Parasitic Pathogens Affecting the CNS

Mark F. WiserDepartment of Tropical Medicine

School of Public Health

Protozoa Affecting the CNSProtozoan 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 DiseasesNaegleria fowleri PAM

Acanthamoeba species GAE; skin or lung lesions; amebic keratitis

Balamuthia mandrillaris GAE; skin or lung lesions

Toxoplasma gondii• cosmopolitan distribution• seropositive prevalence rates vary

• generally 20-75%• generally causes very benign

disease in immunocompetent adults• congenital transmission• AIDS associated

• tissue cyst forming coccidia• predator-prey life cycle• felines are definitive host• infects wide range of birds and

mammals (intermediate hosts)

Definitive Host• adult forms• sexual

reproduction

Intermediate Host• immature forms• asexual

reproduction

chronic stage = bradyzoites

acute stage = tachyzoites

• 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)

Human Transmission

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 disease

until symptoms subside and evidence of immunity

active retino-choroiditis

until symptoms subside and evidence of immunity

+ corticosteriod (anti-inflammatory)

asymptomatic children (<5) 3-6 weeks prevents

retinochoroiditis

immuno-compromised

4-6 weeks after symptoms subside + continued prophylaxis

+ folinic acid in AIDS

Raw Meat Cat Feces • cook meat thoroughly

(66oC, 150oF) • wear gloves when

handling • wash hands after

• clean litter box promptly (<24 hr)

• wear gloves • keep cat in house • cover sand box • control strays

Prevention

Frenkel et al (1995) AJTMH 53:458

But dog contact is highly correlated with Toxoplasma transmission.

Several studies show no correlation between cat contact and Toxoplasma.

An Enigma

Some Helminths Affecting the CNS

Disease Agent Predominant Tissues Cysticercosis Taenia solium

(pork tape worm) Muscle and brain

Hydatid Disease Echinococcus species

Liver (75%) and lungs (15%)

Schistosomiasis Schistosoma species Liver or bladder

Paragonimiasis Paragonimus Lungs Angiostrongylus cantonensis (rat lung worm)

Lungs Eosinophilic Meningitis Gnathostoma

spinigerum Various organs

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?