Week 25 Parasitic

infections:
Protozoans

Entamaoeba histolytica
Toxoplasma gondii,
Cryptosporidium parvum,
Giardia lamblia,
Trichomonas vaginalis
 Protozoan and helminthic
diseases introduction

• Organisms are not highly virulent

or can’t replicate in the host
– severity of infection depends on
infecting dose
• Usually organisms are acquired
over time
– chronic infections unlike viruses or
bacteria
 Important factors in
disease
• 1) Exposure/ entry
• 2) Adherence
• 3) Replication
• 3) Cell/ Tissue damage
• 4) Immunopathology
• 5) Disruption/ evasion/
inactivation of host cell
defenses
 Exposure/ entry
• M/C’ ly exogenous:
– enter through ingestion or through
compromised skin integrity or bites
from arthropods
• exception is Toxoplasma
– can enter transplacentally
• Limited range of organs and
tissues they can survive in
– eg. intestinal protozoa can not cause
skin infections only intestinal
infections
• Usually a large inoculum size is
needed
 Adherence

• 1) Non-specific
– mechanical, mouth biting parts
• eg. Giardia:
– ventral disk to clasp onto intestinal
epithelium

• 2) Specific
– adhesins on parasites attach to
surface glycoproteins or NAG or
fibronectin
• eg. E. histolytica:
– surface lectin binds to hoist CHO on
 Replication
• Protozoans
– intra or extracellular replication
• Helminths
– no replication
– Temperature specific reproduction
(species dependent)
• eg. L. donovani: optimal
reproduction at 370C
– affects bone marrow, SP, LV
• L. tropica: optimal reproduction at 250C –
330C
Cell and tissue damage
• Toxins:
– not nearly as toxic as bacterial
toxins
• eg. Proteases, phospholipases
– eg. E. histolytic: proteases to
degrade host cell basement
membrane and phospholipases to
lyse host cell neutrophils
• Helminths:
– damage is due solely to size,
movement and longevity/
persistence
• eg. mechanical blockage of
 Immunopathology
• Can cause all 4 types of
cellular hypersensitivity:
– 1) anaphylactic (IgE mediated)
• eg. Helminths, trypansomes
– 2) cytotoxic (complement,
ADCC)
• eg. T. cruzi
– 3) immune complex
• eg. Malaria, Schistosomiasis
– 4) delayed (T cell mediated)
• eg. Leishmanias, Schistosomiasis
 Disruption/ evasion/
inactivation of host cell
defenses
• Evade host immune system for
disease process to be
maintained
• 1) Modify Ag expression:
– mimicry (Ags similar to host cells) or
masking (acquire host cell molecules to
mask Ag site)
• 2) Intracellular survival:
– eg. live in host cell macrophages
• 3) Immunosuppression:
– various strategies
 Food for thought?
• ??Link between food/ chemical
allergies & parasites and body
temperature
– Viability and migration of parasites is
temperature sensitive: lose allergy
symptoms with fever?
• Lower than normal body temperatures allow
parasites to develop and remain viable
– Low body T (>10C below 98.60F) also associated
with arthritis, depression, epilepsy, asthma,
mental confusion, eczema and other skin
condition (dry, coarse skin, hair loss etc.)
» Ingestion, and fermentation, of offending
foods release gases/ chemicals that trigger
parasite migration/ feeding, compromising
vasculature and therefore, causing signs and
symptoms of allergies
– Alan Hunter, Ph.D., MBRCP; Food and Chemical
Allergies: An original discovery; Townsend Letter
for Doctors and Patients, October 2004, pp. 67-
74
– Raise T by Marmorek (Genestra),
 Treatment of parasitic
infections
• Difficult because:
– 1) Eukaryotes (like fungi)
– 2) Chronic, prolonged
infections
– 3) Multiple developmental
stages
– 4) Multiple infections possible
– 5) Increased risk with
malnutrition and HIV+ co-
infection
– 6) Increased risk with poverty
 Lab diagnosis
• Culture is not important (unlike
bacteria)
• Use microscopy:
– characteristic morphology
• Serology:
– ELIZA, Western blot, Immunofluorescence
• Molecular:
– PCR, nucleic acid probes
• Need to know lifecycles:
– preliminary diagnosis by signs and
symptoms, geography, transmission
• know where and when to sample
• Need to have appropriate sample
 Protozoans
• Amoeba:
• unicellular with 2 stage lifecycle:
– 1) trophozoite:
• motile, feeding stage, replicate by
binary fission, move by pseudopods
– stay in this phase as long as the
environment is optimal
– 2) cyst stage:
• enters this stage when environment
changes (eg. decrease temperature or
moisture) sessile, quiescent, resistant,
infective
• M/C ’ly fecal- oral transmission
• Control by chlorination/ filtration
of water and proper sanitation
Entaemoeba histolytica
trophozoite and cyst
 Entamoeba histolytica
pathogenesis
• Ingestion of cysts:
– ST acid induces change to pathogenic
trophozoite in duodenum
• Release cytotoxin:
– change host cell membrane permeability
to Ca2+
• extensive localized necrosis in colonic
epithelial cells
• Can lead to ulceration, inflammation
and hemorrhage
– and deeper penetration into peritoneal
cavity and then to LV, LU, brain and HT
• Destroyed by ambient O2 levels:
 Epidemiology

• Worldwide but highest in

tropical and sub-tropical areas:
– especially with poor sanitation or
contaminated water

• Can be transmitted by:

– flies, cockroaches, ants etc.,
• sewage contaminated drinking
water
– MSM
 Clinical syndromes
• 1) Asymptomatic carriers:
– infected with low virulent strain
(eg. E. dispar), or low inoculum or
have balanced immune system
• pass cysts in stools
• 2) Intestinal amoebiasis:
– abdominal pain, cramping, colitis
with diarrhea and/ or many bloody
stools
• 3) Extra-intestinal
– systemic signs like fever,
leukocytosis, rigors
Amebic LV abscess
Amebic pneumonia
 Lab dx/ treatment/
prevention
• Cysts in stool, trophozoites in
tissue
– 1) Need multiple stool samples
– 2) Serology or PCR or DNA probes

• Treatment:
– ABCs: metronidazole, iodoquinol

• Prevention:
– Water treatment (SSKI, Citrocidal, oil
of oregano, solid phase filter, boil,
bottled)
 Toxoplasma gondii
• Similar to intestinal protozoans
except
– infect blood/ tissues rather than
enterocytes

• Life cycle:
– cats eat infected rodents
• microbe present in cat feces
– 3 to 4 days later infective cysts
develop
» fecal-oral spread to mice or to
Trophozoite and
Tachyzoites
 Epidemiology
• Transmission is by:
– 1) improperly cooked contaminated
meat/ meat juices
– 2) contaminated soil
– 3) contaminated cat feces
• infective oocysts in cat litter
– 4) transplacental
– 5) increased risk if defective CMI
• eg. HIV, organ transplants, chronic
corticosteroids, chemotherapy
– usually due to activation of a latent
infection not due to new exposure
 Clinical syndromes
• 1) M/C’ ly benign and
asymptomatic
• 2) Symptomatic iff move through
blood to invade tissues (LU, HT,
CNS , eye), lymphoid organs
– a) acute disease:
• chills, fever, H/A, myalgia,
fatigue, lymphadenitis
– heterophile negative mononucleosis
like syndrome
– b) chronic disease:
• lymphadenitis, rash, hepatitis,
myocarditis, encephalomyeletis,
Chorioretinitis
 Congenital disease
• 1) Iff acquired during first
semester:
– spontaneous abortion, stillbirth,
severe disease
• 2) Iff acquired during 2nd or 3rd
trimester:
– epilepsy, encephalitis,
microencephaly, chorioretinitis +/-
blindness, anemia, jaundice,
neurological signs (retardation,
seizures, microencephaly, hearing loss)
 Congenital
toxoplasmosis
 Disease if
immunocompromised
• Neurological:
– diffuse encephalopathy,
meningoencephalitis, SOL
• Major cause of encephalitis
in AIDS:
– M/C’ ly multifocal (> 2 SOLs):
• hemiparesis, seizures, visual
impairment, confusion, lethargy
– Also affect eye, lung, testes
 Lab diagnosis
• 1) Serology:
– indirect ELIZA for rising IgM
titers
• not useful if HIV/ AIDs (anergy)
• 2) Microscopy of biopsy
sample:
– definitive diagnosis from LN,
Brain, Myocardium, CFS,
amniotic fluid, bronchoaveolar
lavage
 Treatment/ prevention
• Treatment:
– 1) Iff normal healthy hosts:
• watchful waiting
– 2) Iff chronic and disseminated infection
in immunocompromised hosts:
• Tx for > 4-6 weeks or 25% relapse rate
• Tx. with pyrimethamine and sulfadiazine,
corticosteroids and other ABCs
• Prevention:
– screen before organ transplants and
early on in HIV
– Pregnant women:
• avoid undercooked meat, wear gloves
when gardening, avoid exposure to cat
 Cryptosporidium parvum
• Intracellular location:
– sporozoites attach just inside brush border of intestinal
epithelium and mature (schizogony)
• Epidemiology:
– Worldwide zoonotic:
• mammals, reptiles, fish
– increased risk with vets and animal handlers
• Transmission:
– Waterborne:
• run-off local waste/ surface water
– resistant to usual water purification
» ozone and usual chlorination
– Oral- anal: MSM
– Fecal- oral: day cares etc.
Cryptosporidum oocytes
 Clinical syndromes
• 1) asymptomatic
• 2) mild, self-limited enterocolitis
– watery, non-bloody diarrhea
• M/C’ ly self-limiting 10 days
• 3) iff immunocompromised (HIV/ AIDS)
– Cryptosporidosis--severe diarrhea:
• > 50 stools per day, tremendous fluid loss
– can be chronic, months to years
– Can possibly become disseminated
 Lab diagnosis
• three consecutive stool samples:
– Un-concentrated (HIV/ AIDS) or
concentrated (centrifuge, etc.)
• Acid fast or indirect
immunofluorescence stain
• Direct ELISA
 Treatment/ prevention/ control
• Treatment:
– No broadly effective therapy
• spiramycin: early on in HIV/AIDS only
– Primarily supportive: water/ electrolytes
• Prevention:
– Concentrated chlorine/ filtration
• Avoid high risk sex and increase personal
hygiene
• Control:
• Difficult
 Flagellated protozoa
• Unlike amoeba:
– move by flagella
• damage is from mechanical irritation and
inflammation
• Giardia lamblia pathogenesis:
– Ingest cysts (only need 10-25 cysts)
• ST acid induces changes to trophozoites
– attach to duodenum and jejunum using ventral
sucking disc
– Very rarely spread beyond the GIT (unlike
Entamoeba)
• cause flattened/ inflammed microvilli
– no tissue necrosis---unlike Entamoeba
 G. lamblia
trophozoite and cyst
 Giardia lamblia epidemiology
• Worldwide sylvatic (wilderness):
– Streams, lakes, mountain streams etc.
• Beavers and muskrats are local reservoirs
• Transmitted by:
– 1) contaminated water:
• resist chlorination (unlike Entamoeba but like
Cryptosporidia) and therefore, need filtration or
boiling
– 2) person to person spread via fecal-oral or oral- anal
practices
• Increased risk with poor sanitation and hygiene,
travel to endemic areas, daycare, oral-anal sex
 Clinical syndromes
• 1) Asymptomatic carriers- 50%
• 2) Symptomatic: range from mild diarrhea
to severe mal-absorption syndromes
– 1-4 week incubation and then sudden onset of:
• foul smelling, watery diarrhea, abdominal cramps,
flatulence and steatorrhea
• M/C’ly spontaneous recovery in 10-14 days
– or chronic disease (multiple relapses):
• especially if IgA deficient or presence of intestinal
diverticula
 Lab diagnosis
• Microscopy or Indirect ELISA or DFA:
– Take multiple stool samples (3 consecutive days)
at onset of symptoms
• Iff negative stool sample but still symptoms:
– duodenal aspiration or Entero-string test or biopsy of
upper SI
• DDX:
– Isospora belli in HIV/ AIDS:
• same loose, foul smelling diarrhea
– can progress to chronic diarrhea with weight loss, anorexia,
fatigue, malaise
• Lab dx:
• concentrate stool sample and use special stain with
Iodine
– iff stain negative but symptomatic use modified acid fast
stain of small bowel biopsy
 Treatment/ prevention
• Treatment:
– quinacrine, metronidazole
• Prevention:
– safe water practices when wilderness
traveling
• boil 10 minutes, filters, treat with
SSKI, citricidal, oil of oregano etc.
– Safe sexual practices
 Trichomonas vaginalis

• Urogenital protozoan:
– Infects urethras and vaginas in women
and urethras and prostate glands in men
• Motile:
– 4 flagella, short undulating membrane
• Lifecycle:
– Monomorphic:
• only has a trophozoite stage
 Clinical syndromes
• 1) Females:
– M/C’ly asymptomatic
• or profuse frothy vaginal
discharge or vaginitis
– extensive
inflammation, erosion,
pruritis, burning,
dysuria

• 2) Males:
– M/C’ly asymptomatic
carriers of infection
• rarely urethritis,
prostatitis or UTIs
Epidemiology/ Tx/ prevention/ control
• Epidemiology:
– Worldwide STD or transmitted by fomites
(contaminated toilet articles/ clothing) or
vaginal birth
• Treatment:
– Metronidazole
• Must treat both partners
– must eliminate carriage in males to eliminate disease
• Prevention/ control:
– Personal hygiene, safe sexual practices, avoid
sharing toilets articles/ clothing
 Lab diagnosis
• Microscopy:
– stained (Giesma) or unstained vaginal/
urethral discharge during PAP smear

• Other:
– culture or monoclonal fluorescent Abs
or nucleic acid probes
• increased vaginal pH
 Quote of the day

• “You have to endure burning to give off

light”

– Victor Frankl
 Quote of the day
• “ I cannot believe that the purpose of life
is to be ‘happy’. I think that the purpose
of life is to be useful, to be responsible, to
be compassionate. It is, above all, to
matter, to count, to stand for something,
to have made some difference that you
have lived at all”

• Leo C. Rosten