L10 Flashcards
(163 cards)
1
Q
Parasitic infections are among the most prevalent diseases in
A
developing countries
• Also common in developed countries
• Typically cause no clinical infections
2
Q
Parasitic infection is distinct from
A
parasitic disease
3
Q
Toxoplasma gondii and hookworm infections are prevalent, but few
A
immunocompetent individuals develop disease
4
Q
Parasitic Disease - Consequence of
A
prolonged, repeated, or high burden infection
5
Q
Parasitic Disease - Usually
A
subacute or chronic
• Rarely fatal • Exceptions:
• Plasmodium falciparum (malaria) – may be rapidly fatal (3-5 days)
• Infections in immunocompromised individuals

6
Q
Many parasitic infections are
A
zoonoses • Caused by agents that infect animals
7
Q
Many human parasites require
A
human and nonhuman hosts to complete their life cycles • Humans are dead-end hosts for some parasites
• Infection occurs but no parasite developmental stage - life cycle not completed
8
Q
• Two parasite types:
A
protozoa and helminths
9
Q
Protozoa - single
A
celled orgs
10
Q
Protozoa - Intracellular (red blood cells, macrophages)
•
A
Unable to withstand environmental dessication (drying)
• Life cycles do not include free environmental stage
11
Q
Protozoa - Extracellular (lumen of GI tract)
•
A
Often transmitted by fecal-oral route
• Life cycles alternate between two forms
• Active trophozoite
• Dormant cyst – withstands environmental desiccation
12
Q
Protozoa - Disease is consequence of
A
parasite replication to high numbers (small inoculum required to initiate infection)
13
Q
• About 65,000 species of
A
protozoa
14
Q
Most protozoa are
A
Most are harmless, free-living inhabitants
of water and soil
• Few are parasites
15
Q
Mastigophora - • Motility primarily by
A
flagella
16
Q
Mastigophora - • Single
A
nucleus
17
Q
Mastigophora - • Sexual reproduction by
A
syngamy
18
Q
Mastigophora - • Division by
A
longitudinal fission
19
Q
Mastigophora - Parasitic forms tend to lack
A
mitochondria and Golgi
apparatus
20
Q
Mastigophora - Most form
A
cysts and are free-living
• Most are solitary
21
Q
Apicomplexa (Sporozoa) - • Most not motile except
A
male gametes
22
Q
Apicomplexa (Sporozoa) - have Complex
A
life cycles
23
Q
Apicomplexa (Sporozoa) - Produce
A
sporozoites following sexual reproduction
24
Q
Apicomplexa (Sporozoa) - • Important in transmission of
A
infections
25
Apicomplexa (Sporozoa) - Most form
oocysts
26
Apicomplexa (Sporozoa) - Entire group is
parasitic
27
Helminths (worms) - are
* Multicellular animals (metazoa)
| * Roundworms, flatworms
28
Helminths (worms) - • Extracellular due to
large size
29
Helminths (worms) - • Protected by
cuticle
30
Helminths (worms) - Larvae can develop into
dormant
| cysts
31
Helminths (worms) - Environmental and animal
reservoirs
| • Do not typically complete life cycle in human
32
Helminths (worms) - Developmental stages take place
outside of human
(definitive hosts) in insect vectors or animal reservoirs (intermediate hosts)
Reproduce sexually
33
Helminths (worms) - • A few species (tapeworms) are
hermaphroditic
34
Helminths (worms) - Most helmiths cause
chronic infections that are tolerated by the human host
35
Helminths (worms) - Disease is not a consequence of
parasitic replication
36
Helminths (worms) - Parasitic burden due to
number of parasites that host initially acquires from environment
37
Helminths: Established infections not
eliminated by host response
• Spontaneously resolve when adult worms reach senescence
38
Parasitic Helminths: large
Tapeworms, flukes, and roundworms
• Adults large enough to be seen with the
naked eye
• From1mmto25minlength
Microscope is necessary to identify eggs and larvae
39
Parasitic Helminths: • Two major groups:
Flatworms and Roundworms
40
Flatworms - • Phylum
Platyhelminthes
41
Flatworms -
Thin
| • Often segmented
42
Flatworms: Subdivisions
Cestodes (tapeworms)
| • Trematodes (flukes)
43
Roundworms - • Phylum
Aschelminthes
44
Roundworms - • Also known as
Nematodes
45
Roundworms -
Elongate
• Cylindrical
• Unsegmented
46
Epidemiology and Public Health
* Transmission
* Multiplication
* Damage/disease
* Treatment and Prevention
47
Parasite Vectors: Most are
arthropods
| Involved in essential steps of parasitic life cycle
48
Female Anopheles mosquito –
malaria •
49
Tsetse flies –
sleeping sickness
50
• Black flies –
river blindness
51
• “Kissing” bugs –
Chagas’ disease
52
• Ticks –
babesiosis
53
Parasitic prevalence dependent on
local conditions favoring arthropod breeding
Stagnant water, foliage
• Suitable animal hosts
54
Reservoirs –
sources of parasites that do not participate directly in transmission
55
Parasite reservoirs: Humans
• Malaria parasites, amoebae
56
Parasite reservoirs: Animals
* Pigs - trichinosis, pork tapeworm
| * Cattle – beef tapeworm, cryptosporidiosis
57
Parasite Entry - Penetration of the - 2
skin (unbroken)
| • Hookworm, schistosomes
58
Parasite Entry = Arthropod-borne
* Bite wounds
* Very efficient – malaria
* Can be transmitted by blood transfusions
59
Parasite Entry - Oral /ingestion 1.
Oral/ingestion
• Contaminated food or water
• Inadequate control of human wastes
• Ascariasis, amebiasis
60
Dependent on parasitic life cycle and
presence or absence of intermediate hosts for trasnmission
61
Schistosomiasis –
snails required to allow parasite to mature
• Snails not present in North
America or Europe
62
Malaria
• Anopheles mosquitoes are present in US and indigenous mosquito pool can be infected
63
• Disease manifestation dependent on
size of inoculum that varies for different parasites
64
Amebiasis –
large inocula
65
Cryptosporidiosis –
few cysts
66
Helminths – directly proportional to initial
inoculum from environment
67
Circumvent host
antibody and cell-mediated immune
responses for survival
* Host plasma protein coatings (blood flukes)Surface antigen variation (trypanosomes)
* Superoxide dismutase secretion (Leishmania) • Protection from host phagolysosome
68
• Life cycles determined by
species and tissue tropisms
69
• Strongyloides – attacks
intestinal wall
70
• Hookworms – attack
intestinal lumen
71
• A particular duffy factor antigen on red blood cell surface is required for
entry of P. vivax malaria parasites
72
Leishmania donovani –
replicates at 37 oC
73
* Visceral leishmaniasis (bone marrow, liver, spleen)
| * Leishmania tropica – replicates at also induce stage-specific transitions
25-30 oC
• Skin infections
• Temperature changes
74
Deep tissue infections -->
chronic inflammation
75
Cysticercosis – dead parasites leak
antigens that
| trigger hypersensitivity in host
76
• Both avenues of symptomology can be
concurrent
77
Most clinical complications occur
years after initial infection
78
Damage from parasitesClinical manifestations may be due to: •
Direct tissue damage by parasite
| • Cytolysis colonic ulcers, liver abscesses • Pathogenic amoeba
79
• Effects of host immune response -
Schistosomiasis, cutaneous filariasis
80
Schistosomiasis
GI or urinary tract bleeding for years
• Heavy, chronic infections can lead to hypertension,
obstructions and cancer
81
• Pork tapeworm (Taenia solium)
```
Adult parasite asymptomatic in intestine
• Larvae may enter blood and infect deep tissues as
cysts
• Asymptomatic in skeletal muscle
• Seizures or hydrocephalus in CNS
```
82
Chagas’ disease (American trypanosomiasis)
Trivial skin lesion asymptomatic or mildly
symptomatic
• Acute infections swollen eyelid (Romaña’s Sign),
lymph node swelling (young children and immunocompromised susceptible to more severe illness and death)
• Indeterminate, symptom-less stage that can last
months to years
• Named after Cecilio Romaña, Argentinian who
described the phenomenon
• Chronic infectionslesions on various organs
(e.g., heart, esophagus, colon or peripheral nervous system); the damage done to organs during this phase is irreversible and tends to weaken the body, sometimes fatally
83
Eradication is successful only when more
| than one of the following are employed:
1. Chemoprophylaxis – preventative drugs
• Chloroquine effective against all 4 species of Plasmodium (but, some becoming resistant)
• Ivermectin for onchocerciasis (river blindness) 2. Immunization
3. Field control measures
• Insecticides (e.g., DDT) sprayed on mosquitoes that rest under eaves after biting
• Sanitation - Potable water
84
• Many parasites masquerade as ‘self’ by coating themselves in
host antigens
85
Some parasites (trypanosomes) continually alter
surface antigens
86
Different proteins/polysaccharides displayed on surfaces at different life stages
Need polyvalent vaccine that contains major
| antigens from all each stage of life cycle
87
Malaria - most important of all protozoan diseases •
“The greatest harm to the greatest number”
Approximately 156 named species of Plasmodium protozoa that infect various species of vertebrates
• Four are known to infect humans and vary in virulence due to red blood cell age preference:
• P. falciparum – all ages of rbcs (greatest mortality)
• P. vivax/P. ovale – reticulocytes and young rbcs
• P. malariae – older rbcs
88
Infected humans are the only reservoir for
Plasmodium that infect humans
89
Malaria: Transmission occurs
9-17 days
| after bite of infected female Anopheles mosquitoes • Symptoms develop 8-30 days later
90
Imported malaria
• Endemic area infection - travelers import parasite to
| nonendemic areas during incubation
91
Induced malaria
| •
Transmission via blood transfusions or needles
92
• Sporozoites inhabit
mosquito salivary glands
93
After mosquito bite, sporozoites travel through bloodstream and enter
liver cells within 30 minutes
• Hepatocellular cycle
• Multiply and mature
• 2 weeksmonths (sometimes years)
94
Release to blood as merozoites
Invade red blood cells, divide and mature (erythrocytic cycle) into trophozoite • Nuclei and organelles
replicate (schizont) • 2-3 days: red blood
cells burst and liberate more merozoites
95
Parasites multiply asexually (
binary fission) in liver and red blood cells
96
Some plasmodia in blood may develop into
gametocytes capable of sexual reproduction in mosquitoes.
97
• Parasite replication can be
synchronous
98
Typical paroxysm
Simultaneous lysis of many RBCs and release of large number of merozoites and other parasitic molecules every 48 -72 hours
• GPI (glycophosphatidylinositol)
• Stimulates tumor necrosis factor (TNF) and IL-1 from macrophages
• Fever, edema, anemia, shock
99
Glycophorin A/Duffy blood group antigen on RBC surface
Black Africans – often Duffy negative
100
• Sickle cell anemia
```
Defective sickle cell hemoglobin
• Red blood cells shaped like a "C"
• Genetic mutation of a single nucleotide
of the β-globin gene
• Glutamate valine
```
101
• Heterozygous individuals (carriers)
Disease less acute
• Malaria parasite causes RBCs to rupture
prematurely, making the plasmodium unable to reproduce
102
Chloroquine - Target parasite’s food vacuole where
hemoglobin is degraded
Toxic heme detoxified
• Chloroquine blocks detoxification and kills parasite
103
• Chloroquine was once the most widely used
drug for chemoprophylaxis and treatment
Now, P. falciparum resistant strains widespread
• Mutation of vacuolar membrane protein that pumps drug out of food vacuole
104
Chloroquine Not effective against
P. vivax/P. ovale liver stages (must employ primaquine)
• P. falciparum/P. malariae do not produce dormant liver
stages
105
Babesia - Destroy
red blood cells
| • Easily confused with P. falciparum
106
Babesia - Babesiosis is endemic in
US
| • Illness nonspecific/difficult to recognize
107
Babesia - B. microti concentrated in same areas as
endemic Lyme disease
Animal reservoir same – white footed mouse
• Transmitted by deer tick (Ixodes scapularis)
108
Babesia Life Cycle - Merozoites injected under skin by
tick
| RBCs invaded
109
Babesia Life Cycle - NO intermediate
liver stage
110
Babesia Life Cycle - Replication via
binary fission
111
Babesia Life Cycle - Lyse
RBCs
• Ticks feed on
infected RBCs to keep cycle
112
Toxoplasma
Infection common in humans, but disease rare
| • Disease can be severe for immunocompromised patients and developing fetuses
113
Toxoplasma three symptoms
```
Three syndromes:
Mononucleosis-like
• Congenital infection
• Brain/heart (immunocompromised)
• Association with schizophrenia?
```
114
Toxoplasma: Survive in
macrophages
| • Prevent acidification and phagolysosome fusion
115
Toxoplasma: Consumption of inadequate
cooked meat (tissue cysts) or food contaminated with cat feces (oocysts)
• Cats harbor sexual cycle
(similar to mosquitoes in malaria)
116
Cysts penetrate
ntestinal wall, enter bloodstream and disseminate
117
Pregnant women are warned not to come into contact with
Toxoplama
-Toxoplasma can cause miscarriage
118
Toxoplasma in cat feces is eaten by
rats, and affects the amygdala of rats. This changes rat behavior.
Infected rats are attracted to cats, and get eaten
119
Infected humans may also affect human behavior. There is some evidence that Toxoplasma infection is linked to
schizophrenia
Surge in schizoprenia occurs in human population at the same time as an 1800s surge in cat popularity as pets
120
Persons infected by Toxoplasma are
three times more likely to die in a car accident
121
Leishmania -
Small protozoans (flagellates)
122
Leishmania - Transmitted by
sandflies (Phlebotomus)
• Tropical/subtropical areas
• Rare in North America/Europe
123
Leishmania - Reservoirs
• Rodents, dogs, other animals, humans
124
Leishmania - Several species
| •
Different tissue tropisms and clinical displays
• Skin ulcers, cutaneous and subcutaneous lesions, and
disseminated visceral leishmaniasis (“Kala azar”)
• Different temperature preferences (25-30 oC vs 37 oC)
125
Leishmania = Promastigote (flagellated) binds to
macrophages
• Superoxide dismutase
produced
126
Leishmania - Converts to
```
amastigote
(no flagella)
• Resistant to lysosomal
enzymes
• Requires low pH for
nutrient uptake (glucose
and proline)
```
127
Leishmania - Antimony-containing
| compounds useful for
treatment
128
• Trypanosoma cruzi
Chagas’ disease (American trypanosomiasis)
• Latin America and southern US • Transmission
• Reduviid (“kissing”) bug
• Grows in intestine, bug bites
and deposits feces, scratching introduces organism into bite
• Illness
• Mild usually, complications 10-20 years later
• Nerve, GI, heart damage
129
• Trypanosoma brucei
```
African sleeping
sickness
• Transmission – tsetse
flies (Glossina)
• Transmitted directly via
bite
• Main reservoirs:
• East Africa – wild game animals
• West Africa – humans and domestic animals (cattle)
```
130
Trypanosomes Illness
Systemic (fever and swollen lymph nodes) and chronic in bloodstream
• Dominant surface antigen (variable surface
glycoprotein) changes to avoid immune system • Antigenic variation via genetic rearrangement (one
expressed locus, multiple ‘silent’ loci that can recombine)
• Months/years later – infect CNS, brain, spinal fluid
131
• Giardia lamblia, Trichomonas vaginalis – flagellates
Frequent in US
| • Waterborne and sexual transmission
132
• Entamoeba histolytica – amoeba
• Common in developing countries
133
• Cryptosporidium, Cyclospora, Isospora – apicomplexans
Non-motile, reproduce by alternating sexual/asexual cycles
| • Foodborne
134
• Microsporidia – not true protozoa (like bacteria)
• Obligate intracellular parasites – small
135
Giardia lamblia and Giardiasis Worldwide zoonosis
Ingestion of water contaminated by feces from animal carriers
• Cysts highly resistant
• Chlorine – waterborne
outbreaks
• Stomach acid –
stimulates cysts to transform to vegetative trophozoites
136
Giardia lamblia
```
Intestinal protozoan
"African shield" morphology
http://web.indstate.edu
Mild, persistent diarrhea
• Not bloody like Entamoeba
• Asymptomatic carriers can
pass cysts for years.
• Daycare & mental institution
epidemics are common.
• Trophozoites attach in the
duodenum using ventral sucking disk, but do not invade • Inflammation leads to
maladsorption of proteins & fat (greasy, foul smelling stools)
```
137
Trichomonas vaginalis
```
Common vaginal flagellate (15% or more of women)
• Occasionally causes vaginitis
• Transmitted by sexual contact
• Men are usually asymptomatic
• Less common, less pathogenic species are
found in:
• GI tract (T. hominis)
• Mouth (T. tenax)
```
138
Entamoeba histolytica
```
Amoebiasis
• Destruction of host tissue (colon)
• Flask-shaped ulcers
• Can spread via bloodstream and produce
abscesses in liver, brain, other organs
• Many humans carry non-pathogenic amoebas
that are indistinguishable (E. dispar)
• Transmitted via fecal-oral route
• Vegetative trophozoite
• Highly resistant cyst

```
139
Entamoeba histolytica
```
Adhere to host cell receptors containing digalactose residues • Attachment via lectin
surface protein • Damage
• Attachment
• Contact-killing
• Pore-forming proteins
(amoebapores)
• Ingestion of killed host cell by ameba
```
140
Entamoeba histolytica • Non-immune hosts
Pathogenic amoebas destroy host phagocytic cells
| neutrophils, non-activated macrophages
141
Entamoeba histolytica • Immune hosts
• Cell-mediated immunity required
• Circulating antibodies not likely important
• Amoebas produce cysteine protease that digests
IgA, IgG and other proteins
142
Cryptosporidium
• Zoonosis
• Often in rural areas but can be spread person to person in crowded urban environments (day care centers)
• Outbreaks with public water systems (ie. Milwaukee, 1993)
• Found in most surface
waters that utilities draw from
143
Cryptosporidium resembles Toxoplasma
* Infectious oocysts produced in intestine and spread to other animals
* Highly resistant to chlorine
* Expelled in huge numbers in watery stools
* Do not invade intestinal epithelial cells or disseminate
* Stay within microvilli of small intestine
* Single episode of diarrhea that lasts ≤ 2 weeks
* Common in Great Britain and United States
144
• Roundworms (nematodes)
Fewmmto20cm
| • No visible body segmentation
145
Ascaris – most frequent infections (Southern US)
```
Eggs require several weeks in
environment to mature to infective
stage
• Eggs are ingested
• Hatch in small intestine and release
larvae that penetrate mucosa • Travel to lung, then to
trachea/pharynx and swallowed
• Mature in GI lumen and eggs released in stool
```
146
• Pinworms (nematodes)
Common in temperate and tropical areas
| • Prevalent in small children and in institutions
147
Enterobius
Eggs do not require maturation stage outside of body
• Transmitted readily by fecal-oral route (ingestion)
• Eggs resist drying and can be transmitted from clothes
or dust
• Hatch in small intestine and larvae mature in large
intestine
• Females travel perianal skin, lay eggs (perianal itching symptom, which facilitates spread)
148
A Helminth Cycle: The Pinworm
Person swallows microscopic eggs
• Picked up from another infected person by direct contact
• Or by touching articles an infected person has touched
• Eggs hatch in the intestine
• Release larvae that mature in to adult worms (about 1
month)
• Male and female worms mate
• Female migrates out of the anus to deposit eggs
• Causes intense itchiness
• Relieved by scratching
• Scratching contaminates the fingers which transfer the eggs
• Eggs spread to others or the original host reinfects him or herself
149
• Hookworms (nematodes)
```
Necator americans, Ancylostoma duodenale
• Penetrate skin as filariform larvae
• Soil contaminated with human, cat or dog stools
and larvae
• Do not require ingestion
• Fecal-cutaneous route
```
150
Distribution and Importance of Parasitic Worms
About 50 species parasitize humans
• Distributed in all areas of the world
• Yearly estimate of worldwide infections- in the billions
151
Intestinal Helminths -
Human hookworm larvae move from skin to heart via blood or lymphatics and become trapped in lung
• Dog/cat hookworms are relegated to skin
• Break through lungs, coughed up, swallowed
• Life cycle continues in small intestine and eggs
released (10,000 – 20,000 eggs/day)
• Chronic anemia
• Hookworms hang onto intestinal mucosa with teeth,
secrete anticoagulant, and suck host’s blood
• Severity proportional to worm burden
152
• Strongyloides stercoralis
Mostly tropical areas but can be anywhere
• Causes intestinal malfunction by perforating intestinal wall producing septicemia
• Can reinfect same host – lethal systemic disease in immunocompromised hosts (kidney transplants)
* Does not require external soil phase
* Direct penetration through skin via feces
* Migration to intestines identical to hookworms
153
Tapeworms
Long, ribbonlike with rectangular segments
(proglottid) that are self-contained units
• Attach to intestinal wall by a head
(scolex) with sucking discs or grooves
• Can penetrate deep tissues and form
infective, cystic larvae
• Acquired by eating raw or undercooked meat
or fish
• Taenia saginata (beef)
• Taenia solium (pork)
• Diphyllobothrium latum (fish)
154
Tapeworm Life Cycle
Life cycle depends on humans (definitive host) and animals (intermediate host)
• Cattle infected by ingesting human feces with eggs
• Eggs hatch, enter bloodstream, lodge in tissues
• Humans infected by eating beef containing larvae
(cysticerci)
• Worms can live in intestine for decades and grow up to
10 m in length
• Fish tapeworm associated with B12 deficiency
• All human infections correlate with consumption of undercooked or raw meat • Cooking destroys larvae
155
Tapeworm Tissue Infections
Deep tissue infections can produce severe disease
• Cysticercosis – T. solium eggs hatches into invasive larvae
• Usually acquired from ingestion of tissue cysticerci from
infected pork
• May be acquired endogenously by autoinfection from
host’s own feces or regurgitation of eggs
• Echinococcosis (cystic hydatid disease)
• Echinococcus granulosus
• Ingestion of infectious eggs rather than tissue cysticerci
• Source – carnivore feces (e.g., dogs, wolves, coyotes)
• Transmission via fecal-oral route, not from
contaminated meat
• Hydatid cysts form in many organs

156
Tissue and Blood Helminths
Ingestion Acquired
• Trichinella spiralis –
trichinosis
• Most infections are
asymptomatic
• Larvae hatch, cross
mucosa, enter lymphatics and blood • Diarrhea/pain
• Encysted larvae in striated/cardiac muscle produce inflammation
• Cysts calcify, but worms can be viable for 30 yrs

157
Tissue and Blood Helminths
Skin Acquired
• Schistosomes (blood flukes)
• Each species has unique geographic distribution,
dependent on snail intermediate host • Schistosomiasis
• Symptoms depend on location of the adult worms and the type of eggs released
• S. haematobium – bladder (eggs released in urine)
• S. mansoni – large intestine (eggs released in stool)
• S. japonicum – small intestine (eggs released in stool)
158
Tissue and Blood Helminths
* Infective cercariae released from snails
* Burrow through skin of people in infected water
* Lose tails and change to schistosomulae that enter blood
* Pass to portal venous system to mature
* Move in pairs (male/female) to small/large intestine, bladder, sexually reproduce and eggs released
159
Schistosomiasis
Eggs trapped in host tissues induce formation of granulomas that undergo fibrosis that can produce disease symptoms years later
• Pathogenesis anomalies:
• Fibrotic reactions to eggs mediated by cytokines and
long-term complications
• Lack of effective immune response to male and female
worms that reside in vascular system for decades
• Worms employ camouflage with host proteins (serum albumin, HLA antigens)
160
Filariasis - Onchocerciasis
(‘river blindness’)
| • Transmission via Simulium black flies
161
Filariasis - Lymphatic filariasis (elephantiasis)
• Transmission via mosquitoes
• Nocturnal microfilarie – more prevalent in blood at
night
162
Filariasis - Geographic distribution limited by
vectors
• Not within the United States
• Humans are not reservoirs
163
Filariasis - Adult filarial worms live in
subcutaneous
tissues
• Microfilariae offspring travel through lympatics
(lymphatic filariasis) or subcutaneous tissue (onchocerciasis)
