Artemisinin-acetylenedicarboxylic acid cocrystal: screening, structure determination, and physicochemical property characterisation

Artemisinin is used to treat malaria, even when caused by multi-drug resistant strains of the Plasmodium parasite; the compound also shows good promise as an anti-cancer drug. However, the usage...

Repurposing Dihydroartemisinin-Piperaquine-Doxycycline as an Antimalarial Drug: A Study in Plasmodium berghei-Infected Mice

Artemisinin-based combination (ACT) therapy is the mainstay for malaria treatment. However, Plasmodium parasite with decreased susceptibility to ACT has emerged. Hence, it is imperative to discover new drugs or explore new drug combinations that can decrease Plasmodium parasite resistance. This study assessed the antiplasmodial activity of dihydroartemisinin-piperaquine- doxycycline (D-P-DX) on mice infected with Plasmodium berghei. Swiss albino mice (25-30g) of both sexes inoculated with 1x107 Plasmodium berghei intraperitoneally were used. The mice were randomly grouped and orally treated with DX (2.2 mg/kg), D-P (1.71/13.7 mg/kg) and D-P-DX daily in curative, suppressive and prophylactic studies. The negative and the positive controls were treated daily with normal saline (0.2mL) and chloroquine (CQ) (10mg/kg), respectively. After treatment, blood samples were assessed for percentage parasitemia, hematological and lipid parameters. Also, the mice were observed for mean survival time. D-P, DX, and D-P-DX produced significant decreases in percentage parasitemia at p<0.05, p<0.01 and p<0.001, respectively when compared to negative control. In the curative study, D-P, DX, and D-P-DX produced 64.9%, 71.1%, and 93.6% parasitemia inhibitions when compared to 70.0% inhibition produced by CQ. Plasmodium berghei -induced alterations in packed cell volume, white blood cells, red blood cells, hemoglobin, high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were significantly restored by DX (p<0.05) and D-P (p<0.01) and D-P-DX (p<0.001) when compared to the negative control. D-P-DX showed significant antiplasmodial activity against Plasmodium berghei- infected mice. It may be clinically useful for the treatment of malaria.

Involvement of translocon complex in hemoglobin import from infected erythrocyte cytoplasm into the Plasmodium parasite

Haemoglobin degradation is crucial for the growth and survival of Plasmodium falciparum in human erythrocytes. Although the process of Hb degradation has been studied in great detail, the mechanisms of Hb uptake remain ambiguous to date. Here, we characterized Heme Detoxification Protein (PfHDP), a protein localized in the parasitophorous vacuole, parasite food vacuole and infected erythrocyte cytosol for its role in Hb uptake. Immunoprecipitation of PfHDP-GFP fusion protein from a transgenic line using anti-GFP antibody and of Plasmodium parasite extract using anti-human Hb antibodies respectively, showed the association of PfHDP/Hb with each other as well as with the members of PTEX translocon complex. Some of these associations such as PfHDP/Hb and PfHDP/Pfexp-2 interactions were confirmed by in vitro protein-protein interaction tools. To know the roles of PfHDP and translocon complex in Hb import into the parasites, we next studied the Hb uptake by the parasite in PfHDP knock-down line using the GlmS ribozyme strategy. PfHDP knock-down significantly reduced the Hb uptake in these parasites in comparison to the wild type parasites. Further, the transient knock-down of one of the members of the translocon complex; PfHSP101 showed considerable reduction in Hb uptake. Morphological analysis of PfHDP-HA-GlmS transgenic parasites in the presence of GlcN showed food vacuole abnormalities and parasite stress, thereby causing a growth defect in the development of these parasites. Together, we implicate the translocon complex in the trafficking of PfHDP/Hb complex in the parasite and suggest a role for PfHDP in the uptake of Hb and parasite development. The study thus reveals new insights into the function of PfHDP, making it an extremely important target for developing new antimalarials.

REVIEW: PERAN NANOPARTIKEL DALAM MENGHAMBAT PERTUMBUHAN PARASIT Plasmodium PENYEBAB MALARIA

Review: The Role of Nanoparticles in Inhibiting the Growth of the Plasmodium Parasite Causing Malarial Disease Malaria is a health problem in Indonesia with the most cases in eastern parts of Indonesia. This study provides an overview of the potential of nanoparticles in inhibiting malaria vectors and the growth of Plasmodium parasites that causes malaria based on the latest literature as reference materials and future research ideas. Nanoparticle can be synthesized using three methods i.e. physical, chemical and biological synthesis. The use of nanoparticles with biological method is highly recommended because they are practicable, environmentally friendly, non-toxic, and easy to reproduce compared to physico-chemically synthesized nanoparticles. Nanoparticles synthesized from several plants can inhibit the growth of Plasmodium parasites with IC50 3–78 g mL–1. This activity is classified as high to moderate in inhibiting the growth of the Plasmodium parasite that causes malaria. The mechanism of inhibition of Plasmodium growth is by increasing the pH of food vacuole due to the reaction of nanoparticles with Ferriprotoporphyrin IX. The high pH in the food vacuole will interfere with metabolic activity by inhibiting the activity of aspartate and cysteine ??protease enzymes so that the parasites will die. Malaria merupakan masalah kesehatan yang dihadapi Indonesia khususnya di beberapa wilayah timur Indonesia. Kajian ini memberikan gambaran potensi nanopartikel dalam menghambat vektor malaria maupun pertumbuhan parasit Plasmodium penyebab malaria berdasarkan literatur terbaru sebagai bahan acuan maupun ide-ide penelitian di masa mendatang. Nanopartikel dapat disintesis menggunakan tiga metode yaitu fisika, kimia dan biologi. Penggunaan nanopartikel dengan metode biologi sangat direkomendasikan karena lebih mudah diterapkan, ramah lingkungan, bersifat non-toksik, dan mudah diperbanyak dibandingkan dengan nanopartikel yang disintensis dari fisiko-kimia. Nanopartikel yang disintesis dari beberapa tanaman dapat menghambat pertumbuhan parasit Plasmodium dengan IC50 3–78 g mL–1. Aktivitas ini tergolong tinggi hingga sedang dalam menghambat pertumbuhan parasit Plasmodium penyebab malaria. Mekanisme penghambatan pertumbuhan Plasmodium dengan cara meningkatkan pH vakuola makanan akibat reaksi nanopartikel dengan feriprotoporpirin IX. Tingginya pH pada vakuola makanan akan mengganggu aktivitas metabolisme dengan cara menghambat aktivitas enzim aspartat dan sistein protease sehingga parasit akan mati.

Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation

Antimalarial antibody responses are essential for mediating the clearance of Plasmodium parasite–infected RBCs from infected hosts. However, the rapid appearance of large numbers of plasmablasts in Plasmodium-infected hosts can suppress the development and function of durable humoral immunity. Here, we identify that the formation of plasmablast populations in Plasmodium-infected mice is mechanistically linked to both hemolysis-induced exposure of phosphatidylserine on damaged RBCs and inflammatory cues. We also show that virus and Trypanosoma infections known to trigger hemolytic anemia and high-grade inflammation also induce exuberant plasmablast responses. The induction of hemolysis or administration of RBC membrane ghosts increases plasmablast differentiation. The phosphatidylserine receptor Axl is critical for optimal plasmablast formation, and blocking phosphatidylserine limits plasmablast expansions and reduces Plasmodium parasite burden in vivo. Our findings support that strategies aimed at modulating polyclonal B cell activation and phosphatidylserine exposure may improve immune responses against Plasmodium parasites and potentially other infectious diseases that are associated with anemia.

A Systematic Review on Automatic Detection of Plasmodium Parasite

Plasmodium parasite is the main cause of malaria which has taken many lives. Some research works have been conducted to detect the Plasmodium parasite automatically. This research aims to identify the development of current research in the area of Plasmodium parasite detection. The research uses a systematic literature review (SLR) approach comprising three stages, namely planning, conducting, and reporting. The search process is based on the keywords which were determined in advance. The selection process involves the inclusion and exclusion criteria. The search yields 45 literatures from five different digital libraries. The identification process finds out that 28 methods are applied and mainly categorizes as machine learning algorithms with performance achievements between 60% and 95%. Overall, the research of Plasmodium parasite detection today has focused on the development with artificial intelligence specifically related to machine and deep learning. These approaches are believed as the most effective approach to detect Plasmodium parasites.

Effect of Mindi Leaf Powder (Melia azedarach L) on Mortality of Anopheles aconitus Instar III Larvae

Background: Malaria is a disease caused by Plasmodium parasite infection wwhich is transmitted through bite of an Anopheles mosquito. Efforts to control malaria can be carried out in various ways, starting from treatment, prevention, to breaking the transmission chain through vectors, both mosquitoes and larvae. Mindi tree contains Azadiractin compounds which are larvicides. Study aims to determine effect of mindi leaf powder (Melia azedarach L) on mortality of Anopheles aconitus instar III larvae.Methods: A true experimental study with a post test only control group design, the object of research was Anopheles aconitus Instar III larvae. The research was conducted at Laboratory of Parasitology, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang. 20 larvae / 100 ml were used. Air temperature and water pH were controlled during observation. Assessment by counting number of mortality larvae and the number of live larvae from each treatment was compared to the control. The data obtained were analyzed by the Kruskal-Wallis statistical test. The LD50 and LD90 were analyzed using Probit analysis.Results: The dose of 0.2 g/100 ml was the minimum dose that killed 100% of larvae of Anopheles aconitus (p = 0.01). In the probit test, LD50 was 0.01 g/100 ml of aquades, while LD90 was 0.06 gram/ 100 ml of aquades.Conclusion: Dose can served as larvicidal (LD90 )was 0.06 g/100 ml of aquades., while LD50 was 0.01 g/100 ml of aquades.