Helminths and Antihelminthics Flashcards

1
Q

Helminths

Overview

A

Nematodes, Trematodes, and Cestodes

  • Complex multicellular animals
    • Differentiated tissues
    • Highly developed reproductive systems
    • Specialized organs for attachment (suckers, hooks and teeth)
  • Do not replicate in the host
  • Transmission through:
    • Fecal oral route
    • Swallowing larval stages in tissues of another host
    • Active penetration of the skin
    • Insect bite
  • Immunoregulatory aspects of helminth infections:
    • Hygiene hypothesis
      • Improvements in hygiene and management of infectious diseases ⇒ ↓ worm burden in developed world ⇒ ? ↑ in autoimmune disorders
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2
Q

Nematodes (Roundworms)

Overview

A
  • Widespread distribution: 500k species
  • Mostly free-living, some parasitic
  • Unsegmented, cylindrical and elongated
  • Covered w/ protective cuticle
  • Complete digestive tract
  • Sexes are separate
  • Differentiation from egg → larva → adult
  • Caenorhabditis elegans
    • Free-living nematode
    • Model for a simple metazoan
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3
Q

Caenorhabditis elegans

Lifecycle

A

Free living nematode.

Model for a simple metazoan.

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4
Q

Intestinal Roundworms

A
  • Transmission by ingestion:
    • Enterobius (pinworm)
      • Also transmitted via inhalation
    • Trichuris (whipworm)
    • Ascaris (large roundworm)
  • Transmission by skin penetration:
    • Necator and Ancyclostoma (hookworms)
    • Strongyloides (small roundworms)
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5
Q

Enterobius vermicularis (Pinworm)

Overview

A
  • Most common roundworm in the temperate zone
  • May be considered a commensal
  • Most common worm infection in the US
  • Infections in children account for the highest percentage of cases
  • ♀ 8-13 mm, ♂ 2-5 mm
  • Life cycle confined to humans: eggs → larva → adult
    • Autoinfection common
    • Worms live in colon
    • Gravid female → several inches out of the anus ⇒ lay eggs perianally
    • Eggs deposited as worms crawl or released as worms dry out and explode
      • Local irritation and itching, especially during the night when eggs are laid
  • Most frequently infections are asymptomatic
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6
Q

Enterobius vermicularis (Pinworm)

Clinical Characteristics

A
  • Transmission: Fecal/oral, ingestion of eggs, inhalation
  • Diagnosis: Scotch tape test, egg ID
  • Treatment and Control: Two doses (10 mg/kg; maximum of 1g each) of Pyrental Pamoate two weeks apart gives a very high cure rate
    • Mebendazole is an alternative
    • Bedding and underclothing must be sanitized between doses
    • Personal cleanliness most effective in prevention
  • Tx the whole family
  • Re-infections common
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7
Q

Soil-Transmitted

Intestinal Helminth Infections

A

Ascaris lumbricoides (large roundworm), Trichuris trichiura (whipworm), and hookworm affect ~ 1 billion people

In children aged < 5 years, these infections cause malnutrition and anemia

Anthelminthic treatment (deworming) improves nutritional status of school-aged children

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8
Q

Trichuris trichiura (Whipworm)

A
  • Transmission: ingestion of fully embryonated eggs
  • ~10 d for full embryonation
  • Larva adhere to small intestine temporarily
  • Adults 3-5 cm long
  • Adult anterior ends embedded in fecal mucosa
  • Light infections ⇒ usu. asymptomatic
  • Heavy infectionsulceration and hemorrhage
    • ± Prolapsed rectum, esp. in children w/ heavy infections
    • May resemble IBD
  • Diagnosis: observing football-shaped eggs in feces
  • Treatment: Mebendazole x 3 days, 200 mg for adults,100 mg for children
  • Accompanying infection treated accordingly
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9
Q

Ascaris lumbricoides

(Large Roundworms)

A
  • Epidemiology:
    • Worldwide distribution, common in tropical or subtropical environments
    • Linked to poor sanitation
    • ~ 1.4 billion infected people
  • ♀ 20-35 cm, ♂ 15-25 cm
  • Avg. worm burden hundreds per capita
  • Transmission: contaminated soil, ingestion of embryonated eggs
  • Each ♀ releases ~ 200k eggs/day
  • Eggs need to be outside host for 2-3 wks to become infective
  • Clinical/Pathogenesis:
    • Larvae lung maturation coughed up swallowed small intestine
    • Do not attach to intestinal wall
    • Swims against peristaltic movement
    • Can penetrate through intestinal wall
    • Asymptomatic, Pneumonitis, 2°asthma attacks, GI perforations, bowel obstructions
    • A few worms living in the intestine may not cause problems
    • Migration intestine → pancreas, bile ducts or into esophagus problematic
    • May live for a year
    • In absence of reinfection, will be gone
    • Usually not lethal, but ~60k die/yr
  • Diagnosis: usu. via eggs in the feces
  • Treatment: Mebendazole x 3 days, 200 mg for adults, 100 mg for children
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10
Q

Hookworms

A
  • Necator americansus (New World hookworm)
    • North and South America, Africa, Asia, Australia, common in Southern US
  • Ancylostoma duodenale (Old World hookworm)
    • Africa, Asia, Australia
  • ~1 billion infected individuals
  • Transmission: penetration of the skin
  • Clinical/Pathogenesis:
    • Lungs swallowed attach to intestinal lining suck blood
    • Loss of blood ⇒ iron deficiency ∝ to worm burden
      • Up to 0.3 ml of blood per day by each adult; ≈ 1 million liters of blood given to the worms each day
    • Pneumonia and eosinophilia as larva migrates
  • Diagnosis: eggs in stool, ± occult blood in stool
  • May live in host for 8-16 years
  • A. caninum (dog hookworm) infections abortive, but causes cutaneous larva migrans
  • Treatment: Mebendazole x 3 days, 200 mg for adults, 100 mg for children
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11
Q

Strongyloides stercoralis

(Small Roundworms)

A
  • arasitic and free-living forms
  • Geographic distribution: Tropical, subtropical, poor sanitation, rural areas
  • Transmission: Filariform larvae infiltrate through the skin
  • Skin lungs small intestine
  • Autoinfection d/t differentiation of rhabdiform larvaeinfective filariforms
  • Disseminated hyperinfection in immunosuppressed pts & usu. fatal
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12
Q

Trichinella spiralis

(“Pork Worm”)

A
  • Worldwide distribution
    • ~2% infected population
  • Morphology:
    • Adult ♀ 3.5 mm x 60 μm
    • Larvae in the tissue (100 μm x 5 μm) coiled in a lemon-shaped capsule (400 μm by 200 mm)
  • Transmission: eating undercooked or raw pork containing encysted larvae
  • Symptoms: causes trichinosis
    • Mild infections may be asymptomatic
    • Larger bolus of infection ⇒ sx according to severity and stage of infection & organs involved
    • Low mortality rate
  • In the intestines: Larvae → mature adults additional larvae muscle
    • Initial infection w/ ± diarrhea
    • Convert muscle cells nurse cells ⇒ support larval growth
    • Acute inflammatory reaction as larvae go into muscle
    • ± Myocarditis, encephalitis (can be d/t vasculitis), eosinophilia
  • Pathogenesis: d/t large # of larvae in vital muscles & host reaction to larval metabolites
    • Muscle fibers become enlarged, edematous, and deformed
    • Paralyzed muscles infiltrated w/ PMNs, eosinophils and lymphocytes
    • Worm ⇒ strong IgE response + eosinophils ⇒ parasite death
  • Diagnosis: Biopsy
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13
Q

Toxocara

A
  • Nematode parasite of dogs (T. canis) and cats (T. catis)
  • Geographic distribution: Worldwide, highest in developing countries
    • ~ 14% of US population infected w/ Toxocara
    • Incidence is higher in inner cities
  • Humans are incidental hosts
  • Children get infected when playing in egg-contaminated dirt
  • Most infections are asymptomatic, esp. in adults
  • Migration of larva in tissue can cause damage:
    • Ocular Lava Migrans (damage to the eye)
    • Visceral Larva Migrans (in heavy infections)
    • Possible effects on cognitive development
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14
Q

Wuchereria bancroftii and Brugia malayi

A

Filarial Parasites

  • 1st parasite identified as being transmitted by mosquitoes
  • Geographic Distribution: Sub Saharan Africa, Madagascar, Caribbean, sporadic in South America
  • Adult worms live in lymphatics ⇒ inflammation ⇒ lymphatics obstruction
  • Produce living embryos called microfilariae
  • Periodically released related to feeding habits of vector
  • Most infections asymptomatic
  • Tropical pulmonary eosinophilia frequently seen in endemic areas
  • Elephantiasis (extreme manifestation)
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15
Q

Onchocerca volvulus

A

Filarial nematode

  • Causes river blindness
  • Transmitted by Simulium species of black flies
  • Subcutaneous nodules
  • ± Microfilariae (living embryos) in cornea and anterior chamber
  • African and American forms known
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16
Q

Loa Loa

(African Eye Worm)

A

Filarial nematode

  • Transmitted by Chrysops species of the mango flies
  • Active migration throughout subcutaneous tissues
  • Migration through tissues is painless
  • Noticed when they traverse conjunctival tissue
17
Q

Dracunculus medinensis

(Guinea worm)

A

Filarial nematode

  • Confined to a small part of W. Africa
  • Will probably be extinct in 5-10 years
  • ♀ up to 1 m long
  • Live in the intestine
  • After mating, gravid ♀ → skin ulcer
  • Use a small stick to slowly wind the worm out of the body through the skin
  • When worm contacts water via ulcer ⇒ larvae released
  • Larvae infect crustaceans (intermediate hosts)
  • Infective larvae come out of the crustaceans into the water
  • People infected by drinking this water
18
Q

Wolbachia

A

Endosymbionts of Filarial Nematodes

  • Intracellular proteobacteria
  • 70% of insect species have Wolbachia as parasitic organisms
  • Most filarial worms (exception Loa Loa) have Wolbachia as symbionts
  • Present in invaginations of body wall and female reproductive organs
  • Provide riboflavin, heme, FAD and nucleotides to the worms
  • Essential for worm fertility and survival
19
Q

Trematodes and Cestodes

(Flatworms)

A

Belong to Phylum Plathyhelminthes

Multicellular flatworms w/ bilaterally symmetrical body

20
Q

Schistosomes

(Blood Flukes)

A

Trematode

  • 3 species infect humans: S. mansoni, S. japonicum, S. hematobium
  • Certain non-human Schistosoma spp. can have abortive infections
  • Geographic distribution: Southeast Asia
  • Transmission: cercariae from snails, swimming, penetration
    • Humans are definitive hosts
    • Snails are intermediate hosts
    • Snails release cercaria(e) ⇒ motile and infect humans by penetrating skin
    • Cercariae adults in veins
  • Clinical/pathogenesis:
    • S. mansoni and S. japonicum: mating pair live in veins of liver, eggs cause inflammatory damage
    • Rectal and colonic polyps (S. mansoni)
      • Dx S. mansoni: stool, egg w/ lateral spine
      • Dx S. japonicum dx: stool, ovum
    • S. haematobium: mating pair live in veins of bladder, eggs cause damage
      • Hematuria
      • Dx: urine, eggs w/ terminal spine
  • Worms may persist for decades
  • Produce eggs at prolific rate:
    • Most secreted in feces or urine
    • Some get deposited in tissues (freq. in liver) ⇒ pathologyfibrosis
  • Host TNF induces egg production
  • Schistosomes covered w/ host antigens, especially MHC
  • Treatment: Praziquantel
21
Q

Cestodes

(Tapeworms)

A
  • Resemble a measuring tape
  • Adults ⇒ head (scolex) and segments (proglottids)
  • scolex w/ hooks or other means ⇒ attach to host intestinal wall
  • Tapeworms are hermaphrodites
  • Each proglottid contains male and female reproductive organs
  • Two categories: intestinal tapeworms and larval tapeworms

Life Cycles of Taenia saginata and T. solium:

22
Q

Taenia saginata

A

Cestodes

  • Geographic distribution: worldwide, common in Central and South America and Africa
  • Cattle and other herbivores: intermediate hosts
    • Ingest vegetation contaminated w/ eggs (orproglottids)
    • In animal’s intestine, eggs release oncosphere → evaginates → larval stageintestinal wallstriated musclescysticercus
    • Cysticercus can survive for several years in the animal
  • Humans: only definitive hosts
  • Transmission: ingestion of undercooked beef containing cysticercus
  • Cysticercus develops over 2 months in small intestine into adult tapeworm (usu. ≤ 5 m, up to 25 m)
  • Can survive for > 30 years
  • Adults produce proglottids (1-2k proglottids/worm) → mature → become gravid → detach from tapeworm → migrate to anus or passed in stool
  • Each gravid proglottid contain 80-100k eggs ⇒ released after proglottid becomes free and passed w/ feces
  • Eggs can survive for months to years in the environment
  • Clinical/pathogenesis: Worm in small intestines
  • *up to 30 ft**
    • Anorexia and diarrhea
  • Diagnosis: Proglottids and eggs in feces
23
Q

Taenia solium

A

Cestodes

  • T. solium lifecycle similar to T. saginata
  • Transmission: undercooked pork, encysted
  • Geographical distribution: worldwide, but commonly in Mexico, Asia
  • Adults (2-7 m)
  • < 1k proglottids w/ 50k eggs each (lasts up to 25 years)
  • Develop not only in humans but also some other animal species (monkeys, hamsters)
  • Humans both definitive and intermediate hosts
  • Cysticerci formed when humans are intermediate hosts (larval infection)
    • In striated muscle, brain, liver, and other tissues
    • Pigs, other animals, humans
  • Clinical/pathogenesis:
    • Worm in small intestines up to 15’ ⇒ anorexia, diarrhea
    • Cysts in CNS ⇒ cysticercosis
  • Diagnosis: proglottids and eggs in feces
24
Q

Cysticercosis

A
  • Caused by Taenia solium
  • Larval cysts in lung, liver, eye and brainblindness and neurological d/o
    • Cerebral cysticercosis ⇒ up to 20% of neurological case (Mexico)
    • Ocular cysticercosisis ⇒ 2.5%
    • Muscular involvement ⇒ up to 10% (India)
    • Neurocysticercosis in the US
  • Ass. w/ Hispanic ethnicity, immigrant status, and exposure to endemic neurocysticercosis areas (Southwest)
25
Q

Echincoccus granulosus

A
  • Dogs: definitive hosts
  • Humans: incidental hosts
  • Small tapeworms
  • Fluid-filled cysts in liver, lungs
    • Contain hydatid sand
  • Dissemination can have severe consequences
  • Caution during surgical procedures
  • Geographic distribution: Africa, Europe, Asia, Middle East, Central and South America, rarely North America
26
Q

Diphyllobothrium lattum

(Fish Tapeworm)

A
  • Acquired by eating undercooked fish containing larval forms
  • Worldwide distribution, common in northern hemisphere
  • Adult worm can reach >10 m in length
  • Adults do minimal damage
  • Occasional attachment to the proximal jejunumclinical vitamin B12 deficiency
27
Q

Nematode Treatment

Overview

A
  • Treats common nematodes (roundworms)
    • Enterobius vermicularis (pinworms)
    • Necator americanus (hookworm)
    • Ascaris lumbricoides (giant round worm)
  • Drugs:
    • Albendazole, Mebendazole
    • Pyrantel
    • Ivermectin
28
Q

Albendazole, Mebendazole

A

Treat nematodes

  • MOA:
    • Binds beta-tubulin ⇒ ⊗ production of tubulin dimers
    • ↓ microtubules in parasitic intestinal cells ⇒ ↓ absorptive function ⇒ depletes glycogen storage ⇒ insufficient energy to produce ATP
  • Indications:
    • All nematodes including trichinosis, Enterobius vermicularis, Necator americanus, Ascaris lumbricoides
    • A single dose of albendazole for Pinworms (Enterobius)
    • Albendazole used to tx Echinococcus (a cestode [tapeworm])
  • Pharmacokinetics: poorly absorbed
  • AEs:
    • GI upset, constipation, diarrhea
    • Contraindicated in pregnancy
29
Q

Pyrantel

A

Treat nematodes

  • MOA: Cholinergic nicotinic receptors in nematodes ⇒ depolarization blockade
  • Indications:
    • Alternate to Albendazole, Mebendazole for nematodes
    • Not widely used b/c other drugs are better
    • Approved for use against Enterobius vermicularis (pinworms)
30
Q

Ivermectin

A

Treat nematodes

  • MOA unclear but may:
    • Glutamate-gated chloride permeability
    • GABA mediated transmission
    • Both will hyperpolarize cell membrane ⇒ paralysis of pharyngeal muscles
  • Indications:
    • Scabies caused by Sarcoptes scabiei (tiny burrowing mite)
      • Alternative to topical permethrin (round worm)
    • Ancylostoma braziliense (cutaneous larva migrans)
    • Onchocerca volvulus (river blindness)
    • Pediculus humanus (lice)
    • Strongyloidiasis
      • A single dose a year can prevent river blindness
  • AEs:
    • Not many side effects
    • Fever, myalgia, and hypotension in severely infected pts d/t release of Ag from nematodes (Mazotti reaction)
31
Q

Praziquantel

A

Used to treat trematodes and cestodes

Outer-surface (tegument) of schistosomes (trematode [flukes]) ⇒ double membrane structure that protects organism from host immune response

  • MOA:
    • Permeability of tegument ⇒ loss of intracellular Ca2+ ⇒ contraction of helminths musculature
    • Causes tegument breakdown ⇒ allows host immune cells access to Schistosoma Ag
    • Mechanism may be similar for other cestodes
  • Indications:
    • Active vs trematodes and cestodes
    • Except Echinococcus ⇒ albendazole used
  • Not many side effects