TOXOPLASMOSIS Dr S GOPALAKRISHNAN M D Asst Prof

TOXOPLASMOSIS Dr. S. GOPALAKRISHNAN. M. D Asst. Prof. Govt. Hospital for Thoracic Medicine Tambaram.

INTRODUCTION l Toxoplasma Gondii is worldwide in distribution. l Most common Chronic infection with Obligate intracellular Protozoan in Humans. l 3 -4 % of all Patients with AIDS may develop CNS Toxoplasmosis at some stage. l Greatest incidence when CD 4 < 100 cells/mm 3 l Decrease in CMI in chronically infected at risk of reactivation of infection.

EPIDEMIOLOGY l Definite Host – l Intermediate CAT Sexual Cycle----Oocyst Host– Human, Mouse, Pig, Sheep. Asexual Cycle----Tissue cyst

EPIDEMIOLOGY Transmission to humans l Oral l Ingestion of under cooked Pork or Lamb meat –tissue cyst. l Exposure to oocysts l Ingestion of contaminated vegetables l direct Contact with cat feces. l l Others Transplacental. l Blood Product Transfusion. l Organ Transplantation. l

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 l Depletion of CD 4 T cells l Decreased production of IL-2 , IL-12, IFN-g l Decreased cytotoxic T-lymphocyte activity.

CLINICAL PRESENTATION Immuno compromised Cerebral l Manifests primarily as toxoplasmic encephalitis l Altered mental status – 75 % l Focal Neurological deficit – 70 % l Motor weakness l Speech Disturbances l Cranial Nerve Palsy l Movement Disorders l Visual Field Defects l Sensory , Cerebellar Dysfunction

Cont… l. Head ache – 56% l. Fever – 45% l. Seizures – 30% Extra Cereberal Ocular l Choreoretinitis – Less common than CMV Lesions adjacent to disc, old scar Multi focal, bilateral lesions typically more confluent, thick, opaque. l Anterior Uveitis

Cont… Pulmonary l Highly Lethal sepsis like syndrome l Difficult to distinguish from Pneumocystis cari. pneumonia Cardiac l Asymptomatic l Cardiac tamponade l Biventricular Failure

IMMUNOCOMPETENT l LYMPHADENOPATHY Common – CERVICAL (Single or Multiple non tender, Discrete) Generalized – 20 -30% l Fever, Myalgia, Rash , Meningo-Encephalitis. l Rare: Pneumonia, Myocarditis, Polymyositis.

DIAGNOSIS * Serology Anti-Ig. G 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… l Ig. M Anti-body tests l. Double sandwich Elisa l. IFA l. Immunosorbent agglutination assay (Ig. M-ISAGA)

SEROLOGY To diagnose – recent infection Serial specimens at 3 weeks apart-4 fold increase in Ig. G titre. OR l Elevated Ig. M, Ig. A or Ig. E titres with differential agglutination test. l l Useful to Identify - HIV at risk of developing toxoplasmosis. 97%-100% HIV with toxo – encephalitis have anti Ig. G anti bodies.

CSF l Non specific l Mild cell count – mononuclear, protein l Intrathecal l Ratio Anti Ig. G antibodies production > 1 supports the diagnosis of toxoplsmic encephalitis l Wright – Giemsa stain of CSF

DNA l POLYMERASE l CSF CHAIN REACTION (PCR) – Sensitivity 50 – 60% - Specificity 100% l Bronchoalveolar lavage fluid l Vitreous and aqueous humor l Blood samples – low sensitivity: toxo. encpha. l Amniotic fluid l Culture – Time consuming

NEURORADIOLOGIC STUDIES CT l Multiple, bilateral, hypodense, contrast- enhancing focal brain lesions – 70 to 80% l Lesions – basal ganglia, hemispheric corticomedullary junction. l Contrast pattern enhancement often with ringlike

MRI l More sensitive than CT l Identify more lesions than seen on CT, new lesions not seen on CT NEWER IMAGING TECHNIQUES 201 T 1 SPECT: Thallium 201 singlephoton emission computed tomography 18 F FDG – PET: Fluoride 18 - Flouro – 2 deoxyglucose positron emission tomography.

Toxoplasmosis

Toxoplasmosis- Response to therapy

Toxoplasmosis

DEFINITE DIAGNOSIS l Excisional l Usually not performed l Reserved therapy Brain Biopsy: for patients who fail to respond to

DIFFERENTIAL DIAGNOSIS l Primary CNS Lymphoma l Mycobacterial l Cryptococcal l Herpes infections meningitis simplex encephalitis l PML l CMV infection l Infectious mononucleosis

MANAGEMENT IN HIV l Therapy empiric in most cases l Neurologic response l 51% by day 3 l 91% by day 14 l Neuroradiologic study repeated 2 -4 weeks after initiation of therapy

Cont… l Acute Therapy l Maintenance Therapy (Secondary Prophylaxis) l Prevention (Primary Prophylaxis) l Discontinuation of Prophylaxis

ACUTE THERAPY l Preferred l Pyrimethamine 200 mg po loading dose followed by 75 -100 mg po qd plus folinic acid 15 -20 mg po qd plus sulfadiazine 1 -1. 5 g po q 6 h - 6 weeks. l Alternatives l Pyrimethamine with folinic acid (as standard) with one of the following: l Clindamycin 600 mg po q 6 h l Clarithromycin 1 g po bid l Azithromycin 1. 2 -1. 5 g po qd l Dapsone 100 mg po qd - 6 weeks

MAINTENANCE THERAPY l Preferred l Pyrimethamine 25 mg po qd & folinic acid 10 mg po qd and Sulfadiazine 500 -1000 mg po q 6 h l Alternative l Pyrimethamine 25 mg po qd & folinic acid 510 mg qd po & Clindamycin 300 -450 mg po q 6 -8 h. l Atovaquone 750 mg po bid

PREVENTION l To eat well cooked meat - internal temperature of 1160 C, or no longer pink inside. l Proper hand washing. l Fruits and vegetables should be washed prior to consumption. l To avoid contact with materials contaminated with cat feces, handling cat litter boxes. l To wear gloves during gardening.

Cont… l Recommended l T gondii - Seropositive patients with CD 4 T cell counts <100 regardless of clinical status. l Patients with CD 4 T cell counts <200 if an opportunistic infection or malignancy develops. l Trimethorprim / sulfamethazole 1 ds tab po qd l Dapsone 50 m po qd & pyrimethamine 50 mg po q week plus & folinic acid 25 mg po q week

DISCONTINUATION OF PROPHYLAXIS l CD 4 T cell counts increase to more than 200 over a period of 3 - 6 months in response to HAART l Restarting prophylaxis in patients CD 4 T cell counts decrease to < 200