75 years' journey of malaria publications in English: what and where?

Malaria has inflicted serious morbidity and mortality across the globe. The major brunt of the disease has been on African, South-East Asian and South American countries. Proportionally, malaria has attracted global research priorities and this is evident from the number of publications related to malaria from across the globe, irrespective of its endemicity. However, formal and exhaustive analyses of these 'malaria publications' are rarely reported. The systematic review and secondary data analyses were done to retrieve information on what has been published on malaria, where is it published, and which countries are major contributors to malaria research.The study presents malaria publications from 1945 to 2020 retrieved using three databases: Web of Science™, Embase® and Scopus®. Exported data were examined to determine the number of publications over time, their subject areas, contributions from various countries/organizations, and top publishing journals.The total number of published records on malaria ranged from 90,282 to 112,698 (due to three different databases). Based on the number of publications, USA, UK, France, and India were identified as the top four countries. Malaria Journal, American Journal of Tropical Medicine & Hygiene, and PLoS One were the most preferred journals, whereas the University of London (Institutions other than LSHTM), the National Institute of Health, the London School of Hygiene and Tropical Medicine, and the University of Oxford appeared to be the top contributing organization.A disproportional contribution to malaria research was observed with non-malaria endemic countries making the largest contribution. Databases differed in their output format and needed standardization to make the outputs comparable across databases.

Genotyping var Gene DBL1α Domain of Severe and Non-severe Plasmodium falciparum Patients.

This study analysed the genetic diversity of DBL1α domain of Plasmodium falciparum var gene in severe and non-severe malaria patients from Delhi and Mewat in Northern India. After confirming P. falciparum infection, samples were cloned and the var gene DBL1α domain was sequenced. Out of 377 cloned DBL sequences, 194 were from severe samples and 183 from non-severe samples. Proportion of DBL1α sequences belonging to groups 1, 4 and 5 were significantly higher in severe isolates as compared to non-severe isolates-group 1 (4.1% vs 1.09%, P = 0.0333), group 4 (69.58% vs 74.31%, P < 0.0001), and group 5 (19.58% vs 10.38%, P < 0.0001). Conversely, higher proportion of group 2 was observed in non-severe isolates (0% vs 3.82%, P = 0.0350). Highest diversity was seen in PoLV4 motif of severe and non-severe isolates and like other DBL1α sequences reported from several geographical areas (Africa, Americas, Asia, and Oceania). A total of 247 DBL1α domain haplotypes were found in this study where 139 (56.27%) haplotypes are novel and not reported from India till date. These findings could aid in developing effective malaria interventions, including vaccine and drug targets, by understanding the existing antigenic diversity and vulnerabilities in the parasite's genetic makeup. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01200-1.

Myco-synthesis of multi-twinned silver nanoparticles as potential antibacterial and antimalarial agents.

In recent days, biogenic and green approaches for synthesizing nanostructures have gained much attention in biological and biomedical applications. Endophytic fungi have been recognized to produce several important biomolecules for use in various fields. The present work describes the use of endophytic fungi isolated from Berberis aristata for the synthesis of multi-twinned silver nanoparticles (MT-AgNPs) and their successful applications in antimicrobial and antimalarial studies. TEM images reveal the formation of multi-twined structures in the synthesized silver nanoparticles. The synthesized MT-AgNPs have shown excellent antibacterial activities against five opportunistic bacteria, viz. Bacillus subtilis (MTCC 441), Pseudomonas aeruginosa (MTCC 424), Escherichia coli (MTCC 443), Klebsiella pneumonia (MTCC 3384), and Aeromonas salmonicida (MTCC 1522). The synthesized MT-AgNPs also exhibit interesting antimalarial activities against Plasmodium falciparum parasites (3D7 strain) by displaying 100% inhibition at a concentration of 1 µg mL-1 against the malaria parasite P. falciparum 3D7. Overall, the results describe a green method for the production of twinned-structured nanoparticles and their potential to be applied in the biomedical, pharmaceutical, food preservation, and packaging industries.

In silico screening of chalcone derivatives as promising EGFR-TK inhibitors for the clinical treatment of cancer.

Epidermal growth factor receptor (EGFR) promotes tumorigenic characteristics and activates cancer-associated signaling pathways such as Wnt/-catenin, transforming growth factor (TGF-ß), and phosphoinositide-3-kinase (PI3K). Several inhibitors have been reported to suppress the activity of EGFR and are being used in cancer treatment. However, patients in the malignant stage of cancer show resistance to those inhibitors, opening a wide space for research to discover novel inhibitors. Therefore, we carried out machine learning and virtual screening to discover novel inhibitors with high affinity against EGFR-TK. Initially, a library of 2640 chalcones were screened out using a machine-learning model developed based on the random forest algorithm, exhibiting high sensitivity and a Receiver Operating Characteristic curve (ROC area) of 0.99. Furthermore, out of the initial 2640 screened compounds, 412 compounds exhibiting potential activity are subjected to evaluation for drug-likeness properties through different filters: Blood-brain barrier penetration, Lipinski's rule, CMC-50 like rule, Veber rule, and Ghose filter, alongside Cell Line Cytotoxicity Prediction. A total of 30 compounds that successfully pass through all these filters are selected for molecular docking. Of these, 6 compounds display substantial binding affinity and closer interaction with the conserved catalytic residues of the target EGFR-TK compared to the reference molecule (erlotinib). Furthermore, molecular dynamics simulation studies were conducted on four compounds (CID-375861, CID-375862, CID-23636403, and CID-259166) to confirm the stability of the docked complexes over a 100 ns simulation trajectory. Additionally, the binding free energy calculations by MMPBSA reveal that these four chalcone compounds exhibit strong affinity towards the EGFR-TK enzyme, with binding free energies of - 65.421 kJ/mol, - 94.266 kJ/mol, - 80.044 kJ/mol, and - 79.734 kJ/mol, respectively. The findings from this investigation highlight a set of promising chalcone compounds that have the potential to be developed into effective drugs for the treatment of various cancers. Further research and development on these compounds could pave the way for novel therapeutic interventions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03858-8.

Deletions of Histidine-Rich Protein 2/3 Genes in Natural Plasmodium falciparum Populations from Cameroon and India: Role of Asymptomatic and Submicroscopic Infections.

The bulk of malaria rapid diagnostic tests (RDTs) target histidine-rich protein 2 of Plasmodium falciparum, the deadliest malaria species. The WHO considers pfhrp2/3 deletions as one of the main threats to successful malaria control and/or elimination; as such, parasites that lack part or all of the pfhrp2 gene are missed by pfHRP2-targeting RDTs. Such deletions have been reported in several African and Asian countries, but little is known in Cameroon and India. Blood samples were collected from individuals living in four areas of Cameroon (Douala, Maroua, Mayo-Oulo, Pette) and India (Mewat, Raipur, Ranchi, Rourkela). Deletions in pfhrp2/3 genes were confirmed if samples 1) had ≥100 parasites/µL by quantitative polymerase chain reaction (PCR), 2) PCR negative for pfhrp2/3, and 3) PCR positive for at least two single-copy genes. The overall proportion of pfhrp2 and pfhrp3 deletions in Cameroon was 13.5% and 3.1%. In India, the overall proportion was 8% for pfhrp2 and 4% for pfhrp3. The overall proportions of samples with both gene deletions (pfhrp2-/3-) were 3.1% in Cameroon and 1.3% in India. In Cameroon, pfhrp2-/3+ and pfhrp2-/3- deletions were common in Maroua (P = 0.02), in asymptomatic parasitemia (P = 0.006) and submicroscopic parasitemia (P <0.0001). In both countries, pfhrp2/3 deletions, including pfhrp2-/3- deletions, were mainly seen in monoclonal infections. This study outlines that double deletions that result in false negative RDTs are uncommon in our settings, and highlights the importance of active molecular surveillance for pfhrp2/3 deletions in Cameroon and India.

Germination of Mansonia altissima (A. Chev.) A. Chev. var. altissima: an endangered valuable timber species in Africa

The in vitro seed germination which results in the production of disease-free seedlings and greenhouse germination of the seeds of Mansonia altissima was investigated in order to establish a better way of germination of the timber species. Five levels of GA3 treatment were used in in vitro germination with three replicate and two seeds were inoculated in each of the jam bottle. Whereas, in greenhouse germination, five levels of different treatments were used, replicated three times and each Petri plate contained 15 seeds. The experiment was repeated twice and the data from each experiment was put together and used for the statistical analysis. The results showed that seeds germination occurred eight days after inoculation in in vitro but in the case of greenhouse germination, it took only five days. For in vitro rapid germination of Mansonia altissima, the MS medium should be supplemented with 1.0 μm of GA3. Equally, in greenhouse germination, the seeds need to be soaked in 1.0 mM of GA3 for 24 hours. Alternatively, in the absence of GA3, the seeds can be soaked in water for 24 hours before broadcasting the seeds on the seedbed for germination, as this will help to identify nonviable seeds.

Mitochondrial genome sequence diversity of Indian Plasmodium falciparum isolates

We have analysed the whole mitochondrial (mt) genome sequences (each ~6 kilo nucleotide base pairs in length) of four field isolates of the malaria parasite Plasmodium falciparum collected from different locations in India. Comparative genomic analyses of mt genome sequences revealed three novel India-specific single nucleotide polymorphisms. In general, high mt genome diversity was found in Indian P. falciparum, at a level comparable to African isolates. A population phylogenetic tree placed the presently sequenced Indian P. falciparum with the global isolates, while a previously sequenced Indian isolate was an outlier. Although this preliminary study is limited to a few numbers of isolates, the data have provided fundamental evidence of the mt genome diversity and evolutionary relationships of Indian P. falciparum with that of global isolates.