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parasit
lok

note: friday we didn't have enough time, so 
we're going to review some of the info about chemical control of HW in 
dogs.

wrt diagnosis of canine HW infections: we discussed the 
microfilarial exam as the traditional front line of diagnosis. check 
blood via filtration or knott concentration method, look for circulating 
microfilariae. we're not looking for an indication of dz severity this 
way. number of mmf does not correlate with number of adult HW. we also 
said that a significant proportion of dogs which have hw in vasculature 
will not have mmf - "occult" HW infxns, most often due to host mounting 
an Ab response which clears mmf from circulation. this can in itself lead 
to interstitial lung dz, as mmf are trapped in lung tissue. 

the 
approach to this from early on has been to develop a number of serology 
techniques, measuring host Ab response (early method, preferred method in 
cats), and measuring presence of dirofilaria Ag in the serum. Soluble Ag 
can be detected in host serum using ELISA method. most tests measure Ag 
elaborated by mature female worms. so it is *possible* albeit improbable 
for a dog with a male only infection to test negative on this test. this 
method isn't used in cats, which often have single sex male infections, 
or have very low numbers of worms present, which may give false negative. 
these tests use immobilized monoclonal antibody, host serum, and a 
monoclonal Ab conjugate. The second monoclonal Ab is against a different 
epitope on the Ag, and it is tagged so that it will produce a color 
change.

the nice thing about Ag test kits is that since they measure a 
product of the worm, the intensity of rxn does correlate with the # of 
adult worms. so you can quantitate your results to some extent. this 
helps you to plan treatment. note that to make a good guess, you do 
assume a 50-50 sex ratio of worms. some of these kits, eg snap test from 
idex, has a "high antigen" spot, which only shows up if you have say over 
20 adult females. so they call that a "semi quantitative" test. 

the 
other nice thing about these tests is that they are very specific, do not 
cross react with dipatalonema reconditum Ag. if you run this test 
routinely, you don't have to worry about morphological differences b/w 
dirofilaria and dipetalonema.

so if the dog is Ag positive...what then?

look at disease severity. class I (asymptomatic) vs class II (moderate)


I: clinical signs absent or infrequent, mild. antigen positive. mmf may 
be positive. rads, HCT, other tests all normal. majority of K9 HW 
infections are class I.

II: (moderate) signs absent or infrequent, mild. 
Ag positive (if high, class III). mmf may be present. rads show disease- 
large R heart, some pneumonitis, enlarged PA. HCT about 20-30%. other 
tests may show moderate changes.

III: (severe) signs usually present and 
maybe severe or persistent. antigen positive - may be high. mmf 
frequently absent. rads show severe disease. HCT often below 20%. other 
tests frequently show abnormalities

IV: (caval syndrome) signs are 
present. cardiac failure occuring. Ag positive. mmf frequently absent. 
rads indicate severedz, hct frequently below 20%, and other tests 
frequently show abnormalities. these are the cases where worms have moved 
back into RH and sometimes vena cava, causing heart +/- liver failure, 
hemoglobinuria, etc. need to react within hours to save dog's life. 
surgical emergency. 

classes I-III are treated medically.

in the 
handout is information about the medications. medical management of K9 HW 
dz requires 3 pronged approach. none of the larval/adult stages respond 
to the same one drug. eg, no one drug kills mmf and adults. drugs that 
treat adults will not kill mmf.

prong I: get rid of the immediate 
problem - adult worms. all the drugs used for this purpose are organic 
arsenicals. old drug of choice was caparsolate. current drug of choice is 
immiticide (melarsamine dihydrochloride). these drugs are potentially 
quite toxic. there is a lower margin of safety with these drugs than we'd 
prefer to have.  Immiticide is given IM into deep epaxial muscles of 
lumbar region. this is an improvement over caparsolate, which needed to 
be given IV and which provoked a lot of tissue site necrosis if given 
extravascularly. it's given in two doses 24 hr apart. the reason for that 
is so that you don't kill all the adults at one time, and because the 
drug is acutely hepatotoxic. this is the "standard" regime. it minimizes 
parasite related thromboembolic complications and drug related 
hepatotoxicity.
alternate regime: give dose I, wait 30 days, then give 
standard regime. this is preferred method for class III dogs with severe 
disease or high antigen levels. these dogs are at highest risk for acute 
thromboembolic complications. the split dose alternative regime will kill 
some worms with the first dose, then allow some recovery time.

all 
adulticide tx is given on an inpatient basis with enforced cage rest. 
embolic complications are related to excersise level. 

class IV dogs are 
treated with surgical removal of worms.

caparsalate (thiacetarsamide) 
was used to tx hw before, and is still out there although no longer being 
manufactured. this drug is given IV, is more toxic, causes necrosis and 
sloughing if it gets outside the blood vessel. it is given in 4 doses, 
twice daily for two days, to minimize potential thromboembolic 
complications and drug toxicity. there is no alternate dosing regime. you 
don't get much effect from first day's dosing. you have to give whole 
course to kill any significant numbers of adult worms. you need a 
threshold of the drug in circulation to produce killing effect. also, 
young female worms are pretty resistant to treatment with caparsolate.


good news about adulticidal tx is that the primary lesion - villous 
endothelial plaques - will resolve 1-3 mos post tx.

prong II: if the dog 
is mmf positive at presentation, it's still mmf positive post adulticide 
tx. you have to get rid of the mmf or they will a) cause diagnostic 
confusion, b) be reservoir for other dogs, or c) cause problems when 
other drugs given in future. best way to get rid of mmf is via 
milbemycin, the active ingredient of interceptor. mmf susceptible at FDA 
approved dose of .5 mg or 500 mcg/kg. rapid clearance - 24-48 hrs. 
problem, though - where do the mmf go when you kill them? mainly they get 
trapped in lungs. as they decompose/autolyse, they may cause acute 
respiratory signs in these dogs. dogs may become febrile, lethargic, may 
vomit - usually w/in 8 hrs of tx. probably you should observe dog for 8 
hrs post tx. this isn't life threatening rxn, but shouldn't be happening 
at home - may be alarming to owner, may ruin furniture or carpets, etc.

also ivermectin has been used for mmf tx, the approved dose is 6-12 
mcg/kg, and that's the dose in heartgard, and that's a preventative dose, 
but it causes a slow, gradual clearance of mmf - generally too slow. up 
to 2 yrs ago, ivermectin at 50 mcg/kg was recommended tx for mmf - and 
has been proven safe - but isn't FDA approved. american HW society has 
now backed off this recommendation due to milbemycin now being available 
and working at an approved dosage. 

dithiazenine (sp) is the only FDA 
approved mmficide, but it's no longer commercially available. 


chemoprophylaxis - prong III. a year's supply of preventative will cost 
$35-40.
a course of adulticide therapy at VHUP including labwork, drug, 
hospitalization is going to be about $500-600 depending on size, length 
of stay, what tests are needed, etc. prevention is definitely cheaper and 
less traumatic than treatment. there is no good reason for any dog to get 
infected with dirofilaria immitis if it is under veterinary care.  drugs 
used are milbemycin (interceptor), at 500 mcg/kg (given monthly); 
heartgard (ivermectin, 6-12 mcg/kg, monthly); and filaribits 
(diethylcarbamazine, 2.5-3 mg/lb daily)

both milbemycin and ivermectin 
(the macrolides, he calls them) can cause a mild reaction in mmf positive 
dogs. you don't want to send clients home with supply of heartgard or 
interceptor not knowing if they are mmf positive or not. there can be a 
mild but unpleasant adverse reaction.  these drugs work not by 
maintaining tissue levels over a month, but by killing off a month's 
worth of accumulated larvae every month. it gets them while they are 
still in the tissues, so you don't get them in the vasculature at all. 
it's like a monthly housecleaning, sweeping out L4s. also, if a client 
skips a month, it's ok. just give it the next month. so 60 day old L4s 
are still susceptible. actually, it's at least two mos, the grace period 
- so you could skip two doses. but don't tell clients that, he says...


with the diethylcarbamazine, if you give it to an mmf positive dog, it 
causes a much more severe and potentially fatal anaphylactic like shock 
reaction. this drug maintains residual levels, killing off L3 as they 
undergo first phase of development. it works more the way you would 
consider classic chemoprophylaxis to work - really more preventive. but 
you must verify mmf negative status before starting tx!

if you don't 
test dogs first, but just put them on milbemycin oxime w/o any testing, 
and dog is positive, that first dose will clear circulating mmf a lot, 
then they'll rebound a bit, up to about half the starting level...but by 
the time you finish the 5th month, you'll be down to zero mmf, and they 
will never recur. this happens in dogs with significant numbers of adult 
worms in their hearts. this is one way of creating an occult infection. 
so here is an argument for working it up before starting mmf tx, and also 
this is why dogs on these drugs for a year or thereafter don't need 
knott's testing. the worms are chemosterilized. you would have to do 
antigen testing. 

note re: collies: the ivermectin related CNS signs 
occurred at 10-20 times the approved dosage of ivermectin in dogs, and 
never at all with milbemycin. this is why Merck adopted a collie as the 
mascot for Heartgard :) no one has ever seen these signs even in rough 
coated collies at the approved dosage.




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