TOXOPLASMOTOXOPLASMOSISSIS

Dr. S.GOPALAKRISHNAN. M.DDr. S.GOPALAKRISHNAN. M.D

Asst. Prof. Asst. Prof.

Govt. Hospital for Thoracic MedicineGovt. Hospital for Thoracic Medicine

Tambaram.Tambaram.

INTRODUCTIONINTRODUCTION

Toxoplasma Gondii is worldwide in distribution.Toxoplasma Gondii is worldwide in distribution.

Most common Chronic infection with Obligate Most common Chronic infection with Obligate

intracellular Protozoan in Humans.intracellular Protozoan in Humans.

3-4 % of all Patients with AIDS may develop 3-4 % of all Patients with AIDS may develop

CNS Toxoplasmosis at some stage.CNS Toxoplasmosis at some stage.

Greatest incidence when CD4 < 100 cells/mmGreatest incidence when CD4 < 100 cells/mm33

Decrease in CMI in chronically infected at risk Decrease in CMI in chronically infected at risk

of reactivation of infection.of reactivation of infection.

EPIDEMIOLOGYEPIDEMIOLOGYDefinite Host – CAT Definite Host – CAT

Sexual Cycle----OocystSexual Cycle----Oocyst

Intermediate Host– Intermediate Host– Human,Mouse,Pig,Sheep.Human,Mouse,Pig,Sheep.

Asexual Cycle----Tissue Asexual Cycle----Tissue

cystcyst

EPIDEMIOLOGYEPIDEMIOLOGY Transmission to humans Transmission to humans Oral Oral

Ingestion of under cooked Pork or Lamb Ingestion of under cooked Pork or Lamb meat –tissue cyst.meat –tissue cyst. Exposure to oocysts Exposure to oocysts

Ingestion of contaminated vegetablesIngestion of contaminated vegetablesdirect Contact with cat feces.direct Contact with cat feces.

OthersOthers Transplacental.Transplacental. Blood Product Transfusion.Blood Product Transfusion. Organ Transplantation.Organ Transplantation.

PATHOGENESISPATHOGENESIS

ORAL INGESTIONORAL INGESTION

TACHYZOITE (INVASIVE FORM)TACHYZOITE (INVASIVE FORM)

DISSEMINATES THROUGH OUT THE BODYDISSEMINATES THROUGH OUT THE BODY

INFECTION ->ANY NUCLEATED CELL->MULTIPLICATION -> INFECTION ->ANY NUCLEATED CELL->MULTIPLICATION -> CELL DESTRUCTION -> NECROTIC FOCI ->CELL DESTRUCTION -> NECROTIC FOCI ->

SURROUNDING INFLAMMATION SURROUNDING INFLAMMATION

TISSUE CYST TISSUE CYST

LIFE LONG CHRONIC INFECTIONLIFE LONG CHRONIC INFECTION

ONSET OF CMIONSET OF CMI

SUSCEPTIBILITY – MECHANISM IN SUSCEPTIBILITY – MECHANISM IN HIVHIV

Depletion ofDepletion of CD4 T cells CD4 T cells

Decreased production of IL-2 ,IL-12,IFN-Decreased production of IL-2 ,IL-12,IFN-

Decreased cytotoxic T-lymphocyte Decreased cytotoxic T-lymphocyte activity.activity.

CLINICAL PRESENTATIONCLINICAL PRESENTATIONImmuno compromisedImmuno compromisedCerebralCerebralManifests primarily as toxoplasmic Manifests primarily as toxoplasmic

encephalitisencephalitisAltered mental status – 75 %Altered mental status – 75 %Focal Neurological deficit – 70 %Focal Neurological deficit – 70 %

Motor weakness Motor weakness Speech Disturbances Speech Disturbances Cranial Nerve PalsyCranial Nerve PalsyMovement Disorders Movement Disorders Visual Field DefectsVisual Field DefectsSensory ,Cerebellar DysfunctionSensory ,Cerebellar Dysfunction

Head ache – 56%Head ache – 56%Fever – 45%Fever – 45%Seizures – 30%Seizures – 30%

Extra CereberalExtra Cereberal Ocular Ocular

Choreoretinitis – Less common than Choreoretinitis – Less common than CMVCMV

Lesions adjacent to disc, old scar Lesions adjacent to disc, old scar

Multi focal, bilateral lesions typically Multi focal, bilateral lesions typically more confluent, thick, opaque.more confluent, thick, opaque.

Anterior Uveitis Anterior Uveitis

Cont…Cont…

Cont…Cont…

Pulmonary Pulmonary Highly Lethal sepsis like syndromeHighly Lethal sepsis like syndromeDifficult to distinguish from Difficult to distinguish from

Pneumocystis cari. pneumoniaPneumocystis cari. pneumonia

Cardiac Cardiac Asymptomatic Asymptomatic Cardiac tamponade Cardiac tamponade Biventricular FailureBiventricular Failure

IMMUNOCOMPETENTIMMUNOCOMPETENT

LYMPHADENOPATHYLYMPHADENOPATHY

Common – CERVICAL (Single or Multiple Common – CERVICAL (Single or Multiple non non

tender,Discrete)tender,Discrete)

Generalized – 20-30%Generalized – 20-30%Fever,Myalgia,Rash , Meningo-Fever,Myalgia,Rash , Meningo-

Encephalitis.Encephalitis.Rare: Rare:

Pneumonia,Myocarditis,Polymyositis.Pneumonia,Myocarditis,Polymyositis.

DIAGNOSISDIAGNOSIS * Serology* Serology

Anti-IgG Antibodies Anti-IgG Antibodies • Peaks within 1-2 months after Peaks within 1-2 months after

infection.infection.• Remain elevated for life.Remain elevated for life.• False negative 10-15%False negative 10-15%• Sabin-feldman dye test-gold Sabin-feldman dye test-gold

standard standard • IFA-indirectIFA-indirect• ElisaElisa

IgM Anti-body testsIgM Anti-body testsDouble sandwich Elisa Double sandwich Elisa IFAIFAImmunosorbent agglutination Immunosorbent agglutination assayassay

(IgM-ISAGA)(IgM-ISAGA)

Cont…Cont…

SEROLOGYSEROLOGY

To diagnose – recent infectionTo diagnose – recent infection

Serial specimens at 3 weeks apart-4 fold Serial specimens at 3 weeks apart-4 fold increase in IgG titre.increase in IgG titre.

OROR Elevated IgM, IgA or IgE titres with Elevated IgM, IgA or IgE titres with

differential agglutination test.differential agglutination test.

Useful to IdentifyUseful to Identify - HIV at risk of developing - HIV at risk of developing toxoplasmosis. 97%-100% HIV with toxo –toxoplasmosis. 97%-100% HIV with toxo –encephalitis have anti IgG anti bodies.encephalitis have anti IgG anti bodies.

CSFCSF

Non specific Non specific

Mild cell count – mononuclear, proteinMild cell count – mononuclear, protein

Intrathecal Anti IgG antibodies productionIntrathecal Anti IgG antibodies production

Ratio > 1 supports the diagnosis of Ratio > 1 supports the diagnosis of

toxoplsmic encephalitistoxoplsmic encephalitis

Wright – Giemsa stain of CSFWright – Giemsa stain of CSF

DNADNA

POLYMERASE CHAIN REACTION (PCR)POLYMERASE CHAIN REACTION (PCR)CSF – Sensitivity 50 – 60%CSF – Sensitivity 50 – 60%

- Specificity 100%- Specificity 100%Bronchoalveolar lavage fluidBronchoalveolar lavage fluidVitreous and aqueous humorVitreous and aqueous humorBlood samples – low sensitivity: Blood samples – low sensitivity:

toxo.encpha.toxo.encpha.Amniotic fluidAmniotic fluid

Culture – Time consumingCulture – Time consuming

NEURORADIOLOGIC NEURORADIOLOGIC STUDIESSTUDIES

C TC T Multiple, bilateral, hypodense, contrast-Multiple, bilateral, hypodense, contrast-

enhancing focal brain lesions – 70 to enhancing focal brain lesions – 70 to

80%80%

Lesions – basal ganglia, hemispheric Lesions – basal ganglia, hemispheric

corticomedullary junction.corticomedullary junction.

Contrast enhancement often with Contrast enhancement often with

ringlike pattern ringlike pattern

MRIMRIMore sensitive than CTMore sensitive than CTIdentify more lesions than seen on Identify more lesions than seen on

CT, new lesions not seen on CTCT, new lesions not seen on CT

NEWER IMAGING TECHNIQUESNEWER IMAGING TECHNIQUES

201T1201T1 SPECT: SPECT: Thallium 201 single-Thallium 201 single-photon emission computed tomographyphoton emission computed tomography

18F FDG – PET: 18F FDG – PET: Fluoride 18 - Flouro Fluoride 18 - Flouro – 2 – 2 deoxyglucose positron emission deoxyglucose positron emission tomography.tomography.

Toxoplasmosis

Toxoplasmosis- Response to therapyToxoplasmosis- Response to therapy

ToxoplasmosisToxoplasmosis

DEFINITE DIAGNOSISDEFINITE DIAGNOSIS

Excisional Brain Biopsy:Excisional Brain Biopsy:

Usually not performedUsually not performed

Reserved for patients who fail to Reserved for patients who fail to respond to therapyrespond to therapy

DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS

Primary CNS Lymphoma Primary CNS Lymphoma

Mycobacterial infections Mycobacterial infections

Cryptococcal meningitis Cryptococcal meningitis

Herpes simplex encephalitisHerpes simplex encephalitis

PML PML

CMV infectionCMV infection

Infectious mononucleosis Infectious mononucleosis

MANAGEMENT IN HIVMANAGEMENT IN HIV

Therapy empiric in most casesTherapy empiric in most cases

Neurologic response Neurologic response 51% by day 351% by day 3

91% by day 1491% by day 14

Neuroradiologic study repeated 2-4 Neuroradiologic study repeated 2-4

weeks after initiation of therapyweeks after initiation of therapy

Cont…Cont…

Acute TherapyAcute Therapy

Maintenance Therapy Maintenance Therapy

(Secondary Prophylaxis)(Secondary Prophylaxis)

Prevention Prevention (Primary Prophylaxis)(Primary Prophylaxis)

Discontinuation of ProphylaxisDiscontinuation of Prophylaxis

ACUTE THERAPYACUTE THERAPYPreferredPreferred

PyrimethaminePyrimethamine 200mg po loading dose 200mg po loading dose followed by 75-100 mg po qd plus followed by 75-100 mg po qd plus folinic acidfolinic acid 15-20 mg po qd plus 15-20 mg po qd plus sulfadiazinesulfadiazine 1-1.5g po q6h - 6 weeks. 1-1.5g po q6h - 6 weeks.

AlternativesAlternatives Pyrimethamine with folinic acid (as Pyrimethamine with folinic acid (as

standard) with one of the following:standard) with one of the following:Clindamycin 600 mg po q6hClindamycin 600 mg po q6hClarithromycin 1g po bidClarithromycin 1g po bidAzithromycin 1.2-1.5g po qdAzithromycin 1.2-1.5g po qdDapsone 100mg po qd - 6 weeksDapsone 100mg po qd - 6 weeks

MAINTENANCE THERAPYMAINTENANCE THERAPY

PreferredPreferredPyrimethaminePyrimethamine 25 mg po qd & 25 mg po qd & folinic acidfolinic acid

10 mg po qd and 10 mg po qd and SulfadiazineSulfadiazine 500-1000 mg 500-1000 mg po po

q 6h q 6h AlternativeAlternative

Pyrimethamine 25 mg po qd & folinic acid Pyrimethamine 25 mg po qd & folinic acid 5-10 mg qd po & Clindamycin 300-450 mg 5-10 mg qd po & Clindamycin 300-450 mg po q6-8h.po q6-8h.

Atovaquone 750 mg po bidAtovaquone 750 mg po bid

PREVENTIONPREVENTION

To eat well cooked meat - internal To eat well cooked meat - internal

temperature of 116temperature of 11600C, or no longer pink C, or no longer pink

inside.inside.

Proper hand washing.Proper hand washing.

Fruits and vegetables should be washed prior Fruits and vegetables should be washed prior

to consumption. to consumption.

To avoid contact with materials contaminated To avoid contact with materials contaminated

with cat feces, handling cat litter boxes.with cat feces, handling cat litter boxes.

To wear gloves during gardening.To wear gloves during gardening.

Cont…Cont… Recommended Recommended

T gondii - Seropositive patients with CD4 T T gondii - Seropositive patients with CD4 T cell counts <100 regardless of clinical status.cell counts <100 regardless of clinical status.

Patients with CD4 T cell counts <200 if an Patients with CD4 T cell counts <200 if an opportunistic infection or malignancy opportunistic infection or malignancy develops.develops.

Trimethorprim / sulfamethazole 1 ds tab Trimethorprim / sulfamethazole 1 ds tab po qdpo qd

Dapsone 50 m po qd & pyrimethamine Dapsone 50 m po qd & pyrimethamine 50 mg po q week plus & folinic acid 25 50 mg po q week plus & folinic acid 25 mg po q weekmg po q week

DISCONTINUATION OF DISCONTINUATION OF PROPHYLAXISPROPHYLAXIS

CD4 T cell counts increase to more CD4 T cell counts increase to more

than 200 over a period of 3- 6 than 200 over a period of 3- 6

months in response to HAARTmonths in response to HAART

Restarting prophylaxis in patients Restarting prophylaxis in patients

CD4 T cell counts decrease to < 200CD4 T cell counts decrease to < 200