Parasitic Infections in Central Nervous System Agnes Kurniawan Dept of Parasitologi FKUI

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BASIC PARASITOLOGY
The science that deals with organisms that take up their abodes Temporarily or permanently On or within other living organisms Procuring food with the relationship of these organisms to their hosts
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CLASSIFICATION
Ecto-parasite : Parasite that lives outside the body of the host (infestation) Endo-parasite : Parasite which lives within the body of the host (infection)
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CLASSIFICATION
Obligate-parasite : Parasites are completely dependent upon the host e.g : Ascaris lumbricoides Facultative-parasite : Parasites are capable of leading both a free and a parasitic existence upon the host e.g : - Strongyloides stercoralis, Tick
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Parasite
Phytoparasite Zooparasite Spirochaeta Virus

Protozoa

Metazoa
Helminths Arthropods

Nematode Trematode Cestode Untan-neurosains sem 4-2008

HOST
Harboring parasite species Usually a larger organism that provides physical protection and nourishment

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DEFINITIVE HOST
The host that harbors the adult or sexual stage of the parasite e.g : - Ascaris lumbricoides man - Plasmodium mosquito Intermediate host : Another animals that take place part or all of the larval or asexual stage e.g : - Plamodium mosquito man - Filaria man mosquito
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RESERVOIR HOST
Animals that harbor the same species of parasites as man and act as additional sources of human infection E.g : - Trichinella spiralis Rh : pig, rat, bear - Brugia malayi Rh : monkey, cat, dog

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VECTORS
Hosts that transmit parasites to man e.g. : mosquitos in malaria / filariasis glossina in sleeping sickness Africa

ZOONOSIS
Animal diseases which can be transmitted to human
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NEMATHELMINTHES
Roundworm , unsegmented Posses a body cavity Have a complete digestive system The sexes are separate

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PLATYHELMINTHES
Flatworms Bilaterally symmetrical Leaf shaped or band shaped Without a body cavity Have no digestive tract Hermaphrodite

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Protozoa
an unicellular animal cell living either in colonies or solitaire which is able to perform all physiological function of its own

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Classification :
E E E E Rhizopoda Mastigophora/Flagellata Cilliophora/Ciliata Sporozoa
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Reproduction
asexual : binary fission, schizogony, cyst formation sexual : Gametogony, sporogony,
conjugation

alternating asexual and sexual

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Pathology
Tissue damage by :

invasion enzyme toxin immune response

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Infection
Acute fatal Sub clinical Chronic/latent Relapse/ acute exacerbation

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Entomology
deals with insects, arachnids, and other arthropods which cause pathology / role in transmission infective agents The arthropods involved may be as : 1. the causal agents 2. intermediate hosts 3. vectors.

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Intermediate hosts
Transmission in a passive capacity. Part or all of the larval or asexual stage may take place in another animal such as the snail , Cyclops or Diaptomus.

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Disease Transmission Depends on :

Infection intensity Anthropophylic High density of vector species Mosquito life span / longevity Supported by Experimental evidence

Role Of Vector In

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DISEASE Cerebral malaria Neurocysticercosis

CAUSE P. falciparum Taenia solium

STAGE Schizont Larva

DEFINITIVE HOST

Mosquito Human

Cerebral toxoplasmosis
Brain abscess
Sleeping sickness

Toxoplasma gondii
E.histolytica
African Trypanosoma

Tachyzoite

Cat

Trophozoites Human
Trypomastigote Human

Granulomatous Ensefalitis Meningoensefalitis (PAM)

Acanthamoeba sp Naegleria fowleri

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Trophozoite Trophozoite

Free living Free living

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Malaria
Trias: fever, anemia and splenomegaly Caused by 4 species of human plasmodial: - P. falciparum - P. vivax - P. malariae - P. ovale

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Plasmodium falciparum
- Main cause of severe / complicated malaria - Specific behaviour: sequestration in deep capillary for schizogony and gametogony process. - Sequestration in : capillary of brain, lung, heart, liver, kidney, gastrointestinal, etc. - Sequestration forms sludge inhibits microcirculation temporary organ dysfunction/ failure.
If patients are cured in this stage no sequel
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Parasite` sequestration

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Severe malaria

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Pathogenesis of Cerebral Malaria

Capillary obstruction mechanism:
Rosetting (erythrocyte segregation ) Cytoadherence (erythrocyte adherence to endothel)

Impaired delivery substrate: hypoglycaemia, hypoxia, anemia Impaired perfusion: shock, acidosis, hypovolemia
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Pathogenesis of Cerebral Malaria

Endotoxin mechanism: NO, cytokines, etc Clotting Increased intracranial pressure: pediatric cases only

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Malaria diagnosis
1. Microscopic (Giemsa, QBC) : to find parasite or parasite product in blood make thick and thin blood smear , stain Diagnosis stage and species 2. Serology (rapid test) : P. falciparum Antigen (HRPII) 3. Detection DNA or RNA parasite (PCR)

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Neurocysticercosis

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Important Taenia species in Indonesia

Taenia saginata; intermediate host: cow Taenia solium; intermediate host: pig, dog

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Taeniasis/cysticercosis in Indonesia

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Cysticercosis
aetiology: cysticercus cellulosae (larvae of the tapeworm T. solium) Larvae are acquired by ingestion of T. solium ova

Microscopically, T. saginata &T. solium eggs are similar

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Cysticercus : a white opalescent vescicle, ovoid to round, measuring 8-15 mm x 5-8 mm containing only one protoscolex May infect many organs Untan-neurosains sem 4-2008 (subcutaneous tissue, brain, eye, muscles).

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Cysticercosis
the onchospheres migrate to the tissues and develop into cysticerci the cysticercus dies and becomes calcified calcified cysticerci in muscle
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Cysticercosis
Location of Cysticercus : subcutaneous tumor (subcutaneous cysticercosis) eye muscle cerebral tumor

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Pathogenesis of Neurocysticercosis
mechanical compression & damage of tissue e.g. granuloma immunopathological eg cellular infiltration late secondary sequelae of cysticercosis e.g. fibrotic scar

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Clinical Manifestions
epilepsy cerebellar ataxia sensory defect acute onset of focal seizures less common: hemiparesis, visual changes and sensory disturbances no fever
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Risk Factors
Immigrant from endemic area poor sanitation, use of sewage for fertilizer and lack of controlled pens for pigs Contact with other household member who often travel to endemic area (carrier)
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Diagnosis
Microscopic: to find Taenia egg examine stools for ova and parasites (3 consecutive days) Serology: antibody detection by enzyme-linked immunotransfer blot (EITB) and ELISA Radiology: 1. CT scan shows the cyst (solitary or multiple and usually 5-20 mm in diameter) and granuloma stages of neurocysticercosis. Most often in the cortex / gray-white junction. 2. MRI
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Cysticercus in the brain (CT Scan)

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Cerebral Toxoplasmosis

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Toxoplasma gondii
Host: man, animal Mode of infection: - ingestion of cyst in raw meats - ingestion of oocyst (in cat faeces) - transplacental - transfusion - organ transplantation - laboratory accident
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Organ damage
depends on host age, virulence and organ infected (CNS and eye: more severe) CNS: - meningoencephalitis - brain abscess (multiple) - aquaductus sylvii congestion hydrocephalus - intracranial calcification - mental and motoric retardation
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Acquired Toxoplasmosis in Immunocompetent Host

Rarely detected (asymptomatic) Lymphadenopathy (self limiting) Fever, headache, myalgia, sore throat, hepatosplenomegaly Retinochoroiditis Myocarditis Encephalitis
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Toxoplasmosis In Immunocompromised Host

Can be fatal Reactivation of congenital and required infection CNS: toxoplasmic encephalitis Pulmonary involvement

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Congenital Toxoplasmosis Disease in Infants

Normal at birth Hepatosplenomegaly Icterus Lymphadenopathy Erythroblastosis Hydrops foetalis Death: 5% - 15%
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Congenital Toxoplasmosis Disease in Infants

Classic triad: 1. Hydrocephalus 2. Intracranial calcification 3. Retinochoroiditis: atrophy of retina & choroid pigmentation 4. + Psychomotoric retardation Tetrade Sabin
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Toxoplasmosis Serology
Acute toxoplasmosis: Serial blood exam: IgG increase significantly after 3 weeks or more (4fold) Conversion: negative to positive IgG and IgM in neonatal blood Polymerase chain reaction

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E. histolytica
cause brain abscess usually occurs in the framework of systemic amebiasis < 10% of patients with a hepatic amebic abscess have cerebral amebiasis the cerebral abscesses are usually multiple with accompanying cerebral edema. abscesses are most commonly located in the cerebral hemisphere, although a cerebellar location is not infrequent
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Pathogenesis
habitat: colon, particularly rectum, sigmoid trophozoites adhere to colonic epithelial cells through the galactose/N-acetyl galactosamine specific lectin
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Pathogenesis
Amebapores human cells become immobile within minutes and lose their cytoplasmic granules, structures and their nucleus
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Amebic colitis
E.histolytica cysteine proteinases digest extracellular matrix proteins trophozoite invasion into and within the submucosal tissues amebic colitis

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chronic amoebiasis colitis portal vein amebic lever abscess hematogenous spread pulmonary amoebiasis abscess brain abscess
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Clinical manifestations
usually preceded by gastrointestinal or hepatic or respiratory symptoms. an abrupt onset of mental status change and/or focal neurologic deficits, headache, nausea, vomiting, delirum, coma, sensorial alteration meningitis can occur cranial nerve involvement is frequent death occurs over 12-72 hours without adequate therapy
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Diagnosis
Serologic tests, such as IFA, ELISA, for specific antibodies to E. histolytica are very helpful in diagnosis of invasive amebiasis Computed tomograph (CT) and nuclear magnetic resonance (NMR) for the brain abscess

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Free living amoeba

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Trofozoit Acanthamoeba sp

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Brain Biopsy

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Naegleria fowleri
Infect immunocompetent host Infective stage : the trophozoites Mode of infection : 1. through the olfactory neuroepithelium 2. nasal passages when water is forced into the nose via diving or jumping or submerged underwater Trophozoites are found in cerebrospinal fluid and tissue Untan-neurosains sem 4-2008 60

Primary Amebic Meningoencephalitis (PAM)

an acute, a deadly disease of the brain characterized by necrotizing and haemorrhagic meningoencephalitis, symptoms usually occurs 3-7 days after infection Aetiology: Naegleria fowleri Epidemiology: individuals with warm water related activities, diving in the river, summer time
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Clinical features
Fever Sore throat Swelling in nose Severe headache Stiff neck and back Nausea, vomiting Confusion, seizures
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Diagnosis
Microscopic examination Culture Immunofluorescent antibody Polymerase chain reaction

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Granulomatous Amebic Encephalitis

Aetiology: Acanthamoeba sp - Acanthamoeba castellani - Acanthamoeba polyphaga - Acanthamoeba culbertsoni - Balamuthia mandrillaris (non free living) free living amoeba capable of causing subacute or chronic in individuals with imunocompetent and compromised and also in animals The trophozoites and cysts are the infective forms entry into the body through the lower respiratory tract, ulcerated or broken skin and Untan-neurosains semsystem 4-2008 64 invade the central nervous by hematogenous dissemination

Clinical features
Subfebris Headache Altered mental status Stiff neck Nausea and vomit Focal neurologic deficit which progresses over several weeks to death
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Trypanosomiasis
1. T. rhodesiense 2. T. gambiense

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African trypanosomiasis/ sleeping sickness

Chancre trypanosoma on port d entre Fever Hepatosplenomegaly Lymphadenopathy (winter bottom sign) Meningoencephalitis: apathy, letharghy, coma and death (T. rhodesiense more virulent)
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Winter bottom sign

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American trypanosomiasis/ Chagas disease

. caused by T.cruzi amastigot forms in macrophages on port d entre granuloma formation unilateral orbital edema and conjunctivitis (romana sign)
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American trypanosomiasis/ Chagas disease

Hepatosplenomegaly, generalized lymphadenopathy Myocarditis Meningoencephalitis, ganglion cell disruption and autonomic function loss resulting in megaesophagus and megacolon

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Diagnosis
1. Finding the parasite (biopsy, blood examination,etc) 2. Culture 3. Inoculation / xenodiagnosis 4. Immunological reactions 5. PCR

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Thank You

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