Le paludisme chez la femme enceinte

Le paludisme chez la femme enceinte

Elements de reflexions

Jambou R

Atelier Paludisme IPM 2003

WHO
At least 24 million
pregnancies are threatened
each year in Africa and
malaria causes up to 15
percent of maternal anaemia
and about 35 percent of
preventable low birth-weight.

Malaria attack

Placental infection


Paludisme et grossesse

La grossesse induit une augmentation du nombre d’accès
Jusqu’à deux mois après l’accouchement
=> Projet Dielmo

(Niagne et al)


Paludisme et grossesse

(WHO 2001)

Placental infection

Intervillous spaces
( fibrine and parasites)

Syncicio-trophoblast Fœtal blood
(pigment in cells)


Classification of infections

1 uninfected
no pigment no parasite

2 chronic infection
only pigment in cells or villosities

3 chronic – active infection
parasites + pigment in cells or in tissu

4 recent infection
Parasites in intervillous spaces without pigment or fibrine

(Blumer et al )


Quel est le poids du paludisme chez les femmes enceintes

en zone urbaine ??

Projet d’étude – Dakar 2000 (AdS) / 2003 (FSP)


Area of study


Population studied

Guediawaye- Dakar
Suburb of Dakar - population 600 000 inhabitants
low and seasonal transmission of malaria around water collections (Niayes)
exchange of populations with the rural areas

omen attending the maternity “Roi Baudoin” of Guediawaye for delivery

-from July to December

- Living in the periphery of Dakar

- no travel declared the two months prior to the delivery

- placental infestation (positive detection of HRP II antigen in the
placental blood)

700 delivering women 10% HRP2 positive placenta

Parasiteamia in blood / weight of birth
4000

3600

3200
Weight

2800

2400

2000

1600

1200

male
800
0,1 1,0 10,0 100,0 1000,0 female

Parasiteamia %

k-means cluster analysis of venous and placental parasiteamia

3,5

3,0

2,5

2,0

1,5
Placenta

1,0

0,5

Cl 1
0,0
Cl 2
Cl 3
-0,5
-0,4 0,2 0,8 1,4 2,0 2,6 3,2 Cl 4

Venous blood


Pregnancy and Classification of the infection
17
4000

15
3600

Weight of birth

Haemoglobin
3200 13

2800
11

2400

9
2000

7
1600

Non-Outlier Max
1200
1 2 3 4
Non-Outlier Min 5
1 2 3 4
CLASSIFICATION
75% 25% CLASSIF

Median 11
46

42 9

Number of pregnancy
38
7

34
AGE

5
30

26 3

22
1 uninfected
2 chronic infection 1
18 3 chronic/active
14
4 recent infection -1
1 2 3 4 1 2 3 4
CLASSIF


Typage des parasites

(Contamin et al)

10
16 9
MSA2 3D7 MSA1 MAD20
14 8
7
12
6
10 5
8 4
3
6
2
4 1
2 0
<= 310 450 > 590
0
<= 275 550 > 800
9

8
10
7
MSA1 RO33
9
6
8 MSA2 FC27
5
7
4
6
3
5
2
4
1
3
0
2 <= 310 460 > 610

1

0 7
<= 325 560
> 800
6
MSA1 K1

5

4

3
Placenta
2

1

Venous Blood 0
<= 340 450
> 635


MSP1 MSP 1 and MSP 2
5,5
5,5
Number of alleles

4,5
4,5
3,5
3,5
2,5
2,5
1,5

MSP 2
1,5
0,5
0,5
-0,5
1 10 100
Parasiteamia (blood) -0,5
-1 0 1 2 3 4 5 6 7

Venous blood MSP 1
MSP2
placenta
5,5
Number of alleles

4,5
No relation between polymorphism of MSA1
3,5
and MSA2
2,5

1,5 No relation between parasiteamia and
polymorphism of MSA2 et MSA1.
0,5

-0,5
1 10 100
Parasiteamia (blood) Atelier Paludisme IPM 2003

Comparaison of the two populations - 1
Size of MSA2 1+2 = from 719 to 992 bp.
FC29 (52,85 %) of parasites

4 alleles by woman
2,1 alleles by venous sample (1.3 alleles for FC29 and 0.8 for 3D7)

54 % of women with different parasites in placenta and blood (by sub typing)
20 % of women with only 50 % of identity
average percent of common allele 14 %.

Size of the product MSA1 A+B = from 349 to 687 bp
RO33 42,86 % of parasites

4,9 alleles by woman (max 8 alleles)
2,6 allele by placenta (max 5) : 0.8 for K1 and MAD20 and 0.9 for RO33
2,2 alleles by venous sample (max 5) : 0.6 for K1 and MAD20 and 1 for RO33

62 % of identity between MSA1 A+B products in the placenta and in the blood
60 % of women with different parasites in placenta and blood (by sub typing)
average percent of common allele 11%.

Comparaison of the two populations - 2

Correlation between polymorphism of MSA1 in the blood and in the placenta

The number of allele of MSA1 increase in the placenta with the number of pregnancy

The percent of common allele of MSA1 between blood and placenta increase
with the number of pregnancy

No correlation between the total number of alleles of MSA1 or MSA2 and
-the type of placental infection
-the use of chemoprophylaxis
-the number of pregancy
-the age of the mother

Amplification of PfCRT :
- 62 out of 71 placentas 82,5 of mutation in codon CRT76
- 54 out of 71 venous sample = 85,7% of mutation in codon CRT76

For 51 women with positive amplification in blood and in the placenta
11,7% had none similar codon

1 Infection locale du placenta

2 pas de relation entre
densité parasitaire sur le
syncico-troph et le poids de
naissance

3 très grand polymorphisme
des souches =>
quelle signification ?


Pourquoi existe t il une infection locale

??


Méthodes d’étude


Différents mécanismes d’adhésion


(Craig et al)


Expression of Variant Surface
Antigens by Plasmodium
falciparum Parasites in the
Peripheral Blood of Clinically
Immune Pregnant Women
Indicates Ongoing Placental
Infection.
(Ofori MF, et al)


Que faire en Pratique ??

1 Développer un vaccin contre l’infection locale ?


unstimulated stimulated


Quel(s) gène(s) Var pour les parasites placentaires



1 Développer un vaccin ?

2 Prophylaxie et Traitement intermittent ?


Prophylaxie

Démarche actuelle
Prophylaxie par la Chloroquine = 300mg/ sem
Recouvrement des coûts

Les problèmes

1 ère CPN tardive = rarement avant le 2eme trimestre

Observance faible = lié au coût / motivation faible

Résistance émergeante = données incomplètes = dispensaires


Les traitements intermittents

Etude du Malawi (depuis 1993)
infection placentaire : 32 % à 23 %
Faible poids de naissance : 23% à 10%.

Proposition : traitement systématique par SP lors des CPN

Problème : résistance rapide à la SP artésunate





3 Protéger contre les vecteurs


La grossesse augmente le nombre de piqûre

Long rang Short rang (with children)

(Lindsay S et al) (Ansell J et al)

Problème = à quelle heure piquent les moustiques ???





3 Protéger contre les vecteurs

4 prendre en charge les carences (fer-folates)
Interaction avec les anti-folates ??

5 Améliorer la prise en charge de l’accouchement


MIM conference

•case management alone is not effective in preventing the
adverse effects of malaria

• selection of the currently available preventive tools
chemoprophylaxis,
intermittent treatment and
insecticide-impregnated bednets
=> determined by local conditions

•all women in endemic areas should receive haematinics
during pregnancy

• current strategies may be less effective in HIV+ women


MIM conference

• appropriate tools are needed to monitor the effectiveness of
current programmes

• new methods are needed to improve the implementation and
compliance with control strategies

• monitoring the effectiveness of impregnated bednets in
different endemic settings

• the cost-effectiveness of interventions in different settings
needs to be assessed


Le paludisme chez la femme enceinte

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