Parasitology 4 Flashcards
Dictyocaulus viviparus what is it, effect on host
Lungworm of cattle
• major pathogen of cattle particularly young calves
• cough, laboured breathing and difficulty walking
• hypersensitivity type 1 reaction
• Adults generally subclinical and act as carriers for young calves
○ develop strong immunity
Dictyocaulus arnfieldi what is it, location and effect on host
Lungworms of equines
- in trachea
only mildly pathogenic
Parelaphostrongylus tenuis what is it and effect on host
Lungworm of deer
No clinical signs with deer
- in abnormal host (cattle, sheep, moose -> produce fatal neurological disease
Parelaphostrongylus tenuis what is it and lifecycle
Lungworm of deer
- eggs laid in cranial venosus sinuses
- Eggs carried to lungs and hatch
- larvae enter alveoli & reach faeces
- L1-L3 develop in snail
- L3 ingested via ingesting infected molluscs
- L3 migrates through abomasal wall to abdominal cavity
- follow nerves to spinal cord
- migrate up spinal cord to subdural space
- Moves to predilection site -> cranial venous sinus
- Undergo moult there and become an adult
Elaphostrongylus cervi what is it, location and effects n host
Lungworm of deer
- snail intermediate host
No clinical signs in normal host
Neurological signs in other ruminants around deer
Aelurostrongylus abstrusus what is it, host, location features and effects on host and which lifecycle
Lungworm of cats Features: • tiny nematode, in alveoli • very common parasite in southern parts of the country, common within cats Effect on host: • generally subclinical • mild cough • weight loss • eosinophilia INDIRECT - slug or snail as intermediate with cats as paratenic host
How to diagnose lungworm infection, 2 ways and describe
1) Baermann technique
The Baermann technique is based on the active migration or movement of larvae.
1) Faeces are suspended in water.
2) The larvae move into the water.
3) They sink to the bottom and can be collected for identification.
2) Larvae with distinct morphology
Metastrongylus apri, salmi, pudendotectus what are they, location lifecycle and effect on host
Lungworm of pigs
Location - bronchi
Lifecycle - Indrecti - intermediate is earthworm which pigs then ingest (L3)
Effects on host
- respiratory airway disease, obstruct airway
- transmit swine influenza virus
Angiostrongylus vasorum what is it, host, location, feature, lifecycle, PPP, clinical signs
Lungworm of dogs - pulmonary artery Barbers pole appearance! Lifecycle - indirect, snail as intermediate host PPP = 4-8 weeks Clinical signs • mild, cough, interstitial pneumonia; • severe cases develop heart failure - Right sided congestive heart failure
Oslerus osleri what is it, host, location, lifecycle, PPP, effects on host
Lungworm of dogs nodules within the trachea DIRECT 1) L1 (infective phase) passed in faeces 2) L1 ingested 3) L1 regurgitated with food & water 4) larva penetrates duodenum 5) migrates to lung (all moults occur) then trachea (predilection site) PPP about 18 weeks Effects on the host • very common in dingoes • clinical signs of airway obstruction
Filaroides hirthi what is it, host, location, lifecycle, effects on host
Lungworm of dogs tiny worm in alveoli Life cycle: DIRECT • L1 passed in faeces Effects on the host: • infection usually inapparent • grossly nodular lesions on the surface of the lungs • fatal with intercurrent disease
Angiostrongylus cantonensis what is it, host, location, clinical signs
Lungworm of rats
Location - pulmonary arteries
Effects on hosts
• NO clinical signs in rats
• in abnormal hosts (dogs, cats, horses, zoo animals) causes severe encephalitis
○ Cause of eosinophilic meningitis in man
Angiostrongylus cantonensis what is it, lifecycle
Lungworm of rats
Lifecycle: INDIRECT LIFECYCLE
1) L1 released into blood stream
2) breaks into alveoli -> coughed up and swallowed -> passed in faeces
3) L1-L3 in snail or slug, prawns and land crabs
4) rat eats snail or slug (do not have to eat L3 can be shed on leaves)
5) larva enters blood stream, migrates to CNS
6) moults to L4 in anterior cerebrum
7) enters venous system and migrates to pulmonary artery (predilection site)
Give 6 characteristics of anthelmintics
1) Spectrum of activity
2) administration
3) safety margin
4) selective toxicity
5) withdrawal period
6) economical
What are the 3 tests for evaluating the efficacy of an anthelmintic
1) Faecal egg count reduction test (FECRT) -> Select animals with worms and treat with anthelmintics and other without
○ Compare pre and post-treatment egg counts -> if effective should reduce egg count by 95%
2) controlled test: control and treated groups -> - Have group with anthelmintics, another group used as negative control, after treatment slaughter all the animals and count the number of worms
○ Most effective test and mainly used for ruminants
3) critical test: treated animals act as controls
- Select animals infected with parasites, treat them and collect faeces for 5-7 days look for presence of faeces, then slaughter and faecal egg count of the animals
What drug inhibits tubulin formation
- Benzimidazole
What drugs act on the nervous system
- Levamisole, morantel, pyrantel, ML, organophosphates, piperazine
What drugs act on decoupling oxidative phosphorylation
- Substituted phenols and salicylanidilies, closantel, oxycylozanide, disophenol, niclosamide
Benzimidazoles mode of action, 3 types and examples
Mode of action:
• inhibits polymerization of tubulin
1) Primary BZ
- Thiabendazole, broad spectrum, not effective against inhibited larvae
TBZ kills migrating larvae of S. vulgaris at 10X dose rate
○ 5 daily doses kills inhibited larvae of Ostertagia
2) Secondary
- Oxibendazole, longer duration of effect
3) Tertiary BZ’s highly effective against inhibited Ostertagia
Benzimidazoles what type of drench, and pharmacological features, are eggs killed
Referred to as “white” drenches
1. form depot in rumen; absorbed in rumen
2. metabolised to primary metabolites - go into GIT tract with anthelmintic activity
3. secondary metabolites formed in the liver, blood surfaces diffuse across gut wall
4. excreted in urine and bile duct (can kill liver fluke)
OVICIDAL - eggs are killed by these chemicals
Benzimidazoles what does it kill in ruminants, horses
Ruminants
- kill all “strongyles”, trichostrongyles & lungworms
- kill inhibited larvae & migrating larvae
- widespread resistance in trichostrongyles of sheep
Horses
- kill adult stages of all strongyles; kill migrating S. vulgaris larvae
- NOT effective against inhibited cyathostomes (except when 5 daily doses used)
- widespread resistance in cyathostomes
Imidazothiazoles main example, mode of action
Levamisole
Mode of action:
• cholinergic agonists at synaptic and extra-synaptic nicotinic acetylcholine receptors (motor end plates)
• depolarisation causes spastic paralysis (continuous action potential)
Imidazothiazoles what type of drench, what is it effective against and does it kill eggs
Liquid clear drench
Activity
- all Gastrointestinal nematodes and lungworms
NOT effective against inhibited larvae and flatworms (cestodes and flukes)
NOT OVICIDAL
Tetrahydropyrimidines give 2 examples, mode of action and general activity
Morantel, Pyrantel Mode of action: • depolarise motor end plates in muscle • same site of action as levamisole Activity: • most GINs; NOT lungworms** • NO effect on inhibited larvae**
Tetrahydropyrimidines pharmakokinetic characteristics and cross resistance
• soluble • administered orally • rapidly absorbed • excreted in urine Cross resistance with levamisole (if resistant to levamisole than resistant to morantel -> not the other way around)
Macrocyclic lactones mode of action and activity on what nematodes
paralysis by binding to GABA gated Cl-ion channels in neurons -> hyperpolarisation -> FLACCID PARALYSIS Activity: • all GINs and arthropods • NOT cestodes or trematodes • extremely potent
Macrocyclic lactones what are the 3 administration routes and how does this change availability
Depending on route different phase
Oral -> High availability at GIT sites of parasites
- improve therapeutic response to nematodes
Subcutaneous -> high systemic availability
- Extended persistence
Pour-on -> large skin depot, erratic percutaneous absorption, oral ingestion (cattle -> lick other animals)
- Large inter-animal variability in exposure and therapeutic response
Macrocytic lactones safety index and environmental affects
Safety index: 20X - wide margin of safety
Environmental effects:
- persists in faeces, kills arthropods - antibacterial properties in the environment
- moxidectin has less effect on dung beetles - more recent environmentally safer
Organophosphates give 2 examples, mode of action, activity against and what animal used in
- Naphthalophos, dichlorovos
Mode of action:
• inhibits acetylcholinesterase – spastic paralysis
Activity:
• highly effective against Haemonchus
• higher doses needed to kill Trichostrongylus, Ostertagia
• erratic against Nematodirus, Chabertia & Oesophagostomum
Use:
• used only in sheep
Heterocyclic compounds give example, mode of action, activity and how given
- Piperazine (diethylene diamine)
Mode of action:
• agonist of GABA receptors - flaccid paralysis
• relies on peristaltic action to remove worms
Activity:
• narrow spectrum - ascarids and nodular worms (number one choice for ascarids)
• given orally
Salicylanilides give example, mode of action, how given, activity against what nematodes and safety
- Closantel Mode of action: • uncouples oxidative phosphorylation -> deprive them of energy Pharmakokinetics: • soluble, given orally • persists for 4-6 weeks Activity: • inactive against most nematodes • cannot penetrate cuticle • highly effective against blood feeders - Haemonchus Safety index - 5x (low)
Octadepsipeptides (Emodepside) mode of action, activity and what animals used for
Mode of action:
• causes flaccid paralysis by binding to the latrophilin receptors in parasitic nematodes
Activity:
• effective against most nematodes
Use:
• currently used in product for dogs and cats - not production animals at this stage
Amino-acetonitrile derivatives (AAD’s) give example, mode of action (what good about it) what used against and the main worm, safety
Monepantel
Mode of action: (unique - so no cross-resistance)
• a nematode-specific ACR-23 nicotinic acetylcholine receptor sub-unit only found in nematodes
○ Open Na ion channels
○ causes spastic paralysis
Activity:
• effective against most GINs in ruminants, except lungworms
• Haemonchus
Large safety index 30
Derquantel mode of action, activity
CRAP
Mode of action:
• nicotinic antagonist causing flaccid paralysis - does not kill nematodes
What 2 anthelmintics are effecive against encysted larvae of small strongyles and at what level
- Fenbendazole @ 10mg/kg/day for 5 days
2. Moxidectin @ 0.4 mg/kg - one dose only
Deworming pups and pregnant bitches what is the treatment times and chemical
Pups
• treatment every 2 weeks prior to weaning
• treatment every 4 weeks after weaning
• treatment every 3 months after 6 months of age (depending on risk factors -> if low risk up to 6 months)
Pregnant bitches (parasites within mammary tissue)
• Fenbendazole @ 50 mg/kg/day (almost 10 times normal dose) from 3 weeks prepartum to 2-15 days postpartum
○ Once infected with this larvae generally infected for life - act as a source of the parasites to the pups
Define Single, double, multiple and cross resistance
- “single” resistance - to one class of drugs
- “double” resistance - when two different parasites develop resistance to different types of anthelmintics
- “multiple” resistance - one parasite developed resistance to more than one anthelmintic
- “side” or “cross” resistance - if worm population developed resistance to one drug within a class (resistance is then given to other drugs in the same class OR cross resistance between classes (one class gives you resistance to another class)
List 8 factors that influence develpment of resistance and which way
1) Polymorphism in nematode population
2) initial frequency of resistance alleles
3) number of genes involved - one gene shorter lag phase
4) fecundity & length of life cycle -> high shorter lag phase
5) resistance genes dominant or recessive - dominant shorter lag phase
6) treatment frequency -> MOST COMMON need to use epidemiology
7) Refugia - leave 20% pop susceptible less selection longer lag phase
8) Pharmacokinetic profile of drug (“tail selection”) -> animals exposed to sub-therapeutic levels of the drug and therefore shorter lag phase
List 5 resistance mechanisms and example for ML, Lev, BZ
1) Reduced drug uptake inside the worm
2) Increased drug efflux -> P-gps (p-glycoproteins) -> transport drugs out of the cells
- Possible ML (macrocyclic lactones)
3) Detoxification (get inside but metabolised rapidly)
- Involves enzymes cytochrome P450
4) Altered target within the worm
- Possible Lev, BZ, ADD
What are the 5 main groups of anthelmintics and what species is resistance the most issue
Have only 5 drug groups
1. BZ’s
2. LEV (Levamisole- Imidazothiazoles
3. OP’s
4. ML’s
5. (closantel) - Amino-acetonitrile derivatives (AAD’s)
SHEEP - most issue, most with low level of resistance which isn’t evident clinically
What molecule does new drugs involve and what is the goal
Trying to block P-gps that increase the efflux of drugs out of the worm
- When use in vitro results in increase efficacy of the drug
- Not done in animals so aren’t there yet
REVERSAL OF ANTHELIMITC RESISTANCE
List and briefly describe 5 tests for anthelmintic resistance
1) egg hatching inhibition using benzimidazoles - count number hatch after exposure
2) tubulin binding assay using benzimidazoles
3) Larval paralysis test using Levamisole/ML - if killed won’t pass through mesh
4) larval development test - Drnchrite test - eggs extracted from faeces and if hatch resistant
5) field test (faecal egg count reduction test - Anthelminitics should reduce FEC to 0 -> resistant is less than 95% reduction
What are 6 important management considerations to help slow anthelmintic resistance
1) check timing and administration of drenches
2) check management practice (pasture, timing)
3) double dose - NOT BZ as decrease lag time
4) Use of rotation and mixtures
5) quarantine drenches for all introduced sheep
6) use monepantel - caution don’t want to get resistance here
