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dr lok
parasit
9.18.97

note: mixedbreed english pointer 
type dog looking for home. from penn lab. on HW study, has HW, will be 
treated prior to adoption, and will be neutered. name is "Petey" and his 
future is dim unless someone will take him home. very friendly and 
rambunctious!!

handout: Filarioidea: Heartworm

so we've transitioned 
out of worms of the GI tract into the tissues of the final host, and away 
from direct life cycle to a life cycle requiring an insect vector.

we 
discussed some human filariasis type diseases. the last thing we 
discussed was onchocercus cervicalis in horses. life cycle, again, 
involved biting gnat as intermediate host/vector, and this parasite 
causes skin dz. etiologic agent was microfilariae living in 
dermis/subcutaneous tissue of host. local hyperimmune response, pruritic, 
scaly skin lesion. in horses this is a nonseasonal dz and can be cleared  
up with ivermectin. horses often get ivermectin for other parasites 
anyway, so control of this parasite is kind of a side benefit.


onchocerca in humans is an agent of ocular disease - we still aren't sure 
if these parasites cause ocular dz in horses. onchocerca are generally 
benign parasites of cattle - can detect microfilaria in skin biopsys in 
animals with no clinical signs.

another filarial parasite

Setaria equina
adults live in peritoneal cavity of horses. transmitted 
by mosquitoes. not that pathogenic. may cause mild peritonitis. may see 
microfilaria in whole blood. no treatment really indicated. these are 
really incidental findings.

bovine counterpart to s.equina is also 
around, and lives in peritoneal cavity of cows, and microfilaria 
circulate in blood.

a parasite kinda like onchocerca, with adults in 
subq tissues and microfilariae concentrating in skin usually at 
midventral line - stephanofilaria - transmitted by the horn fly. 
microfilaria can cause a mild skin reaction in cows along the ventral 
midline. microfiliria are very tiny, easy to tell from onchocerca by 
size. 

DIROFILARIA IMMITIS: the k9 heartworm

again. we're in the 
filarioidea, similar to the spiruroidea in that they are tissue dwelling 
nematodes, not gut dwelling nematodes

we will also look at dipetalonema 
in dogs, which also has circulating microfilaria but isn't very 
pathogenic at all. so it's important to differentiate between them. 


remember filarial life cycle

general nematode cycle: 
L1-->L2-->L3-->L4--->"L5" immature adult
L1 -3 usually outside host. L3 
usually infective. 

use this as a template for learning all the nematode 
life cycles 

filarial growth:

microfilaria are kind of motile embryos - 
they are infective to the arthropod vector.

L3 develop within vector and 
are injected into host.

the development of microfilaria occurs in the 
uterus of the adult female. 

Dirofilaria immitis is a simple worm, 
simple mouth tube with sensory papillae at cephalic end. very long worms, 
females are about 30 cm in length- so can cause damage by size alone. 
adults are found in cardiopulmonary circulation. the microfilaria are 
elaborated into peripheral blood where they are snagged by mosquitoes.


again - mosquito gets blood meal and ingests microfilaria. mf's migrate 
into specific tissue of mosquito (malphigian tubules) and develop into 
L1-->L2-->L3 in about 2 weeks. can make it one week at higher ambient 
temperatures. 
the L3 migrates through abdomen into mouth parts of 
mosquito and sits in lumen of mouth thing and migrates out onto the host 
skin and then invades through the bite wound. so imagine the L3 sitting 
right around the bite site. they get lethargic and hang out near the bite 
site, but within 3-5 days, they molt to L4s. L4 is the longest lived 
larval stage. it will migrate through subq tissues through fascia going 
all over host, finding its way into cardiovasculature. within 90 days, 
will molt to L5 within heart/pulmonary arteries. within 192 days, those 
will be adults, they will mate, and females will begin elaborating 
microfilaria into peripheral circulation usually by day 192. so PPP about 
6 mos.
the microfilaria can be seen in peripheral blood, on a blood 
smear. can use knott concentration technique. mff is the diagnostic 
stage. there are several techniques for isolating them from whole k9 
blood.

epidemiology: back in the 1960s HW infxn in dogs was almost 
strictly limited to gulf coast area. in mid70s, HW was unknown in central 
NY - cornell vets didn't worry about it. but now, dirofilaria immitis has 
opened its range - all up the east coast, up the mississippi, all around 
the great lakes, over at minneapolis/St.Paul, SF bay area, texas, and all 
across the eastern 2/3 of the country, really. HW is good at gaining a 
foothold in a variety of ecological habitats. the US/Canada border has HW 
on both sides, all he way across, pretty much.

d.immitis has two kinds 
of hosts. hosts other than dogs that allow worms to mature and reproduce 
are "alternate hosts" - wild canids, sea lions, and domestic and wild 
felids. felids do not maintain circulating microfilaria for a long time 
during their infection. but they still act as natural reservoirs for some 
small period of time.  also, there are "dead end" hosts, that allow 
parasite to mature, but not to reproduce - many species including man, 
raccoons, beavers, bears. adults can live inside them, often encysted in 
the lung - but they do not get microfilaremia. these species are not 
significant reservoirs of infection. 

HW DISEASE: 
slide: classic HW 
picture: R atrium open, holding huge bolus of adult heartworms. when you 
see this, you might assume the etiology of HW dz is based on obstructive 
phenomena but that isn't really the case. in fact, HW don't appear in RA 
like that. usually, they are up in the pulmonary arteries, but when the 
animal dies they fall into the heart. predilection site is really the 
pulmonary artery. the word "heartworm" is a misnomer. you should call 
them "pulmonary artery worms"
the intima of the PA is roughened in 
animals with chronic HW infection. this is because microscopically you 
can see little villi or plaques of endothelial cells have formed on the 
intimal lining. these plaques can be large in heavily infected animals. 
these placques are the primary pathologic lesion. they impede blood flow. 
this results in pulmonary hypertension, increased workload on R heart, R 
heart failure

radiograph: HW infected dog chest. PA sacculated, dilated. 
exhibits "dendrification" of PA. another type of event that occurs in HW 
infection is thromboembolus - clots form in PA and embolize to lung. this 
happens mostly when worms die. can occur when you kill them, or when they 
die naturally (normal life 5-7 yrs). think about it. a dead worm will 
have clot form around it, will embolize into the lung. 

we see decreased 
exercise tolerance. can't increase CO the way they should. we will 
discuss this in the HW lecture later. can see heart failure, ascites, 
edema. clinical signs usually seen include coughing, labored breathing, 
exercise intolerance. less common - wt loss, anorexia, heart failure, 
general debilitation.

having said all this - plenty of normal healthy 
dogs are running around with sizable dirofilaria immitis worm burdens. 
"clinically silent" cases. three factors determine clinical presentation:


1. relationship between host size, size of cardiovascular system, and 
number of worms. what's the worm burden?

2. what's the exercise level? 
signs are worse during exercise. couch potato dogs won't show signs of 
disease as much.

3. chronicity of infection. all the changes occur 
gradually over time. arterial lesions do not show up overnight. it takes 
time to see them, and time for pulmonary hypertension to cause heart 
changes, and so forth. length of time of infection is a main factor too.


number of circulating microfilaria has nothing to do with the level of 
disease or the number of adults! can have severe disease and no mff, or 
many adults and few mff, or whatever.

the adult heartworm is the 
etiology of the dz. the microfilaria are pretty non pathogenic.

so, this 
is a chronic dz. however, there is one case where acute signs can be 
developed - if dog has VENA CAVA SYNDROME. in VCS, due to compromised 
myocardium in RA, there is decreased output from RA, allowing retrograde 
movement of worms into vena cava, and sometimes they can even damage the 
liver! this is a rare manifestation. now worms are actually in the right 
heart. animals become acutely ill, can collapse, this can be fatal in 
24-48 hrs. dogs will be recumbent with hemoglobinuria, pale mms, high 
worm burdens. here you can surgically remove the adult worms and hope to 
resolve some of the problem. you use a jugular venotomy. specialized 
instruments exist for this purpose.

another type of HW infection.

remember: mff are diagnostic stage that we classically use to diagnose 
this infxn. what if dogs mount immune response and clear mff from 
circulation? this is an occult HW infection - hidden. adults are still 
there. these animals are still just as much at risk of disease.  so now 
we have serologic assays for HW infection, to look for HW antigen or 
whatever. the primary reason we see occult infxn is immune mediated 
clearance of mff from circulation. usually, mff are trapped in lung - can 
see infl dz in lung.  some drugs used to prevent HW infections can 
chemosterilize adults and can result in occult infxn as well. also a 
single sex infxn will produce no mff. old adults won't reproduce.. 


10-60 % of infections in given group of infections will be occult!
so you 
use serology to diagnose them.

renal dz and hepatic dz signs have been 
reported as secodary signs but are not the chief concern. 

HW can also 
be found in ectopic sites. slide: adult dirofilaria immitis in dog eye. 
also seen in subq or peripheral vascular areas sometimes requiring sx 
removal.

Feline HW DZ: epidemiology:
worms only live about 1-2 yrs in 
cats
many cats can clear the infxn
aberrant migration more common, 
CNS/brain more common. cats get more thromboembolic dz in response to 
spontaneously dying hw though.
dx is harder because cats usually are 
nonmicrofilaremic most of the time. also cats have lower adult worm 
burdens,
[boy. i'm fallingasleep again .sorry!]

signs in cats - acute  
or chronic. same signs - cough, vomit (not usualyl seen in dogs , 
dyspnea.  
exercise intolerance. 


dx/tx: microfilaria is used for dx. 
can get via blood lysis or other screening techniques. also can use 
serologic test for antigens.

one other filarial infxn of dogs - 
dipetalanemia reconditum. transmitted through fleas, not mosquitoes.very 
small worm. lives in sq tissues.
nonpathogenic but annoyingly can confuse 
diagnosis of HW. but serology will tell them apart.

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