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EMOP XII Turku/bo, Finland, 20-24 July, 2016 Parasites are forever

Prevention of congenital toxoplasmosis

Jean Dupouy-Camet
Accredited laboratory for diagnosis of congenital toxoplasmosis, Cochin Hospital,
Paris Descartes University France

Worldwide zoonosis with variable seroprevalence

> 60 % 40-60 % 20-40 % 10-20 % < 10 %

Pappas , 2009

Clinical patterns of infections during pregnancy

Most of the time asymptomatic in mothers in 75 % of ftus & newborns
treatment ?)

(prenatal

Sometimes symptomatic in mothers : flu or dengue-like syndrome, severe in ftus & newborns: retinitis,
hepatosplenomegaly, brain calcifications, hydrocephalus, foetal death

lymph nodes enlargement, blood monocytosis

Risk of infection increases with the pregnancy age but incidence of severe forms decreases
%

Average risk :

100 90 80 70 60 50 40 30 20 10 0 0 13 26 39 semaines de gestation Weeks of pregnancy

T. Ancelle, Parasitologie, Cochin Paris Descartes

Fetal infection : (29 %)

clinical signs

Daprs D.Dunn et coll . Lancet 1999;353:1829-33

hydrocephalus & calcifications at fetal echography :

brain calcifications

Chorioretinitis
- Can be diagnosed years after birth - Clinical signs & prognosis depend on inflammatory reaction and localization (blindness if macular)

Active lesion

Scar

Sources of infection during pregnancy in Europe

(Cook et al, 2000)

Contact with cats is not a risk factor !

Significant factors : Raw undercooked lamb Raw undercooked beef Raw other meat Contact with soil Travel outside Europe/US

OR OR OR OR OR

3.1 1.7 4.1 1.8 2.3

Social pressure to eat raw food in Europe !

Carpaccio

Raw foodism & new diets : instinctive eating, Paleolithic diet..

Meat consumption is not a risk factor in Egypt

Goats, sheeps & toxoplasmosis

Seroprevalence ranging from 33 to 50 % of goats & 95 to 100 % of sheeps in El Fayoum (Ghoneim et al. 2010) & positive PCR from blood Very few reports milk or cheese as source of human toxoplasmosis
Chiari CA, Neves DP 1984. Toxoplasmose humana adquirida atravs da ingesto de leite de cabra. Mem Inst Oswaldo Cruz 79: 337-340.

Very few studies on the survival of tachyzotes in goat milk !

Samples of goat milk spiked with small numbers of tachyzotes were positive for 3 days at 4 C, while samples of goat milk spiked with large numbers of tachyzotes were positive for 7 days at 4 C. (Journal of Eukaryotic Microbiology, 1999)

Prevention for toxoplasmosis

1.Primary prevention : hygienic rules
2.Secondary prevention : antibody screening, spiramycin, antenatal & neonatal diagnosis

3.Tertiary prevention : antenatal and post natal treatment

Teaching hygienic rules is not easy !

Information given by books or magazine 16 fold risk reduction

Information given by physicians 6 fold risk reduction (NS)

Written information 14 fold risk reduction Oral information 6 fold risk reduction (NS)
BEH n16 (16 avril 1996

French official hygienic rules

Complicated

Difficult to read
Illustrate only gardening !

Primary prevention in the NY Times

Primary prevention in the NY Times Some rules are lacking : raw vegetables, gardening !! Contaminated meat not very clear: contaminated by cats ? raw meat is not mentioned..

The French programme

Implemented 30 years ago by Desmonts, Chevallier, Garin, Couvreur
Observation of numerous congenital cases (no precise baseline data) Based at first on serologic surveillance & spiramycin

Prevention program in the law

1978: mandatory Toxoplasma serology for the medical certificate before wedding
1983: hygienic rules given to unprotected women during pregnancy 1985: mandatory Toxoplasma serology at the first prenatal medical exam 1992: mandatory monthly Toxoplasma serology for non protected pregnant women 2006: National reference Center (Reims, Pr I Villena)

Seroconversion during pregnancy

Treatment by spiramycin (prevents
transplacental passage ?)

9M IU tid

Prenatal diagnosis
At least 4 weeks after infection At least after 16 weeks of pregnancy

Prenatal diagnosis on amniotic fluid

Positive Negative

sulfadiazinpyrimetamine or sulfadoxinpyrimetamine

Echography every month

If severe lesions

spiramycin

Pregnancy interruption At birth : clinical examination, serology, echography

Prenatal diagnosis by PCR on amniotic fluid

First results published by our lab in 1990 & 1992 targeting P30 gene Our results in 1999

1992

1990

Neonatal diagnosis
Clinical examination of the newborn Fundus examination Transfontanellar echography

Serology
Evolution of antibodies for 12 months OR Comparative WB

Neonatal diagnosis : Comparative WB

N M N M N M N

positive neonatal diagnosis

negative neonatal diagnosis

Infected new born

Treatment : sulfadoxine pyrimethamine or sulfadiazine pyremethamine during at least 12 months + folinic acid Blood cells counts every month Eye examination every 3 months

Evaluation of the French program

No snap shot of the epidemiological situation at onset of the program 30 years ago
Difficult(impossible ?) to evaluate the impact of the program

Still more than 1000 cases of congenital toxoplasmosis in France (2007-2010)

Report of the NRC

Of which : - 72 ftal deaths, stillbirth & abortions - 29 severe cases (hydrocephalus, retinitis)
-Around 300 cases for 800 000 births/year

A discussed effectiveness of the prenatal treatment

SYROCOT Thiebaut R, Leproust S, Chene G, Gilbert R. Lancet. 2007 Jan 13;369(9556):115-22.

Analysis of 26 cohorts
1438 treated mothers :
weak evidence that spiramycin started within 3 weeks of seroconversion reduced mother-tochild transmission compared with treatment started after 8 or more weeks

550 infected live born infants:

no evidence that prenatal treatment significantly reduced the risk of clinical manifestations

No major incidence of the type of screening on the delay of detection of ocular toxoplasmosis Freeman, K. et al. 2008

Monthly screening : France Every 3 months : Italy, Austria Neonatal : Poland, Scandinavia

However, for some authors, congenital toxoplasmosis should be diagnosed and treated early during pregnancy

Prenatal treatment decreases severe sequelae incidence from 20 to 3.5 %

Conclusions
Is there still a need for screening congenital toxoplasmosis ?

Incidence of some screened congenital diseases (France)

Disease
Incidence / 1000 births

Congenital Toxoplasmosis
Moderate & severe forms

Severe forms

Rubella Congenital syphilis Phenylketonuria* Surrenal hyperplasia* Cystic fibrosis* Hypothyroidism*

*From Ardaillou & Le Gall, 2007,

0.4 0.05 0.02 0 0.008 0.06 0.06 0.25 0.3

Perel et al, 2011, Villena et al, 2010

A 48% seroprevalence in pregnant women (Alexandria)

Estimated number of cases of congenital toxoplasmosis in Egypt

pregnancies / year Ab prevalence : population at risk : contamination : estimated fetal transmission : 48 % 52 % 0.3 % 30 % 1. 04 millions 3100 2 millions

> 1000 estimated cases/year

Conclusions
Is there still a need for screening congenital toxoplasmosis ? YES
There is a cost : a choice of society

Annual cost of the French program : 100 millions $

Prevention of costs

Costs of congenital defects

Costs in US of congenital defects
(Stillwaggon et al., 2011): Fetal death Mild visual defect Severe visual defect Mild cognitive defect Severe cognitive defect 7 M $ 0.5 M $ 1 M $ 1 M $ 2.7 M $

Costs for the whole life of a severely disabled person > 4 M $

Costs could be reduced by a minimum program

A. Hygienic rules if seronegativity when pregnancy is identified
B. Repeated echographies at regular intervals (termination if severe lesions) ethics, religion

C. Neonatal screening & treatment of infected newborns (1 year)

Options ? : A or B or C, A+ B, A + C, A+ B + C

From the ethical and medical point of view : prevention seems compulsory

Buteconomical pressurecrisis !

A 48% seroprevalence in pregnant women (Menoufia)

Seroprevalence ranging from 42 to 48 % in pregnant women (El Fayoum)