Parasitic Infections 2 Flashcards
Trypanosomiasis
_____ from genus ____
Parasitic flagellate protozoa
Trypanosoma
true parasite
Trypanosomiasis
Infect variety of hosts – 2 of them cause fatal human diseases known as
African trypanosomiasis (sleeping
sickness)
American trypanosomiasis (Chagas disease)
neglected parasitic infections targeted by CDC
Chagas caused by
T. cruzi – mostly rural areas of Latin America
Sleeping sickness caused by
T. brucei – mostly rural Africa
Trypanosoma cruzi is transmitted to animals and people by
insect vectors found only in the Americas
- Blood-sucking “kissing bugs” of the subfamily Triatominae
- Nocturnal, bite you while you are asleep prefer to bite on face - attracted to face - breathing - warm air
Trypanosoma cruzi routs of infections
vectorborne (bight), contaminated food and drinks (sugary drinks - attract bugs), congenital transmission (placenta), and (rarely) blood transfusions or organ transplants
No direct contact transmission
Trypanosoma cruzi Vectors are endemic from
Mexico, Central America, and South America, but Chagas disease have occurred worldwide
T. cruzi infection cycles
mobile vs non-mobile T. cruzi
T. cruzi can infect any ___ cell
nucleated
Bad luck: cardiomyocytes, smooth muscle cells, neurons
cells w/o nuclei - platlets, red blood cells
vsg protein
Variant surface glycoprotein - temporary skins - undergo recombination of pieces of genes - diff types of glycoproteins
there are several large polymorphic glycoproteins on their surface (all tropsamsomes) - Over 1,100 possible versions!
allows for chronic infections that can last a lifetime - by time antibodies devoloped for one another grows back
why vsg protein makes it so hard to diagnose
hapen to take sample when low paracetemia - wont see it - need to take multiple samples
T. cruzi is not a true neurotropic pathogen unlike
its close homologue T. brucei
How does T. cruzi enter the CNS
choroid plexi
CNS only when uncontrolled for a very long time (high levels, high chance into CNS)
T. cruzi has an acute and a chronic phase
if untreated, infection is lifelong - immune can kill 99% but that last 1% comes back
Acute phase of T. cruzi
mostly asymptomatic or mild, general symptoms
Chagomas or Romaña’s sign are unique to Chagas (swelling of the eyelids on the side of the face near the bite wound or where the bug poop was accidentally rubbed into the eye) high inflammation at site of entry
Mostly in children, and immune status will determine if it develops severe complications (cardiac or CNS infection)
chronic phase of T. cruzi infection
After the acute phase resolves, even with treatment it enters a chronic phase
Most people remain asymptomatic (chronic indeterminate)
~30% will develop life-threatening symptoms (chronic determinate): cardiac, intestinal, or nervous infection
Most deaths are due to hearth failure – 1/3rd are due to clinical meningoencephalitis
Congenital and non-vectorborne infections are considered acute
diagnosis of T. cruzi
Acute phase – direct visualization of parasites on blood smears
Chronic phase – serologic testing since parasites are no longer detectable
Acute phase can be treated - chronic phase
has no treatment - treat symptoms
T. cruzi treatment
Two drugs are used – side effects are common and increase in severity with age
Not recommended for adults (>18 years)
drug - depends on age and health conditions
Chronic phase - treatment by cardiologist, gastroenterologist, or neurologist - always have escapes - cannot take drugs forever
sleeping sickness is caused by
two subspecies of Trypanosoma brucei
> 90% of cases caused by T. brucei gambiense - west - less pathogenic
rest by T. brucei rhodesiense. - east - neurotropic - also in flies - change behavior - inc hunger, inc food, inc chance transmit
African trypanosomiasis is transmitted by
the tsetse fly, which is found only in rural Africa
resuvars for African trypanosomiasis
large resuvars - hard to control
Animals, especially livestock, can also be infected
Only way of infection is vectorborne, but animals represent an important reservoir - implicated on dissemination
Rare reports of transplacental infection
If untreated both African trypanosomiasis are
fatal
tale tale symptom of CNS African trypanosomiasis
disrupt 24hr sleep cycle
T. brucei cycle
T. brucei and VSG
Also have cycling expression of VSG, expressing only one at any given time
Larger repertoire, >1,500 versions of VSG can be expressed
T. brucei neurotropism
shows neurotropism - CSF is preferred fluid for replication
Initially enters the Choroid plexus through fenestrated capillaries (later on BBB collapses)
Expresses metalloproteinases that degrade basal lamina of the BCSFB - side effect they lose their VSG coat - induces great inflammatory response - disregulated - BBB colapses
because neurotropic - all infections involve CNS
T. brucei infection involves 2 stages
Hemolymphatic phase – dividing blood and lymph - parasite is found in the peripheral circulation (mild, general symptoms), but it has not yet invaded the CNS
Neurological phase – parasites have invaded the CNS
Subspecies of T. brucei radically different
T. b. rhodesiense - east
reaches neurological phase in days/weeks - death within months
b. gambiense - west
stays on hemolymphatic phase for months/years, with CNS invasion usually ~3 years after - death ensues 6 – 7 years if untreated
T. brucei diagnosis
is direct visualization of parasite – loads of T.b. rhodesiense are substantially higher than T.b. gambiense in any fluid
Serologic testing for T.b. gambiense works, but is used for screening purposes only and the definitive diagnosis is visualization on CSF (difficult to find on blood smears)
T. brucei treatment
Therapy depends on the subspecies involved (east vs west) and on the stage of the disease - follow up examinations for up to 2 – 3 years are necessary to prevent relapse
- Reason there are different therapies is the nature of the BBB!
- Second phase drug can cause seizures
Both first and second stage drugs are highly effective
Helminth CNS manifestations
Can produce various CNS manifestations: meningoencephalitis, brain abscesses (granulomas), and cerebral vasculitis
Helminth infections from
contaminated food or water
Nematodes (roundworms) - Trichinella spiralis
Trematodes (flukes) - Schistosoma spp
Cestodes (tapeworms) - Taenia solium
neurotropic helminths
most are not true neurotropic - easier to treat - but also a lot of general symptoms
True neurotropic: Angiostrongylus, Baylisascaris, Toxocara – less
common - Higher mortality due to delayed diagnosis - because they are neurotropic!
helmith immune response
Schistosoma spp (Schistosomiasis) most by
Most infections by S. japonicum, S. mansoni, or S. haematobium
Another of CDC’s neglected tropical diseases
In terms of socioeconomical burden, 2nd only to malaria
Schistosoma spp complete life cycle in
in snale
expose - snale infeted by body of water
Water-borne – contaminated freshwater
Intermediate host, water snails, needed for cycle
Schistosoma spp areas at risk
Schistosoma spp cycle
Schistosoma spp Symptoms are caused by
body’s reaction to eggs
Eggs that become lodged in tissues cause inflammation and scarring
Larvae may also migrate to the spinal cord or the cerebral
vasculature and shed eggs there - neuroinflammation
Repeated Schistosoma spp infections cause
anemia, malnutrition – without treatment can persist for years
Schistosoma spp Spectrum of neurological manifestations is
species dependent
Brain infection is most frequent S. japonicum
Other two species, although rarely, can affect the spinal cord and eventually the brain
Neuroschistosomiasis
Neuroschistosomiasis damage
Chronic phase is characterized by seizures, focal signs, and intracranial hypertension due to single or multiple brain granulomas.
Intracranial hemorrhages may occur damage of small leptomeningeal or parenchymal blood vessels induced by parasites (worm not go into parachima but eggs can)
Another example of CNS disease NOT caused by pathogen invading the CNS
S. mansoni and S. haematobium
almost never CNS - when is, in spinal cord
Transverse myelitis - intense inflammation around parasite
Usually lower levels of spinal cord - flaccid paralysis, sphincter dysfunction and sensory loss
May develop into abscesses - low back pain, saddle anesthesia, sphincter dysfunction, and weakness or paralysis of lower limbs
Rarely, acute paraplegia due to occlusion of the anterior spinal artery by the parasite
S. mansoni and S. haematobium clinical manifestations
Most are due to uncontrolled inflammatory response against the eggs, the worm is killed
Schistosomiasis diagnosis
Symptoms are general – most cases do not involve CNS
Diagnosed through the detection of parasite eggs in stool or urine specimens
Schistosomiasis risk factors
Commonly places with poor sanitation
School-age children at risk
Women doing domestic chores involving water at risk
Eco-tourism and popularity of “exploring off the normal areas”
S. japonicum is restricted to
(most probable to cause CNS infection)
restricted to Indonesia and parts of China and Southeast Asia (none in japan)
Other Schistosoma spp are also restricted geographically
Schistosomiasis treatment
Safe and effective medication is available: Praziquantel
taken for 1-2 days to treat all Schistosoma infections
CNS involvement - Praziquantel associated with corticosteroids
Surgical decompression of the spinal canal is still an option in some cases to treat transverse myelitis
Schistosomiasis prevention
large-scale treatment of at-risk population groups, access to safe water, improved sanitation, hygiene education, and snail control
Neurocysticercosis is caused by
By larva form of Taenia solium
Larvae ≠ tapeworm
common CNS parasitic infection
T. solium (neurocysticercosis)
Another of CDC’s neglected tropical diseases [disease of immigrants - when immigrated already infected with disease]
T. solium Larvae vs tapeworm
tapeworm - grow in intestine to very long
larva can infect any organ, but clinical manifestation are always due to CNS infection
T. solium area
Most common cause of focal onset epilepsy in Central and South America
T. solium life cycle
Pigs and humans become infected by ingesting eggs [humans ingest undercooked pork containing cysticerci]
**Eggs hatch **in the intestine, invade the intestinal wall and reach vasculature - dissemination
[taeniasis (infection by adult tapeworm]
Once reach other tissues, they **develop into cysticerci **
Cysts in the brain results in neurocysticercosis.
Once attached, progottids are released in feces in great numbers for long periods of time
progottid
small segment of worm
every progottid release lots of eggs all the time
Cysts, (cysticerci), can develop in
the muscles, the eyes, the brain, and/or the spinal cord.
Generally, only cysts in brain and/or spinal cord will cause symptoms
Neurocysticercosis symptoms
only cysts in brain and/or spinal cord will cause symptoms
Cause seizures and/or headaches (these are more common)
[get in parenchyma] Confusion, difficulty with balance, brain swelling, and excess fluid around the brain (these are less common) [block canalls - hydrosephilus]
what determines Neurocysticercosis severity
Parasite load will determine severity low loads will be asymptomatic
Usually not fatal, but brain damage is irreversible [lots of cysts - can be fatal]
Cysticerci are
liquid-filled vesicles including an invaginated scolex
Neurocysticercosis cysts in CNS
may be located anywhere within the CNS: Parenchymal brain cysticerci, subarachnoid and ventricular cysticerci, or spinal cord cysticerci
Not clear how they enter the CNS – accepted notion is bloodstream
___ cysts can get very large due to ___
Extraparenchymal
osmosis
The cysts are eventually killed, and they become calcified
Neurocysticercosis diagnosis
Symptoms are general – parasite material not readily accessible
Preferred criteria - brain imagining techniques [Cysts can be easily seen on brain imagining techniques - if calcified - have been infected for years]
Histological
Serological
Epidemiological
Neurocysticercosis treatment
has to be individualized [b/c symptoms could be due to many reasons]
Live cysticerci can be treated with albendazole or praziquantel
Seizures can be treated with anticonvulsants
Hydrocephalus can be treated surgically
Excessive inflammation with corticosteroids
