1.0 INTRODUCTION

Malaria is a disease caused by a group of intracellular parasites belonging to the

Plasmodium genus (Marcilla et al, 2014). Different species of Plasmodium are

known to cause malaria in mammals and among these species, Plasmodium

falciparum is considered to be the most dangerous species that prevails mostly in

Africa (CDC, 2015). This species of the parasite is found mostly in the tropical and

subtropical areas of the world. Latest estimate released by World Health

Organization (2016) on P. falciparum infection in Africa, showed that in 2015

alone approximately 212 million cases of malaria were recorded with about 429

000 deaths, mostly among under five children and pregnant women.

Sialic acid dependent and sialic acid independent pathways are the two major

invasion pathways that have been implicated for the invasion of P. falciparum

parasite into the erythrocyte (Satchwell, 2016). The sialic acid dependent pathway

is being governed by ligands from the erythrocyte binding-like (EBL) family and

the reticulocyte binding-like (Rh) family, except for Rh1 which mediates sialic acid

independent invasion (Ord et al., 2012).

Sialic acid is a familyof negativelycharged monosaccharide which is a nine carbon

acidic sugar, found as terminal residues in glycans of the glycoconjugates of

eukaryotic cell surface or as components of capsular polysaccharides or

lipooligosaccharides of some pathogenic bacteria (Li and Chen, 2012). It has been

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considered as one of the most important molecule in life due to its peculiar strategic

location and its structural diversity (Chen and Varki, 2010).

Sialidase is an enzyme that catalyses the removal of terminal sialic acid residues

attached to glycoproteins and glycolipids on erythrocytes, which is the initial step

taken in the breakdown of glycoconjugates. The enzyme is widely spread across

different organisms such as fungi, bacteria and protozoa (Engstler et al., 1993;

Miyagi et al., 2008; Hayre et al., 2012). Sialidase acts on and cleaves sialic acid

found on the surface of erythrocytes by desialylating them, thereby exposing the

masked galactosyl residues (Akin-Osanaiye et al, 2013).

Sialidase has significant roles in many physiological and pathological processes in

biological system which includes; immunological regulation, viral infection,

process and spread of disease, microbes binding that leads to infection among

others (Varki and Varki, 2007). For invasion of pathogens into the cell, sialidase

and trans-sialidase are involved in the cleavage of sialic acid from the surface of

erythrocytes (Varki and Varki, 2007).

Female anopheles mosquitoes are responsible for the transmission of malaria into

the mammalian host. Sporozoites from the vectors are injected into the host

(vertebrate) via saliva during a blood meal (Cowman and Crabb, 2006) and after

then, the sporozoites infect the host’s liver cells where it undergoes rapid asexual

reproduction of merozoites that invade circulating erythrocytes (Dhangadamajhi et

al, 2010; Soulard et al. 2015). Multiple ligand proteins are expressed in P.

falciparum, which are used to recognize specific targets on erythrocyte surface.

The major targets found on the erythrocyte surface are terminal sialic acid on O-

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linked glycan chains attached to glycophorins, which are the most abundant

erythrocytes surface glycoproteins (Varki and Gagneux, 2009).

Specific ligand-receptor interactions are required between the parasite and the

erythrocyte for the successful invasion of P. falciparum (Duraisingh et al., 2003).

The two major ligand families that are implicated in these interactions, are the

micronemal protein from the erythrocyte binding ligands (EBL) family (EBA-175,

EBA-140, EBA-181 and EBL-1) and the rhoptry proteins from the reticulocyte

binding homolog (PfRH) (PfRH1, PfRH2a, PfRH2b, PfRH3, PfRH4, and PfRH5)

(Ord et al., 2012; Koch and Baum, 2016). These families of liga