Malaria is one of the most devastating infectious diseases of humans. It is problematic clinically and economically as it prevails in poorer countries and regions, strongly hindering socioeconomic development. The causative agents of malaria are unicellular protozoan parasites belonging to the genus Plasmodium. These parasites infect not only humans but also other vertebrates, from reptiles and birds to mammals. To date, over 200 species of Plasmodium have been formally described, and each species infects a certain range of hosts.
The inhibition of Plasmodium cytosolic phenylalanine tRNA-synthetase (cFRS) by a novel series of bicyclic azetidines has shown the potential to prevent malaria transmission, provide prophylaxis, and offer single-dose cure in animal models of malaria. To date, however, the molecular basis of Plasmodium cFRS inhibition by bicyclic azetidines has remained unknown.
Despite decades of research into the development of a vaccine to combat the malaria parasite, a highly efficacious malaria vaccine is not yet available. Different whole parasite-based vaccine approaches, including deliberate Plasmodium infection and drug cure (IDC), have been evaluated in pre-clinical and early phase clinical trials.
Chemical matter is needed to target the divergent biology associated with the different life cycle stages of Plasmodium. Here, we report the parallel de novo screening of the Medicines for Malaria Venture (MMV) Pandemic Response Box against Plasmodium asexual and liver stage parasites, stage IV/V gametocytes, gametes, oocysts and as endectocides. Unique chemotypes were identified with both multistage activity or stage-specific activity, including structurally diverse gametocyte-targeted compounds with potent transmission-blocking activity, such as the JmjC inhibitor ML324 and the antitubercular clinical candidate SQ109.
The COVID-19 pandemic has resulted in massive global disruptions with considerable impact on the delivery of health services and national health programmes. Since the detection of the first COVID-19 case on 5th March 2020, the Royal Government of Bhutan implemented a number of containment measures including border closure and national lockdowns.
Antimalarial agents used as monotherapy are increasingly ineffective due to the emergence of Plasmodium resistant strains. Artemisinin (Arte), extracted from Artemisia annua, presents a good efficiency against the Plasmodium strains and is currently used to treat malaria. To avoid the appearance of new resistant strains to artemisinin, the use of Artemisinin-based Combination Therapy (ACT) with another antimalaria agent was recommended by WHO to provide an effective cure and delayed resistance.
Traditionally attributed only to Plasmodium falciparum, Plasmodium vivax has recently been reported to cause a significant burden of complicated malaria cases. The present study aimed to delineate the clinical spectrum and identify predictors for severe disease. This was a prospective observational cohort study conducted at a tertiary care hospital in North India. Patients with acute febrile illness (AFI) aged at least 14 years were included if they were diagnosed with vivax malaria based on rapid kits or peripheral smears.
The high burden of malaria and HIV/AIDS prevents economic and social progress in developing countries. A continuing need exists for development of novel drugs and treatment regimens for both diseases in order to address the tolerability and long-term safety concerns associated with current treatment options and the emergence of drug resistance.
Gene targeting approaches have recently demonstrated the essential role for the malaria parasite of membrane transport proteins involved in lipid transport and in the maintenance of membrane lipid asymmetry, representing emerging oportunites for therapeutical intervention. This is the case of ATP2, a Plasmodium-encoded 4 P-type ATPase (P4-ATPase or lipid flippase), whose activity is completely irreplaceable during the asexual stages of the parasite. Moreover, a recent chemogenomic study has situated ATP2 as the possible target of two antimalarial drug candidates.
The malaria parasite has an extraordinary ability to evade the immune system due to which the development of a malaria vaccine is a challenging task. Extensive research on malarial infection in the human host particularly during the liver stage has resulted in the discovery of potential candidate vaccines including RTS,S/AS01 and R21. However, complete elimination of malaria would require a holistic multi-component approach. In line with this, under the World Health Organization's PATH Malaria Vaccine Initiative (MVI), the research focus has shifted towards the sexual stages of malaria in the mosquito host.