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 . 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 [[2–8]]. Moreover, P. vivax has a wider geographical range, potentially exposing more people to risk of infection (2.85 billion across three continents) [[9–11]], 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 . 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 [[15–17]]. In 2009-2010, the prevalence of P. vivax among malaria in children in Nouakchott represented 97.1% .
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) [[19–21]]. 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 [[22–24]]. It is implicated in multiple chemokine inflammation, inflammatory diseases, and cancer and might play a role in HIV infection [[25–27]]. 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 [[28–33]].
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) [[34–36]]. The FYA/FYB frequency shows marked geographic disparities; the FYB allele is highly predominant in Africa, while the FYA allele is dominant in Asia . 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 [[38–40]]. This variant is commonly associated with the FYB allele (corresponding to the FYB
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
) . The FYB
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
mutation is rare and so far appears to be present only in the Melanesian and Tunisian population) [[41–44]]. 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 [[47–50]] 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) [[51–53]] or even three polymorphisms (C265T, G298A and G145T→ Ala49Ser) (FYX3) . The point mutation G298A alone did not cause a decrease of the Fyb expression . This allele is also named FYB* in the present study. Eight combinations of alleles (FYA, FYB, FYB*, FYX [FYX1, FYX2 and FYX3], FYA
) 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 . However, several reports have provided evidence for P. vivax infections among Duffy-negative patients [[55–59]], 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.