Parasitology Basic Science Paul A' Gulig, Ph'D'

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Parasitology - Basic SciencePaul A. Gulig, Ph.D.

• I. Parasitism - A relationship between organisms
  where one (the parasite) gains food and shelter
  from another (the host) which suffers from the
  relationship. This is opposed to mutualism where
  both benefit or commensalism where one gains but
  the other is not harmed.

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II. Types of organisms - A. protozoa -
single celled eukaryotes 1. intestinal and
urogenital 2. blood and tissue B. helminths
(worms) 1. cestodes (tapeworms) 2.
trematodes (flukes) 3. nematodes
(roundworms) C. arthropods 1. Cimex
lectularius (bed bug)
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III. Importance - Table 51-1 A. Billions of
cases worldwide - lots of morbidity B. Malaria
causes over 1 million deaths/year C. There ARE
many parasitic diseases endemic to the U.S.
Table 51-2 D. Even for those that are not
endemic - travelers and immigrants bring them
here.
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Pathogenesis A. Encounter 1. Geographic
distribution - regions of world as well as
regions of U.S. 2. One or more hosts (notice
difference between simple vectors versus
replication within the non-human host) 3.
Arthropod vectors bites 4. Oral (food and
water)
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5. Direct penetration of intact epidermis
(different from bacteria and viruses) 6. Some
are human only 7. Occupational, activity
relationships 8. Considered exogenous
infections (although some are often asymptomatic,
depending on conditions, not considered normal
flora)
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B. Entry (Table 51-3) 1. Oral, epidermis,
bites, sexual 2. Specific adherence by
protozoans just like bacteria 3. Worms -
biting, sucking mouthparts
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C. Spread 1. Some do, some don't 2. Some
travel through body in a complex, orderly
process 3. Tissue specificity often seen
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D. Evade defenses 1. Most of these are
chronic infections therefore evasion of even
specific adaptive immunity is important 2.
Antigenic mimicry, Antigenic cloaking (masking),
Antigenic variation 3. Nonspecific
generalized stimulation of immunoglobulin
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E. Multiplication 1. Often specific to
different hosts, dependent on life cycle form
2. Inappropriate host causes special forms of
disease 3. Not often cultured
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F. Damage 1. Generally no toxins, except
damaging enzymes 2. Parasite burden in tissue
(migration, blockage, pressure) 3.
Immunologic a. Inflammation b. Type 1
Hypersensitivity reactions c. Type 2
Cytotoxicity d. Type 3 Immune complex e.
Type 4 DTH CMI
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F. Damage 4. Bleeding and loss of
blood 5. Cysts, etc. in tissues 6.
Allowing spread of bacteria from gut 7. The
infective dose often directly relates to severity
of disease (e.g., a few worms is no big deal,
many worms can be lethal) 8. Repeated
encounter can be additive
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G. Move to new host (Table 51-3) 1. Direct
human to human 2. Human to animal/vector to
human 3. Human dead end (accidental) host
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Diagnosis A. Most often seeing organism in
patient sample (macroscopic - worms, microscopic
- others) 1. Feces, urine, blood, biopsy,
endoscopic, Entero (string) test 2.
Radiographic observation of damage 3.
Eosinophilia - only seen with tissue-invasive
worms 4. Serology 5. Nucleic acid-based
coming soon
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VI. Treatment A. Because eukaryotic and
highly varied life forms - new sets of drugs B.
Some antibacterials still useful C. Need to
know general classes, few specific examples,
mechanisms of action, toxicities
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1. Anti-protozoals (inhibit replicating
organisms, similar to bacteria) a. Heavy metals
- arsenic and antimony - Leishmania b.
Aminoquinolones (numerous targets) - chloroquine,
quinine - Malaria c. Trimethoprim, sulfa drugs
- Folic Acid - Toxoplasma, Malaria d. Protein
synthesis - Malaria, Babesia, Entamoeba,
Cryptosporidium e. Metronidazole - DNA -
Entamoeba, Giardia, Trichomonas f. Quinolones -
Ciprofloxacin - Malaria
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2. Anti-helminth (disrupt adults) a.
Mebendazole, thiabendazole - microtubule - broad
spectrum b. Pyrantel pamoate - muscle relaxant
- Ascaris, Enterobius, Hookworm c. Piperazine -
muscular paralysis - Ascaris, Enterobius d.
Ivermectin - muscular - Filaria e. Niclosamide
- oxidative phosphorylation - Cestodes f.
Praziquantel - muscle, tegument - Broad spectrum
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SPECIFIC AGENTS AND DISEASES I. Protozoa A.
Urogenital - Trichomonas vaginalis - already
covered by Dr. Poff B. Intestinal protozoa
(Table 53-1) 1. Entamoeba histolytica -
amoebic dysentery, invasive disease 2. Giardia
lamblia non-invasive diarrhea 3. There are
numerous commensal (normal flora) intestinal
amoeba (don't memorize names) 4. Two cellular
forms - trophozoites (replicating) and cysts
(survival outside host)
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C. Entamoeba histolytica (life cycle Fig.
53-1) 1. Amoebic dysentery abdominal pain,
cramps, diarrhea, dysentery, bloody stools,
colitis 2. Liver and systemic infection -
fever, leukocytosis, rigors 3. Encounter
a. worldwide - temperate developing
(5-10 carriers) U.S. (1 - 2 carriers) b.
fecal-oral (hygiene, sanitation), cysts in stool,
trophs in intestine and tissues
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4. Entry - Ingestion of cysts - trophs
in large intestine - specific adhesin 5.
Spread Yes - invasive of gut
epithelium - even to liver and
elsewhere 6. Evasion of defenses a. Killing
of PMNs and macrophages b. IgG/IgA protease
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Trophozoite with ingested RBCs
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6. Damage a. Cytotoxin b. Flask-shaped
ulcers in gut c. Secondary bacterial infection
from invasion d. Liver abscess 7. Move to new
hosts - yes - cysts in feces 8. Treatment
metronidazole 9. Diagnosis a.
microscopy Cysts in stool, biopsy, ingested
RBCs definitive b. serology in U.S.
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D. Giardia lamblia - flagellate (life cycle Fig.
53-2) 1. asymptomatic to mild diarrhea to
severe diarrhea (cramps, gas, smell,
steatorrhea), 10-14 days or longer 2.
Encounter a. worldwide including U.S. i.
sylvatic from animals ii. human-human
fecal-oral, hygiene, sanitation, sexual b.
cysts in water
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3. Entry a. stomach acid cyst to
trophozoite b. attach to small intestine with
sucking disk 4. Spread - none
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Trophozoite
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5. Damage - malabsortion diarrhea 6. Move to
new hosts - yes - fecal-oral, sexual 7.
Treatment Metronidazole 8. Diagnosis - Cysts
or trophs in stool, string test
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E. Blood and tissue protozoa (Table 52-1) 1.
Plasmodium species - we will concentrate on the
most common (P. vivax) and most lethal
(P. falciparum) a. malaria - complex life
cycles with sexual and asexual cycles in
different hosts b. over 1 million deaths/year
- mainly Africa (life cycle Fig. 52-1) c.
Incubation period - 8-30 days, depending on
species d. influenza-like symptoms paroxysms
(fever, chills, rigors) every 36 to 48 hours,
depending on species e. sickle cell trait and
P. falicparum
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f. Encounter i. Not endemic to U.S. (imported
cases, but few mosquito reported) - tropics,
subtropics ii. mosquito bite (Anopheles) with
sporozoites (U.S. does have Anopheles) prevent
encounter with mosquito g. Entry and Spread -
circulatory system to liver
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h. Multiplication - liver (exoerythrocytic) -
schizogony (asexual) i. release merozoites
into blood that infect RBCs (erythrocytic cycle -
more asexual) ii. differentiation into
gametocytes - blood meal for mosquitoes (sexual
cycle) iii. P. vivax only invades young,
immature RBCs iv. P. falciparum no specificity
for RBCs (more infected cells, more severe
disease)
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i. Evasion of defenses i. intracellular
shielding ii. antigenic variation of major
surface protein (MSP-1)
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j. Damage i. both - lysed hepatocytes, RBCs,
plugged capillaries ii. P. falciparum - RBCs
adhere to capillaries including brain, RBC lysis,
kidney (blackwater fever) more deaths
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k. Diagnosis - microscopic examination of blood
smears (Fig. 52-3) i. P. falciparum
numerous rings/RBC and high number of infected
RBCs, no Schüffner dots ii. P. vivax single
ring/RBC and lower number of infected RBC, has
Schüffner dots l. Treatment - chloroquine and
primaquine, among others
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2. Trypanosoma cruzi (life cycle Fig. 52-8) -
Chaga's Disease a. Disease - i.
asymptomatic - mostly ii. acute - rash, edema
on face (site of bite), flu-like symptoms most
common when symptoms occur, but acute can cause
death iii. chronic rare but serious ?
g.i. tract nerve damage leading to megacolon
? heart - conductive problems and
cardiomyopathy, sudden death
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b. Encounter- South, Central, North America,
rare in U.S. (southern states) i. "kissing
bug" reduviid bug vector (epimastigote
replicative form) c. Entry, Spread,
Multiplication i. bug defecates on wound
releasing trypomastigotes that get rubbed into
wound and vasculature ii. convert to
amastigotes that invade and replicate in host
cells
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d. Damage unclear mechanism i. fibrosis
(autoimmunity?) ii. nerve damage e.
Diagnosis clinical, serology, blood smear
microscopy f. Treatment - not very good,
especially for late complications g.
Prevention clear houses of bugs, use netting
for sleeping
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II. Helminths worms see Tables 54-1, 54-2,
55-1 for summary
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A. Nematodes (roundworms) (Fig. 54-1) 1.
Enterobius vermicularis (small pinworm - 1 mm)
(life cycle Fig. 54-3) a. asymptomatic to
perianal itching, pruritis b. Encounter - in
U.S. - ingestion of egg c. Entry - larvae
from small intestine to large intestine d.
Spread - none - intraluminal only
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e. Multiplication - adults in large intestine,
female migrates to anus to lay eggs at
night f. Move to new hosts - yes - stable
eggs in environment, scratching, autoinfection
prevent by cleanliness g. Diagnosis -
scotch tape test eggs from perianal region in
morning h. Treatment - pyrantel pamoate,
mebendazole
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2. Hookworms - Ancylostoma duodenale and Necator
americanus (Life cycle Fig. 54-4) - 700,000
infected in U.S. a. Symptoms i. allergic
reaction in feet upon entry through skin
(temporary ground itch) ii. pneumonitis during
migration through lungs iii. g.i. - nausea,
vomiting, diarrhea iv. anemia due to feeding of
adult worms in intestines
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b. Encounter and Entry i. Filariform larvae
in soil from human feces ii. Need warm, moist
soil - southern U.S. iii. Penetrate intact
skin (unusual fecal-cutaneous route) c. Spread
and Multiplication i. Circulation ii.
Lungs iii. Coughed, swallowed iv. Adults
intestines v. Feed off blood vi. Eggs in feces
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d. Damage i. skin penetration ii. lung
migration iii. blood loss e. Move to new human
host yes f. Diagnosis - Observe
characteristic eggs in stool g. Treatment -
mebendazole pyrantel pamoate h. Prevention -
hygiene, sanitation, shoes
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2. Strongyloides stercoralis (life cycle Fig.
54-4) a. Strongyloidiasis - asymptomatic to
pneumonitis (migrating larvae) heavy loads -
bowel inflammation and ulceration, diarrhea,
vomiting, sepsis
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b. Encounter and Entry - in warm regions of
U.S. (but also North) i. mainly human, but
some animals possible including pets ii.
fecal contamination iii. penetration of
intact skin by filariform larvae in soil
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c. Spread and Multiplication i. filariform
larvae invade from skin to blood to lungs to
stomach to intestines ii. mature to adults
in intestines release eggs hatch to rhabditiform
larvae (not invasive) iii. rhabditiform
larvae in soil mature to either free-living
adults (different from hookworms) or filariform
(infective) larvae
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d. Damage i. migrating larvae in lungs adults
in intestines ii. autoinfection - rhabditiform
in intestines mature to filariform (rare) -
bacterial infection because of gut invasion
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iii. hyperinfection - gt80 mortality - drugs,
immune suppression - rhabditiform larvae change
to filariform in host (large scale) - screen
transplant or immune suppressed patients - lung
symptoms common, but can go anywhere -
bacterial infection because of gut invasion
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e. Move to new human hosts - yes - rhabditiform
larvae, eggs in feces f. Diagnosis - observe
rhabditiform larvae in stool, eggs rare,
eosinophilia g. Treatment - thiabendazole
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3. Ascaris lumbricoides (large roundworms -
20-35 cm) (life cycle Fig. 54-2) a. ascaris
infection - over 1 billion worldwide! b. few
worms - no symptoms heavy burden -
respiratory, blockage c. Encounter - human
only, ingestion of egg poor sanitation warm
climate
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d. Entry - Oral, filariform larvae in small
intestine e. Spread - yes i. larvae
penetrate intestinal wall ii. into blood
iii. eventually to lung iv. coughed up
v. swallowed
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f. Multiplication - adults - small intestine -
eggs g. Damage i. pneumonitis if many worms
in lungs peritonitis (bacteria) ii. occlusion
of intestines iii. danger of induced migration
by other treatments
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h. Spread to new hosts - yes - fecal oral i.
Diagnosis - eosinophilia eggs in stool j.
Treatment - mebendazole
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6. Ancylostoma braziliense (dog/cat
hookworm) Life cycle Fig. 54-4, see Table
55-1) a. Cutaneous Larva Migrans, creeping
eruption, ground itch
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b. Encounter, Entry, Spread,
Multiplication i. found in warm regions of
U.S. (here) ii. contamination of soil with
animal feces containing filariform larvae iii.
larvae penetrate skin and migrate iv. cannot
differentiate
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c. Damage - create tracks of migration for
weeks to months d. Diagnosis - clinical,
eosinophilia e. Treatment thiabendazole f.
Prevention - pet owner education - cover the
sandbox
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7. Toxocara canis and T. cati (See Table
55-1) Dog and cat ascarid worms - inappropriate
human infection a. visceral larva migrans b.
Encounter - dog and cat definitive hosts,
ingestion of eggs from feces c. Entry
oral d. Spread - yes - larva migrate through
tissues but do not develop further
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e. Mulitplication - No - wrong host f.
Damage - migration of larvae through tissues,
inflammatory response g. Diagnosis i.
eosinophilia ii. epidemiology
(dogs/cats) iii. symptoms (depends on worm
burden) iv. serology
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h. Treatment - anti-worm, corticosteroids i.
Prevention - keep animal feces out of mouth!
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B. Cestodes (tapeworms) (Life cycle 54-5) 1.
General characteristics a. body segments head
scolex, others proglottids b. no intestines
- absorb nutrients c. hermaphroditic (don't
need male and female in same host) d. complex
life cycles - pay attention to forms encountered
by different hosts e. usually asymptomatic,
except passage of proglottids in stool, possible
nausea
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2. Taenia solium (pork) - rare in U.S. Taenia
saginata (beef) - common in U.S. Diphylobothrium
latum (fish) common a. Encounter - ingest
meat with larvae of worm (cysticercus) b. Entry
- Oral - larvae mature to adult in intestine c.
Spread No
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d. Multiply i. proglotids can mutliply to
form chains several meters long ii. break off
and are excreted in feces
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e. Damage - consumption of nutrients in
intestines (vitamin B12 for D.l., some intestinal
irritation f. Move to new host i. Taenia -
eggs ingested by pigs/cows, migrate into tissue
and form larvae ii. D.l. more complicated -
intermediate in copepod eaten by fish to form
larvae
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g. Diagnosis - eggs in stool h. Treatment
niclosamide i. Prevention - sanitation
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1. Cysticerosis inappropriate infection by
pork tapeworm only (life cycle Fig. 54-5, 55-4,
see Table 55-1) a. asymptomatic to mental
problems, depending on burden and site
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b. Encounter and Entry i. ingestion of egg
of Taenia solium (pork tapeworm) in human feces
prevalent in Mexico ii. eggs hatch in stomach
releasing onchosphere iii. autoinfection by
ingestion of eggs released by tapeworm infection
or regurgitation of eggs into stomach from
intestines iv. compare with ingestion of
larval stage (cysticerci) in pork
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c. Spread - onchosphere penetrates intestines
and migrates in blood to tissues d.
Multiplication - none in human by this route
(compare with tapeworm infection) - humans are
dead-end host (unless someone gets eaten by
someone or something!)
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e. Damage - onchosphere develops into
cysticercus, which cannot develop further -
calcification and inflammation in brain, muscle,
eye, heart, lung f. Diagnsosis eosinophilia,
radiology g. Treatment - praziquantel,
steroids, surgery
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C. Flukes - Schistosomes - (life cycle 55-7) 1.
schistosomiasis 200 million infections, 3
species 2. Encounter and Entry (Fig.
55-6) a. throughout world, but not in
U.S. i. S. mansoni - South America, Africa,
Middle East ii. S. japonicum - East
Asia iii. S. haematobium - Africa, Middle
East
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b. invasion of skin by cercarial forms (some
skin symptoms - rash) 3. Spread a. into
blood - portal vein b. mating pairs migrate
to terminal tissue i. S. mansoni and S.
japonicum - mesenteric veins ii. S.
haematobium - urinary bladder
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4. Multiplication - eggs released a.
nonspecific complaints during egg shedding
(fever, chills, malaise, inflammation) b. S.m.
and S.j. eggs into intestines, liver c. S.h.
eggs into bladder 5. Evasion of defenses -
antigenic cloaking by binding host proteins
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6. Damage a. inflammatory and fibrotic
response to eggs in tissues b. penetration
damage c. S. mansoni and S. haematobium -
intestinal and liver symptoms d. S. haematobium
- urinary symptoms, bladder cancer correlation
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7. Spread to new host - indirectly a. shed
eggs develop into miracidia that infect
snails b. snails release infectious cercaria
8. Diagnosis a. eggs in stool or urine b.
eosinophilia 9. Treatment - praziquantel,
anti-inflammatories 10. Prevention - sanitation
(see Table 55-2)
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