2: Antihelminthics Flashcards
how do parasites differ from other parasites?
- multiply outside of their definitive host
- evade immune system: chronic infections last for lifetime of host
what is the most common helminth infection?
ascaris
describe echinococcosis:
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- from echinococcus granulosus (dog tapeworm)
- infection: large, hydatid cysts in liver, lung, brain
- anaphylactic rxn can occur if cyst ruptures
- follows ingestion of eggs in dog feces
- intermediate host: sheep
- ddx: CT scan or biopsy of infected tissue
- tx: albendazole and surgical excision of intact cysts
describe taeniasis (pork):
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- from Taenia solium (pork tapeworm)
- infection: intestines - diarrhea, but most asymptomatic
- follows ingestion of larvae in undercooked pork
- ddx: detection of proglottids in stool
- tx: niclosamide
describe cysticercosis:
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Taenia solium larvae
- infection: cysticerci in brain - seizures, headache, vomit - and in eyes
- follows ingestion of eggs from human feces
- ddx: CT, MRI, or biopsy
- tx: praziquantel, albendazole, and/or surgery
describe taeniasis (beef):
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Taenia saginata (beef tapeworm)
- infection: intestine but no cysticerci, most asymptomatic
- follows ingestion of larvae in undercooked or raw beef
- ddx: detection of proglottids in stool
- tx: niclosamide
describe diphyllobothriasis:
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Diphyllobothrium latum (fish tapeworm)
- intestinal disease
- follows ingestion of larvae in undercooked or raw fish
- ddx: detection of characteristic eggs in stool
- tx: niclosamide
life cycle of pork/beef tapeworms
eggs in environment -> cattle/pigs ingest plants contaminated by eggs or gravid proglottids -> oncospheres hatch, penetrate intestinal wall, and circulate to musculature -> oncospheres develop into cysticerci in muscles -> humans infected by ingesting raw/undercooked meat
how does cysticercosis develop in humans?
oncospheres hatch in intestine, invade wall, and migrate to striated muscles, brain, liver, and other tissues -> develop into cysticerci
describe enterobiasis (pinworm disease):
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Enterobius vermicularis
- infection: pruritis ani, white worms visible in stool or perianal region
- follows infestion of eggs (humans only host)
- ddx: scotch tape test
- tx: mebendazole or pyrantel pamoate
what is the most common helminthic infection in US?
pinworm
describe ascariasis (roundworm):
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Ascaris lumbricoides
- infection: larvae grow in intestine - abdominal sx, including obstruction; may pass through blood to lungs
- second most common to pinworms
- follows ingestion of soil containing eggs
- ddx: detection of characteristic eggs in stool
- tx: pyrantel pamoate or mebendazole
describe trichuriasis (whipworm):
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Trichuris trichiura
- infection: usually asymptomatic, but can get abdominal pain, diarrhea, flatulence, rectal prolapse
- follows ingestion of soil with eggs
- ddx: identify characteristic eggs in stool
- tx: mebendazole
describe hookworm disease:
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Ancyclostoma duodenale, Necator americanus
- infection: attaches to intestinal mucosa - anorexia; ulcer-like sx, chronic intestinal blood loss - anemia
- follows direct skin penetratino by larvae found in soil
- ddx: identify characteristic eggs in stool
- tx: pyrantel pamoate or mebendazole
describe strongyloidiasis (threadworm):
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Strongyloides stercoralis
- infection: benign in healthy folks, can be fatal in immunocompromised due to dissemination to CNS or other deep organs (hyperinfection syndrome)
- follows direct skin penetration by larvae found in soil
- ddx: identify larvae in stool
- tx: thiabendazole, albendazole, or ivermectin
describe onchocerciasis (river blindness):
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Onchocerca volvulus
- infection: subcutaneous nodules, prurutic skin rash, ocular lesions -> blindness
- follows bite of blackfly
- ddx: detection of microfilariae in skin biopsy
- tx: ivermectin and/or surgery
describe visceral larva migrans:
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Toxocara canis
- infection: young kids - matures in intestines, then migrates to liver, brain, eyes
- only larvae cause disease
- follows ingestion of eggs from dog feces
- ddx: detect larvae in tissue
- tx: mebendazole or thiabendazole
describe filariasis (elephantiasis):
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Wuchereria bancrofti or Brugia malayi
- infection: block flow of lymph, causes edematous arms, legs, and scrotum
- follows bite of infected female Anopheles and Culex mosquitos
- ddx: microfilariae in blood
- tx: combo of diethylcarbamazine and albendazole
describe trichinosis: -what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Trichinella spiralis
- encysts in tissue
- follows eating encysted larvae in undercooked pork
- allergic manifestations treated for sx and not with antihelminthic drugs
- ddx: locating coiled, encysted larvae in muscle biopsy
- tx: early stages - thiabendazole, no tx for late stages
describe dracunculiasis:
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Dracunculus medinensis
- infection: skin inflammation and ulceration
- follows drinking water containing intermediate host copepods in which the larvae live
- ddx: find head of worm in skin lesion or larvae released from a skin lesion following contact with water
- tx: removing subcutaneous worms by surgery
describe loiasis:
- what worm?
- describe infection sx?
- transmission?
- intermediate host?
- diagnosis?
- treatment?
- Loa loa
- infection: larvae crawl under skin, leaving characteristic tracks; enter eye - visible in subconjunctival space around iris
- follows by deer fly bites; no animal reservoirs and humans are only definitive host
- ddx: detection of microfilariae in blood
- tx: diethylcarbamazine
top 5 trematodes (flukes)
- clonorchis sinensis (Chinese or oriental liver fluke)
- Paragonimus westermani (lung fluke)
- Schistosoma mansoni (blood fluke)
- Schistosoma haematobium (blood fluke)
- Schistosoma japonicum (blood fluke)
what are three benzimidazoles on the market?
- mebendazole (first in class)
- thiabendazole (toxicity limits use)
- albendazole (useful in GI and tissue infections)
benzimidazoles mechanism of action
- binds to tubulin only in helminths
- inhibits formation of microtubules (caps them on plus end, continue to be shortened on minus end)
what is the drug of choice for cysticercosis? what is this drug also used to treat?
albendazole
- pinworms
- hookworms
- ascariasis
- trichuriasis
- strongyloidiasis
metabolism of albendazole
variable absorption
-rapidly turned into albendazole sulfoxide - active
what is mebendazole used for?
- pinworms
- hookworms
- ascariasis
- trichuriasis
why is thiabendazole no longer preferred?
due to toxicity and potential teratogen
what is praziquantel used for?
highly effective against cestodes and trematodes
-no activity against nematodes
drug of choice for all schistosomiasis
- two or three doses yield high cure rates
- used in mass treatment programs
single dose kills 100% of taenia saginata, taenia solium, and Diphyllo…. latum (but doesn’t kill solium eggs)
mechanism of action of praziquantel
at low concentrations - increased muscular activity
- contraction and spastic paralysis
- worms detach from blood vessel walls
- migrate from mesenteric veins to the liver
at high concentrations - tegumental damage and exposes a number of tegumental antigens (more effective here)
-clinical effect correlates with tegument changes
may also disrupt calcium homeostasis
what is the drug of choice for strongyloidiasis and onchocerciasis?
ivermectin
what is ivermectin, structurally?
a semisynthetic macrocyclic lactone
mechanism of action of ivermectin
- paralyzes microfilariae
- binds to Glu-activated Cl- channels found in nematode nerve or muscle cells
- causes hyperpolarization by increasing intracellular [Cl-]
- also binds with high affinity to GABA-gated and other ligand-gated Cl- channels
- allows host cytotoxic cells to adhere
- does not kill adult worms, but blocks release of progeny!
besides onchocerciasis, what is ivermectin also used for?
- ascariasis
- enterobiasis
- strongyloidiasis
- filariasis
what is pyrantel pamoate? what is it used for?
broad-spectrum antihelminth
- available OTC
- highly effective for treatment of pinworms and ascaris
- active against adult and immature worms (not against migratory stages or ova)
mechanism of action of pyrantel pamoate
- depolarizing neuromuscular blocking agent
- causes release of ACh and inhibiton of AChE
- worms are paralyzed and expelled
clinical uses of pyrantel pamoate
- ascariasis - one dose is 85-100% effective
- pinworms - 2 doses two weeks apart - 95% cure rate
AE of pyrantel pamoate
mild and infrequent
scabies:
- what causes it?
- infection causes what?
- treatment?
- Sarcoptes scabiei
- infection: itching dermatosis - female mites burrow superficially beneath the stratum corneum and deposit up to 3 eggs/d; itching and rash from sensitization rxn directed against excreta in burrows
- tx: permethrin cream (5%) and may need to pretreat with 6% salicylic acid if crusted scabes
treatment of lice
treat live lice if detected
- 10 min application of 1% permethrin or pyrethrins
- requires 2nd application 10d later
chronic infestations - 0.5% malathion
newer pediculicides contain benzyl alcohol, dimethicone, or SPINOSAD
