Transcript Intestinal Protozoa Mark F. Wiser Department of Tropical Medicine Flagellates: • Giardia lamblia • Dientamoeba fragilis • Chilomastix mesnili • Trichomonas hominis • Enteromonas hominis • Retortamonas intestinalis Ameba: •

Intestinal Protozoa
Mark F. Wiser
Department of Tropical Medicine
Flagellates:
• Giardia lamblia
• Dientamoeba fragilis
• Chilomastix mesnili
• Trichomonas hominis
• Enteromonas hominis
• Retortamonas intestinalis
Ameba:
• Entamoeba histolytica
• Entamoeba dispar
• Entamoeba coli
• Entamoeba hartmanni
• Endolimax nana
• Iodamoeba bütschlii
Apicomplexa:
• Cryptosporidium hominis
• Cryptosporidium parvum
• Cyclospora cayetanensis
• Isospora belli
Other:
• Blastocystis hominis
• Balantidium coli
INTESTINAL PROTOZOA
unicellular eukaryotic organisms
Fecal-Oral Transmission Factors
• poor personal hygiene
• food handlers
Control/Prevention
• institutions
• improve personal hygiene
• children in day care centers • especially institutions
• developing countries
• treat asymptomatic carriers
• highly endemic
• eg, family members
• poor sanitation
• health education
• travelers diarrhea
• hand-washing
• water-borne epidemics
• sanitation
• food handling
• male homosexuality
• protect water supply
• oral-anal contact
• treat water if questionable
• zoonosis
• boiling
• Entamoeba = no
• iodine
• Cryptosporidium = yes
• not chlorine
• Giardia = controversial
Giardia lamblia
• worldwide distribution
• higher prevalence in
developing countries (20%)
• 1-6% in temperate countries
• most common protozoa
found in stools
CYST
•infective stage
•passed in feces
• ~200 million clinical
cases/year
• giardiasis
• often asymptomatic
• acute or chronic diarrhea
• fecal-oral life cycle
TROPHOZOITE
•replicative stage
•small intestine
Adhesive Disk and Attachment
Clinical Features and Symptoms
Range of Outcomes
• asymptomatic/latent
• acute short-lasting diarrhea
• chronic/nutritional disorders
Acute Symptoms
Subacute/Chronic
• recurrent diarrheal
episodes
• cramps uncommon
• sulfuric belching, anorexia, nausea frequent
• can lead to weight loss
and failure to thrive
• 1-2 week incubation
• sudden explosive, watery diarrhea
• bulky, frothy, greasy, foul-smelling stools
• no blood or mucus
• upper gastro-intestinal uneasiness, bloating, flatulence,
belching, cramps, nausea, vomiting, anorexia
• usually clears spontaneously (undiagnosed), but can
persist or become chronic
Pathogenesis
• epithelial damage
• villus blunting
• crypt cell hypertrophy
• cellular infiltration
• malabsorbtion
• enzyme deficiencies
• lactase (lactose
intolerance)
Possible Mechanisms
• mechanical irritation
• obstruction of absorption
Entamoeba histolytica
• cosmopolitan distribution
• worldwide incidence: 0.2-50%
• no animal reservoirs
cyst
• typical fecal-oral life cycle
• inhabits large intestine
• facultative virulent pathogen
• estimated 50 million cases/year
• 100,000 deaths/year
Entamoeba dispar
• morphologically identical
• non-pathogenic
trophozoite
Pathogenesis of Amebiasis
• NON-INVASIVE
• ameba colony on intestinal mucosa
• asymptomatic cyst passer
• non-dysenteric diarrhea, abdominal
cramps, other GI symptoms
• INVASIVE
• necrosis of mucosa  ulcers, dysentery
• ulcer enlargement  dysentery, peritonitis
• metastasis  extraintestinal amebiasis
• cessation of cyst production
• ulcers with raised borders
• little inflammation between lesions
• ‘flasked-shaped ulcer’
• trophozoites at boundary of necrotic
and healthy tissue
• trophozoites ingesting host cells
• dysentery (blood and mucus in feces)
Ulcer Enlargement and
Disease Progression
• ameba expand laterally and
downward into lamina propria
• localized sloughing (ulcers coalesce)
• perforation of intestinal wall
• peritonitis
• 2o bacterial infections
• local abscesses
• ameboma (=amebic granuloma)
ameboma = inflammatory thickening of
intestinal wall around the abscess (can be
confused with tumor)
Extraintestinal Amebiasis
• metastasis via blood stream
• primarily liver (portal vein)
• other sites less frequent
• ameba-free stools common
• high antibody titers
Amebic Liver Abscess
• chocolate-colored ‘pus’
• necrotic material
• usually bacteria free
• lesions expand and
coalesce
• further metastasis, direct
extension or fistula
Pulmonary Amebiasis
• rarely primary
• rupture of liver abscess
through diaphragm
• 2o bacterial infections
common
• fever, cough, dyspnea,
pain, vomica
Cutaneous Amebiasis
• intestinal or hepatic fistula
• mucosa bathed in fluids
containing trophozoites
• perianal ulcers
• urogenital (eg, labia,
vagina, penis)
Facultative Pathogenicity
• 85-90% of infected individuals
are asymptomatic
• ~10% of the symptomatic will
develop severe invasive disease
Molecular Epidemiology
• molecular probes used to survey for
E. dispar and E. histolytica
• E. dispar ~10-fold > E. histolytica
• discrete endemic pockets of E. histolytica
• many asymptomatic E.h. infections
• ~10% of the E.h. infections are
associated with invasive amebiasis
• ~25% seropositive for E. histolytica in
endemic areas
pathogenecity
ability to cause disease
(genetic component)
virulence
relative capacity to cause
disease (degree of pathology)
• a pathogen has an inherent ability to
break host cell barriers
• virulence usually correlates with ability
to replicate within host
• various degrees of virulence may be
exhibited depending on conditions
• penetration of mucus layer
• contact-dependent killing of epithelial cells
• breakdown of tissues (extracellular matrix)
• contact-dependent killing of neutrophils,
leukocytes, etc.
Cryptosporidium
• fecal-oral transmission (coccidian type
life cycle)
• two species infecting humans
• C. parvum: cattle and other mammals
• C. hominis: only humans
• first human case reported in 1976
• initially believed to be rare and exotic
• now known to be common human
pathogen
• self-limiting diarrhea in
immunocompetent persons
• profuse, watery diarrhea associated
with AIDS (life threatening)
Cryptosporidium
Life Cycle
• Infectious form = oocyst
• Sporozoites ‘invade’
intestinal epithelial cells
• Merogony
• produce merozoites
• Gametogony
• produce micro- and
macrogametes
• Sporogony
• produce sporozoites
• completed on host cell
• thin (autoinfection) or
thick walled oocysts
Molecular Epidemiology
• 2 major genotypes identified:
• genotype 1 (C. hominis)
• only human sources
• non-infective for mice or calves
• anthroponotic transmission
• genotype 2 (C. parvum)
• human and bovine sources
• infective for mice and calves
• zoonotic transmission
• other genotypes (eg, C. felis,
dog type, etc) rare
• isolated only from AIDS patients
Water Borne Outbreaks of
Cryptosporidiosis in the USA
Year Location
1984
1987
1988
1991
1992
1992
1993
Braun Station, TX
Carrolton, GA
Los Angeles, CA
Pennsylvania
Jackson County, CO
Lane County, OR
Madison, WI
% Inf. suspected cause(s)
0.2
1.3
0.06
1.5
-
sewage contaminated well
water-treatment deficiencies
inoperative swimming pool filters
water-treatment deficiencies
water-treatment deficiencies
oocysts in filter washback water
fecal accident in swimming pool
spring thaw, water-treatment
1993 Milwaukee, WI
40.3
deficiencies
1994 Clark County, NV
0.008 fecal accident in swimming pool
Modified from Graczyk et al, Parasitol. Today 13:348 (1997)
Human Cryptosporidiosis
• epidemic diarrhea in institutions and hospitals
• highly transmissible (19% household members)
The Milwaukee Outbreak
NEJM 331:161 (1994)
• massive cryptosporidiosis outbreak
following spring thaw
• >400,000 people may have been affected
• based on clinical symptoms (acute watery
diarrhea)
• ~100-fold higher prevalence of Cryptosporidium
oocysts in stools than normal
• other enterics (including Giardia, bacteria,
viruses) were at ~normal levels
• treated water had high levels of turbidity
3/23-4/5/1993
• oocysts identified in ice made during this period
Symptoms of 205 patients with
Confirmed Cases of Cryptosporidiosis
During the Milwaukee Outbreak
SYMPTOMS
Watery Diarrhea
mean=12d; med=9d (1-55d)
mean=19/d; med=12/d (1-90)
39% recurred after days free
Abdominal Cramps
Weight Loss
med=10lb (1-40lb)
Fever
med=38.3 (37.2-40.5)
Vomiting
%
93
84
75
57
48
Pathogenesis
DIARRHEA
• enterocyte malfunction
(osmotic)
• impaired absorption
• enhanced secretion
• inflammatory diarrhea
• mucosal invasion
• leukocytes in stools
• secretory diarrhea
• toxin associated
• watery
• enterocytes damaged
or killed
• villus atrophy (blunting)
•  Na+ absorption
•  intercellular
permeability
• crypt cell hyperplasia
•  Cl- secretion
• inflammation in lamina
propria
• cytokines and
neurohormones?
• enhanced secretion of
antibodies (IgA)?
Diagnosis of Intestinal Protozoa
• suspect: acute or chronic GI symptoms
• confirmed: detection of parasite in feces
• copro-antigens or molecular probes
• Cryptosporidium
• acid-fast stain
• Giardia
• 3 non-consecutive days (inconsistent excretion)
• duoenal aspirates or biopsy
• presumptive treatment in chronic cases
• Entamoeba
• histolytica vs dispar
• sigmoidoscopy (lesions, aspirates, biopsy)
• extra-intestinal disease
Diagnosis of Extraintestinal Disease
• symptoms associated with
specific organ
• history of dysentery
• hepatic
• right upper quadrant pain
• enlarged liver
• serology (current or past?)
• imaging (CT, MRI,
ultrasound)
• abscess aspiration
• only select cases
• reddish brown liquid
• trophozoites at abscess wall
Treatment
Giardia
Drug of Choice
• metronidazole
(Flagyl)
• 750 mg/tid/5d
• >90% cure rate
Alternatives
• tinidazole
(single dose)
• paromomycin
(pregnancy)
• quinicrine
• furazolidone
Entamoeba
asymptomatic
• iodoquinol or
paromomycin
symptomatic
• metronidazole or
tinidazole
• followed by
lumenal agents
drain liver abscess
• only with high
probability of
rupture!
Cryptosporidium
• no highly effective
drugs
• paromomycin has
modest benefit
• supportive care
• rehydration
• nutritional
support
• anti-motility
agents