Plasmodium Falciparum Rifins: Role in malaria pathogenesis

Abstract

Malaria kills an estimated 600,000 people each year, especially children under five years who reside in sub-Saharan Africa. Malaria fatalities are associated with severe forms such as cerebral malaria, acute respiratory failure, severe anaemia, renal failure, hypoglycaemia, and pulmonary oedema. Although the underlying pathogenic mechanisms in immune responses and parasite immune evasion, cytoadherence of parasitized red blood cells, and rosetting are enumerated, the mechanisms are not fully understood. P. falciparum parasite-derived surface protein, repetitive interspersed family (RIFIN) genes are involved in rosetting, blocking microcirculation, and playing a role in malaria pathogenesis; it is unclear which RIFIN family genes are involved in the various pathogenic mechanisms in malaria. RIFINs are the extensive malaria family genes expressed throughout the malaria parasite stages, indicating their diverse roles. Malaria pathogenesis occurs in erythrocyte-stage infection, and the expression of RIFINs at this phase could play a diverse role in the various pathogenic mechanisms. They are involved in major phenomena such as cytoadherence, merozoite evasion, and immune evasion. RIFINs aid in the immune evasion of P. falciparum through various molecular interactions by binding to the inhibitory receptors LAIR1, LILRB1, and LILRB2. RIFINs in severe forms of malaria (such as cerebral malaria and severe anaemia) require a considerable understanding to target and control malaria severity and mortality. RIFINs are implicated in severe malaria and are discussed together with other variant surface antigens such as STEVORS or PfEMP1 in the specific pathophysiology of malaria. This review details the role of RIFINs in the various malaria pathophysiological mechanisms underlying severe malaria and mortality