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parasit
lok
11/5/97

ectoparasites of small and large animals


note: tomorrow afternoon we're switching micro and parasit lectures. 
don't worry about it just show up.

ok. we have handouts on ectoparasites 
of small and large animals. we're running low on time so we'll just go 
over the important parts. only the important parts will be on the exam. 
ok. here we go.

looking at handout for small animal ectoparasites:


really not going to do much about lice b/c the whole life cycle occurs on 
the host, control is easy - most dogs are treated with some lindane based 
shampoo 1xweekly x four weeks, cats treated with carbaryl or rotenone. 
also new agents for flea control that stand a good chance of also getting 
the lice due to long residual activity. louse problems can be serious if 
not treated but are easy to control with once weekly topical 
insecticides.

most significant ectoparasitism in dogs/cats is flea 
infestations. complete metamorphoses. immature stages occur OFF host, 
larval growth off host. eggs not adhesive - laid on host but fall OFF 
host. so eggs, larvae, pupae are in environment. it was found that 
distribution of eggs/larvae in household tracks well with pathways that 
dogs frequent. often hotspots exist where animals jump down off of sofas, 
chairs, etc. 

0-l-l-l-p-a : probably takes 20-24 days under optimum 
conditions (but can have extended dormancy)

egg stage: 2-5 days
larva:

larva: entire larval development 7-14 days
larva:
pupa: will mature and 
hatch in about 14 -30 days (can remain dormant up to 60 days if no host 
is available - or even up to a year!) think 2 wks to a month, though.

adult: on the host all the time

egg and pupae are resistant to 
conventional chemical pesticides. if you treat environment with 
pyrethrins, carbamates, other chemicals, the pupal stage will survive and 
can remain dormant and resistant for a long time, so adults will emerge 
from it, and need to be dealt with, in 2 wks to 1 mos time, or possibly 
longer.

pathogenesis in fleas - if you consider them as int hosts for 
tapeworms, there's nothing to add to that...the main thing is flea bites 
as a sort of acute insult to host - they form an itchy wheal, like any 
other insect bite - flea injects saliva with antigenic stuff in it, and 
causes acute reaction. also they will in some cases sensitize the host 
against further flea bites. in the sensitized host, subsequent exposure 
to the antigen will elicit a generalized dermatologic response - all 
previous bite sites will flare up again, causing a generalized very 
pruritic dermatitis. hairloss in ventral abdominal area, base of tail, 
hind quadrant of body is typical distribution of FAD.  probably more than 
the acute bite problem is this sensitization and the flaring up of 
dermatitis in response to one single flea bite.  you'll hear more about 
this in the dermatology course. but just remember this for now, that 
there can be a systemic itchy generalized reaction.

we talked before 
about three objectives of flea control. 
most problematic, most client 
education needed, is breaking flea life cycle in environment. classicly, 
topic tx of infested hosts has NOT been sufficient to alleviate a flea 
problem. this is b/c all the flea biomass was in environment. you have to 
explain this to the client. new topicals may change the way we deal with 
this. but conventionally we use pyrethrins, organophosphates, and 
carbamates. we have a 2-4 wk period within which we need insecticidal 
activity in the environment. we have to get the larvae that are there, 
adn the adults which arise from existing pupae, which may not come out 
for a month (or more...). ideal thing would be to use something with 
residual activity of at least 30 days.this would include carbamates, many 
organophosphates, and some growth regulators. their activity is going to 
encompass at least thirty days. why not just use those? well, their 
knockdown capability is less than 100%. they won't kill all of the fleas. 
so what's the alternative? use a nonresidual in repeated doses - they may 
last 2-5 days in the environment, so you use them weekly or something. 
classic ones of this type are pyrethrins.  this has pros and cons. in a 
way we want them to be nonresidual so they degrade and we don't have 
toxins lying around ready to target nontarget organisms. but for 
practical flea control, a client won't want to apply stuff frequently 
because it's a pain in the ass. the rare client will comply with this 
program but not many. but these products do have quick knockdown of 100% 
of population.

so, most commercial flea preps for environmental flea 
control now combine both types into one preparation. a pyrethrin for 
quick knockdown, and a carbamate like Sevin or something for residual 
activity. 

quick kill
pyrethrins
resmethrin, permethrin, tetrametrhin


organophosphates eg dichlorvos
botanicals eg rotenone

these quick kill 
nonresiduals can be microencapsulated, to give them some residual 
activity

residuals include carbamates (carbaryl, bendiocarb) and 
organophosphates like malathion, chlorpyrifos (these can also be 
microencapsulated to INCREASE their residual activity beyond 30 days - up 
to 6 mos. this chlorpyrifos is in duratrol)

so microencapsulation 
technology is really useful, but ads are often misleading.

growth 
regulators:

methoprene, pyriproxyfen
both mimic activity of naturally 
occuring insect hormone called juvenile hormone or JH. "jh analogs". 
the 
JH in hemolymph of flea is naturally present in high amounts during 
larval period - it cues molting from larval to larval stage. titer then 
drops off, and larva molts to pupal stage. so juvenile hormone maintains 
the juvenile state. so, if you apply these analogs like methoprene to the 
environment, you keep titer artificially high - larvae do not mature into 
pupae. they never get the signal to mature. they just molt to a nonviable 
supernumerary larval stage and die out. these are not found in mammals so 
are not toxic to mammals, are great for environmental flea control around 
small children. what are the problems with them? they have no activity 
against adult fleas. they do nothing to the adult flea. you need to 
quickly get rid of adult fleas because they are the immediate problem. so 
there are commercial preparations which combine this stuff with 
pyrethrins - like siphotrol plus. even some OTC flea products have this 
stuff in it with pyrethrins. pyriproxyfen is pretty stable under UV light 
so is pretty good - methoprene breaks down under UV so isn't good 
outside, but is good inside. both of these, if applied correctly, have a 
residual activity of 30-40 days (assuming no UV breakdown of methoprene)


another environmental control technology - lufenuron/program. 
lufenuron 
is a metabolic inhibitor. mode of action - inhibits chitin synthase which 
polymerizes chitobious monomers into chitin. causes abnormal formation of 
many cuticular structures in developing fleas. the "egg tooth" which 
forms on embryo is affected, so larvae may not be able to hatch. 
lufenuron is given orally to dogs and cats. when adult fleas bite the 
animal, the eggs they lay are exposed to it, and any larvae that might 
emerge will be abnormal (most eggs won't even hatch). this is great 
stuff, b/c of convenience. clients like to give pills to control fleas. 
zero nontarget toxicity. disadvantage - it's great for breaking the life 
cycle, but it happens over time. it does NOTHING to the adult fleas. you 
still need an adulticide. so if you're interested in fast results, you 
have to augment this some kind of conventional control program. lufenuron 
will do it on its own over 2-3 mos and that's fine if there is no acute 
problem going on, eg if this is prophylactic. but if there is already an 
acute problem you have to augment with more conventional methods.

later 
on you'll hear -= heck, right now, milbemycin oxime, in some of the HW 
tablets, is now available with lufenuron so there's a single oral tablet 
for HW and fleas - this is Novartis' Sentinel. disadvantages?
keep in 
mind that  the flea must bite the host to get a dose - so if animal is 
allergic, you really need to use something else, because you do not want 
the animal being bitten!

some inert abrasive aerogels - fleabusters - 
their program involves applying small sodium polyborate crystals to home 
environment - these have little to no nontarget toxicity - they abrade 
cuticle of larvae, and act as poisons to larval fleas. some concern about 
health effects of these crystals if inhaled by people in the house. 


treatment of host: old way was to use stabilized pyrethrins - 
microencapsulized formulations.  never really lived up to their label 
claims. but immitocloprid aka advantage, and  fipronil/phenylpyrazoles 
aka frontline, do work. both last at least one month on the animal, very 
effective for a month. fipronil claims up to two months but recommends 
monthly application. the other nice thing is that their mode of action is 
a whole different mechanism - you don't have to worry about compounding 
neurotoxic effects of organophosphates. if you apply environmental 
organophosphate, you don't want to also use that on your pet. but these 
bind to GABA gated chloride channels, blocking them. work differently 
from organophosphates, carbamates, and pyrethrins, and last a month in 
the haircoat of the host - these are the big things. so finally, we have 
something with the 30 day residual activity needed to break environmental 
life cycle! if fleas hatch within 30 days, these agents should be able to 
get them. these claim to be effective with no other environmental 
control, and field data seems to support this. so these two agents are 
good. immitocloprid/advantage has a fast knockdown - kills adults in 
haircoat very quickly. good for allergic animals. but it is fairly water 
soluble, washes off easily. fipronil/frontline, however, goes into 
sebaceous glands, isn't easily washed off or soluble. if it does wash 
off, it seems that stuff comes up from sebaceous glands - animal kind of 
self re-treats itself after bathing.

skipping to ticks on dogs/cats - 
don't sweat the biology of these guys. remember ripicephalus is the 
domestic dog tick, dermacentor and ixodes are the woodland ticks. 
chemical control methods used for these ticks - probably the best thing 
is amitraz, the active ingredient in preventic collar. inhibits 
attachment of ticks onto host skin. this collar seems to give good 
residual control and prevention of tick attachment. another big plus with 
fipronil is that it also claims to kill dermacentor and ripicephalus for 
30-50 days - and probably also kills ixodes. 

mange mites/ear mites. 
just remember ivermectin is good against sarcoptes scabei in dogs, at 200 
mcg/kg subcutaneously. before giving that dose make sure the dog is mmf 
negative!! do an mmf check. retreat in two weeks. 

feline mites 
notoectes or whatever - lime/sulfur dips. ivomec is effective but safety 
not confirmed. note that ivomec isn't licensed at this therapeutic dose 
in dogs or cats.

otodecties - thiobendazole tx of choice historically, 
but 200 mcg/kg subcu of ivomec also works.

demodex- if you have a 
generalized infestation you have to treat it with amitraz. it comes as 
mitaban, and is used topically at 2 wk intervals up to 6 times. it may be 
worth noting that milbemycin oxime has some activity against these mites, 
but you have to give a really high dose - 500 mcg/kg daily for 30-60 
days. this drug is licensed to use MONTHLY at that dose. you're using a 
5-10 year supply of interceptor this way. so it is more practical to use 
the amitraz. 

large animal handout - 

direct your attention to for each 
spp we discuss scabies or mange. cattle, sheep, goats, horses, and we 
talk about a triad of mange mites in these spp.

sarcoptes scabei

psoroptes
chorioptes
any of these can be found in cattle, sheep, goats, 
or horses. they each present with a classic kind of presentation on body 
of host. lesions and location is characteristic in all types.

cattle: 
sarcoptes localize in sparsely haired areas, psoroptes localizes over 
trunk area where hair is thick, chorioptes localizes in extremites - 
hocks, tailbase. 

sheep/goats
horses 
this is also true. same as in 
cows. so you can speciate based on location of lesions, in many cases. in 
horses, also, we see the triad of mites causes some different lesions - 
sarcoptic lesions are dry, psoroptic lesions are serous wet mange, adn 
chorioptes is around hocks/tailbase.

all three mites susceptible to 
licensed dose of ivomec, 200 mcg/kg for cows, sheep, goats, horses. also 
look at the little control program built up for cattle lice. that amounts 
to kind of a generic control program for most other ectoparasites 
(arachnid). coumaphos is safe for lactating dairy cows (organophosphate); 
ectaban/permethrin is safe, and fenthion a systemic is also safe and 
used. the systemics have long withdrawal period, though.
so, you can use 
one of these topicals along with ivomec and you're covered.

horses - 
culicoides dermatitis is well characterized. results from fly feeding. 
synthetic pyrethrins are agent of choice. 

swine- we discussed sarcoptic 
mange as being a very critical problem in swine. again, as sort of a 
theme we see arising here, they are susceptible to ivomec. 300 mcg/kg is 
licensed dose - quickly and effectively controls sarcoptic mange, often 
used prophylactically in preparturient sows. also that dose works for 
louse and tick control in swine.

curious note: swine also are plagued by 
fleas. ctenocephalides are commonly seen  on swine, and the human flea 
also - use same control as on dogs/cats.

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dr guerrero

principles of anthelmintic use

[note: tomorrow we will get a lecture on 
parasites of swine- lecture and slides are on the web, FYI. note also 
that next week on thursday we have 2 lectures scheduled but we can have 
only one lecture and then a quick review of swine parasites.- 15 min 
review. there will be a swine question on the final.]

so. principles of 
anthelmintic use. note: last four pages of chandout has 4 charts. first 
three should say bovine endectoside chart and the last one should say 
equine.

ok. so. 
control measures of helminth infections are heavily 
dependent on use of anthelmintics, so vet can break cycle of 
transmission.

you have trematodes in water, nematodes in soil, cestodes 
in soil/int hosts. with chemotherapy you can break the cycle. 

ideal 
anthelmintic properties:
broad spectrum
nontoxic and safe to animal and 
human
rapidly excreted
no residues in milk/meat
easy to administer
cost 
effective

ideal anthelmintic would get rid of all the types of worms and 
all the stages of them. we don't have one drug to do this. however....


in late 1940s the only one was phenothiazine, given at about 1 gram/kg. 
by about 1960, thiabendazole was around, and was given at only 88 mg/kg. 
now almost linearly we've developed higher and higher potency drugs with 
lower doses. ivermectin in the early 80s can be given at micrograms/kg. 
now, we have doramectin and eprinomectin which are at similar potencies. 

we want broad spectrum properties - 
should be effective against all 
stages of all genera
should be effective against L4!!! in cattle - very 
important, most pathogenic
in horses should be useful against large and 
small strongyles, parascaris equorum, and bots (gasterophilus larvae)

in 
dogs/cats useful against hookworms, heartworms, roundworms

any ideal 
anthelmintic should get all these. they should be nontoxic to animal and 
user. ivermectin is very safe for animal and user with about a 30x safety 
range. benzimidazoles also very save at 10-100x recommended dose.

commonly used organophosphates have narrow safety margines. only about 
1-3x recommended dose. OPs inhibit acetylcholinesterase in parasites and 
mammals, 

herd tx is hard because you have to guess wt, if you guess too 
low, you underdose, which can trigger development of resistance. if you 
overguess, you can see toxicity esp if using organophosphates.

rapid 
metabolism and excretion important b/c less tissue residue and withdrawal 
times in production animals. fenbendazole - zero milk reduction. 
eprinomectin: zero meat and milk production. eprinomectin is first 
approved anthelmintic with complete zero withdrawal time.

plasma 
concentration of types of avermectins:sometimes plasma and milk profiles 
match - ivermectin has a high concentration in milk while it is high in 
plasma - so you can't use ivermectin in lactating dairy cows. however, 
eprinomectin has very high plasma concentrations and very low 
concentrations in milk - negligible - below 20 ng. so epinomectin has no 
withdrawal time requirement (ivomec-eprinex). also very safe.

ease of 
administration also important for vet and consumer. injectable and oral 
preps are favored. injectables esp subcu preferred in cattle. IM 
injections may make blemishes in carcass which inspectors won't like. 
also speed of administration with subq preps. oral forms in ruminants are 
given as paste or drench. drench is suspension or solution given with 
dosing tube. also can use medicaated salt blocks or feed mixes. most 
recent formulations for oral admin are sustained release boluses - they 
are engineered to maintain constant release of active compound over time.  
this allows control for a long time, allowing animal to be maintained 
almost parasite free.

objective of tx - maintain aniamls free of 
parasites. break transmission cycle. 

tx of sick animals esp in cherds 
is not very convenient b/c of quick ingestion of L3s and quick 
reinfection of animals. so removal of parasites from a chost doesn't mean 
instant return to good health. objective is to prevent reinfection. think 
prevention.

it's more rewarding to concentrate on chemoprophylactic 
strategies that reduce ingestion of L3s, causing pasture clean up. this 
is the idea of persistence of anthelmintics. rule of thumb for pasture 
cleanup is to treat at times of year when pasure conditions are becomeing 
optimal for development of larvae.

many formulations of anthelmintics 
exist. classify into three types:
benzimidazoles, imidazothiazoles, and 
avermectins. only avermectins offer persistent activity, which is 
dependent on type and formulation. duration of persistency also heavily 
dependent on molecule and formulation.

IVOMEC 1% claims 21 days 
persistence against ostertagia and dictyocaulus, and 14 days against 
haemonchus placei, trichostrongylus axei, cooperia spp, and 
oesophagostomum

tremendous variation

ivomec plus has the same 
persistence activity. but when you use the pour on formulation applied to 
the skin, persistence is much less. only 14 days against ostertagia, etc.


dectomax injectable has 21 days against ostertagia. 

ivomec SRsustained 
release bolus - 135 days against many spp of nematodes

so persistency is 
very dependent on type of molecule AND formulation
the bolus delivers 12 
mg ivermec a day for 135 days. target animals are 275-660 lbs, over 12 
wks old, ruminating. if animal isn't ruminating, the bolus will go into 
abomasum.


when you give this bolus there is a rapid increase in level, 
and then sustained delivery 12 mg/day, then rapid drop off at 135 days. 
rapid drop off == reduced chance of developing resistance.

this gives 
almost complete control of pasture contamination - with injectable form, 
you have reinfection occuring; with bolus, b/c of constant release, 
reinfection is completely controlled for at least 6 mos. 

this reflects 
in bw gains - animals will gain more weight when treated with the bolus. 
so in large animal medicine, esp production animals, you have to talk 
about return on investment. 

ivomec maximizer - in sheep, there is an SR 
bolus called maximizer, not in USA yet, but used in australia and NZ - 
the cylinder contains a series of tablets, which dissolve in about a 
month. so there is a pulse release over a period of time. 

with normal 
conventional bolus - you remove adult polupation, control pastures, and 
prevent reinfection - but with longer sr bolus, you also get many other 
benefits - 

palatability is a must for ease of administration in canine, 
feline, and equine patients. horses remember bad tasting formulations 
such as oral telmin b powder. palatability is crucial in compliance of HW 
control (beef chewables and tablets) - small animals in particular - you 
rely on owner to tx, and they won't if dog doesn't like it...

factors in 
client compliance:
frequency of administration - convenience is 
important. least freqent dosing has most compliance. reminders are 
important (heart stickers on calendar). infrequent dosing reduces 
forgetfulness problems.
ease of administration - type of administration 
is important, as is palatability. heartgard was at first a tablet, the 
beef chewable worked better, dogs like it, increased compliance.

motivation - educate client re: disease seriousness, consequences of 
noncompliance
understanding directions - they must be clear, how to use 
meds, how to use reminders, when to get refills, confirmation. in much of 
the US, vets use HW preventives for 6 mos. some use 12 mos not because 
they need to, but b/c owners forget to come back every 6 mos, and 12 mos 
schedule increases compliance.

patient compliance - palatability!

factors in dog compliance: 
ease of administration
potential for tablet 
rejection
impact of palatability

dog preference studies: three trials 
with three PIs in three states - illinois, PA, AL. 331 dogs dosed. 
products were offered by hand, both simultaneously. given 1-4 hrs post 
feeding. they alternated hands daily. same person offered throughout 
trial. of the 318 dogs, 302 preferred chewables. 8 preferred tablets

so 
make it easy to do and remember, confirm client's technique.

also - ease 
of use - go back to production animals - pour on formulations have been 
used for ectoparasites in cattle and more recently for ecto and 
endoparasites using ivomec pouron. until a month ago, these couldn't be 
used if it was going to rain in the next 6 hrs, but now, they've made 
this new avomec derivative that doesn't wash out, and now that's not a 
problem. 
swine and poultry usually dosed with water additives or 
primixes/top dressings, which are very useful in swine. most tx in swine 
are mixing with feed or top dressing (sprinkle on food) esp with sows


can use anthelmintics several ways

therapeutically - to tx sick/infected 
animals - eg immiticide for HW, anthelmintics in august to tx lambs to 
rid them of L3s, tx of sick ewes before parturition to prevent PPR


prophylactically - ivomec/equvalan q 8 wks to prevent verminous colic, 
monthly preventives for HW in dog/cat, tx of ewes to prevent PPR.

try to 
establish a tx cycle to coincide with production cycle and seasons and so 
forth.

in ewes around parturition there is a rise in fecal egg counts 
due to decreased immunity, which contaminates environment and causes 
infections in lambs, which then produce more eggs, further contaminating 
pasture. this causes lots of L3 to show up on pasture. so if you tx ewe 
in late winter/early spring to reduce PPR, you won't get the L3s on 
pasture. so you won't have the heavy infection of lambs. 

piperazines:

little use in horse/dog
limited spectrum
anticholinergic - induce 
hyperpolarization of nerve membranes causing flaccid paralysis. quite 
safe, though (?). effective against bzm resistant small strongyles (um, 
so they are used in horse, i guess)

avermectins/milbemycins. most modern 
- macrocyclic lactones
milbemycins discovered in 1973. insecticidal, 
acaricidal
avermectins found in 1975
insecticidal, acaricidal, 
nematocidal

these all share the macrocycle core structure
these are all 
fermentation products of streptomycins which act in common way - interact 
with glutamate gated Cl- ion channels in neurons and muscle cells, 
causing paralysis of parasites. abamectin, ivermectin, etc. 


benzimidazoles and probenzimidazoles act by inhibiting polymerization of 
microtubules in nematode intestinal cells - cause starvation by blocking 
glucose absorption. some are efficacious against cestodes, too. but only 
the proglottids. few have any effect on scolex, and to eliminate cestodes 
you must eliminate scolex. base molecule is thiabendazole. 


imidazothiazoles - eg levamisole - still used as injectable and pour on 
in cattle. (note in chart - PO = pour on, not per os)


tetrahydropyrimidines also used in horses and dogs (pyrantel) and cattle 
(morantel) - both are cholinergic agonists, causing spastic paralysis

in 
chandout is a lot of charted info. group, family mode of action. 
chopefully you can complement information with information on internet. 
there is some resistance info in handout you should also read. 

chave a 
nice day.




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