Malaria is a tropical threatening disease caused by Plasmodium parasites, resulting in 409,000 deaths in 2019. The delay of mortality and morbidity has been compounded by the widespread of drug resistant parasites from Southeast Asia since two decades. The emergence of artemisinin-resistant Plasmodium in Africa, where most cases are accounted, highlights the urgent need for new medicines.
Studies of the malaria parasites infecting various non-human primates (NHPs) have increased our understanding of the origin, biology and pathogenesis of human Plasmodium parasites.
Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controlling the physiological level of intracellular calcium in many cell types, including red blood cells (RBCs). It is, therefore, postulated that genetic differences in the activity or expression level of PMCA4 alters intracellular Ca2+ levels and affects RBC hydration, modulating the invasion and growth of the Plasmodium parasite within its target host cell.
Malaria is a potentially lethal parasitic disease due to infection by Plasmodium parasites, transmitted by Anopheles mosquito vectors. Various preventative measures may be recommended for travellers who visit endemic areas. The diagnosis is generally evoked in the context of a febrile patient returning from an endemic zone. Nevertheless, symptoms and clinical signs may be difficult to interpret, and fatal cases may only be diagnosed retrospectively with laboratory techniques, specific pathological features and patient history. The present work reports a case of fatal cerebral malaria diagnosed post-mortem, along with the techniques that allowed identification of the causative agent.
Malaria, caused by Plasmodium parasites, is a major global public health problem. To assist an understanding of malaria pathogenesis, including drug resistance, there is a need for the timely detection of underlying genetic mutations and their spread. With the increasing use of whole-genome sequencing (WGS) of Plasmodium DNA, the potential of deep learning models to detect loci under recent positive selection, historically signals of drug resistance, was evaluated.
In the last few decades, considerable efforts have been made towards the development of efficient vaccines against malaria. Whole-sporozoite (Wsp) vaccines, which induce efficient immune responses against the pre-erythrocytic (PE) stages (sporozoites and liver forms) of Plasmodium parasites, the causative agents of malaria, are among the most promising immunization strategies tested until present.
Emerging Plasmodium parasite drug resistance is threatening progress towards malaria control and elimination. While recent efforts in cell-based high-throughput drug screening have produced first-in-class drugs with promising activities against different Plasmodium life cycle stages, most of these antimalarial agents have elusive mechanisms of action.
Plasmodium parasites, the cause of malaria, have a complex life cycle, infecting alternatively vertebrate hosts and female Anopheles mosquitoes and going through intra- and extra-cellular development in several organs of these hosts. Most of the ~5000 protein-coding genes present in Plasmodium genomes are only expressed at specific life stages, and different genes might therefore be subject to different selective pressures depending on the biological activity of the parasite and its microenvironment at this point in development.
Many stages of the complex Plasmodium parasite life cycle, the eukaryotic pathogen that causes malaria, are extracellular and motile. This motility is essential for life cycle progression, and two studies in this issue of EMBO Molecular Medicine (Hopp et al, 2021; Ripp et al, 2021) examine the motility of two of these life cycle stages.
Humoral immunity is critical for limiting Plasmodium parasite infections and the severity of malaria. Naturally acquired immunity against malaria occurs inefficiently and protection is relatively short-lived.