Transcript TOXOPLASMOSIS

TOXOPLASMOSIS
Dr. S.GOPALAKRISHNAN. M.D
Asst. Prof.
Govt. Hospital for Thoracic Medicine
Tambaram.
INTRODUCTION

Toxoplasma Gondii is worldwide in distribution.

Most common Chronic infection with Obligate
intracellular Protozoan in Humans.

3-4 % of all Patients with AIDS may develop
CNS Toxoplasmosis at some stage.

Greatest incidence when CD4 < 100 cells/mm3

Decrease in CMI in chronically infected at risk of
reactivation of infection.
EPIDEMIOLOGY

Definite Host –
CAT
Sexual Cycle----Oocyst

Intermediate Host– Human,Mouse,Pig,Sheep.
Asexual Cycle----Tissue cyst
EPIDEMIOLOGY
Transmission to humans
 Oral




Ingestion of under cooked Pork or Lamb
meat –tissue cyst.
Exposure to oocysts
 Ingestion of contaminated vegetables
 direct Contact with cat feces.
Others



Transplacental.
Blood Product Transfusion.
Organ Transplantation.
PATHOGENESIS
ORAL INGESTION
TACHYZOITE (INVASIVE FORM)
DISSEMINATES THROUGH OUT THE BODY
INFECTION ->ANY NUCLEATED CELL->MULTIPLICATION ->
CELL DESTRUCTION -> NECROTIC FOCI ->
SURROUNDING INFLAMMATION
TISSUE CYST
LIFE LONG CHRONIC INFECTION
ONSET OF CMI
SUSCEPTIBILITY – MECHANISM IN
HIV

Depletion of CD4 T cells

Decreased production of IL-2 ,IL-12,IFN-g

Decreased cytotoxic T-lymphocyte activity.
CLINICAL PRESENTATION
Immuno compromised
Cerebral
 Manifests primarily as toxoplasmic
encephalitis
 Altered mental status – 75 %
 Focal Neurological deficit – 70 %
 Motor weakness
 Speech Disturbances
 Cranial Nerve Palsy
 Movement Disorders
 Visual Field Defects
 Sensory ,Cerebellar Dysfunction
Cont…
Head
ache – 56%
Fever – 45%
Seizures – 30%
Extra Cereberal
Ocular
 Choreoretinitis – Less common than CMV
Lesions adjacent to disc, old scar
Multi focal, bilateral lesions typically
more confluent, thick, opaque.
 Anterior Uveitis
Cont…
Pulmonary
 Highly
Lethal sepsis like syndrome
 Difficult to distinguish from
Pneumocystis cari. pneumonia
Cardiac
 Asymptomatic
 Cardiac
tamponade
 Biventricular Failure
IMMUNOCOMPETENT
LYMPHADENOPATHY
Common – CERVICAL (Single or Multiple
non
tender,Discrete)
Generalized – 20-30%
 Fever,Myalgia,Rash , Meningo-Encephalitis.
 Rare: Pneumonia,Myocarditis,Polymyositis.

DIAGNOSIS
* Serology
Anti-IgG Antibodies
•
Peaks within 1-2 months after infection.
•
Remain elevated for life.
•
False negative 10-15%
•
Sabin-feldman dye test-gold standard
•
IFA-indirect
•
Elisa
Cont…

IgM Anti-body tests
Double sandwich Elisa
IFA
Immunosorbent agglutination assay
(IgM-ISAGA)
SEROLOGY
To diagnose – recent infection
Serial specimens at 3 weeks apart-4 fold
increase in IgG titre.
OR
 Elevated IgM, IgA or IgE titres with differential
agglutination test.


Useful to Identify - HIV at risk of developing
toxoplasmosis. 97%-100% HIV with toxo –
encephalitis have anti IgG anti bodies.
CSF

Non specific

Mild cell count – mononuclear, protein

Intrathecal Anti IgG antibodies production

Ratio > 1 supports the diagnosis of
toxoplsmic encephalitis

Wright – Giemsa stain of CSF
DNA

POLYMERASE CHAIN REACTION (PCR)
 CSF
– Sensitivity 50 – 60%
- Specificity 100%
 Bronchoalveolar lavage fluid
 Vitreous and aqueous humor
 Blood samples – low sensitivity: toxo.encpha.
 Amniotic fluid

Culture – Time consuming
NEURORADIOLOGIC STUDIES
CT

Multiple, bilateral, hypodense, contrast-
enhancing focal brain lesions – 70 to 80%

Lesions – basal ganglia, hemispheric
corticomedullary junction.

Contrast enhancement often with ringlike
pattern
MRI
 More
sensitive than CT
 Identify more lesions than seen on
CT, new lesions not seen on CT
NEWER IMAGING TECHNIQUES
201T1 SPECT: Thallium 201 singlephoton emission computed tomography
18F FDG – PET: Fluoride 18 - Flouro – 2
deoxyglucose positron emission
tomography.
Toxoplasmosis
Toxoplasmosis- Response to therapy
Toxoplasmosis
DEFINITE DIAGNOSIS

Excisional Brain Biopsy:
 Usually
not performed
 Reserved
therapy
for patients who fail to respond to
DIFFERENTIAL DIAGNOSIS

Primary CNS Lymphoma

Mycobacterial infections

Cryptococcal meningitis

Herpes simplex encephalitis

PML

CMV infection

Infectious mononucleosis
MANAGEMENT IN HIV

Therapy empiric in most cases

Neurologic response

 51%
by day 3
 91%
by day 14
Neuroradiologic study repeated 2-4 weeks
after initiation of therapy
Cont…
 Acute
Therapy
 Maintenance
Therapy
(Secondary Prophylaxis)
 Prevention (Primary Prophylaxis)
 Discontinuation
of Prophylaxis
ACUTE THERAPY

Preferred
 Pyrimethamine
200mg po loading dose
followed by 75-100 mg po qd plus folinic acid
15-20 mg po qd plus sulfadiazine 1-1.5g po
q6h - 6 weeks.

Alternatives

Pyrimethamine with folinic acid (as standard)
with one of the following:
 Clindamycin
600 mg po q6h
 Clarithromycin 1g po bid
 Azithromycin 1.2-1.5g po qd
 Dapsone 100mg po qd
-
6 weeks
MAINTENANCE THERAPY

Preferred
 Pyrimethamine
25 mg po qd & folinic acid 10
mg po qd and Sulfadiazine 500-1000 mg po
q 6h

Alternative
 Pyrimethamine
25 mg po qd & folinic acid 510 mg qd po & Clindamycin 300-450 mg po
q6-8h.
 Atovaquone 750 mg po bid
PREVENTION

To eat well cooked meat - internal temperature
of 1160C, or no longer pink inside.

Proper hand washing.

Fruits and vegetables should be washed prior to
consumption.

To avoid contact with materials contaminated
with cat feces, handling cat litter boxes.

To wear gloves during gardening.
Cont…

Recommended
 T gondii - Seropositive patients with CD4 T cell
counts <100 regardless of clinical status.
 Patients with CD4 T cell counts <200 if an
opportunistic infection or malignancy develops.
 Trimethorprim
/ sulfamethazole 1 ds tab
po qd
 Dapsone 50 m po qd & pyrimethamine 50
mg po q week plus & folinic acid 25 mg
po q week
DISCONTINUATION OF
PROPHYLAXIS

CD4 T cell counts increase to more than
200 over a period of 3- 6 months in
response to HAART

Restarting prophylaxis in patients CD4 T
cell counts decrease to < 200