Parasitic Pathogens
Affecting the CNS
Mark F. Wiser
Department of Tropical Medicine
School of Public Health
Protozoa Affecting the CNS
Protozoan Disease
Toxoplasma gondii Associated with congenital
defects and AIDS
African Trypanosomes African Sleeping Sickness
Plasmodium falciparum Cerebral Malaria
Entamoeba histolytica Rare invasion of the brain
Free-living ameba Rare cases
Amebas Affecting the CNS
• Entamoeba histolytica
– normally found in large
intestine
– can become invasive
(primarily liver)
• Free-living Amebas
Ameba Diseases
Naegleria fowleri PAM
GAE; skin or lung lesions;
Acanthamoeba species
amebic keratitis
Balamuthia mandrillaris GAE; skin or lung lesions
Toxoplasma gondii
• cosmopolitan distribution
• seropositive prevalence rates vary Definitive Host
• generally 20-75% • adult forms
• generally causes very benign • sexual
disease in immunocompetent adults reproduction
• congenital transmission
• AIDS associated Intermediate Host
• tissue cyst forming coccidia • immature forms
• predator-prey life cycle • asexual
• felines are definitive host reproduction
• infects wide range of birds and
mammals (intermediate hosts)
chronic stage =
bradyzoites
acute stage =
tachyzoites
Human
Transmission
• ingestion of sporulated
oocysts (cat feces +
incubation)
• ingestion of zoites
(undercooked meat)
• congenital infection (only
during acute stage)
• organ transplants
• chronic infection in
donor
• immunosuppression
• blood transfusions (only
during acute stage)
Acquired Postnatal Toxoplasmosis
• 1-2 week incubation period
• acute parasitemia persists for several
weeks until development of tissue cysts
• often asymptomatic (>80%)
• a common symptom is
lymphadenopathy without fever
• occasionally mononucleosis-like
(fever, headache, fatigue, myalgia)
• likely persists for life of patient
• immunosuppression can lead to
reactivation (eg, organ transplants)
Congenital Toxoplasmosis
• 1o infection must occur during or
shortly before pregnancy
• can only occur once
• 1/3 will pass infection to fetus
• incidence ~1 per 1000 births
• severity varies with age of fetus
• move severe early in pregnancy
• more frequent later in pregnancy
• infection can result in: spontaneous
abortion, still birth, premature birth,
or full-term ± overt disease
• typical disease manifestations include:
retinochoroiditis, psychomotor disturbances,
intracerebral calcification, hydrocephaly,
microcephaly
Prevalences of Outcomes
5-10% death
8-10% severe brain and eye damage
10-13% moderate-severe visual
impairment
58-72% asymptomatic at birth, many
developing retino-choroiditis
or mental impairment later
Toxoplasmic Encephalitis
• common complication associated
with AIDS during the 1980's
• recrudescence of latent infection
• multifocal disease associated with
immunosuppression
• lesions detectable with CT or MRI
• little spread to other organs
• symptoms include: lethargy, apathy,
incoordination, dementia
• progressive disease convulsions
• usually fatal if untreated
Diagnosis
• various serological tests
• active (acute) vs chronic
infection
• compare samples at 2 week
intervals
• IgM > IgG; Ab titers
• seldom by direct parasite
demonstration
• biopsy
• inoculation into mice or cell
culture (only acute stage)
• CT scans or MRI for
toxoplasmic encephalitis
Treatment
recommended: anti-folates (pyrimethamine + sulfadiazine)
clindamycin for patients not tolerating sulfadiazine
spiramycin for prophylatic use during pregnancy
Condition Duration Comments
symptomatic until symptoms subside
disease and evidence of immunity
active retino- until symptoms subside + corticosteriod (anti-
choroiditis and evidence of immunity inflammatory)
asymptomatic prevents
3-6 weeks
children (<5) retinochoroiditis
4-6 weeks after symptoms
immuno-
subside + continued + folinic acid in AIDS
compromised
prophylaxis
Prevention
Raw Meat Cat Feces
• cook meat thoroughly • clean litter box
(66oC, 150oF) promptly (<24 hr)
• wear gloves when • wear gloves
handling • keep cat in house
• wash hands after • cover sand box
• control strays
An Enigma
Several studies show no
correlation between cat
contact and Toxoplasma.
But dog contact is highly
correlated with Toxoplasma
transmission.
Frenkel et al (1995)
AJTMH 53:458
Some Helminths
Affecting the CNS
Disease Agent Predominant Tissues
Taenia solium
Cysticercosis Muscle and brain
(pork tape worm)
Echinococcus Liver (75%) and lungs
Hydatid Disease
species (15%)
Schistosoma
Schistosomiasis Liver or bladder
species
Paragonimiasis Paragonimus Lungs
Angiostrongylus
cantonensis Lungs
Eosinophilic
(rat lung worm)
Meningitis
Gnathostoma
Various organs
spinigerum
Taenia solium and Cysticercosis
• adult tapeworm infects GI tract of humans
• larval stages infect tissues causing
cysticercosis or neurocysticercycosis
• most common parasitic disease of the CNS
• endemic throughout much of the developing
world
– especially prevalent in Central and South America,
Sub-Saharan Africa, Southeast Asia and Central
and Eastern Europe
• prevalence of 3.6% in some regions of Mexico
• greatest cause of acquired epilepsy worldwide
Cysticercosis in the
United States
• has become an important parasitic disease,
particularly in California
• estimated that 1000 new cases of
neurocysticercosis will be diagnosed each
year
• increasing prevalence attributed to the
migration of large numbers of rural
immigrants from developing countries
• also improvements in neuro-imaging leading
to better diagnosis
http://www.dpd.cdc.gov/dpdx/
Disease States
• Taeniasis = adult tapeworm in small intestine
– Usually asymptomatic (eggs or proglottids in feces)
– Vague abdominal symptoms occasionally report
• Cysticercosis = T. solium larvae in human
tissues (eg, muscle)
– Usually asymptomatic
– Painless subcutaneous nodules in arms and chest
• Neurocysticercosis (NCC) = cysts in the central
nervous system
– Most severe manifestation
Pathogenesis of Cysticerci
• larva (cysticercal cysts) survive up to
5 years
• living larva produce little inflammation
• death of larva leads to inflammation
and edema resulting in symptoms
• cellular reaction eventually destroys
parasite and leaves a calcified nodule
Clinical Manifestations
• presentation is varied—depends on stage,
number, size and location of cysts
• seizures/convulsions most common
symptoms
• blocked circulation of CSF can lead to
intracranial hypertension or hydrocephalus
• occasionally large cysts can mimic tumors
• can also cause a variety of mental and
motor changes
Diagnosis
• onset of epileptic seizures
• person from endemic area
• CT scans and MRI are
most useful
– 1-2 cm cystic lesions
– with or without edema and
inflammation
• some serological tests
available
– problems with sensitivity
and specificity
Treatment
• symptomatic treatment (eg,
antiepileptic drugs)
– spontaneous cures noted especially in
children
• praziquantel and albendazole kill the
cysts faster
– limited clinical benefit
– administer with corticosteroids (anti-
inflammatory)
• surgical excision of cysts was previous
treatment
Prevention and Control
• Enhanced personal hygiene
• Thorough cooking/ freezing of pork to
kill cysticerci
• Enhanced environmental sanitation
– proper disposal of human feces
• Agricultural inspection of pork
• Vaccination of pigs?