Human Parasitology Exam II (Lectures 9-17)

Nematode classification

*classification based on morphology

*2 classes

1. adenophorea

   • cellular hypodermis (tissue that contains individual cells)

   • no phasmids (specialized sensory structure).

2. secernenta

   • syncytial hypodermis (no cell boundaries)

   • have phasmids

Nematode habitats

1. free-living (most)

   • they don’t need a host

   • ecosystem processes

   • decomposition

   • nutrient cycling

   • aquatic

   • soil

2. parasitic

   • plants

     • ag importance

     • destruction of ~10% of all crops

   • vertebrates

     • major medical importance

     • > 3 billion humans

Nematode general morphology

1. roundworm

2. elongate, cylindrical, both ends tapered.

3. “tube within tube”

   • body wall

   • digestive tract

nematode adult morphology (the body wall)

• body wall

  • collagen

  • covers entire body surface + lines openings.

• hypodermis

  • formation of cuticle during molting

  • morphology used in classification

    • cellular→ class adenophorea

    • syncytial→ class secernentea

• muslce layer beneath hypodermis

nematode adult morphology (digestive tract)

• complete digestive tract

  • mouth→ gut→ anus

• 3 major regions

  1. foregut: lined with cuticle

     • mouth

       • circular opening

       • may have lips (# varies among spp.)

     • buccal cavity

       • between mouth + esophagus

       • useful for ID

       • not present in all spp.

       • size + shape vary

       • may have teeth or cutting plates (thickening of cuticles)

     • esophagus

       • esophageal glands: digestive enzymes

     • muscular: forces food through, esophago-intestinal, and valve into midgut.

  2. Midgut

     • no cuticle

     • single layer of cells: microvilli which helps with absorption

  3. Hindgut

  • lined with cuticle

  • anus

  • pseudocoelom

    • fluid filled with cavity between body wall + digestive tract.

    • hemolymph: transport solutes and structural

    • hydrastatic skeleton: support and locomotion

Nematode reproductive system for males

*dioecious + sexually dimorphic (male and female look different)

• testes

• sperm (pseudopodia)

• bursa (used to wrap around a female to mate)

Nematode reproductive system for females

• ovary→ produces oocytes

  • sperm penetrates oocyte which initiates the process of eggshell formation.

• eggshell

  • chitinous layer

  • lipid layer

    • resistance to desiccation (drying out) and penetration by H2O → solutuble substances

  • proteinaceous layer

    • uterine secretions

    • some spp.

Nematode Nervous System

1. commissures

   • circumesophageal (around the esophagus)

   • rectal

2. ventral nerve cord

3. sense organs

   • labial papillae

     • mechanoreceptors

     • ex.pressure

   • cephalic papillae

     • mechanoreceptors

   • amphids

     • chemoreceptors

   • phasmids

     • chemoreceptors

     • characters used in taxonomic classification

     • absent→ class adenophorea

     • present→ class secernentea

Neurotransmission (2 types of nerve fibers) of nematodes

1. excitatory nerve fibers

   • release Ach at neuromuscular junctions

   • depolarize muscle membranes

   • increase in AP

   • increase in Ach→ depolarization→ increase in AP

2. inhibitory nerve fibers

   • release gammaaminobutyric acid (GABA)

   • binds to receptors on muscle + is inhibitory

   • hyperpolarizes muscle membranes

   • decrease in AP.

   • increase in GABA→ hyperpolarization → decrease in AP

Drug treatments for nematodes

• some interfere with neuromuscular transmission.

• paralysis → flaccid (limp) or spastic (tense)

piperazine

• blocks Ach

• hyperpolarizes muscle membranes

• flaccid paralysis (loses mortality)

• worm expelled by host

ivermectin

• stimulates release of GABA

• hyperpolarizes muscle membranes

• flaccid paralysis

• worm expelled by host

pyrantel

• inhibits cholinesterase (normally inactivared Ach)

• spastic paralysis

albendazole + mebendazole

• inhibit polymerization of tubulin into microtubules

• impaired glucose uptake

• unable to maintain E production

• immobilization → death

nematode cuticle process of molting

1. larva grows

2. secretes exsheathing fluid

3. cuticle detaches from hypodermis (secrete a new cuticle).

4. hypoderis secretes new cuticle

5. old cuticle broken down by enzymes and ruptures

6. larva exits

nematodes routes of infection

• oral

• skin penetration

• vector

trichuris trichiura life cycle

1. unembryonated eggs in feces

2. embryonation (L1→ L2→ L3)

3. L3 inside egg

4. embryonated eggs ingested

5. eggs hatch in SI

6. L3 penetrate into intestinal wall

7. molt 2x

8. adult

   • return to SI lumen

   • migrate to cecum + LI.

trichuris trichiura egg morphology

• very thick wall

• opercular knobs

trichuris trichiura adult morphology

• ant end: slender

• post end: thicker

• commonly called “whipworm”

• male: coiled post end

trichuris trichiura pathology

• adults burrow into mucosa + feed

  • trauma to intestinal lining

  • this trauma is called “colitis”

1. chronic hemorrhage + anemia: ~0.005 ml blood/worm/day lost in stools.

2. increased peristalsis in LI: rectal prolapse (to come out)

3. trichuris dysentery syndrome (TDS)

   • children

   • ex. 200 worms in a child and the child would needs an increase does of Fe 4.25 mg/day.

   • systemic effects

     • stunted growth

     • impaired cognitive function

     • finger + toe clubbing

4. children → heavy infections (children love to play in the dirt and trichuris trichiura live in the soil)

trichuris trichiura diagnosis

• eggs in feces

trichuris trichiura treatment

• mebendazole

• albendazole

ascaris lumbricoides life cycle

1. unembryonated eggs in feces

2. embryonation

3. L2 inside egg

4. egg ingested

5. hatch in SI

6. molt 2x (=L4)

7. enter circulation

8. migrate to lungs

9. L4 coughed up and swallowed

10. molt to adult in SI.

ascaris lumbricoides eggs morphology

• mammilated

  • proteinaceous layer (outermost)

  • thick, bumpy

  • absorbs bils → golden brown

  • VERY RESISTANT

• lipid layer (innermost)

  • ascarosides

  • unique to ascaris

  • eggshell impermeable to H2O soluble substance

ascaris lumbricoides adult morphology

• large

  • males: 30 cm x 3mm

  • females: 35 cm x 5mm

• mouth surrounded by 3 lips

• female

  • 27 million eggs in uterus.

  • releases 200,000 eggs per day.

  • massive contamination

ascaris lumbricoides pathology

1. migration

   • L2 get lost + die

   • ex. spleen, liver, brain

     • inflammation

     • granuloma (contains the threat from spreading)

2. pulmonary

   • L2 damage lung capillaries

   • blood pools + tissue damage

   • lung congestion

   • secondary bacterial infection

3. Intestinal

   • pain

   • allergic response to waste (rashes and asthma)

   • obstruction

   • pierce intestine→ peritonitis → death

   • wander

ascaris lumbricoides diagnosis

eggs in feces

ascaris lumbricoides treatment

• albendazole, mebendazole

• ivermectin

• surgery

hookworms life cycle

1. unembryonated eggs in feces

2. embryonation

3. L1 hatch

4. feed on feces + molt 2x

5. L3 (penetrates your foot)

6. L3 enters circulation

7. migrate to lungs

8. molt to L4

9. L4 coughed up + swallowed

10. molt → adult → live in SI

    • 2 species:

      1. ancylostoma duodenale

      2. necator americanus

hookworm egg morphology

• oval, thin shell

• difficult to identify spp.

hookworm adult morphology

• ant end curved dorsally

• large buccal cavity

  • teeth or cutting plates

• males

  • copulatory bursa

hookworm pathology

1. invasion

   • L3 enter sin

   • ground itch

   • local rash + irritation → inflammatory reaction to bacteria

2. migration

   • lungs

   • L3 break out of capillaries + into alveoli

   • pneumoia + coughing

3. intestinal

   • most serious stage

   • burrow into intestinal mucosa → feed on blood (anticoagulants)

   • blood loss

     • Na ~ 0.03 ml blood/worm/day

     • Ad ~0.2 ml blood/worm/day

     • worms survive 2-14 years

   • anemia

   • stunted growth + cognitive function

hookworm diagnosis

eggs in feces

hookworm treatment

1. albendazole + mebendazole

2. iron therapy

Necator americanus (hookworm)

• from SE US + South America '

• Buccal cavity

  • anterior: 4 cutting plates

  • posterior: 4 teeth

ancylostoma duodenale (hookworm)

• from Europe, Asia, Africa

• buccal cavity

  • anterior: 2 cutting plates (each with 2 teeth)

Trichinella spiralis life cycle

1. ingests L1 in uncooked meat (pig is DH)

2. (in SI) L1 released + enter lining

3. 4 molts→ adults

4. L1 produced

5. (pig becomes IH) L1 enter skeletal muscle cells

6. nurse cell develops

7. host must be ingested for cycle to continue

Trichinella spiralis morphology

• very small

  • females: ~ 3mm

  • males: ~ 1.5 mm

• stichocytes

  • glandular cells in esophagus

  • excretory-secretory antigen (ESA)

• live in SI

  • intramulticellular in epithlial cells (within many cells)

• female

  • ovoviviparous → L1

    • they do produce eggs but do not release the eggs. Instead, they hatch inside the uterus.

Trichinella spiralis pathology

1. intestinal phase (mild)

   • worms penetrate intestinal mucosa.

   • lesions + inflammation

   • nausea, diarrhea, fever, abdominal pain

2. migration phase (severe)

   • L1 migrating through body → muscle pain

   • tongue, diaphragm, jaw→ difficulty breathing, chewing, swallowing

3. inflammatory phase (moderate)

   • strong immune rxn to larvae

   • heart damage, nerve disorders

• disease called trichinosis

Trichinella spiralis diagnosis

1. ELISA

   • detects antibody against ESA

2. muscle biopsy

3. clinical symptoms

Trichinella spiralis treatment

1. mebendazole + albendazole

2. relieve symptoms

   • bed rest

   • corticosteroids

   • O₂

Anisakis simplex life cycle

• marine mammals= DH

• crustaceans= 1st IH

• fish= 2nd IH

• humans ingests raw/insufficiently cooked fish → ingests L3 = accidental host

Anisakis simplex pathology

• L3 invade stomach wall or intestinal wall

1. Acute

   • intense abdominal pain

   • nausea + vomitting

2. Chronic

   • Abscesses (pocket of pus)

   • granulomas

Anisakis simplex diagnosis

1. gastrointestinal symptoms

2. endoscopy or x-ray

Anisakis simplex treatment

1. removal

2. albendazole

Dracunculus medinensis life cycle

1. human ingests H2O containing copecods with L3

2. L3 penetrate stomach/intestinal wall → enters sub-q tissue → molts to adult + mates

3. male dies → female migrates to skin surface (legs) → blisters

4. female emerges from blister → ovoviviparous → L1 into H2O.

5. L1 eaten by copecod (IH) → into hemocoel → molts to L3.

dracunculus medinensis pathology

1. blister

   • abscessed → pain

   • 2^o bacterial infection

2. non-emergent worms

   • do not reach skin surface

   • die → calcified

   • arthritis

     • inflammation of one or more joints

dracunculus medinensis diagnosis

itchy, red blister with worm

dracunculus medinensis treatment

• windworm on stick

• pouring cold water can help stimulate the worm to come out faster

parasitologist’s dilemma

• eradication may lead to lower death rate

• if birth rate stays same, then pop size will increase

• problem: if pop cannot be supported by available resources → decline in quality of life

general characteristics of filarial nematodes

1. live in blood or tissues

2. transmitted by vector

3. ovoviviparous

   • eggs hatch in uterus + microfilariae (mf) released

4. mf

   • advanced embryos

   • ingested by vector during blood meal

   • periodicity

     • in peripheral (hands, arms, legs…) blood only @ certain time

Wolbachia sp

• intracellular gram negative bacterium

  • ~75% of all insects

  • reprofunctions + sex determination

• endosymbiont of many filarial spp

  • all stages

  • hypodermis (part of body wall) + repro tissue

• LPS (lipopolysaccharide) → inflammatory response → pathology

• doxycycline (antibiotic)

  • kills wolbachia (a bacterium)

  • adult filarial worms stunted + less mf develop

Wulchereria bancrofti life cycle

• when mosquito takes a blood meal, saliva lumbricants and anticoagulants goes into the blood along with the L3.

• L3 molts twice and becomes an adult

• adults prodice sheathed microfilariae that migrate into lymphatic and peripheral blood circulation.

Wulchereria bancrofti pathology

• incubation phase

  • asymptomatic

  • no detectable microfilaremia (not developed yet)

• inflammatory phase (acute)

  • response to antigen from dying/degenerating adults

  • episodic adenolymphangitis (ADL)

  • attacks of fever, chills, and edema

• Obstructive phase (chronic)

  • 10-20 yr after 1st exposure

  • lymph tissue blocked

    • worms, granulomas, fibrous tissue, fat.

  • lymphoedema

    • legs, genitlas, arms, breats

    • hydrocele → swelling in scrotum

Wulchereria bancrofti diagnosis

• mf in blood @ peak periodicity

• Ciruclating Filarial Antigen (CFA) test

  • ELISA

  • droplet any time

• ultrasound

  • worms in lymhatics

Wulchereria bancrofti treatment

• exercise limb

• chemotherapy → combination of

  • DEC= diethylcarbamazine → damages cuticle → immune response goes up

  • albendazole

  • ivermectin (=mectizan)

• Hygiene

  • wash

  • shoes

  • antibiotic creams

Wulchereria bancrofti control

• WHO

  • eradication

  • elimination

• Why possible?

  • no animal reservoir

  • simple, accurate diagnostic tests

  • treatment

    • effective + inexpensive

    • large scale once/yr

    • variety of options/combos (resistance goes down)

    • collateral health benefits

  • plans of action

  • drug companies

Brugia malayi (Lymphatic filariasis)

• adults

  • female= 55 mm

  • male= 25 mm

• mf

  • periodicity= night

  • vector= mosquito

• same as W.bancrofti in

  • life cycle

  • pathology

  • diagnosis

  • treatment

*only difference is the size. It’s a bit smaller than bancrofti

Onchocerca volvulus life cycle

1. blackfly (genus simulium) takes a blood meal (L3 larvae enter the bite wound)

2. subcutaneous tissues

3. adults in subcutaneuous nodule

4. adults produce unsheathed microfilariae that typically are found in skin and in lymphatics of connective tissues, but also occasionally in peripheral blood, urine, and sputum.

5. blackfly takes a blood meal (ingests microfilariae)

6. microfilariae penetrate blackfly’s midgut and migrate to thoracic muslces.

7. L1 larvae

8. L3 larvae

9. migrate to head and blackfly’s proboscis

   • mf

     • no periodicity

     • stay in skin + phototaxis

   • vector

     • blackfly (simulian spp.)

     • scarifies skin → pool of blood

Onchocerca volvulus pathology

1. onchocercomas

   • benign

   • may cause disfigurement but does not cause too much problem.

2. onchocerciasis

   • disease of skin + eyes

   • mf

     • alive= little pathology

     • dead/degenerating: host immune reponse

   • acute skin lesions: mf in skin

     • persistant, itchy rash

     • 2^o infections

     • skin thickens + local nymph enlarge

   • chronic skin lesions

     • skin thickened + discolored → “lizard”

     • loss of skin elasticity

     • hanging groins

       • femoral + inguinal lymph nodes enlarge + hand in loose skin

   • ocular lesion

     • mf invade eye + die

     • inflammatory rxn → blindness

Onchocerca volvulus diagnosis

• skin raised + thin slice with razor

• in saline on slide → microscope → mf

• do NOT draw blood

Onchocerca volvulus treatment

• ivermectin → kills mf

• Doxycycline → kills adult worm

• surgery

Onchocerca volvulus control

• carter center river blindness program

• since 1996 in 11 countries in Americas + Africa

• mectizan (merce)

• eliminated in

  • Columbia (2013)

  • Ecuador (2014)

  • Mexico (2015)

  • Guatemala (2016)

Loa Loa life cycle

1. fly (genus chrysops) takes a blood meal (L3 larvae enter bite wound)

2. adults in subcutaneous tissue

3. adults produce sheathed microfilariae that are found in spinal fluid, urine, sputum, peripheral blood and in the lungs.

4. fly takes a blood meal (ingests microfilariae)

5. microfilariae shed sheaths, penetrate fly’s midgut, and migrate to thoracic muscles

6. L1 larvae

7. L3 larvae

8. migrate to head and fly’s sproboscis

loa loa pathology

• mild

• adults wander in sub-Q tissue

• calabar swelling

  • inflammatory rxn

  • localized, painful temporary

• migration across eye

loa loa diagnosis

• mf in blood

loa loa treatment

• surgery

• ivermectin + DEC

dirofilaria immitis (heartworm) life cycle

1. mosquito takes a blood meal (L3 larvae enter the bite wound)

2. adults in pulmonary arteries, and heart

3. adults produce microfilariae that typically are found in peripheral blood

4. mosquito takes a blood meal (ingests microfilariae)

5. microfilariae penetrate mosquito’s midgut and migrate to Malpighian tubules

6. L1 larvae

7. L3 larvae

8. migrate to head + mosquito’s proboscis

9. lesions in pulmonary vessels

dirofilaria immitis pathology

• heart function impaired

• fatigue + loss of condition

• cough + respiratory problems

dirofilaria immitis diagnosis

• mf in blood

dirofilaria immitis treatment

1. immiticide

   • contains arsenic

   • toxicity → low margin of safety

   • kills adult worms (they live in the heart)

   • contraindicated in caval syndrome

     • worms in venae cava + rt atrium → block blood vessels

2. surgery

   • risky + expensive

human health

state of complete physical, mental, and social well-being, and not merely the absence of diease of infirmity (WHO)

public health

“the science and art of preventing disease, prolonging life, and promoting health through the organized efforts and informed choices of society, organizations, public and private communities, and individuals.” ~CEA Winslow

epidemiology

• basic science of public health

• branch of medical science that studies facts which determine presence + absence of diseases + disorders

ascaris model life cycle

• direct

• no IH

• no amplification

buidling ascaris model

r= per capita reproductive rate

rA= net reproductive rate

β= per capita transmission rate

• chances the egg will actually get ingested + develop into an adult

using model to control Ascaris infections

• increase parasite elimination

  • Aμ₁: increase μ₁ by treating host

    • chemotherapy

  • Eμ₂: increase μ₂ by killing eggs in ext env. (ascaris eggs are very resistant to the ext env so this methoid would be difficult).

• decrease parasite transmission (β)

  • ↓ contact (ex. washing your hands)

  • ↓ # of eggs (killing adult worms to prevent laying eggs)

  • ↓ # hosts

  • ↓ rA ( decreasing the rate of eggs being produced)

*best way to control is chemotherapy + education

eradication

• no longer exists anywhere in the world

• seldom (rare) realistic

elimination

• localized eradication

• no longer exists in a specfic geographical region

smallpox eradication - 1980

• R_o= 2

• natural exposure → long-lasting immunity

• vax

  • long-lasting protective immunity

  • 1 dose

  • easy to adminster

  • effective delivery + education campaign

  • fear of disease → public acceptance

• no animal reservoir

• govt cooperation

• $$$

• however most important? → vax

why parasite elimination + eradication are difficult

• no vax available for any

• Dracunculus

  • only parasite sp that may soon be eradicated

  • not bc of vax

  • because of education + other control measures

• living standards are bad

• poor sanitation

• poor hygiene

• poor meat insepction

• lack of education

enterobius vermicularis life cycle

1. eggs on perianal folds

2. embryonated eggs ingested by human

3. larvae hatch in small intestine

4. adults in lumen of cecum

5. gravid female migrates to perianal region at night to lay eggs

   • retroinfection

     • eggs hatch in perianal area

     • L1 migrate back

   • autoinfection

     • hosts ingests eggs produced by worms in body

enterobius vermicularis morphology

• eggs

  • flattened side

• adults

  • alae

  • female → pinworm

  • male → curved posterior

enterobius vermicularis pathology

• most asymptomatic

• damage within intestine + around anus → inflammation + bacterial invasion

• sleeplessness + irritiability

enterobius vermicularis diagnosis

• scotch tape test

enterobius vermicularis treatment

• pyrantel

• albendazole

• mebendazole

Protozoa

1. unicellular eukaryotes

2. heterotrophs

3. ~ 45,000 spp.

Order Amoebida (Phylum Rhizopoda) habitat

• most free-living

• some in intestinal tract

Order Amoebida (Phylum Rhizopoda) symbioses w/ human

• most commensals +/0

• a few parasite +/-

Order Amoebida (Phylum Rhizopoda) 3 genera in humans

• entamoeba

• endolimax

• iodamoeba

Genus entamoeba nucleus

• distribution of peripheral chromatin (PC)

• size + position of endosome

  • chromatin mass

  • small or large

  • centric or eccentric

Genus entamoeba life cycle

• trophozoite

  • feeding stage

  • lives in host

• cyst

  • exists host

  • resistant

  • transmission stage

  • chromatoidal bars

    • deposits of nucleic acids

    • morphology differs between spp

    • young cysts vs. old cysts

Entamoeba trophozoites morphology

• ~25 μm diameter

• crypts of LI

• starch + mucus

  • Nucleus

    • endosome= small + centric

    • PC= fine, evenly distributed

Entamoeba cyst morphology

• 10-20 μm diameter

• young cyst

• chromatoidal bar with rounded ends

entamoeba noninvasive pathology

1. noninvasive intestinal disease (luminal)

   • minor abdominal pain, cramps, diarrhea

   • asymptomatic

   • most self-resolve in a few months

   • pass cyst → carrier

entamoeba invasive Amoebic Colitis pathology

• amoebic colits (infection at the colon)

  • trophozoites release secretagogue

    • substance that stimulates secretion of another substance → mucus secretion increase → depletion

  • gal/galNAc lectin

    • protein with high binding specificity for particular carbohydrate

    • on surface of trophozoite, binds galactose with high affinity

      • cytoadherence binds to surface of host cell

    • host cells that lack Gal residue on surface glycoportins → resistant

  • Amebapores → host cell lyses

  • cysteine proteases → tissue destruction

• leads to flask-shaped ulcers, bleeding, electrolyte loss

amoebic colitis symptoms

• symptoms take 2-4 weeks to develop

• diarrhea, fever, nausea, vomiting

• 10-20 stools per day → dehydration

acute necrotizing colitis - tissue death

• rare, but exteremely severe

• most of mucosa is involved

• severe bloody diarrhea

• mortality exceeds 50%

Extraintestinal amoebiasis pathology (not in the intestine)

• perforate intestial wall → peritonitis

• enter circulatory system → ectopic sites → abscesses

• amoebic liver abscesses

  • months to years after intial infection

  • fever, hepatomegaly, pain

• pulmonary amoebiasis

  • direct extension of liver abscesses through diaphragm

  • cough, chest pain, dyspea + fever

• no cycts formed → dead end

Entamoeba histolytica diagnosis

• cysts in feces (luminal amoebiasis)

• ELISA: detect antibody