ToxoplasmosisToxoplasmosisin twenty in twenty minutesminutesMichael AddidleMichael Addidle

Clinical MicrobiologistClinical Microbiologist

PathlabPathlab

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Background knowledgeBackground knowledge Toxoplasmosis in immunocompetent Toxoplasmosis in immunocompetent

hosthost Congenital toxoplasmosisCongenital toxoplasmosis Toxoplasmosis in an Toxoplasmosis in an

immunocompromised patient (HIV)immunocompromised patient (HIV) Ocular toxoplasmosisOcular toxoplasmosis Take Home MessagesTake Home Messages

Transmission of toxoplasma Transmission of toxoplasma to humansto humans

Ingestion of cat faeces(litter trays, salads)

Ingestion of undercooked meats containing oocysts or bradyzoites

TOXOPLASMOSIS

Case vignette: 25 year old male presents with Case vignette: 25 year old male presents with 2 week history of malaise and marked bilateral 2 week history of malaise and marked bilateral

cervical lymphadenopathycervical lymphadenopathy What is the differential?What is the differential? What tests should be done?What tests should be done?

•Relative lymphocytosis, mild transaminitis, Relative lymphocytosis, mild transaminitis, Toxo IgM +ve and Toxo IgG positive. Toxo IgM +ve and Toxo IgG positive. EBV(VCA) and CMV IgM negative. HIV EBV(VCA) and CMV IgM negative. HIV negativenegative•Is the diagnosis of toxoplasmosis correct.?Is the diagnosis of toxoplasmosis correct.?•Should the patient be treated?Should the patient be treated?•How long will the toxoplasma IgM be How long will the toxoplasma IgM be positive for?positive for?In immunocompetent individuals acute In immunocompetent individuals acute toxoplasmosis asymptomatic in up to 80% of toxoplasmosis asymptomatic in up to 80% of individuals.individuals.

LymphadenopathyLymphadenopathy In toxoplasmosis, In toxoplasmosis,

lymphadenopathy usually lymphadenopathy usually bilateral and mildly tender. bilateral and mildly tender. Can take 4-6 months to Can take 4-6 months to settle completely.settle completely.

Usually cervical.(posterior), Usually cervical.(posterior), but occasionally axillary or but occasionally axillary or groingroin

Positive toxoplasma IgM Positive toxoplasma IgM serology results often have serology results often have a history of a history of lymphadenopathy on the lymphadenopathy on the request form.request form.

Pitfalls in toxoplasma Pitfalls in toxoplasma serologyserologySummarySummary

Beware cross reactive Toxoplasma Beware cross reactive Toxoplasma IgMs from strong positive EBV or IgMs from strong positive EBV or CMV IgMsCMV IgMs

A toxoplasma IgM may hang around A toxoplasma IgM may hang around for anything up to 2 yearsfor anything up to 2 years

Unusual to get a IgM positive IgG Unusual to get a IgM positive IgG negative toxo result. negative toxo result.

Case Vignette: 29 yr old Case Vignette: 29 yr old pregnant(13/40) lady with cervical pregnant(13/40) lady with cervical

lympadenopathy and fever. She lympadenopathy and fever. She has just got a kitten for the has just got a kitten for the

impending new arrival.impending new arrival. What tests would you order?What tests would you order? FBC, LFTs, EBV, CMV, Toxo FBC, LFTs, EBV, CMV, Toxo

serology, HIV.serology, HIV. Toxoplasma IgM positive, Toxoplasma IgM positive,

Toxoplasma IgG positive. HIV, CMV Toxoplasma IgG positive. HIV, CMV and EBV serology negative.and EBV serology negative.

Is the foetus at risk?Is the foetus at risk?

Yes Yes Risk of toxoplasma transmission from Risk of toxoplasma transmission from

mother to baby increases with mother to baby increases with gestational age. 6% at 13 weeks to gestational age. 6% at 13 weeks to 72% at 36 weeks.72% at 36 weeks.

Risk of serious symptoms/foetal Risk of serious symptoms/foetal damage resulting from congenital damage resulting from congenital infection is highest in early pregnancy infection is highest in early pregnancy and decreases with gestational age. and decreases with gestational age.

What further investigations What further investigations would you carry out?would you carry out?

Ensure EBV and CMV serology is negative.Ensure EBV and CMV serology is negative. Go back and check Toxoplasma serology on the Go back and check Toxoplasma serology on the

booking bloods.booking bloods. Refer to ObstetricianRefer to Obstetrician Check Toxoplasma IgG avidityCheck Toxoplasma IgG avidity

(Antibodies gradually become more avid (Antibodies gradually become more avid (strength of attachment to antigen) as time (strength of attachment to antigen) as time from primary infection increases, therefore from primary infection increases, therefore high avidity more likely to represent high avidity more likely to represent remote/distant infection. This is useful because remote/distant infection. This is useful because of the length of time that Toxo IgM remains of the length of time that Toxo IgM remains positive for)positive for)

Toxoplasma avidity testing Toxoplasma avidity testing in pregnancyin pregnancy

Would you do a Would you do a Toxoplasma IgG Toxoplasma IgG avidity test on avidity test on this lady?this lady?

Probably not , Probably not , not going to not going to determine determine whether whether infection actually infection actually happened during happened during pregnancy.pregnancy.

Obstetric follow upObstetric follow up

If congenital toxoplasmosis is suspected on If congenital toxoplasmosis is suspected on basis of serology, obstetrician will monitor by basis of serology, obstetrician will monitor by serial ultrasounds and offer amniocentesis at serial ultrasounds and offer amniocentesis at 20-22 wks.20-22 wks.

Spiramycin until term for pregnant mother Spiramycin until term for pregnant mother with proven toxoplasma infection… unlesswith proven toxoplasma infection… unless

If congenital infection of foetus is confirmed If congenital infection of foetus is confirmed by PCR of amniotic fluid then treatment of by PCR of amniotic fluid then treatment of mother with pyrimethamine and sulphadiazine mother with pyrimethamine and sulphadiazine instead. (and baby will need treated as well instead. (and baby will need treated as well when born)when born)

AmniocentesisAmniocentesis

Clinical presentation of Clinical presentation of congenital toxoplasmosiscongenital toxoplasmosis

Chorioretinitis, blindness, Chorioretinitis, blindness, seizures, hydrocephalus, seizures, hydrocephalus, microcephaly, intracranial microcephaly, intracranial calcifications, encephalitis, calcifications, encephalitis, mental retardation, mental retardation, lympadenopathy, lympadenopathy, hepatosplenomegaly, anemia and hepatosplenomegaly, anemia and rash.rash.

Congenitally infected infants may Congenitally infected infants may be asymptomatic at birth but be asymptomatic at birth but then develop symptoms during then develop symptoms during childhood.(chorioretinitis, childhood.(chorioretinitis, developmental delays)developmental delays)

PCR may help to confirm PCR may help to confirm diagnosis in neonate.diagnosis in neonate.

Toxoplasma IgG negativity or Toxoplasma IgG negativity or disappearance on serial testing is disappearance on serial testing is only way to exclude congenital only way to exclude congenital infection in neonates.infection in neonates.

28 year old HIV patient presents with 3 week 28 year old HIV patient presents with 3 week history of headache, fever and focal seizures history of headache, fever and focal seizures

of his right arm. Compliance with anti-of his right arm. Compliance with anti-retrovirals has been poor.retrovirals has been poor.

What is the differential diagnosis?What is the differential diagnosis?

Cryptococcal meningitis, TB, Cryptococcal meningitis, TB, cerebral cerebral toxoplasmosis, lymphomatoxoplasmosis, lymphoma

What investigations would you perform?What investigations would you perform?

CT BrainCT BrainCD4 count (usually less than 100 in HIV CD4 count (usually less than 100 in HIV cerebral toxo), toxoplasma serology.cerebral toxo), toxoplasma serology.CSF examination including cryptococcal CSF examination including cryptococcal antigen and TB culture.antigen and TB culture.Consider toxoplasma PCR on CSF based Consider toxoplasma PCR on CSF based on CD4 count and radiological findings.on CD4 count and radiological findings.

CT findingsCT findings

Multiple ring Multiple ring enhancing lesions, enhancing lesions, often with often with associated oedemaassociated oedema

Main differential is Main differential is lymphoma, cerebral lymphoma, cerebral metastases.metastases.

CT may occasionally CT may occasionally be negative. MRI is be negative. MRI is also an option.also an option.

Edinburgh in the Early Edinburgh in the Early 90’s90’s

HIV rife amongst the HIV rife amongst the IDU population.IDU population.

Whole ward dedicated Whole ward dedicated to AIDS related illness to AIDS related illness at the Edinburgh ID at the Edinburgh ID hospital (Amongst hospital (Amongst patients, PCP most patients, PCP most common but always a common but always a few with cryptococcal few with cryptococcal meningitis and meningitis and cerebral cerebral toxoplasmosis)toxoplasmosis)

Toxoplasma PCRToxoplasma PCR Expensive. Discuss with clinical microbiologist at reference lab where Expensive. Discuss with clinical microbiologist at reference lab where

sample is going to.sample is going to.

Diagnosing Congenital infection in the NewbornDiagnosing Congenital infection in the NewbornAmniotic fluid 10 mL. (Collect at delivery if possible). Amniotic fluid 10 mL. (Collect at delivery if possible). Fresh placental biopsy. Fresh placental biopsy. Cord blood – 1 mL in EDTA tube. Cord blood – 1 mL in EDTA tube.    Diagnosing Intrauterine infection in the foetusDiagnosing Intrauterine infection in the foetusAmniotic fluid; 10 mL Amniotic fluid; 10 mL Foetal blood (EDTA tube) Foetal blood (EDTA tube) Amniotic fluid is the preferred sample. Amniotic fluid is the preferred sample.    Heavily Immunocompromised patientHeavily Immunocompromised patient Blood – 5 mL EDTA tube Blood – 5 mL EDTA tube CSF – 2 mL CSF CSF – 2 mL CSF Tissue biopsy - Lymph node, cardiac biopsy, brain biopsy etc. Tissue biopsy - Lymph node, cardiac biopsy, brain biopsy etc.    Ocular toxoplasmosisOcular toxoplasmosis Vitreous fluid Vitreous fluid

Ocular toxoplasmosisOcular toxoplasmosis Diagnosis is usually Diagnosis is usually

clinical.clinical. Usually in congenital or Usually in congenital or

immunocompromised immunocompromised cohorts. However can cohorts. However can occur occasionally in occur occasionally in immunocompetent adults.immunocompetent adults.

Supportive evidence of Supportive evidence of +ve toxoplasma IgG abs+ve toxoplasma IgG abs

PCR on vitreous fluid for PCR on vitreous fluid for difficult cases.difficult cases.

Exclude syphilis infection.Exclude syphilis infection.

Take Home MessagesTake Home Messages Toxoplasmosis is not uncommonToxoplasmosis is not uncommon Be aware of the relative importance of Be aware of the relative importance of

toxoplasmosis in different clinical toxoplasmosis in different clinical scenarios eg immunocompetent, scenarios eg immunocompetent, congenital, immunocompromised.congenital, immunocompromised.

Be aware of the tests that are available Be aware of the tests that are available for diagnosis, including the IgG avidity for diagnosis, including the IgG avidity test and the PCR test and when they are test and the PCR test and when they are best utilised.best utilised.

Be sure a positive Toxoplasma IgM is Be sure a positive Toxoplasma IgM is genuine.genuine.