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Egyptian society of Parasitologists United: new associated member of

the EFP

Hundreds of members affiliated through > 30 national societies

• EFP promotes exchange of knowledge & research

• EFP holds EMOP conferences every 4 years– Awards Young

Scientists in "Basic Parasitology" & “Applied Parasitology“

– Scholarships to cover registration fees for young parasitologists

http://europfedpar.monsite-orange.fr/

European Federation of Parasitologists

Newsletter

EMOP XII Turku/Åbo, Finland, 20-24 July, 2016

“Parasites are forever”

Prevention of congenital

toxoplasmosis

Jean Dupouy-CametAccredited laboratory for diagnosis of

congenital toxoplasmosis, Cochin Hospital, Paris Descartes University

France

Pappas , 2009

> 60 %

40-60 %

20-40 %

10-20 %

< 10 %

Worldwide zoonosis with variable seroprevalence

• Most of the time asymptomatic– in mothers– in 75 % of fœtus & newborns (prenatal treatment ?)

• Sometimes symptomatic– in mothers : flu or dengue-like syndrome, lymph

nodes enlargement, blood monocytosis

– severe in fœtus & newborns: retinitis, hepatosplenomegaly, brain calcifications, hydrocephalus, foetal death…

Clinical patterns of infections during

pregnancy

T. Ancelle, Parasitologie, Cochin Paris Descartes

Risk of infection increases with the pregnancy age but incidence of severe

forms decreases

0

10

20

30

40

50

60

70

80

90

100

0 13 26 39

semaines de gestation

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

Average risk :

Fetal infection : (29 %)

%

clinical signs

Weeks of pregnancy

brain calcifications

hydrocephalus & calcifications at fetal echography :

- Can be diagnosed years after birth

- Clinical signs & prognosis depend on inflammatory reaction and localization (blindness if macular)

Chorioretinitis

Active lesion Scar

Contact with cats is not a risk factor !

Significant factors :•Raw undercooked lamb OR 3.1•Raw undercooked beef OR 1.7•Raw other meat OR 4.1•Contact with soil OR 1.8 •Travel outside Europe/US OR 2.3

Sources of infection during pregnancy in Europe

(Cook et al, 2000)

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 através da ingestão de leite de cabra. Mem Inst Oswaldo Cruz 79: 337-340.

Very few studies on the survival of tachyzoïtes in

goat milk !

• Samples of goat milk spiked with small numbers of tachyzoïtes were positive for 3 days at 4° C, while samples of goat milk spiked with large numbers of tachyzoïtes 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 n°16 (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

If severe lesions

At birth : clinical examination, serology, echography

Pregnancy interruptio

n

Echography every month spiramycin

sulfadiazin-pyrimetami

ne or

sulfadoxin-pyrimetami

ne

Prenatal diagnosis by PCR on amniotic fluid

19921990

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

Our results in 1999

• Clinical examination of the newborn• Fundus examination

• Transfontanellar echography

• Serology– Evolution of antibodies for 12 months– OR Comparative WB

Neonatal diagnosis

Neonatal diagnosis : Comparative WB M 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

Of which :- 72 fœtal deaths,

stillbirth & abortions- 29 severe cases

(hydrocephalus, retinitis…)

-Around 300 cases for 800 000 births/year

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

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-to-child 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 ?

Disease Incidence / 1000 births

Congenital Toxoplasmosis 0.4 Moderate & severe forms 0.05 Severe forms 0.02

Rubella 0

Congenital syphilis 0.008

Phenylketonuria* 0.06

Surrenal hyperplasia* 0.06

Cystic fibrosis* 0.25

Hypothyroidism* 0.3

*From Ardaillou & Le Gall, 2007, Perel et al, 2011, Villena et al, 2010

Incidence of some screened congenital diseases (France)

A 48% seroprevalence in pregnant women (Alexandria)

Estimated number of cases of congenital toxoplasmosis in

Egyptpregnancies / year 2 millions

population at risk : 52 % 1. 04 millions

Ab prevalence : 48 %

contamination : 0.3 % 3100

estimated fetal transmission : 30 %

> 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 7 M $– Mild visual defect 0.5 M $– Severe visual defect 1 M $– Mild cognitive defect 1 M $– Severe cognitive defect 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

But…economical pressure…crisis !

A 48% seroprevalence in pregnant women (Menoufia)

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