Helminths and Antihelminthics

Question 1

Helminths

Overview

Answer 1

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

Question 2

Nematodes (Roundworms)

Overview

Answer 2

• 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

Question 3

Caenorhabditis elegans

Lifecycle

Answer 3

Free living nematode.

Model for a simple metazoan.

Question 4

Intestinal Roundworms

Answer 4

• 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)

Question 5

Enterobius vermicularis (Pinworm)

Overview

Answer 5

• 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

Question 6

Enterobius vermicularis (Pinworm)

Clinical Characteristics

Answer 6

• 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

Question 7

Soil-Transmitted

Intestinal Helminth Infections

Answer 7

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

Question 8

Trichuris trichiura (Whipworm)

Answer 8

• 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 infections ⇒ ulceration 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

Question 9

Ascaris lumbricoides

(Large Roundworms)

Answer 9

• 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

Question 10

Hookworms

Answer 10

• 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

Question 11

Strongyloides stercoralis

(Small Roundworms)

Answer 11

• 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 larvae → infective filariforms
• Disseminated hyperinfection in immunosuppressed pts & usu. fatal

Question 12

Trichinella spiralis

(“Pork Worm”)

Answer 12

• 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

Question 13

Toxocara

Answer 13

• 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

Question 14

Wuchereria bancroftii and Brugia malayi

Answer 14

Filarial Parasites

• 1^st 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)

Question 15

Onchocerca volvulus

Answer 15

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

Question 16

Loa Loa

(African Eye Worm)

Answer 16

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

Question 17

Dracunculus medinensis

(Guinea worm)

Answer 17

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

Question 18

Wolbachia

Answer 18

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

Question 19

Trematodes and Cestodes

(Flatworms)

Answer 19

Belong to Phylum Plathyhelminthes

Multicellular flatworms w/ bilaterally symmetrical body

Question 20

Schistosomes

(Blood Flukes)

Answer 20

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) ⇒ pathology ⇒ fibrosis
• Host TNF induces egg production
• Schistosomes covered w/ host antigens, especially MHC
• Treatment: Praziquantel

Question 21

Cestodes

(Tapeworms)

Answer 21

• 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:

Question 22

Taenia saginata

Answer 22

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 stage → intestinal wall → striated muscles → cysticercus
  • 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

Question 23

Taenia solium

Answer 23

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

Question 24

Cysticercosis

Answer 24

• Caused by Taenia solium
• Larval cysts in lung, liver, eye and brain ⇒ blindness 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)

Question 25

Echincoccus granulosus

Answer 25

• 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

Question 26

Diphyllobothrium lattum

(Fish Tapeworm)

Answer 26

• 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 jejunum ⇒ clinical vitamin B12 deficiency

Question 27

Nematode Treatment

Overview

Answer 27

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

Question 28

Albendazole, Mebendazole

Answer 28

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

Question 29

Pyrantel

Answer 29

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)

Question 30

Ivermectin

Answer 30

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)

Question 31

Praziquantel

Answer 31

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