5Transmission of toxoplasma to humans Ingestion of cat faeces(litter trays, salads)TOXOPLASMOSISIngestion of undercooked meatscontaining oocysts or bradyzoites
6What is the differential? What tests should be done? Case vignette: 25 year old male presents with 2 week history of malaise and marked bilateral cervical lymphadenopathyWhat is the differential?What tests should be done?Relative lymphocytosis, mild transaminitis, Toxo IgM +ve and Toxo IgG positive. EBV(VCA) and CMV IgM negative. HIV negativeIs the diagnosis of toxoplasmosis correct.?Should the patient be treated?How long will the toxoplasma IgM be positive for?In immunocompetent individuals acute toxoplasmosis asymptomatic in up to 80% of individuals.
7LymphadenopathyIn toxoplasmosis, lymphadenopathy usually bilateral and mildly tender. Can take 4-6 months to settle completely.Usually cervical.(posterior), but occasionally axillary or groinPositive toxoplasma IgM serology results often have a history of lymphadenopathy on the request form.
8Pitfalls in toxoplasma serology Summary Beware cross reactive Toxoplasma IgMs from strong positive EBV or CMV IgMsA toxoplasma IgM may hang around for anything up to 2 yearsUnusual to get a IgM positive IgG negative toxo result.
9Case Vignette: 29 yr old pregnant(13/40) lady with cervical lympadenopathy and fever. She has just got a kitten for the impending new arrival.What tests would you order?FBC, LFTs, EBV, CMV, Toxo serology, HIV.Toxoplasma IgM positive, Toxoplasma IgG positive. HIV, CMV and EBV serology negative.
10Is the foetus at risk? Yes Risk of toxoplasma transmission from mother to baby increases with gestational age. 6% at 13 weeks to 72% at 36 weeks.Risk of serious symptoms/foetal damage resulting from congenital infection is highest in early pregnancy and decreases with gestational age.
11What further investigations would you carry out? Ensure EBV and CMV serology is negative.Go back and check Toxoplasma serology on the booking bloods.Refer to ObstetricianCheck Toxoplasma IgG avidity(Antibodies gradually become more avid (strength of attachment to antigen) as time from primary infection increases, therefore high avidity more likely to represent remote/distant infection. This is useful because of the length of time that Toxo IgM remains positive for)
12Toxoplasma avidity testing in pregnancy Would you do a Toxoplasma IgG avidity test on this lady?Probably not , not going to determine whether infection actually happened during pregnancy.
13Obstetric follow upIf congenital toxoplasmosis is suspected on basis of serology, obstetrician will monitor by serial ultrasounds and offer amniocentesis at wks.Spiramycin until term for pregnant mother with proven toxoplasma infection… unlessIf congenital infection of foetus is confirmed by PCR of amniotic fluid then treatment of mother with pyrimethamine and sulphadiazine instead. (and baby will need treated as well when born)
15Clinical presentation of congenital toxoplasmosis Chorioretinitis, blindness, seizures, hydrocephalus, microcephaly, intracranial calcifications, encephalitis, mental retardation, lympadenopathy, hepatosplenomegaly, anemia and rash.Congenitally infected infants may be asymptomatic at birth but then develop symptoms during childhood.(chorioretinitis, developmental delays)PCR may help to confirm diagnosis in neonate.Toxoplasma IgG negativity or disappearance on serial testing is only way to exclude congenital infection in neonates.
16What is the differential diagnosis? 28 year old HIV patient presents with 3 week history of headache, fever and focal seizures of his right arm. Compliance with anti-retrovirals has been poor.What is the differential diagnosis?Cryptococcal meningitis, TB, cerebral toxoplasmosis, lymphomaWhat investigations would you perform?CT BrainCD4 count (usually less than 100 in HIV cerebral toxo), toxoplasma serology.CSF examination including cryptococcal antigen and TB culture.Consider toxoplasma PCR on CSF based on CD4 count and radiological findings.
17CT findingsMultiple ring enhancing lesions, often with associated oedemaMain differential is lymphoma, cerebral metastases.CT may occasionally be negative. MRI is also an option.
18Edinburgh in the Early 90’s HIV rife amongst the IDU population.Whole ward dedicated to AIDS related illness at the Edinburgh ID hospital (Amongst patients, PCP most common but always a few with cryptococcal meningitis and cerebral toxoplasmosis)
19Toxoplasma PCRExpensive. Discuss with clinical microbiologist at reference lab where sample is going to.Diagnosing Congenital infection in the NewbornAmniotic fluid 10 mL. (Collect at delivery if possible).Fresh placental biopsy.Cord blood – 1 mL in EDTA tube.Diagnosing Intrauterine infection in the foetusAmniotic fluid; 10 mLFoetal blood (EDTA tube)Amniotic fluid is the preferred sample.Heavily Immunocompromised patientBlood – 5 mL EDTA tubeCSF – 2 mL CSFTissue biopsy - Lymph node, cardiac biopsy, brain biopsy etc.Ocular toxoplasmosisVitreous fluid
20Ocular toxoplasmosis Diagnosis is usually clinical. Usually in congenital or immunocompromised cohorts. However can occur occasionally in immunocompetent adults.Supportive evidence of +ve toxoplasma IgG absPCR on vitreous fluid for difficult cases.Exclude syphilis infection.
21Take Home Messages Toxoplasmosis is not uncommon Be aware of the relative importance of toxoplasmosis in different clinical scenarios eg immunocompetent, congenital, immunocompromised.Be aware of the tests that are available for diagnosis, including the IgG avidity test and the PCR test and when they are best utilised.Be sure a positive Toxoplasma IgM is genuine.