Parasitic Infections 1 Flashcards
“Parasitic infections of the CNS” medically is a
Catchall expression for all non-bacterial, non-viral, and non-fungal infections
(ameba - not parasite but when get consider parasitic infection)
Parasitic burden
Tremendous burden to public health in the developing world
Increased tourism, migratory movements, and the AIDS epidemic have facilitated the spread of formerly geographically restricted parasitic infections
Parasites are diverse in
mechanisms and pathology
clinical manifestations
Difficult diagnosis
- Nonspecific symptoms, poor reliability of serological tests
What is a parasite
Organism that lives on or in a host organism from which it gets food
true vs accadental parasite
True parasite – humans are required to complete life cycle
Accidental – humans are a dead-end hosts; no benefit to either
Three main clinical classes of parasites
protozoa, helminths, and ectoparasites
Protozoans
microscopic, unicellular eukaryotes, free-living or parasitic in nature
harder to kill - more similar to own cells - anti parasitics high side effects
Helminths
large, multicellular organism, free-living or parasitic
cestodes (tapeworms); nematodes (roundworms); trematodes (flukes)
Ectoparasites
animals that attach or burrow into the skin and feed on the host for relatively long periods of time (days to weeks)
Mostly ticks, fleas, lice, and mites
vectors for pathogens - not pathogens themselves
Main CNS parasitic infections
most common CNS parasitic infections (3)
Amoebic that invade CNS
Naegleria, Acanthamoeba, and Balamuthia
Free-living, environmental organisms
Amoeba clinical manifestations
PAM and GAE have different
etiologies, risk factors, duration of illness, clinical features, and laboratory and imaging findings
___ survive despite treatment for Amoebic infections
<5%
PAM Naegleria fowleri (N. fowleri) can - to brain/cells
Fulminant (liquify brain), acute disease - necrosis of frontal lobes
N. fowleri can phagocytose entire neurons! (+ eat neurons)
PAM Acute inflammatory response
contributes to damage - no space in brain
rapid and potent
health status with PAM
Immunocompromised and immunocompetent individuals alike
heath status not matter
Naegleria fowleri more common in
warmer regions and warmer months
N. fowleri is a thermophilic protist - lake, hot spring - climate change, changing endemic areas.
Also poorly chlorinated pools, hot tubs, and thermally polluted water bodies (industrial discharge - change water temp)
N. fowleri life cycle
3 stage life cycle: amoeboid trophozoites,
flagellates, and cysts
Amebic trophozoites are the infective form
Flagellates are temporary, non-feeding, cells
Both trophozoites and flagellated forms are found in CSF
Cysts are survival form – dormant, stress resistant
Cysts never reported in brain tissue 1 case report of infection after inhalation of cysts
how does N. fowleri get into CNS
Enters CNS via the nose - swimming or diving (why main pathology - frontal lobes)
also become infected after using a neti pot or bathing with contaminated water
You CANNOT get infected by drinking or person-to- person contact
steps N. fowleri get into CNS
(adhesion) Binds to olfactory mucosa and penetrates respiratory epithelium
- Nfa1 is an adhesin localized to tips of pseudopodia - adhesion and
chemotactic behavior
Migrates through olfactory nerves into CNS [eats through, neurotropic]
Nitric oxide production and pore-forming proteins - necrosis
Several PAMPs - intense immune response
Lysis of immune cells releases more cytotoxic compounds
= significant destruction of brain parenchymal tissue = PAM
clinical presentation of N. fowleri
can mimic that of bacterial meningitis, but progresses rapidly - coma and death within days
Mouse models show protective immunity can be developed - irreversible damage occurs too fast
commonality of survival - identity fast and young
N. fowleri is suspected in cases
with recent history of freshwater exposure
N. fowleri CSF analysis
similar to bacterial meningitis (low glucose, elevated proteins, and polymorphonuclear cells)
N. fowleri
Visualization on CSF
Antigen detection
Serological testing
Brain imaging studies
Visualization on CSF can be missed on gram stains
Antigen detection assays can be performed on CSF or tissue sample, along with PCR - very few labs in US do them
Serological testing (measures antibody production) does not work as patients die too soon - no antibodies
Brain imaging studies can be normal early to findings of diffuse hemorrhages or infarctions with high inflammation later on the disease - depends on when do imaging
Toxoplasma can infect
any warm-blooded animal - Present worldwide
In immunosuppressed individuals Toxoplasma causes
toxoplasmosis
Multisystem disease, CNS involvement rare but most severe complication
immunosuppressed - aids, pregnant etc.
Toxoplasma is known for its
altering behavior of host to promote dissemination (by host been eaten by a feline) - once infect host looks for cat even if normally hate/avoid cat
Because humans can’t be eaten by cats, we are a dead-end host (accidental parasite)
___ are the only known reservoir of Toxoplasma
Felines
can undergo sexual reproduction else where - something special about GI tract in cat
Oocysts cycle Toxoplasma
Oocysts shed in cat’s feces
Oocysts picked up by intermediate hosts in nature
Oocysts sporulate, infecting muscle and neural tissue
Felines eat intermediate hosts, restarting cycle again
Ways humans get infected
Livestock infected by picking up oocysts from the environment
Food or water contaminated with cat feces or by contaminated environmental samples
Blood transfusion or organ transplantation
Transplacentally from mother to fetus
Estimated that ____ of the world is infected with Toxoplasma
1/3
40 – 50 million people in US
Toxoplasma is latent as
cysts in the muscles and the brain in health people
if in heart - very problematic
is the leading cause of death due to foodborne illness in the United States
Toxoplasma
One of the 5 neglected parasitic infections of the United States
Toxoplasma treatment
No current cure for infection - active infection can be treated, but latent cysts are resistant
once infected - infected for life
how Toxoplasma infects CNS
Toxoplasma CNS involvement almost always as an
opportunistic infections
One of the original AIDS-defining illnesses
Encephalitic syndrome - necrotic center surrounded by tachyzoites
Reactivation of cysts, which are already inside brain
Sudden fever, seizures, increased intracranial pressure, and decreased level of consciousness even coma
____ is the most common cause of infectious
Toxoplasma
retinochoroiditis (eye infection)
Can also gain access to CNS as a complication
Toxoplasma is more common in
hot and humid climates – oocysts are very sensitive to cold conditions
Toxoplasma responsible for “Cat Ladies”?
Most severe complication of Plasmodium falciparum infection
Cerebral malaria
only Plasmodium falciparum can cause CNS infection
Cerebral malaria GCS
GCS - lower number less concuss
Unarousable coma (GCS ≤ 9) with the presence of malaria infected red blood cells in the peripheral circulation
definition of CM and pathway from illness to death
Sudden fever - seizures - cloudiness or loss of consciousness
P. falciparum extensively modifies the surface of
RBC, leading to sequestration in the brain’s microcapillaries and “rosetting“ which contributes to the pathology.
CM clinical symptoms child vs adult
coma
sezures
SE
systemic complecations
neurological defects
retinopathy
prognosis
Status epilepticus
is a medical emergency associated with significant morbidity and mortality. SE is defined as a continuous seizure lasting more than 30 min, or two or more seizures without full recovery of consciousness between any of them.
Plasmodium spp species that are human pathogens
____ are ubiquitous
All the others are____
___ causes CM
5
P. falciparum
P. vivax
P. ovale
P. malariae
P. knowlesi
P. falciparum and P. malariae
restricted to certain geographical regions (most in Africa, Asia, or Oceania)
P. falciparum is the only one that causes CM - ~80% of all deaths from malaria
CM Infection happens during
a female Anopheles mosquito bloodmeal
Depends also on climatic factors such as temperature, humidity, and rainfall
Plasmodium spp involves ___ hosts
2 hosts: mosquito & animals (humans are almost exclusive for some of the Plasmodium spp)
From mosquito - liver stage (fast replication - bursts liver cells)
From liver stage - blood stage
From blood stage - mosquito
Blood stage parasites are responsible for the clinical disease
P. falciparum infection
Neuroimaging
CSF analysis
Diagnosis is confirmed by
In children
P. falciparum infection treatment
Quinine is the drug of choice; artemisinin and artemether can also be used together with other drugs
There is a growing problem of drug resistance
Related symptoms if untreated can be as fatal as CM: hypoglycemia, pulmonary edema, renal failure, internal bleeding, and hepatic dysfunction
different human and environmental factors can affect P. falciparum treatment
immune status (pregnancy), genetics (sickle cell trait or Duffy blood group), agricultural work, deforestation, lack of housing
sickle cell - immune to malara (infectious disease influence evolution)
Best way to control malaria
control de mosquito (because v hard to treat)- nonprofit efforts
