Protozoa - antiparasitic agents

• coccidia
• unsporulated oocysts in feces

• 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

• 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

host-specific.  Canines will not infect felines, etc, neither infect humans.  (crypto)

• sporulated oocysts (96hrs after shedding) can survive a year in moist, protected environment.
• Killed in freezing or high temps
• sporulation at 20-40 C

• coccidia form, non pathogenic to animals (just carried)
• zoonotic

• based on signalment, history, clinical signs and oocytes present in feces.  
• Oocytes are not definitive, could be pseudoparasite

• Eimeria
• looks like isospora, is non-pathogenic to dogs.
• parasite of deer and rabbits.

• Sulfadimethoxine (Albon): ONLY drug approved
• Ponazuril: newer drugs, off-label, may be effective

Albon, used in coccidia.  (also Ponazuril)

new drug, off-label for Coccidia

• Felines ONLY DEFINITIVE HOST
• any warm blooded animal intermediate host
• most important coccidian parasite
• ZOONOTIC

where parasite can perform sexual reproduction

• 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

toxoplasma life cycle, when organisms penetrate intestinal wall and replicate throughout body as tachyzoites (no sexual reproduction)

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

• 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.

infective

non-infective

• 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

• most asymptomatic, young more likely to show signs
• myositis (muscle)
• chorioretinitis (lesions in eye)
• meningoencephalitis (brain)
• pneumonia
• lymphadenopathy
• abortion

• 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)

Clindamycin hydrochloride for 2-3 weeks.

• 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

• large % of humans have had toxo, asymptomatic
• chorioretinitis, meningoencephalitis, myositis, abortion, pneumonia, lymphadenopathy, brain lesions in AIDS patients

• most serious toxo infection
• asymptomatic at birth usually
• signs of infection later in life
• loss of vision, hearing, mental retardation, death

• 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

• 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?

• direct, no intermediate hosts
• Trophozoites and cytses pass in feces, contaminate soil and water
• final host ingests
• zoonotic?

• maldigestion, malabsorption and hypermotility (diarrhea), caused by damage to enterocytes
• profuse watery diarrhea, possible vomiting, abdominal cramps, fever.  
• No melena or hematochezia, possible mucus.

• 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

• companion animal parasite council
• authority on parasites
• suggest direct smear, fecal float with centrifugation and ELISA or immunofluorescent assay with repetitions for Giardia diagnosis

• 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

• 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

• d/c: giardia duodenalis
• human: giardia lambia

• 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

• 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

• 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

• 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

• 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

VD in cattle, bulls asymptomatic, cows get metritis, vaginitis, abortion, pyometra

sinuses, mouth, esophagus, genital tract of birds (URI, some genital infections)

pigs.  Cook your pork!  Zoonosis

• 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.

human STD with green frothy discharge and itching.  More than 8 million new cases yearly

• Giardia, primarily from direct smear.  
• Trichomonas has jerky, random movement
• giardia has falling leaf movement

• polymerase chain reaction
• amplify DNA, make it easier to find

• agents that are destructive to protozoa
• Giardia and coccidia most common d/c parasites
• Metronidazole
• Sulfadimethoxine (albon)

• agents that are destructive to parasitic worms
• antinematodal (Roundworms, hookworms, whipworms)
• anticestodal (tapeworms)
• antitrematodal (flukes)

• NITROIMIDAZOLE (makes DNA lose helix and break apart)
• BANNED IN FOOD-PRODUCING
• 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

• 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

keratoconjunctivitis sicca

• 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

• 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)

• 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)

• topical (transdermal), contains praziquantel.  
• Paralysis and death of nematodes
• round: tox canis, cati, leonina
• hook: ancylostoma

• 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

• tapeworms
• dogs: taenia pisiforms (rodents)
• dipylidium caninum (fleas)
• echinococcus sp (encysted in liver)
• cats: taenia taeniaeformis
• dipylidium caninum

• 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

• flukes, HUGE. 
• no labeled products, use praziquantel, sometimes fembendazole
• d/c: paragonimus kellicotti (most common)
• alaria
• nanophyetus salmincola
• dogs: heterobilharzia americana
• cats: playnosomum fastosum

• 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

cough up blood from respiratory tract

• 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

• 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

• 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.

heartworm associate respiratory disease

• 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.

• 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)

how to prep slide to look for microfilaria

false heartworm, but smaller, blunted head and shepherd's crook tail.

• 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

• 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

• 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)

• antibiotics produced by streptomyces (microorganism found in soil)
• agonist of glutamate-gated chloride channels, hyperpolarize cells
• ivermectin (heartgard), selamectin (revolution), moxidectin (proheart)

• 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

• 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

• 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

• 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)

• 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

break life cycle.  Must kill adults and control pre-adults (can't kill pupae)

• 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

• 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

• 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

• 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

• fipronil
• imidacloprid
• spinosad
• metaflumizone
• dinotefuran
• nitenpyram
• selamectin

• flea adulticide in vectra (with pyriproxyfen, 3D also includes permethrin)
• nicotinic receptor inhibitor
• repels ticks
• quick onset, topical

• 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)

• insect growth inhibitor, prevents chiton synthesis, controls immature fleas (larvae and eggs)
• sentinel and program
• voltage gated sodium channels (?)

• prevents pupation with hormones
• methoprene (frontline plus)
• pyripoxyfen (vectra)

• insect growth regulator, stops pupation of larvae with hormones
• in vectra, with dinotefuran (vectra 3D, also permethrin)

• insect growth regulator, stops pupation of larvae with hormones
• in frontline plus with fipronil

• 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

• synthetic pyrethrins (there are several generations) insecticide
• More potent than natural.  
• Not safe in cats

• second generation pyrethroid (synthetic insecticide)
• flea control products like Hartz
• safe for dogs, not for cats

• 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
• REPELS MOSQUITOS, BITING FLIES, CHEWING LICE
• Looks like organophosphate toxicity, no antidote, hyperexcitability, muscle tremors, depression, ataxia, vomiting, anorexia, seizures, death

• 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

• 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

• 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.

• 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