Dr. Zhou - Lecture 19 Flashcards
1
Q
What is Medical Parasitology
A
- Study of eukaryotic parasites
- 7/8 tropical diseases
- Easily spread: travel
- Common property: CANNOT live outside host
- 2 major categories of studying infections and diseases
2
Q
What are the 2 major categories of studies of infections + diseases?
A
- Protozoa: small, single-celled
- Helminth worms: small to very big (10m)
3
Q
What causes sleeping sickness?
A. Plasmodium
B. Trypanosomes
A
Trypanosomes
4
Q
Protozoa
A
- Kingdom: Protista (algae + protozoa)
- Single celled, animal-like: Amoebas, Ciliates, Flagellates, Sporozoans
- Structure:
Cytoplasmic membrane
Cytoplasm
Usually w/ flagellum
5
Q
What are the 4 kingdoms?
A
- Protista
- Plants
- Animals
- Fungi
6
Q
Sporozoan parasite structure:
A
- Cytostome (mouth)
- ER (makes protein)
- Nucleus
- Food vacuole
- Mito (energy)
- Membrane
7
Q
Protozoan Life Processes
A
- Aquatic
- Obligate parasites (have to live inside host)
- Chronic or acute diseases
8
Q
What are the chronic and acute diseases of protozoa, and what are they caused by?
A
- Amebiasis (amebic dysentery): bacteria and stomach aches; Entamoeba
- Sleeping sickness (caused by brain damage): Trypanosoma bruci
- Chagas disease (severe tissue damage): Trypanosoma cruzi
STD: Trichomonas vaginalis
9
Q
Life Cycle - Reproduction
A
- Asexual: binary fission
- Sexual: Conjugate; exchange DNA; segregate
10
Q
How many and what are the major phases in protozoan life cycle?
A
- Reproduction
- Encystment
11
Q
Life Cycle - Encystment
A
- Cyst formation under adverse conditions:
- Round w/ protective coating
- Survive w/o food, water, and at high temp
12
Q
What are the 4 phyla of protozoans?
A
Amoebas
Ciliates
Flagellates
Sporozoan
13
Q
Infective Amoebas: General Properties
A
- Pseudopodia (fake foot)
- Trophozoite (actively growing)
- ONLY binary fission
- Form cysts
- Major diseases (most NOT pathogenic):
- Amoebiasis: diarrhea + blood stool; Entamoeba histolytica
- Brain infection: naegleria, acanthamoeba
14
Q
Amoebiasis
A
- Caused by Entamoeba histolytica
- Intestinal disease (100,000 deaths/yr)
- Sign of infection: intestinal mucosa
- Symptoms: Mostly diarrhea, dysentery (blood stool), abdominal pain, fever, fatigue, weight loss
- Tissue damage: cell ingestion (enzymes dissolving tissue, ulcerations)
- Severe cases: extra-intestinal infections
- Liver: amoebic hepatitis
- Lung: pulm amoebiasis
- Less frequent: spleen, adrenals, kidney, skin brain
* 10% fatality rate
15
Q
Epidemiology of Amoebiasis:
A
- Tropical + subtropical disease (US: 0.1-0.5% infection rate; tropical: 5-8% - raw sewage = fertilizer)
- Spread by asymptomatic chronic carriers
- Healthy carriers: cyst formation
- Unhealthy carriers: active dysentery: NOT infectious –> cysts CANNOT form
16
Q
Entamoeba Histolytica life cycle
A
- Metacysts: each cell in the cyst
- Mature cyst –> excystment –> metacysts –> metacysts are released into environ–> grow into trophozoite –> new cyst formation
17
Q
Amoebiasis: Diagnosis
A
- Based on stool exams
- Symptoms
Parasites have: - Ingested RBCs
- 4 nuclei in cysts
18
Q
Amoebiasis: Treatmetn
A
- Drugs targeting parasites in both stool + tissues
- Iodoquinol
- metronizazole
- Dehydroemetine
- Chloroquine
19
Q
Amoebic brain infections
A
- Caused by N. fowleri and Acantheomoeba
- Common, free-living protozoans
- Accidental parasites
- Live in lakes, hot springs, swimming pools, hot tubs, moist soil
- CAN survive w/o hosts
- Primary amoebic meningoencephalitis (N. fowleri) - invades nasal mucosa
- Granulomatous amoebic encephalitis (acantheomoeba) - invades broken skin; conjunctiva, lung, eye
20
Q
Amoebic infections of Brain: Pathogenesis
A
- Naegleria infection starts at nose –> amoeba burrows in, multiplies –> travels into brain –> primary acute meningoencephalitis
Meningoencephalitis: ; fast, massive destruction of brain + spinal tissues, causing hemorrhage + coma, and eventually death in ~1 wk
Symptoms: hemorrhage + coma, death in 1 wk
21
Q
Ameobic Brain Infections: Treatment
A
- Naegleria meningoencephalitis advances too fast to have effective treatment
- Some drugs if started early can work: Amphotericin B, sulfadiazine, tetracycline, ampicillin
- Acanthamoeba invades broken skin, conjunctiva, lung, and urogenital epithelia
- Special risks: ppl w/ eye injuries or abrasions from contact lenses
- Course of infection longer than naegleria - gives time for treatment
22
Q
Amoebiasis:
A. Intestinal disease
B. Brain infection
A
Intestinal disease
80% caused by enterotoxigenic E. Coli
23
Q
Intestinal Ciliate Properties
A
- B. Coli
The Ciliates:
- Cilia: movement
- 2 nuclei - macro + micro nucleus
- Sexual + asexual reproduction
- Trophozoites and mature cysts
24
Q
B. Coli Disease
A
Balantidiosis: infection in intestinal mucosa. Quite widespread
25
B. Coli Natural habitat
- Large intestines of pigs, and other domestic animals
| - Primates: cysts in feces
26
Anatomy of B. Coli
```
Macronucleus
Micronucleus
Vacuole
Cytostome
Cilia tufts
```
27
B. Coli - infection + symptoms
- Intestinal mucosa
- Irritation, injury, NV, diarrhea, dysentery, abdominal pain (colic)
Healthy ppl: Resistant; usually NOT pathogenic
28
B. Coli treatment
PO tetracycline
| - If fails: dodoquinol, nitrimidazine, or metronidazole
29
B. Coli Prevention
Prevent food or drink contamination w/ pig manure
30
Flagellates
- Mastigophorans
| - Common feature: long filamentous flagella
31
Flagellates - diseases
Mild diseases:
- Trichomoniasis
- Giardiasis
Debilitating:
- Trypanosomiasis
- Leismaniasis
Others:
- T. Vaginalis (STD): urogenital pathogen; vaginal infections. Has flagella + undulating membranes (both used for movement)
- T. Tena: gingival (rare infection)
- T. hominis: intestinal species (rare infection). NON-patho
32
Trichomonads (shape, properties, disease, reservoir, mode of transmission)
- Small, pear-shaped protozoa w/ 4 flagella + an undulating membrane
- No cysts
- MOST IMPORTANT PATHO: T. Vaginalis - trichomoniasis (STD)
- Reservoir: human urogenital tract (50% asymptomatic)
- Mode of transmission: sexual contact, communal bath, public facilities, mother to child
33
Trichomoniasis
- 2nd most prevalent STD
- Most common in young women
- Most common: chlamydia (bacterium)
C. Trachomatis - bacterium that ONLY infects humans
34
Trichomoniasis - Symptoms
Females:
- Foul smelling, green-yellow vaginal discharge
- Vulvitis
- Cervicitis
- urinary frequency + pain
Males:
- Urethritis
- Milky discharge
- Prostate infection
35
Trichomoniasis - Treatment
- PO + vag metronidazole
| - BOTH sexual partners have to be treated
36
Trichomoniasis is caused by:
A. an amoeba
B. Flagellate
Flagellate
37
Giardia lamblia (G. lamblia) and Giardiasis (definitions, outbreak cause)
Giardiasis: infection + disease caused by G. lamblia
- Prominent cause of diarrhea
G. lamblia is most common flagellate isolated in clinical specimens
Outbreaks:
- Traveler's diarrhea -
- Hikers + campers drink from fresh mountain streams
- Kids in daycare centers
38
Giardiasis Treatment
- Quinacrine
| - Metrodinazole
39
Hemoflagellates
- Vector-borne blood parasites (VERY dangerous)
- Flagellates in blood + tissue
- 2 major species:
* Trypanosoma
* Leishmania
- Life threatening diseases
- Spread via blood-sucking insects
- Complicated life cycles
40
Hemoflagellates: Developmental stages (4)
1. Amastigote: no free flagellum (round cell no flagella)
2. Promastigote: w/ 1 free anterior flagellum
3. Epimastigote: flagellate stage, w/ both flagellum + undulating membrane
4. Trypomastigote: large, fully formed stage of Trypanosoma
BUT: NOT ALL HEMOFLAGELLATES HAVE ALL STAGES
41
Leishmania stages
1. Amastigote (intracellular in human MPs)
| 2. Promastigote (found in sand fly gut; INFECTIVE to humans)
42
T. Brucei stages
3. Epimastigote (in salivary gland of tsetse fly)
| 4. Trypomastigote (in biting mouthparts of tsetse fly; INFECTIVE to humans)
43
T. Cruzi stages
1. Amastigote (intracellular in human MPs, liver, heart, spleen
2. Promastigote
3. Epimastigote (in gut of reduviid (kissing) bug)
4. Trypomastigote (in feces of reduviid bug; TRANSFERRED to humans)
44
Trypanosoma and Trypanosomiasis
2 major typanosoma species:
- T. brucei: African sleeping sickness
- T. cruzi: Chagas disease
45
T. brucei disease, species, and principle vector
Disease: sleeping sickness
2 subspecies:
- T. b. gamibense: West Africa
T. b. rhodesiense: East Africa
Principle vector: tsetse flies
46
T. brucei infection pathogenesis
- Tsetse flies get infected by feeding on infected rservoir hosts (antelope, lion, cow, goat, human) --> trypanosomes multiply in fly gut --> migrates to salivary glands --> develop into infectious stage --> transfers into bite wounds on new hosts to lymphatics + blood
T. b. gamibense: chronic, may not affect brain for several years
T. b. rhodesiense: acute, affects brain in 3-4 wks
47
Patho of sleeping sickness
- Intermittent fever
- Enlarged spleen
- Swollen lymph nodes
- Joint pain
- Personality change, sleep disturbances (sleepy during the day, sleepless at night)
- Advance neuro disorders:
* Muscular tremors, shuffling gait, slurred speech, epileptic seizures, paralysis
* Death: coma, 2ndary infections, heart damage
48
Sleeping sickness: Treatment + Prevention
Treatment:
- Chemo: successful if admin before brain
* Treating brain infections: expensive - melarsoprol-toxic arsenic-based drug (one of most ancient potent poisons, death dose is 0.1-0.2g) OR DFMO (less toxic)
Control tsetse pop:
- Insecticides (difficult since some are resistant)
Sudan and Zaire: 20-40% of pop infected
49
Why Can't the immune system defeat Trypanosome?
- Trypanosomes make a large # of surface antigen in succession
- Antibodies made by host fail to stop bugs w/ new antigen
- Eventually overwhelms host
- Hard to immunize bc there's >100 diff antigenic variations
50
Chagas disease
- Disease causing heart damage (enlarged heart filled w/ amastigotes of T. cruzi)
- Caused by T. cruzi
- Millions of cases, thousands of deaths in Latin America
51
T. Cruzi infection
Insect host: kissing bugs w/ trypanosomes in hind gut; discharge it in feces
- Found in Central + South America: share habitat w/ humans
So parasite is well adapted to habits of both kissing bugs + hosts
Infection happens when bug poops near bite wounds, and inoculation by rubbing bug feces into wounds
52
Chagas Disease: patho
Major patho:
- Fever
- Swelling lymph nodes, spleen, and liver
- Favored targets: heart muscle + large intestine
* Heart enlargement + death in 2 yrs
53
Chagas Disease: Treatment
- Nifurtimox + benzonidazole for early treatment
| - Damaging ADRs (protozoans are also eukaryotic, so similar physiology to human cells = toxicity to human cells)
54
Leishmaniasis
- Caused by Leishmania
- Cutaneous leishmaniasis: capillary infections = extensive tissue damage
- Tranmitted among mammals by phlebotomine flies (sand flies)
- Endemic to equatorial regions
- Special risks: Travelers + immigrants
- Death by tissue destruction
55
Leishmania Life Cycle:
Infected sand fly has promastigotes in gut --> bite/inoculate parasite into new host (human, other mammal) --> migrates to spleen + RBCs --> free + intracellular amastigotes in spleen + RBCs taken up by another sand fly
56
Sporozoans
- Aka Apicomplexan parasites
- No locomotor organells in mature stage
- Sexual + asexual reproduction
57
Most human patho sporozoans:
2 most important:
- Plasmodium: malaria
- Toxoplasma: toxoplasmosis
- Cryptosporidium: cryptosporidiosis (no severe issues)
58
Malaria
- Dominant protozoan disease for centuries
- Caused by plasmodium
- Italian: mal = bad; aria = air
- Exposure to bad air from swamps: lots of mosquitos
- Most common in Africa
- = or > serious than COVID
59
Malaria symptoms:
- Chills + fever at regular intervals followed by sweating: 48-72 hrs bc of synchronous rupturing of RBCs
- Anemia in young kids; organ rupture from accumulated cell debris (spleen, liver, kidneys)
- Long recovery: up to 5 yrs
60
Plasmodium
- Obligate intracellular sporozoan
4 species:
- P. malariae
- P. vivax
- P. falciparum
- P. ovale
Most severe malaria caused by P. falciparum (P. falc). Causes:
- Persistent fever
- Rapid pulse
- Cough
- Weakness for wks w/o relief
- Acute phase: High death rate
61
Plasmodium Transmission:
- Mostly by female Anopheles mosquitoes
- Occasionally by sharing needles
- Blood transfusions
- Mother to child through umbilical cord blood
62
Plasmodium Complex life Cycle
2 distinct phases:
- Asexual (happens in human host)
- Sexual
63
Plasmodium Complex Life Cycle - Asexual phase
Asexual phase 1: exoerythrocytic development (happens in liver)
- Starts from outside RBC
- Start: mosquito injects anticoagulant saliva into capillary --> asexual plasmodium cells (sporozoites) get injected --> sporozoites reach liver --> undergo schizogony (asexual division), making many daughter parasites, merozoites --> liver cells erupt --> releases numerous mature merozoites into circulation
- 5-16 days
Asexual phase 2: Erythrocytic development
- Released merozoites invade RBCs --> feed on Hb, making schizonts cells (cells filled w/ merozoites) --> RBCs bursts (start of symptoms (chills, fever) when large # bursts)--> releases more merozoites --> merozoites turn into macrogametocytes (female) + microgametocytes (male)
64
Plasmodium Complex Life Cycle - Sexual phase
Mosquitos bring gametes into stomach --> fertilization --> diploid cells (oocyst) implants into stomach wall --> undergo multiple mitotic divisions, releasing sporozoites --> sporozoites migrate to salivary glands and available for next infection
65
Malaria - Genetic Change
- Changed human genetics protects against malaria
- Certain mutations in Hb, HbS gives protection
- Hb-C: protection w/o fitness cost (3% pop)
- Hb-S: protection w/ cost - sickle cell anemia in s/s pts (homo recessive)
- Hetero mutation (S/s): better survival than no mutations, no sickle cell anemia
- Large % of Africans carry Hb S mutations: 20% pop
66
Malaria - Diagnosis + Control
```
Diagnosis:
(Best - first 2)
- Stained blood smear
- Antibodies
- DNA-PCR analysis
```
Control:
- Pesticides: DTT (best)
- ISSUE: Pesticide resistant mosquitos
67
Malaria - Treatment:
Non-resistant strains: Chloroquine - less toxic ADRs
Resistant strains: use mefloquine or quinine
Eliminating parasites from liver: primaquine or proguenil
68
Toxoplasma gondii (T. gondii) and Toxoplasmosis
- Exposure rate: 90% (very common pathogen)
Most cases:
- Mild
- Sore throat
- Lymph node enlargement
- Low grade fever
Immunodeficient pts:
- Brain lesions
- Fetal disruption of heart + lungs
69
Toxoplasmosis in pregnant women:
- 33% (1/3) chance fetus transmission
- Pregnant women can be infected through contact w/ infected pets or undercooked meat
Causes:
- Still birth
- Liver failure
- Hydrocephalus
- Convulsions
- Retina damage + blindness
70
Why is it so hard to control trypanosome infections?
A. they replicate fast
B. antigenic changes
Antigenic changes
