---start----

imd
5/7
littman

rant: if you are getting a handout from 
the pile and someone else takes the one you were about to pick up, do not 
give him or her the evil eye, because it is highly unlikely that that 
person intended to take the handout your were aiming for. it's always a 
mob scene up there by the handouts.

any questions from before?
ok. well, 
we were talking before about Lyme Disease. There is no "s" the Lyme part 
of that. Lyme is to Lymes as Prostate is to Prostrate.

if you say "Lymes 
disease" or "Lymes titer" it sounds like someone saying "Prostrate 
gland."

Toxoplasmosis: lots of research on this. people with HIV get 
relapses of old toxo infections and have a lot of CNS problems. so people 
are looking at whether or not people with AIDS should own cats - a study 
showed no correlation b/w cat ownership and toxo in AIDS patients. people 
usually get it from eating dirt at a picnic when they're young, or eating 
steak tartare or other raw meat. 

organism: toxoplasma gondii, a 
protozoan, that is not spp specific and isn't cell type specific - it can 
infect just about anything. 

cats = definitive hosts, shed oocysts
many 
other spp including birds == intermediate hosts

lives in many cells - 
myocytes, neurons, monocytes, pneumocytes, hepatocytes, whatever. a very 
successful parasite b/c usually doesn't kill the host. animals develop 
bradyzoite cysts, the latent forms, and when animal is eaten by another 
animal it spreads. 

you know that in the cat, there are sporozoites, and 
so oocysts are shed - very tiny oocysts. when you do a fecal, the most 
common kind of coccidial oocyst you find is isospora oocyst. many people 
especially pregnant people are afraid when vets say they see toxo but 
usulaly it isn't even toxo you see, it is isospora. toxo oocysts are 
rare. get a micrometer on your microscope. the toxo oocyst is really 
small compared to isospora - only about 1/4 the size of isospora, 1/8 
size of toxocara 

even then, when you find a tiny coccidian oocyst that 
might be toxo, realize that it looks like hammondia hammondi and another 
thing. cats are not sick while shedding. they usually shed for a week or 
two after infection and then never shed again. 

besides the oocysts, 
which only come from the cat, there is another form called the 
tachyzoite, the fast growing form. these small, banana shaped tachyzoites 
are seen in definitive and intermediate hosts and do not sexually 
reproduce. 
experimental cats - if fed mouse brains from mice infected 
with toxoplasma, many cats have cysts in their adrenal glands. when 
tachyzoites no longer can replicate due to immune respose, then 
bradyzoites develop in the tissue cysts - can be stuffed all into one 
cyst. are viable organisms, protected from immune system of host, 
probably viable for life of host. with immunosuppression or stress or 
chemo or whatever, the bradyzoites may be able to come out and cause a 
relapse, cause active toxo.

good news - shouldn't be transplacental toxo 
transmission if bradyzoites are reactivated, b/c they usually just cause 
local irritation, animal should be able to stop them again when immune 
memory comes out.

infection is common; disease is rare. serosurveys show 
many animals have positive toxo titers. some people feel in the US that 
especially among farm cats, about 64% have toxo Ab. 30% in other study. 
many raccoons have toxo Ab, meaning they have eaten small animals that 
are infected OR they have been in areas where cats have shed infective 
oocysts. raccoons do not eat that much meat. so toxo is around.

mainly 
we worry about toxo in fetus - can cause retardation, miscarriage, other.

we discuss undercooked meat that would have bradyzoites in it that can 
cause active infection. raw milk too. high incidence of toxo in goats, 
can shed in milk. also other ways - gardening, etc. there is one outbreak 
writeup from people having a picnic near a horse stable. horses came by, 
roughed up the dust, kicked up some oocysts, got dust on sandwiches, 
people got active toxo. flulike signs, swollen glands, fever, headache. 
unless you had a seizure or ocular signs or something you wouldn't know 
it was toxo. this cluster of people all knew eachother, told MD they were 
all sick, and it got diagnosed.

[dr littman is now having a private 
converstaiton with stacey solovei, a fourth year student unfortunate 
enough, i suppose, to be handling one of her cases right now or 
something.]

so we can get toxo many ways. cats usually are eating 
infected animals like mice, birds, whatever. it is rare that a cat will 
eat tachyzoites - would be odd to eat an actively sick animal. or cat may 
ingest sporulated oocysts from other cats that shed oocysts. 
prepatent 
period is different for each form. if cat eats bradyzoite cysts in meat, 
there is about 100% probability cat will shed oocysts for a week or two, 
and PPP will be very short, a few days - if cat previously uninfected! 
during this time, toxo is multiplying in intestine but cat is not usually 
sick, doesn't have diarrhea. during period of shedding, most cats don't 
even have measurable titers. if the cat eats tachyzoites, less than 50% 
chance of shedding, and will take about 3 wk PPP. if cat eats oocysts, 
same as tachyzoites. after shedding, cat is a carrier. if 
immunosuppressed or sick with active toxo for some reason, it could be 
presenting in that second week or so but usually they are NOT sick while 
shedding. 

the main thing you see on histo is necrosis. cells are 
invaded by toxo, recognized by immune system, destroyed by CMI response. 
as toxo comes out of the cell after replicating, will rupture the cell. 
toxo likes lung in particular so some cats get pneumonitis (cat in boston 
died suddenly 2 days post spay due to toxo - luckily owner allowed 
postmortem! they were worried about surgical error or postop complication 
- but it was toxo brought on by stress). also in cats we see 
cholangiohepatitis, cholangitis, icterus, or fat cat may develop fatty 
change of the liver. the heart  - a dog suddenly died of toxoplasma 
myocarditis. ocular toxo more common in cats than dogs - can cause 
chorioretinitis, anterior uveitis, iritis, etc. CNS signs can occur in 
dogs and cats. encephalitis. dogs get muscle problems, especially youg 
dogs, can have rigid contracture esp of hind legs, with scarring and 
inability to flex legs. can be toxo or another extraintestinal coccidia, 
neospora caninum. they restained some old slides from dogs previously 
dxed with toxo and found that some had neospora caninum. no cross 
reactivity, but some different staining properties. so that is confusing. 
if you think of toxo and it is negative, try neospora titer. also it is 
possibly too early for titer to be high enough - it's slower to produce 
an Ab response. 

fetus - place where toxo can do much damage. fertility 
problems may be present in animal. 

we always ask, when we have the idea 
of infectious dz that might be toxo, does the animal eat cat feces? many 
breeders feel dogs should be fed raw meat. this makes us cringe. we 
shouldn't feed raw meat to pets. we wouldn't feed it to ourselves for the 
very same reason. sarcocystis could be in there, neospora, trichinella, 
etc. we already talked about enlarged LNs - see handout for list of many 
signs and pathologies that occur.

with ocular form - sometimes people do 
titers on aqueous humor, or antigen ELISA test, or PCR. so in addtion to 
biopsies, or bronchoalveolar lavage or whatever, some people will take 
some aqueous humor. CSF tap is another biggie.

myositis more common in 
dogs than cats. can be very stiff. think of dz that cause joint/muscle 
pain - toxo should be on that list. 

vague GI signs - v/d/ulcers, 
intestinal granuloma, fever, "poor doer"

if very sick with active toxo 
and you do a CBC you might see leukopenia with inappropriate left shift - 
degenerate left shift - poor px. might have low albumin, high ALT, CPK, 
SAST, hypoproteinemia - all depends which organs are most affected. 

IgG 
vs IgM. you need to know which kind of antibody your lab is testing for. 
IgM rises first, and IgG rises more slowly. if an animal has active toxo, 
either the first time or during relapse, IgM will be high quickly and 
will then fade in a few months. IgG might be high due to infection from 
years ago. nothign to do with active dz process. it's interesting that 
the conversion of excitement of immune system to put out a lot of IgM and 
then switch to IgG doesn't occur in FIV cats which continue to put out 
IgM for longer times. 

so when DR L was getting pregnant, she had to 
teach her OB about these. she asked him to do a toxo titer. he told her 
they were always negative. and, yes, her prebreeding titer was negative. 
then the day after the birth she had another titer that was also 
negative. a few years later she had a miscarriage and read up on toxo. 
then, she found out the lab had tested her only for IgM - because they 
only wanted to know if present clinical signs were due to toxo. they 
weren't checking for exposure. you need to do an IgG. so she had someone 
here take some blood from her, and she tested it here, and she had a high 
toxo titer. so she told her OB about this. prebreeding titers should be 
IgG titers. you have to find out if your lab does this. if you have 
positive IgG prebreeding, you do not have to worry about reexposure. 
there is no evidence that a reactivated infection will go to the fetus. 
if you have negative prebreeding titer, you can test for IgM every 
trimester. 

here, if IgG titer is positive you can do a convalescent 
titer for free. 

IgG is long lived, not helpful except as prebreeding 
titer, really. in many places, they have IgM and IgG titers, also ELISA 
for antigen, and they can do more accurate diagnosing.  you can't compare 
lab to lab with results though. you need to compare results from the same 
lab, ideally on the same day - they should save some serum from the 
pretiter and run it again with the convalescent titer. some very sick 
animals have negative titers b/c they didn't seroconvert yet, they may be 
so ill their immune system is slow...

note: if you do IgM titers every 
trimester and you do find seroconversion ....early in pregnancy, spread 
is less likely but more damaging to fetus. if you seroconvert during 
pregnancy, you have to decide either to abort or take the risk. it's 
possible they can do other newer fancier tests. in later trimesters, they 
may be able to treat for it, and there is less risk of serious damage. 
tell clients to talk to their MD or DO or chiropractor or whatever. :) 
there is enough litigation in the world...

clindamycin - years ago we 
used to have to give sulfa and antifolates and we saw lots of side 
effects and had to give vit B supplements and it didn't work that well. 
clindamycin works better. use high doses, sometimes this causes diarrhea 
and you have to go to tribrissen, and you need to treat for a long time 
esp with ocular or CNS disease. 

our old friend doxycycline can treat 
mice with toxo but isn't used in other spp. 

there is a drug you can 
give preventively during time immediately postinfection that will 
decrease oocyst shedding. some people say we should add it to cat food 
but that sounds silly b/c animal might not be eating cat food anyway, 
cats don't get toxo from cat food. if there is CNS or eye involvement may 
use steroids to decrease inflammation. also they are working on vaccines. 
companies are looking for new vaccines b/c we won't sell so much FVRCP 
anymore, and we won't sell FIP vaccine...maybe we should vaccinate cats 
with the european vaccine to decrease oocyst shedding. one reason not to 
use it is if there is less oocyst shedding around outside, women will not 
be routinely exposed early in life, are more likely to encounter toxo 
when pregnant. not sure how that will sort out. 

recommendations for 
pregnant women-= do not eat raw meat, do not change litter - although 
fresh feces are ok, takes 24 hrs to sporulate and become infective. if 
animal has stool stuck to fur try to clean it up right away. cover 
sandboxes, wear gloves while gardening. wash hands while eating and 
cooking. don't taste undercooked food. don't adopt new cat while 
pregnant. do prebreeding IgG titers and maybe IgM titers each trimester.


toxo in drinking water - find the article on the internet - Bowie WR et 
al. toxo in unfiltered water, reported in Lancet. 100 people got toxo 
this way.

next hour - if you want to review, she will review stuff for 
you.
---end---