monitoring congenital toxoplasmosis - escmid

Monitoring congenital toxoplasmosis

F. PeyronHôpital de la Croix Rousse

Lyon. FranceBertinoro 4/10/10 1

Infant from mother who seroconverted during pregnancy

2 situations

• -Ante and /or perinatal work up negative

• -Ante and /or perinatal work up positive

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Situation I

Ante and /or perinatal work up negative

>70 % of the cases

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Congenital toxoplasmosis

Severe malformations

Sub clinical forms ;Late onset of ocular

lesions

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At BirthA healthy looking baby born from

mother who seroconverted

Ante natal negative work-up

and

Perinital negative work-up

Do not rule out a congenital infection

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Healthy baby with negative work-up

• We can not rule out a congenital infection on the basis of a negative work-up.– sensitivity of perinatal test : 75%– Late maternal infection

How to know?

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How to know?

• One year of serological follow up

• Without treatment

Mandatory !Bertinoro 4/10/10 7

How to rule out a congenital infection?

1 year follow- up

Maternal IgGIn utero

IgG at birth Decreasing titers NegativationAt 1 year

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One year of serological follow-up

• Rhythm of sampling:

– Every month, 2 or 3 months ?

– Don’t harass the baby (and the mother)

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Do not stop folow-up before a negative serology

• Post natal serological troughNon infected infant

Maternal antibodies

Infected infant

1 year

Infected infant

BirthBertinoro 4/10/10 10

If serology is still positive at 1 year

• Congenital toxoplasmosis

• Benefit of starting treatment ?

• Funduscopy CT scan if no ultrasound at birth

• Follow up

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Situation II

Ante and /or perinatal work up positive

<30 % of the cases


Congenital Toxoplasmosis

Clinical presentation at birth

Asymptomatic in majority of cases


The classic triad

• Hydrocephalus

• Intracerebral calcifications

• Retinochoroiditis

Very rareBertinoro 4/10/10 14

Clinical presentation


16Bertinoro 4/10/10

Fœtal infectionIgM /IgAAt birth

Persisting IgG

Is he infected?Yes


II. Congenital toxoplasmosis

-Treatment


Treatment : 12 months

• Pyrimethamine1 mg / kg once daily months Sulfadiazine50 mg / kg / day twice dailyFolinic acid 50 mg every 7 days

• After 2 months :• Pyrimethamine1.25 mg / kg every 10 days

Sulphadoxine 25 mg / kg every 10 days Folinic acid 50 mg every 7 days



Post natal treatment :Reduction of sequellae

•Pyrimethamine+ sulfonamidesGiven 1 year to infected newborns

•Rational : unclear (long lasting parasitemia ?)

•No activity against cysts

1 year

? ?

Non consensus

Treatment efficacy


• On the outcome– No RCT– Available studies biased :

• Recruitment• Ante natal treatment effect• Age of pregnancy at maternal contamination• Length of follow-up

– Toscane study (year treatment versus 3 months)

II. Congenital toxoplasmosis

-Follow upAnd outcome


Evolution of serologyMind the traps!

Bertinoro 4/10/10 241year 2 years 4years 6 years

treatment

Chorioretinitis

negativation

rebound

An

tibo

dies


A healthy looking baby

-If brain ultrasonography is normal:

No neurologic sequelaeBertinoro 4/10/10 25


A healthy looking baby

will he develop ocular lesions?


Risk factors for retinochorioditisduring the first 2 years

• Delay of >8 weeks between maternal seroconversion and treatment onset

• Female gender

• Cerebral calcifications


Lyon cohort

• Early diagnosis and treatment

• Ophtalmogical follow-up:• every 3 months for the first 2 years• yearly thereafter



Lyon cohort2060 live born children

72 %not infected(negative serology)

22%

Infected7%

symptomatic

6 % lost to follow-

up

Mother to child transmission

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Outcome of congenital toxoplasmosis

• Ocular lesion (s) in 79 children (24 %)

• (Majority of them inactive when diagnosed)

• No bilateral visual impairment

Among 327 infected childrenMedian follow up 6 years (6 months-14 years)

30

Age at diagnosis of first retinal lesion

long term followlong term follow--up of 327 congenitally infected up of 327 congenitally infected childrenchildren


5 10210 age in year

50 %

58 % 76 %76 %95%95%

Importance of long term follow upImportance of long term follow up


Same cohort 6 years later

Findings at last ophthalmic examination

• 27 new ocular lesions19 peripheral

(maximum age of occurrence = 17 years)

• 4 new ocular events

• No bilateral visual impairment

median follow up = 11 years ( + 6 years)

• 71 % (232/327) of children: no lesions

• 18 % (60/327): retinochoroiditis only

• 11 %: neurological sign ± retinochoroiditis

• cranial calcifications: 31 children

• hydrocephalus: 6

• microcephalus: 1

Other manifestations of congenital toxoplasmosis


Reactivation of ocular toxoplasmosisduring pregnancy

• 18 women with ocular lesions (35 pregnancies)

• 7 recurences during pregnancy

• No congenital infections


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102 patients (different cohort)

• Enrolled at the beginning of the French program

• 42 ocular lesions (41.2%, biased)– 10 diagnosed between 10- 19

years– 12.7% reduced visual acuity – 11.8% at least one recurrence

• 11 intracranial calcifications

• Majority cope well

Follow-up >18 years

35

102 adults with congenital toxoplasmosis

• Age range : 18- 33 years

• Psychological General Well-Being Index (PGWBI)

• Visual functioning (VF14) questionnaire



Study cohort(n = 102)

General population (age-matched)

Mean Standard deviation Mean Standard deviation

Anxiety 71.2 19.3 72.2 19.6

Positive well-being

64.7 17.0 64.0 18.7

Vitality 64.7 15.2 68.0 18.5

Depressed mood

85.9 17.9 83.5 17.1

Self-control 80.7 16.0 82.5 17.2

General health

84.7 16.1 78.4 18.4

Global score 74.7 14.2 73.7 15.3

Quality of life

74.7 73.7

Quality of life in 102 adults with congenital toxoplasmosis

• VF14 (visual functional impairment)

• Score range 0-100

• Results : 97.3

• Localization of ocular lesion does not predict visual performance


Conclusion


In our settingParents and adolescents are told


that Congenital toxoplasmosis

• Is a chronic ophthalmologic disease

• which has an overall good prognosis

• But lasts all the life


• Well designed clinical trials (ante and post natal treatments)– 2 French studies

• Ante natal treatment • Post natal 3 months/12 months

What we urgently need

?

The biggest danger for the fetus is not T.gondii but mother’s anxiety

What ever you decide


-Educational programme

- Reference laboratory

- Well trained clinicians


monitoring congenital toxoplasmosis - escmid

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