Malaria therapy, experimental, and epidemiological studies have shown that erythrocyte Duffy blood group-negative people, largely of African ancestry, are resistant to erythrocyte Plasmodium vivax infection. These findings established a paradigm that the Duffy antigen is required for P. vivax erythrocyte invasion. P. vivax is endemic in Madagascar, where admixture of Duffy-negative and Duffy-positive populations of diverse ethnic backgrounds has occurred over 2 millennia. There, we investigated susceptibility to P. vivax blood-stage infection and disease in association with Duffy blood group polymorphism. Duffy blood group genotyping identified 72% Duffy-negative individuals (FY*B ES /*B ES ) in community surveys conducted at eight sentinel sites. Flow cytometry and adsorption-elution results confirmed the absence of Duffy antigen expression on Duffy-negative erythrocytes. P. vivax PCR positivity was observed in 8.8% (42/476) of asymptomatic Duffy-negative people. Clinical vivax malaria was identified in Duffy-negative subjects with nine P. vivax monoinfections and eight mixed Plasmodium species infections that included P. vivax (4.9 and 4.4% of 183 participants, respectively). Microscopy examination of blood smears confirmed blood-stage development of P. vivax, including gametocytes. Genotyping of polymorphic surface and microsatellite markers suggested that multiple P. vivax strains were infecting Duffy-negative people. In Madagascar, P. vivax has broken through its dependence on the Duffy antigen for establishing human blood-stage infection and disease. Further studies are necessary to identify the parasite and host molecules that enable this Duffyindependent P. vivax invasion of human erythrocytes.erythrocyte | evolution | DARC | Madagascar

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The three GYPB-E-B hybrid genes reported here constitute the first evidence of recombination events between GYPB and GYPE. As these GYPB-E-B hybrid genes drive the S-s- blood phenotype, it is important to know they are a limitation for the current blood group genotyping methods, including those performed by commercial platforms.

Summary:Parasite loads o f different tissues w ere assessed in guinea pig foetus after maternal infection. Twelve fem ale guinea pigs w ere infected w ith 1 0 0 cysts o f the 7 6 K strain o f Toxoplasma g o n d ii by the oral route. Inoculation w as performed 2 0 ± 5 days (G 2 0) or 4 0 ± 5 days (G 4 0) after the beginning o f gestation. G estational a g e w as determined by progesterone assay. M aternal and foetal organ samples w ere taken 6 0 days after the beginning of gestation. Parasite loads (from placenta, am niotic fluid (AF), cord blood (CB), foetal brain, liver, lung and spleen) w ere assessed by a real-time PCR quantification using fluorescence resonance energy transfer (FRET) hybridization probes on the Light C ycler®. C ongenital transmission w as proven by the presence of parasites in blood or tissue samples o f the foetus in 8 4 .6 % ( 1 1 /1 3 ) and 1 0 0 % ( 1 6 /1 6 ) o f cases after inoculation on G 2 0 and G 4 0 , respectively. The quantitative analysis o f our results after inoculation at G 2 0 and G 4 0 has allo w e d us to determinate the positive parasitic loads as a function o f the origin o f the sample and the period of inoculation. The parasite loads expressed as log (p a ra site /g ) w ere low in AF and CB samples: 1 .4 9 ± 0 .5 0 and 1 .0 5 ± 0 .1 0 at G 2 0 and 1.21 ± 0 .3 6 and 1 .2 0 ± 0 .4 2 at G 4 0 respectively. In contrast the placenta and the different foetal tissues had higher parasite burdens: 2 .8 9 ± 0 .5 4 to 5 .3 0 ± 0 .5 1 at G 2 0 and 2 .8 1 ± 0 .7 1 to 3 .6 5 ± 0 .5 9 at G 4 0 . All the placentae w ere positive for parasites even in the tw o cases with no proven transmission. Real time quantitative PCR using the hybridization probe w as a very sensitive and reproducible technique to study the kinetics o f congenital toxoplasmosis in the guinea pig model w ich is close to that o f humans.KEY WORDS : congenital toxoplasmosis, parasite load, guinea-pig, real-time PCR.R ésu m é : D é t e r m in a t io n p a r PCR q u a n t it a t iv e en t e m p s r é el d e la c h a r g e t o x o p l a s m iq u e d e t is s u s d e f oe t u s d e c o b a y e s a p r è s in f e s t a t io n m a t er n e l l e Les charges toxoplasmiques de différents tissus de foetus de cobaye ont été déterminées après infestation maternelle. Douze cobayes gestantes ont été infestées avec 100 kystes de la souche 7 6 K pa r voie orale. C ette infestation a eu lieu après le début de la gestation soit à 2 0 jours (± 5 ) (G20), soit à 4 0 jours (± 5 ) (G 4 0 ) de gestation. Le prélèvement des organes foetaux a été effectué à 6 0 jours de gestation (G 6 0 ) soit cinq jours avant terme. Les charges parasitaires (Placenta, liquide amniotique (L A ), sang de cordon (SC), foie, cerveau, poumon, et rate) ont été déterminées pa r PCR quantitative en temps réel (technique Sonde-sonde) sur Light-Cycler®. L'analyse qualitative de nos résultats nous a permis d'affirmer une transmission maternofoe tale (organes foetaux e t/o u sang de INTRODUCTION_____ ______

Background Red blood cell alloimmunization is the first cause of fetal and neonatal anemia. Alloimmunizations with anti‐PP1Pk or anti‐P can cause recurrent miscarriages and hemolytic disease of the fetus and newborn in the 2nd and 3rd trimesters of pregnancy. We report on a pregnant patient immunized with anti‐P and a history of recurrent miscarriages. Case Report This P2k (GLOB:‐1; P1PK:‐1,3) patient had a first pregnancy marked by a caesarean at 38 weeks of gestation (WG) for non‐reassuring fetal heart rate. Then, she had three early spontaneous miscarriages. The fifth pregnancy began with a high titer of anti‐P at 128. Early initiation of treatment with Intravenous Immunoglobulins (IVIg) and plasma exchanges (PE) starting at 5 WG permitted us to reduce the titer of anti‐P below 32. A healthy infant was delivered by caesarean at 38 WG without anemia at birth and no exchange transfusion was required. Discussion and Review of the Literature The P and Pk antigens are expressed on placental, trophoblastic, and embryonic cells. This explains why P1k (GLOB:‐1; P1PK:1,3), P2k (GLOB:‐1; P1PK:‐1,3), or Tj(a‐)/p (GLOB:‐1; P1PK:‐1,‐3) patients are prone to recurrent abortions in the first trimester of pregnancy. A literature review demonstrated 87% (68/78) of miscarriages in p patients. However, publication biases are possible with the most severe cases being reported. Conclusion Immunizations to P and PP1Pk antigens differ from others in their physiopathology and precocity. The association of PE and IVIg seems to be an effective treatment in the management of anti‐PP1Pk or anti‐P fetomaternal incompatibilities.