Protozoa - antiparasitic agents

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Protozoa - antiparasitic agents
2013-12-09 22:18:24
clin path
protozoal diseases and antiparasitic agents in veterinary clinical pathology
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  1. isospora canis/felis
    • coccidia
    • unsporulated oocysts in feces
  2. isospora life cycle
    • unsporulated oocysts in feces
    • oocysts sporulate in environment (outside body) in 96 hours
    • sporulated oocysts are ingested, invade intestinal wall, develop to mature form in smal and/or large intestine
    • mature produce and release oocysts into feces
  3. clinical signs of coccidia
    • often none.  
    • puppies and kittens: chronic diarrhea, weight loss, poor hair coat (unthriftiness), pot-belly
    • severe: anorexia, vomiting, depression, death
    • adults: most immune.  Can shed in feces but be asymptomatic
  4. Transmission of coccidia
    host-specific.  Canines will not infect felines, etc, neither infect humans.  (crypto)
  5. Coccidia environmental factors
    • sporulated oocysts (96hrs after shedding) can survive a year in moist, protected environment.
    • Killed in freezing or high temps
    • sporulation at 20-40 C
  6. Cryptosporidium parvum
    • coccidia form, non pathogenic to animals (just carried)
    • zoonotic
  7. diagnosis of coccidia
    • based on signalment, history, clinical signs and oocytes present in feces.  
    • Oocytes are not definitive, could be pseudoparasite
  8. coccidia pseudoparasite
    • Eimeria
    • looks like isospora, is non-pathogenic to dogs.
    • parasite of deer and rabbits.
  9. Treatment of coccidia
    • Sulfadimethoxine (Albon): ONLY drug approved
    • Ponazuril: newer drugs, off-label, may be effective
  10. Sulfadimethoxine
    Albon, used in coccidia.  (also Ponazuril)
  11. Ponazuril
    new drug, off-label for Coccidia
  12. Toxoplasma gondii
    • any warm blooded animal intermediate host
    • most important coccidian parasite
  13. Final host
    where parasite can perform sexual reproduction
  14. Life cycle of toxoplasma gondii (both intermediate and definitive)
    • Cats infected by ingesting TISSUE of infected intermediate host (rodent or bird)
    • Toxo penetrates intestinal wall and repicates throughout body as tachyzoites (extra-intestinal cycle) (non-sexual)
    • Same time, invade and replicate within intestinal epithelial cells (entero-epithelial cycle), culminating in sexual formation of unsporulated oocysts, shed for 7-10 days one time in life
    • immune response, shedding and tachyzoite  stops, bradyzoites formed, contained in tissue, remain for life
    • oocysts sporulate in 24-72 hours in soil or vegetation
    • mammals and birds ingest oocysts
    • penetrates small intestinal mucosa, multiplies in cells
    • spreads through body in lymph and cascular systems, tissue cysts with bradyzoites in many tissues (no oocyte production)
    • cat eats tissue of intermediate host or sporulated oocyst
  15. extra-intestinal cycle
    toxoplasma life cycle, when organisms penetrate intestinal wall and replicate throughout body as tachyzoites (no sexual reproduction)
  16. entero-epithelial cycle
    toxoplasma life cycle, when organisms invade and replicate within intestinal epithelial cells.  Culminates in sexual reproduction, formation of unsporulated oocysts which are shed for 7-10 days in feces
  17. bradyzoites and tachyzoites
    • toxoplasma life cycle. 
    • tachyzoites: extra-intestinal cycle, small crescents, only present in definitive host (feline)
    • bradyzoites: post-immune response in cat or in intermediate host, cysts full of organisms contained in tissue that stay forever.
  18. sporulated oocysts
  19. unsporulated oocysts
  20. transmission of toxoplasma
    • ingestion of infected mammalian or avian tissue (undercooked meat like pork)
    • ingestion of sporulated oocysts (feline feces, soil, water, vegetation)
    • transplacental or transmammary transmission of TACHYZOITES, so must be recent infection
  21. clinical signs of toxoplasma
    • most asymptomatic, young more likely to show signs
    • myositis (muscle)
    • chorioretinitis (lesions in eye)
    • meningoencephalitis (brain)
    • pneumonia
    • lymphadenopathy
    • abortion
  22. diagnosis of toxoplasma
    • fecal float: rarely see animal during shedding, so limited use
    • antibody assays: shows infection, not whether it is current or past
    • Serum: seronegative when shedding oocytes, seropositive after the fact. If seropositive, NOT SHEDDING
    • titers: NOT SHEDDING. shows exposure/immunity (positive IgG), recent/active infection (IgM), active infection if symptomatic, look for fourfold increase in IgG in paired titers (recent infection)
  23. Treatment of toxoplasma
    Clindamycin hydrochloride for 2-3 weeks.
  24. Transmission of human toxoplasma (5)
    • ingestion of sporulated oocysts (only infected if sporulated): 1. cat feces in litter for 24-72 hours, fecal-oral
    • 2. contact with oocyst contaminated soil (gardening and playing in soil)
    • 3. eating undercooked infected meat, esp lamb and pork (most common)
    • 4. unwashed fruit and veggies
    • 5. transplacental
  25. Side effects in human toxoplasma
    • large % of humans have had toxo, asymptomatic
    • chorioretinitis, meningoencephalitis, myositis, abortion, pneumonia, lymphadenopathy, brain lesions in AIDS patients
  26. Transplacental toxo infection in humans
    • most serious toxo infection
    • asymptomatic at birth usually
    • signs of infection later in life
    • loss of vision, hearing, mental retardation, death
  27. prevention of human toxoplasma
    • cook meat
    • wear gloves when changing kitty litter or gardening
    • wash hands after handling litter or soil
    • wash and peel fruits and veggies
    • don't change litter or garden if immunocompromised or pregnant.  
    • Don't get rid of the cat
  28. Giardia forms (2)
    • trophozoites (motile ciliated stage in small intestine)
    • cysts (resistant stage for environmental transmission
    • We think there are different strains for dog/cat/human
    • Many strains and hosts, none intermediate (everyone sheds cysts).  technically zoonotic?
  29. giardia life cycle
    • direct, no intermediate hosts
    • Trophozoites and cytses pass in feces, contaminate soil and water
    • final host ingests
    • zoonotic?
  30. clinical signs of giardia
    • maldigestion, malabsorption and hypermotility (diarrhea), caused by damage to enterocytes
    • profuse watery diarrhea, possible vomiting, abdominal cramps, fever.  
    • No melena or hematochezia, possible mucus.
  31. diagnosis of giardia
    • intermediate shedding of cysts/trophozoites and mistaken ID can cause false neg and pos
    • direct saline fecal smear (trophozoites) within 10 minutes, stain with iodine
    • fecal flotation with centrifugation (cysts), ZnSO4 and fecal trichome stain
    • Fecal ELISA (Snap)
    • direct fluorescent antibody assay
    • REPEAT TESTS due to intermittant shedding
  32. CAPC
    • companion animal parasite council
    • authority on parasites
    • suggest direct smear, fecal float with centrifugation and ELISA or immunofluorescent assay with repetitions for Giardia diagnosis
  33. Giardia treatment
    • dogs and cats
    • Metronidazole: extra-label therapy, efficacy only 50-60%
    • Fenbendazole: effective, combine with metronidazole
    • DrontalPlus (Febantel, pyrantel pamoate, praziquantal): daily for 3 days.
    • Bathe and shampoo
    • remove feces promptly
    • clean anus
  34. zoonoses of giardia
    • more likely to get from environment than animal (pets, wildlife, beavers), but water supplies can be contaminated.
    • Outer shell allows surviving in environment for a long time, resistant to chlorine
  35. giardia strain in d/c vs human
    • d/c: giardia duodenalis
    • human: giardia lambia
  36. entamoeba histolytical (entamoebiasis) appearance and life cycle
    • round with four nuclei when mature.
    • dog, cat, pig, rat, human, only primates pass cysts
    • REVERSE ZOONOSIS, dog ingests cysts from human feces (or contaminated)
    • live in LARGE INTESTINE, sometimes in liver, brain, perianal skin and genitalia
    • cyst becomes 8 amoebulae that become trophozoites
  37. entamoeba histolytica transmission, clinical signs, diagnosis, treatment
    • transmission: ingestion of human feces or contaminated food/water
    • clinical signs: chronic, erodes and ulcerates colonic mucosa (diarrhea, red blood)
    • diagnosis: direct smear (need to see trophozoite) or biopsy of colonic mucosa
    • Treatment: metronidazole
  38. Balantidium coli (balantidiasis) life cycle, appearance, hosts
    • ciliated protozoa, huge, kidney-shaped nucleus
    • Commensal of domestic animals (one benefits, one not affected), esp dogs, pigs, humans, NOT CATS
    • ingest cyst in contaminated food/water (uncooked pork), excystation in small intestine, trophozoites in large intestine
    • Cysts passed as infective, no sporulation
  39. Balantidium coli clinical signs, diagnosis, treatment, zoonoses
    • clinical signs: ulcerative colitis (severe bloody diarrhea)
    • diagnosis: fecal float (cysts and trophozoites) or direct smear (saline, see moving trophs)
    • treatment: tetracycline or metronidazole
    • zoonotic: cysts in feces of infected dogs can infect, but major reservoir for humans is PIGS--COOK MEAT
  40. trichomonas (trichomaniasis) appearance and life, symptoms
    • pear-shaped, 3 flagella tails, attached flagella makes "fin"
    • lives in intestinal (LARGE INTESTINE, maybe cecum) and reproductive tract, birds, cattle, digs, cat, non-human primate, guinea pig, pig
    • Commensal in dogs and cats, but opportunistic so if compromised, acute, voluminous diarrhea
  41. tritrichomonas foetus
    VD in cattle, bulls asymptomatic, cows get metritis, vaginitis, abortion, pyometra
  42. trichomonas gallinae
    sinuses, mouth, esophagus, genital tract of birds (URI, some genital infections)
  43. tritrichomonas suis
    pigs.  Cook your pork!  Zoonosis
  44. trichomonas diagnosis, treament, zoonoses
    • diagnosis: direct smear (movement is jerky and random), culture, PCR (amplify to make easier to find)
    • treatment: metronidazole
    • zoonosis: not sure.  Chronic diarrhea and STD (trichomonas vaginalis) very common.
  45. trichomonas vaginalis
    human STD with green frothy discharge and itching.  More than 8 million new cases yearly
  46. What is trichomonas confused with and how can you differentiate?
    • Giardia, primarily from direct smear.  
    • Trichomonas has jerky, random movement
    • giardia has falling leaf movement
  47. PCR
    • polymerase chain reaction
    • amplify DNA, make it easier to find
  48. Antiprotozoal agents (most common)
    • agents that are destructive to protozoa
    • Giardia and coccidia most common d/c parasites
    • Metronidazole
    • Sulfadimethoxine (albon)
  49. antihelmintic agents
    • agents that are destructive to parasitic worms
    • antinematodal (Roundworms, hookworms, whipworms)
    • anticestodal (tapeworms)
    • antitrematodal (flukes)
  50. metronidazole
    • NITROIMIDAZOLE (makes DNA lose helix and break apart)
    • active against anaerobic bacteria and most protozoa (esp giardia, entamoeba, trichomonas, balantidium)
    • off-label (no approved product)
    • side effects: head shaking and salivation in cats, lethargy, anorexia, v/d, CNS in chronic or OD
    • caution in nursing or pregnant
    • Oral (tablet, liquid) or IV
  51. sulfonamides
    • includes Sulfadimethoxine (albon), inhibits folic acid synthesis in parasite
    • puppies and kittens with coccidia
    • Side effects: excessive salivation and vomiting in cats, renal issues and urine precipitation if not well hydrated, irreversible KCS in some dogs, hypersensitivity
  52. kcs
    keratoconjunctivitis sicca
  53. benzimidazoles
    • fenbendazole (panacur), albendazole (valbazen), mebendazole (telmintic), febantel (rintal)
    • broad-spectrum dewormer (round, hook, whip, lung, heart, 1 tape), binds to protein B tubulin (microtubules in cytoskeleton)
    • round: tox...canis, cati and leonina
    • hook: ancylostoma, uncinaria
    • whip: trichuris vulpus
    • cestode: taenia pisiformis (tape from rodents)
    • giardia (fenbendazole and albendazole
  54. Fenbendazole
    • benzimidazole, broad-spectrum antihelminic (B tubulin)
    • off-label in cats and for giardia, flukes, lung worms
    • oral, rarely problems (vomiting), mix with food
    • giardia, trematodes (lung fluke), capillaria and aelurostrongylus (lung worms), ascarids (tox...canis, leonina), hook (ancylostoma, uncinaria), whip (trichuris vulpis), tape (taenia)
  55. pyrantel pamoate
    • strongid, heartgard plus, drontal, drontal plus, nemex
    • activates nicotinic receptors at neuromuscular junctions (seizures in parasite)
    • approved by FDA for dogs, off label for cats
    • Roundworms (tox canis, leonina)
    • hook (ancylostoma, uncinaria)
    • stomach worm (physaloptera)
  56. emodepside
    • topical (transdermal), contains praziquantel.  
    • Paralysis and death of nematodes
    • round: tox canis, cati, leonina
    • hook: ancylostoma
  57. organophosphates
    • nematodes in d/c, in flea/tick collars and yard sprays
    • irreversibly inactivates acetylcholinesterase
    • dichlorvos (task)
    • drug interactions, high potential for toxicity, esp cats and young or debilitated
  58. cestodes in d (3) and c (2)
    • tapeworms
    • dogs: taenia pisiforms (rodents)
    • dipylidium caninum (fleas)
    • echinococcus sp (encysted in liver)
    • cats: taenia taeniaeformis
    • dipylidium caninum
  59. praziquantel
    • droncit, drontal, drontal plus
    • alters Ca contentration inside cells, paralysis
    • ALL COMMON CESTODES in d/c and schistosoma trematodes
    • no puppies (<4 wk), kittens (<6 wk)
    • occasional v/d, salivation, sleeplessness, lethargy
  60. trematodes
    • flukes, HUGE. 
    • no labeled products, use praziquantel, sometimes fembendazole
    • d/c: paragonimus kellicotti (most common)
    • alaria
    • nanophyetus salmincola
    • dogs: heterobilharzia americana
    • cats: playnosomum fastosum
  61. dirofilaria immitis
    • heartworm, nematode
    • kill with adulticide (can't make any more), no adulticide in cats.  Melarsomine dihydrochloride (immiticide)
    • cats get fewer heartworms that live less time, USUALLY get emboli
  62. hemoptysis
    cough up blood from respiratory tract
  63. melarsomine
    • immiticide (arsenic).  Approved for dogs
    • Deep IM injections, 3x, 1, wait a month, 2, 24h, 3.  
    • Risk of thromboembolism, esp in pulmonary
    • low safety, calculate dose carefully.
    • side effects: edema, tenderness, PAIN AT INJECTION, anorexia, vomiting, depression, fever, signs of pulmonary emobolism are coughing, fever, hemoptysis, death
    • NO CATS
    • can't be made or gotten any more
  64. Heartworm life cycle
    • adult HW make immature microfilaria, send to bloodstream
    • Mosquito eats microfilaria, develops into infective larval stage (L3) in mosquito
    • L3 passes into next dog mosquito feeds from, develops into L4
    • L4 migrates through tissue, esp pulmonary.  
    • Adult heartworms live in pulmonary artery and heart, take 3-4 months to mature (6 months all together)
    • 6 months for infection to be patent (adults mature and reproduce to make microfilaria)
    • NEEDS mosquito stage to mature
  65. Heartworm and cats
    • larval development doesn't take as long, L4 in pulmonary often mistaken as asthma or bronchitis.
    • HW only live 7-8 months.
    • Need to be on HWP to stop bronchial damage later in life.
  66. HARD
    heartworm associate respiratory disease
  67. stages of heartworm
    • staged from 1-4
    • stage 1: asymptomatic to chronic soft cough, exercise intolerance, lethargy.
    • stage 4: critical, pulmonary damage from huge worm burden, bad prognosis.
  68. Heartworm diagnosis
    • ELISA snap test looks for antibody against HW antigen, but only sees adulte female.  
    • + is 100% accurate
    • many false - : male infection, not adult (too early, not 6 months yet), immune suppressed, operator error, VERY few worms
    • Confirmation: ECHO, chest rads, clinical signs, blood smear to look for microfillaria (modified knott's test for slide, watch for acanthochylonema (blunt head, crook tail)
  69. modified knott's test
    how to prep slide to look for microfilaria
  70. acanthocheilonema reconditum
    false heartworm, but smaller, blunted head and shepherd's crook tail.
  71. heartworm microfilaricides
    • kill heartworm larvae.  
    • ivermectin, salamectin, milbemycin, hyperpolarize by agonizing glutamate gated chloride channels, flaccid paralysis
    • 3 doses ivermectin (heartgard plus), adulticide, 6 months milbemycin (sentinel).  Include doxycycline.  
    • Pre-Ivermectin and doxy protect against wolbachia, prevent pulmonary pathology
  72. wolbachia
    • rickettsial organism that goes hand in hand with dirofilaria, causing many symptoms of treatment.  
    • Treat with 3 months of ivermectin (heartgard plus) and doxycycline before melarsomine to prevent pulmonary pathologies
  73. Heartworm chemoprophylaxis
    • HWT before starting treatment, must be at least 6 months old and test if missed more than 2 months.
    • ivermectin (heartgard), selamectin (revolution), milbemycin (sentinel), moxidectin (proheart)
  74. avermectin
    • antibiotics produced by streptomyces (microorganism found in soil)
    • agonist of glutamate-gated chloride channels, hyperpolarize cells
    • ivermectin (heartgard), selamectin (revolution), moxidectin (proheart)
  75. ivermectin
    • heartworm chemoprophylaxis and microfilaricide, nematode larvae, sarcoptic mange, otodectes cynotis, demodex
    • heartgard, avermectin derivative
    • agonist of glutamate-gated chloride channels, hyperpolarize cells
    • Heartgard plus also has pyrantel pamoate (round and hook)
    • Heartgard for cats controls hook, not round
    • Side effects: neurotoxicity in collie-type, mydriasis, salivation, ataxia, depression tremors
  76. selamectin
    • heartworm chemoprophylaxis and microfilaricide, adult fleas, eggs, larvae, otodectes cynotis, sarcoptic mange (scabies), ticks (not many), roundworm and hookworm in cats
    • revolution, topical avermectin derivative
    • agonist of glutamate-gated chloride channels, hyperpolarize cells
  77. moxidectin
    • heartworm chemoprophylaxis, adult and larval hookworms
    • Proheart, avermectin derivative
    • 6 month sustained release IV.
    • agonist of glutamate-gated chloride channels, hyperpolarize cells
    • recalled in 2004, risk map in 2008, removed restrictions in 2013
    • must be older than 6 months
  78. milbemycin oxime
    • heartworm chemoprophylaxis and microfilaricide, roundworm, hookworm, whipworm, demodex
    • Sentinel with lufenuron, flea eggs (flea growth inhibitor)
    • NOT avermectin derivative (longer half life, still agonist of glutamate-gated chloride channels, hyperpolarize cells)
  79. ctenocephalides felis life cycle
    • fleas.  16-day life cycle (min)
    • Eggs laid in hair coat fall off animal into environment
    • larvae develop in environment, eating adult feces (digested blood)
    • larvae become PUPAE, can be DORMANT FOR MONTHS (no way to kill at this stage)
    • vibration, heat and increased CO2 cause expupation, emergent fleas find host and feed
    • can survive 3 days after feeding off host
  80. to prevent flea infestation
    break life cycle.  Must kill adults and control pre-adults (can't kill pupae)
  81. Fipronil
    • flea adulticide (frontline) and tick
    • Blcok Cl ions through GABA and glutamate
    • spray or topical
    • fleas and ticks (fleas in 24h in dog and 36h in cat, slowest)
    • monthly application (3-4 week less protected)
    • getting wet reduces activity
  82. imidacloprid
    • flea adulticide (advantage, advantix includes permethrin)
    • nicotinic receptor inhibitor
    • topical
    • fleas within 12h in dog and 24h in cat (faster than frontline, slower than vectra)
    • q28 days (3-4 week less protected)
    • possible breakdown after water exposure, less than frontline
  83. vectra
    • flea adulticide, dinotefuran and pyriproxyfen (pre-adult fleas)
    • dogs only
    • nicotinic receptor inhibition
    • adult fleas, flea eggs, flea larvae, flea pupae (?)
    • Quickest topical onset, within 2 hours, death within 6 hours.
    • "repels" ticks, get through legs without bite
  84. nitenpyram
    • capstar
    • oral flea adulticide (adults only), kills within 20-30 minutes, finishes within 3-4 hours, lasts 24 hours in dogs, 36 hours in cats
    • nicotinic receptor inhibitor
  85. flea adulticides
    • fipronil
    • imidacloprid
    • spinosad
    • metaflumizone
    • dinotefuran
    • nitenpyram
    • selamectin
  86. dinotefuran
    • flea adulticide in vectra (with pyriproxyfen, 3D also includes permethrin)
    • nicotinic receptor inhibitor
    • repels ticks
    • quick onset, topical
  87. insect growth inhibitor
    • works against immature stages of fleas (eggs, larvae)
    • interfere with chiton synthesis, stops egg from hatching or kills larva (no exoskeleton)
    • voltage-gated sodium channels (?)
    • Lufenuron (program and sentinel)
  88. Lufenuron
    • insect growth inhibitor, prevents chiton synthesis, controls immature fleas (larvae and eggs)
    • sentinel and program
    • voltage gated sodium channels (?)
  89. insect growth regulator
    • prevents pupation with hormones
    • methoprene (frontline plus)
    • pyripoxyfen (vectra)
  90. pyripoxyfen
    • insect growth regulator, stops pupation of larvae with hormones
    • in vectra, with dinotefuran (vectra 3D, also permethrin)
  91. methoprene
    • insect growth regulator, stops pupation of larvae with hormones
    • in frontline plus with fipronil
  92. botanical insecticides
    • pyrethrins
    • natural from chrysanthemum flowers
    • interrupts neurotransmission (Na channel) causing paralysis and death
    • ticks, fleas, lice, mheyletiella mites and mosquitos
    • aerosol, spray, fogger, shampoo, mist
    • multiple applications (not persistent)
    • no baby cats or dogs
  93. pyrethroids
    • synthetic pyrethrins (there are several generations) insecticide
    • More potent than natural.  
    • Not safe in cats
  94. phenothrin
    • second generation pyrethroid (synthetic insecticide)
    • flea control products like Hartz
    • safe for dogs, not for cats
  95. permethrin
    • third generation pyrethroid (synthetic insecticide)
    • canine flea/tick shampoos, foggers, sprays
    • proticall, advantix, defend exspot, vectra 3D (with dinotefuran, pyriproxyfen)
    • NOT SAFE FOR CATS, separate after application for 24-48h
    • Looks like organophosphate toxicity, no antidote, hyperexcitability, muscle tremors, depression, ataxia, vomiting, anorexia, seizures, death
  96. Amitraz
    • tick control, demodex, preventic collar
    • Promeris (with metaflumizone)
    • dogs 12 wk and older, NO CATS
    • paralyzes tick mouth parts (can't transmit disease), then kills. 
    • can cause dyspnea, swelling of lips, tongue, face, urticaria
  97. flea collars
    • fipronil, pyrethrins, permethrin and/or methoprene molded into collar to diffuse or leak for several months
    • variabe effect, inconsistent dosage, side effects
    • break-away in cats or strangle
  98. environmental flea control
    • control environment, wash, vacuum, cut nearby branches, spray with knockout (stops larvae from becoming pupae) pump spray
    • remove pets and food/water dishes from house before spraying, air out before return.  Birds longer
    • pyrethrins in yard, avoid direct contact with pets.
  99. demodicosis therapy
    • only treat demodex if generalized, immune suppressed. All animals have own demodex at hair follicle.
    • amitraz (dip): toxic (sedation, lethargy, ataxia, hypotension, v/d, hypothermia), yohimbe as antidote, use eye ointment, gloves, wahs, no stress for 24h
    • milbemycin oxime: 1 mg/kg = 50%, 2 mg/kg = 90%, expensive, lasts for months
    • high-dose ivermectin: gradually step up dose and monitor for neuro, no shepherds