toxoplasmosis dr. s.gopalakrishnan. m.d asst. prof. govt. hospital for thoracic medicine tambaram
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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