CNS TOXOLASMOSIS

1. CNS TOXOPLASMOSIS
BY: DIANA TABANSI
JAN 13TH 2018

2. INTRODUCTION
 Toxoplasmosis is the leading cause of focal central
nervous system (CNS) disease in AIDS
 It is the most common cause of cerebral abscess in
immunocompromised patients when the absolute CD4
count is less than 100 u/L
 The causative organism is Toxoplasma gondii (T. gondii),
an obligate intracellular protozoan parasite

3.  CNS toxoplasmosis in HIV-infected patients is usually a
complication of the late phase of the disease.
 Typically, lesions are found in the brain and their effects
dominate the clinical presentation.

4.  The decision to treat a patient for CNS toxoplasmosis is
usually empiric. Primary therapy is followed by long-
term suppressive therapy, which is continued until
antiretroviral therapy can raise CD4+ counts above 200
cells/µL.

5. EPIDEMIOLOGY
 Clinical CNS toxoplasmosis occurs in 3-15% of patients with
AIDS in the United States.
 Some clinically silent lesions come to diagnosis only at
autopsy. Clinical CNS toxoplasmosis occurs in as many as 50-
75% of patients in some European countries and in Africa.
 The probability of developing reactivated toxoplasmosis is as
high as 30% among AIDS patients with a CD4 count
<100 cells/microL who are toxoplasma seropositive and are
not receiving effective prophylaxis or antiretroviral therapy.

6.  The most common site of reactivation is the central
nervous system (CNS).
 Recently in a epidemiologic study in Mexico city with
320 AIDS patients, the main conditions related to
HIV/AIDS were brain toxoplasmosis (42%), cerebral
cryptococcosis (28%), tuberculous meningitis (8.7%),
lymphoma (non-Hodgkin) (3.75%), acute HIV infection
(3.4%), and AIDS dementia complex (3%).

7.  The incidence rate has decreased due to the use of highly
active antiretroviral therapy (HAART) and prophylaxis
against Pneumocystis jiroveci infections with
trimethoprim-sulfamethoxazole, which is also effective
against toxoplasmosis

8. EPIDEMIOLGY IN JAMAICA

10. LIFE CYCLE OF T. GONDII
 Toxoplasmosis is a disease caused by Toxoplasma
gondii, an intracellular obligate protozoal parasite.
T. gondii has three forms:
 and the sporozoite (contained in oocysts)
 the tachyzoite (the rapidly reproducing form),
 the bradyzoite (a slower reproducing form contained in
tissue cysts)

13. PATHOPHYSIOLOGY
 CNS toxoplasmosis results from infection by the
intracellular parasite Toxoplasma gondii.
 It is almost always due to reactivation of old CNS
lesions or to hematogenous spread of a previously
acquired infection. Occasionally, it results from primary
infection.

14. CLINICAL PRESENTATIONS
 CNS toxoplasmosis begins with constitutional symptoms
and headache.
 Later, confusion and drowsiness, seizures, focal
weakness, and language disturbance develop.
 Without treatment, patients progress to coma in days to
weeks.
 Extracerebral involvement can also be seen including but
not limited to pneumonitis, chorioretinitis, etc.

15.  On physical examination, personality and mental status
changes may be observed. Seizures, hemiparesis,
hemianopia, aphasia, ataxia, and cranial nerve palsies
may be evident. Occasionally, symptoms and signs of a
radiculomyelopathy predominate.

16. DIFFERENTIAL DIAGNOSIS
 The differential diagnosis of CNS toxoplasmosis includes the
following:
 CNS Lymphoma in HIV
 Mycobacterial infection (eg, tuberculous abscess,
tuberculoma)
 Fungal infection (eg, cryptococcosis, candidiasis)
 Chagas disease
 Bacterial abscess (eg, Nocardia)
 Neurosyphilis
 Cardioembolic Stroke
 Cytomegalovirus Encephalitis in HIV
 Progressive Polyradiculopathy in HIV
 Vacuolar Myelopathy in HIV
 Progressive Multifocal Leukoencephalopathy

17. SEROLOGIC STUDIES
 Serologic studies in patients with CNS toxoplasmosis
may demonstrate rising titers of anti-toxoplasma
immunoglobulin G (IgG) antibodies. An
immunoglobulin M (IgM) antibody response is seen in
cases of newly acquired toxoplasmosis or Toxoplasma
encephalitis.

18.  However, anti-Toxoplasmagondii IgG detection may be
unreliable in immunodeficient individuals who fail to
produce significant titers of specific antibodies. In one
study, 16% of patients with a clinical diagnosis and 22%
of patients with a histologic diagnosis of toxoplasmosis
had undetectable anti-T gondii IgG levels. Causes of
false-negative results also include recent infection and
insensitive assays

19. DEFINITIVE DIAGNOSIS
Definitive diagnosis of CNS toxoplasmosis requires the
following :
 Compatible clinical findings
 Identification of one or more mass lesions by CT, MRI,
or other radiographic testing
 Detection of T gondii in a clinical sample
Detection of T gondii DNA on polymerase chain reaction
(PCR) testing of cerebrospinal fluid (CSF) samples may
facilitate the diagnosis and follow-up of toxoplasmosis in
patients with AIDS. In a study using the B1 gene, rapid
PCR showed a sensitivity of 83.3% and specificity of
95.7%.

20.  CSF findings may also include elevated protein and variable
glucose and WBC counts. The presence of Epstein-Barr virus
DNA in the CSF favors the diagnosis of lymphoma
 Lumbar puncture may be contraindicated because of increased
intracranial pressure.
 For many clinicians, therefore, CNS toxoplasmosis is an
empiric diagnosis that relies on clinical and radiographic
improvement in response to specific anti-T gondii therapy.
 In patients who fail to respond to specific therapy, brain
biopsy can be used to secure a clinical sample for testing.

21. IMAGING
 A brain CT scan or MRI with and without contrast is
indicated for all patients presenting with altered mental status,
headaches, seizures, or focal neurologic signs.
 MRI clearly is the superior technique but is not available
universally.
 Single or multiple hypodense or hypointense lesions in white
matter and basal ganglia with mass effects may be observed
on CT or MRI scans.
 Lesions may enhance in a homogeneous or ring pattern with
contrast .

27. IMAGING
 Single lesions favor the diagnosis of lymphoma over that
of toxoplasmosis. However, while multiple lesions are
more common than single lesions in toxoplasmosis, in
one study 27% of patients had a single lesion on CT
scan. In the same study, 14% had a single lesion on MRI.
 MRI is more sensitive than CT scan in detecting
multiple lesions.

28. IMAGING
 If the initial imaging study is normal or shows atrophy or
focal signal abnormalities (but no mass lesion), diagnostic
consideration should be given to meningitides, AIDS
dementia complex, or progressive multifocal
leukoencephalopathy.
 If imaging shows one or more focal mass lesions with
impending herniation, an open biopsy with decompression is
indicated.
 Treatment for lymphoma, toxoplasmosis, or other
opportunistic infections and neoplasms is initiated, depending
on biopsy results.

29. SCINTIGRAPHY
 Where available, thallium-201 single-photon emission
computed tomography (201 TI SPECT) or
18fluorodeoxyglucose positron emission tomography
(18FDG-PET) may be useful in distinguishing between
lymphoma and toxoplasmosis.
 Lymphoma shows an increased uptake as compared with
toxoplasmosis. These tests have high specificity but low
sensitivity.

30. BRAIN BIOPSY
Indications for brain biopsy include either of the following:
 Single mass lesion and negative serologic results
 No response to 14 days of empiric therapy
Diagnostic yield of stereotactic biopsies increases with the
number of specimens obtained.

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32. Histologic findings include the following (also see the
images below):
 Lymphocytic meningitis, individual cyst-containing
lesions
 Astroglial and microglial nodules
 Associated lymphocytic vasculitis
 Diffuse encephalitis

34. TREATMENT AND PROPHYLAXIS

35. PRIMARY PROPHYLAXIS
 Toxoplasma-seropositive patients who have CD4 counts <100
cells/μL should receive prophylaxis against TE (toxoplasma
Encephalitis ) .
 The one double-strength-tablet daily dose of
trimethoprimsulfamethoxazole (TMP-SMX), which is the preferred
regimen for Pneumocystis jirovecii pneumonia (PCP) prophylaxis, is
effective against TE and is recommended .
 TMP-SMX, one double-strength tablet three times weekly, is an
alternative .
 dapsone-pyrimethamine plus leucovorin, which is also effective
against PCP .

36. SECONDARY PROPHYLAXIS
 Start after acute treatment of toxoplasmosis .
 combination of pyrimethamine plus sulfadiazine plus
leucovorin is highly effective as suppressive therapy for
patients with TE and provides protection against PCP .
 Pyrimethamine plus clindamycin is commonly used as
suppressive therapy for patients with TE who cannot
tolerate sulfa drugs not provide protection against PCP .
Pyrimethamine 25–50 mg PO daily + sulfadiazine 2000–
4000 mg PO daily (in 2 to 4 divided doses) + leucovorin
10–25 mg PO daily.
 Alternative Regimen: Clindamycin 600 mg PO q8h +
(pyrimethamine 25–50 mg + leucovorin 10–25 mg) PO
daily ; must add additional agent to prevent PCP

37. PREVENTION
 To prevent primary toxoplasmosis, patients should avoid
eating undercooked meat and should wash their hands
carefully after contact with soil or cats.
 Patients who are seropositive for Toxoplasma should be
started on prophylaxis against CNS toxoplasmosis if
their CD4+ count drops below 100 cells/μL

38. REFERENCES
 https://www.ncbi.nlm.nih.gov/pubmed/2585580
 https://www.medscape.com/invitation/viewTracker.d
o?src=house_6
 https://www.sciencedirect.com/science/article/pii/S1
930043315300698
 http://www.hivmanual.hk/content.html?gonum=34

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