Vivax malaria in Mauritania includes infection of a Duffy-negative individual

  • Nathalie Wurtz1, 2Email author,

    Affiliated with

    • Khadijetou Mint Lekweiry3, 4, 5,

      Affiliated with

      • Hervé Bogreau1, 2,

        Affiliated with

        • Bruno Pradines1, 2,

          Affiliated with

          • Christophe Rogier1, 2, 6,

            Affiliated with

            • Ali Ould Mohamed Salem Boukhary3,

              Affiliated with

              • Jamal Eddine Hafid4,

                Affiliated with

                • Mohamed Salem Ould Ahmedou Salem3,

                  Affiliated with

                  • Jean-François Trape2, 7,

                    Affiliated with

                    • Leonardo K Basco1, 2 and

                      Affiliated with

                      • Sébastien Briolant1, 2

                        Affiliated with

                        Malaria Journal201110:336

                        DOI: 10.1186/1475-2875-10-336

                        Received: 19 September 2011

                        Accepted: 3 November 2011

                        Published: 3 November 2011

                        Abstract

                        Background

                        Duffy blood group polymorphisms are important in areas where Plasmodium vivax is present because this surface antigen is thought to act as a key receptor for this parasite. In the present study, Duffy blood group genotyping was performed in febrile uninfected and P. vivax-infected patients living in the city of Nouakchott, Mauritania.

                        Methods

                        Plasmodium vivax was identified by real-time PCR. The Duffy blood group genotypes were determined by standard PCR followed by sequencing of the promoter region and exon 2 of the Duffy gene in 277 febrile individuals. Fisher's exact test was performed in order to assess the significance of variables.

                        Results

                        In the Moorish population, a high frequency of the FYB ES /FYB ES genotype was observed in uninfected individuals (27.8%), whereas no P. vivax-infected patient had this genotype. This was followed by a high level of FYA/FYB, FYB/FYB, FYB/FYB ES and FYA/FYB ES genotype frequencies, both in the P. vivax-infected and uninfected patients. In other ethnic groups (Poular, Soninke, Wolof), only the FYB ES /FYB ES genotype was found in uninfected patients, whereas the FYA/FYB ES genotype was observed in two P. vivax-infected patients. In addition, one patient belonging to the Wolof ethnic group presented the FYB ES /FYB ES genotype and was infected by P. vivax.

                        Conclusions

                        This study presents the Duffy blood group polymorphisms in Nouakchott City and demonstrates that in Mauritania, P. vivax is able to infect Duffy-negative patients. Further studies are necessary to identify the process that enables this Duffy-independent P. vivax invasion of human red blood cells.

                        Keywords

                        Plasmodium vivax Duffy blood group Mauritania polymorphism malaria

                        Background

                        Malaria remains one of the most important parasitic infections in the world, with almost 225 million cases of infection and 0.78 million deaths in 2009, mainly in Africa, Asia and South America [1]. It is caused by infection with one or more of five species of Plasmodium parasites. Plasmodium vivax is the second most common cause of malaria in the world after Plasmodium falciparum, with more than 80 million clinical cases annually. Unlike P. falciparum, P. vivax rarely causes mortality, but it can potentially lead to severe complications and is thereby responsible for considerable morbidity and economic loss in endemic countries [[28]]. Moreover, P. vivax has a wider geographical range, potentially exposing more people to risk of infection (2.85 billion across three continents) [[911]], and it is more difficult to control because of the hypnozoïte forms of the parasite [12, 13]. The presence of P. vivax in Mauritania was first reported in 1948 [14]. More recently, several studies conducted in Nouakchott, the capital of Mauritania, revealed a high proportion of P. vivax, followed by Plasmodium ovale and P. falciparum; autochthonous malaria cases exist but are relatively uncommon [[1517]]. In 2009-2010, the prevalence of P. vivax among malaria in children in Nouakchott represented 97.1% [18].

                        One of the main biological differences between P. vivax and other human malaria parasites is that only P. vivax merozoites use the human Duffy antigen/chemokine receptor (DARC) to invade red blood cells (RBCs) [[1921]]. The Duffy antigen was originally identified as a blood group antigen on the surface of RBCs, but it has since been found to be expressed in endothelial cells and neurons [[2224]]. It is implicated in multiple chemokine inflammation, inflammatory diseases, and cancer and might play a role in HIV infection [[2527]]. The DARC gene (also referred to as FY or Duffy), located on chromosome 1, comprises two exons and produces a protein that has a glycosylated external N-terminal domain, seven transmembrane domains and a short cytosolic C-terminal domain that is not coupled to G-proteins or other known intracellular effectors [[2833]].

                        DARC has two main variant forms, Fya and Fyb antigens, which differ by a single amino acid (Gly42Asp) in the NH2 extracellular domain of the polypeptide and are encoded by the alleles FYA and FYB, respectively, which are differentiated by a single base substitution (G125A) [[3436]]. The FYA/FYB frequency shows marked geographic disparities; the FYB allele is highly predominant in Africa, while the FYA allele is dominant in Asia [37]. The Duffy blood group has four major phenotypes: Fy(a+b+), Fy(a+b-), Fy(a-b+) and Fy(a-b-). Duffy expression is disrupted by a T to C substitution in the gene's promoter region at nucleotide -33, preventing the binding of the h-GATA-1 erythroid transcription factor and resulting in the null expression of the Duffy gene in erythroid cells only [[3840]]. This variant is commonly associated with the FYB allele (corresponding to the FYB ES allele, ES stands for "erythroid silent"), although the same mutation has been detected and associated with the FYA allele in individuals living in P. vivax-endemic region of Papua New Guinea (FYA ES ) [41]. The FYB ES allele is almost fixed in West and Central Africa, and as a consequence, the Fy(a-b-) (null) phenotype is predominant among populations of West and Central African descent. This phenotype is rare among Caucasian, Amerindian, Indian and Asian populations. The FYA ES mutation is rare and so far appears to be present only in the Melanesian and Tunisian population) [[4144]]. Other rare variants have been described, most notably the FYX allele, which occurs mainly in Caucasians [45, 46] and is characterized by a weak expression of Fyb antigen (Fybweak).

                        Some authors [[4750]] have attributed the FYX allele to a single polymorphism of the FYB allele (C265T→Arg89Cys) (FYX1), while others have indicated two (C265T and G298A→Ala100Thr) (FYX2) [[5153]] or even three polymorphisms (C265T, G298A and G145T→ Ala49Ser) (FYX3) [54]. The point mutation G298A alone did not cause a decrease of the Fyb expression [47]. This allele is also named FYB* in the present study. Eight combinations of alleles (FYA, FYB, FYB*, FYX [FYX1, FYX2 and FYX3], FYA ES and FYB ES ) result in 32 different genotypes (Additional files 1 and 2).

                        Malaria therapy, as well as experimental and epidemiological studies, have shown that erythrocyte Duffy blood group negative individuals, mostly of African ancestry, are resistant to P. vivax infection [21]. However, several reports have provided evidence for P. vivax infections among Duffy-negative patients [[5559]], suggesting that there are P. vivax strains that have acquired a Duffy-independent mechanism of erythrocyte invasion. Little is known about the frequency of Duffy polymorphisms in Mauritanian populations, especially in P. vivax-infected individuals. The objective of the present study was to evaluate the Duffy blood group allelic and genotype frequencies in the city of Nouakchott and to compare these frequencies between P. vivax-infected and uninfected febrile patients.

                        Methods

                        Study populations

                        This study was conducted in the capital and largest city of Mauritania, Nouakchott, which is located on the Atlantic coast of the Sahara Desert (18°.11'N; 16°.16'W). The city is divided into nine districts and consists of approximately 800,000 inhabitants. Nouakchott features an arid climate with a short wet season extending from July to September. The city has five hospitals and eleven health centres. Between 2007 and 2009, Lekweiry et al conducted a preliminary study on the incidence of malaria in Nouakchott [17].

                        Capillary blood samples from 439 febrile outpatients from all Nouakchott districts who were seen in the two main hospitals of the city (National Hospital and Chiekh Zayed Hospital) and in the District Health Center of Teyarett were collected onto Whatman 3 MM filter paper. A subset of 277 patients were enrolled in this study to evaluate Duffy blood group. Of these 277 patients, 110 had a positive P. vivax diagnosis and 167 were not infected with Plasmodium but their individual data on the place of residence and/or ethnic group membership were available.

                        Consent

                        This study was reviewed and approved by the Mauritanian National Ethics Committee.

                        Genomic DNA extraction

                        Blood samples were spotted onto Whatman 3 MM filter paper, dried, and stored at room temperature until use. DNA was extracted with the MagMAX™-96 DNA Multi-Sample Kit according to the manufacturer's instructions using a MagMAX™ Express-96 Magnetic Particle Processor (Applied Biosystems, Courtaboeuf, France).

                        Identification of Plasmodium species by real-time PCR

                        Plasmodium detection was performed by real-time LightCycler® PCR (Roche, Meylan, France). The following oligonucleotides primers and probes designed with Primer Express software v2.0 (Applied Biosystems) were used: forward-5'-TTTATGTATTGGTATAACATTCGG-3', reverse-5'-GGCAAATAACTTTATCATAGAATTGAC-3' and probe-5'-FAM- TACACTACCAACACATGGGGCTACAAGAGGT-BBQ-3' for P. falciparum aquaglyceroporin gene (AJ413249); forward-5'-GTGGCCGCCTTTTTGCT-3', reverse-5'-CCTCCCTGAAACAAGTCATCG-3' and probe-5'-HEX- CATCTACGTGGACAACGGGCTCAACA-BHQ1-3' for P. vivax enoyl-acyl carrier protein reductase gene (AY423076); forward- 5'-GAGGAATGGTCACCATGTAGTGT-3', reverse-5'-CAAATTTCAGTTTCAAGGTCACTTAA-3' and probe-5'-HEX- ATTTTTTGCATCAACCTTTCTTCTAGCCC -BHQ1-3' for Plasmodium malariae circumsporozoïte gene (S69014); and forward-5'-CCAAGCCCAGATAATAAGGAAGGT3', reverse-5'-TTCGTGCACTTCAACTTACATTCAGT-3' and probe-5'-FAM-TTATTGTCCTCTGGGTTTGGAACTTTGCC-BBQ-3' for P. ovale P25 ookinete surface protein gene (AB074973) (Eurogentec, Angers, France). Each parasite species was detected separately. Individual PCR amplifications were carried out using 4 μl of 5× concentrate Master Mix (LightCycler® TaqMan® Master, Roche), 0.8 μM of each primer, 0.1 μM of probe and 5 μL of template DNA in a final volume of 20 μL. The thermal cycling conditions were 95°C for 10 min and 45 cycles of 95°C for 10 sec and 60°C for 30 sec, followed by a cooling step of 40°C for 30 sec. For each PCR run, two negative controls (water and human DNA) and a positive control (DNA from each species) were used. Fluorescence acquisition was performed at the end of each extension step.

                        Duffy blood group genotyping

                        Duffy blood group genotypes were assessed using PCR amplification of the human Duffy antigen/chemokine receptor gene (NG_011626.1) followed by sequencing. The promoter region that flanks the GATA box motif (a fragment of 392 bp) was amplified using the following primers, which were designed with the NCBI/Primer-BLAST online tool [60]:

                        forward-5'-CCCAAGGCCAGTGACCCCCATA-3' and reverse-5'-AGAGGGAGCTAGGAGGCTAGCAT-3' (Eurogentec). To determine the Duffy RBC polymorphism, a 541-bp fragment spanning part of intron and exon 2 was amplified using the following primers (also designed with the NCBI/Primer-Blast online tool [60]): forward-5'-CCTGCAGAGACCTTGTTCTCCCAC-3' and reverse-5'-AGCAGCAAAGCCTGGGCAAAGG-3' (Eurogentec).

                        The reaction mixture for both PCR amplifications included 10 μl of genomic DNA, 2.5 μl of 10× reaction buffer (Eurogentec), 0.5 μM of each primer, 200 μM of deoxynucleoside triphosphate mixture (dGTP, dATP, dTTP and dCTP) (Euromedex, Souffelweyersheim, France), 1.5 mM of MgCl2 and 2.5 units of RedGoldStar® DNA polymerase (Eurogentec) in a final volume of 25 μL. The thermal cycler (T3 Biometra, Archamps, France) was programmed as follows: an initial 94°C incubation for 2 min followed by 40 cycles of 94°C for 30 sec, 58°C for 30 sec and 72°C for 25 sec for the promoter region and 40 cycles of 94°C for 30 sec, 58°C for 30 sec and 72°C for 35 sec for the segment covering part of intron and exon 2. A final 5-min extension step was performed at 72°C for both regions. The PCR products were loaded on 1.5% agarose gel containing 0.5 μg/mL ethidium bromide. Amplicons were purified using the QIAquick 96 PCR BioRobot Kit and an automated protocol on the BioRobot 8000 workstation (Qiagen, Courtaboeuf, France). The purified fragments were sequenced using the BigDye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems) using the primers described above. The sequencing reaction products were purified using the BigDye XTerminator® Purification Kit (Applied Biosystems) in accordance with the manufacturer's instructions. The purified products were sequenced using an ABI Prism 3100 analyser (Applied Biosystems). Sequences were analysed using Vector NTI advance™ software (version 11, Invitrogen, Cergy Pontoise, France).

                        Statistical analysis

                        Fisher's exact test was used to compare the proportions of Duffy genotypes in relation to P. vivax infection and ethnic origin (GraphPad Prism v5.01). The significance level was fixed at P < 0.05.

                        Results

                        Plasmodium species diagnosis

                        The results obtained by real-time PCR were in accordance with the previous data obtained for species diagnosis (Malaria Rapid Diagnostic Test, microscopy and nested PCR performed by [17]). Of 277 outpatients, 110 were positive for P. vivax. These patients came from various Nouakchott districts (Additional file 3).

                        Duffy genotypes in febrile uninfected patients and P. vivax-infected patients from Nouakchott

                        The promoter region and exon 2 of the Duffy gene from each sample selected for the study were amplified and sequenced (Additional file 3). A comparison of Duffy genotypes, phenotypes and allele frequencies according to the ethnic groups between P. vivax-infected and malaria-free patients is presented in Tables 1 and 2. The Moorish population represented the majority of patients (83%). Only a few patients belonged to the other ethnic groups: Poular (4%), Soninke (1%) and Wolof (1%). Information on ethnic origin was not available for some patients (11%), but these patients were included in the study because they were positive for P. vivax. The complete sequence of the Duffy gene was obtained for 258 patients (93%).
                        Table 1

                        Comparison of Duffy genotypes among uninfected and Plasmodium vivax-infected patients in ethnic groups from Nouakchott, Mauritania.

                        ethnic groups

                        Duffy

                        number of uninfected patients No = 167 (%[95%CI])

                        number of P. vivax-infected patients No = 110 (%[95%CI])

                        p-value

                         

                        genotypes

                        predicted phenotypes

                           

                        Moor

                        FYA/FYA

                        positive

                        11 (7.6 [3.9-13.3])

                        3 (3.8 [0.8-11.0])

                        0.388

                         

                        FYA/FYB

                        positive

                        24 (16.6 [11.0-23.8])

                        22 (28.6 [18.8-40.0])

                        0.0548

                         

                        FYA/FYB*

                        positive

                        5 (3.5 [1.1-7.9])

                        1 (1.3 [0.0-7.0])

                        0.6674

                         

                        FYA/FYB ES

                        positive

                        19 (13.2 [8.1-19.8])

                        16 (20.8 [12.4-31.5])

                        0.1757

                         

                        FYB*/FYB ES

                        positive

                        0 (0)

                        1 (1.3 [0.0-7.0])

                        0.3484

                         

                        FYB/FYB

                        positive

                        22 (15.3 [9.8-22.2])

                        16 (20.8 [12.4-31.5])

                        0.3504

                         

                        FYB/FYB*

                        positive

                        2 (1.4 [0.2-4.9])

                        2 (2.6 [0.3-9.1])

                        0.612

                         

                        FYB/FYB ES

                        positive

                        21 (14.6 [9.3-21.4])

                        16 (20.8 [12.4-31.5])

                        0.2599

                         

                        FYB ES /FYB ES

                        negative

                        40 (27.8 [20.6-35.9])

                        0 (0)

                        < 0.0001 +

                        Poular

                        FYB ES /FYB ES

                        negative

                        8 (100)

                        0 (0)

                        ND

                        Soninke

                        FYA/FYB ES

                        positive

                        0 (0)

                        2 (100)

                        0.4667

                         

                        FYB ES /FYB ES

                        negative

                        2 (100)

                        0 (0)

                        0.4667

                        Wolof

                        FYB ES /FYB ES

                        negative

                        1 (100)

                        1 (100)

                        ND

                        Unknown

                        FYA/FYB

                        positive

                        0 (0)

                        6 (26.1 [10.2-48.4])

                        ND

                         

                        FYA/FYB*

                        positive

                        0 (0)

                        1 (4.3 [0.1-21.9])

                        ND

                         

                        FYA/FYB ES

                        positive

                        0 (0)

                        2 (8.7 [1.1-28.0])

                        ND

                         

                        FYB/FYB

                        positive

                        0 (0)

                        1 (4.3 [0.1-21.9])

                        ND

                         

                        FYB/FYB ES

                        positive

                        0 (0)

                        13 (56.6 [34.5-76.8])

                        ND

                        ND

                        ND

                        ND

                        12

                        7

                        ND

                        + Fisher's Exact Test

                        ND: non determined

                        Table 2

                        Comparison of allelic frequencies of the Duffy Blood Group System among uninfected and Plasmodium vivax-infected patients in ethnic groups from Nouakchott, Mauritania.

                        ethnic groups

                        Alleles

                        Allelic frequencies (%[95%CI])

                        p-value

                          

                        uninfected patients

                        P. vivax -infected patients

                         

                        Moor

                        FYA

                        24.3 [19.5-29.7]

                        29.2 [22.2-37.1]

                        0.3058

                         

                        FYB

                        31.6 [26.3-37.3]

                        46.8 [38.7-55.0]

                        0.0019 +

                         

                        FYB*

                        2.4 [1.0-4.9]

                        2.6 [0.7-6.5]

                        1

                         

                        FYB ES

                        41.7 [35.9-47.6]

                        21.4 [15.2-28.8]

                        < 0,0001 +

                        Poular

                        FYB ES

                        100

                        0

                        ND

                        Soninke

                        FYA

                        0

                        100

                        ND

                         

                        FYB ES

                        100

                        0

                        0.0667

                        Wolof

                        FYB ES

                        100

                        100

                        ND

                        Unknown

                        FYA

                        0

                        19.6 [9.4-33.9]

                        ND

                         

                        FYB

                        0

                        45.7 [30.9-61.0]

                        ND

                         

                        FYB*

                        0

                        21.7 [0.1-11.5]

                        ND

                         

                        FYB ES

                        0

                        32.6 [19.5-48.0]

                        ND

                        + Fisher's Exact Test

                        ND: non determined

                        In the Moorish population, the prevalence rate of the FYB ES /FYB ES genotype (Fy(a-b-) phenotype) was 27.8% (n = 40) and 0% among uninfected and P. vivax-infected individuals, respectively (p < 0.0001, Fisher's exact test). This was followed by a high level of FYA/FYB, FYB/FYB, FYB/FYB ES and FYA/FYB ES genotype frequencies (Fy(a+b+), Fy(a-b+), Fy(a-b+) and Fy(a+b-) phenotypes, respectively) in both P. vivax-infected and uninfected patients. Low frequencies were detected for the FYA/FYA, FYA/FYB*, FYB*/FYB ES and FYB/FYB* genotypes (Fy(a+b-), Fy(a+b+), Fy(a-b+) and Fy(a-b+) phenotypes, respectively) in both infected and uninfected patients. In the other ethnic groups (Poular, Soninke and Wolof), only the FYB ES /FYB ES genotype was found in uninfected patients, whereas the FYA/FYB ES genotype was observed in two P. vivax-infected patients, Soninke ethnic.

                        One P. vivax-infected patient presented the FYB ES /FYB ES genotype, resulting in a Duffy-negative phenotype. This patient was a two-year-old female, belonging to the Wolof ethnic group and living in the district of Dar Naim.

                        Discussion

                        Recent reports on P. vivax infections suggest that this parasite may be evolving and adapting to new epidemiological contexts, becoming not only more virulent but also more frequent in countries where the incidence has traditionally been low [[912, 61, 62]]. The evaluation of Duffy blood group polymorphisms is important in areas where P. vivax prevails, as the Duffy antigen serves as a receptor on the surface of RBCs. Until now, few studies have reported the presence of P. vivax in Mauritania [[15, 17, 18, 29, 63]] and only one study assessed the distribution of Duffy polymorphisms in Nouakchott [64]. In the present work, the evaluation of Duffy blood group genotypes was undertaken in diverse/multiple human populations that included P. vivax-infected, uninfected, Duffy-positive and Duffy-negative people to i) assess the Duffy gene polymorphism within a cosmopolitan African community and ii) determine whether P. vivax is able to penetrate into RBCs in Duffy-negative patients, who have been thought to be resistant to P. vivax infection [21].

                        The Mauritanian population has a highly heterogeneous ethnic composition. It is primarily constituted of Moors (an ethnicity with a mix of Arab and Berber ancestry) who live in the North of the country and various black ethnic groups, including Soninke, Wolof and Poular, in the South. Duffy gene polymorphism among different ethnic groups is a characteristic of this blood system and has been used as a marker of ethnic composition as well as an indicator of the evolution of human populations. In 1986, Lepers et al undertook the study of Duffy blood group in 107 individuals belonging to different ethnic groups and residing in Nouakchott [64]. In the overall population, 27% of the individuals were Duffy-positive, whereas the others were Duffy-negative. The proportion of Duffy- positive individuals differed according to the ethnic groups: 54% of Moors were Fy+, while only 2% of black ethnic groups were Fy+.

                        In the current study, slight differences were observed in the global population: 78% of the individuals were Fy+ and 22% were Fy-. The FYA/FYB genotype was the most common, followed by the heterozygotes FYA/FYB ES and FYB/FYB ES and the homozygous FYB alleles. It should be noted that no patient had the phenotype Fy(a+bweak) or Fy(a-bweak), as the allele FYX was not present in the population.

                        When compared to other North African populations, the frequencies of FYA and FYB alleles are similar to that observed in the Tunisian people [44, 65], while the allelic frequency of FYB ES and the lack of FYX are similar to what is observed in Morocco [66]. Overall, FYA and FYB alleles are mainly represented in Europe, while the allele FYB ES is predominant in Africa [37].

                        The presence of P. vivax in Mauritania was first reported in 1948 [14] and confirmed in two recent studies suggesting autochthonous P. vivax transmission in some patients who had never travelled outside Nouakchott [15, 17]. RBCs of Duffy-negative individuals seem to be naturally resistant to invasion by the P. vivax human malaria parasite [21]. The present study describes for the first time that one Duffy-negative patient living in Nouakchott, i.e., in North Africa, was infected with P. vivax. The identification of P. vivax was performed by real-time PCR, and the Duffy genotypes were determined by sequencing, making it unlikely that a parasite other than P. vivax was involved.

                        Our data thereby confirmed the suspicion of some authors, who also believe that P. vivax could be evolving to use receptors other than Duffy to invade erythrocytes in patients in Brazil [55, 56], Kenya [59], and more recently, in Madagascar [57], Angola and Equatorial Guinea [58]. As suggested in previous studies [57, 58], Duffy-positive individuals may serve as reservoirs for P. vivax, allowing this parasite to infect hepatocytes of Duffy-negative individuals and select for new P. vivax strains with the capacity to invade Duffy-negative erythrocytes.

                        Conclusions

                        Further analyses are needed to understand the dynamics of the Duffy gene and its possible contribution as a modulator in the susceptibility to malaria. The data obtained in the present study emphasize the importance of the evaluation of Duffy blood group genotypes in P. vivax malaria endemic areas. The results of the present study support the hypothesis that Duffy-negative individuals from North Africa could be infected by P. vivax and that this parasite may be rapidly evolving to use other receptors than Duffy to invade the erythrocytes. Further longitudinal studies on P. vivax and host-parasite interactions are required to test the validity of these hypotheses. Furthermore, a better understanding of the alternative pathways used by P. vivax to invade human RBCs should become a research priority.

                        Declarations

                        Acknowledgements and funding

                        The authors thank the direction and the staff of the National Hospital, the Chiekh Zayed Hospital and the District Health Center of Teyarett for their aid in recruiting patients and the patients for kindly agreeing to participate in the study.

                        The authors are grateful to the programme "For Women in Science" granted by L'Oréal-UNESCO foundation and the French Centre for the welcome and the international trade.

                        This study was supported by the Délégation Générale pour l'Armement and the Direction Centrale du Service de Santé des Armées (grant no. 10co404).

                        Authors’ Affiliations

                        (1)
                        Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Recherche Biomédicale des Armées, Allée du médecin colonel Eugène Jamot
                        (2)
                        Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR
                        (3)
                        Laboratoire de Biotechnologies, Faculté des Sciences et Techniques, Université de Nouakchott
                        (4)
                        UFR Biologie et Santé, Département de Biologie, Faculté des Sciences Semlalia, Université Cadi Ayyad
                        (5)
                        Laboratoire Aliments, Environnement et Santé (LAES), Faculté des Sciences et Techniques, Université Cadi Ayyad
                        (6)
                        Institut Pasteur de Madagascar
                        (7)
                        Laboratoire de Paludologie, Institut de Recherche pour le Développement

                        References

                        1. WHO Global Malaria Programme: World Malaria Report. Geneva: World Health Organization; 2010.
                        2. Anstey NM, Russell B, Yeo TW, Price RN: The pathophysiology of vivax malaria. Trends Parasitol 2009, 25:220–227.PubMedView Article
                        3. Barcus MJ, Basri H, Picarima H, Manyakori C, Sekartuti , Elyazar I, Bangs MJ, Maguire JD, Baird JK: Demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in northeastern Indonesian Papua. Am J Trop Med Hyg 2007, 77:984–991.PubMed
                        4. Genton B, D'Acremont V, Rare L, Baea K, Reeder JC, Alpers MP, Muller I: Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea. PLoS Med 2008, 5:e127.PubMedView Article
                        5. Kochar DK, Das A, Kochar SK, Saxena V, Sirohi P, Garg S, Kochar A, Khatri MP, Gupta V: Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in northwestern India. Am J Trop Med Hyg 2009, 80:194–198.PubMed
                        6. Parakh A, Agarwal N, Aggarwal A, Aneja A: Plasmodium vivax malaria in children: uncommon manifestations. Ann Trop Paediatr 2009, 29:253–256.PubMedView Article
                        7. Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM: Vivax malaria: neglected and not benign. Am J Trop Med Hyg 2007,77(6 Suppl):79–87.PubMed
                        8. Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M, Lampah DA, Price RN: Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Med 2008, 5:e128.PubMedView Article
                        9. Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, Temperley WH, Kabaria CW, Tatem AJ, Manh BH, Elyazar IR, Baird JK, Snow RW, Hay SI: The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis 2010, 4:e774.PubMedView Article
                        10. Guerra CA, Snow RW, Hay SI: Defining the global spatial limits of malaria transmission in 2005. Adv Parasitol 2006, 62:157–179.PubMedView Article
                        11. Guerra CA, Snow RW, Hay SI: Mapping the global extent of malaria in 2005. Trends Parasitol 2006, 22:353–358.PubMedView Article
                        12. Baird JK: Resistance to therapies for infection by Plasmodium vivax . Clin Microbiol Rev 2009, 22:508–534.PubMedView Article
                        13. Sattabongkot J, Tsuboi T, Zollner GE, Sirichaisinthop J, Cui L: Plasmodium vivax transmission: chances for control? Trends Parasitol 2004, 20:192–198.PubMedView Article
                        14. Sautet J, Ranque J, Vuillet F, Vuillet J: Quelques notes parasitologiques sur le paludisme et l'anophélisme en Mauritanie. Med Trop (Mars) 1948, 8:32–39.
                        15. Cortes H, Morillas-Marquez F, Valero A: Malaria in Mauritania: the first cases of malaria endemic to Nouakchott. Trop Med Int Health 2003, 8:297–300.PubMedView Article
                        16. Gautret P, Legros F, Koulmann P, Rodier MH, Jacquemin JL: Imported Plasmodium vivax malaria in France: geographical origin and report of an atypical case acquired in Central or Western Africa. Acta Trop 2001, 78:177–181.PubMedView Article
                        17. Lekweiry KM, Abdallahi MO, Ba H, Arnathau C, Durand P, Trape JF, Salem AO: Preliminary study of malaria incidence in Nouakchott, Mauritania. Malar J 2009, 8:92.PubMedView Article
                        18. Lekweiry KM, Basco LK, Salem MS, Hafid JE, Marin-Jauffre A, Weddih AO, Briolant S, Bogreau H, Pradines B, Rogier C, Trape JF, Boukhary AO: Malaria prevalence and morbidity among children reporting at health facilities in Nouakchott, Mauritania. Trans R Soc Trop Med Hyg 2011, in press.
                        19. Gelpi AP, King MC: Duffy blood group and malaria. Science 1976, 191:1284.PubMedView Article
                        20. Mercereau-Puijalon O, Menard D: Plasmodium vivax and the Duffy antigen: a paradigm revisited. Transfus Clin Biol 2010, 17:176–183.PubMedView Article
                        21. Miller LH, Mason SJ, Clyde DF, McGinniss MH: The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N Engl J Med 1976, 295:302–304.PubMedView Article
                        22. Hadley TJ, Lu ZH, Wasniowska K, Martin AW, Peiper SC, Hesselgesser J, Horuk R: Postcapillary venule endothelial cells in kidney express a multispecific chemokine receptor that is structurally and functionally identical to the erythroid isoform, which is the Duffy blood group antigen. J Clin Invest 1994, 94:985–991.PubMedView Article
                        23. Horuk R, Peiper SC: Chemokines: molecular double agents. Curr Biol 1996, 6:1581–1582.PubMedView Article
                        24. Peiper SC, Wang ZX, Neote K, Martin AW, Showell HJ, Conklyn MJ, Ogborne K, Hadley TJ, Lu ZH, Hesselgesser J, Horuk R: The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor. J Exp Med 1995, 181:1311–1317.PubMedView Article
                        25. He W, Neil S, Kulkarni H, Wright E, Agan BK, Marconi VC, Dolan MJ, Weiss RA, Ahuja SK: Duffy antigen receptor for chemokines mediates trans-infection of HIV-1 from red blood cells to target cells and affects HIV-AIDS susceptibility. Cell Host Microbe 2008, 4:52–62.PubMedView Article
                        26. Horne KC, Li X, Jacobson LP, Palella F, Jamieson BD, Margolick JB, Martinson J, Turkozu V, Visvanathan K, Woolley IJ: Duffy antigen polymorphisms do not alter progression of HIV in African Americans in the MACS cohort. Cell Host Microbe 2009, 5:415–417. author reply 418–419PubMedView Article
                        27. Smolarek D, Hattab C, Hassanzadeh-Ghassabeh G, Cochet S, Gutierrez C, de Brevern AG, Udomsangpetch R, Picot J, Grodecka M, Wasniowska K, Muyldermans S, Colin Y, Le Van Kim C, Czerwinski M, Bertrand O: A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines. Cell Mol Life Sci 2010, 67:3371–3387.PubMedView Article
                        28. Chaudhuri A, Polyakova J, Zbrzezna V, Williams K, Gulati S, Pogo AO: Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite. Proc Natl Acad Sci USA 1993, 90:10793–10797.PubMedView Article
                        29. Collins WE, Nguyen-Dinh P, Sullivan JS, Morris CL, Galland GG, Richardson BB, Nesby S: Adaptation of a strain of Plasmodium vivax from Mauritania to New World monkeys and anopheline mosquitoes. J Parasitol 1998, 84:619–621.PubMedView Article
                        30. Donahue RP, Bias WB, Renwick JH, McKusick VA: Probable assignment of the Duffy blood group locus to chromosome 1 in man. Proc Natl Acad Sci USA 1968, 61:949–955.PubMedView Article
                        31. Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ, Miller LH: A receptor for the malarial parasite Plasmodium vivax : the erythrocyte chemokine receptor. Science 1993, 261:1182–1184.PubMedView Article
                        32. Neote K, Mak JY, Kolakowski LF Jr, Schall TJ: Functional and biochemical analysis of the cloned Duffy antigen: identity with the red blood cell chemokine receptor. Blood 1994, 84:44–52.PubMed
                        33. Rot A, Horuk R: The duffy antigen receptor for chemokines. Methods Enzymol 2009, 461:191–206.PubMedView Article
                        34. Langhi DM Jr, Bordin JO: Duffy blood group and malaria. Hematology 2006, 11:389–398.PubMedView Article
                        35. Tournamille C, Le Van Kim C, Gane P, Cartron JP, Colin Y: Molecular basis and PCR-DNA typing of the Fya/fyb blood group polymorphism. Hum Genet 1995, 95:407–410.PubMedView Article
                        36. Mallinson G, Soo KS, Schall TJ, Pisacka M, Anstee DJ: Mutations in the erythrocyte chemokine receptor (Duffy) gene: the molecular basis of the Fya/Fyb antigens and identification of a deletion in the Duffy gene of an apparently healthy individual with the Fy(a-b-) phenotype. Br J Haematol 1995, 90:823–829.PubMedView Article
                        37. Howes RE, Patil AP, Piel FB, Nyangiri OA, Kabaria CW, Gething PW, Zimmerman PA, Barnadas C, Beall CM, Gebremedhin A, Ménard D, Williams TN, Weatherall DJ, Hay SI: The global distribution of the Duffy blood group. Nat Commun 2011, 2:266.PubMedView Article
                        38. Iwamoto S, Li J, Sugimoto N, Okuda H, Kajii E: Characterization of the Duffy gene promoter: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals. Biochem Biophys Res Commun 1996, 222:852–859.PubMedView Article
                        39. Iwamoto S, Omi T, Kajii E, Ikemoto S: Genomic organization of the glycoprotein D gene: Duffy blood group Fya/Fyb alloantigen system is associated with a polymorphism at the 44-amino acid residue. Blood 1995, 85:622–626.PubMed
                        40. Tournamille C, Colin Y, Cartron JP, Le Van Kim C: Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet 1995, 10:224–228.PubMedView Article
                        41. Zimmerman PA, Woolley I, Masinde GL, Miller SM, McNamara DT, Hazlett F, Mgone CS, Alpers MP, Genton B, Boatin BA, Kazura JW: Emergence of FY*A(null) in a Plasmodium vivax -endemic region of Papua New Guinea. Proc Natl Acad Sci USA 1999, 96:13973–13977.PubMedView Article
                        42. Albuquerque SR, Cavalcante Fde O, Sanguino EC, Tezza L, Chacon F, Castilho L, dos Santos MC: FY polymorphisms and vivax malaria in inhabitants of Amazonas State, Brazil. Parasitol Res 2010, 106:1049–1053.PubMedView Article
                        43. Kasehagen LJ, Mueller I, Kiniboro B, Bockarie MJ, Reeder JC, Kazura JW, Kastens W, McNamara DT, King CH, Whalen CC, Zimmerman PA: Reduced Plasmodium vivax erythrocyte infection in PNG Duffy-negative heterozygotes. PLoS One 2007, 2:e336.PubMedView Article
                        44. Sellami MH, Kaabi H, Midouni B, Dridi A, Mojaat N, Boukef MK, Hmida S: Duffy blood group system genotyping in an urban Tunisian population. Ann Hum Biol 2008, 35:406–415.PubMedView Article
                        45. Chown B, Lewis M, Kaita H: The Duffy Blood Group System in Caucasians: Evidence for a New Allele. Am J Hum Genet 1965, 17:384–389.PubMed
                        46. Daniels GL, Anstee DJ, Cartron JP, Dahr W, Issitt PD, Jorgensen J, Kornstad L, Levene C, Lomas-Francis C, Lubenko A, Mallory D, Moulds JJ, Okubo Y, Overbeeke M, Reid ME, Rouger P, Seidl S, Sistonen P, Wendel S, Woodfield G, Zelinski T: Blood group terminology 1995. ISBT Working Party on terminology for red cell surface antigens. Vox Sang 1995, 69:265–279.PubMedView Article
                        47. Olsson ML, Smythe JS, Hansson C, Poole J, Mallinson G, Jones J, Avent ND, Daniels G: The Fy(x) phenotype is associated with a missense mutation in the Fy(b) allele predicting Arg89Cys in the Duffy glycoprotein. Br J Haematol 1998, 103:1184–1191.PubMedView Article
                        48. Pogo AO, Chaudhuri A: The Duffy protein: a malarial and chemokine receptor. Semin Hematol 2000, 37:122–129.PubMedView Article
                        49. Tournamille C, Le Van Kim C, Gane P, Le Pennec PY, Roubinet F, Babinet J, Cartron JP, Colin Y: Arg89Cys substitution results in very low membrane expression of the Duffy antigen/receptor for chemokines in Fy(x) individuals. Blood 1998, 92:2147–2156.PubMed
                        50. Yazdanbakhsh K, Rios M, Storry JR, Kosower N, Parasol N, Chaudhuri A, Reid ME: Molecular mechanisms that lead to reduced expression of duffy antigens. Transfusion 2000, 40:310–320.PubMedView Article
                        51. Gassner C, Kraus RL, Dovc T, Kilga-Nogler S, Utz I, Mueller TH, Schunter F, Schoenitzer D: Fyx is associated with two missense point mutations in its gene and can be detected by PCR-SSP. Immunohematology 2000, 16:61–67.PubMed
                        52. Parasol N, Reid M, Rios M, Castilho L, Harari I, Kosower NS: A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype. Blood 1998, 92:2237–2243.PubMed
                        53. Reid ME, Rios M, Roye K, Chaudhuri A, Pogo O, Yazdanbakhsh K, Coghlan G, Kosower N, Parasol N: Molecular basis of FYX. Transfusion 1998.,38(102S):
                        54. Castilho L, Rios M, Pellegrino J Jr, Saad ST, Costa FF, Reid ME: A novel FY allele in Brazilians. Vox Sang 2004, 87:190–195.PubMedView Article
                        55. Cavasini CE, de Mattos LC, Couto AA, Couto VS, Gollino Y, Moretti LJ, Bonini-Domingos CR, Rossit AR, Castilho L, Machado RL: Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region. Malar J 2007, 6:167.PubMedView Article
                        56. Cavasini CE, Mattos LC, Couto AA, Bonini-Domingos CR, Valencia SH, Neiras WC, Alves RT, Rossit AR, Castilho L, Machado RL: Plasmodium vivax infection among Duffy antigen-negative individuals from the Brazilian Amazon region: an exception? Trans R Soc Trop Med Hyg 2007, 101:1042–1044.PubMedView Article
                        57. Menard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR, Ratsimbasoa A, Thonier V, Carod JF, Domarle O, Colin Y, Bertrand O, Picot J, King CL, Grimberg BT, Mercereau-Puijalon O, Zimmerman PA: Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA 2010, 107:5967–5971.PubMedView Article
                        58. Mendes C, Dias F, Figueiredo J, Mora VG, Cano J, de Sousa B, do Rosario VE, Benito A, Berzosa P, Arez AP: Duffy Negative Antigen Is No Longer a Barrier to Plasmodium vivax - Molecular Evidences from the African West Coast (Angola and Equatorial Guinea). PLoS Negl Trop Dis 2011, 5:e1192.PubMedView Article
                        59. Ryan JR, Stoute JA, Amon J, Dunton RF, Mtalib R, Koros J, Owour B, Luckhart S, Wirtz RA, Barnwell JW, Rosenberg R: Evidence for transmission of Plasmodium vivax among a duffy antigen negative population in Western Kenya. Am J Trop Med Hyg 2006, 75:575–581.PubMed
                        60. NCBI/Primer-Blast [http://​www.​ncbi.​nlm.​nih.​gov/​tools/​primer-blast/​]
                        61. Galinski MR, Barnwell JW: Plasmodium vivax : who cares? Malar J 2008,7(Suppl 1):S9.PubMedView Article
                        62. Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, Alonso PL, del Portillo HA: Key gaps in the knowledge of Plasmodium vivax , a neglected human malaria parasite. Lancet Infect Dis 2009, 9:555–566.PubMedView Article
                        63. Lekweiry KM, Boukhary AOMS, Gaillard T, Wurtz N, Bogreau H, Hafid JE, Trape JF, Bouchiba H, Salem MSOA, Pradines B, et al.: Molecular surveillance of drug-resistant Plasmodium vivax using pvdhfr , pvdhps and pvmdr1 markers in Nouakchott, Mauritania. J Antimicrob Chemother 2011, in press.
                        64. Lepers JP, Simonneau M, Charmot G: [The Duffy blood group system in the population of Nouakchott (Mauritania)](in French). Bull Soc Pathol Exot Filiales 1986, 79:417–420.PubMed
                        65. Jeddi Blouza A, Loukil I, Mhenni A, Ben Rayana C, Hmida S: [Blood groups and open-angle glaucoma in Tunisia](in French). J Fr Ophtalmol 2007, 30:493–496.PubMedView Article
                        66. Fernandez-Santander A, Kandil M, Luna F, Esteban E, Gimenez F, Zaoui D, Moral P: Genetic relationships between southeastern Spain and Morocco: New data on ABO, RH, MNSs, and DUFFY polymorphisms. Am J Hum Biol 1999, 11:745–752.PubMedView Article

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                        This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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