Le paludisme chez la femme enceinte

Atelier Paludisme IPM 2003

Le paludisme chez la femme enceinte

Elements de reflexions

Jambou R


At least 24 millionpregnancies are threatened each year in Africa and malaria causes up to 15 percent of maternal anaemiaand about 35 percent ofpreventable low birth-weight.

WHO

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)


(WHO 2001)

Paludisme et grossesse


Placental infection

Fœtal blood

Intervillous spaces( fibrine and parasites)

Syncicio-trophoblast(pigment in cells)


Classification of infections

1 uninfectedno 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)


Parasiteamia in blood / weight of birth

malefemale

Parasiteamia %

Weight

800

1200

1600

2000

2400

2800

3200

3600

4000

0,1 1,0 10,0 100,0 1000,0

700 delivering women 10% HRP2 positive placenta


Cl 1Cl 2Cl 3Cl 4

k-means cluster analysis of venous and placental parasiteamia

Venous blood

Plac

enta

-0,5

0,0

0,5

1,0

1,5

2,0

2,5

3,0

3,5

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


CLASSIFICATION

We

ightofbirth

1200

1600

2000

2400

2800

3200

3600

4000

1 2 3 4

CLASSIF

Haem

oglobin

5

7

9

11

13

15

17

1 2 3 4

AG

E14

18

22

26

30

34

38

42

46

1 2 3 4

CLASSIF

Num

berofpregnancy

-1

1

3

5

7

9

11

1 2 3 4

Non-Outlier MaxNon-Outlier Min75%

Median

25%

Pregnancy and Classification of the infection

1 uninfected2 chronic infection 3 chronic/active 4 recent infection

Atelier Paludisme IPM 2003(Contamin et al)

Typage des parasites


Placenta

Venous Blood

MSA2 3D7

0

2

4

6

8

10

12

14

16

<= 275 550 > 800

MSA1 MAD20

0123456789

10

<= 310 450 > 590

MSA2 FC27

0

1

2

3

4

5

6

7

8

9

10

<= 325 560> 800

MSA1 RO33

0

1

2

3

4

5

6

7

8

9

<= 310 460 > 610

MSA1 K1

0

1

2

3

4

5

6

7

<= 340 450> 635


Venous bloodplacenta

MSP1

Parasiteamia (blood)

Num

bero

f alle

les

-0,5

0,5

1,5

2,5

3,5

4,5

5,5

1 10 100

MSP 1 and MSP 2

MSP 1

MSP

2

-0,5

0,5

1,5

2,5

3,5

4,5

5,5

-1 0 1 2 3 4 5 6 7

No relation between polymorphism of MSA1 and MSA2

No relation between parasiteamia and polymorphism of MSA2 et MSA1.

MSP2

-0,5

0,5

1,5

2,5

3,5

4,5

5,5

1 10 100

Parasiteamia (blood)

Num

bero

f alle

les


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

4 alleles by woman2,1 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 identityaverage 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 RO332,2 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 blood60 % of women with different parasites in placenta and blood (by sub typing) average percent of common allele 11%.


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

Comparaison of the two populations - 2

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 polymorphismedes souches =>quelle signification ?


Pourquoi existe t il une infection locale

??


Méthodes d’étude


Différents mécanismes d’adhésion


(Craig et al)


Expression of Variant SurfaceAntigens by Plasmodium falciparum Parasites in the Peripheral Blood of ClinicallyImmune Pregnant Women Indicates Ongoing PlacentalInfection.

(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

Résistance émergeante = données incomplètes = dispensaires

Observance faible = lié au coût / motivation faible

1 ère CPN tardive = rarement avant le 2eme trimestre

Démarche actuelleProphylaxie par la Chloroquine = 300mg/ semRecouvrement des coûts

Les problèmes


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


Long rang Short rang (with children)

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

La grossesse augmente le nombre de piqûre

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


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

• selection of the currently available preventive toolschemoprophylaxis,intermittent treatment andinsecticide-impregnated bednets

=> determined by local conditions

•all women in endemic areas should receive haematinicsduring pregnancy

• current strategies may be less effective in HIV+ women

MIM conference


• appropriate tools are needed to monitor the effectiveness ofcurrent programmes

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

• monitoring the effectiveness of impregnated bednets indifferent endemic settings

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

MIM conference

Le paludisme chez la femme enceinte

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