Immunity against malaria develops slowly and only after repeated exposure to the parasite. Many of those that die of the disease are children under five years of age. Antibodies are an important part of immunity, but which antibodies that are protective and how these should be measured are still unclear. We discuss the pros and cons of ELISA, invasion inhibition assays/ADCI, and measurement of affinity of antibodies and what can be done to improve these assays, thereby increasing the knowledge about the immune status of an individual, and to perform better evaluation of vaccine trials. 1. Introduction Malaria kills around one million people every year [1, 2]. There is no vaccine against the disease, and resistance against medications is increasing. The symptoms of malaria include fever and anemia, and most of the deaths are caused by the parasite Plasmodium falciparum. The merozoite form of the parasite invades red cells, grows to form ring-, trophozoite- and schizont stages, and after rupture of the infected red cell new merozoites are released that are ready to enter uninfected red cells. Merozoite invasion is a process that takes only a few minutes [3], but it involves several complex receptor-ligand interactions. Initial attachment of the merozoite is mediated by merozoite surface proteins such as MSP1 and MSP2, and is followed by reorientation of the merozoite where apical membrane antigen 1 (AMA1) is of importance [4, 5]. Other ligands such as erythrocyte-binding antigens (EBAs), for example, EBA140, EBA175, and EBA181 and P. falciparum reticulocyte-binding homologues (PfRhs), including PfRh1, PfRh2, PfRh4, and PfRh5 have also shown to be involved in the invasion process [6–9], even though the exact function of each antigen is not known. Genetic polymorphisms exist for many of the above-mentioned ligands, and based on some genes like MSP2, parasites can be grouped into two major allelic types: 3D7 and FC27. Serine repeat antigens (SERAs) are proteases that take part in forming a protein complex that is associated with the merozoite surface [10–12], and entry into the red blood cell is finally completed by an actin-myosin motor movement [13, 14]. Individuals who live in malaria endemic areas eventually develop immunity, but only slowly and after repeated exposure [15, 16]. Many of those that die of malaria are small children. During pregnancy, women have a greater risk of succumbing to malaria, and the fetus is also at risk [17]. Immunity against severe disease often develops before complete immunity is formed. It is known that antibodies are
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