Management of Toxoplasmosisdr. Rizky Perdana,SpPD,KPTI,FINASIM

CaseWoman, 25 years oldNO symptoms and signs of infectionsSerology test for toxoplasma : IgM (+) and IgG (+)Plans to married????

CaseMan, 30 years oldNo Symptoms, only lymphadenopathy on cervical Lab test :PCR TB (-)Serology test for toxoplasma : IgM (+) and IgG (+)??????

CaseWomen, 25 years oldFirst pregnancyFirst trimester gestational ageNo symptoms and signsSerology test for toxoplasma : IgM (+) and IgG (+)??????

CaseMan, 18 years oldHIV-AIDS (+)Lymphadenopathy, malaise, loss of body weightSerology test for toxoplasma : IgM (-) and IgG (+)?????

Toxoplasma: Human TransmissionInfection in humans typically through ingestion Raw/undercooked meatEstimated to occur in of T. gondii infections in U.S.Parasite isolated from 32% pork chops, 4% lamb chops (1960s)Ingestions of oocyst from cat feces or soilWater or food contaminated with oocystsAlso transplacental transmission Mother acquires infection during gestation

Toxoplasma Transmission

Toxoplasmosis

Toxoplasmosis: Clinical SignsUsually asymptomatic (80-90%)Flu-like illnessLymphadenopathySelf-limitingToxoplasmic encephalitis (AIDS)Congenital toxoplasmosisRetinochoroiditis

Clinical SignsToxoplasmosis encephalitisOcular ToxoplasmosisLymphadenopathyCongenital Toxoplasmosis

Differential Diagnosis of Lymphadenopathy

ToxoplasmosisInf. MonoLymphomaLymphadenopathy Without Other Symptoms+++++++Pharyngitis+++++Monocytosis, Eosinophilia+++++++Atypical Lymphocytes++++++Anemia0++++Positive Heterophil0++++0Altered Liver Function0++++++Hilar Lymphadenopathy+++++Lymph Node PathologyReticulum CellsGerminal CellsBizarre Cells

Toxoplasma infectionHealthy human usually only mild symptoms the parasites are killed by antibody.

Antibody cannot enter brain and eye, nervous cell cannot regenerate Central Nervous System are common target destruction.

Ring-enhancing lesion

Toxoplasmosis ocular lesions

Toxoplasma: At Risk for Severe DiseaseCongenitally infected fetuses and newbornsEstimated 400-4000 cases each year in the U.S.Immunologically impaired individuals, most commonly with defects in T-cell-mediated immunityHematologic malignanciesBone marrow and solid organ transplantsAIDS, e.g. leading to toxoplasmic encephalitis

Toxoplasmosis in PregnancyPrimary infection in first semester pregnant women abortus, still birth, or congenital toxoplasmosis

Congenital Toxoplasmosis

Congenital Toxoplasmosis

H I V Immunity CD4 < 200Candidosis oro-pharyngeal 80.8%Tuberculosis 40.1%Cytomegalovirus 28.8%

Pneumonia P.carinii (PCP) 13.4%Opportunistic infectionsRSCM** Djauzi S, Djoerban Z (Ed). Penatalaksanaan infeksi HIV di pelayanan kesehatan dasar. Edisi kedua. Jakarta: Balai Penerbit FKUI; 2003+ Tanpa konfirmasi laboratoriumEnchepalitis Toxoplasma+ 17.3%

Toxoplasma: DiagnosisSerologic testing.Observation of parasites in patient specimens.Isolation of parasites from blood or other body fluids, by intraperitoneal inoculation into mice or tissue culture.PCR (for congenital infections in utero).

Blood Test Procedure in Pregnancy

Serologic Detection of Toxoplasma During Pregnancy

Test 1(before 2 months of pregnancy)Test 2(in second trimester)Test 3(in third trimester)GroupIgG +ve (any titer);

IgM -veNo test;

No treatmentNo test;

No treatmentI infection before pregnancy;

No risk (Note 1)IgG +veRepeat IgG after 3 weeks;II Possible infection soon after conception;IgM +veTreat if high or rising titerSlight risk (Note 2)IgG -veTreat if IgG +ve;Treat if IgG +ve;III No previous infection;IgM -veDont treat if IgG -veDont treat if IgG -veIf seroconversion, high risk (Note 3)

Test serum for presence of Toxoplasma-specific IgG antibodiesIgG Negative :Not infected Retest in 3 weeks if acute infection suspectedIgG Positive :InfectedTo determine approximate time of infection, test serum for presence of Toxoplasma-specific IgM antibodiesIgG Positive, IgM Negative:Infected for more than 6 month IgG Negative, IgM Positive:Infected within last 2 years or false-positive IgM resultTest serum for IgG avidity statusIgG avidity high:Infected at least 12 weeks previouslyIgG avidity low:Recent Infection possibleObtain 2nd sample 3 weeks after 1st sent both samples to a Toxoplasma Reference Laboratory for confirmation before any intervention

Latent Toxoplasmosis and Active Infection in HIV-positive PatientsCohort 715 HIV (+)IgG Anti-T.gondii360 (+)355 (-)AfterFour YearsAcute ToxoplasmosisYes 13 %*Yes 0.3 %*No 3 %No47 43 cerebral3 ocular1 B.M.NPV = 99.7 %30 % IgG rise3 6 % IgM18 % IgAZufferrey J, et al. Eur J Clin Microb Infect Dis 1993 ;12:590-5

Toxoplasmosis: TreatmentConsideration should NOT depend on cat exposure.Treatment may or may not be indicated based on presence of active disease, immune status, site of infection.Prevention most important in seronegative pregnant women and immunodeficient patients.

Drugs Of Choice :PyrimethamineandSulfadoxineMode of action:Pyrimethamine inhibits DNA synthesis by interfering with folate synthesis.Sulfadoxine prevents PABA synthesis by inhibiting the enzyme dihydropteroate synthetase.

Alternate Drugs :SpiramycinSulfadiazineandMode of action:Spiramycin inhibits RNA synthesis.Sulfadiazine inhibits PABA synthesis by interfering dihydropteroate synthetase.

Immunologically Normal PatientsThe Sanford Guide To Antimicrobial Therapy 2007

Toxoplasma infectionRegimen suggested Acute illness without lymphadenopathy No specific tx unless severe/persistent symptoms or evidence of vital organ damageAcquired via transfusion (lab. accident)Treat as for acute chorioretinitisActive Chorioretinitis; meningitis, lowered resistance due to steroids or cytotoxic drugs[Pyrimetamine 200mg once on 1st day 50-75 mg(q24h)] + [Sulfadiazine 1-1.5 mg po qid] + [Leucovorine (folinic acid) 5-20 mg 3x/week] # treat beyond resolution of signs/symptoms; cont Leucovorin 1 week after stopping Pyr.Acute in pregnant womenSpiramycin 827-2335 mg po q8h (w/o food) until term or until fetal infectionFetal/CongenitalManagement complex. Combo tx with Pyrimetamine+Sulfadiazin+Leucovorin

Acquired Immunodeficiency Syndrome (AIDS)The Sanford Guide To Antimicrobial Therapy 2007

ToxoplasmaPrimary treatmentAlternative treatmentCerebral Toxoplasmosis[Pyrimetamine 200mg x 1 po then 75 mg/day po] + [Sulfadiazine 1-1.5 mg po q6h] + [Leucovorine (folinic acid) 10-20 mg/day po] treat 4-6 week after resolution of signs/symptoms and then suppresive txORTMP-SMX 10-50 mg/kg/day po or iv divided q12h x 30 daysPyrimetamine + folinic acid (as in primary regimen) + 1 of the following =Clinda 600 mg po/iv q6hClarithro 1 gm po bidAzithro 1.2-1.5 gm po q24hAtovaquone 750 mg po q6h treat 4-6 week after resolution of signs/symptoms and then suppresive txPrimary prophylaxis AIDS pts-IgG toxo antibody + CD4 count < 100/mclTMP-SMX-DS 1 tab po q24h OR TMP-SMX-SS 1 tab po q24hDapsone 50 mg po q24h + Pyrimetamine 50 mg po q wkORAtovaquone 1500 mg po q24hSuppresive treatmentSulfadiazine 500-1000 mg po 4 x/day + (folinic acid) 10-25 mg po q24h DC if CD4 count > 200 x 3 moClinda 300-450 mg q6-8h + Pyrimetamine 25-50 mg po q24h ORAtovaquone 750 mg po q6-12h

Prevention and ControlEducationAvoid ingestion of and contact with cysts or sporulated oocystsCook meat to well done with no visible pink in centerWash hands thoroughly after handling raw meat or vegetablesAvoid areas with cat fecesChange litter every day (before sporulation)Wear disposable gloves when disposing of cat litter, working in garden, cleaning childs sandboxSerologic screening for pregnant women