Infeksi Parasit pada Sistem Saraf dan Jiwa

• Sistem Saraf dan Jiwa

- Toxoplasma gondii
- Taenia solium
- Trypanosoma brucei rhodensiense
- Trypanosoma brucei gambiense

• Pembuluh darah sistem saraf dan jiwa

P. falciparum
 PENYAKIT PENYEBAB STADIUM HOSPES
DEFINITIF

NEMATODA
Eosinophilic meningoencephalitis Angiostrongylus Larva Tikus
cantonensis
CESTODA
Hydatidosis Echinococcus granulosus Larva Anjing

Cysticercosis Taenia solium Larva Manusia

Coenurosis Multiceps Larva Anjing
PROTOZOA
Cerebral toxoplasmosis Toxoplasma gondii Takizoit Kucing

Cerebral malaria P. falciparum Schizont Nyamuk

Sleeping sickness African Trypanosoma Trypomastigote Manusia
Granulomatous Ensefalitis* Acanthamoeba sp. Trofozoit Hidup bebas

Meningoensefalitis (PAM)* Naegleria fowleri Trofozoit

Toxoplasma
gondii
(toxoplasmosis
)
Siklus Hidup Toxoplasma gondii

Infeksi primer

Anak-anak dan dewasa

10% limfadenitis, 90%

korioretinitis, sesekali asimptomatik
myocarditis atau myositis

Infeksi laten
(asimptomatik)

Reaktivasi pada pasien dengan status

immunocompromised (pasien dengan
AIDS, transplantasi organ, kanker, atau
pasien yang sedang mengonsumsi
imunosupresan

Toxoplasmic encephalitis
 Toxoplasmic Encephalitis
(TE)
Acute toxoplasmosis in hosts who do not have AIDS but are
immunodeficient (leukemia, cancer treatment) may be newly acquired or
may be reactivation  intense proliferation of tachizoites.
TE occursin 10–50% of HIV-infected patients
who are seropositive for
antibodies to T. gondii and who have CD4 count < 100 cells/mm3.
The greatest risk is among patients with a CD4+ T lymphocyte count < 50
cells/mm3
The most common affected area: the basal ganglia but other lessions may
involve cerebellar & brain stem areas.

Bradyzoite in brain tissue

Pathogenesi
s

 Following oral infection

 The tachyzoite (invasive form) disseminates

throughout the body

 Tachyzoites infect any nucleated cell, where they multiply

and lead to cell destruction and production of necrotic
foci surrounded by inflammation

 The onset of cell-mediated immunity against T gondii

is accompanied by the transformation of the parasite
into tissue cysts resulting in lifelong chronic infection
Clinical
manifestations
Depend on the lesion location:
• Characteristically, TE has a subacute onset with focal neurologic abnormalities
(frequently accompanied by headache, altered mental status, and fever).
• The most common focal neurologic signs are motor weakness and speech
disturbances
• Brain stem involvement : cranial nerve lesions and many patients exhibit
cerebral dysfunction with disorientation, altered mental status, lethargy,
coma.
• In some patients, neuropsychiatric symptoms : paranoid psychosis, dementia,
anxiety, and agitation may be the major manifestations.
• Spinal cord involvement : motor or sensory disturbances of single or multiple
limbs, bladder or bowel dysfunctions, or both and local pain.
Clinical
manifestations
• Seizures
• Cerebellar signs
• Movement disorders
• Meningeal signs are rare

Other organs involvement:

Myocarditis, pneumonitis and
retinochoroiditis
 Diagnosi
 CSF examination → parasite
• Biopsy s
• Inoculation into mice or cell culture (only acute stage)
• PCR testing for DNA or mRNA
→ acute infection

 Blood examination → Ab specific

Classix Dx : detection of specific IgG & IgM
IgM : appear 2 weeks after infection (acute phase), than
decline.
IgG : appear later & maximal 2 months after infection, than
decrease to a relatively low & persist for live  proof of
previous infection

Problem : sometimes IgM still + months – years.

 Diagnosi
s AIDS patients, neuroimaging techniques (CT scans or MRI) usually
 In
demonstrate the abscesses as multiple ring-enhancing lesions with
mass effect and surrounding edema.
 They may be seen in the cortico-medullary junction.
 Patients with ring-enhancing brain lesions on CT scan or MRI along with
positive IgG antibody to T gondii, and CD4 count below 200 cells/mm3
should receive empiric therapy.
 Aclinical and radiological response to the specific therapy

will support the diagnosis of TE.
 Patients who fail to show a radiographic or clinical response within 2
weeks of therapy should have a brain biopsy performed.
 If the biopsy confirms TE, a switch to an alternative therapy should be
considered.
Diagnosi
s
 TREATMEN
T Acute infection
(significant increase of IgG, parasite or DNA/RNA
+)

Initial therapy (6 weeks)

Suppressive therapy
Asymptomatic TE
CD4+ >200 Lifelong unless
cells/mm3 immune
for ≥ 6 months in reconstruction occur
response (CD4+ >200
too stop
T HAARTsuppressive therapy cells/mm3)

CD4+ decreases to <200 cells/mm3

To restart suppressive therapy

*HAART: Highly Active Antiretroviral

Therapy
 TREATMEN
T Non acute infection
( no significant increase of IgG, parasite or DNA/RNA
-)

Empiric therapy 2 weeks

Good response No response

(clinical and (clinical and
radiological) radiological)
Continue therapy until 6 brain
weeks biopsy
Suppressive therapy Toxo Toxo -
(lifelong or intermittent +
depend Alternative other treatment
on number of CD4) therapy
TREATMEN
T
INITIAL THERAPY – for at least 6
weeks

• Pyrimethamine + sulfadiazine +
leucovorin
(folinic acid)

• Alternatives:
Pyrimethamine + clindamycin +
leucovorin

• Adjunctive steroids should be used only if there is a

mass effect or significant edema
 TREATMEN
T
 MAINTENANCE (SUPPRESSIVE) THERAPY should be lifelong
unless immune reconstitution inflammatory syndrome (IRIS)
occurs:
Pyrimethamine + sulfadiazine + leucovorin
The relapse rate on the regimens: approximately 25%
Alternatives
Pyrimethamine + clindamycin + leucovorin
PROPHYLAXI
S
PRIMARY PROPHYLAXIS
• Patients who are seropositive for Toxoplasma & CD4 count <
100
cells/mm3  should receive prophylaxis against TE

Trimethoprim-sulfamethoxazole (TMP-SMX)

• Primary prophylaxis should be discontinued in patients who

responded to highly active antiretroviral therapy (HAART) with
an increase in CD4 count to > 200 cells/mm3 for at least 3
months.

• Prophylaxis should be reintroduced if the CD4 count decreases to

< 100 cells/mm3.
 MALARIA
Malaria remains the world’s most devastating human parasitic infection,
afflicting more than 500 million people and causing from 1.7 million to
2.5 million deaths each year. (WHO)
Life cycle of Plasmodium
sp
 Malaria
sequestration
• In P. falciparum infection, parasites sequestered in the deep capillary
of internal organs i.e. brain, lung, kidney, liver, intestine etc
 Pathogenesi
s
Sequestered parasites (P.falciparum) in brain
capillaries

Cerebral
malaria
How is intravascular
parasite capable on
inducing neuronal
dysfunction ?
Changes of
erythrocytes
• Malaria lives and multiply in
red blood cells, also
express new antigen on the
surface of infected
erythrocytes
Pf-EMP1 (var-gene)
 Pathogenesi
s
PRB
C

Pf-EMP-
1
Pf-Erythrocyte membrane protein-1 will adhere to the endothel
receptors of brain capillary

ELAM VCAM CD-36 TSP

ICAM-1
ENDOT
Cytoadhesion
theory

Cytoadhesion will slow/obstruct blood flow 

tissue
hypoxia & increase intra cranial pressure 
Clinical
Manifestation
Within acute infection period
• Diffuse encephalopathy: impaired of consciousness,
seizures
• Brainstem signs: dysfunction of vital signs
• Focal neurological sign: hemipareses,
speech difficulties etc
• Cranial nerve palsies: vision and hearing
disturbances etc
 Diagnos
is
• Positive asexual stages of P. falciparum in blood smear, but without
bacterial or viral infections or any metabolism disorder
Diagnosi
s
Diagnos
is

Malaria RDT
(rapid diagnostic
test
Treatment

• Prompt parasitological confirmation by microscopy or

alternatively by RDTs is recommended in all patients
suspected of malaria before treatment is started.
• Treatment solely on the basis of clinical suspicion should
only be considered when a parasitological diagnosis is
not accessible.
• Very rapid antimalaria drugs such as artemisinin
injection and supportive treatment for other organ
failures
Malaria
algorithm
 Post Malaria Neurological
Syndrome
• Development of new neurological or psychiatric symptoms within
two months of acute illness of malaria (range 6 hours – 60 days)
• In Thailand 1.2 per 1000 patients
• Causal is still not clear, but immunological mechanism is possible
Taenia
solium
(Taeniasis)
Life cycle of Taenia
solium
 Taeniasis and
cysticercosis
• The human as definitive hosts:
- carrier by containing adult stage in the intestine
→
taeniasis
- clinical manifestation by containing encysted
larvae stage in various tissues → cysticercosis
(in central nervous tissue → neurocysticercosis)
Neurocysticercosis
(NCC)
• Disease caused by infection of the human
central nervous system with larvae of Taenia
solium
• Is recognized as an important public health
problem in developing countries and in USA,
since the discovery of CT and MRI scanning
 Cysticerci of T.
solium
• The cysticercus must survive in the muscle or other
tissue for weeks to months in order to complete the life
cycle
• The viable cysticercus appears as a thin-walled, oval cyst,
 1 cm in
diameter
 Cysticerci of T.
solium

The cysticerci modify the host immune response by many

ways:
 secrete taeniaestatin ( serine proteinase inhibitor) which
prevent complement activation, lymphocyte activation
and cytokin production of the host
 Cysticerci of T.
solium
 outer coat of cysticerci consist of sulfated polysaccharides
that are discarded and triggered complement away from
the cyst wall
 parasite paramyosin is thought to inhibit classical pathway
complement activation
Cysticerci of T.
solium
 parasites cultivate prostaglandins and low molecular weight
molecules that diminish inflammation and alter host response
to Th-2
parasites break down immuno globulins and make use as
source of amino acids.
 Cysticerci of T.
solium

 When parasite degenerate → vigorous of host

inflammatory response that associated with Th-1
cytokines: Interferon γ and IL-2
 Although the cysticerci reach their mature size
within a few weeks, there is
typically a period of several years between
exposure and onset of symptoms → Acute onset
Clinical
manifestation
Location Symptoms

Ventricle Hydrocephalus due to mechanical

obstruction → ICP ↑
Basilar cisternal Arachnoiditis → meningeal signs
(seizures), communicating
hydrocephalus, vasculitis → stroke
Brain parenchym Seizures: focal then generalization
or generalized
Ocular Visual changes

Spinal Myelopathy
Diagnosis of
NCC

• Is commonly difficult due to unavailability of biopsy

or autopsy materials (except in cases with ocular
involvement)
• Neuroimaging is not always pathognomonic (a
cystic lesion with mural nodule= invaginated
scolex)
• Diagnostic criteria depends on clinical history,
serologic tests, neuroimaging study and
exposure.
Flow chart of diagnosis of NCC

History & physical examination

CT scan and MRI

Serology such as ELISA to detect specific antibody

against cysticercus in blood or CSF
Treatment of
NCC

Differentiate between active and

Inactive* NCC, in addition to
cyst’s localization
↓
Anthelmintic administration plus steroid

*Inactive is where parasite is no longer viable or

degenerated
Trypanosoma
sp.
(tripanosomiasis
)
Life cycle of T.b. gambiense and T.b.
rhodesiense
 Trypanosoma
brucei
• Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense
• Extracellular parasite injected by tse tse fly
Reservoir
s
T.b. T.b.
gambiense rhodesiense
 Variant Surface Glycoprotein
 (VSG)
Is the predominant surface
antigen
 Prevent trypanosome lysis
by complement alternative
pathway and enables the
parasite to avoid specific
immune response via
antigenic variation (creating
new antigen for every
successive parasitemia)
 Variant Surface
Glycoprotein
• VSG also induce auto antibodies by polyclonal B-
cell activation and cytokine synthesis
• The autoantibodies are against erythrocyte, liver,
cardiolipids, DNA & RNA, myelin of CNS →
related to clinical symptoms
Immunology and
Immunopathology
 Sleeping
sickness
• Is an endemic parasitic diseases solely occur in Africa and
transmitted by biting of tse tse fly
• The chancre (mm – cm) is the initial lesion and
characterized by local erythema, oedema, heat,
tenderness but a lack of any suppuration.
 Human African
Trypanosomiasis
• After a painful tsetse puncture, the chancre (mm –
cm) as the
primary lesion will disappear within 2 – 3 weeks
• Two stages of disease:
- haemolymphatic stage
- meningoencephalitic stage
 Stage 1:
haemolymphatic
• Intermitten fever due to
invasion of
parasites in blood
circulation.
• Fever episodes are
associated with
headaches, malaise,
exhaustion, anorexia,
myalgia, arthralgia
 Stage 1:
haemolymphatic
• Parasites will enter reticulo-endothelial system of the
host (adenolymphatic, spleen & liver)  winterbuttom
sign (lymphadenopathy of subclavicula), splenomegaly
& hepatomegaly
 Stage 1:
haemolymphatic
• Few insignificant neurological and endocrine disorder
may show the
involvement of CNS (before any changes of CSF):
- day time somnolence & night insomnia
- psychiatric signs (irritability, changes of character or
emotion)
- impotence, amenorrhea, infertility etc
 Stage 2:
meningoencephalitic
• This stage develops gradually and insidiously over a
period of months or
years
• Nevertheless, the clinical signs still reversible for an
extended period of
time,
 Stage 2:
meningoencephalitic
• The main symptoms are classified into
- psychiatric: irritability, lassitude, headache,
changes of personality,
suicidal tendency, violence
etc
- motor system: tremors, hypertonia,
ataxia
- sensory: hyperaesthesia (Kerandel’s sign)
- sleep disturbance: alternation of sleep-
wake cycle
 Stage 2:
meningoencephalitic
• The development of neurological manifestation becomes
progressive 
CNS invasion is indicated by CSF 5 wbc cell/µl or positive
trypanosome
• At terminal phase, demyelinated and atrophy of CNS
occur  dementia,
epileptic fits, cerebral edema, coma, systemic organ
failure  patient dies
 Diagnosi
s 1:
Stage
- Thick and thin blood smear
- Antibody detection (card
agglutination test)
- Biopsy of invaded organ (liver,
spleen, lymphatic system, bone
marrow)

Stage 2:
CSF examination: > 5 wbc/uL,
trypanosome (+) ,
IgM specific (+)
 Treatment

Distinguish between stage 1 from stage 2 is difficult

because of overlap or intermediate stages

Drug toxicity particularly the one that breakthrough

blood brain barrier
 Treatme
nt
• Suramin and pentamidine for haemolymphatic stage
• Meningoencephalitic stage  differentiate between early and late
encephalitic stages due to high risk of drug toxicity such as
melarsoprol and eflornithine (cross blood brain barrier) → cause
PTRE (post treatment reactive encephalitis)