Parasitic Pathogens Affecting the CNS

Mark F. Wiser Department of Tropical Medicine School of Public Health

Protozoa Affecting the CNS

Protozoan

Toxoplasma gondii

Disease Associated with congenital defects and AIDS African Trypanosomes

Plasmodium falciparum Entamoeba histolytica

Free-living ameba African Sleeping Sickness Cerebral Malaria Rare invasion of the brain Rare cases

Amebas Affecting the CNS

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Entamoeba histolytica

– normally found in large intestine – can become invasive (primarily liver) • Free-living Amebas

Ameba

Naegleria fowleri Acanthamoeba

species

Balamuthia mandrillaris

Diseases

PAM GAE; skin or lung lesions; amebic keratitis GAE; skin or lung lesions

Toxoplasma gondii

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cosmopolitan distribution seropositive prevalence rates vary

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generally 20-75%

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generally causes very benign disease in immunocompetent adults

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congenital transmission

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AIDS associated

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tissue cyst forming coccidia

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predator-prey life cycle

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felines are definitive host

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infects wide range of birds and mammals (intermediate hosts)

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Definitive Host adult forms sexual reproduction

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Intermediate Host immature forms asexual reproduction

chronic stage = bradyzoites acute stage = tachyzoites

Human Transmission

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ingestion of sporulated oocysts (cat feces + incubation) ingestion of zoites (undercooked meat) congenital infection (only during acute stage) organ transplants

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chronic infection in donor

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immunosuppression blood transfusions (only during acute stage)

Acquired Postnatal Toxoplasmosis

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1-2 week incubation period acute parasitemia persists for several weeks until development of tissue cysts

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often asymptomatic (>80%)

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a common symptom is lymphadenopathy without fever

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occasionally mononucleosis-like (fever, headache, fatigue, myalgia) likely persists for life of patient immunosuppression can lead to reactivation (eg, organ transplants)

Congenital Toxoplasmosis

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1 o infection must occur during or

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shortly before pregnancy

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can only occur once

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1/3 will pass infection to fetus incidence ~1 per 1000 births severity varies with age of fetus

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move severe early in pregnancy

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more frequent later in pregnancy infection can result in: spontaneous abortion, still birth, premature birth, or full-term ± overt disease

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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

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common complication associated

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with AIDS during the 1980's recrudescence of latent infection multifocal disease associated with

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immunosuppression lesions detectable with CT or MRI little spread to other organs symptoms include: lethargy, apathy, incoordination, dementia progressive disease

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convulsions usually fatal if untreated

Diagnosis

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various serological tests active (acute) vs chronic infection

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compare samples at 2 week

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intervals IgM > IgG;

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Ab titers seldom by direct parasite demonstration

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biopsy

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inoculation into mice or cell culture (only acute stage) CT scans or MRI for toxoplasmic encephalitis

Treatment

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recommended: anti-folates (pyrimethamine + sulfadiazine)

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clindamycin for patients not tolerating sulfadiazine

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spiramycin for prophylatic use during pregnancy Condition symptomatic disease active retino choroiditis asymptomatic children (<5) immuno compromised Duration until symptoms subside and evidence of immunity Comments until symptoms subside and evidence of immunity 3-6 weeks + corticosteriod (anti inflammatory) prevents retinochoroiditis 4-6 weeks after symptoms subside + continued prophylaxis + folinic acid in AIDS

Prevention Raw Meat

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cook meat thoroughly (66 o C, 150 o F)

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wear gloves when handling

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wash hands after

Cat Feces

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clean litter box promptly (<24 hr)

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wear gloves

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keep cat in house

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cover sand box

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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 Cysticercosis Hydatid Disease Schistosomiasis Paragonimiasis Eosinophilic Meningitis Agent Taenia solium (pork tape worm)

Echinococcus

species Schistosoma species Paragonimus

Angiostrongylus

cantonensis (rat lung worm)

Gnathostoma

spinigerum Predominant Tissues Muscle and brain Liver (75%) and lungs (15%) Liver or bladder Lungs Lungs 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

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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

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onset of epileptic seizures person from endemic area CT scans and MRI are most useful

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1-2 cm cystic lesions

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with or without edema and inflammation some serological tests available

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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

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Enhanced personal hygiene Thorough cooking/ freezing of pork to kill cysticerci Enhanced environmental sanitation

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proper disposal of human feces Agricultural inspection of pork Vaccination of pigs?