Toxoplasmosis Learning Objectives - PowerPoint Presentation

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Toxoplasmosis Learning Objectives - PPT Presentation

Introduction Life Cycle Epidemiology Pathologenesis Clinical Overviews Diagnosis Serology Neuroimaging CSF examination Presumptive diagnosis Brain Biopsy algorithm Treatment Prophylaxis Prognosis ID: 804479

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Slide1

ToxoplasmosisLearning ObjectivesIntroductionLife CycleEpidemiologyPathologenesisClinical OverviewsDiagnosisSerologyNeuroimagingCSF examinationPresumptive diagnosisBrain Biopsy algorithmTreatmentProphylaxisPrognosisKey PointsSummarySelf Assessment

Cerebral Toxoplasmosis

Drs Sam Nightingale & Sylviane

Defres

Sam

Nightingale is a neurology registrar and MRC clinical research fellow. He runs the UK wide multi-centre PARTITION study looking at factors effecting the CNS penetration of

antiretrovirals

and the role of the CNS as a sanctuary site for HIV.

Sylviane

Defres

is an infectious diseases specialist registrar and clinical research fellow working on the NIHR funded ENCEPH-UK programme, a series interrelated of studies which include looking at the early clinical predictors of encephalitis and of outcome, with the aim of improving that outcome. Edited by Prof Tom Solomon, Dr Agam Jung and Dr Sam Nightingale

This module provides an overview of the CNS manifestations of toxoplasmosis infection.

Slide2

Learning Objectives

By the end of this session you will be able to:

Understand the epidemiology of toxoplasmosis

Recall the life cycle of the pathogen

Toxoplasma

gondii

Describe the clinical features of CNS toxoplasmosis.

Recognise which stage of HIV is at risk and give examples of other conditions predisposing to the disease. Outline the differences between presumptive and definitive diagnosis of toxoplasmosis and correctly identify which treatment approach is appropriate in a given clinical scenario. State the first-line and alternative treatments for CNS toxoplasmosis. Describe appropriate preventative measures and prophylaxis for those at risk.

Slide3

Introduction

Cerebral toxoplasmosis is caused by infection with

Toxoplasma

gondii

an intracellular coccidian protozoan parasite that infects birds, mammals and humans. It has a worldwide distribution.

Although the first cases of cerebral toxoplasmosis were described in infants with congenitally acquired cerebral toxoplasmosis the most clinically evident cerebral toxoplasmosis is associated with HIV infection. Those with other causes of

immunosuppression

are also susceptible, including transplant recipients (particularly heart, lung kidney & bone marrow) and patients with

haematological malignancies such as Hodgkin's disease. Also immunosuppression due to drugs including steroids and Anti-TNF therapies.As with other opportunistic infections the incidence of toxoplasmosis in HIV infection has been dramatically reduced as a result of antiretroviral therapy. Despite this, cerebral toxoplasmosis remains the most important neurological opportunistic infection in HIV infected patients around the world.

Cerebral toxoplasmosis- Axial T1-weighted MRI following gadolinium showing thick walled ring enhancing lesion with

oedema, mass effect and midline shift (Image courtesy of Dr Ian Turnbull).

Slide4

Life Cycle of

Toxoplasma

gondii

exists in 3 forms,

oocysts

tachyzoites & tissue cysts (bradyzoites).Although almost any mammal and some birds can be infected by T. gondii, only felines (wild & domesticated cats) can complete the reproductive cycle (definitive hosts). Felines (definitive hosts):Ingest all forms, in which invasion & replication can occur in the gut epithelium

Excrete infectious oocysts in

faecesNon-felines (intermediate hosts):Ingest oocysts

which invade & replicate in the gut epithelium

Disseminates to tissues where they

encyst

, within the host cell cytoplasm and lie dormant

Acquisition of

T.gondii

Ingestion of

oocysts

from the environment (contaminated water or food,

soil or cat

faeces

)

Ingestion of tissue cysts (

bradyzoites

) in meat (raw or undercooked)

In addition, in humans:

Vertical transmission from mother who acquires infection during gestation

(pregnancy)

Less commonly:

Blood transfusion or organ transplantation (have been reported

from heart, lung, kidney or bone marrow)

Consumption of unpasteurized goat’s milk

Oocysts

may remain viable in the environment for as long as 18 months

See pictures of the

T.gondii

forms & a diagram illustrating its life cycle on the following 2 pages.

Slide5

Life Cycle: Different forms of

Toxoplasma

gondii

Oocyst

(

unsporulated

)

Sporulated

oocysts (contain sporozoites)Sporulation occurs in environment.Tachyzoites

(able to invade

host Cells)Tissue cyst;

Bradyzoites

Slide6

Life Cycle of

Toxoplasma

gondii

III

Slide7

Epidemiology I

Seroprevalence

rates of toxoplasmosis vary significantly among countries.

Rate of approximately 15% in USA

Rates between 50-88% in some Western European and African countries.

There has been a 25-40% decline in the

seroprevalence

over a 10 year period from 1994-2004, shown below in USA & some western countries, but rises in other parts of the world. This appears to be due to a fall in incidence infection in childhood and therefore leaves more women susceptible in pregnancy

Human susceptibility varies according to several factors including proximity to cats, dietary habits, climate, and sanitation. In France, for example, the higher

seroprevalence

is probably due to a high consumption of raw and lightly cooked meat.9% (was 22%)

70%

4.3 %

11-15%

(was 25%)

50-60%

(was 80-90%)

Slide8

Epidemiology II: HIV

Cerebral toxoplasmosis is an AIDS defining illness and usually occurs at CD4 counts below 100 cells/mm

. It is very rare over 200 CD4 cells/mm

Knowledge of the patient's country of origin is rarely helpful as the commonest cause of a CNS mass lesion in a HIV person is toxoplasmosis, even in areas where tuberculosis is endemic.

The

seroprevalence

rate of toxoplasmosis in HIV infected patients is similar to that of the general populationThe incidence of infection in cat owners is equal to that in non-cat ownersIncidence CNS toxoplamosis has decreased from 5.4/1000 person-yrs (1990-92) to 2.2/1000 (96-98) with HAART and the use of effective anti- T.gondii prophylactic regimens

Interestingly, cerebral toxoplasmosis is rare in the paediatric HIV population.

In those HIV positive individuals with a CD4 count <100 and who are seropositive for T.gondii

there is a 30% probability of developing reactivated toxoplasmosis if effective prophylaxis is not taken.

20-47% of HIV positive individuals not on treatment (

ARVs

or prophylactic antibiotics) are likely to go on to get cerebral toxoplasmosis.

Slide9

Pathogenesis

T.gondii

enters

via the intestinal epithelial cells where they can then spread to lymph nodes and distant organs via the blood or lymph systems.

It can invade virtually all cell types and survives within a vacuole with cells, where it is protected from the host’s

humoral

and cellular immune system.Due to parasite competition, the host cell will disintegrate releasing tachyzoites that invade surrounding tissues.If the tachyzoites differentiate into bradyzoites this replication and disintegration process takes longer. These bradyzoites must transform into tachyzoites to invade surrounding tissues

In healthy individuals, the immune system effectively eliminates fast replicating tachyzoites

& the bradyzoites replicate slowly enough that no serious damage occurs. Left unchecked by the immune system, fast replicating

tachyzoites

invade and kill multiple cells resulting in large lesions. If this occurs in the brain and is untreated the damage could lead to hydrocephalus,

retinochoroidenitis

or fatal necrotic encephalitis.

Slide10

Pathogenesis

There are 3

clonal

strains of

T.gondii

Strain I

Strain II

Strain III

Congenital toxoplasmosis

AIDS

Severe ocular disease

Strain 3 is seen much more commonly in animals than humans, but when it does occur in humans causes severe ocular disease. Strain 2 is the most common in humans.

Atypical and recombinant strains have been identified with increasing frequency in regions other than USA & Europe, some of which have been associated with more severe disease even in the

immunocompetent

Slide11

Pathology

Most commonly there are multiple areas of focal

necrotising

encephalitis which contain tissue cysts and extracellular

tachyzoites

Multiple

miliary

granulomas

or a diffuse necrotising encephalitis can occur.This high power view of toxplasma tachyzoites (small arrow) in the brain shows numerous small blue parasites through the parenchyma. They may have emerged from the bradycyst seen towards the right hand side (large arrow).

Slide12

Clinical Overview 1 – Congenital infection

Transplacental infection

Transplacental infection can result in spontaneous abortion, stillbirth or a child with a mental or physical handicap.

Incidence maternal infection during pregnancy ranges 1-8/2000 (highest in France)

Immunocompetent

women, infected prior to pregnancy, virtually never transmit

gondii

to the

foetus

.Immunocompromised women may have parasitaemias

during pregnancy despite

preconceptional infection.Acute infection in the mother is usually asymptomatic.

Maternal diagnosis is best made by paired serology 2 weeks apart.

Risk of

foetal

infection increases with advancing gestational age at the time of maternal

seroconversion

15% risk of transmission @ 13 weeks gestation

44% risk of transmission @ 26 weeks gestation

71% risk of transmission @ 36 weeks gestation

Slide13

Clinical Overview 2 – Congenital infection

Sequelae

transplacental

foetal

infection

Intracranial lesions (calcification or ventricular dilatation),

Disseminated infection in infancy,

Serious neurological impairment (

eg seizures in infancy, microcephaly, cerebral palsy) Retinochoroiditis

Intracranial lesions & neurological impairment are more likely to occur the earlier the

seroconversion is(this is not the case for

retinochoroiditis

). Stillbirth or neonatal death is rare.

80% of live-born infected infants show no signs of congenital toxoplasmosis. Of the 20% that do show signs of congenital toxoplasmosis:

14% have

retinochoroiditis

9% have intracranial lesions: of which ~5% have serious neurological

sequelae

The risk of bilateral visual impairment worse

than 6/12

Snellen

ranges from 2-9%.

RIGHT: Severe active

toxoplasma

chorioretinitis

Slide14

Clinical Overview 3 – Congenital infection

Diagnosis of

foetal

infection prenatally

Purposes:

Mainly to aid the decision of whether to change the prenatal treatment from

spiromycin

pyrimethamine

-sulfonamide, although there is little evidence that the latter is any more effective.

Also to aid any decision regarding Termination Of Pregnancy Exclusion of foetal infection prenatally to prevent unnecessary postnatal treatment

Best method of diagnosis:

PCR amniotic fluid; accuracy varies between labs and techniques. Sensitivity of PCR increases with gestational age at maternal

seroconversion

(33% 1st to 76% 2nd & 3rd trimester)

Foetal

USS to see intracranial calcification or hydrocephalus (only appear after 21 weeks gestation)

Slide15

Clinical Overview 4 –

Immunocompetent

adult

Primary infection;

Usually asymptomatic in 80-90% of cases

In the remainder there is usually a flu-like illness with lymphadenitis

Bilateral symmetrical non-tender lymph nodes

20-30% have constitutional symptoms of fever chills and sweats.

Also headaches,

myalgias

, pharyngitis, maculopapular rash or hepatosplenomegaly may occur Usually self limiting, lasting approximately weeks to months. Very rarely myocarditis,

pericarditis, pyomyositis

, pneumonitis, hepatitis or encephalitis can occur

Chorioretinitis

T.gondii

is one of the commonest causes of

chorioretinitis

immunocompetent

hosts. It is a differential of CMV retinitis. Typically it is acquired congenitally or

postnatally

. In this circumstance, there is usually bilateral eye involvement with scarring and frequent recurrences due to reactivation. Clusters of episodes can occur after prolonged disease free intervals. Older individuals are at higher risk of reactivation than younger

Adults with acute infection usually have unilateral eye disease

and there is an absence of prior scarring

It can occur without other CNS involvement and is treated in the same manner as CNS toxoplasmosis. ( see later)

Latent infection can persist for life

Slide16

Clinical Overview 5 –

Immunocompromised

Adult

Whilst CNS toxoplasmosis can occur during the primary infection, this is rare and it usually represents reactivation of latent infection. Primary infection in the

immunocompromised

host can be severe and life threatening.

Most commonly this reactivation is in HIV positive individuals but the clinical presentation below can be similar in those who are

immunocompromised

for other reasons.

Cerebral abscesses are the most common form of reactivation.

Extracerebral toxoplasmosis is much harder to determine the incidence of: Series have shown ocular, pulmonary and disseminated infection. Rare cases involve bladder, skin, liver, lymph nodes and pericardium. Often these are only detected at autopsyPatients present with focal neurological signs relating to one or more mass lesions in the CNS, although a diffuse encephalitis can occur.

Headache, confusion, fever, behavioral changes & altered mental status are common. Focal neurological defects & seizures are also common.

Extrapyramidal signs and movement disorders can occur as there is a predilection for deeper structures in the region of the basal ganglia and midline.

Onset can be insidious with fever and confusion, or acute with

symptoms appearing over hours.

Although headache with fever is common,

meningitic

signs are unusual.

Slide17

Diagnosis

The threshold for investigation should be low in any HIV positive individual presenting with focal neurology, encephalopathy or seizures. The important differentials in this context are primary CNS lymphoma (PCNSL) and

tuberculous

granulomata

or abscess.

Definitive diagnosis can only be achieved by brain biopsy, however this can usually be avoided by using serology,

neuroimaging

and observing response to presumptive treatment.

LEFT: T1-weighted MRI with contrast showing a developing

tuberculoma in the left Sylvian fissue. Image courtesy of Dr Milne Anderson.RIGHT: T1-weighted MRI with gadolinium showing primary CNS lymphoma in HIV. Image courtesy of Tom Solomon.

Slide18

Toxoplasma

Microbiology/ Serology

IgM

appears within 1 week of the acute infection.

IgG

becomes positive in approximately 2 weeks.

Serology in acute infection;

IgM

positive &

IgG

negative at the start, with both positive two weeks later is indicative of acute infection. But typically both are positive.IgG avidity testing may help. IgG antibodies made early in infection bind to antigen less avidly than antibodies produced later. So the presence of high avidity suggests infection occurred at least 3-5 months earlier.

CNS toxoplasmosis is almost always a reactivation

and serology is positive in 85% of cases.Although the absence of antibodies makes the diagnosis less likely, they do NOT exclude the diagnosis.

Seronegative

cases can occur as a result of loss of antibody with increasing

immunosuppression

or rarely in primary infection.

IgM is rarely positive and usually not helpful.

PCR testing has variable sensitivities and specificities; newer probes are being investigated.

Culture is rarely performed but may be useful in neonates.

Slide19

Neuroimaging

MRI is more sensitive than CT. Toxoplasmosis usually causes multiple solid or cystic spherical lesions with ring enhancement, surrounding

oedema

and mass effect. The below image shows a T1-weighted MRI with gadolinium showing toxoplasmosis with mass effect:

They can be located anywhere in the CNS but have a predilection for the grey/white interface or basal ganglia. The more lesions there are, the more likely the cause is toxoplasmosis.

RIGHT: Coronal MRI, T2-weighted, showing bilateral toxoplasmosis (arrows).

Alone, neither MRI nor CT can differentiate among the multiple possible

aetiologies

of brain lesions in AIDS patients.

Differential diagnosis includes:

Cryptococcosis

Histoplasmosis

Aspergillosis

Tuberculosis

Trypanosomiasis

CNS lymphoma

Slide20

Neuroimaging

A single lesion

favours

lymphoma, but there is overlap and no appearance is

pathognomonic

. CNS

tuberculomas

appear similar to toxoplasmosis on imaging. Around 60% of these will have an abnormal chest x-ray. Progressive multifocal

leucoencephalopathy

(PML) does not produce mass effect.DWI/SPECTThere has been some interest in diffusion weighted MRI or thallium SPECT (Single Photon Emission Computed Tomography) scans to differentiate between focal encephalitis, abscesses and lymphoma.

However the differences are neither specific nor sensitive so these tests are not routinely used. They may be of some value in cases where brain biopsy is not possible, for example due to location of the lesion (see further reading).

RIGHT: Cerebral toxoplasmosis. Axial T1-weighted MRI following gadolinium showing two thick walled ring enhancing lesions within the right basal ganglia with mild local mass effect. Image courtesy of Dr Ian Turnbull.

Slide21

CSF Examination

Lumbar puncture is frequently contraindicated due to the presence of a mass lesion and can usually be avoided, as suggestive radiology with positive serology is sufficient evidence to start presumptive treatment for toxoplasmosis.

The CSF usually shows a mononuclear

pleocytosis

with normal glucose ratio. PCR for toxoplasmosis in the CSF is specific (96-100%) but has a low sensitivity. CSF antibody testing is unhelpful.

The detection of Epstein-Barr virus (EBV) in the CSF by PCR indicates primary CNS lymphoma. PCR for Mycobacterium tuberculosis is positive in the CSF in 60% of

tuberculous

abscesses.

Tuberculous

granuloma may occur in association with TB meningitis.

Slide22

Presumptive diagnosis

In HIV positive individuals with a CD4 count< 100 cells/

μl

there is a 90%

probablity

toxoplamsa

encephalitis if;

IgG

positive,

No effective prophylaxis was being taken ANDThere are multiple ring enhancing lesions on the neuroimagingIf all 3 are not present then biopsy or other diagnostic tests should be performed. This includes PCR testing for other organisms like EBV, Mycobacterium tuberculosis, Cryptococcus neoformans in patients with focal brain lesions who were on prophylaxis or were seronegative.

Definitive diagnosis rests with demonstration of the parasite in biopsy material from an affected area of brain.

If there has been no response to treatment within two weeks, then a biopsy should be considered. With a single cerebral lesion, particularly if serology is negative, biopsy should be performed prior to treatment, as primary CNS lymphoma needs to be considered.See British HIV Association (BHIVA) algorithm on following page.

Slide23

Brain Biopsy Algorithm

Slide24

Treatment I

Immunocompetent

, non-pregnant, patients generally do not require treatment unless their symptoms are severe. Treatment is the same as for

immunosuppressed

, though usually lower doses are possible and duration is for 2-4 weeks whereas in

immunsuppressed

duration of therapy for the acute

atage

is 6 weeks.

st line therapy for cerebral toxoplasmosis is pyrimethamine combined with sulphadiazine or clindamycin . Pyrimethamine is myelotoxic & should be given together with folinic acid. Folic acid, although cheaper, is ineffective as it cannot be converted in the presence of Pyrimethamine. Allergy & side effects are common with this regime. Along with bone marrow suppression it may cause rash, nausea or vomiting.

Suladiazine

too may cause rash, fever, leukopaenia, hepatitis, nausea or vomiting or crystalluria.

Clindamycin

is an effective alternative to

Sulphadiazine

in patients with Sulfonamide allergy or difficulty swallowing pills. Side effects may include, rash, fever, nausea

diarrhoea

including

Clostridium

difficile

associated

diarrhoea

Alternatives include

Pyrmethamine

folinic

acid) +

azithromycin

Pyrimethamine

folinic

acid) +

atovaquone

Sulphadiazine

atovaquone

Co-

trimoxazole

can also be considered if

pyrmethamine

is not tolerated

The same dosage as for

Pneumocystis

jiroveci

(previously known as

Pneumocystis

carinii

or, PCP).

Other drugs are under evaluation including

Clarithromycin

Slide25

Treatment II

There may be less relapses with the

pyrmethamine

folinic

acid) +

suphadiazine

combination, however it does have a higher incidence of

cutaneous

hypersensitivity reactions.

Also if on this combination, additional prophylaxis for Pneumocystis jirovecii is not required.Treatment is for 6 weeks. Often an improvement can be observed within the first few days. During the 1st 2 weeks of treatment a careful neurological examination is more important than radiographic studies. Indeed repeat imaging should be deferred for 2-3 weeks unless there has been clinical worsening or lack of clinical improvement. If there has been no clinical or radiological improvement after two weeks of adequate therapy, the diagnosis is probably not toxoplasmosis. Alternative diagnoses should be considered and a brain biopsy may be necessary.Resistance to the frequently used drug combinations has not yet been convincingly described, so changing the toxoplasmosis therapy is not useful in such cases.

After the treatment course of 6 weeks is Completed, the doses can be reduced for

secondary prophylaxis.

Slide26

Treatment III: Adjunctive Therapies

Steroids often lead to temporary improvement in primary CNS lymphoma (PCNSL) lesions. This makes diagnosis difficult if using steroids when treating presumptively for toxoplasmosis as both toxoplasmosis and PCNSL will improve on this treatment.

Anti-

convulsants

These should be given to those with a history of seizures but

should not be given routinely for seizure prophylaxis to all patients with cerebral toxoplasmosis

Surgical decompression

Surgical decompression is occasionally necessary in severe cases where there is potentially fatal mass lesions with midline shift.

Steroids

Steroids may be necessary to reduce intracranial pressure, however in those with advanced

immunosuppression

the duration of steroid treatment should be limited due to the risk of further opportunistic infection.

Indications may include radiographic evidence of midline shift, signs of critically elevated intracranial pressure or clinical deterioration within the first 48 hours of therapy.

Slide27

Prophylaxis

Patients with negative

toxoplasma

serology

These individuals should be

counselled

about

avoiding eating undercooked meat and about the

risks of infection form cats. This is not specifically

to avoid household cats entirely but may include

using gloves when carefully cleaning out cat litter. Primary Prophylaxis All IgG-positive patients with less than 100 CD4 cells/μl require primary prophylaxis with co-trimoxazole (same dose as for PJP prophylaxis). In cases of allergy to co-trimoxazole

, desensitization may be considered. Alternatives are

dapsone plus pyrimethamine or high-dose dapsone alone.

Primary prophylaxis can be discontinued if CD4 count remains >200 cells/

μl

for at least three months.

Secondary Prophylaxis

Following treated CNS infection, maintenance therapy should be continued until CD4 is above 200 cells/

μl

for 6 months. If the CD4 count drops below 200 again, prophylaxis should be reinstated.

If immune reconstitution does not occur, lifelong maintenance therapy is necessary.

In secondary prophylaxis the same drugs are used as for primary therapy, but at half the dose.

Slide28

Prognosis

Prognosis depends on whether or not immune restoration can be achieved. Residual neurological impairment occurs in around 40% and seizures are common.

Relapses may occur long after treatment due to

intracerebral

persistence, sometimes at CD4 counts significantly higher than associated with the initial infection. Enhancement on MRI indicates that lesions have become active.

Slide29

Key Points

Toxoplasmosis is the most common cause of multiple mass lesions in advanced HIV. It can also present with a diffuse encephalitis.

Toxoplasma

gondii

is excreted in cat

faeces

, and forms tissue cysts in animals including humans.

Infection is usually asymptomatic. 30-65% of the world's population have been exposed through contaminated water or undercooked meat.

The differential diagnosis in HIV includes primary CNS lymphoma and tuberculosis. In most situations presumptive treatment for toxoplasmosis can be given and response to treatment observed.Following successful treatment, prophylactic anti-toxoplasma therapy should be continued until immune function has been restored.

Slide30

Summary

Having completed this session you will now be able to:

Recall the life cycle of the pathogen

Toxoplasma

gondii

Describe the clinical features of CNS toxoplasmosis.

Recognise

which stage of HIV is at risk and give examples of other conditions predisposing to the disease.

Outline the differences between presumptive and definitive diagnosis of toxoplasmosis and correctly identify which treatment approach is appropriate in a given clinical scenario.State the first-line and alternative treatments for CNS toxoplasmosis.Describe appropriate preventative measures and prophylaxis for those at risk. Further reading:Neuroradiology (2006) 48:715–720. Analysis of the utility of diffusion-weighted MRI and apparent diffusion coefficient values in distinguishing central nervous system toxoplasmosis from lymphoma. Paul C. Schroeder et al.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Centers for Disease Control and Prevention, National Institutes of Health, Infectious Diseases Society of America/ HIV Medicine Association. 2009.

Slide31

Question 1

Indicate whether it would be appropriate to give presumptive treatment for toxoplasmosis and observe response for the following situation:

A 32-year-HIV positive lady from India presents with decreased GCS. Her partner says she has been unwell for 2 weeks with fever, headache and weight loss. MRI shows multiple enhancing mass lesions, and diffuse

meningeal

enhancement. Chest X-ray is

abnormal.

Toxoplasma

serology is positive.

Yes

Slide32

Question 1

meningeal

enhancement. Chest X-ray is

abnormal.

Toxoplasma

serology is positive.

Yes

INCORRECT

Although the symptoms would fit, the prominent headache and neck stiffness suggest a

meningeal inflammation. This is confirmed by

meningeal

enhancement on MRI. This is not a feature of toxoplasmosis. The lesions are more likely to be due to tuberculosis. Remember,

toxoplasma

serology is often positive due to asymptomatic exposure.

Click here to move on to the next question

Slide33

Question 1

meningeal

enhancement. Chest X-ray is

abnormal.

Toxoplasma

serology is positive.

Yes

CORRECT

Although the symptoms would fit, the prominent headache and neck stiffness suggest a

meningeal

inflammation. This is confirmed by

meningeal

enhancement on MRI. This is not a feature of toxoplasmosis. The lesions are more likely to be due to tuberculosis. Remember,

toxoplasma

serology is often positive due to asymptomatic exposure.

Click here to move on to the next question

Slide34

Question 2

Indicate whether it would be appropriate to give presumptive treatment for toxoplasmosis and observe response for the following situation:

A 42-year-old HIV positive male, with a CD4 count of 20 cells/

. Presents with 2 week history of progressive right leg weakness and is now finding it difficult to walk. MRI shows 2 enhancing mass lesions in the left internal capsule, and a smaller lesion in the right temporal lobe.

Toxoplasma

serology is positive.

Yes

Slide35

Question 2

A 42-year-old HIV positive male, with a CD4 count of 20 cells/

Toxoplasma

serology is positive.

Yes

INCORRECT

This is a typical history for toxoplasmosis. He should be treated presumptively with

pyrimethamine

and sulphadiazine. Clinicial

and radiological response to treatment should be monitored closely. If it is toxoplasmosis, some improvement should be noted by 2 weeks.

Click here to move on to the next question

Slide36

Question 2

A 42-year-old HIV positive male, with a CD4 count of 20 cells/

Toxoplasma

serology is positive.

Yes

CORRECT

This is a typical history for toxoplasmosis. He should be treated presumptively with

pyrimethamine

and

sulphadiazine

Clinicial

and radiological response to treatment should be monitored closely. If it is toxoplasmosis, some improvement should be noted by 2 weeks.

Click here to move on to the next question

Slide37

Question 3

Indicate whether it would be appropriate to give presumptive treatment for toxoplasmosis and observe response for the following situation:

A 32-year-old man with advanced HIV infection presents with a

generalised

seizure. CT shows a 1.5cm

2cm enhancing mass lesion in the right thalamus.

Toxoplasma

serology is negative.

Yes No

Slide38

Question 3

A 32-year-old man with advanced HIV infection presents with a

generalised

seizure. CT shows a 1.5cm

2cm enhancing mass lesion in the right thalamus.

Toxoplasma

serology is negative.

Yes

INCORRECT

A single lesion may be CNS lymphoma, particularly if toxoplasma serology is negative. However in this situation the lesion may be difficult to biopsy due to its position and a trial of toxoplama

treatment may be appropriate. If the mass effect is not too great a lumbar puncture should be performed for CSF EBV to confirm lymphoma.

Click here to move on to the next question

Slide39

Question 3

A 32-year-old man with advanced HIV infection presents with a

generalised

seizure. CT shows a 1.5cm

2cm enhancing mass lesion in the right thalamus.

Toxoplasma

serology is negative.

Yes

CORRECT

A single lesion may be CNS lymphoma, particularly if

toxoplasma

serology is negative. However in this situation the lesion may be difficult to biopsy due to its position and a trial of

toxoplama

treatment may be appropriate. If the mass effect is not too great a lumbar puncture should be performed for CSF EBV to confirm lymphoma.

Click here to move on to the next question

Slide40

Question 4

Select true or false for the below statement:

Toxoplasmosis is the most common cause of space occupying lesions in HIV.

True

False

Slide41

Question 4

Toxoplasmosis is the most common cause of space occupying lesions in HIV.

True

False

INCORRECT

This is true even in areas in which TB is endemic.

Click here to move on to the next question

Slide42

Question 4

CORRECT

This is true even in areas in which TB is endemic.

Click here to move on to the next question

Toxoplasmosis is the most common cause of space occupying lesions in HIV.

True

False

Slide43

Question 5

Select true or false for the below statement:

Cerebral toxoplasmosis is an AIDS defining illness.

True

False

Slide44

Question 5

Cerebral toxoplasmosis is an AIDS defining illness.

True

False

INCORRECT

Cerebral toxoplasmosis usually occurs at CD4 counts below 100 cells/

and is an AIDS defining illness.

Click here to move on to the next question

Slide45

Question 5

Cerebral toxoplasmosis is an AIDS defining illness.

True

False

CORRECT

Cerebral toxoplasmosis usually occurs at CD4 counts below 100 cells/

and is an AIDS defining illness.

Click here to move on to the next question

Slide46

Question 6

Select true or false for the below statement:

Co-

trimoxizole

is the first line treatment for toxoplasmosis.

True

False

Slide47

Question 6

Co-

trimoxizole

is the first line treatment for toxoplasmosis.

True

False

INCORRECT

Pyrimethamine and

sulphadiazine

are the first line treatment. Co-

trimoxizole is a recognised alternative.

Click here to move on to the next question

Slide48

Question 6

Co-

trimoxizole

is the first line treatment for toxoplasmosis.

True

False

CORRECT

Pyrimethamine and

sulphadiazine

are the first line treatment. Co-

trimoxizole

is a

recognised

alternative.

Click here to move on to the next question

Slide49

Question 7

Select true or false for the below statement:

Toxoplasma

serology is diagnostic in the presence of suggestive imaging.

True

False

Slide50

Question 7

Toxoplasma

serology is diagnostic in the presence of suggestive imaging.

True

False

INCORRECT

Asymptomatic exposure to

toxoplasma

gondii

is common and positive serology is found in 30-65% worldwide. Negative serology makes diagnosis less likely. Click here to finish the question

Slide51

Question 7

Toxoplasma

serology is diagnostic in the presence of suggestive imaging.

True

False

CORRECT

Asymptomatic exposure to

toxoplasma

gondii

is common and positive serology is found in 30-65% worldwide. Negative serology makes diagnosis less likely.

Click here to finish the session

Slide52

Congratulations on completing this module and thank you for using NeuroID: elearning.We hope to see you at a NeuroID: Liverpool Neurological Infectious Diseases Course soon.Download a certificate and then to finish the session CLICK HERE.

Slide53

Liverpool Medical Institution, UK NeuroID : Liverpool Neurological Infectious Diseases CourseEver struggled with a patient with meningitis or encephalitis, and not known quite what to do?Then the Liverpool Neurological infectious Diseases Course is for you!For Trainees and Consultants in Adult and Paediatric Neurology, Infectious Diseases, Acute Medicine, Emergency Medicine and Medical Microbiology who want to update their knowledge, and improve their skills.

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