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parasit
10/23/97
farrell

sporozoa

today we're going to talk 
about apicomplexa
these are all intracellular organisms with an apical 
complex
these are grouped into the coccidia - mainly intestinal organisms 
(eimeria, isospora, cryptosporidium, etc),
the piroplasmidia (babesia, 
theileria, and cytauxzoon), and haemosporidia - blood/arthropod 
transmitted parasites - hemoproteus, leukocytozoon, and plasmodium. we'll 
discuss this last group today.

generalized life cycle of a coccidian 
(intestinal organism) 
parasites are present in oocyst in environment, 
containing sporozooites, which are released when the oocyst is ingested 
and gets into duodenum. then schizogeny occurs within intestinal mucosa, 
and then macro or micro gametocytes occur, zygotes are formed, and new 
sporozooites are formed

in terms of terminology - 
we always start life 
cycle with infective stage:

sporozoite (always the infective stage) ---> 
enters cell and begins to grow and then it divides. Early on it is a 
trophozoite (active feeding and growing stage) and then it divides by 
schizogeny (multiple fissure - replication of nuclei followed by 
cytokinesis) --> the new merozoites are released, and they also possess 
the apicomplex, so --> invade new cells --> asexual reproduction 
(schizogeny)

depending on species, the cycle shown above can go on 
indefinitely, with more merozoites being released, invading new cells, 
reproducing, etc.
eventually, some of the merozoites enter into cells and 
become gametocytes (pre-gametes), which are male or female. generally 
then there is either fusion between male and female gametocytes, or the 
male one undergoes replication to form mature gametes, which are then 
released and which then invade cells harboring female gametes which are 
then fertilized, forming the zygote.
generally then there is division 
within the zygote - we call this process sporogony. so the first division 
is meiotic, then that is followed by mitotic division, to form multiple 
progeny which are sporozoites. this then is the basic coccidian life 
cycle

host infected by sporozoite--->asexual repro within cells by 
schizogeny aka multiple fission-->invasion of cells and formation of m 
and f gametocytes----------> fertilization and zygote-->division of 
zygote by sporogony to form sporozoites.

we're going to talk about a 
whole bunch of parasites over the next couple of days. all have this 
basic life cycle. in simplest form in intestinal coccidian, everything 
occurs at one site,in one cell type, in one host - eg, it all goes on in 
intestinal epithelial cells. the only thing happening outside the host is 
sporogony- sporulation, which occurs in the oocyst. in other species, 
things are different. there may be set numbers of cycles before 
gametogenesis, there may be different cells where different parts of 
cycle occur. sometimes sexual and asexual repro occur in different hosts. 
sometimes sexual repro occurs in a vector eg with plasmodium. 

general 
life cycle of blood borne sporozoan
this is for human malaria plasmodium 
vivax

the sporozoites are delivered into the person by the bite of an 
infected mosquito - they are in salivary gland of mosquito. 


sporozoites-->through blood-->into hepatocytes-->asexual 
repro-->merozoite release-->invasion of erythrocytes-->continuous asexual 
repro within erythrocytes until person dies or is cured. at some point, 
some merozoites become gametocytes (asexual repro continues at same 
time)-->mosquito takes blood meal, ingests gametocytes--->maturation of 
gametes in mosquito GI-->zygote formation-->migration of zygote to 
stomach of mosquito-->formation of oocyst-->formation of 
sporozoites-->release of sporozoites into body cavity-->migration to 
salivary glands

so technically, mosquito is definitive host for 
plasmodium vivax, b/c that is where sexual repro takes place. 

slide: 
blood containing trophozoites within RBC, merozoites in RBC, and 
gametocytes (not sure if those are in RBC)

there are malaria organisms 
in birds with near identical life cycles. these are mosquito transmitted 
infections, in which trophozoite stages and schizonts/merozoites and 
gametocytes are found in rbcs of infected hosts. in many parts of the 
world there are highly pathogenic plasmodium spp of birds. most of these 
in the US are innocuous. they are not highly pathogenic, but they are 
common. so if you do bird work, or wildlife work, or whatever, and you do 
blood smears on birds you may see this. it isn't a sign of disease unless 
it is a pathogenic species. the way you know it is plasmodium is that all 
the stages are present in the peripheral blood. 

there is another 
parasite closely related to plasmodium - hemoproteus - a ubiquitous 
parasite of birds. not transmitted by mosquitoes, but by midges, 
hippoboscid flies. these differ from malaria b/c schizogony occurs not in 
rbcs but in endothelial cells. the only stage seen in peripheral blood is 
the gametocyte. not highly pathogenic, but very widespread. you would 
routinely find these in blood of wild birds. can tell it isn't plasmodium 
b/c only gametocytes are in rbcs. no schizonts or trophozoites in rbcs. 


leukocytozoon simondi - a parasite of ducks. leukocytozoon is transmitted 
by black flies, simulium. life cycle in black fly is identical to 
plasmodium in mosquito. fly delivers sporozoites to bird, sporozoites 
enter into liver cells, hepatocytes--->are released and enter macrophages 
of multiple tissues eg lung, spleen, liver, etc and undergo schizogony in 
mphages. some of these organisms enter into red cells or wbcs and become 
gametocytes. the only stages seen in peripheral blood are gametocytes. 
schizogony occurs in tissue macrophages. gametocytes are taken up by 
black fly when it bites the bird. 
in the us there are some pathogenic 
leukocytozoon infections. one is this one, l.simondi of ducks, the other 
is l.smithi of turkeys. these are pretty host specific for ducks and 
turkeys. not a lot of cross reactivity. pathology relates to division of 
organism within tissue macrophages. compared to nonpathogenic 
hemoproteus, leukocytozoon replicates a lot faster and destroys many more 
cells. basically young animals which suffer from this disease - 
ducklings, poults...animals get lethargic, may be anemic, show ruffled 
feathers,weight loss, shortness of breath, probably related to 
destruction of lung tissue due to schizogony in alveolar mphages. can be 
fatal in young animals. older animals usually survive. animals that 
recover generally have immunity. so older animals are more resistant on a 
flock basis. infections with this occur sporadically in the us. smithi 
more common in the south, simondi all over. there have been fewer and 
fewer outbreaks more recently, b/c people know that you shouldn't raise 
ducks and turkeys around black flies. so control mechanism: don't start 
commercial operation in areas with lots of black flies. so you see 
sporadic outbreaks that may be highly lethal to young birds. to control 
prevent black flies from biting birds. eg screens, etc. 
l.simondi may be 
carried from wild ducks to domestic ducks as well. 
the gametocytes 
markedly distort infected cells. you can't even tell if it's a red cell 
or white cell. organism takes up most of cell, pushing nucleus to the 
side. these are easy to distinguish from hemoproteus.

Piroplasms: these 
are the organisms transmitted by ticks. they have no spore/oocyst 
formation. they have a teardrop shape to them, hence piroplasm. 


babesia: invades erythrocytes of mammalian hosts. important worldwide. 
many spp - b.bovis, b.canis, etc. one highly pathogenic species was 
eradicated by a tick reduction program. babesia is now important in dogs. 
used to occur in horses but not for a long time. 
life cycle: (b.canis)

tick puts sporozoites into dog-->sporozoites enter erythrocytes-->limited 
schizogony forms 2-4 merozoites per sporozoite-->continues indefinitely, 
merozoites are released, invade other cells, divide, etc

we aren't sure 
if the forms found in rbcs are gametocytes or merozoites or whatever. but 
we know that a tick feeding on infected host picks up infected cells. 
cells appear in tick gut that seem to be male and female gametocytes. 
fertilization occurs, zygote is formed, and finally multiple zygote like 
stages called kinetes are formed. these kinetes can either make their way 
into hemolymph and then to salivary glands and divide into sporozoites, 
or they can go to the ovary and divide and enter into tick eggs. so next 
generation of ticks will be infected with babesia. so babesia is 
primarily a parasite of the tick. the vector for b.canis is 
riphicelphalus sanguineus, which is a three host tick using three dogs. 
if an adult tick is infected, eggs are infected, larval ticks are 
infected, and can transmit infection to a dog. if larval tick is not 
infected, it can be infected by a dog, and then the nymph can transmit 
infection, as can adult. "transtadial" transmission - infection of nymph 
resulting in persistent adult infection. 

the fact that some babesia 
infections are easily controlled is that some babesia spp are transmitted 
by one host ticks, so dipping hosts and controlling ticks can get rid of 
it. with three host tick,it is much harder to get rid of.

where is this 
found? a lot in southern US - FL, GA, etc. sporadically throughout the 
rest of US including PA. can do serology for b.canis. 

pathology relates 
to disruption of erythrocyte, which is the only infected cell. organism 
destroys erythrocytes, causing anemia, occlusion of small vessels. it's a 
regenerative anemia so you will see reticulocytosis. diagnosis is by 
detecting organism in peripheral blood smears, usually. getting blood 
from an ear stick is perhaps more efficient - they may concentrate in 
small capillaries. splenomegaly occurs, fever, lethary, wt loss,etc. 
inmany parts of the world, b.canis seems much more virulent than that 
here. often coombs tests are positive on the blood of an infected animal, 
so some erythrocyte destruction may be immune mediated. in US, only some 
animals become coomb's positive. sometimes you see hemoglobinuria in the 
face of large scale destruction of erythrocytes - more common with more 
virulent strain. Berenil is used for treatment but it isn't commercially 
available in the US. most diagnosis is by serology but only a couple labs 
do that. if an animal recovers it is probably going to remain infected 
for life. no sterile immunity occurs. if animal is immunosuppressed - eg, 
splenectomized,on steroids, stressed out from moving house, etc - 
infection can recrudesce. almost 100% of the time with splenectomy. 


there is another babesia on handout - b.gibsoni in NE USA in dogs, and 
CA. we do not know the vector. can tell from b. canis, which is a large 
babesia, because it is much smaller in size. 

babesia caballi - in 
horses, mainly in FL,no reported cases lately. horses entering us are 
tested for this and infected animals are not allowed in. vector is 
dermacentor, a one horse tick. b.caballi may have been eliminated from 
US. 

two other minor facts - 
ehrlichia canis - there is an infection 
present in dogs transmitted by the same vector, as b.canis, occuring 
mainly in WBCs, you can see a morula looking structure in the WBC. the 
pathology is weird - can get pancytopenia including thrombocytopenia b/c 
it gets into bone marrow. animals can exhibit bleeding disorders. lots of 
concurrent infections in the south of b.canis and ehrlichia canis. the 
b.canis associated anemia then is not regenerative, due to the ehrlichia. 
so you can have a much more severe, less responsive anemia with a 
coinfection, which is likely since they use the same vector.

there are 
babesia infections that have been seen in humans - a vole or rodent sp 
that is transmitted by ticks. 

cytauxzoan: sporozoites inoculated by 
ticks.
normally seen only in african antelope. 
schizogony occurs in 
mphages in lymphoid organs, produces small piroplasm organism which 
invades RBCs. cases have occured in cats in MO, TX,GA, and AR. only 
domestic cats. 100% fatal very rapidly. we know it has a tick vector. 
seen in rural area, probably with a bobcat reservoir. domestic cat is 
accidental host. usually dies within a week. fever, anemia, weakness. 
cases on the rise.

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