidazole
  • Tinidazole
Prevention
  • Handwashing
  • Water treatment
  • Insecticide
  • Insect repellent
  • Protective clothing
  • Insecticides
  • Insect repellent
  • Bed nets
  • Protective clothing
  • Treatment of sex partners
  • Condoms

ELISA: enzyme-linked immunosorbent assay

DFA: direct immunofluorescence assay

NAAT: nucleic acid amplification assay

PCR: polymerase chain reaction

Differential Diagnosis

  • Amebic dysentery: also known as amebiasis, is an infection caused by Entamoeba histolytica (E. histolytica). Symptoms can range from mild diarrhea to severe dysentery, and complications include liver abscess. Identification of E. histolytica in the stool or through serologic testing will give the diagnosis. Management includes metronidazole or paromomycin.
  • Traveler’s diarrhea: a gastroenteritis that is usually caused by bacteria or viruses in the local water, such as enterotoxigenic E. coli (ETEC) or norovirus. Symptoms occur after consumption of contaminated water or food, and include watery diarrhea, malaise, and abdominal cramping. The diagnosis is clinical and the illness is self-limited. 
  • Cryptosporidiosis: an infection with Cryptosporidium. Patients will have watery diarrhea, abdominal cramping, nausea, and fever that lasts 2–3 weeks, but can be more persistent and severe in immunocompromised patients. Diagnosis is with identification of the organism in a stool specimen. Cryptosporidiosis is generally self-limited, but may require nitazoxanide in persistent or severe cases.  
  • Small intestinal bacterial overgrowth: defined as excessive bacteria growing in the small intestine, and can result due to alteration in the intestinal anatomy or motility. Symptoms can range from mildly symptomatic to chronic diarrhea, weight loss, and malabsorption. Bacterial cultures and breath tests can establish the diagnosis. Management includes antibiotics and correction of nutritional deficiencies.
  • Celiac disease: an immunologically mediated disease resulting in mucosal inflammation and villous atrophy in the small bowel due to gluten. Symptoms include abdominal bloating and foul-smelling diarrhea. Patients may also have nutritional deficiencies and weight loss due to malabsorption. The diagnosis is established with serologic markers and small bowel biopsy. Management requires a strict, gluten-free diet.
  • Inflammatory bowel disease (IBD): includes Crohn’s disease and ulcerative colitis. Inflammatory bowel disease is characterized by chronic inflammation of the gastrointestinal (GI) tract due to a cell-mediated immune response to the GI mucosa. Symptoms include diarrhea, abdominal pain, weight loss, and extraintestinal manifestations. Diagnosis includes imaging, endoscopy, and biopsy. Management involves steroids, aminosalicylates, immunomodulators, and biologic agents.
  • Lactose intolerance: an intolerance to lactose-containing foods due to lactase deficiency. Symptoms include crampy, abdominal pain, bloating, nausea, and diarrhea. Diagnosis is based on the association with lactose-containing foods and a lactose hydrogen breath test. Management includes restriction of dietary lactose and enzyme replacement.

References

  1. Riedel, S., Jawetz, E., Melnick, J. L., & Adelberg, E. A. (2019). Jawetz, Melnick & Adelberg’s Medical microbiology (pp. 723-727). New York: McGraw-Hill Education.
  2. Leder, K. (2019). Giardiasis: Epidemiology, clinical manifestations, and diagnosis. UpToDate, Retrieved December 09, 2020, from https://www.uptodate.com/contents/giardiasis-epidemiology-clinical-manifestations-and-diagnosis
  3. Bartelt, L. (2020). Giardiasis: Treatment and prevention. UpToDate, Retrieved December 09, 2020, from https://www.uptodate.com/contents/giardiasis-treatment-and-prevention
  4. Pearson, R.D. (2020). Giardiasis. [online] MSD Manual Professional Version. Retrieved December 11, 2020, from https://www.msdmanuals.com/professional/infectious-diseases/intestinal-protozoa-and-microsporidia/giardiasis
  5. Nazer, H. (2018). Giardiasis. In Cagir, B. (Ed.), Medscape. Retrieved December 11, 2020, from https://emedicine.medscape.com/article/176718-overview
  6. Gladwin, M., & Trattler, B. (2008). Clinical microbiology made ridiculously simple (4th edition). Miami: MedMaster.

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