GIARDIASIS

LECTURE (4)

Dr. Khalid AL-Attabe

D.M C.A.B.M

COLLEGE OF MEDICINE

MISAN UNIVERSITY

2010-2011

Flagellates2 groups of parasites:

1- intestinal , oral and reproductive track flagellates

•Giadria Lamblia

•Trichomonas hominis

•Trichomonas tenax

•Trichomonas vaginalis

•Chilomastix mesnili

•Other flagelates

2- blood and tissue-dwelling flagellates

Haemoflagellates:

• These parasites live in the blood, lymph, and tissue spaces and are typically transmitted from one host to another by blood-feeding arthropods The most important genera are Trypanosoma and Leishmania.

Definition

• Giardia duodenalis, also known as Giardia intestinalis or Giardia lamblia, is the most common human protozoan enteric pathogen worldwide and is the only Giardia species infecting humans and many other mammals.

Definition

• Giardia duodenalis, also known as Giardia intestinalis or Giardia lamblia,

• It causes endemic and epidemic diarrheal illnesses, but the parasite is most often carried asymptomatically by humans.

Giardiasis

• The Pathogen • Discovered in 1681, this

eukaryotic parasite has a simple life cycle alternating between trophozoite and cyst stages.

Giardiasis

• The pear-shaped, flagellated trophozoites (10 to 15 μm long and 5 to 15 μm wide) contain two nuclei and resemble a “face” microscopically.

• Trophozoites proliferate in the small bowel and may be identified in the liquid stools of symptomatic patients.

GiardiasisGiardia intestinalis =(lamblia)

Trophozoites Cysts

Giardiasis

• Encystation in the jejunum yields the immediately infective cyst stage (10 to 12 μm long and 7 to 10 μm wide) identified in fecal samples . The oval cysts are resistant to chlorine and can survive in water for up to 3 months. The hardiness of Giardia cysts makes this parasite one of the most frequently identified water-borne pathogens

Epidemiology

• Transmission of G. duodenalis infection occurs directly by person to person or indirectly by ingestion of contaminated water or, less often, food.

• Person-to-person, fecal-oral transmission and small-scale water contamination result in endemic infection,

• whereas epidemic disease is recognized when food or large-scale drinking water contamination occurs.

Epidemiology

• The infection is transmitted by the ingestion of as few as 10 to 100 G. duodenalis cysts.

• Persons of all age groups are susceptible to this infection,

• although exclusive breast-feeding may lower the risk for infection in young children;

• the milk antimicrobial protein lactoferrin kills Giardia trophozoites in vitro, and maternal immunoglobulin A (IgA) can neutralize Giardia antigens and provide important passive immunity to nursing infants.

•

Epidemiology

• In the developing world, infection is nearly universal by the age of 5 years, but recurrent infections are not uncommon, thus indicating that the primary immune response to infection is incompletely protective.

Epidemiology

• In the developed countries infection is generally sporadic, with certain groups of individuals at higher risk,

• including children (particularly those attending daycare centers),

• male homosexuals • and the ingestion of untreated

surface water), • and international travelers.

Epidemiology

• A notable association of travel to Russia (particularly St. Petersburg) with the acquisition of G. duodenalis infection is amply documented.

Epidemiology

• Although both T- and B-cell–mediated immune mechanisms appear necessary to eradicate infection,

• immunocompromised patients with hypogammaglobulinemia (e.g., common variable immunodeficiency, X-linked hypogammaglobulinemia) are primarily those at increased risk for prolonged, sometimes intractable infection.

• Patients infected with human immunodeficiency virus (HIV) do not generally experience more severe disease.

Epidemiology

• G. duodenalis does not clearly exhibit enhanced virulence in patients with HIV infection or selective IgA deficiency.

• Individuals with selective IgA deficiency are typically relatively deficient in IgA but produce low levels of IgA that appear sufficient to promote clearance of Giardia infection.

Epidemiology

• Similar to other enteric infections,• achlorhydria or hypochlorhydria

enhances the likelihood of infection, and proton pump inhibitors may increase the risk for giardiasis. Although humans are the main reservoir of G. duodenalis infection, genetically related species infect humans,

Pathobiology

• G. duodenalis is strictly a small bowel, noninvasive enteric pathogen. Infection is initiated by ingestion of the cyst form of the parasite, which releases two trophozoites aided by the pH and protease conditions of the upper part of the small bowel.

Pathobiology

• Trophozoites firmly attach to the small bowel mucosa by means of a disc-shaped sucker on the ventral surface, aided initially by surface lectin and subsequently by contractile parasitic proteins and the negative pressure created by the parasite's beating flagella.

Pathobiology

• Attachment is most often patchy and imprints the mucosa, thereby creating localized microvillus damage.

• A well-established sequeles of this pathology is inhibition of mucosal digestive enzyme activity.

• In some patients, these events culminate in the onset of symptoms after an incubation period of 6 to 15 days.

Pathobiology

• As trophozoites migrate distally in the small bowel, higher bile concentrations stimulate encystation and result in excretion of the environmentally resistant, but immediately infective, cyst form of the parasite.

Pathobiology

• The histopathologic response to G. duodenalis infection varies and imperfectly correlates with the clinical findings.

• In asymptomatic patients, electron microscopy often reveals evidence of ultrastructural changes in microvilli not observed by light microscopy.

Pathobiology

• Surprisingly, small bowel biopsies of symptomatic patients examined by light microscopy are also usually normal but may reveal

• villous atrophy, • crypt hyperplasia, • and an inflammatory lamina propria infiltrate

consisting of polymorphonuclear leukocytes, plasma cells, and lymphocytes.

• Lymphoid nodular hyperplasia has been associated with giardiasis and hypogammaglobulinemia.

Pathobiology

• The pathophysiology of Giardia infection is complex and incompletely understood. One of the unresolved puzzles is how G. duodenalis causes a broad spectrum of disease ranging from asymptomatic infection to acute and sometimes chronic diarrhea.

Pathobiology

• Two major postulates accounting for disease variability have been proposed.

• First, experimental animal and human infections suggest that Giardia strains vary in virulence, although specific essential virulence genes have yet to be identified.

• Secound G. duodenalis undergoes surface antigenic variation , that is most likely stimulated by the host immune response or the intestinal

Pathobiology • The mechanisms by which infection with

G. duodenalis results in diarrhea appear to be multifactorial.

• 1- documented disaccharidase deficiencies

• 2- the ultrastructural and histopathologic changes observed in association with some G. duodenalis infections are consistent with the clinical observation of malabsorption in infected patients.

Pathobiology

• 3-Experimental animal and in vitro epithelial cell infections also reveal increased intestinal permeability, impaired glucose and amino acid–dependent sodium absorption,

• 4- in some instances, net sodium and chloride secretion

Pathobiology

• 5-The patchy distribution of G. duodenalis infection in contrast to the large surface area of the small bowel and the absence of overt abnormalities in gut architecture in the majority of symptomatic individuals suggest that the parasite may secrete one or more factors that alter intestinal transport. Only limited experimental data support this hypothesis

Pathobiology

• 6- the mucosal immune response may contribute to intestinal secretion through the release, for example, of cytokines known to stimulate chloride secretion by intestinal epithelial cells.

Pathobiology

• The mechanisms by which infection with G. duodenalis results in diarrhea appear to be multifactorial.

• First, documented disaccharidase deficiencies • Second, the patchy distribution ,the parasite

may secrete one or more factors that alter intestinal transport.

• Third, the mucosal immune response may contribute to intestinal secretion through the release,

Clinical Manifestations

• Giardiasis is manifested as one of three clinical forms:

• The asymptomatic carrier state (accounting for most infections);

• Acute, self-limited diarrheal illnesses; • Persistent (lasting >2 weeks) or chronic (lasting

>30 days), • Sometimes relapsing diarrhea associated with

malabsorption • In young children in the developing world,

growth retardation (i.e., stunting).

Clinical Manifestations

• Diarrhea develops in about 40 to 50% of infected persons,

• and the majority of Giardia infections are self-limited,

• consistent with the existence of effective host defenses.

• Experimental studies suggest that intestinal secretory IgA, helper T lymphocytes (CD4+), and interleukin-6 production are central to resolution of infection.

Clinical Manifestations

• Symptomatic patients experience • anorexia and nausea combined • with, most characteristically, explosive,

watery, foul-smelling diarrhea with increased passage of gas.

• Only low-grade fever occurs, • and the blood white cell count is normal.• Leukocytes and blood are not present in

feces, • and even mucus in stool is rare.

Clinical Manifestations

Nevertheless, the diarrheal illness caused by G. duodenalis is indistinguishable from that caused by other small bowel enteric pathogens.

In those with persistent or chronic illness, malabsorption (including fats, vitamin B12, and lactose) may be associated with foul-smelling, oily stools that float and prominent weight loss.

Clinical Manifestations

Lactose intolerance may last for several weeks after successful therapy for giardiasis.

Rare associations with G. duodenalis infection include urticaria, cholecystitis, pancreatitis, arthritis, retinal arteritis, and iridocyclitis.

Diagnosis

• Demonstration of the cysts• or, rarely, trophozoites of G.

duodenalis in concentrated, stained fecal specimens is the traditional approach to diagnosis.

Diagnosis

• and symptoms may begin before the organism is detectable in stool. Examination of two stools after concentration and staining for parasite forms

• or by direct immunofluorescence assay to detect intact organisms or an enzyme-linked immunosorbent assay to detect soluble Giardia stool antigens generally yields the diagnosis in more than 90% of infected individuals.

•

Diagnosis • The use of an “enterotest” (i.e.,

gelatin capsule-string test) or endoscopy to detect trophozoites in the upper part of the small bowel is rarely necessary for patient management.

• Polymerase chain reaction approaches remain experimental. Repeat stool examinations for “test of cure” after treatment are not necessary.

Management

• Treatment is with a single dose of Tinidazole 2 g,

• or Metronidazole 2 g once daily for 3 days

• or 400 mg 8-hourly for 10 days.

Treatment

• The metronidazole and tinidazole are most often the drugs of choice and are more than 90% effective.

• Tinidazole offers the advantage of single-dose treatment and is approved for therapy by the U.S. Food and Drug Administration (FDA) for children (>3 years old) and adults.

• The adult dosage is 2 g orally, whereas the pediatric dosage is 50 mg/kg.

•

Treatment

• Notable side effects include• a metallic taste• and gastrointestinal and central

nervous system (e.g., headache, vertigo) symptoms. Rarely, transient leukopenia and neutropenia, peripheral neuropathy,

• and seizures have been reported.•

Treatment

• Nitazoxanide, a broadly active antiprotozoal and anthelmintic agent, is FDA approved for treatment in children (>1 year old) and adults and is available as a suspension. The dosage is 100 to 500 mg orally twice daily for 3 days for children or adults, respectively.

• Clinical efficacy is 80% or better. • Nitazoxanide is well tolerated, with only

headache, nausea, and diarrhea occurring more often with nitazoxanide treatment than with placebo.

Treatment

Metronidazole is frequently used at a dosage of 250 mg orally three times daily for 5 days.

Treatment

• Alternative therapies include furazolidone and albendazole. Furazolidone is approximately 80% effective, FDA approved, and available as a suspension. The adult dosage is 100 mg orally (1.25 to 2 mg/kg/dose four times a day for 7 to 10 days

• for children >1 month old) four times a day for 7 to 10 days.

•

Treatment

• Furazolidone may precipitate hemolysis in patients with glucose-6-phosphate deficiency and is contraindicated in patients taking monoamine oxidase inhibitors.

•

Treatment

• Albendazole, a benzimidazole, has excellent in vitro activity against Giardia isolates and clinical efficacy when given for 5 or more days. The dosage is 400 mg (or 15 mg/kg/day for 5 to 7 days in children) orally daily for 5 days. Gastrointestinal side effects may occur.

Treatment

• Treatment failures may occur with any of these standard therapies, consistent with in vivo and in vitro data, thus suggesting that strain-dependent drug resistance exists and may be induced during therapy.

Treatment

• The nitroimidazoles and furazolidone inhibit aldehyde dehydrogenase and may precipitate a disulfiram-like reaction if taken with alcohol.

Treatment

• None of these therapeutic alternatives are clearly safe in pregnancy, for which the poorly absorbed oral aminoglycoside paromomycin has been suggested.

Treatment

• Metronidazole is an alternative in pregnancy for serious cases, although its use in pregnancy remains controversial because well-controlled human studies on its safety are lacking (FDA category B).

Treatment

• Quinacrine (mepacrine), an effective but potentially toxic therapy, is no longer available

• in the United States. • Limited clinical data suggest that

dual drug therapy offers benefit in recalcitrant infections.

Prevention

• Because G. lamblia is transmitted by environmentally resistant cysts and does not stimulate complete protective immunity,

• prevention of infection requires public health measures to ensure the availability of clean water

• and education to promote excellent personal hygiene for interruption of the infection cycle.

Prevention

• Boiling of water for 1 minute • or treatment with two to four drops of household

bleach • or 0.5 mL of a 2% tincture of iodine per liter for at

least 60 minutes (overnight if the water is cold) before drinking renders cysts noninfective.

• Although a commercial vaccine for cats and dogs is available, the antigenic variability of G. lamblia and the ill-defined correlates of protective immunity hinder human vaccine development for this infection.

Giardia – Life cycle

Giardia – Electron micrographs

Giardia – Ventral Disc

Giardia - Peru

GiardiasisThe Real Thing

PROTOZOAL INFECTIONS

Site of infection Disease Organisms involved

Trypanosomiasis

African Trypanosoma brucei gambienseTrypanosoma rhodesiense

South American Trypanosoma cruzi

Toxoplasmosis Toxoplasma gondii

Gastrointestinal/mucosal AmoebiasisGiardiasisCryptosporidiosisCyclosporiasis

Trichomoniasis

Entamoeba histolyticaGiardia lambliaCryptosporidium parvumCyclospora cayetanensisTrichomona hominis

CRYPTOSPORIDIOSIS

Cryptosporidium parvum is a coccidian protozoal parasite of humans and domestic animals.

Infection is acquired by the faecal-oral route through contaminated water supplies.

CRYPTOSPORIDIOSISThe incubation period is approximately 7-

10 days, and is followed by

watery diarrhoea and abdominal cramps. The illness is usually self-limiting, but in immunocompromised patients, especially those with AIDS, the illness can be devastating, with persistent severe diarrhoea and substantial weight loss

CYCLOSPORIASISCyclospora cayetanensis is a

newly recognised coccidian protozoal parasite of humans. It has been reported from Nepal, the Indian subcontinent and South America.

CYCLOSPORIASIS

• Infection is acquired by ingestion of contaminated water.

• The incubation period is approximately 2-11 days, and is followed by

• acute onset of diarrhoea with abdominal cramps.

CYCLOSPORIASIS• The disease is more severe in

immunocompromised individuals. Diagnosis is by detection of oöcysts on faecal microscopy.

• Treatment may be necessary in a few cases, and the agent of choice is

• Co-trimoxazole 960 mg 12-hourly for 7 days.

CYCLOSPORIASIS• The disease can remit and relapse.

Although usually self-limiting, the illness may last as long as 6 weeks with significant associated weight loss and malabsorption.

TrichomoniasisTrichomonas vaginalis

Trophozoites

Trichomonas vaginalis – Life Cycle

Trichomonas - Pathogenicity

Contact – dependent cytotoxicity

Trichomonas and HIV